baylor university medical center, dallas, texas proceedings/2013 vol...volume 26 number 4 october...

Volume 26

Number 4

October 2013

To access Baylor’s physicians, clinical services, or

educational programs, contact the Baylor Physician

ConsultLine: 1-800-9BAYLOR (1-800-922-9567)

Baylor University Medical Center, Dallas, Texas

Baylor University Medical Center Proceedings

Volume 26, N

umber 4 • October 2013

Pages 361–448

www.BaylorHealth.edu/Proceedings

Indexed in PubMed, with full text available through PubMed Central

405 Fibromuscular dysplasia of the renal artery as a cause of secondary hypertension

A. Y. Hundae, C. A. Hebert, and J. M. Schussler

407 Slow group beating D. L. Glancy and V. N. Lathia

408 Continuous murmur and cardiac failure in a 53-year-old woman

D. L. Glancy and E. B. Hanna

410 Amlodipine overdose T. Patel, D. Tietze, and A. N. Mehta

Historical Studies 417 Consults for confl ict: the history of ethics consultation Elliot B. Tapper

Editorials 423 What’s going on in dental education? Eric S. Solomon

425 An unforgettable, perpetual medical student, 1961 S. Robert Lathan

Book Reviews 427 Review of For the Love of Wild Th ings (Dimijian) Daniel E. Polter

428 Review of Sifting Shades (Khan) Harbans Lal

From the Editor 432 Facts and ideas from anywhere William C. Roberts

Miscellany

386 Avocations: Photograph by Dr. Rosenthal

412 Baylor news

416 Clinical research studies enrolling patients

429 Reader comments: Cardiac rehabilitation in fi refi ghters (S. N. Kales, D. M. Baur, D. Hostler, and D. L. Smith; author reply: R. Berbarie, J. Adams, and T. Bilbrey)

442 Selected published abstracts of Baylor researchers

447 Instructions for authors

Multipatient Studies 363 Migraine disability, healthcare utilization, and

expenditures following treatment in a tertiary headache center

F. G. Freitag, H. Lyss, and G. R. Nissan

368 Advance care planning knowledge and documentation in a hospitalized cancer population

A. Barakat, S. A. Barnes, M. A. Casanova, M. J. Stone, K. M. Shuey,

and A. M. Miller

373 Incidence and severity of respiratory insuffi ciency detected by transcutaneous carbon dioxide monitoring after cardiac surgery and intensive care unit discharge

E. E. Lagow, B. Leeper, L. W. Jennings, and M. A. E. Ramsay

376 Outcome assessment of 603 cases of concomitant inferior turbinectomy and Le Fort I osteotomy

R. Movahed, C. Morales-Ryan, W. R. Allen, S. Warren, and L. M. Wolford

Single-Patient Studies 382 Copper defi ciency (hypocupremia) and pancytopenia

late after gastric bypass surgery S. D. Robinson, B. Cooper, and T. V. Leday

387 Isolated atrial amyloidosis and the importance of molecular classifi cation

V. Podduturi, D. R. Armstrong, M. A. Hitchcock, W. C. Roberts,

and J. M. Guileyardo

390 Th e Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis

M. C. Denny and A. D. Fotino

393 Unusual dermal pleomorphic calcifi cations in a case of infl ammatory breast carcinoma

A. R. Yactor, M. Zarghouni, J. C. Wang, R. R. Hamilton, and J. J. Spigel

396 Basal cell adenoma of the breast M. Van Vrancken, M. Mir, and W. Herlihy

398 Critical lower limb ischemia from an embolized Angio-Seal closure device

C. Cianci, R. C. Kowal, G. Feghali, S. Hohmann, R. C. Stoler,

and J. W. Choi

401 Th e myth of the Bernheim syndrome M. S. Chung, J. M. Ko, T. Chamogeorgakis, S. A. Hall, and W. C. Roberts

361

Editorial BoardJenny Adams, PhD W. Mark Armstrong, MDJoanne L. Blum, MD, PhDC. Richard Boland Jr., MDJennifer Clay Cather, MDEvangeline T. Cayton, MDJames W. Choi, MDCristie Columbus, MDBarry Cooper, MDR. D. Dignan, MDGregory G. Dimijian, MDMichael Emmett, MDAndrew Z. Fenves, MD Giovanni Filardo, PhD Adrian E. Flatt, MDJames W. Fleshman, MDDennis R. Gable, MD

D. Luke Glancy, MDL. Michael Goldstein, MDPaul A. Grayburn, MDBradley R. Grimsley, MDJoseph M. Guileyardo, MDCarson Harrod, PhDH. A. Tillmann Hein, MDDaragh Heitzman, MDPriscilla A. Hollander, MD, PhDRonald C. Jones, MDRoger S. Khetan, MDGöran B. Klintmalm, MD, PhDSally M. Knox, MDJohn R. Krause, MDJoseph A. Kuhn, MDZelig H. Lieberman, MDJay D. Mabrey, MD

Michael J. Mack, MDGavin M. Melmed, JD, MBA, MDRobert G. Mennel, MDDan M. Meyer, MDMichael Opatowsky, MDJoyce A. O’Shaughnessy, MDDighton C. Packard, MDGregory J. Pearl, MDRobert P. Perrillo, MDDaniel E. Polter, MDIrving D. Prengler, MDChet R. Rees, MDRandall L. Rosenblatt, MDLawrence R. Schiller, MDW. Greg Schucany, MDJeff rey M. Schussler, MDS. Michelle Shiller, DO

Michael J. Smerud, MDMarvin J. Stone, MDC. Allen Stringer Jr., MDWilliam L. Sutker, MDGary L. Tunell, MDBeverlee Warren, MA, MSWilson Weatherford, MDLawrence S. Weprin, MDF. David Winter Jr., MDLarry M. Wolford, DMDScott W. Yates, MD, MBA, MS

Residents/FellowsMina Benjamin, MDKyle Gummelt, DOBrittany D. Shoemake, MD

Editor in Chief Associate Editor Founding EditorWilliam C. Rob erts, MD Michael A. E. Ramsay, MD George J. Race, MD, [email protected]

Volume 26, Number 4 • October 2013

Baylor University Medical Center ProceedingsThe peer-reviewed journal of Baylor Health Care System, Dallas, Texas

Editorial StaffManaging Editor Administrative Liaison Design and ProductionCynthia D. Orticio, MA, ELS Dana M. Choate, MBA, RHIA, CHP Aptara, [email protected]

Baylor University Medical Center Proceedings (ISSN 0899-8280), a peer-reviewed journal, is published quarterly (January, April, July, and October). Proceedings is indexed in PubMed and CINAHL; the full text of articles is available both at www.BaylorHealth.edu/Proceedings and www.pubmedcentral.nih.gov. Th e journal’s mis-sion is to communicate information about the research and clinical activities, con-tinuing education, philosophy, and history of the Baylor Health Care System.

Funding for the journal is provided by the following:

• Baylor Health Care Sys tem Foundation• Helen Buchanan and Stanley Joseph Seeger Endowment for SurgeryFunding is also provided by donations made by the medical staff and sub scrib-ers. Th ese donations are acknowledged each year in the April or July issue. For more information on supporting Proceedings and Baylor Health Care System with charitable gifts and bequests, please call the Foundation at 214-820-3136. Donations can also be made online at http://give.baylorhealth.com/.Statements and opinions expressed in Proceedings are those of the authors and not necessarily those of Baylor Health Care System or its board of trustees.

Guidelines for authors are available at http://www.baylorhealth.edu/Research/Proceedings/SubmitaManuscript/Pages/default.aspx.

Subscriptions are off ered free to libraries, physicians affi liated with Baylor, and other interested physicians and health care professionals. To add or remove your name from the mailing list, call 214-820-9996 or e-mail [email protected]. POSTMASTER: Send address changes to Baylor Scientifi c Publications Offi ce, 3500 Gaston Avenue, Dallas, Texas 75246.

Advertising is accepted. Acceptance of advertising does not imply endorsement by Baylor University Medical Center. For information, contact Cindy Orticio at [email protected].

Permission is granted to students and teachers to copy material herein for educational purposes. Authors also have permission to reproduce their own articles. Written permission is required for other uses and can be obtained through Copyright.com.

Copyright © 2013, Baylor University Medical Center. All rights reserved. Printed in the United States of America on acid-free paper. Press date: September 8, 2013.

To access Baylor’s physicians, clinical services, or educational programs, contact the Baylor Physician ConsultLine: 1-800-9BAYLOR (1-800-922-9567).

361

363363

Headache is among the most common disabling pain complaints. While

many patients are managed in primary care or referral neurology prac-

tices, some patients have refractive situations that necessitate referral to

a tertiary headache center. Increasing frequency of headache is strongly

associated with increasing disability and workplace absenteeism as well

as increased healthcare utilization. Previous studies have demonstrated

that headache care in a dedicated tertiary center is associated with a

decrease in headache frequency and improvement in other characteris-

tics that persist over extended periods of time. Previous studies have not

examined the impact of this treatment on subsequent healthcare utilization

and associated expenditures. In this study we examined the changes in

healthcare utilization and expenditures as well as the impact on disability

and workplace productivity with treatment in a tertiary headache care

center that used initial treatment settings of inpatient and outpatient care

and considered the difference between those with episodic migraine and

those with chronic migraine and its complications. Tertiary care was found

to produce positive reductions in disability, healthcare utilization, and ex-

penditures. These results suggest that earlier tertiary-level intervention may

avoid the complications of migraine that occur in some patients and the

increasing costs and utilization of care associated with higher disability.

Inpatient dedicated programs for headache were developed to care for patients with diffi cult-to-resolve headaches. Patients treated in dedicated headache treatment centers have been shown to realize more robust outcomes. Th ese programs seek

to provide comprehensive assessment and treatment for patients and address the lifestyle, behavior, and physical factors that con-tribute to disease management. A variety of outcomes may be considered for headache management, including pain severity, headache frequency, amount of medication taken, quality of life, disability, productivity, healthcare costs, and absenteeism and “presenteeism,” which describes patients’ limited function-ing from headache at work. Existing outcome studies of head-ache treatment have focused almost exclusively on measures of headache attributes, with results reported in the US Headache Consortium Inpatient Treatment guidelines (1). Th ese studies have noted signifi cant reduction in the frequency and severity of headaches over both short-term and long-term assessments when headaches were treated in an integrated inpatient pro-gram. Disability or healthcare costs have largely gone unstudied

From the Comprehensive Headache Center, Baylor Neuroscience Center, Baylor

University Medical Center at Dallas (Freitag, Nissan); and Heidi Lyss Consulting,

Moraga, California (Lyss). Dr. Freitag is now with the Medical College of

Wisconsin.

Corresponding author: Frederick G. Freitag, DO, Department of Neurology,

Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226

(e-mail: [email protected]).

(1), and few studies have evaluated the outcomes of treatment for patients in tertiary headache centers in which hospitalization has not been a component of the treatment program. Some re-search has evaluated the eff ects of migraine on quality of life. Th e Migraine Disability Assessment Score (MIDAS®) was developed in 1997 to assess the impact of periodic migraine on lost time and productivity at work, at home, and in family activities (2–4) in patients with episodic headache. Episodic headache has been defi ned as headache that occurs on 14 or fewer days per month, whereas chronic headache has been defi ned as occurring on 15 or more days a month for at least 3 months (5). Th e MIDAS was not developed for use in patients with daily or nearly daily headache. Mathew and colleagues (6) examined the MIDAS tool in patients with very frequent headaches in a tertiary setting and found that even among these patients, treatment outcomes could be assessed with the MIDAS. In an earlier study (7), we found a correlation between higher MIDAS scores and greater healthcare expenditures and utilization and found that greater reductions in MIDAS scores correlated with greater reductions in healthcare utilization. In recent years, increasing interest has focused on utilization of healthcare resources and correspond-ing costs of care (8–10). Given both the fi ndings and limits of studies to date that look at the various impacts of migraine, the current research was conducted to assess the following variables before and after treatment in a specialized tertiary headache treatment center: 1) changes in episodic and chronic migraine headache attributes; 2) changes in quality of life as measured by patient MIDAS scores; 3) changes in healthcare utilization and costs; and 4) changes in patient absenteeism and presenteeism at work and in family and community functions.

METHODSParticipants were treated at a tertiary headache center at a

large teaching hospital. Th e inpatient program as well as the

Migraine disability, healthcare utilization, and expenditures following treatment in a tertiary headache centerFrederick G. Freitag, DO, Heidi Lyss, MBA, and George R. Nissan, DO

Proc (Bayl Univ Med Cent) 2013;26(4):363–367

connected outpatient program provide comprehensive multi-disciplinary assessment and treatment. Th e patient’s diagnosis was determined by the treating physician, without necessar-ily aligning with the International Classifi cation of Headache, while treatment setting and specifi c treatments were determined by the clinician with the patient. Diagnoses included in this study were episodic migraine and chronic migraine, with and without medication overuse. Specifi c medical therapies were not evaluated separately.

Patients selected for outpatient treatment were provided with acute and preventive medications for their headaches. Th ey were instructed in lifestyle modifi cation and were off ered a va-riety of nonpharmacologic strategies as part of comprehensive treatment. Not all patients treated on an outpatient basis were provided with a full array of nonpharmacologic strategies due to limited access to care for some of these services. Patients treated as inpatients not only received acute and preventive medica-tions, but also were discontinued from other acute medications that had been causing medication overuse headache. Th is dis-continuation has been demonstrated to play a signifi cant role in treatment outcome (11–13). Inpatients were treated with intravenous dihydroergotamine and given additional adjunc-tive intravenous medications based on their clinical situation in order to break their headache cycle. In addition to receiving the educational component as did the outpatient group, in-patients were evaluated by psychological services, underwent counseling, and received behavioral interventions including biofeedback, physical therapy, and dietary education. Many of these services were provided during their hospitalization, and some were continued following the patient’s discharge to the outpatient setting.

All new patients to the center were invited to participate in the study. Th ese patients came to the tertiary headache center from a range of geographic locales around the United States. Th ose who expressed interest in participating provided written informed consent using a form approved by the hospital insti-tutional review board. Five hundred consecutive new patients to the clinic were included in this evaluation process. Enrollment occurred on a continuing basis over a period of approximately 6 months. Of the 500 patients approached to participate in this study, 371 completed the fi rst phase of the data collection and 294 completed the follow-up phase of the data collection (Figure 1).

Th e fi rst phase of data collection consisted of a series of self-reported questionnaires regarding headache traits, prior treatments, use of healthcare resources related to headaches and general health, and associated expenses incurred, includ-ing both out-of-pocket and insurance-reimbursed expenses. In addition, participants were required to complete a MIDAS survey for the prior 3 months before their fi rst visit, and their resulting score was used to assess their headache frequency. Th e data from the healthcare utilization questionnaires examined the 6 months prior to their fi rst visit to the tertiary headache center. In addition they were informed that they would be asked to complete a similar assessment following their initial assessment and treatment at the center. Th e second phase was

conducted at least 3 months and less than 6 months after completion of the patient’s fi rst treatment program at the clinic and/or in the inpatient treatment unit. Th e fi nal col-lection of data occurred approximately 1 year after the fi rst patient was enrolled.

Patient data were blinded to the physician reviewer through a numeric code assigned to each patient. An administrator of the center maintained the log of the patients, their contact information, and their assigned numeric codes. All data were entered into an Excel spreadsheet by the center administrator and provided to the physician reviewer.

RESULTSTh e total population that provided complete data consisted

of 294 patients; 94 of these patients had episodic migraine diagnoses, 153 had chronic migraine diagnoses, and 47 had other headache diagnoses, such as tension-type headache, cluster headache, and posttraumatic headache, representing a hetero-geneous group that provided too few patients with any one diagnosis to provide meaningful assessment. Th eir data, while included in the data set comparing inpatient versus outpatient treatment groups (Table 1), were not further examined as a separate group in this study.

Patients’ initial data demonstrated that they had headaches on more days than not and had MIDAS scores far in excess of the MIDAS score range used to describe patients as sig-nifi cantly disabled. Patients were seen by their prior treating physician an average of once per month. Emergency depart-ment utilization averaged at least one visit every 6 months, and an inpatient treatment in the patient’s home locale had occurred an average of once every 2 years. Estimated healthcare expenditures averaged more than $10,000 per year. Follow-ing treatment at the tertiary level, signifi cant reduction in

Figure 1. Subject enrollment outcomes.

500 patients signed informed consent and provided initial demographic data

371 provided initial utilization and

expenditure data 100 were lost to follow-up

29 withdrew consent

247 patients with migraine or chronic migraine diagnoses completed

follow-up data collection

47 patients with other headache diagnoses

completed follow-up data collection

94 with episodic migraine diagnoses

153 with chronic migraine diagnoses

77 patients with migraine or

chronic migraine diagnoses did not complete

follow-up data collection

Baylor University Medical Center Proceedings Volume 26, Number 4364

healthcare utilization occurred broadly and robustly in both the inpatient group and outpatient group, aside from the fi nd-ing that inpatient readmission occurred more frequently in those who were initially treated at the tertiary care center as inpatients (Table 1).

Th e migraine population of patients in the study represented a group with more signifi cant frequency of migraines—an aver-age of 17 days per month—compared to the US population, with its average of approximately 2 headache days per month. Even the episodic migraine group treated at the tertiary head-ache center on an outpatient basis averaged 23.2 headache days for the 3 months prior to their fi rst visit to the center, roughly half the average number of headache days experienced by a typi-cal new patient to the center who was admitted for inpatient treatment of episodic migraine. Th e episodic migraine group overall was somewhat younger on average and less prone to comorbid diseases, with a shorter headache history of 12.5 years compared with 15.3 years for the chronic migraine population. During the 90 days prior to initial treatment at the tertiary cen-ter, the outpatient episodic migraine group not only experienced 50% fewer headache days than the inpatient migraine group, but also had approximately 50% lower MIDAS scores, one third the emergency department visits, and one fi fth the prior hospital admissions compared with the group treated by the center as inpatients. Following initial treatment, the inpatient migraine group realized more robust reductions in healthcare costs (–47%), physician visits (–73%), emergency department visits (–80%), and subsequent inpatient care (–88%) than the outpatient treatment group (–22%, –6%, –12%, and +510%, respectively). Th e mean length of initial hospitalization was 7.4 days, and its costs were included in the posttreatment assess-ment. Subsequent hospital admissions increased substantially in the outpatient group (Table 2).

About half of the patients with chronic migraine were diag-nosed with concomitant medication overuse (Table 3), whether they initiated treatment in the outpatient or inpatient setting

at the tertiary headache center. Th ose with chronic migraine without medication overuse were treated at the center as out-patients approximately half as often as they were treated as inpatients. By contrast, those with medication overuse headache with chronic migraine were twice as likely to be treated as outpa-tients since many migraines with medication overuse are not toxic and outpatient bridge treatments can be eff ective for transition of this condition. All four groups were close in mean age and frequency of comorbid medical illnesses. Chronic migraine pa-tients with medication overuse tended to have a longer history of disease than chronic migraine patients without medication overuse. Headache days per 3 months prior to the initial visit and MIDAS scores were highest in the population with medica-tion overuse, regardless of treatment setting. Th ese same patients had the greatest reduction in these same parameters over the evaluation period. Physician and emergency department visits declined by roughly the same level of magnitude in all treat-ment groups. Hospital admissions decreased by roughly 50% in those with chronic migraine without medication overuse headache who were treated as outpatients and in those with medication overuse who were treated as inpatients. Conversely, a signifi cant increase in readmissions occurred in the other two chronic migraine groups.

Healthcare costs changed to only a limited degree in patients with chronic migraine, with the exception of those chronic mi-graine patients with medication overuse who were treated in a multidisciplinary inpatient unit. For this group, post-inpatient treatment costs declined by one third from pretreatment costs. Overall, healthcare costs were 2 to 3 times higher in patients with medication overuse as compared to the non–medication overuse chronic migraine population.

DISCUSSIONTh e burden of migraine and chronic migraine has been dem-

onstrated in the American Migraine Prevalence and Prevention Study. Despite this result, these disorders receive little in the way

Table 1. Patient characteristics and outcome data for migraine treatment for all patients, treated in both inpatient and outpatient settings

Parameter All inpatient initial treatment All outpatient initial treatment

Number of patients 116 178

Age (mean in years) 48.9 49.3

Number of comorbid medical illnesses 2.54 1.48

Headache disease duration (years) 14.2 14.6

Pretreatment Posttreatment Change Pretreatment Posttreatment Change

Cost/6-month period $6698 $4384 –34.5% $5484 $4290 –21.8%

Number of headache days/3 months 56.6 42.4 –25.1% 47.2 35.7 –24.4%

MIDAS 83.4 27.1 –67.5% 77.1 14.9 –80.7%

Number of MD visits for headache/6 months 6.58 1.36 –79.3% 6.18 1.31 –78.8%

Number of ED visits for headache/6 months 1.65 .53 –67.9% 1 .73 –27%

Number of inpatient admissions/6 months 0.29 .37 +27.6% .26 .18 –30.7%

MIDAS indicates Migraine Disability Assessment Score; MD, physician; ED, emergency department.

Migraine disability, healthcare utilization, and expenditures following treatment in a tertiary headache center 365October 2013

of specifi c acute and appropriate levels of preventive care (14). Th e signifi cance of this absent or insuffi cient care, even in the episodic migraine population, has been underrecognized. Th e direct costs for migraine are expected to exceed $11 billion an-nually and be over $2500 per person with migraine compared to matched controls (14). Th e Aff ordable Care Act will require delivery of quality care in a cost-eff ective manner. One issue that is rarely considered in this process is the burden on the employer and employee in lost time and productivity related to the disorder. Migraines cost employers $2444 per year per patient for women in their peak productive years who have episodic migraine, and

over $7100 per year for those with chronic migraine. In men, this increases to over $4100 per year per patient with episodic migraine and almost $13,000 per year for chronic migraine (15). As with many disorders, the greatest costs of treatment will be for a small percentage of patients who have frequent headache and poor response despite being provided with the best-evidence treatments. In the present study, we have demonstrated that there are patients who have realized substantial benefi ts from treatment in the tertiary setting. Th ese improvements have been realized in parameters of headache frequency, disability, healthcare utiliza-tion, and the costs of that care.

Table 2. Patient characteristics and outcome data for patients with episodic migraine, treated in both inpatient and outpatient settings

Parameter Inpatient initial treatment Outpatient initial treatment

Number of patients 25 69

Age (mean in years) 46 47

Number of comorbid medical illnesses 2.2 2.1

Disease duration (years) 9.9 13.5

Pretreatment Posttreatment Change Pretreatment Posttreatment Change

Cost/6 months $4787 $2531 –47% $2468 $1928 –21.8%

Number of headache days/3 months 47.2 43 –8.9% 23.2 19.9 –14.2%

MIDAS 82.1 42.8 –47.9% 43.8 8.9 –79.7%

Number of MD visits/6 months 8.8 2.42 –72.5% 3.5 3.3 –5.7%

Number of ED visits/6 months 1.68 .33 –80.3% .59 .52 –11.8%

Number of inpatient admissions/6 months .48 .06 –87.5% .1 .61 +510%


Table 3. Patient characteristics and outcome data for patients with chronic migraine, with or without medication overuse headache, treated in both inpatient and outpatient settings

Parameter

Chronic migraine without medication overuse Chronic migraine with medication overuse

Outpatient treatment Inpatient treatment Outpatient treatment Inpatient treatment

Number of patients 27 46 57 23

Age (years) 48 50 52 50

Comorbid medical disorders 2.8 2.8 2.7 2.8

Disease duration 14 14 15.9 18

Pre-treatment

Post -treatment

% Change

Pre-treatment

Post -treatment

% Change

Pre-treatment

Post -treatment

% Change

Pre-treatment

Post -treatment

% Change

Cost/6 months 2724 2646 –2.8% 3677 3518 –0.4% 7859 7529 –4.2% 6671 4502 –32.5%

Headache days/3 months 54.4 48.1 –11.5% 59.2 53.3 –9.9% 75.5 49 –35.1% 65 23 –64.6%

MIDAS 55.1 27.6 –49.9% 83 39.6 –53.4% 123.9 25.4 –79.5% 91 21.5 –76.4%

MD visits/6 months 5.18 .56 –89.2% 6.8 1.27 –81.3% 10 1.88 –81.2% 7.9 2.8 –64.5%

ED visits/6 months 1.27 .38 –70.3% 1.41 .63 –55.3% 1.79 .95 –46.9% 1.38 .4 –71%

Inpatient admissions/6 months .42 .18 –57.1% .26 .81 +211% .51 .72 +41% .48 .2 –58.3%



Th is study suff ers from issues that create some challenges in evaluation, including patients lost to follow-up and verifi able ac-curacy of fi nancial reporting data. Second, the diagnoses assigned to the patients were clinically applied and hence did not neces-sarily meet the International Headache Classifi cation criteria. Another issue relates to the nature of the comorbidities and the failure to secure behavioral or psychiatric diagnoses as part of these comorbidities. A study by Lafata and colleagues suggested that the diagnosis of depression as comorbidity to headache may be a driver of the costs of healthcare delivery in these patients (16). In addition, specifi c data regarding neuroradiological services were not collected. Lastly, while we have obtained an appreciation of the disease duration of headache and some of the issues that might impact response to treatment, we did not collect detailed data to assess for the extent and quality of care of patients prior to initiation of tertiary headache care.

Comprehensive programs for episodic migraine appear from our fi ndings to be eff ective in positively impacting multiple headache parameters for patients. Th ese patients as a whole, regardless of treatment setting, experienced signifi cant reduction in healthcare utilization. A decrease in MIDAS score results in a substantial reduction in disability parameters. Regardless of the diagnosis or how refractive the patient’s headache has been to previous treatments, it is likely that patients would benefi t from tertiary care and realize decreased disability, fewer headache days, and lower healthcare utilization after treatment.

Patients initially treated as inpatients, while improving across the various parameters in similar levels of magnitude compared to the outpatient group, never “caught up” with the outpatient group over the time frame of evaluation. Rather, they had improvements that led them to resemble the baseline for the outpatient group.

Th e chronic migraine groups were on average older, with more comorbid medical disorders and a longer average dura-tion of disease than that found in the episodic migraine groups. Th ose with medication overuse were again older and with longer disease duration than those without medication overuse. Pa-tients with chronic migraine without medication overuse were more closely aligned with the episodic migraine groups, though again they had a tendency to have higher service utilization, MIDAS scores, and costs of care than the episodic group. With treatment, however, this group tended to resemble a composite of the episodic migraine groups. Th ose patients with chronic migraine with medication overuse and those with chronic mi-graine without medication overuse who were treated initially as inpatients tended to have headache days, MIDAS scores, healthcare utilization, and costs of healthcare higher than any of the other groups and to realize smaller declines in healthcare costs with tertiary treatment.

Factors such as patient compliance with the program over the extended course were not evaluated as part of this study, but have been shown to be a critical factor in the potential to reverse

the course of a chronic disorder such as high-frequency mi-graine (17). Ongoing assessment of treatment programs, patient selection, and evaluation of other therapeutic and diagnostic issues may aff ord greater clarity and guidance to the process of optimizing treatment outcomes in a cost-eff ective manner.

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14. Hawkins K, Wang S, Rupnow M. Direct cost burden among insured US employees with migraine. Headache 2008;48(4):553–563.

15. Serrano D, Manack AN, Reed ML, Buse DC, Varon SF, Lipton RB. Cost and predictors of lost productive time in chronic migraine and episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Value Health 2013;16(1):31–38.

16. Elston Lafata J, Moon C, Leotta C, Kolodner K, Poisson L, Lipton RB. Th e medical care utilization and costs associated with migraine headache. J Gen Intern Med 2004;19(10):1005–1012.

17. Seok JI, Cho HI, Chung CS. From transformed migraine to episodic migraine: reversion factors. Headache 2006;46(7):1186–1190.

Migraine disability, healthcare utilization, and expenditures following treatment in a tertiary headache center 367October 2013

To have a better understanding of our patients’ knowledge of advance

directive planning and execution, as well as communication with their

oncologists regarding their wishes, we conducted a survey on our in-

patient hematology-oncology services. A total of 68 unique hospitalized

patients with a diagnosis of cancer completed surveys. Surveys were

given to all oncology patients regardless of their reason for admission.

Overall, 29% of the patients reported having had a discussion with their

oncologist regarding their wishes if they became seriously ill or near

death. Of those who did have this conversation, the majority said that

they, rather than their physician, initiated it. Although the vast majority

of patients (97%) knew what a living will was, only 54% had one in

place. Twenty patients had a discussion with their oncologist, and 14

of them (70%) had a living will. This percentage was higher than in the

group that did not have a conversation with their physician (48%; 23

of 48 patients), but the difference was not statistically significant. Most

cancer patients admitted to an inpatient oncology unit either did not have

or did not recall having a discussion with their oncologist regarding end-

of-life issues. This study gives us a baseline of information in evaluating

future interventions directed to improve the quality of patient-physician

communication regarding end-of-life planning.

The diagnosis of cancer provides challenges to patients, their families, and their medical providers. Initially, the objective for medical oncologists is to fi nd a cure or at least a treatment to reduce symptoms and prolong sur-

vival of their patients. Having a discussion about an advance directive (AD) or end-of-life (EOL) issues with patients at this time may seem counter-intuitive to physicians. More impor-tantly, it may be seen by patients as a confi rmation of their fear that they are going to die from this disease. Many times this conversation is avoided until the disease progresses or is refrac-tory, or the conversation never occurs.

Ideally individuals should have suffi cient time to think about and discuss these issues with health care providers and others long before they have a life-threatening disease. Th e 2005 Gallup Public Opinion Poll reported that 40% of Americans over age 18 had a living will (1). Various other public opinion polls report fi gures of 25% to 40%. In a survey of primary care physicians in Northeast-ern Ohio, 97.5% of physicians reported comfort with discussing advance care planning, yet reported having those discussions with

From the Baylor Charles A. Sammons Cancer Center (Stone, Shuey, Miller), the

Department of Quantitative Sciences (Barnes), and the Department of Internal

Medicine (Casanova), Baylor University Medical Center at Dallas. Dr. Barakat is

now at the Tulsa Cancer Institute, Tulsa, Oklahoma.

Corresponding author: Alan M. Miller, MD, PhD, Baylor Sammons Cancer Center,

Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX 75246


only 43% of appropriate patients (2). Th us, even though health care providers understand the benefi t of EOL discussions with their patients, they initiate such discussions less than half the time.

Oncology patients have a relatively high chance of dying from their disease, yet a national survey of physicians caring for cancer patients concluded that most physicians did not discuss EOL options until symptoms were signifi cant and/or there were no further treatment options (3). A recent study by Zhang et al of 603 patients with advanced cancer reported that only 31% of pa-tients had EOL discussions with their physicians (4). In that study EOL discussions were associated with signifi cantly lower health care costs in the fi nal week of life. Th e majority of cancer patients surveyed in one German study wanted their physician to initiate a discussion about writing an AD only if their physician thought it appropriate (5). Almost 80% of physicians in that study thought that they should initiate the discussion if appropriate, but only 17% thought it should be a routine matter as compared to 27% of the patients and 46% of healthy controls.

Another study of patients admitted to a hematology-oncol-ogy inpatient service in Virginia provided information about their preferences and attitudes toward AD and which physicians they preferred to host the discussion (6). Of the 75 patients enrolled in the study, nearly all (95%) thought that discussing an AD was very or somewhat important, but only 41% had an existing AD. When asked which physician they would prefer to discuss AD with if it were necessary, 48% indicated their oncologist—but only 7% of the patients actually had this dis-cussion with their oncologist. In a report by Mack et al in a study of over 2000 patients with stage IV lung or colorectal cancer, 73% had EOL discussions identifi ed by at least one source; however, oncologists documented EOL discussion with only 27% of their patients (7).

We conducted a survey on the hematology-oncology in-patient service at Baylor University Medical Center at Dallas

Advance care planning knowledge and documentation in a hospitalized cancer populationAyman Barakat, MD, Sunni A. Barnes, PhD, Mark A. Casanova, MD, Marvin J. Stone, MD, Kathleen M. Shuey, MS, RN, and Alan M. Miller, MD, PhD


regarding AD and patient-physician communication. Th e pur-pose of the survey was to establish baseline information to use to evaluate the eff ectiveness of future interventions regarding AD and EOL planning.

METHODSFrom September 2011 to May 2012, inpatients in the on-

cology and blood and marrow transplantation units at Baylor University Medical Center at Dallas were surveyed to determine the frequency and eff ectiveness of EOL discussions between patients and their oncologists. Surveys were given to all oncology patients regardless of the reason of their admission, excluding only those who were unable to speak English and those in any type of medical isolation.

A printed questionnaire with 26 questions was created and distributed (Table 1), along with a cover letter explaining the project. In addition, one of the research nurses verbally ex-plained the project to each patient. After completing the survey, patients placed it in an envelope, sealed it, and returned it to a nurse. Completed surveys were collected on a weekly basis.

Approval for the study was obtained from the Baylor Uni-versity Medical Center at Dallas institutional review board. Th e surveys had no patient-identifying information; therefore, the results were anonymous.

Univariate analysis was performed using χ2 tests, and mul-tivariate analysis was done using logistic regression with Proc Logistic. Th e SAS statistical analysis system (SAS Institute Inc., Cary, NC) was used for data analysis. Statistical signifi cance was defi ned as P < 0.05 with a two-tailed test. Categorical variables were expressed as percentages and continuous variables as mean ± SD, unless otherwise stated.

RESULTSSurveys were distributed to 100 oncology patients, and 91

completed surveys were returned. Twenty-three patients submit-ted more than one survey over diff erent hospital admissions, and only their original survey data were included in the primary analysis.

Th ere was a balance of patients by gender: 46% were women and 54% were men (Table 2a). About 74% of the sample was in the age group of 50 to 69 years. Of the patients responding, 47 had a blood cancer diagnosis, while the others either had a solid tumor diagnosis or were unsure of their diagnosis. A further breakdown of tumor types is included in Table 2a; information on the stage of disease or treatment type was not collected.

One of the most important factors in designing this study was to assess the frequency with which our oncologists were having EOL discussions with their patients. Even though the patients were of variable ages and diagnoses, only 29% (n = 20) of the patients indicated that they had had a conversation with their oncologist regarding their EOL wishes. Women re-ported having this conversation slightly more often than men (35% vs 24%, P = 0.42), but the diff erence was not signifi cant. Similarly, patients over the age of 60 reported having an EOL discussion more often than younger patients (36% vs 22%, P = 0.29), but again, the diff erence was not signifi cant. Finally, the

percentage of patients who reported having a conversation with their oncologist was not statistically diff erent between those with a blood cancer versus a solid tumor (28% vs 33%).

Out of the 20 patients who had a discussion with their oncologist, 12 patients (60%) said they, not their doctor, initi-ated the discussion. As shown in Table 2b, 16 or the 20 patients (80%) agreed or strongly agreed that their treating oncologist was comfortable having a discussion on EOL issues; 3 (15%) responded neutral, and only one person strongly disagreed with this statement. None of the patients who had an EOL discussion with their oncologist felt uncomfortable having this discussion, and none were dissatisfi ed with the amount of time they spent having this discussion. Most patients who took the survey stated

Table 1. Survey items to determine factors associated with advance care planning in a hospitalized cancer population

1. Location/unit name

2. Have you completed this questionnaire before?

3. Cancer diagnosis

4. Date of diagnosis (month and year)

5. Gender

6. Current age

7. Have you ever had a discussion with your oncologist regarding your

wishes when you become very ill or close to dying?

8. Did they initiate it, or did you?

9. My oncologist was comfortable having this discussion.

10. I was comfortable having this discussion with my oncologist.

11. I was satisfied with the amount of time my oncologist spent having this

discussion with me.

12. Have you had a discussion with any other health care provider(s)

regarding your wishes when you become very ill or dying?

13. How often do you visit your treating oncologist?

14. How often do you visit your primary care provider?

15. Describe your relationship with your treating oncologist.

16. Describe your relationship with your primary care provider.

17. I trust my treating oncologist.

18. I trust my primary care provider.

19. I am comfortable asking my treating oncologist questions regarding my

care.

20. I am comfortable asking my primary care provider questions regarding

my care.

21. My treating oncologist encourages me to ask questions related to my

care.

22. My primary care provider encourages me to ask questions related to

my care.

23. My treating oncologist explained why I was admitted to the hospital in a

way I could understand.

24. Do you know what a living will is?

25. Do you have a living will or an advance directive?

26. Please enter today’s date.

Advance care planning knowledge and documentation in a hospitalized cancer population 369October 2013

they had a good to a very good relationship with their treat-ing physician, and over 90% of the patients felt comfortable asking their doctors questions regarding their treatment and care. Almost all the patients said they were encouraged by their oncologist to ask questions related to their care. Interestingly, although the majority of patients (96.9%) knew what a living will was, only 53.9% had one at the time of the survey.

Seventy-one percent of those who had a discussion with their oncologist also reported that they had a living will or other AD versus 48% among those who did not have a discussion with their oncologist (P = 0.16). Of those patients who had a discussion with either their oncologist or another provider, 70% stated that they had a living will, while 45% did not (P = 0.73).

We did fi nd that older patients (over 60 years) were more likely to have a living will or other AD: 67% in the over-60 group vs 40% in the <60 age group (P = 0.05). Th ere was not a diff erence in the percentage having a living will based on cancer type (solid vs blood) or gender. In a multivariate logistic model, age >60 years was the only patient characteristic that was signifi cantly associated with having a living will or AD (odds ratio 2.98; 95% confi dence interval [1.02, 8.67]). No additional variables listed in Table 3 were signifi cant in this model.

DISCUSSIONTh e results of our survey showed a slightly higher percentage

of patients (54%) with an AD compared with other reports.

Table 2. Key survey responses from oncology inpatients related to factors associated with advance care planning

2a. Demographic variables Level % (n)

Gender Male 54.4% (37)

Female 45.6% (31)

Age 20–29 4.4% (3)

30–39 7.4% (5)

40–49 2.9% (2)

50–59 32.4% (22)

60–69 41.2% (28)

>70 11.8% (8)

Cancer diagnosis Blood cancer 69.1% (47)∗

Solid tumor 30.9% (21)†

Frequency of visits with their treating oncologist >Weekly 52.5% (31)

Monthly 37.3% (22)

~Every 3 months 5.1% (3)

<Every 3 months 5.1% (3)

No response (9)

2b. Patient-physician relationship questions for the 20 patients who had a conversation with their oncologist regarding end-of-life wishes Positive Neutral Negative

My oncologist was comfortable having this discussion. 80% 15% 5%

I was comfortable having this discussion with my oncologist. 90% 10% 0%

I was satisfied with the amount of time my oncologist spent having this discussion with me. 89% 11% 0%

I trust my treating oncologist. 98% 2% 0%

I trust my primary care provider. 83% 11% 6%

I am comfortable asking my treating oncologist questions regarding my care. 100% 0% 0%

I am comfortable asking my primary care provider questions regarding my care. 92% 5% 3%

My primary care physician encourages me to ask questions related to my care. 77% 16% 7%

My treating oncologist encourages me to ask questions related to my care. 97% 3% 0%

My treating oncologist explained why I was admitted to the hospital in a way I could understand. 98% 2% 0%

∗ Lymphoma, 14; multiple myeloma, 6; acute myeloid leukemia, 11; acute lymphoblastic leukemia, 2; chronic lymphocytic leukemia, 4; leukemia not otherwise specified, 7;

myelodysplastic syndrome, 3.

†Colon, 3; liver, 3; melanoma, 2; breast, 2; pancreas, 2; lung, renal cell, gastrointestinal stromal tumor, 1 each; unknown or unspecified, 6.


Various reports show that between 25% and 40% of the general population has living wills or other AD (1, 2, 4). In a study of oncology inpatients in a Virginia teaching hospital, 41% had an AD. In a study of cancer patients in a Veterans Adminis-tration Hospital, 47% had a documented AD, and 81% had some documentation in their chart that referred to their EOL preferences (8).

Our survey demonstrated a trend to a higher likelihood of having an AD for those patients who have had a discussion with their oncologist and/or other health care provider. Only a minority of our patients (29%) had an EOL discussion with their oncologist, and these results were similar to the 31% reported by Zhang et al (4). In addition, patients who had a discussion with their oncologist reported feeling comfortable with the discussion and the length of the conversation. In the report of the Virginia patients, only 7% reported having an AD discussion with their oncologist; moreover, only 23% said they would like to discuss AD with their oncologist (5). When Snyder and colleagues surveyed primary care physicians regarding their understanding of and experience with advance care planning (2), they found that only 43% reported having those discussions with the appropriate patients; 44% felt that the discussions took too much time, and most felt that the appropriate time to have the conversation was in the estimated last 6 months of life (6). Th e inclusion of other specialists and mid-level providers may help overcome the time constraints that some physicians face.

Th is study has a few limitations that must be acknowledged. As with all surveys, the fi ndings are self-reported, and a con-venience sample of patients willing to par-ticipate was used. Information on stage or current treatment was not requested. Keating et al reported that many physicians delayed EOL discussions until there was symptom-atic progression and/or limited options (3). We do not have suffi cient data to judge if that occurred with our patients. Our popu-lation included patients undergoing blood and marrow transplants for hematologic malignancy, patients with complications of chemotherapy, as well as patients with advanced-stage disease. In addition, our inpatient population may be quite diff er-ent from that of a usual cancer outpatient population or many inpatient populations. We see a high percentage of patients with malignancies of the hematologic system, and many undergo autologous and allogeneic blood stem cell transplantation with curative intent. A smaller percentage of the patients surveyed had solid malignancies. Although no signifi cant diff erences were seen between patients with hematologic versus solid tu-mor malignancies, we did fi nd that a higher percentage of patients with blood malignan-

cies had an AD. Due to the small sample size, there is a lack of statistical power for subgroup analysis for many of the compari-sons presented. However, the counts and percentages are shown so readers can conclude for themselves the clinical relevance of the diff erences seen in this study.

Although we do not have the information, it is likely some patients in our study were admitted with end-stage disease. In the report by Mack et al, all patients had advanced solid tumor malignancies. In that study, oncologists documented EOL discussion with only 27% of their patients, but over 70% had EOL care discussions identifi ed by at least one source (7). Th e percentage reporting discussions with their oncologist was similar to our fi ndings; in contrast, in our population few of the patients reported having such a conversation with another health care provider. Th is may refl ect diff erences in involvement of palliative care teams or other providers. Th e one factor in our population that reached statistical signifi cance was age, with a higher percentage of those over 60 having had an EOL discus-sion compared to the younger patients. Th is is consistent with trends in the general population, with the likelihood of having a living will increasing with age (1).

Unfortunately, there is little formal training available for physicians regarding EOL discussions. A study done at Duke University Medical Center involved having medical residents take part in a short intensive course to improve communica-tion with patients at the end of their life. Th e group of resi-dents who participated in the course demonstrated signifi cant

Table 3. Percentage of inpatient oncology patients with a living will based on various factors

Variable

Patients with a living will or

advance directive∗P

value

Had a discussion with their oncologist Yes

No

71% (12/17)

48% (23/48)

0.16

How often visited oncologist Weekly or more often

Less than weekly

66% (19/29)

41% (11/27)

0.11

Had a discussion with either their

oncologist or another health care

provider

Yes

No

70% (16/23)

45% (19/42)

0.07

Age <60

≥60

40% (13/32)

67% (22/33)

0.05

Cancer type Solid tumor

Blood

40% (8/20)

60% (27/45)

0.18

Gender Male

Female

58% (21/36)

48% (14/29)

0.46

Relationship with oncologist Very good

<Very good

60% (27/45)

40% (8/20)

0.14

Relationship with primary care

physician

Very good

<Very good

57% (17/30)

51% (18/35)

0.67

∗Numbers in parentheses show the number answering that they had a living will or advance directive over the total

number answering the question. Three individuals who answered the variable question did not answer whether or

not they had a living will or advance directive.

Advance care planning knowledge and documentation in a hospitalized cancer population 371October 2013

increases in their overall skill ratings in the delivery of bad news as compared to a control group of residents, and the patients of the residents involved in the course reported greater trust in their oncologists than did the patients of control oncologists (9). Others have reported similar benefi ts following interven-tions to improve physician communication. Fallowfi eld et al showed that British oncologists attending a 3-day intensive communications skills seminar demonstrated signifi cant im-provement (10); similar interventions with oncology nurses also yielded positive results (11). Th rough interventions based on our survey fi ndings, we hope to improve the frequency and quality of EOL discussions. Twelve domains of physicians’ skills were defi ned by focus groups of patients, family mem-bers of those who died with a chronic disease, and health care workers. Th e domains may provide a framework to focus on physicians’ skill at providing high quality EOL care (12). Such a framework presents essential skills for oncologists—both those in training and those in practice—to attain to better serve their patients.

It has been shown that in the last week of life, advanced cancer patients who reported having an EOL discussion with physicians had signifi cantly lower health care costs. Higher costs were associated with worse quality of death (4). A recent report documented that EOL care for Medicare benefi ciaries varies widely and is highly intensive, and these fi ndings are exhib-ited over a wide spectrum of hospital classifi cations (13). Our fi ndings indicate that more needs to be done to ensure that patients with cancer have timely discussions regarding EOL discussions and that they have understood the information provided. Th is will involve eff orts of their oncologists as well as other members of the health care team, to include palliative care practitioners and oncology mid-level providers. Temel et al has reported that non–small cell lung cancer patients who had early palliative care consultation had a more accurate assessment of their prognosis (14). Utilizing the information gathered in this study as a baseline, further quality improvement endeavors will be developed and implemented. Specifi cally, we will use the information obtained in this patient survey to evaluate future eff orts to improve EOL discussions and AD planning. Eff orts will include implementation of programs designed to improve physicians’ communication skills around EOL discussions and greater incorporation of palliative care and other providers, in-cluding mid-level providers, to complement the oncologist’s role in providing information to patients. Even though patients who had discussions with the oncologist reported comfort on their part and that of the oncologist, this represented only 30% of the patients surveyed. Th e survey did not address the physician perspective, but by providing increased awareness, better tools,

and additional resources, it is hoped that more oncologists will address these issues with their patients. Our philosophy is to bring all available measures to bear in order to further advance the necessary and appropriate components of advance care planning in the oncology setting.

1. Gallup AM, Newport F, eds. Th e Gallup Poll: Public Opinion 2005. Lanham, MD: Rowman and Littlefi eld, 2006.

2. Snyder S, Hazelett S, Allen K, Radwany SM. Physician knowledge, attitude, and experience with advance care planning, palliative care, and hospice: results of a primary care survey. Am J Hosp Palliat Care 2012 Jul 12 [Epub ahead of print].

3. Keating NL, Landrum MB, Rogers SO Jr, Baum SK, Virnig BA, Huskamp HA, Earle CC, Kahn KL. Physician factors associated with discussions about end-of-life care. Cancer 2010;116(4):998–1006.

4. Zhang B, Wright AA, Huskamp HA, Nilsson ME, Maciejewski ML, Earle CC, Block SD, Maciejewski PK, Prigerson HG. Health care costs in the last week of life: associations with end-of-life conversations. Arch Intern Med 2009;169(5):480–488.

5. Sahm S, Will R, Hommel G. What are cancer patients’ preferences about treatment at the end of life, and who should start talking about it? A comparison with healthy people and medical staff . Support Care Cancer 2005;13(4):206–214.

6. Dow LA, Matsuyama RK, Ramakrishnan V, Kuhn L, Lamont EB, Lyckholm L, Smith TJ. Paradoxes in advance care planning: the complex relationship of oncology patients, their physicians, and advance medical directives. J Clin Oncol 2010;28(2):299–304.

7. Mack JW, Cronin A, Taback N, Huskamp HA, Keating NL, Malin JL, Earle CC, Weeks JC. End-of-life care discussions among patients with advanced cancer: a cohort study. Ann Intern Med 2012;156(3):204–210.

8. Ahluwalia SC, Chuang FL, Antonio AL, Malin JL, Lorenz KA, Walling AM. Documentation and discussion of preferences for care among patients with advanced cancer. J Oncol Pract 2011;7(6):361–366.

9. Alexander SC, Keitz SA, Sloane R, Tulsky JA. A controlled trial of a short course to improve residents’ communication with patients at the end of life. Acad Med 2006;81(11):1008–1012.

10. Fallowfi eld L, Jenkins V, Farewell V, Saul J, Duff y A, Eves R. Effi cacy of a Cancer Research UK communication skills training model for oncologists: a randomised controlled trial. Lancet 2002;359(9307):650–656.

11. Razavi D, Delvaux N, Marchal S, Bredart A, Farvacques C, Paesmans M. Th e eff ects of a 24-h psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study. Eur J Cancer 1993;29A(13):1858–1863.

12. Curtis JR, Wenrich MD, Carline JD, Shannon SE, Ambrozy DM, Ramsey PG. Understanding physicians’ skills at providing end-of-life care per-spectives of patients, families, and health care workers. J Gen Intern Med 2001;16(1):41–49.

13. Morden NE, Chang CH, Jacobson JO, Berke EM, Bynum JP, Murray KM, Goodman DC. End-of-life care for Medicare benefi ciaries with cancer is highly intensive overall and varies widely. Health Aff (Millwood) 2012;31(4):786–796.

14. Temel JS, Greer JA, Admane S, Gallagher ER, Jackson VA, Lynch TJ, Lennes IT, Dahlin CM, Pirl WF. Longitudinal perceptions of progno-sis and goals of therapy in patients with metastatic non-small-cell lung cancer: results of a randomized study of early palliative care. J Clin Oncol 2011;29(17):2319–2326.


373Proc (Bayl Univ Med Cent) 2013;26(4):373–375

Patients undergoing coronary artery bypass surgery and/or heart valve

surgery using a median sternotomy approach coupled with the use of

cardiopulmonary bypass often experience pulmonary complications in

the postoperative period. These patients are initially monitored in an

intensive care unit (ICU) but after discharge from this unit to the ward

they may still have compromised pulmonary function. This dysfunction

may progress to significant respiratory failure that will cause the patient

to return to the ICU. To investigate the severity and incidence of respira-

tory insufficiency once the patient has been discharged from the ICU to

the ward, this study used transcutaneous carbon dioxide monitoring to

determine the incidence of unrecognized inadequate ventilation in 39

patients undergoing the current standard of care. The incidence and

severity of hypercarbia, hypoxia, and tachycardia in post–cardiac surgery

patients during the first 24 hours after ICU discharge were found to be

high, with severe episodes of each found in 38%, 79%, and 44% of

patients, respectively.

Respiratory complications after cardiac surgery have been shown to result in prolonged hospital length of stays and increased costs of care (1, 2). A retrospective review of these patients at our institution demonstrated a 5% to

10% early intensive care unit (ICU) readmission rate with the main diagnosis of respiratory failure. If the patients at risk could be identifi ed by better monitoring, perhaps an earlier interven-tion could be made that would prevent the need to return to the ICU and the increased costs involved. To that end, this prospec-tive observational study analyzed the adequacy of ventilation and oxygenation by measuring transcutaneous carbon dioxide (tcpCO2) and peripheral hemoglobin saturation (SpO2) when the postoperative cardiac surgery patient was initially admitted to the ward from the ICU.

METHODSInstitutional review board approval was obtained at Baylor

University Medical Center at Dallas to enroll patients under-going major open cardiac surgery between October 2009 and October 2012. All patients were between the ages of 18 and 85. Patients were excluded for any prior use of an investigational device/drug within the last 30 days, any condition that would require extensive time off the nursing unit during the fi rst 24

From Baylor University Medical Center at Dallas (Lagow, Leeper, Ramsay),

and the Annette C. and Harold C. Simmons Transplant Institute, Dallas, Texas

(Jennings).

Corresponding author: Michael A. E. Ramsay, MD, FRCA, Department of

Anesthesiology and Pain Management, Baylor University Medical Center at

Dallas, 3500 Gaston Avenue, 2nd Floor, Roberts Hospital, Dallas, TX 75246


hours (e.g., hemodialysis), allergy to the ear probe, or an inabil-ity to undergo all protocol requirements. Prior to enrollment, all patients were screened for study eligibility and their medical history was reviewed. Informed consent was obtained preceding any study procedure, and 51 patients were enrolled.

All patients received a standard general anesthetic appropri-ate for cardiac surgery and were transported to the ICU im-mediately postoperatively. Following overnight or appropriate recovery in the ICU, patients were discharged to the cardiac telemetry ward, where they received the usual standard of care. To meet discharge criteria, all patients had to be separated from ventilatory support and require only supplemental oxygen via nasal cannula. Th e goals of this study were to determine the incidence of unrecognized respiratory depression during usual and customary care of these patients, and also to determine how well patients tolerated the sensor and how secure it was following placement. Th erefore, the data obtained from the device were not made available to the caregivers, including both the physicians and the bedside nurse, but were recorded and reviewed later.

Upon arrival to the telemetry fl oor, a TOSCA 500® or TCM TOSCA® (Radiometer Medical ApS, Brønshøj, Den-mark) monitor was attached to an earlobe of the patient. Th e TOSCA is approved by the US Food and Drug Administration for simultaneous continuous monitoring of tcpCO2, functional oxygen saturation, and pulse rate in adults and children (Post Market Approval #K063434). Th e monitor provides informa-tion on both oxygen saturation and carbon dioxide levels (3–7). Th e tcpCO2 reading from the TOSCA has been shown to cor-relate well with arterial carbon dioxide levels (PaCO2) (8–10). Th e TOSCA probe is attached to the earlobe and is heated to facilitate blood fl ow and capillary vasodilation below the sensor. Th e sensor temperature may be set between 37°C and 45°C in

Incidence and severity of respiratory insufficiency detected by transcutaneous carbon dioxide monitoring after cardiac surgery and intensive care unit dischargeElaine E. Lagow, RN, CCRC, Barbara “Bobbi” Leeper, MN, RN, CCRN, Linda W. Jennings, PhD, and Michael A. E. Ramsay, MD

steps of 0.5°C with an accuracy of ±0.2°C. Th e manufacturer recom-mends that the probe be heated to 42°C to adequately enhance blood fl ow, with a change in probe site every 12 hours to prevent thermal burn (9, 11). Two models of the TOSCA monitor were utilized in this study, the TOSCA 500 and the TCM TOSCA. Th e TOSCA 500 monitor stores all measured patient results every 3 seconds and was used earlier in the study, followed by the TCM TOSCA model, which stores all measured patient results every 10 seconds. Computer software enables data collected from the monitor to be exported to other programs. Th erefore, SpO2, tcpCO2, and heart rate data every 3 or 10 seconds were available for analysis.

Hypercarbia for this study was classifi ed as mild (tcpCO2 42–49 mm Hg), moderate (tcpCO2 50–59 mm Hg), or severe (tcpCO2 ≥60 mm Hg). Hypoxia for this study was classifi ed as mild (SpO2

91%–85%), moderate (SpO2 84%–80%), or severe (SpO2 ≤79%). Tachycardia for this study was classifi ed as mild (pulse rate 80–90 bpm), moderate (pulse rate 91–119 bpm), or severe (pulse rate ≥120 bpm). Events for the study were cataloged singularly into events of tcpCO2 ≥60 mm Hg, SpO2 saturation ≤79%, and pulse rate ≥120 bpm. Events were also cataloged with combinations of SpO2 saturation of ≤79% with a tcpCO2 ≥60 mm Hg; SpO2 saturation of ≤79% with a pulse rate ≥120 bpm; and SpO2 saturation ≤79% with pulse rate ≥120 bpm plus a tcpCO2 ≥60 mm Hg.

RESULTSA total of 51 patients were enrolled in the study, 15 women

and 36 men, with a mean age of 63 years. Forty-fi ve of the patients were white or Hispanic and six were black. Twelve of the 51 patients were not included in the fi nal analysis: three withdrew consent prior to the probe being applied; one was in the ICU for an extended period of time and was transferred directly to the rehabilitation hospital, bypassing the telemetry unit; and the remaining eight patients experienced machine malfunction and/or staff error. Twenty-six of the patients were attached to the TOSCA 500 for up to 24 hours from Decem-ber 2009 through January 2011. Th irteen were attached to the TCM TOSCA for up to 24 hours from March 2012 through October 2012.

Th e total number of actual recorded hours for all 39 patients was 713 hours: 18% of patients had ≤9 hours, 31% had >9 to <20 hours, and 51% had ≥20 hours. Th e tcpCO2 sensor was functional for a mean of 74% of potential recorded time. Th e O2 saturation sensor was functional for a mean of 90% of this time. Twelve patients who were connected to the monitors asked to discontinue the study due to the inconvenience of the probe or annoyance with the alarm on the machine. Th e total time


monitored in this group was 141 hours. Th ere were three fi les that recorded only the fi rst 12 hours.

One patient returned to the ICU with respiratory distress the third day after transfer to the ward. Th e study was designed to monitor only the fi rst 24 hours posttransfer and therefore did not detect this event when the data were reviewed. However, the patient did exhibit periods of desaturation during the fi rst 8 hours posttransfer, and the oxygen delivery rate was increased from 4 L per minute via nasal cannula to 5 L per minute per nursing unit protocol.

Figure 1 summarizes the number of hypercarbic, hypoxic, and tachycardic events, and Table 1 summarizes the duration of these events. Overall, there were 41 moderate or severe hypercarbic events. Th e total duration of tcpCO2 ≥60 mm Hg was 39.03 ± 72.24 (SD) minutes, ranging from 0.05 to 280 minutes, with a median of 13 minutes. Th e total duration of tcpCO2 50 to 59 mm Hg was 129.6 ± 218.1 minutes, ranging from 0.05 to 1092 minutes with a median of 67 minutes. Th e total duration of SpO2 saturation ≤79% in patients experienc-ing hypoxic episodes was 4.4 ± 9.9 minutes, ranging from 0.1 to 49.7 minutes with a median of 1.1 minute. A pulse rate

Table 1. Median duration of hypercarbic, hypoxic, and tachycardic events in 39 patients after cardiac surgery

based on transcutaneous carbon dioxide monitoring in the intensive care unit

Event

Number of patientswith at least one

event

Median total duration (minutes)

Mild hypercarbia (42–49 mm Hg) 35 303

Moderate hypercarbia (50–59 mm Hg) 26 67

Severe hypercarbia (≥60 mm Hg) 15 13

Severe oxygen desaturation (≥79%) 31 1.1

Severe tachycardia (≥120 bpm) 17 3.1

Figure 1. Number of patients experiencing hypercarbic, hypoxic, and tachycardic events among 39 patients monitored

after cardiac surgery using transcutaneous carbon dioxide monitoring in the intensive care unit.

≥120 beats/minute occurred in 17 patients, with a total duration of 11.8 ± 20.5 minutes, ranging from 0.1 to 78.0 minutes with a median of 3.1 minutes. Th irty-one percent of these tachycardic patients had a history of atrial fi brillation. As shown in Figure 2, 21% of the patients experienced all three symptoms of severe hypercarbia, hypoxia, and tachycardia in the fi rst 24 hours after discharge from the ICU.

DISCUSSIONWe presented results of 39 postoperative cardiac surgery

patients during their fi rst 24 hours following transfer from the ICU to the telemetry fl oor, showing that the incidence and severity of hypercarbia, hypoxia, and tachycardia were high. Th e continuous monitoring of tcpCO2, SpO2, and pulse rate pro-vides earlier identifi cation of severe respiratory depression, and therefore would lead to earlier intervention and possibly prevent a return to the ICU. Monitoring is particularly important for patients with a history of pulmonary disease, which may increase postoperative complications and ICU stay. A well-tolerated pa-tient monitoring technology that accurately, automatically, and continuously tracks transcutaneous carbon dioxide levels has the potential to greatly improve the timeliness of a response to a failing patient and improve patient safety and outcomes. Th e episodes of severe hypoxia, hypercarbia, and tachycardia detected in this study indicate a need for improved monitoring of this patient population.

Th ere were several limitations to our study. First, although 51 patients agreed to participate, we were able to analyze data for only 39 patients. Of those 39, approximately 76% of po-tential monitored hours were captured. Th e study monitor TOSCA 500 was upgraded to the TCM TOSCA during the trial. Several patients asked to have the monitor removed early due to continued alarming and comfort level being restricted due to “one more wire” being attached to them. Th e monitor may have been better tolerated by patients if it were wireless. Some of the technical problems encountered may have been avoided with better education for the nursing staff .

Th e clinical signifi cance of our fi ndings will need to be determined by a larger study, where the monitor information is provided to the nurses and an intervention protocol put in place. Monitoring tcpCO2, SpO2, and pulse rate through a single sen-sor could provide an advantageous and convenient method of early detection of potential severe respiratory depression.

AcknowledgmentsFunding for this study was wholly provided by the Car-

diovascular Research Foundation of the Baylor Heart and Vas-cular Institute. Th e monitors were provided by Radiometer (Brønshøj, Denmark).

1. Ng CS, Wan S, Yim AP, Arifi AA. Pulmonary dysfunction after cardiac surgery. Chest 2002;121(4):1269–1277.

2. Weissman C. Pulmonary complications after cardiac surgery. Semin Car-diothorac Vasc Anesth 2004;8(3):185–211.

3. Eberhard P, Gisiger PA, Gardaz JP, Spahn DR. Combining transcutane-ous blood gas measurement and pulse oximetry. Anesth Analg 2002;94(1 Suppl):S76–S80.

4. Bernet-Buettiker V, Ugarte MJ, Frey B, Hug MI, Baenziger O, Weiss M. Evaluation of a new combined transcutaneous measurement of PCO2/pulse oximetry oxygen saturation ear sensor in newborn patients. Pediatrics 2005;115(1):e64–e68.

5. McBride ME, Berkenbosch JW, Tobias JD. Transcutaneous carbon diox-ide monitoring during diabetic ketoacidosis in children and adolescents. Paediatr Anaesth 2004;14(2):167–171.

6. Dullenkopf A, Bernardo SD, Berger F, Fasnacht M, Gerber AC, Weiss M. Evaluation of a new combined SpO2/PtcCO2 sensor in anaesthetized paediatric patients. Paediatr Anaesth 2003;13(9):777–784.

7. Kagawa S, Otani N, Kamide M, Gisiger PA, Eberhard P, Severinghaus JW. Initial transcutaneous PCO2 overshoot with ear probe at 42 degrees C. J Clin Monit Comput 2004;18(5–6):343–345.

8. Rohling R, Biro P. Clinical investigation of a new combined pulse oxim-etry and carbon dioxide tension sensor in adult anaesthesia. J Clin Monit Comput 1999;15(1):23–27.

9. Gisiger PA, Palma JP, Eberhard P. OxiCarbo, a single sensor for the non-invasive measurement of arterial oxygen saturation and CO2 partial pressure at the ear lobe. Sens Actuators B Chem 2001;76(1–3):527–530.

10. Parker SM, Gibson GJ. Evaluation of a transcutaneous carbon dioxide monitor (“TOSCA”) in adult patients in routine respiratory practice. Respir Med 2007;101(2):261–264.

11. Radiometer Basel AG. TOSCA 500 Operating Manual for USA. Basel, Switzerland, Radiometer Basel, June 2007.

October 2013 375Incidence and severity of respiratory insuffi ciency detected by TcPCO2 after cardiac surgery and ICU discharge

Figure 2. Percentage of patients experiencing severe-only hypercarbic, hypoxic,

and tachycardic events after cardiac surgery based on transcutaneous carbon

dioxide monitoring in the intensive care unit.

From the Department of Oral and Maxillofacial Surgery, Texas A&M University

Baylor College of Dentistry and Baylor University Medical Center at Dallas.

Corresponding author: Larry Wolford, DMD, 3409 Worth Street, Suite 400, Dallas,

TX 75246 (e-mail: [email protected]).

This retrospective study assessed the outcome of 603 patients under-

going partial inferior turbinectomies (PIT) in association with Lefort I

osteotomy. The study included 1234 patients from a single private prac-

tice; these patients had dentofacial deformities and underwent Lefort I

osteotomy procedures. For the full patient group, 888 patients (72%)

were women; in the turbinectomy group, 403 (67%) were women. The

anteroposterior, transverse, and vertical dimensions of the mandible,

maxilla, and occlusal plane of each subject were assessed, in addition to

cephalometric analysis and determination of the presence or absence of

temporomandibular joint disorders. PIT, when indicated, was performed

after downfracture of the maxilla, providing access to the turbinates where

approximately two thirds of the total turbinate volume was removed and

septoplasty was completed if indicated. Hypertrophied turbinates causing

significant nasal airway obstruction were present in 603 (49%) of the

1234 patients undergoing Le Fort I osteotomy. The results of this study

showed that PIT performed simultaneously with Le Fort I osteotomy is a

safe method of managing nasal airway obstruction related to hypertro-

phied turbinates with minimal complications.

The nasal turbinates or conchae are curled thin bone shelves that protrude from the lateral nasal walls medially into the nasal breathing passage covered with glandular, erectile, and mucosal tissues. Th ree turbinates are ar-

ranged in horizontal parallel rows on each side of the nose. Th e inferior turbinate is the largest, followed by the middle, and the superior turbinate is the smallest. Th e turbinates divide the nasal airway into four air passages, which guide the inhaled air to fl ow in a steady stream around the largest possible surface of cilia. In the presence of normal anatomy, the inferior turbinates play a major role in fi ltering, warming, and humidifying the nasal airway, with approximately 80% of the airfl ow occurring around the inferior turbinates. Th e sympathetic and parasympathetic nervous systems are responsible for change in the turbinate size according to physiologic requirements (1). Th is is a cyclical set of events, which is aff ected by increasing or decreasing the volume of blood contained in the associated erectile tissue.

Large or swollen turbinates may lead to decreased air fl ow through the nasal passage. Allergic exposure to environmental elements and allergens, in addition to persistent infl ammation within the sinuses, can lead to turbinate swelling. Anatomical

and traumatic factors can also play a role in this process. De-formed and enlarged inferior turbinates are the main causes of nasal airway obstruction, followed by allergic rhinitis (2, 3). Epidemiologic studies in European countries have shown that up to 20% of the population has chronic nasal obstruction caused by turbinate hypertrophy (4). Th e most common causes of hypertrophied turbinates are allergic and nonallergic nasal hyperactivity, followed by septal deviation (5). Th e sequela of chronic nasal obstruction is mouth breathing, which results in a lower and anteriorly placed tongue and a lower position of the mandible. Th is consequently decreases the tonicity of the facial muscles as a result of decreased fl ow of the nasal airway due to anatomical obstruction (6–8). Based on functional matrix theory, put forth by Moss et al (9), the lack of nasal breath-ing can signifi cantly aff ect the development of dentofacial and craniofacial structures. In an individual with obstructed nasal airway, disharmony of normal breathing and abnormal tone and stimulation of facial muscles could be the cause of a narrow and posteriorly positioned mandible, in addition to a hypoplastic maxilla, associated with open bite (10–12).

Th e allergic turbinate hypertrophy can be managed with medications, such as corticosteroids, and if this approach fails, surgery may be necessary (13). When a deviated septum is iden-tifi ed, the turbinate associated with the aff ected side is usually enlarged. In such cases, the septum can be addressed along with the enlarged turbinate. Chronic nasal stuffi ness, caused by peren-nial allergic rhinitis, is amenable to turbinate surgery (14).

Multiple surgical modalities have been advocated to address the hypertrophied turbinate, including turbinate outfracture, electrocautery, reduction by a microdebrider, cryosurgery, coab-lation, laser reduction, partial or total turbinate resection, use of radiofrequency, submucous turbinate resection, and vidian neurectomy (13, 15–19). Th e aim of this retrospective study was to perform an outcome assessment of partial inferior tur-binectomies (PIT) performed simultaneously with Lefort I os-teotomies and analyze the related data for complications, gender

Outcome assessment of 603 cases of concomitant inferior turbinectomy and Le Fort I osteotomyReza Movahed, DMD, Carlos Morales-Ryan, DDS, MSD, Will R. Allen, DDS, Scott Warren, DDS, MD, and Larry M. Wolford, DMD


distribution, and morphological association with the maxilla and mandible.

METHODSA retrospective study was conducted on 1234 consecutive pa-

tients (888 women, 346 men) from the senior author’s (Wolford) private practice (Dallas, Texas) undergoing Le Fort I osteotomy from 1995 to 2011. Th ese patients required Le Fort I osteotomies for correction of dentofacial deformities, and a signifi cant num-ber of patients also required temporomandibular joint (TMJ) surgery. Institutional review board exemption was obtained.

Th e surgical technique for PIT was as follows. In the max-illary osteotomies, prior to mobilization, the nasal mucosa was carefully dissected off the nasal fl oor, the lateral nasal wall up to the base of the inferior turbinate, and off the inferior aspect of the nasal septum. Th e septum was separated from the maxillary nasal crest. Th e maxilla was downfractured and mobilized, with care taken to preserve the nasal mucosa intact. Using a 15 blade, an incision was made bilaterally, just lateral to the septum, extending from the posterior to the anterior aspect of the nose. Retracting the mucosal tissue laterally exposed the entire body of the turbinates (Figure 1a). Th e portion of the turbinates to be resected was isolated and excised using scissors (Figure 1b). Hemostasis was achieved using a Bovie cautery. If a nasoseptoplasty was indicated, the mucosa was dissected off the septum and an appropriate procedure performed to correct the septal deformity. Th e na-sal mucosa was approximated using 4.0 chromic gut sutures in a running fashion, incorporating all four mucosal fl aps. Postsurgical imaging on a typical patient demonstrated the reduced turbinates (Figure 2c, 2d).

Th ere were three diagnostic criteria for hypertrophic tur-binates: 1) a history of consistent diffi culty breathing through the nose; 2) clinical and radiographic evidence of the turbinates blocking the majority of the nasal airway; and 3) predominant mouth breathing when sleeping. Evaluations included medical history; clinical assessment; standardized x-rays; dental models; clinical pictures; morphological evaluation of maxilla, mandible, and occlusal plane angle; evaluation of external and internal

nasal deformities; and determi-nation of any current respiratory problems. In cases prior to 2008, radiographic images were obtained with the Quint Sectograph, and af-ter 2008 with cone beam computed tomography (CT) scan. Th ese ra-diographs were taken in the normal course of patient treatment.

Lateral cephalograms, antero-posterior radiographs, and cone beam CT scans were analyzed to determine the transverse, vertical, and anteroposterior dimensions of the maxilla and mandible as well as the occlusal plane angulation. Th e maxilla and mandible were catego-

rized into hypoplastic, hyperplastic, and normal groups. Th e oc-clusal plane angle was labeled as normal, low, or high angle.

Th e total patient group (n = 1234) was also evaluated for the presence of and correlation between hyperplastic turbinates and TMJ surgery. Th e TMJ surgeries performed included TMJ disc repositioning using the Mitek anchor technique (Mitek Inc, Norwood, MA) and TMJ reconstruction using TMJ Concepts (Ventura, CA) total joint prostheses. Th e gender variation and correlation to PIT were evaluated. Descriptive statistics and Pear-son’s correlation analysis were utilized to evaluate the results.

RESULTSAmong the 1234 patients enrolled in the study, 888 (72%)

were women, and 346 (28%) were men. In 603 cases (49%), partial turbinectomies were required. In this subgroup, 403 (67%) were women and 200 (33%) were men (Table 1). A total of 278 patients (23%) required septoplasty. Th e mean age of the patients at surgery was 28 years (range, 13–58 years), and the average follow-up period was 24 months (range, 12–48 months). Figures 2 to 4 illustrate results from typical patients.

Th e morphological characteristics of the maxilla and man-dible were independently evaluated by clinical study models and cephalometric analysis. For patients who required turbinec-tomies, 84% had maxillary hypoplasia in the anteroposterior dimension, 52% in the transverse dimension, and 48% in the vertical dimension. Th e mandibular morphological association with PIT included mandibular hypoplasia in the anteroposterior direction (72%) with normal transverse (97.9%) and vertical (94.9%) dimensions (Table 2). Th e anteroposterior hypoplastic maxilla and anteroposterior hypoplastic mandible had a strong morphological association with hypertrophied turbinates (r = 0.95; P < 0.05) (as illustrated in Figures 3a–3c, 4a–4c). In 69% of high occlusal plane angle cases, there was a strong correla-tion with hypertrophied turbinates (Figure 5a). Th e remaining cases had a normal occlusal plane angle (27%), with only 4% associated with a low occlusal plane angle (Table 2).

Of the 603 patients, 296 (49%)—including 215 (73%) women and 81 (27%) men—received concomitant TMJ surgery, Lefort I osteotomy, and PIT. Th e remaining 307 patients—188

Outcome assessment of 603 cases of concomitant inferior turbinectomy and Le Fort I osteotomyOctober 2013 377

Figure 1. (a) The maxilla has been downfractured (arrow) and an incision made through the nasal mucoperiosteum to

expose the right inferior turbinate. (b) The partial resection of the bilateral inferior turbinates has been completed.

a b

(61%) women and 119 (39%) men—received PIT and Lefort I osteotomy with no TMJ surgical intervention (Table 1).

All the patients were followed immediately postoperatively and at long-term follow-up of 12 to 48 months. Chart review showed no signifi cant long-term complications associated with PIT.

DISCUSSIONHypertrophied turbinates can be addressed with various

means, from conservative therapy (20) to surgical modalities. In

Figure 2. Computed tomography scans of a typical patient before and after the procedure. (a) Axial view demonstrates hypertrophied turbinates (arrows) and the

nasal septum that appears reasonably straight. (b) Coronal view demonstrates hypertrophied turbinates (arrow) occupying the majority of the nasal cavity. (c) After

turbinectomy, along with the maxillary osteotomies, the axial view shows the patient’s improved nasal airway. The cut is just inferior to the remaining turbinates.

(d) Coronal view shows the reduced turbinates and improved nasal airway.

Table 2. Skeletal morphological characteristics that correlate with turbinate hyperplasia

Anteroposterior Vertical Transverse

Maxilla

Normal 12% 13% 45%

Hypoplasia 84%* 48% 52%

Hyperplasia 4% 39% 3%

Mandible

Normal 10% 95% 98%

Hypoplasia 72%* 2.5% 0.8%

Hyperplasia 18% 2.5% 1.2%

Occlusal plane

Normal 27%

Low 4%

High 69%*

*P ≤ 0.05.

Table 1. Patient gender by procedure

Procedure Male Female

Lefort I osteotomy and PIT (N = 603) 200 (33%) 403 (67%)

Subgroup with no TMJ surgery (N = 307) 119 (39%) 188 (61%)

Subgroup with TMJ surgery (N = 296) 81 (27%) 215 (73%)

PIT indicates partial inferior turbinectomies; TMJ, temporomandibular joint.


a b

c d

Figure 3. (a–c) A typical patient with hypertrophied turbinates associated with a retruded maxilla and mandible and

high occlusal plane angle facial morphology. (d–f) The patient seen after surgery, which included TMJ reconstruc-

tion as well as mandibular and maxillary advancement in a counter-clockwise direction, genioplasty, and partial

turbinectomies.

a

d

c

f

b

e

describes the association of upper re-spiratory obstruction and changes in the neuromuscular system that alters the bony, soft tissue, craniofacial, and dental structures.

When addressing hypertrophied turbinates along with correction of dentofacial deformities, especially in the case of performing Le Fort I osteotomies, postsurgical patency of the airway should be considered (31–33). When the Le Fort osteotomy is performed, the maxilla can be mo-bilized, repositioned, and stabilized in any of four possible directions, af-fecting the associated and adjunctive soft tissues (34). In 1997 Kunkel and Hochban (35) utilized the acoustic rhinometry concept introduced by Hilberg et al in 1989 (36) to evaluate the eff ect of maxillary movement on the nasal volume. Erbe et al in 2001 completed acoustic and rhinometry evaluation of 21 maxillary advance-ment and impaction cases and con-cluded that in anterior and superior maxillary repositioning, there was no signifi cant change in airfl ow resis-tance (37). Haarmann et al (2009) investigated the changes in nasal air-ways after Le Fort I osteotomies with concomitant nasal septoplasty and

inferior turbinectomies using anterior rhinomanometry and acoustic rhinometry. Th e results of their analysis supported the improvement of the functional airway after surgery (38).

Th e simultaneous reduction of inferior turbinates is of im-portance in cases requiring maxillary superior repositioning for management of upper airway obstruction in the presence of hypertrophied turbinates. Multiple publications have addressed and reported case series on the subject (38–40).

In the reviewed sample size (n = 603), no signifi cant long-term postsurgical complications related to the nasal airway were identifi ed. Th e most common complications from turbinate surgery are hemorrhage, atrophic rhinitis, and ozena (41). Th e reduction of the appropriate volume of the inferior turbinate is of importance, taking into account the presented histological factors and maintenance of mucociliary function. Th e resection of the entire turbinate increases the patency of the nasal airway but increases the chance of intraoperative and postoperative heavy bleeding, while having a long-term chance of chronic nasal crusting (42–44).

Presently there is no exact consensus on the volume of re-duction or the method utilized for PIT. Based on this case series, clinical outcomes, and preservation of the function of the nose, the recommended reduction of the hypertrophied inferior turbinates should equal about two thirds of the original

patients with dentofacial deformities, the Le Fort I osteotomy provides direct access to the full extent of the inferior turbinates and the septum. Th e patients in this study with hypertrophied turbinates were treated with PIT in combination with maxillary and mandibular osteotomies with correction of the occlusal plane to a normal angulation as well as TMJ surgery when indicated to provide optimal function, facial balance, decrease in pain, and good airway (Figure 3d–3f, 4d–4f, 5b). A female predominance was seen in the data reviewed. Approximately 67% of the turbinectomy cases, and 73% of concomitant tur-binectomy and TMJ surgery cases, involved female subjects. A strong correlation has been established between hypertrophied inferior turbinates, hypoplastic maxilla and mandible, as well as a steep occlusal plane. Our fi ndings correlate with other stud-ies evaluating the morphology of mouth breathing and nasally obstructed patients (6, 21–23).

Th e association of mouth breathing, dentofacial deformi-ties, and upper airway obstruction has been explored in the orthodontic, otolaryngology, and maxillofacial surgery literature (24). It still remains a controversial subject with no general consensus achieved (25–28). Harvold et al (29), in their primate studies, induced obstruction of the nasal airway and generated morphological changes in dental and craniofacial parameters. McNamara (30) proposed a physiological mechanism that


volume (45–47). Excessive reduction of turbinate tissue could cause the rare empty nose syndrome (ENS). ENS is associ-ated with poor regrowth of sensory nerves, which are damaged during aggressive turbinectomies. In ENS, the nasal airway is unobstructed, but the aff ected patients sense an unsatisfactory struggle to breathe (48, 49). Ear, nose, and throat specialists presently believe that ENS is a diagnosis with no criteria for its identifi cation and in general recommend conservative reduction of the turbinates for its prevention (50).

In conclusion, PIT is a predictable and safe procedure per-formed simultaneously with Lefort I osteotomy for patients identifi ed with hypertrophic inferior turbinates and nasal airway obstruction. A notable pattern was established in our patient population, which clinically associates female patients with high

occlusal plane, hypoplastic maxilla, and mandible complex as the predictable group for hyperplastic turbinates requiring PIT. In assessing this study, it is important to understand that most patients associated with the senior author’s practice are retro-gnathic patients, with associated TMJ disorders, which could have an eff ect on the patient sample. Th e relation between TMJ disorders and hypertrophied turbinates is also noteworthy, and a larger multicenter controlled group will be necessary for estab-lishing its implication. Our recommendation is that in patients with dentofacial deformity undergoing Le Fort I osteotomy, the general status of the patients’ breathing and nasal structures should be taken into consideration for concomitant surgical intervention.

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Figure 5. (a) The lateral cephalometric tracing illustrates typical facial morphology

with hypertrophied turbinates, including a retruded maxilla and mandible and a

high occlusal plane angle. (b) The treatment plan for this patient included maxil-

lary and mandibular counter-clockwise rotation with reconstruction of the TMJs

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genioplasty. The chin point advanced forward 18 mm, improving the patient’s

profile as well as significantly improving the functional airway.


Figure 4. (a–c) The patient has a high-angle Class II end-on occlusion before surgery. (d–f) After surgery, the patient has a good functional occlusion with

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35. Kunkel M, Hochban W. Th e infl uence of maxillary osteotomy on nasal airway patency and geometry. Mund Kiefer Gesichtschir 1997;1(4):194–198.

36. Hilberg O, Jackson AC, Swift DL, Pedersen OF. Acoustic rhinometry: evaluation of nasal cavity geometry by acoustic refl ection. J Appl Physiol 1989;66(1):295–303.

37. Erbe M, Lehotay M, Göde U, Wigand ME, Neukam FW. Nasal airway changes after Le Fort I—impaction and advancement: anatomical and functional fi ndings. Int J Oral Maxillofac Surg 2001;30(2):123–129.

38. Haarmann S, Budihardja AS, Wolff KD, Wangerin K. Changes in acoustic airway profi les and nasal airway resistance after Le Fort I osteotomy and functional rhinosurgery: a prospective study. Int J Oral Maxillofac Surg 2009;38(4):321–325.

39. Turvey TA, Hall DJ, Warren DW. Alterations in nasal airway resis-tance following superior repositioning of the maxilla. Am J Orthod 1984;85(2):109–114.

40. Epker BN, Turvey T, Fish LC. Indications for simultaneous mobilization of the maxilla and mandible for the correction of dentofacial deformities. Oral Surg Oral Med Oral Pathol 1982;54(4):369–381.

41. Dawes PJ. Th e early complications of inferior turbinectomy. J Laryngol Otol 1987;101(11):1136–1139.

42. Fradis M, Golz A, Danino J, Gershinski M, Goldsher M, Gaitini L, Malatskey S, Armush W. Inferior turbinectomy versus submucosal dia-thermy for inferior turbinate hypertrophy. Ann Otol Rhinol Laryngol 2000;109(11):1040–1045.

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Hypocupremia, or copper deficiency, is a rare and underrecognized cause

of bone marrow dysplasia. Most cases of copper deficiency in adults oc-

curred historically in patients receiving total parenteral hyperalimentation

or total parental nutrition. More recently, with the obesity epidemic and

the prevalence of gastric bypass, cases of malabsorption-related cop-

per deficiency have occurred. Copper deficiency can lead to significant

cytopenias and possible neurologic sequelae, which can be misdiagnosed

and mismanaged. Unfortunately, a delay in diagnosis and appropriate

treatment may lead to permanent neurologic damage. We describe a

woman with previous gastric bypass surgery who presented with pan-

cytopenia and bone marrow biopsy findings consistent with a myelodys-

plastic syndrome with excess blasts. She was found to be significantly

copper deficient. With replacement copper therapy, her cytopenias quickly

resolved. We discuss the distinctive clinical and hematologic features of

this rare cause of significant cytopenias and provide recommendations

for monitoring and treatment of such patients. Moreover, this case is an

important reminder that bariatric patients should have routine follow-ups

after surgery and continue dietary supplements indefinitely.

Copper defi ciency is exceedingly rare in the normal popu-lation. Historically, most cases of copper defi ciency in adults occurred in patients receiving total parenteral hy-peralimentation or total parental nutrition (TPN) (1).

However, after bariatric surgery, copper supply is critical, as it appears to be required for the absorption and utilization of iron, already known to be malabsorbed in this setting. Copper is present in a number of metalloproteins, and it is required as a cofactor in many redox reactions. More than 90% of copper is bound to ceruloplasmin, an α2-globulin with ferroxidase activity. Th e copper-dependent ferroxidase hephaestin converts iron to the ferric (Fe3+) state for its transport by transferrin (2). Th ere is an increasing recognition of hypocupremia associated with anemia as a complication following TPN and bariatric surgery, specifi -cally in the case of gastric resection or bariatric gastric reduction surgery (3). One characteristic associated with copper defi ciency is an anemia that is unresponsive to iron supplementation but may present with pancytopenias and features of myelodysplastic syndrome (MDS). We report such a patient, discuss the distinc-tive clinical and hematologic features of this rarity, and provide recommendations for monitoring and treatment.

From the Baylor Charles A. Sammons Cancer Center (Robinson, Cooper) and

the Department of Pathology (Leday), Baylor University Medical Center at Dallas.

Corresponding author: Temekka V. Leday, MD, PhD, Department of Pathology,

Baylor University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246


CASE PRESENTATIONA 51-year-old Caucasian woman presented to our outpatient

clinic for evaluation of pancytopenia. In July 2012, a com-plete blood count was performed (Table 1). Her hematocrit was 33.2%, white blood cell count was 5.5 K/uL, and platelet count was 207 K/uL. In September 2012, reevaluation revealed worsening of the pancytopenia (Table 1). She received a transfu-sion of packed red blood cells and her hematocrit increased, but the eff ect was transient. At this point, the patient was referred to our offi ce, where we performed a bone marrow biopsy. Th e aspirate revealed a hypercellular marrow with a mild increase in blasts (5%–6%) and trilineage dyspoiesis, morphologic fi ndings consistent with refractory anemia with excess blasts (RAEB-1).

In taking the patient’s history, we found that she had under-gone a gastric bypass procedure 20 years earlier. On her fi rst visit to our offi ce, her weight was 200 pounds (body mass index 34.1 kg/m2). She had diff use musculoskeletal pain related to fi bro-myalgia. Since the bypass, she was taking oral iron for anemia. She was prescribed lithium for bipolar disorder and had been taking it for 6 years. She had no neurologic complaints, and she denied any excess tobacco or alcohol use. She took clonazepam, pregabalin, vitamin B12, furosemide, promethazine, tramadol, an oral multivitamin, and vitamin D. At the time of her visit to our offi ce in October 2012, her hematocrit was 30.2%; white blood cell count, 3.8 K/uL; and platelet count, 138 K/uL. Her lactate dehydrogenase was 134 IU/L, antinuclear antibody was nonreactive, ferritin was 354 ng/mL, and reticulocyte count was 3.1%.

Th e peripheral blood smear demonstrated pancytopenia with marked changes in red blood cells (Figure 1). Th ere was a normo-chromic, normocytic anemia with marked anisopoikilocytosis that included occasional ovalocytes and dacryocytes. A distinct dimorphic red blood cell population was not evident. Among the leukocytes, there was neutropenia with relative eosinophilia and basophilia. White blood cells were morphologically normal.

Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass surgerySara D. Robinson, MD, Barry Cooper, MD, and Temekka V. Leday, MD, PhD


Platelets were mildly decreased in number with occasional large platelets present. Bone marrow aspirate smears contained scattered small particles with cellular marrow (Figure 2). Th ere was left-shifted granulocytic maturation with increased numbers of blasts (4%–6%) and promyelocytes. Morphologi-cally, blasts were typical of myeloid blasts. Auer rods were not present. Features of dysgranulopoiesis included asynchronous maturation and occasional hyposegmentation of neutrophils. Many of the early granulocytic precursors (blasts and promy-elocytes) contained multiple small cytoplasmic vacuoles. Th e erythroid lineage demonstrated left-shifted maturation with in-creased numbers of pronormoblasts and basophilic normoblasts, many of which contained multiple small cytoplasmic vacuoles. Th ere were mild megaloblastoid changes and dyserythropoietic changes to include nuclear irregularities, nuclear lobulation, and nuclear fragmentation. Th e myeloid to erythroid ratio demon-

strated a slight erythroid predominance at 1.7:1. Megakaryocytes were adequate in number with occasional dyspoietic forms. Prussian blue–stained aspirate smears showed mildly increased iron stores with storage iron and sideroblastic iron identifi ed. Ringed sideroblasts were not observed.

The core biopsy specimen dem-onstrated a hypercellular marrow for the patient’s age (70%–80%) with all lineages represented (Figure 3). Th e bi-opsy contained scattered immature cells. Megakaryocytes were adequate for cellu-larity, with focal clusters and occasional dyspoietic forms to include hypolobate and hyperlobate nuclei (Figure 3). A reti-culin stain showed mildly to moderately increased reticulin fi brosis.

Flow cytometry studies performed on the bone marrow aspirate found increased eosinophils (19%) with no increase in myeloblasts (3%) or hematogones (2%). Cytogenetic analysis of the bone marrow aspirate was performed and an MDS fl uorescence in situ hybridization (FISH) panel was found to be negative for deletions of chromosome loci 5q31, 7q31, and 20q, with no evidence of monosomy 7 or trisomy 8. FISH for a core binding factor subunit β rearrangement was negative. Chromosome analysis revealed a normal 46,XX female karyotype.

Given the bone marrow morphologic fi ndings, MDS was strongly considered, although the patient was young for this diagnosis (median age 70) and had normal marrow cytogenet-ics. We also considered drug-induced cytopenias, with lithium or pregabalin considered the most likely inciting substances. However, lithium is generally associated with a leukocyto-sis, and pregabalin most commonly causes thrombocytope-nia rather than pancytopenia. Nonetheless, these drugs were stopped. Given her history of bariatric surgery, which can have malabsorption-related complications, we checked her copper and zinc levels. Th e latter was within normal limits; however, the patient’s copper level was extremely low (<20 mcg/dL; reference range 70–175 mcg/dL), so we initiated therapy with copper gluconate 4 mg orally three times a day. Two weeks later, her white count had improved, and approximately 6 weeks after initiation of copper replacement therapy, our patient’s complete blood count had normalized (Table 1). Her copper level had risen from <20 to 101 mcg/dL. She resumed lithium and her blood counts remained normal.

DISCUSSIONMDS is characterized by ineff ective hematopoiesis and

functional abnormalities of hematopoietic lineages. In about one third of patients, this disease can transform into acute my-eloid leukemia. Th e World Health Organization classifi cation of MDS, updated in 2008, indicates that the features that de-fi ne MDS include blood cytopenias, ineff ective hematopoiesis,

Table 1. Complete blood cell counts and plasma copper levels in our patient over time

7/2012 9/2012

10/2012(following

transfusions)

10/2012(following

coppersupplements) 12/2012

Hematocrit (%) 33.2 20.7 31.0 30.2 39.3

White blood cells (K/uL) 5.5 1.9 2.3 3.8 8.6

Neutrophils (%) 64 33 27 29 78

Bands (%) 0 2 2 1 0

Lymphocytes (%) 17 37 32 40 12

Monocytes (%) 12 16 14 18 7

Eosinophils (%) 3 12 25 11 2

Basophils (%) 4 0 0 0 1

Platelets (K/uL) 207 121 137 138 152

Plasma copper (mcg/dL) <20 101

Figure 1. Peripheral blood smear with pancytopenia and anisopoikilocytosis of

the red blood cells (Wright, ×400).

Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass surgeryOctober 2013 383

dyserythropoiesis, dysgranulopoiesis, dysmegakaryopoiesis, and increased myeloblasts (4). RAEB-1 is defi ned by cytopenias with unilineage or multilineage dysplasia and 5% to 9% blasts in bone marrow or 2% to 4% blasts in the peripheral blood. RAEB-1 is considered an intermediate-risk subtype of MDS. In the absence of specifi c cytogenetic abnormalities, MDS is a diagnosis of exclusion, and the diagnosis should only be made after careful review of clinical history and elimination of envi-ronmental or other nonclonal disorders that can result in my-elodysplasia. Congenital diseases and other enzyme defi ciencies are known to demonstrate myelodysplastic changes in a single lineage; however, trilineage dysplasia is unlikely in these entities. Substances with toxic eff ects such as chloramphenicol or arsenic can lead to dysplasia in all cell lines.

Copper defi ciency has been reported to result in an MDS-like picture. Patients often present with anemia, neutropenia, and, less commonly, thrombocytopenia (1, 5). Copper is present in a number of metalloproteins that are vital for normal homeo-stasis and include such enzymes as cytochrome-c oxidase, do-pamine β-hydroxylase, and superoxide dismutase. It is unclear how copper defi ciency causes anemia and other cytopenias. A decrease in the copper-dependent enzymes (ceruloplasmin and cytochrome-c) that aid in iron metabolism and transportation has been proposed as a potential factor for anemia (6). Mito-chondria from copper-defi cient animals are defi cient in cyto-chrome oxidase activity and fail to synthesize heme from ferric iron and protoporphyrin at the normal rate, leading to mito-chondrial iron accumulation (7, 8). Th e mechanism underlying neutropenia in hypocupremia remains unknown. Suggested eti-ologies have included destruction of myeloid progenitor cells in

the bone marrow, inhibition of diff erentiation and self-renewal of CD34+ hematopoietic progenitor cells, impaired egress of neutrophils from the bone marrow, and increased clearance of neutrophils from the circulation (9, 10).

Th e anemia of copper defi ciency often is associated with the presence of ringed sideroblasts and occurs in a number of clinical settings, including a microcytic, macrocytic, or nor-mocytic anemia. Marked vacuolization of both erythroid and myeloid precursors has been consistently reported in bone marrow (1–7, 11). Megaloblastic changes, ringed sideroblasts, and multilineage dyspoiesis characteristic of MDS have been described (3, 10–13). In comparison, our patient’s bone mar-row had numerous myeloid and erythroid precursors with cyto-plasmic vacuolization, but lacked ringed sideroblasts. Of note, our patient’s bone marrow demonstrated increased numbers of myeloblasts (4%–6%) with trilineage dysplasia, suggesting RAEB-1. A case report described a 19-year-old man with intes-tinal amyloid and secondary copper defi ciency that presented with trilineage dysplasia and increased numbers of immature cells, up to 19% (13). Th ough originally interpreted as blasts morphologically consistent with lymphoblasts, the immature cells in question turned out to be hematogones, or B lympho-cyte precursors. Hematogone hyperplasia has been described in association with copper defi ciency secondary to zinc excess, with bone marrow fi ndings that overlap with MDS (13, 14). Sixteen patients were reported with copper defi ciency over a 5-year period, 94% of which had hematologic features as their initial manifestation. Of the seven patients who had a bone marrow biopsy done, only one had an appearance consistent with RAEB-1 (15).

Figure 2. Morphologic changes in marrow precursors in copper deficiency, some of which mimic a myelodysplastic syndrome. (a) Early myeloid and erythroid

precursors with cytoplasmic vacuoles (Wright, ×1000). (b) Myeloid blast and vacuolated early erythroid precursors (Wright, ×1000). (c) Megaloblastoid change and

dyspoiesis in late-stage erythroid precursors (Wright, ×1000). (d) Dyspoietic ring neutrophil and vacuolated promyelocyte (Wright, ×1000).

a b

c d


Gastric surgery seems to be an increasingly common cause of acquired copper defi ciency that can go unrecognized for years (16). Acquired copper defi ciency can cause a myelopathy in humans (17) and is usually accompanied by the more typical anemia and leukopenia. Spinal and peripheral nerve injury can occur; patients can present with subacute gait disorders and prominent sensory ataxia and/or spasticity. Magnetic resonance imaging shows subcortical white matter changes, atrophy of the cerebellum, as well as signal changes in dorsal columns (15)—neurologic defi cits similar to those of vitamin B12 de-fi ciency. Th ough copper supplementation generally prevents further neurologic deterioration, improvement in neurologic symptoms with treatment is variable (18, 19). It is unclear if our patient’s history of fi bromyalgia or diff use musculoskeletal pain was related to her copper defi ciency. She had no focal neurologic defi cits at the time of initial examination, and musculoskeletal symptoms persisted after copper repletion.

Copper is an essential trace element absorbed in the stom-ach and proximal duodenum, both of which can be altered in bariatric surgery. Unfortunately, there have been no studies

addressing the appropriate dose, duration, or form of copper supplementation, nor are there specifi c guidelines for replacing low serum copper. Commonly used salts include copper gluconate, copper sulfate, and copper chloride. Because of the need for long-term therapy, parenteral therapy is not recommended, although intrave-nous copper can be used for several days as a bridge to the oral form. A 60-year-old man with early onset copper defi ciency af-ter Roux-en-Y surgery was supplemented daily with 4 to 10 mg of oral copper (20). Monitoring the patient’s blood copper lev-els every few months for the fi rst year to confi rm normal serum levels is important to establish the appropriate dose. Our case is an important reminder that bariatric patients should have routine follow-ups after surgery and continue dietary sup-plements indefi nitely. Abnormalities on routine laboratory tests should prompt a search for vitamin and trace mineral de-fi ciencies, as early detection can prevent debilitating symptoms.

1. Wasa M, Satani M, Tanano H, Nezu R, Takagi Y, Okada A. Copper defi ciency with pancytopenia during total parenteral nutrition. JPEN J Parenter Enteral Nutr 1994;18(2):190–192.

2. Green R. Trace metal defi ciency. In Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Prchal JT, eds. Williams Hematology. New York: McGraw-Hill, 2011:609.

3. Halfdanarson TR, Kumar N, Li CY, Phyliky RL, Hogan WJ. Hematological manifestations of copper defi ciency: a retrospective review. Eur J Haematol 2008;80(6):523–531.

4. Swerdlow SH, Campo E, Harris NL, Jaff e E, Pileri S, Stein H, Th iele J, Vardiman J. WHO Classifi cation of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer, 2008:439.

5. Dunlap WM, James GW 3rd, Hume DM. Anemia and neutropenia caused by copper defi ciency. Ann Intern Med 1974;80(4):470–476.

6. Huff JD, Keung YK, Thakuri M, Beaty MW, Hurd DD, Owen J, Molnár I. Copper defi ciency causes reversible myelodysplasia. Am J Hematol 2007;82(7):625–630.

7. Gregg XT, Reddy V, Prchal JT. Copper defi ciency masquerading as my-elodysplastic syndrome. Blood 2002;100(4):1493–1495.

8. Cizewski-Culotta V, Gitlin JD. Disorders of copper metabolism. In Scriver CR, Sly WS, eds. Metabolic Disorder and Molecular Basis of Inherited Disorders. New York: McGraw-Hill, 2001:3105–3126.

9. Percival SS. Neutropenia caused by copper defi ciency: possible mecha-nisms of action. Nutr Rev 1995;53(3):59–66.

10. Peled T, Glukhman E, Hasson N, Adi S, Assor H, Yudin D, Landor C, Mandel J, Landau E, Prus E, Nagler A, Fibach E. Chelatable cellular copper modulates diff erentiation and self-renewal of cord blood-de-rived hematopoietic progenitor cells. Exp Hematol 2005;33(10):1092–1100.

11. Fong T, Vij R, Vijayan A, DiPersio J, Blinder M. Copper defi ciency: an important consideration in the diff erential diagnosis of myelodysplastic syndrome. Haematologica 2007;92(10):1429–1430.

Figure 3. Hypercellular marrow for age with occasional dyspoietic megakaryocytes. (a) Hypercellular

marrow particle with all lineages represented (hematoxylin and eosin, ×200). (b, c) Dyspoietic changes in

megakaryocytes (hematoxylin and eosin, ×600).

a

b c

Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass surgeryOctober 2013 385

12. Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins WD, Levinson BS, Bhushan V, Kroft SH. Zinc-induced copper defi ciency: a report of three cases initially recognized on bone marrow examination. Am J Clin Pathol 2005;123(1):125–131.

13. Koca E, Buyukasik Y, Cetiner D, Yilmaz R, Sayinalp N, Yasavul U, Uner A. Copper defi ciency with increased hematogones mimicking refractory anemia with excess blasts. Leuk Res 2008;32(3):495–499.

14. Sutton L, Vusirikala M, Chen W. Hematogone hyperplasia in copper defi ciency. Am J Clin Pathol 2009;132(2):191–199.

15. Gabreyes AA, Abbasi HN, Forbes KP, McQuaker G, Duncan A, Morrison I. Hypocupremia associated cytopenia and myelopathy: a national retrospective review. Eur J Haematol 2013;90(1):1–9.

16. Kumar N, Ahlskog JE, Gross JB Jr. Acquired hypocupremia after gastric surgery. Clin Gastroenterol Hepatol 2004;2(12):1074–1079.

17. Kumar N. Copper defi ciency myelopathy (human swayback). Mayo Clin Proc 2006;81(10):1371–1384.

18. Goodman BP, Chong BW, Patel AC, Fletcher GP, Smith BE. Copper defi ciency myeloneuropathy resembling B12 defi ciency: partial resolu-tion of MR imaging fi ndings with copper supplementation. AJNR Am J Neuroradiol 2006;27(10):2112–2114.

19. Spinazzi M, De Lazzari F, Tavolato B, Angelini C, Manara R, Armani M. Myelo-optico-neuropathy in copper defi ciency occurring after partial gastrectomy. Do small bowel bacterial overgrowth syndrome and occult zinc ingestion tip the balance? J Neurol 2007;254(8):1012–1027.

20. O’Donnell KB, Simmons M. Early-onset copper defi ciency following Roux-en-Y gastric bypass. Nutr Clin Pract 2011;26(1):66–69.

Avocations

A lilac breasted roller from Botswana. Photo copyright © Jed Rosenthal, MD. Dr. Rosenthal is a cardiologist in Dallas, Texas (e-mail: [email protected]).


387387

Amyloid is identified microscopically as an amorphous extracellular hyaline

material that exhibits “apple-green” birefringence with Congo red stains.

Amyloid is not a chemically distinct entity, and currently available molecular

methods are capable of identifying over 20 amyloidogenic precursor proteins.

Some of the more common diseases associated with amyloidosis include

plasma cell dyscrasias, chronic inflammatory disorders, hereditary-familial

mutations involving transthyretin, Alzheimer’s disease, and so-called “senile”

or age-related amyloidosis. The amyloid deposits in these various diseases

may be isolated to a single organ such as the heart or brain, or the amyloidosis

may be systemic. The senile types of cardiac amyloidosis can result from

overproduction of atrial natriuretic factor or from accumulation of otherwise

normal or wild-type transthyretin. We present the case of an 83-year-old

hospitalized woman with known atrial fibrillation and previous pacemaker

implantation who had cardiac arrest unresponsive to attempted resuscitation.

Autopsy disclosed prominent amyloidosis involving the left atrium, and subse-

quent molecular studies identified the amyloidogenic material as alpha atrial

natriuretic factor. Since the clinical management and genetic implications of

the various diseases associated with amyloidosis are markedly different, we

stress the importance of molecular classification whenever possible.

Although identifi ed microscopically as an extracellular amorphous eosinophilic material with “apple-green” birefringence by Congo red staining, amyloid is not a chemically distinct entity (1). Furthermore, the tissue

distribution of amyloid among the various subtypes may be systemic or isolated to a single organ such as the heart or brain, producing completely diff erent clinical syndromes. Th e more common disorders associated with amyloid deposition include immunocyte or plasma cell dyscrasias, chronic infl ammatory disorders, genetic (familial) disorders, Alzheimer’s dementia, and so-called “senile” or age-related amyloid deposition. Also, within the “senile” amyloidosis category, involvement may be systemic or isolated to the heart, and two distinct subtypes of senile cardiac amyloidosis have been described. In isolated atrial amyloidosis (IAA), amyloid accumulates due to an overproduc-tion of alpha-atrial natriuretic factor or protein (alpha-ANF, alpha-ANP) (2), whereas in senile systemic amyloidosis, the amyloid is derived from native or wild-type transthyretin, a transport protein produced by the liver (3). Since amyloidosis may cause abnormal cardiac function, including restrictive heart

From the Department of Pathology, Baylor University Medical Center at Dallas.

Corresponding author: Joseph M. Guileyardo, MD, Department of Pathology, Baylor

University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail:

[email protected]).

disease, conduction disorders, arrhythmias, and death, the clini-cal diagnosis and pathologic identifi cation of this disorder are important (1). Furthermore, amyloid subtyping may inform therapy, and molecular typing may have profound implications for family members (4).

CASE STUDYAn 83-year-old woman was admitted to Baylor University

Medical Center at Dallas with new-onset dyspnea and bilateral pulmonary infi ltrates on chest radiograph. In the past a pace-maker had been implanted for “permanent” atrial fi brillation, and she was on warfarin with a recorded international normal-ized ratio of 4.4. Also, she was a long-term rehabilitation facility resident, and her problems included osteoarthritis, a hip fracture a year earlier, and poor mobility. On examination there was lower-extremity edema and muscle weakness, and she fatigued quickly. Her body mass index was 21.4 kg/m².

Th e patient was admitted to the telemetry fl oor and given diuretics. Th e night of admission, acute hypercapnic respira-tory failure prompted admission to the intensive care unit, and bilevel positive airway pressure support was initiated. Her blood pressure was 130/70 mm Hg; heart rate, 75 beats/minute; and respiratory rate, 34 breaths per minute. A grade 2/6 holosystolic murmur was audible at the cardiac apex. Computed tomograph-ic examination of the chest disclosed right atrial enlargement, biapical pulmonary opacities (pneumonia versus edema), and pleural eff usions (left > right). A brain natriuretic peptide was 314 pg/mL (normal ≤100 pg/mL), and an alanine transaminase was 67 U/L (normal 9–60 U/L). Troponin I was 0.03 ng/mL (normal <0.05 ng/mL). Transthoracic echocardiogram disclosed a normal left ventricular cavity size and normal systolic function with an ejection fraction of 55%; a dilated right atrium and right ventricle with preserved right ventricular systolic function; mild to moderate tricuspid regurgitation; an estimated right ventricular systolic pressure of 46 mm Hg; a dilated left atrium; mild aortic regurgitation; and a small pericardial eff usion.

Isolated atrial amyloidosis and the importance of molecular classificationVarsha Podduturi, MD, Danielle R. Armstrong, DO, Michael A. Hitchcock, MD, William C. Roberts, MD, and Joseph M. Guileyardo, MD


Shortly after intubation and placement of a central line, she developed ventricular fi brillation and pulseless electrical activity and died.

At necropsy, the pericardial sac contained 100 mL of clear fl uid. Th e pacemaker leads were well seated. Th e heart weighed 460 g. Th e subepicardial adipose tissue was markedly increased, causing fl otation of the heart in formalin. Th e epicardial surface was smooth and devoid of adhesions. Th e heart was examined through parasagittal incisions after fi xation. Th e left atrial ap-pendage was markedly dilated. Both atrial cavities were quite large and roughly dilated to similar degrees. Brown discolor-

ations were present in the left atrial endocardium (Figure 1). Th e right ventricular cavity and the coronary sinus were dilated.

Microscopically, there were amyloid deposits within the walls of both atria (confi rmed by Congo red stains), but these deposits were much more prominent within the left atrial wall (Figure 2). Congo red stains of the ventricular walls were negative.

CD138 immunostain and kappa and lambda in situ hybrid-ization studies of the spinal bone marrow did not reveal plasma-cytosis or cellular clonality. Postmortem serum immunofi xation electrophoresis was also negative for monoclonal peaks.

To further characterize the amyloid deposits, paraffi n blocks were submitted to the Mayo Clinic Laboratories, where mo-lecular amyloid subtyping by liquid chromatography-tandem mass spectrometry was performed on peptides extracted from Congo red–positive/microdissected areas of paraffi n-embedded left atrial tissue. Th e resultant diagnosis was amyloidosis, atrial natriuretic factor type, in the left atrium of the heart.

Th e remainder of the autopsy revealed moderate cerebral and aortic atherosclerosis, centrilobular hepatic congestion, mild arteriolar nephrosclerosis with prominent medullary congestion, and a previous right thyroidectomy with residual left lobe nodu-lar goiter. A small leiomyoma was present at the gastroesopha-geal junction, and several small gastrointestinal stromal tumors of the stomach wall were seen. Acute and chronic bronchitis was present microscopically, but there was no bronchopneu-monia.

DISCUSSIONAlthough more than 20 amyloidogenic precursor proteins

have been identifi ed by current molecular methods (5), some forms are more common than others. Furthermore, the subtypes of amyloidosis have markedly diff erent clinical implications. For example, AL amyloidosis, a common systemic form, is due to overproduction of immunoglobulin components associated with immunocyte dyscrasias, and eff ective treatment may re-quire chemotherapy. AA amyloidosis, in contrast, may be associ-ated with chronic infl ammatory disorders, and therapy involves control of the underlying condition. Hereditary-familial forms of amyloidosis may be associated with mutations involving pro-duction of an abnormal form of transthyretin (prealbumin), and

Figure 1. Sagittal section of the heart showing a markedly dilated left atrium

with brown endocardial discolorations.


Figure 2. The left atrium showing heavy amyloid deposits. (a) Congo red stain, ×100. (b) “Apple-green” birefringence apparent on Congo red stain (polarized), ×100.

a b

389Isolated atrial amyloidosis and the importance of molecular classification

management may include genetic counseling and consideration for liver and heart transplantation.

Th e so-called senile or age-related forms of cardiac amy-loidosis can be further divided into two major groups. In one form an otherwise normal or wild type of transthyretin mol-ecule accumulates to form amyloid deposits for generally un-known reasons (6). In so-called IAA, amyloid deposition is limited to the cardiac atria (predominantly the left) as a result of overproduction of atrial natriuretic factor. Th is subtype of amyloidosis has been cited as one of the most common forms of amyloidosis. Th e clinical implications of this disorder remain controversial. IAA is frequently associated with atrial fi brillation, but whether this accumulation is its cause is not known. One theory postulates a vicious circle in which atrial dilatation and fi brillation lead to overproduction of atrial natriuretic factor and amyloid deposition, which further exacerbates fi brillation and dilatation (7).

Overall, cardiac amyloidosis remains the primary determi-nant of prognosis in patients with systemic amyloidosis (3). However, regardless of the subtype of cardiac amyloidosis, this diagnosis may be clinically elusive, and management of these patients may be diffi cult. Th e gold standard for diagnosis of cardiac amyloidosis remains endocardial biopsy, but indirect evidence for diagnosis includes echocardiographic evidence of amyloidosis and histologic confi rmation of amyloid in non-cardiac tissues.

Diagnostic eff orts can be rewarding, as shown by the case above, since a diagnosis of amyloidosis may help explain func-tional cardiac disturbances and a patient’s failure to respond to therapeutic and supportive measures, even if amyloid is only

one contributor to the problem. Furthermore, as previously stated, the clinical implications and management of the various subtypes of amyloidosis are profoundly diff erent; therefore, we encourage molecular subtyping of these disorders whenever possible. Fortunately, such testing is now reasonably available; however, research is still needed in order to improve our under-standing of the clinical implications and optimal management of the various forms of cardiac and systemic amyloidosis as we proceed into this era of precision medicine. Furthermore, this case illustrates, once again, the relevance of traditional autopsy, especially when combined with modern and precise molecular tools to elucidate the true nature of a patient’s disease.

AcknowledgmentWe thank Jong M. (Jamie) Ko, BA, for photographic and

technical assistance.

1. Kumar V, Abbas A, Fausto N, Aster J. Robbins and Cotran Pathologic Basis of Disease, 8th ed. Philadelphia: Saunders/Elsevier, 2010.

2. Steiner I, Hájková P. Patterns of isolated atrial amyloid: a study of 100 hearts on autopsy. Cardiovasc Pathol 2006;15(5):287–290.

3. Kapoor P, Th enappan T, Singh E, Kumar S, Greipp PR. Cardiac amy-loidosis: a practical approach to diagnosis and management. Am J Med 2011;124(11):1006–1015.

4. Gertz MA. Th e classifi cation and typing of amyloid deposits. Am J Clin Pathol 2004;121(6):787–789.

5. Loo D, Mollee PN, Renaut P, Hill MM. Proteomics in molecular diag-nosis: typing of amyloidosis. J Biomed Biotechnol 2011;2011:754109.

6. Picken M, Dogan A, Herrera G. Amyloid and Related Disorders, Surgical Pathology and Clinical Correlations. New York: Humana Press, 2012.

7. Goette A, Röcken C. Atrial amyloidosis and atrial fi brillation: a gender-de-pendent “arrhythmogenic substrate”? Eur Heart J 2004;25(14):1185–1186.

October 2013

From the Department of Medicine, Tulane University School of Medicine, New

Orleans, Louisiana.

Corresponding author: A. Domnica Fotino, MD, MPH, Assistant Professor,

Department of General Internal Medicine and Geriatrics, Tulane University Health

Sciences Center, 1430 Tulane Avenue, SL-16, New Orleans, LA 70112 (e-mail:

[email protected]).

Sarcoidosis is a granulomatous disease of unclear etiology, which com-

monly presents with cough, dyspnea, chest pain, fever, weight loss, ar-

thralgias, and erythema nodosum. Heerfordt-Waldenström syndrome,

a rare presentation of sarcoidosis, is characterized by the presence of

parotid gland enlargement, facial palsy, anterior uveitis, and fever. Here

we present a case of a 59-year-old nonsmoking African American woman

who presented with 3 days of progressively worsening left facial droop,

difficulty swallowing, and blurred vision. Over the prior 4 months, she

had had a productive cough, fevers, night sweats, and an unintentional

30-pound weight loss. Physical examination revealed a left facial droop

involving the forehead, cheek, and chin with an inability to close the

left eyelid. Her serum angiotensin-converting enzyme level was twice

the upper limit of normal. Prominent hilar markings were identified on

chest x-ray, but no focal opacity was seen. Fine-needle aspiration of a

preauricular lymph node revealed noncaseating granulomas consistent

with granulomatous lymphangitis. The patient was given a diagnosis of

Heerfordt-Waldenström syndrome, or uveoparotid fever. Treatment with

a high-dose steroid improved her parotid gland enlargement, facial palsy,

and anterior uveitis.

CASE REPORTA 59-year-old nonsmoking African American woman pre-

sented with a 3-day history of progressively worsening left facial droop, diffi culty swallowing, and blurred vision. Over the prior 4 months, she had had a productive cough, fevers, night sweats, and an unintentional 30-pound weight loss. Physical examina-tion revealed a swollen left cheek and left facial droop involving the forehead, cheek, and chin. She was unable to close her left eyelid completely. Her posterior pharynx was erythematous, but no areas of oropharyngeal fl uctuance were noted. Tender, mobile submandibular and cervical lymph nodes were palpable bilater-ally, but more prominently on the left. Chest, lung, abdominal, and extremity exams were unremarkable. No rashes were noted. Th e remainder of the neurologic exam was normal.

Blood cultures, tuberculosis testing, and HIV antibody test-ing were negative. Antinuclear antibody and extractable nuclear antigen profi les were within normal limits. Serum angiotensin-converting enzyme (ACE) levels were twice the upper limit of normal. Rheumatoid factor was not checked on initial presen-tation. Computed tomography (CT) of the chest showed hilar

lymphadenopathy with bibasilar interstitial lung disease. CT of the neck soft tissues demonstrated enlarged lymph nodes, the largest of which measured 3.2 × 1.2 cm (Figure 1). Esophagogas-troduodenoscopy showed pharyngeal edema but no evidence of obstruction. Th e patient’s ophthalmologic exam was notable for impaired corneal sensation, punctate epithelial erosions in both eyes, and no overt fl are or leukocytes seen on slit lamp exam. Fundi were normal in appearance. Fine-needle aspiration of a left preauricular lymph node revealed multinucleated giant cells and noncaseating granulomas consistent with granulomatous lymphangitis (Figure 2). No bacteria or viruses were grown on culture of the biopsied lymph node. Th e patient was given a diagnosis of Heerfordt-Waldenström syndrome, or uveoparotid fever, which is a rare initial presentation of sarcoidosis.

DISCUSSIONGiven the patient’s acute onset of unilateral facial droop,

the diff erential diagnosis includes vascular, infectious, granu-lomatous, neoplastic, and autoimmune causes of cranial nerve VII injury (Table 1). Th e principal vascular causes of unilat-eral facial weakness are ischemic stroke and intraparenchymal hemorrhage involving the cranial nerve VII nucleus. Infectious causes of unilateral facial palsy include herpes simplex virus–associated Bell’s palsy, Lyme disease, HIV, and varicella zoster virus–associated Ramsay-Hunt syndrome. Tuberculosis, orofa-cial granulomatosis, and sarcoidosis are granulomatous diseases that cause unilateral facial palsy. In tuberculosis, the mastoid, middle ear, or petrous bone is often involved (1, 2). In sarcoi-dosis, neoplasms such as lymphoma and adenocarcinoma, and autoimmune etiologies such as systemic lupus erythematosus and Sjögren’s disease, the paralysis is thought to be related to infl ammation or compression of cranial nerve VII.

Sarcoidosis is a systemic disease characterized by granu-loma formation. Typical clinical fi ndings include cough, dyspnea, chest pain, fever, weight loss, arthralgias, and

The Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosisM. Carter Denny, MD, MPH, and A. Domnica Fotino, MD, MPH

390 Proc (Bayl Univ Med Cent) 2013;26(4):390–392

syndrome and are caused by a granulomatous infl ammatory re-action. Th e facial nerve palsy is associated with epineural granu-lomas and perineural infl ammatory infi ltrates of cranial nerve VII (12). Anterior uveitis classically presents with infected con-junctiva, blurred vision, or eye pain (13). Th is patient’s blurred vision and eye pain were thought to be related to uveitis. Th e patient had already received high-dose steroids for 3 days at the time of the full ophthalmologic exam, which may explain why the slit lamp and funduscopic exams were fairly unremarkable. Salivary gland involvement likely led to the pharyngitis seen on esophagogastroduodenoscopy and the patient’s diffi culty swallowing.

erythema nodosum. Only 5% of sarcoidosis cases have neu-rologic involvement, with the most common manifestation being facial nerve palsy (3–6). Heerfordt-Waldenström syn-drome, also called uveoparotid fever, is characterized by the presence of parotid gland enlargement, facial nerve palsy, anterior uveitis, and fever (7–9). Dr. Christian Heerfordt fi rst described this constellation of symptoms in 1909 (10). Dr. Jan Waldenström made the observation that this syndrome was associated with sarcoidosis in 1937 (11). Isolated case reports have described Heerfordt-Waldenström syndrome, but the exact prevalence is not known.

Th e parotid gland enlargement and cervical lymphadenopa-thy observed in this patient are typical of Heerfordt-Waldenström

Figure 1. CT of the neck soft tissues demonstrating prominent cervical lymphadenopathy.

Figure 2. Preauricular lymph node biopsy showing a noncaseating granuloma.

Table 1. Etiologies of facial nerve palsyIschemic stroke of the pons•

Intraparenchymal hemorrhage of the pons•

Herpes simplex virus–associated Bell’s palsy•

Human immunodeficiency virus•

Lyme disease•

Varicella zoster virus–associated Ramsay-Hunt syndrome•

Sarcoidosis•

Tuberculosis•

Adenocarcinoma•

Lymphoma•

Sjögren’s syndrome•

Systemic lupus erythematosus•

The Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis 391October 2013

Th e diagnosis of Heerfordt-Waldenström syndrome is made by the constellation of symptoms along with an el-evated serum ACE level and lymph node biopsy demonstrat-ing noncaseating granulomas. Granulomas in sarcoidosis are known to produce ACE; however, the serum ACE level does not always correlate precisely with disease activity (14, 15). As with other manifestations of sarcoidosis, corticosteroids are the mainstay of treatment. Immunosuppressants such as mycophenolate mofetil, cyclosporine, and infl iximab can be utilized in patients whose symptoms are refractory to steroids (16, 17). When complete eye closure is not possible, the pa-tient should use artifi cial tears while awake, use lubricant eye ointment at night, and cover the aff ected eye during sleep to prevent exposure keratopathy. If the facial nerve palsy is not treated with steroids, the likelihood of permanent facial paralysis is increased. When the facial paralysis is misdiag-nosed as being a simple Bell’s palsy, the opportunity to treat the systemic sarcoidosis is missed. Th is patient had marked improvement of symptoms after 4 days of prednisone therapy. Two months after discharge, her facial nerve palsy, parotitis, fevers, and uveitis had resolved.

AcknowledgmentsWe would like to acknowledge Adrian J. Baudy IV,

MD, Department of Internal Medicine at Tulane University School of Medicine, for his contributions to the care of this patient.

1. Ropper AH, Samuels MA, eds. Adams and Victor’s Principles of Neurology, 9th ed. New York: McGraw Hill, 2009:1329–1332.

2. Grave B, McCullough M, Wiesenfeld D. Orofacial granulomatosis—a 20-year review. Oral Dis 2009;15(1):46–51.

3. Newman LS, Rose CS, Maier LA. Sarcoidosis. N Engl J Med 1997;336(17):1224–1234.

4. Stern BJ, Krumholz A, Johns C, Scott P, Nissim J. Sarcoidosis and its neurological manifestations. Arch Neurol 1985;42(9):909–917.

5. Poate TW, Sharma R, Moutasim KA, Escudier MP, Warnakulasuriya S. Orofacial presentations of sarcoidosis—a case series and review of the literature. Br Dent J 2008;205(8):437–442.

6. Tamme T, Leibur E, Kulla A. Sarcoidosis (Heerfordt syndrome): a case report. Stomatologija 2007;9(2):61–64.

7. Petropoulos IK, Zuber JP, Guex-Crosier Y. Heerfordt syndrome with unilateral facial nerve palsy: a rare presentation of sarcoidosis. Klin Monbl Augenheilkd 2008;225(5):453–456.

8. Evanchan J, Barreiro TJ, Gemmel D. Uveitis, salivary gland swelling, and facial nerve palsy in a febrile woman. JAAPA 2010;23(5):46, 48–50.

9. Young RC Jr, Rachal RE, Cowan CL Jr. Sarcoidosis—the beginning: historical highlights of personalities and their accomplishments during the early years. J Natl Med Assoc 1984;76(9):887–896.

10. Waldenström JG. Some observations of uveoparotitis and allied condi-tions with special reference to the symptoms from the nervous system. Acta Medica Scandinavica 1937;91(1–2):53–68.

11. Said G, Lacroix C, Planté-Bordeneuve V, Le Page L, Pico F, Presles O, Senant J, Remy P, Rondepierre P, Mallecourt J. Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients. Brain 2002;125(Pt 2):264–275.

12. Agrawal RV, Murthy S, Sangwan V, Biswas J. Current approach in diagnosis and management of anterior uveitis. Indian J Ophthalmol 2010;58(1):11–19.

13. Baudin B. Angiotensin I-converting enzyme (ACE) for sarcoidosis diag-nosis. Pathol Biol (Paris) 2005;53(3):183–188.

14. Turner-Warwick M, McAllister W, Lawrence R, Britten A, Haslam PL. Corticosteroid treatment in pulmonary sarcoidosis: do serial lavage lym-phocyte counts, serum angiotensin converting enzyme measurements, and gallium-67 scans help management? Th orax 1986;41(12):903–913.

15. Th omas KW, Hunninghake GW. Sarcoidosis. JAMA 2003;289(24):3300–3303.

16. Londner C, Zendah I, Freynet O, Carton Z, Dion G, Nunes H, Valeyre D. Treatment of sarcoidosis. Rev Med Interne 2011;32(2):109–113.


393393

Inflammatory breast carcinoma is a rare and aggressive type of breast

cancer that is definitively diagnosed by histologic evaluation show-

ing invasive tumor cells in the dermal lymphatic system. Associated

dermal calcifications are not typically identified. We report an unusual

case in which inflammatory breast carcinoma led to the presence of

pleomorphic dermal calcifications identified on the initial mammo-

graphic examination.

CASE REPORTA 52-year-old woman presented for her yearly left breast

diagnostic mammogram with recently developed erythema of the left breast. She had a history of right mastectomy for inva-sive ductal carcinoma and multifocal ductal carcinoma in situ (DCIS) in 2005 and left breast lumpectomy for focal DCIS in 1993.

Routine and magnifi cation mammogram views of the left breast revealed interval development of increased density in the upper inner quadrant with associated pleomorphic calcifi ca-tions in a segmental distribution, skin thickening, as well as dermal pleomorphic calcifi cations (Figure 1). Subsequent skin punch biopsy yielded infi ltrating ductal carcinoma with dermal lymphatic invasion and coarse dermal calcifi cations (Figure 2). Physical and mammographic examination fi ndings of dermal thickening and erythema consistent with infl ammatory breast cancer corresponded to the pathologic diagnosis of dermal lym-phatic invasion.

DISCUSSIONInflammatory breast cancer is a rare and aggressive

type of breast cancer making up less than 5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, young age of onset, and lower overall survival compared with other breast cancers (1). It is suspected clinically when there is skin thickening, edema, and erythema and is often initially misdiagnosed as a benign infectious process. The diagnosis is confirmed by biopsy with histologic analysis showing invasive tumor cells in the dermal lymphatics; however, the dermal layer does not typically have associated calcifications. We present this case as an example of inflammatory breast

From the Department of Radiology, Baylor University Medical Center at Dallas.

Corresponding author: Amy R. Yactor, MD, Department of Radiology, Baylor

University Medical Center at Dallas, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail:

[email protected]).

cancer with associated dermal calcifications identified on mammography definitively diagnosed by skin punch biopsy. To the best of our knowledge, a similar case has not been reported.

Fine pleomorphic calcifications are well known for being associated with malignancy in the breast parenchyma, most notable for the association with DCIS, particularly when identified in a segmental, branching, or linear pattern (2). It is very rare, however, to have similar appearing pleomor-phic calcifications within the affected lymphatic system and further distant metastatic sites. A few reported cases have been described of metastatic axillary lymph nodes contain-ing pleomorphic calcifications. The two cases reported by Walsh et al found that one patient had similar appearing calcifications in the ipsilateral breast, and another patient had an asymmetric density without associated calcifica-tions in the ipsilateral breast parenchyma (3). In another series of 50 patients with metastatic axillary disease, 3% had intranodal calcifications identified mammographically (4). The presence of similar appearing pleomorphic dermal calcifications in inflammatory breast carcinoma has not yet been reported.

It is rare to have dermal calcifi cations that are associ-ated with malignancy. When calcifi cations are located in the dermal layer, they are typically thought to be benign, and if confi rmed to be dermal in location on tangential mam-mogram views, no additional workup is needed (5). Th e American College of Radiology BI-RADS lexicon describes mammographic fi ndings using a standard nomenclature, and benign calcifi cations include those that are located in the skin (6). Typical skin calcifi cations are usually related to a chronic infl ammatory process such as folliculitis and are most often located in sebaceous glands in the dermal layer. Th ese most often appear as small, well-demarcated calcifi cations with lucent centers rather than as pleomorphic calcifi cations, as seen in this patient (7).

Unusual dermal pleomorphic calcifications in a case of inflammatory breast carcinomaAmy R. Yactor, MD, Mehrzad Zarghouni, MD, Jean C. Wang, MD, Raynal R. Hamilton, MD, and Joseph J. Spigel, MD


AcknowledgmentsThe authors thank William G.

Herlihy, MD, in the Department of Pathology at Baylor University Medi-cal Center at Dallas for providing the histopathologic images.

1. Robertson FM, Bondy M, Yang W, Yamauchi H, Wiggins S, Kamrudin S, Krishnamurthy S, Le-Petross H, Bidaut L, Player AN, Barsky SH, Woodward WA, Buchholz T, Lucci A, Ueno NT, Cristofanilli M. Inflammatory breast cancer: the disease, the biology, the treatment. CA Cancer J Clin 2010;60(6):351–375.

2. Burnside ES, Ochsner JE, Fowler KJ, Fine JP, Salkowski LR, Rubin DL, Sisney GA. Use of microcalcifi cation descriptors in BI-RADS 4th edition to stratify risk of malignancy. Radiology 2007;242(2):388–395.

3. Walsh R, Kornguth PJ, Soo MS, Bentley R, DeLong DM. Axillary lymph nodes: mammo-graphic, pathologic, and clinical correlation. AJR Am J Roentgenol 1997;168(1):33–38.

4. Bjurstam NG. Radiography of the female breast and axilla. With special reference to diagnosis of mammary carcinoma. Acta Radiol Suppl 1978;357:107–117.

5. Loff man Felman RL. Th e tattoo sign. Radiology 2002;223(2):481–482.

6. D’Orsi CJ, Bassett LW, Berg WA, et al. Breast Imaging Reporting and Data System: ACR BI-RADS—Mammography (4th ed). Reston, VA: American College of Radiol-ogy, 2003.

7. Picca DA, Shaw de Paredes E. Calcifi cations in the breast: A radiologic perspective. Applied Radiol 2003;32(9):29-37.

Figure 1. (a) Routine left lateromedial oblique and (b) left craniocaudal diagnostic mammogram images

show an area of increased density with associated pleomorphic calcifications in a segmental distribution

in the upper inner breast (blue arrows) and skin thickening with pleomorphic dermal calcifications (white

arrows). Thin radiopaque markers indicate the sites of scars from previous surgery. (c) Magnification

90-degree lateromedial and (d) magnification craniocaudal views better demonstrate the increased

density and pleomorphic calcifications in the upper inner left breast (blue arrows) and associated skin

thickening with dermal microcalcifications (white arrows).

a b

c d

Figure 2. Photomicrographs of the specimen from the skin punch biopsy on (a) low power and (b) medium power show infiltrating ductal carcinoma in the dermal

layer (black arrows) and coarse fragmented microcalcifications in the dermal layer (blue arrows). (c) Photomicrograph of the specimen from a different site in the

deep dermis on high power shows coarse fragmented calcifications (blue arrows) with an adjacent focus of invasive ductal carcinoma (black arrow).

a b c



From the Department of Pathology, Baylor University Medical Center at Dallas.

Corresponding author: Michael Van Vrancken, MD, MPH, Department of Pathology,



Salivary gland-like neoplasms of the breast are a known entity. A single

novel case of basal cell adenoma of the breast is presented, and the

presentation, treatment, and morphologic features of this case are dis-

cussed.

Although still relatively uncommon, in recent years sali-vary gland-like neoplasms of the breast have become increasingly recognized as an entity. In a 2003 review of salivary gland-like tumors of the breast, several le-

sions were described, including pleomorphic adenoma, adenoid cystic carcinoma, benign and malignant myoepitheliomas, sy-ringomatous carcinoma, adenomyoepithelioma, acinic cell car-cinoma, oncocytic carcinoma, and mucoepidermoid carcinoma (1). Subsequently, a case series of basal cell adenocarcinoma of the breast was presented (2). However, basal cell adenoma of the breast appears to be exceedingly rare with no cases reported in recent reviews (1, 3, 4). Here we present a case of basal cell adenoma of the breast along with its histologic and immuno-histochemical profi le.

CASE REPORTA 90-year-old white woman with prior mitral valve prolapse

repaired in 2004 and hypothyroidism presented with a 3-year history of an enlarging left nipple. No biopsies or imaging had been performed. On examination, the left nipple was larger than the right one, and the skin over it had a slightly purplish discoloration compared to the right. Th ere was no nipple dis-charge and no enlargement of the axillary or supraclavicular lymph nodes.

A mammogram was essentially negative, and a sonogram of the left breast showed a separate subcentimeter hypoechoic density in the 11:00 position located approximately 1 cm from the nipple, adjacent to the larger clinically apparent mass. Both lesions were excised. Histologically, the larger lesion within the left nipple was relatively well circumscribed and composed of a lobulated proliferation of epithelial elements. Th ere was promi-nent palisading of cells at the periphery of the epithelial nests, giving the lesion a “basaloid” appearance (Figure). Additionally, there were focal areas showing slightly more proliferation with cytologic monotony and mildly increased mitotic activity. No

features of malignancy were present. Immunohistochemically, most cells stained positive for p63, and smooth muscle actin highlighted the myoepithelial cells within the lesion. Overall, the histologic and immunohistochemical profi le most closely resembled a basal cell adenoma. Th e separate lesion located at the 11:00 position 1 cm from the nipple was characterized by mostly benign breast tissue with apocrine metaplasia, apocrine cysts, and focal ectatic ducts.

DISCUSSIONSalivary gland-like neoplasms of the breast are well docu-

mented (1). Most are pleomorphic adenomas with only in-frequent examples of other salivary gland-like neoplasms (1). From an embryological standpoint, the occurrence of salivary gland-like neoplasms in the breast should not be too surprising considering the breast and salivary glands are both modifi ed sweat glands. Both are tubuloacinar glands, which share many histologic features. Th erefore, overlapping pathologic features is not an unreasonable expectation. Basal cell adenomas are classically associated with the salivary glands. First described by Kleinhasser and Klein in 1967 (5), they were formally included in the World Health Organization classifi cation in 1991 (6). According to the Armed Forces Institute of Pathology registry, basal cell adenomas are rare, accounting for about 2% of all benign salivary gland tumors (7). Most of these lesions occur in the major salivary glands (75% parotid and 5% submaxillary gland) in adults. Th ere is a 2:1 female predilection. Grossly, these lesions are fairly well circumscribed and solitary and can be treated with conservative excision with a low recurrence rate.

Histologically, there are fi ve morphologic variants of basal cell adenoma. Th e solid type is the most common, followed by the trabecular and trabecular-tubular types. Th e membranous and pure tubular variants are the least common. All variants lack a myxochondroid matrix, as seen in pleomorphic adenomas, and have a fi brous stroma. Th e most common pattern of prolifera-tion is that of cytologically bland basaloid cells with periph-eral palisading seen within the cellular nests. All variants can

Basal cell adenoma of the breastMichael Van Vrancken, MD, MPH, Mariam Mir, MD, and William Herlihy, MD

Basal cell adenoma of the breast 397

demonstrate cystic change, keratinization, and squamous whorls (8). Although morphologically inapparent, there is myoepithe-lial diff erentiation in all variants of basal cell adenoma. Th ese myoepithelial cells can be demonstrated by immunohistochemi-cal stains for smooth muscle proteins.

Th e main diff erential diagnosis of basal cell adenoma in-cludes basal cell adenocarcinoma. Findings can be subtle be-tween the two entities; therefore, it is important to distinguish between them. Basal cell adenocarcinoma diff ers from basal cell adenoma by virtue of its infi ltrative spread, perineural and lymphovascular invasion, and variable degree of cytologic atypia and mitotic activity. Additionally, immunohistochemi-cal stains can help in diff erentiating these two entities. Basal cell adenocarcinomas have been known to express p53, BCL2, and epidermal growth factor receptor (9). In the present case, the lesion was well circumscribed and encapsulated with no evidence of an infi ltrative pattern of growth. No perineural or vascular invasion was identifi ed. Th e cells were monoto-nous with minimal cytologic atypia and focal areas of mildly increased mitotic activity. Overall, these features best fi t with a basal cell adenoma.

Figure. Morphology of basal cell adenoma of the breast. (a) Low-magnification picture showing the relationship to the overlying skin. Note the well-circumscribed

edge of the lesion with the underlying dermis (hematoxylin and eosin, ×40). (b) Medium magnification emphasizing the trabecular architecture with fibrotic stroma

(hematoxylin and eosin, ×200). (c) High magnification of the lesion showing cellular nests of monotonous cells with minimal cytologic atypia. Note the peripheral

palisading (hematoxylin and eosin, ×400). (d) Immunohistochemical stain for p63, a nuclear stain, showing positive staining in many of the tumor nuclei (×400).

1. Pia-Foschini M, Reis-Filho JS, Eusebi V, Lakhani SR. Salivary gland-like tumours of the breast: surgical and molecular pathology. J Clin Pathol 2003;56(7):497–506.

2. Flynn C, Kadivar M, Kwon MY, Bonzanini M, Haines GK 3rd, Tavassoli FA. Basal cell adenocarcinoma arising in salivary gland metaplasia of the breast: a novel salivary gland-type tumor developing in the breast. Hum Pathol 2012;43(10):1764–1771.

3. Cox KL, Korourian S, Klimberg VS. Unusual tumors of the breast. Curr Probl Surg 2009;46(7):514–590.

4. Foschini MP, Eusebi V. Rare (new) entities of the breast and medullary carcinoma. Pathology 2009;41(1):48–56.

5. Kleinsasser O, Klein HJ. Basal cell adenoma of the salivary glands. Arch Klin Exp Ohren Nasen Kehlkopfheilkd 1967;189(3):302–316.

6. Seifert G, Sobin LH. Histological typing of salivary gland tumors. In World Health Organization International Histological Classifi cation of Tumors, 2nd ed. New York: Springer-Verlag, 1991.

7. Ellis GL, Auclair PL. Tumors of the salivary glands. In Atlas of Tumor Pathology, 3rd series, Fascicle 11. Washington, DC: Armed Forces Institute of Pathology, 1996.

8. Zarbo RJ. Salivary gland neoplasia: a review for the practicing pathologist. Mod Pathol 2002;15(3):298–323.

9. Nagao T, Sugano I, Ishida Y, Hasegawa M, Matsuzaki O, Konno A, Kondo Y, Nagao K. Basal cell adenocarcinoma of the salivary glands: comparison with basal cell adenoma through assessment of cell proliferation, apoptosis, and expression of p53 and bcl-2. Cancer 1998;82(3):439–447.

October 2013

a b

c d


Vascular closure devices were introduced in the early 1990s in an effort

to reduce time to hemostasis, enable early ambulation, and improve the

comfort of patients undergoing femoral artery access for endovascular

procedures. Many of these devices leave a foreign component in or

around the artery, which can lead to complications such as hematoma,

pseudoaneurysm, infection, or limb ischemia. Here we present a case

where device embolization led to arterial occlusion and critical limb

ischemia.

CASE REPORTA 51-year-old woman with ventricular premature complex-

induced cardiomyopathy was referred to Baylor University Med-ical Center at Dallas for an electrophysiology study and possible radiofrequency ablation. Her right common femoral artery was accessed for the procedure, and the electrophysiology study and radiofrequency ablation were performed without incident.

An Angio-Seal (St. Jude Medical, St. Paul, MN) was em-ployed to close the femoral artery puncture site. Th e Angio-Seal device consists of three bioabsorbable components to actively seal the arteriotomy. Th e anchor is placed against the inside of the arterial wall. Th e collagen plug sits on top of the arteriotomy in the tissue tract. Th e suture and compaction tube cinch the anchor and collagen together to form a secure seal (Figure 1). In this patient, as the compaction tube was advanced, the suture snapped near the sheath. Th e compaction tube was removed and the suture cut near the skin surface. Th is resulted in par-tial hemostasis with some continued oozing but no pulsatile fl ow or hematoma. Complete hemostasis was obtained with manual compression. Th e patient was observed overnight and discharged the next morning without incident.

Several days later she began to experience right leg claudi-cation after walking 100 feet. On examination, she had a cool right lower extremity with diminished peripheral pulses. Ex-amination of the left lower extremity was normal. A computed tomography scan was performed at an outside hospital and revealed critical right tibioperoneal trunk stenosis. Intravenous heparin therapy was initiated, and she was transferred to Baylor University Medical Center at Dallas.

She underwent an aortobifemoral angiogram performed via a 5 French left common femoral micropuncture. Digital subtrac-

From the Division of Cardiology, Department of Internal Medicine (Cianci, Kowal,

Feghali, Stoler, Choi), and the Department of Vascular Surgery (Hohmann), Baylor

Heart and Vascular Hospital and Baylor University Medical Center at Dallas.

Corresponding author: James W. Choi, MD, Cardiology Consultants of Texas,

621 N. Hall Street, Suite 400, Dallas, TX 75226 (e-mail: jameswchoi@yahoo.

com).

tion angiography of both limbs demonstrated a large amount of thrombus in the distal right popliteal artery extending into the tibioperoneal trunk. Th e anterior tibial artery was occluded at the ostium. Th ere was a 99% stenosis at the tibioperoneal trunk (Figure 2). Manual and rheolytic thrombectomy were performed, and a 4 French Cragg-McNamara infusion cath-eter was placed in the distal right popliteal artery for alteplase thrombolysis. After 36 hours of intermittent thrombolysis, a large thrombus burden remained and operative embolectomy was performed in the distal popliteal and proximal tibial arter-ies. In addition, the remnants of the Angio-Seal closure device (string and collagen plug) were removed from the distal popliteal artery. She tolerated the procedure well and peripheral pulses returned to normal. She was discharged 2 days later.

DISCUSSIONFor several decades, manual compression followed by hours

of bedrest was the sole method of femoral artery puncture site

Critical lower limb ischemia from an embolized Angio-Seal closure deviceChris Cianci, DO, Robert C. Kowal, MD, PhD, Georges Feghali, MD, PhD, Stephen Hohmann, MD, Robert C. Stoler, MD, and James W. Choi, MD

Figure 1. Angio-Seal vascular closure device components. Image courtesy of

St. Jude Medical.

hemostasis. Compression requires a trained medical professional to maintain pressure on the access site for up to 30 minutes, depending on sheath size, anticoagulation status, and several other patient and procedural characteristics. While this method is highly eff ective, it can also be extremely uncomfortable for the patient and labor intensive for the medical staff .

In the early 1990s vascular closure devices (VCDs) were introduced as an alternative to manual compression, and today a variety of VCDs are available. Th e appeal of early ambulation and enhanced patient comfort, as well as the reduction of cost associated with manual compression and in-hospital observation, has made the use of VCDs commonplace. It is estimated that over 1 million VCDs are used yearly in the United States (1).

Despite widespread use, the superiority of VCDs over manual compression in terms of complications has not been defi nitively proven. Th ere are no large randomized clinical trials comparing complication rates of manual compression to those of VCDs. Several large metaanalyses and registries have yielded confl icting data regarding superiority (2–9). Tavris et al reviewed 166,680 patients from the American College of Cardiology-National Cardiovascular Data Registry database who underwent cardiac catheterization in 2001. In this cohort, 53,655 patients received a VCD to obtain hemostasis, while 113,025 patients


received manual compression. Th e risk of experiencing any vascular complication was 1.1% in the VCD group and 1.7% in the manual compression group (P < 0.001) (9). In 2004, Nikolsky et al conducted a metaanalysis of 30 studies involv-ing 37,066 patients undergoing cardiac catheterization. In this study vascular complication rates were higher in the patients who received a VCD (odds ratio 1.34; 95% confi dence interval 1.01–1.79) (6).

Complications related to VCDs may be broadly classifi ed into three categories: hemorrhagic, obstructive, and infective (10). Th e most feared complication of VCDs is limb ischemia. Th is can occur as a result of embolization, thrombosis, or occlu-sion from the intravascular component of the device (11). Sev-eral studies have reported the incidence of lower limb ischemic complications following Angio-Seal use (12–16). Th alhammer et al reported their single-center experience with Angio-Seal–related ischemic complications. Th ey noted 14 instances of symptomatic lower limb ischemia in 7376 patients (0.2%) un-dergoing catheterization between 2003 and 2006 (12). Castelli et al discovered 4 cases of lower limb ischemia in 175 patients who received an Angio-Seal following cardiac catheterization (2.3%) (13). One possible explanation for the wide variation in ischemic complication rates may be operator experience. Balzer et al clearly demonstrated that VCD delivery success rates increased as the operator’s experience and familiarity with the device increased (17).

Limb ischemic symptoms can present acutely in the min-utes after device deployment, but may also have a subacute presentation with claudication in the days or weeks following the procedure (18). Endovascular approaches to treat limb is-che mia caused by VCDs have been described, but most authors recommend direct surgical cutdown, retrieval of the device, and defi nitive arterial repair, most often with venous patch plasty (10). Steinkamp et al reported on their experience using ex-cimer laser and balloon angioplasty in 13 patients with lower limb ischemic symptoms as a result of either vessel occlusion or stenosis related to an Angio-Seal device. Four of the 13 patients had complete vessel occlusion while the remaining 9 had lower-extremity vessel stenosis. All patients were successfully treated and experienced increased walking distance and an improved ankle-brachial index immediately following the procedure and at 3- and 6-month follow-up (19).

Although endovascular or open surgical treatment of limb ischemia resulting from VCDs can be limb sparing, it can be associated with additional signifi cant morbidity. Wille et al de-scribed several cases of limb ischemia resulting from Angio-Seal deployment (18). One patient required a four-compartment fasciotomy of the lower leg to treat reperfusion-induced com-partment syndrome. In addition, the lateral skin defect needed split skin grafting 6 weeks after the procedure. A second pa-tient experienced postoperative groin infection that required debridement, sartorius muscle transposition, and a prolonged course of intravenous antibiotics. Fortunately, our patient had no postoperative sequelae.

While VCDs may reduce the time to ambulation and dis-charge, enhance patient comfort, improve staff effi ciency, and

Figure 2. Angiogram showing thrombus in the right popliteal artery with an

occluded anterior tibial artery.

reduce costly in-hospital monitoring, they can expose patients to additional risks, which can be life and limb threatening. Physicians, nurses, and ancillary staff must be aware of such risks, recognize early signs of potential problems, and act ex-peditiously.

1. Turi ZG. Overview of vascular closure devices. Endovasc Today April 2004:19–20.

2. Dauerman HL, Rao SV, Resnic FS, Applegate RJ. Bleeding avoidance strat-egies. Consensus and controversy. J Am Coll Cardiol 2011;58(1):1–10.

3. Marso SP, Amin AP, House JA, Kennedy KF, Spertus JA, Rao SV, Cohen DJ, Messenger JC, Rumsfeld JS; National Cardiovascular Data Regis-try. Association between use of bleeding avoidance strategies and risk of periprocedural bleeding among patients undergoing percutaneous coro-nary intervention. JAMA 2010;303(21):2156–2164.

4. Applegate RJ, Sacrinty MT, Kutcher MA, Kahl FR, Gandhi SK, Santos RM, Little WC. Trends in vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention via the femoral artery, 1998 to 2007. JACC Cardiovasc Interv 2008;1(3):317–326.

5. Ahmed B, Piper WD, Malenka D, VerLee P, Robb J, Ryan T, Herne M, Phillips W, Dauerman HL. Signifi cantly improved vascular complications among women undergoing percutaneous coronary intervention: a report from the Northern New England Percutaneous Coronary Intervention Registry. Circ Cardiovasc Interv 2009;2(5):423–429.

6. Nikolsky E, Mehran R, Halkin A, Aymong ED, Mintz GS, Lasic Z, Ne-goita M, Fahy M, Krieger S, Moussa I, Moses JW, Stone GW, Leon MB, Pocock SJ, Dangas G. Vascular complications associated with arteriotomy closure devices in patients undergoing percutaneous coronary procedures: a meta-analysis. J Am Coll Cardiol 2004;44(6):1200–1209.

7. Tavris DR, Dey S, Albrecht-Gallauresi B, Brindis RG, Shaw R, Weintraub W, Mitchel K. Risk of local adverse events following cardiac catheterization by hemostasis device use—phase II. J Invasive Cardiol 2005;17(12):644–650.

8. Sanborn TA, Ebrahimi R, Manoukian SV, McLaurin BT, Cox DA, Feit F, Hamon M, Mehran R, Stone GW. Impact of femoral vascular closure

devices and antithrombotic therapy on access site bleeding in acute coro-nary syndromes: Th e Acute Catheterization and Urgent Intervention Tri-age Strategy (ACUITY) trial. Circ Cardiovasc Interv 2010;3(1):57–62.

9. Tavris DR, Gallauresi BA, Lin B, Rich SE, Shaw RE, Weintraub WS, Brindis RG, Hewitt K. Risk of local adverse events following cardiac catheterization by hemostasis device use and gender. J Invasive Cardiol 2004;16(9):459–464.

10. Kalapatapu VR, Ali AT, Masroor F, Moursi MM, Eidt JF. Techniques for managing complications of arterial closure devices. Vasc Endovascular Surg 2006;40(5):399–408.

11. Rilling WS, Dicker M. Arterial puncture closure using a collagen plug, I. (Angio-Seal). Tech Vasc Interv Radiol 2003;6(2):76–81.

12. Th alhammer C, Aschwanden M, Jeanneret C, Labs KH, Jäger KA. Symp-tomatic vascular complications after vascular closure device use following diagnostic and interventional catheterisation. Vasa 2004;33(2):78–81.

13. Castelli P, Caronno R, Piff aretti G, Tozzi M, Lomazzi C. Incidence of vas-cular injuries after use of the Angio-Seal closure device following endovas-cular procedures in a single center. World J Surg 2006;30(3):280–284.

14. Abando A, Hood D, Weaver F, Katz S. Th e use of the Angioseal device for femoral artery closure. J Vasc Surg 2004;40(2):287–290.

15. Kirchhof C, Schickel S, Schmidt-Lucke C, Schmidt-Lucke JA. Local vascular complications after use of the hemostatic puncture closure device Angio-Seal. Vasa 2002;31(2):101–106.

16. Eidt JF, Habibipour S, Saucedo JF, McKee J, Southern F, Barone GW, Talley JD, Moursi M. Surgical complications from hemostatic puncture closure devices. Am J Surg 1999;178(6):511–516.

17. Balzer JO, Scheinert D, Diebold T, Haufe M, Vogl TJ, Biamino G. Postinterventional transcutaneous suture of femoral artery access sites in patients with peripheral arterial occlusive disease: a study of 930 patients. Catheter Cardiovasc Interv 2001;53(2):174–181.

18. Wille J, Vos JA, Overtoom TT, Suttorp MJ, van de Pavoordt ED, de Vries JP. Acute leg ischemia: the dark side of a percutaneous femoral artery closure device. Ann Vasc Surg 2006;20(2):278–281.

19. Steinkamp HJ, Werk M, Beck A, Teichgräber U, Haufe M, Felix R. Ex-cimer laser-assisted recanalisation of femoral arterial stenosis or occlusion caused by the use of Angio-Seal. Eur Radiol 2001;11(8):1364–1370.

Critical lower limb ischemia from an embolized Angio-Seal closure deviceOctober 2013 400

401401

From the Division of Cardiology, Department of Internal Medicine (Chung,

Ko, Hall, Roberts), the Department of Pathology (Roberts), the Department of

Cardiothoracic Surgery (Chamogeorgakis), and the Baylor Heart and Vascular

Institute (Ko, Roberts), Baylor University Medical Center at Dallas. Ms. Chung is

currently a medical student at Texas Tech University Health Science Center and

Paul L. Foster School of Medicine, El Paso, Texas.

Corresponding author: William C. Roberts, MD, Baylor Heart and Vascular Institute,



The Bernheim syndrome has been a topic of discussion for over a

century. It has been reported to be caused by severe rightward move-

ment of the ventricular septum resulting in compression of the right

ventricular cavity leading to right-sided heart failure without pulmonary

congestion. Hemodynamic findings have been described in a few pa-

tients with the so-called Bernheim syndrome. We describe a patient

in whom the ventricular septum dramatically decreased the size of

the right ventricular cavity and yet peak systolic pressures in both the

right ventricle and pulmonary trunk were identical. Thus, it is difficult

to view the Bernheim syndrome as a real entity.

In 1910, Hippolyte Bernheim (1840–1919) (Figure 1) described 10 patients with signs and symptoms of right-sided heart failure, and necropsy in each disclosed a thick left ventricular free wall and ventricular septum with the

latter bulging into the right ventricular cavity (1). He titled this original article “Venous asystole in hypertrophy of the left heart with associated stenosis of the right ventricle.” In that article Bernheim included two drawings, one of a normal heart and one with a thickened left ventricular wall with the thick ventricular septum protruding toward the right ventricular cavity (Figure 2). In 1915, Bernheim published a similar article (2), this time titling it “Right ventricular stenosis caused by displacement of the septum in eccentric hypertrophy of the left ventricle and resulting venous asystole.”

During the next century, a number of articles appeared describing “the Bernheim syndrome.” Although Bernheim described 10 cases in his original article, most subsequent articles have been only case reports (3–11), with few exceptions (1, 12–22). Most subsequent articles were necropsy studies, and most supported the concept of the Bernheim syndrome’s being a real entity. Th ere were exceptions. Evans and White (12) (Figure 1) studied 33 patients at necropsy with considerable left ventricu-lar hypertrophy (heart weight >750 g) and then reviewed their medical records to determine whether signs and symptoms of right-sided heart failure were isolated or simply preceded signs of left-sided heart failure (dyspnea). Th ese authors found

no instance . . . of isolated early signs or symptoms of right-sided failure . . . [and] concluded from . . . [their] analysis,

as well as from prior experience, that . . . [they had] yet to encounter any unquestionable case of so-called Bernheim’s syndrome . . . [and that] it would appear sensible to drop this designation.

In 1955, Selzer and colleagues (6) (Figure 1) described a 62-year-old man with severe hypertension (blood pressure 260/140 mm Hg) hospitalized because of nausea, hepatomegaly, distended neck veins, and clear lung fi elds. Right-sided cardiac catheterization disclosed identical peak systolic pulmonary arte-rial and right-ventricular pressures (87 mm Hg) and identical right atrial mean and right ventricular end-diastolic pressures (18 mm Hg). A few days later, the patient died rather suddenly. His heart weighed 690 g. A cross-section of the cardiac ventricles in this patient is shown in Figure 3. Selzer et al argued right-fully that “‘encroachment’ of the cardiac septum on the cavity of the right ventricle appears to be a normal phenomenon, or may be an accentuation of normal conditions by left ventricular hypertrophy.” Th e authors further argued “that the theoretic criteria for the pathologic diagnosis of the Bernheim syndrome have not been fulfi lled by the majority of cases [reported].” Th ese authors concluded by stating “that the necropsy fi nd-ings alleged to ‘prove’ the existence of Bernheim’s syndrome are based on misconceptions of the normal relationship and are therefore unacceptable. . . . [Th e authors] hoped that the term [the Bernheim syndrome] eventually will be dropped from current terminology.” Surprisingly, Selzer and associates did not emphasize or even mention the lack of right ventricular infl ow or outfl ow obstruction documented hemodynamically in their patient.

Despite the convincing arguments against the concept of the Bernheim syndrome by Evans and White and by Selzer

The myth of the Bernheim syndromeMonica S. Chung, BS, Jo Mi Ko, BA, Themistokles Chamogeorgakis, MD, Shelley A. Hall, MD, and William C. Roberts, MD


Figure 3. Cross-section of the cardiac ventricles in a 62-year-old man reported

by Selzer et al (6). LV indicates left ventricle; VS, ventricular septum; RV, right

ventricle.

and colleagues, cases purported to represent this syndrome continued to be published during the next decades, includ-ing its mention in a recent prominent cardiologic text (23). Described herein is a patient in whom the ventricular septum from apex to base nearly obliterated the right ventricular cavity and yet cardiac catheterization 40 days before cardiac trans-plantation had shown identical pulmonary arterial and right ventricular peak systolic pressures.

CASE STUDYA 71-year-old hypertensive retired college professor

apparently had been well until age 48 years when he had a large myocardial infarct, and at age 54, probably a second myocardial infarct followed shortly by percutaneous coro-nary intervention with stents inserted in both right and left anterior descending coronary arteries. During subsequent years he developed evidence of severe heart failure, runs of

ventricular tachycardia, atrial fi brillation, and a murmur consistent with mitral regurgitation. An intracardiac defi brillator was inserted when he was 63 years old. Th e left ventricular ejection fraction on some occasions was as low as 10%.

When seen at Baylor University Medical Center at Dallas initially in December 2012, he had evidence of severe pulmonary congestion, which rapidly resolved with anti–heart failure drugs. His lungs then were normal to auscultation and by radiography. In April 2013, a right-sided cardiac catheterization was performed (Figure 4). The pulmonary arterial mean wedge pres-sure was 12 mm Hg. His body mass index was 24 kg/m². Just prior to cardiac transplantation (performed in May 2013), he was on 18 medi-cations.

The explanted heart, which weighed 505 g, had extensive left ventricular and ventricular

Figure 1. Portraits of (a) Hippolyte Bernheim, MD, (b) Paul D. White, MD,

and (c) Arthur Selzer, MD.

Figure 2. Illustration in Hippolyte Bernheim’s original article (1): (a) Bernheim syndrome and

(b) normal heart.


a

b c

a b

Figure 4. Hemodynamic tracings from cardiac catheterization in our patient: (a) right atrium; (b) pulmonary artery; (c) right ventricle, and (d) pulmonary capillary

wedge pressure, all in mm Hg.

septal scarring with enormous dilatation of the left ventricular cavity and compression of the right ventricular cavity by the ventricular septum (Figures 5 and 6).

COMMENTSAfter review of previous articles, including photographs of

the heart (3, 6–8, 13, 15–18), none actually showed in our view

compression of the right ventricular cavity by the ventricular septum. In our patient, however, there was marked left ventricular dilatation with clear compression of the right ventricular cavity. Peak systolic pressures in both the right ventricle and pulmonary trunk, however, were identical, indicating the absence of “right ventricular stenosis” despite the appearance thereof from examina-tion of the explanted heart. Th us, we agree with Evans and White

Figure 5. Explanted basal portion of the heart of our patient. The arrow shows

a slit-like right ventricular (RV) cavity. The left ventricular (LV) cavity is severely

dilated, and its wall is focally scarred. The ventricular septum (VS) protrudes

severely toward the right ventricular cavity.

Figure 6. Explanted 1-cm thick slices of the ventricles caudal to the basal portion

of the heart in our patient. The arrows show the extremely small right ventricular

(RV) cavity. LV indicates left ventricle; VS, ventricular septum.

c

a

d

b

The myth of the Bernheim syndrome 403October 2013

and with Selzer et al that “the Bernheim syndrome” is a nonentity and should be dropped from our medical lexicon.

1. Bernheim H. Venous asystole in hypertrophy of the left heart with associ-ated stenosis of the right ventricle. Rev De Med 1910;30:785–801.

2. Bernheim H. Right ventricular stenosis caused by displacement of the septum in eccentric hypertrophy of the left ventricle and resulting venous asystole. J Des Practiciens 1915;29:721.

3. Atlas D, Eisenberg H, Gaberman P. Bernheim’s syndrome: report of a case. Circulation 1950;1:753–758.

4. Wilson EB Jr, Zimmerman SL. Bernheim’s syndrome considered in the light of a fatal case. Am J Med Sci 1950;220(3):257–261.

5. Chapman E, Cronkhite L, Bland E. Bernheim’s syndrome. Am Prac Dig Treat 1951;2:449–450.

6. Selzer A, Bradley HW, Willett FM. A critical appraisal of the concept of Bernheim’s syndrome. Am J Med 1955;18(4):567–576.

7. Slavkovic J, Konecni J, Stankovic S, Vrocic M. Bernheim’s syndrome. Srp Arh Celok Lek 1955;83(1):107–113.

8. Gray JD, Laufer ST. Bernheim’s syndrome terminating in nephrosis. Can Med Assoc J 1955;73(12):947–951.

9. Broustet P, Bricaud H, Cabanieu G, Fontan F, Dallochio M, Rieux M. A case of Bernheim’s syndrome causing stenosis of aortic orifi ce. Bord Chir 1959;1:49–52.

10. Morace G, Guarnieri E. Observations on Bernheim’s syndrome with contribution of 2 clinical cases. Riv Crit Clin Med 1960;60:137–153.

11. Drago EE, Aquilina JT. Bernheim’s syndrome. Am J Cardiol 1964;14:568–572.

12. Evans LR, White PD. Massive hypertrophy of the heart with special reference to Bernheim’s syndrome. Am J Med Sci 1948;216:485–491.

13. Russek HI, Zohman BL. The syndrome of Bernheim. Am Heart J 1945;30:427–441.

14. East T. Bernheim’s syndrome. Br Heart J 1945;8:235. 15. East T, Bain C. Right ventricular stenosis; Bernheim’s syndrome. Br Heart

J 1949;11(2):145–154. 16. Dvorak L. Stenosis of the right ventricle (Bernheim’s syndrome). Cas Lek

Cesk 1950;89(37):1021–1025. 17. Russek HI. Aortic stenosis and Bernheim’s syndrome. J Am Med Assoc

1953;152(6):551. 18. Russek HI, Zohman BL. Th e diagnosis of Bernheim’s syndrome. Trans

Am Coll Cardiol 1954;3:100–106. 19. Michel D, Herbst M, Bock K. Angiocardiographic fi ndings in Bernheim’s

syndrome. Fortschr Geb Rontgenstr Nuklearmed 1957;86(2):181–188.20. Herbst M, Hartleb O, Bock K. Clinical and angiocardiographic con-

fi rmation of Bernheim’s syndrome. Fortschr Geb Rontgenstr Nuklearmed 1959;91:679–689.

21. Sanen FJ. Stenosis of the right ventricle caused by excentric hypertrophy of the left ventricle or ventricular septum (Bernheim’s syndrome). Z Kreislauff orsch 1960;49:331–336.

22. Henein MY, Xiao HB, Brecker SJ, Gibson DG. Bernheim “a” wave: obstructed right ventricular inflow or atrial cross talk? Br Heart J 1993;69(5):409–413.

23. Webb GD, Smallhorn JF, Th errien J, Redington AN. Diseases of the heart, pericardium, and pulmonary vasculature bed. In Zipes DP, Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: a Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier, 2005:1587.


405405

Fibromuscular dysplasia is an uncommon cause of secondary hyperten-

sion. When the resulting hypertension cannot be successfully treated

with medications, balloon angioplasty has been shown to be successful

by disrupting the “webs” of tissue in the renal artery. We present a case

of secondary hypertension due to fibromuscular dysplasia and the suc-

cessful treatment with balloon angioplasty.

CASE DESCRIPTIONA 61-year-old woman was referred to Baylor University

Medical Center at Dallas for severe hypertension, uncon-trolled on several medications. Approximately 1 year earlier, she had been evaluated for “food poisoning” and headache. At that time she was found to have a systolic blood pressure of 180 mm Hg. She subsequently developed a left parietal bleed. She was treated with carvedilol and hydrochlorothi-azide, but because of her age, the sudden onset, and the severity of the hypertension, secondary causes were sus-pected. A meta-iodobenzylguanidine test was performed. It was believed to be positive, and a left adrenalectomy was performed. Despite medical therapy and the adrenal gland resection, she continued to have severe hypertension, with blood pressures in excess of 180 mm Hg systolic at home. A magnetic resonance angiogram (MRA) of her renal arteries showed “beads on a string” in her right renal artery. As this was suggestive of fi bromuscular dysplasia (FMD), she was referred for invasive renal artery angiography. Th e angiogram demonstrated FMD and balloon angioplasty was successfully performed (Figure). On follow-up clinic visits, her blood pressure had normalized on only a low dose of angiotensin-converting enzyme inhibitor.

DISCUSSIONFMD is a disease of unknown etiology that results in

“webs” of tissue which perturb the flow of blood through arterial vasculature. It commonly involves the renal and carotid arteries, although it can involve vertebral, iliac, sub-clavian, and visceral arteries. Disease manifestation may vary widely depending on the arterial segment involved and its severity (1). In adults, women account for about 90% of the cases.

From the Divisions of Cardiology (Hundae, Schussler) and Nephrology (Hebert),

Department of Internal Medicine, Baylor University Medical Center at Dallas; and

the Texas A&M Health Science Center, College of Medicine (Hebert, Schussler).

Corresponding author: Jeffrey M. Schussler, MD, 621 North Hall Street, Suite 500,

Dallas, TX 75226 (e-mail: [email protected])

Renal FMD accounts for about 70% of this disease process. In adults it accounts for about 10% of renovascular hyperten-sion. FMD of the renal arteries is bilateral in about 40% of patients (2). Clinical manifestations are usually a consequence of decreased fl ow across the renal webs.

Severe resistant hypertension, a sudden rise in blood pressure, and increased serum creatinine upon initiation of angiotensin-converting enzyme inhibitors are common presentations of FMD and should be included in the diff er-ential diagnosis when young women present with accelerated hypertension, especially if there is intolerance to antihy-pertensive medication. Abdominal bruits can sometimes be heard.

Angiography is the gold standard for the diagnosis of FMD, but the diagnosis can be made by noninvasive tests (3). Com-puted tomographic angiography is good at detecting FMD. Duplex ultrasound is highly operator and center dependent, but can suggest the diagnosis. MRA has a sensitivity of about 20% and is not as diagnostic for FMD. “Beading” is an im-portant and common angiographic fi nding and is present in >90% of cases.

Treatment options include both medical therapy and revascularization. Conservative treatment involves adequate control of blood pressure with antihypertensive drugs, but stenosis may lead to renal dysfunction and loss of renal pa-renchyma. Other limitations of medical therapy include the need for frequent monitoring of blood pressure and renal function.

Revascularization can cure hypertension in more than half of the cases and can lower the blood pressure in another 25% of the cases. Percutaneous balloon angioplasty has become the preferred method of revascularization with a low complication rate and good results (4, 5). Stents are typically used only as a bailout (i.e., if there is dissection or disruption of the renal artery), but are not typically necessary to achieve a hemody-namically satisfactory result.

Fibromuscular dysplasia of the renal artery as a cause of secondary hypertensionAneley Y. Hundae, MD, Christopher A. Hebert, MD, and Jeffrey M. Schussler, MD


1. Olin JW, Pierce M. Contemporary management of fi bromuscular dys-plasia. Curr Opin Cardiol 2008;23(6):527–536.

2. Lüscher TF, Keller HM, Imhof HG, Greminger P, Kuhlmann U, Lar-giadèr F, Schneider E, Schneider J, Vetter W. Fibromuscular hyperplasia: extension of the disease and therapeutic outcome. Results of the Univer-sity Hospital Zurich Cooperative Study on Fibromuscular Hyperplasia. Nephron 1986;44(Suppl 1):109–114.

3. Slovut DP, Olin JW. Fibromuscular dysplasia. N Engl J Med 2004;350(18):1862–1871.

4. Alhadad A, Mattiasson I, Ivancev K, Gottsäter A, Lindblad B. Revas-cularisation of renal artery stenosis caused by fi bromuscular dysplasia: eff ects on blood pressure during 7-year follow-up are infl uenced by duration of hypertension and branch artery stenosis. J Hum Hypertens 2005;19(10):761–767.

5. Kløw NE, Paulsen D, Vatne K, Rokstad B, Lien B, Fauchald P. Percuta-neous transluminal renal artery angioplasty using the coaxial technique. Ten years of experience from 591 procedures in 419 patients. Acta Radiol 1998;39(6):594–603.

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Figure. (a) Right renal artery demonstrating fibromuscular dysplasia (FMD) and a classic “stacked coins” or “beads on a string” appearance (arrow). (b) An angioplasty

balloon (5 × 20 mm) was inflated in the area of FMD (arrow), (c) with successful result (arrow). Note that while there is reduction of the visible “webs” of tissue, the

final result does not demonstrate complete resolution of the angiographic appearance of the FMD.

a b c

407407

From the Sections of Cardiology, Departments of Medicine, Louisiana State

University Health Sciences Center and the Interim Louisiana State University

Public Hospital, New Orleans.

Corresponding author: D. Luke Glancy, MD, 7300 Lakeshore Drive, #30, New

Orleans, LA 70124 (e-mail: [email protected]).

A 63-year-old man came to the emergency department because he was lightheaded and dyspneic and felt “skipped heart beats.” An electrocardiogram showed sinus P waves at a rate of 44 per minute and repeated

sequences of a right ventricular escape complex that occurred nearly simultaneously with one of the sinus P waves, a con-ducted normal QRS complex with a P-R interval of 0.19 seconds, and a ventricular premature complex with a retro-grade P wave that reset the sinus node (Figure).

Th e problem was the slow sinus rate. It allowed the right ventricular pacemaker to escape and, by causing temporal dispersion of repolarization after the conducted QRSs, fa-cilitated reentrant ventricular premature complexes with retrograde atrial conduction that reset the sinus node, thus slowing it further. Th ere are many causes of sinus bradycar-dia. Among them are medications. Th is hypertensive man was taking clonidine 0.3 mg twice a day and diltiazem 90 mg twice a day, both orally. Th e combination of two or more drugs that can slow the sinus node, such as beta-adrenergic

blocking drugs, non-dihydropyridine calcium-channel block-ers, and clonidine, has on occasion caused profound sinus bradycardia (1, 2) and may also result in signifi cant atrio-ventricular nodal block (3).

1. Mills TA, Kawji MM, Cataldo VD, Pappas ND, O’Meallie LP, Breaux DM, Glancy DL. Profound sinus bradycardia due to diltiazem, vera-pamil, and/or beta-adrenergic blocking drugs. J La State Med Soc 2004;156(6):327–331.

2. Byrd BF 3rd, Collins HW, Primm RK. Risk factors for severe brady-cardia during oral clonidine therapy for hypertension. Arch Intern Med 1988;148(3):729–733.

3. Packer M. Combined beta-adrenergic and calcium-entry blockade in angina pectoris. N Engl J Med 1989;320(11):709–718.

Proc (Bayl Univ Med Cent) 2013;26(4):407

Slow group beatingD. Luke Glancy, MD, and Viral N. Lathia, MD

Figure. Electrocardiogram recorded in the emergency department. See text for explication.

Electrocardiographic Report

From the Sections of Cardiology, Departments of Medicine, Louisiana State

University Health Sciences Center and the Interim Louisiana State University

Public Hospital, New Orleans.

Corresponding author: D. Luke Glancy, MD, 7300 Lakeshore Drive, #30,

New Orleans, LA 70124 (e-mail: [email protected]).

A 53-year-old woman fi rst had a heart murmur noted at age 3. She was symptom free until age 47 but since then has had repeated episodes of cardiac failure. On this occasion she noted increasing shortness of breath,

bilateral leg edema up to her knees, and a 10-lb weight gain over a week’s time. Increasing her furosemide from 20 to 40 mg daily did not relieve her symptoms.

On physical examination, this small, slender woman had a blood pressure of 140/84 mm Hg, bilateral expiratory wheezes, and crackles at both lung bases. Neck veins were elevated to 15 cm above the angle of Louis, and there was 1–2+/4+ edema up to her knees. A 2+/4+ right ventricular lift was felt at the left sternal edge. A hyperdynamic 4+/4+ left ventricular impulse was felt and a third heart sound was heard in the anterior axillary line. A 4+/6+ continuous murmur peaked at the second heart sound and was best heard

in the second left intercostal space. Th ere are many causes of continuous murmurs. When the intensity of the murmur peaks at the second heart sound and the murmur is loudest in the second left intercostal space or just below the medial portion of the left clavicle, the cause is almost always a patent ductus arteriosus. When the murmur is maximal elsewhere, the cause usually is not a ductus.

An electrocardiogram (Figure) recorded at half standard, i.e., 1 mV = 5 mm, showed sinus rhythm with atrial premature complexes, biatrial enlargement, left axis deviation of the QRS

Continuous murmur and cardiac failure in a 53-year-old womanD. Luke Glancy, MD, and Elias B. Hanna, MD

Figure. Electrocardiogram recorded in a 53-year-old woman with a continuous murmur and congestive heart failure. See text for explication.

Electrocardiographic Report


409

complex (–35°), and left ventricular hypertrophy with repolar-ization abnormality, including a long QT interval (405 ms with a QTc of 473 ms). Although left ventricular hypertrophy with repolarization abnormality, i.e., a wide angle between the QRS and the ST-T vectors, is classically seen with pressure overload of the left ventricle, such as occurs with systemic hypertension or aortic stenosis, this repolarization change may occur whenever left ventricular hypertrophy is severe, no matter the cause (1).

Th e chest radiograph demonstrated a huge cardiac silhouette, prominent pulmonary vasculature, bilateral pulmonary edema, and scoliosis of the spine, which is more common in patients with congenital heart disease than in the general population.

In the past, patients with patent ductus arteriosus occa-sionally have lived to be far older than our patient (2), but for 75 years now closure of the arterial duct, fi rst by surgical ligation (3) and more recently by catheter-delivered closure devices (4), has been available as a highly eff ective and rela-tively low-risk cure for the malformation. Consequently most arterial ducts are now closed in infancy or early childhood. Our patient, however, has always refused any invasive treat-ment. In her, the duct is large enough to allow a moderately large left-to-right shunt that over time has produced severe left atrial and left ventricular enlargement. Although her left

ventricular ejection fraction 18 months ago was 50% as judged by echocardiogram, the left ventricle clearly is failing and the resulting pulmonary arterial hypertension has caused right ventricular and right atrial enlargement. Th is has been ac-centuated by chronic obstructive pulmonary disease caused by her smoking 1½ packs of cigarettes per day for 25 years and manifested by a forced expiratory volume in 1 second of 35% and wheezing even when she is not in overt cardiac failure, and by a hemoglobin of 17 g/dL and a hematocrit of 53% on the current admission.

Th e patient responded to medical treatment for congestive heart failure but was lost to follow-up after discharge.

1. Liebman J. Electrocardiography in congenital heart disease. Patent ductus arteriosus. In Macfarlane PW, Lawrie TDV, eds. Comprehensive Electro-cardiology: Th eory and Practice in Health and Disease, vol. 1. New York: Pergamon Press, 1989:754–762.

2. Campbell M. Patent ductus arteriosus: some notes on prognosis and on pulmonary hypertension. Br Heart J 1955;17(4):511–533.

3. Gross RE, Hubbard JP. Surgical ligation of a patent ductus arteriosus. Report of fi rst successful case. JAMA 1939;112(8):729–731.

4. Masura J, Walsh KP, Th anopoulous B, Chan C, Bass J, Goussous Y, Gavora P, Hijazi ZM. Catheter closure of moderate- to large-sized patent ductus arteriosus using the new Amplatzer duct occluder: immediate and short-term results. J Am Coll Cardiol 1998;31(4):878–882.

Continuous murmur and cardiac failure in a 53-year-old womanOctober 2013


We describe the case of a 24-year-old woman who intentionally ingested

between 400 and 600 mg of amlodipine along with a large number of

simvastatin and trazodone tablets.

CASE HISTORYA 24-year-old white woman with a past history of depression

being treated with sertraline presented to the emergency depart-ment with nausea, vomiting, and diarrhea after ingesting 400 to 600 mg of amlodipine and unknown quantities of simvastatin and trazodone. Th e quantities ingested were deduced based on the last refi ll date and contacting the pharmacy. Th e patient had one previous suicide attempt while in high school. She reported a recent altercation with her estranged husband and a history of alcohol abuse and rehabilitation. She was sober until the night of the overdose, when she had a beer. She smoked 30 cigarettes each day and denied the use of any illicit drugs.

In the emergency department, she was euthermic with a heart rate of 99 beats/minute, in no distress, but with a blood pressure of 72/34 mm Hg. Her skin was cold and clammy. Her laboratory results at presentation are shown in Table 1. She received 3 L of normal saline and 1 L of 5% dextrose in normal saline in the emergency department. Because the hy-potension remained refractory, vasopressor agents were initiated with dopamine and norepinephrine followed by vasopressin and phenylephrine. Th e patient was intubated for airway protection. Glucagon was started with a 10 mg bolus followed by a continu-ous infusion at 10 mg/h. A 20% fat emulsion (Intralipid) was started with a 1.5 mg/kg bolus over 10 minutes followed by 0.25 mL/kg/h. A calcium gluconate drip was started at a rate of 1 g/h. In addition, an intravenous insulin infusion was started at a rate of 70 units/h along with 10% dextrose. Th e patient started developing metabolic acidosis in spite of an intravenous isotonic bicarbonate infusion. Continuous venovenous hemodi-alysis without any ultrafi ltration was started for the worsening metabolic acidosis and the anuria. Intravenous hydrocortisone was administered at a dose of 50 mg every 8 hours.

On the second day of hospitalization, a chest radiograph showed worsening bilateral pulmonary infi ltrates. With numer-ous catecholamines, the heart rate was up to 140 beats per min-ute and the respiratory rate increased to 35 breaths per minute. A fractional inspired oxygen concentration (FiO2) at 100% was

From the Department of Nephrology, Texas Health Presbyterian Hospital, Dallas,

Texas (Patel); the Department of Sports Medicine, Ohio State University, Columbus,

Ohio (Tietze); the Division of Nephrology, Department of Internal Medicine, Baylor

University Medical Center, Dallas, Texas (Mehta); and the Department of Internal

Medicine, Texas A&M Health Science Center, College of Medicine (Mehta).

Corresponding author: Ankit N. Mehta, MD, 3601 Swiss Avenue, Dallas, TX

75204 (e-mail: [email protected]).

instituted. Ultrafi ltration was started with continuous veno-venous hemodialysis. Dopamine and lipid emulsion infusions were discontinued as hemodynamic stability improved.

By the third hospital day, the patient’s heart rate had slowed, but leukocytosis developed. Meropenem and levofl oxacin were added. Phenylephrine was tapered, and albumin 25 g every 8 hours was started to aid in vasopressor tapering.

By the fourth day of hospitalization, the FiO2 was reduced to 60% with maintenance of good oxygen saturation. A chest radiograph showed improvement in the pulmonary infi ltrates. Th e high-dose insulin drip was discontinued and the calcium gluconate drip was decreased to 0.5 g/hour. Vancomycin was started for methicillin-resistant Staphylococcus aureus coverage and the intravenous bicarbonate was stopped. Th e following day, vasopressin and norepinephrine were tapered off .

Two days later, glucagon and calcium gluconate were discon-tinued. Th e patient was extubated on the ninth day of admission and transitioned to intermittent hemodialysis. Th e patient’s continued kidney failure was attributed to acute tubular necrosis from hypotension and rhabdomyolysis. Th e rhabdomyolysis reached a peak creatine phosphokinase of 5035 U/L 50 hours after ingestion. Th is eventually resolved without the need for continued hemodialysis 17 days after continuous venovenous hemodialysis was fi rst initiated. Her creatinine at the time of discharge was 1.7 mg/dL. She was discharged home 23 days after admission.

DISCUSSIONAmlodipine, a dihydropyridine calcium channel blocker, has

a half-life of approximately 30 to 50 hours and a large volume of distribution (2 L/g). Its slower and longer (up to 72 hours) duration of action, relative lack of negative inotropy, and once-daily dosing has made it preferred over other calcium channel blockers (CCBs) such as verapamil or nifedipine. CCBs such as amlodipine reduce calcium fl ux through voltage-gated slow

Amlodipine overdoseTapan Patel, MD, David Tietze, MD, and Ankit N. Mehta, MD

(L-type) calcium channels. Th e major toxic eff ect of an overdose is refractory hypotension, due to both vasodilation and impaired cardiac metabolism and contractility. Tissue ischemia and lactic acidosis ensue. Blockade of calcium channels in other tissues, such as pancreatic beta cells, also has other important adverse consequences (i.e., reduced insulin release).

Intravenous volume expansion (using sodium bicarbon-ate–containing solutions to simultaneously attempt to correct the lactic acidosis) and multiple vasopressors are routinely initiated, but this treatment is often ineff ective (1) because the primary mechanism of hypotension is arterial muscle relax-ation and not hypovolemia. Calcium infusion provides a direct antidote and may be helpful; however, the response to calcium is also often inadequate (2). Given its relatively benign inter-vention, even in the presence of high serum concentrations

acutely, calcium is still often utilized in these patients. Glu-cagon may be infused because it activates myocardial adenyl-ate cyclase and thus increases cardiac cyclic adenosine mono-phosphate levels, which results in an inotropic eff ect. High-dose insulin infusion together with adequate glucose to maintain normal glucose levels—so-called “hyperinsulinemia/euglycemia therapy”—has been shown to be very eff ective in experimen-tal models of CCB overdose (3, 4). Insulin has a direct positive cardiac inotropic action and may also improve myocardial carbo-hydrate oxidation, which is of-ten impaired in these patients. Finally, intravenous lipid infu-sions have recently been used to treat lipid-soluble drug over-doses (5–8). Raising serum lipid levels can markedly increase the drug’s volume of distribution and thereby reduce its eff ective plasma level. Furthermore, pro-vision of triglycerides provides an alternative energy source for the myocardium.

1. Harris NS. Case records of the Mas-sachusetts General Hospital. Case 24-2006. A 40-year-old woman with hypotension after an over-dose of amlodipine. N Engl J Med 2006;355(6):602–611.

2. Kerns W 2nd, Kline J, Ford MD. Beta-blocker and calcium channel blocker toxicity. Emerg Med Clin North Am 1994;12(2):365–390.

3. Lheureux PE, Zahir S, Gris M, Derrey AS, Penaloza A. Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care 2006;10(3):212.

4. Azendour H, Belyamani L, Atmani M, Balkhi H, Haimeur C. Severe amlodipine intoxication treated by hyperinsulinemia euglycemia therapy. J Emerg Med 2010;38(1):33–35.

5. Orr K, Bailie R. Th e use of Intralipid in the management of a mixed overdose. J Intens Care Soc 2010;11(4):268–269.

6. West PL, McKeown NJ, Hendrickson RG. Iatrogenic lipid emul-sion overdose in a case of amlodipine poisoning. Clin Toxicol (Phila) 2010;48(4):393–396.

7. Young AC, Velez LI, Kleinschmidt KC. Intravenous fat emulsion ther-apy for intentional sustained-release verapamil overdose. Resuscitation 2009;80(5):591–593.

8. Turner-Lawrence DE, Kerns Ii W. Intravenous fat emulsion: a potential novel antidote. J Med Toxicol 2008;4(2):109–114.

Table 1. Laboratory results obtained during the patient’s early hospitalization for amlodipine overdose

Test Admit

Hours after ingestion

12 h 24 h 36 h 50 h 80 h 110 h 140 h

Sodium (mEq/L) 140 139 141 138 140 137 135 138

Potassium (mEq/L) 4.2 4.1 3 3.4 3.9 4.3 5.5 4.5

Chloride (mEq/L) 107 113 111 104 107 105 102 103

Carbon dioxide (mEq/L) 17 13 17 25 23 21 24 26

Blood urea nitrogen (mg/dL) 15 17 18 9 5 3 14 20

Creatinine (mg/dL) 2.6 2.7 2.2 1.1 1.3 1.1 1.2 1

Glucose (mg/dL) 150 418 328 135 103 292 160 147

Calcium (mg/dL) 9.3 7.2 7.2 8.2 8.5 9.4 9.7 9.3

Protein (g/dL) 7.3 n/a n/a 4.6 4 4.5 4.9 5.3

Phosphorus (mg/dL) 5.5 0.8 2.3 1.8 4.2 2.1 4.3 3.9

Magnesium (mg/dL) 1.6 1.4 1.7 1.9 1.6 1.6 1.9 1.8

Albumin (g/dL) 4.2 n/a n/a 2.3 1.9 2.4 2.4 2.3

Bilirubin (mg/dL) 1.1 n/a n/a 2.4 1.9 1.8 2.3 4.1

Alkaline phosphatase (U/L) 46 n/a n/a 46 34 47 67 98

Aspartate aminotransferase (U/L) 11 n/a n/a 180 184 108 94 88

Alanine aminotransferase (U/L) 18 n/a n/a 44 52 40 41 49

pH 7.3 7.27 7.24 7.42 7.3 7.48 7.42 7.54

Partial pressure of oxygen (mm Hg) 124 149 84 79 47 154 180 93

Partial pressure of carbon dioxide (mm Hg) 26 21 43 41 50 31 41 32

Oxygen saturation (%) 98.1 98.9 94.6 99.3 77.2 99.4 99.3 98

White blood cells (K/uL) 14.3 n/a 24.7 n/a 33.8 26.5 27.4 23.4

Hemoglobin (g/dL) 13.4 n/a 11 11.5 10.5 9 8.5 8.8

Hematocrit (%) 39.4 n/a 33.4 34.1 31.2 26.6 24.8 25.4

Platelets (K/uL) 307 n/a 159 n/a 63 68 84 91

Creatine phosphokinase (U/L) 46 57 296 2547 5035 2189 1457 1191

Amlodipine overdoseOctober 2013 411

■ U.S. News & World Report names Baylor University Medical Center at Dallas no. 1 in Dallas-Fort Worth metro area, no. 2 in TexasBaylor University Medical Center at Dallas

(BUMC) has been ranked no. 1 in the Dallas–Fort

Worth area and no. 2 in Texas for 2013–2014

by U.S. News & World Report. BUMC, which has

been included in the U.S. News & World Report

rankings for more than 20 years, was ranked

nationally for 2013 in seven medical specialties:

gastroenterology and gastrointestinal surgery

(no. 16 in the nation), nephrology (no. 18 in the

nation), pulmonology (no. 22 in the nation), ortho-

pedics (no. 24 in the nation), gynecology (no. 32 in

the nation), neurology and neurosurgery (no. 36 in

the nation), and diabetes and endocrinology (no. 38

in the nation). The hospital is also high-performing

in cancer, cardiology and heart surgery, geriatrics,

urology, and ear, nose, and throat.

In its metro-area rankings, U.S. News &

World Report gives consumers information about

high-performing hospitals in their backyard. This

year, the magazine ranked three Baylor Health

Care System (BHCS) hospitals: Baylor Regional

Medical Center at Plano, Baylor All Saints Medical

Center at Fort Worth, and BUMC.

“Dallas–Fort Worth is an extremely com-

petitive health care environment with some of

the most recognized health care organizations

in the country,” said Joel Allison, president and

CEO of BHCS. “So we are certainly honored and

humbled for Baylor University Medical Center

to be ranked no. 1 in the metroplex and for two

additional Baylor hospitals to also be ranked. This

recognition is a testament to the dedication of

our talented, compassionate caregivers.”

■ New blood test detects colon cancer before it develops A new blood test developed in the

Gastrointestinal Cancer Research Lab at Baylor

Research Institute (BRI) is showing very promising

results for finding cancer-related microRNA in the

blood before a tumor develops in the colon. In

a seminal study published in the Journal of the

National Cancer Institute, the BRI investiga-

tors studied several hundred patients with co-

lorectal polyps and cancers and reported that

measuring levels of miR-21 in the blood could

accurately identify up to 92% of patients with

colorectal cancer. Not only is this test good for

noninvasively identifying patients who already

have colorectal cancer, but it can accurately

identify up to 82% of patients with advanced

colon polyps, which present the highest risk

for developing into colorectal cancers several

years later.

“The development of this biomarker is

highly encouraging because the high mortal-

ity rates associated with colorectal cancer

are a consequence of late detection of this

disease, underscoring the need for improved

early detection, prevention, risk assessment,

and intervention,” said Ajay Goel, PhD, director

of epigenetics and cancer prevention at BRI.

Early detection of advanced colorectal polyps

and cancers is considered the most relevant

target for screening strategies and the best ap-

proach to improving survival of these patients.

“This blood-based test could be transformative

in how we screen patients for colorectal cancer;

it would save lives and could result in major

savings of health care dollars,” said Michael

A. E. Ramsay, MD, president of BRI.

■ BRI enters license agreement for SJIA treatment BRI, the research arm of BHCS, has signed

an agreement with Novartis to nonexclusively

license Baylor’s patents for Ilaris (canakinumab),

a drug used to treat systemic onset juvenile

idiopathic arthritis (SJIA) that utilizes interleu-

kin-1 beta antagonists. On May 10, 2013, the

US Food and Drug Administration approved

Ilaris for the treatment of active SJIA in patients

aged 2 years and older. Ilaris is the first IL-1

beta inhibitor approved for SJIA and the only

treatment approved specifically for SJIA. Ilaris is

administered subcutaneously once a month.

“This agreement adds to the success and

reputation of the scientists and the scientific

platform at Baylor Research Institute,” said

Michael A. E. Ramsay, MD, president. “The

institute is a world-class center for human

immunology research, and this is an excellent

example of precision medicine.”

At BRI, Virginia Pascual, MD, and colleagues

have shown that oversecretion of IL-1 beta plays

a significant role in SJIA and, most important,

that blocking IL-1 beta activity is clinically ben-

eficial. “It is very rewarding to learn that our

original findings have now been validated in

multicenter trials involving hundreds of children

around the world,” Dr. Pascual said. “The best

part is that we now have an effective treatment

for an otherwise devastating disease.”

■ Baylor shows progress building programs in geriatric care When the Deerbrook Charitable Trust gave

BHCS a 3-year, $12 million grant in 2011, they

had a specific goal in mind for the gift. They

wanted an interdisciplinary team of health care

professionals to plan, develop, and execute

programs that advance the field of geriatric

care. Baylor nursing was up to the challenge.

Nursing leaders Rosemary Luquire, PhD, RN,

FAAN, NEA-BC, senior vice president and

chief nursing officer, and Dora Bradley, PhD,

RN-BC, vice president of nursing professional

development, along with Cynthia Krause, vice

president, BHCS Foundation, set out to build

a five-pronged program that addresses care

of the older adult. The five programs are as

follows:

Center for Learning Innovation and Practice.•

The center team is in the process of de-

veloping a virtual learning simulator for

APPOINTMENT AND ACCOLADESDavid Klein, MD, MBA, has been named

president of Baylor All Saints Medical Center

at Fort Worth. Klein served as interim president

since July 2012 before assuming his role and

practiced general surgery for 14 years before

becoming a full-time hospital administrator.

Robert L. Coffman, PhD, an investigator at

the Baylor Institute for Immunology Research,

has been honored as one of two recipients of

the 2013 Novartis Prize for Basic Immunology.

Dr. Coffman, who is also the vice president

and chief scientific officer at Dynavax, shares

the prize with Tim R. Mosmann, PhD, direc-

tor of the Human Immunology Center at the

University of Rochester. The Novartis Prize is

given once every 3 years and is considered the

most prestigious award in immunology.

David J. Ballard, MD, PhD, BHCS

chief quality officer and executive director

of the Institute for Health Care Research

and Improvement, received the John M.

Eisenberg Article-of-the-Year in Health

Services Research Award from Health

Services Research journal. Dr. Ballard was

singled out for the article “The Effectiveness

of Implementing an Electronic Health Record

on Diabetes Care and Outcomes.”

Baylor news


health care professionals and caregivers

to learn more about improving care of the

older adult.

Partnership with nursing homes.• Through

partnerships with three nursing homes in

Garland and three nursing homes in Irving,

Baylor nurses monitor patients’ conditions

after discharge and offer education to the

staff. Jobeth Pilcher, EdD, RN-BC, explained

that Baylor “is starting to see a decrease

in readmission rates at those nursing

homes.”

Transitional care model.• When elderly pa-

tients who suffer the effects of heart fail-

ure and pneumonia are discharged from

a Baylor facility, caregivers follow up with

them after 30 days, either in person or on

the phone, to check on their condition, an-

swer questions, and ensure that they are

adhering to treatment regimens.

RECENT GRANTS• Analysis and dissemination of

patient-centered outcomes and its impact on patients

Principal investigator: Ian McCarthy, PhD

Sponsor: Agency for Healthcare

Research and Quality

Funding: $145,259

Award period: 7/1/2013–6/30/2014

• Systems biology of cardiovascular biomarkers in psoriasis

Principal investigator: Gerlinde

Obermoser, MD

Sponsor: National Psoriasis

Foundation

Funding: $100,000

Award period: 6/15/2013–6/15/2014

• Dendritic cell asialoglycoprotein receptor as a novel target for controlling graft-versus-host disease and allograft rejection

Principal investigator: Sangkon Oh, PhD

Sponsor: National Institutes of Health

Funding: $368,480

Award period: 6/1/2013–5/31/2014

• Controlling allergen-specific Th2-type responses by targeting dendritic cell surface lectins

Principal investigator: Sangkon Oh,

PhD


Funding: $232,885

Award period: 7/1/2013–6/30/2014

• Systems analysis vaccine responses in healthy and hyporesponsive humans

Principal investigator: A. Karolina Palucka, MD


Funding: $3,059,835

Award period: 7/1/2013–6/30/2014

• North Texas Hepatitis B Consortium: clinical site for the Hepatitis B Network

Principal investigator: Robert Perrillo, MD

Sponsor: The University of Texas

Southwestern Medical Center

Funding: $114,527

Award period: 6/1/2013–5/31/2014

• Novel treatment and screening strategies in heritable gamma- hydroxybutyric aciduria

Principal investigator: Lawrence

Sweetman, PhD

Sponsor: Washington State University/

National Institutes of Health

Funding: $138,839

Award period: 12/1/2012–11/30/2013

• National Psoriasis Foundation medical research fellowship program 2013

Principal investigator: Alan Menter, MD

Sponsor: National Psoriasis Foundation

Funding: $40,000

Award period: 7/1/2013–6/30/2014

• Implementing a bundle for intensive care unit delirium—the IBID project

Principal investigator: Andrew Masica,

MD

Sponsor: Agency for Healthcare Research

and Quality

Funding: $291,506

Award period: 7/1/2013–6/30/2014

• Harnessing human dendritic cell subsets for improved mucosal vaccines

Principal investigator: Yong-Jun Liu, MD


Funding: $4,177,256 (fully funded at

$4,362,911)

Award period: 5/1/2013–4/30/2014

• JC virus and human colorectal neoplasia

Principal investigator: C. Richard Boland,

MD


Funding: $120,319 (6-month; fully

funded at $251,332)

Award period: 2/1/2013–1/31/2014

• Familial and early onset colorectal cancer

Principal investigator: C. Richard Boland, MD


Funding: $78,140 (3-month; fully funded

at $312,561)

Award period: 5/1/2013–4/30/2014

• New-onset post-CABG atrial fibrillation Principal investigator: Giovanni Filardo, PhD


Funding: $672,982 (fully funded at

$711,867)

Award period: 5/1/2013–4/30/2014

Inpatient geriatric volunteer program com-• bating delirium

School of nursing consortium• To share the knowledge they have gleaned

with a broader audience, Baylor’s Center for

Learning Innovation and Practice sponsored

a 2-day interprofessional conference in June:

the 2013 Care of the Older Adult: Real World

Applications. The conference attracted more

than 200 attendees from 12 states. In ad-

dition to featuring prominent speakers, the

conference introduced its audience to some

unique applications of assistive and learning

technologies, including a glow-in-the-dark

toilet seat, a talking pill dispenser, and a

GPS device that alerts when an elderly family

member wanders off. “These kinds of assis-

tive technologies offer some pretty creative

solutions to tackling the real-world challenges

of aging,” said Pilcher.

■ Baylor Medical Center at Frisco expands emergency department Baylor Medical Center at Frisco opened

its newly expanded emergency department

in August 2013, which more than tripled the

emergency department’s footprint with a total of

9031 square feet. It is located on the east side

of the main hospital campus. “We’re expanding

to meet the growing demand for emergent care

in Frisco,” said William Keaton, CEO of Baylor

Frisco. “As Frisco remains one of the fastest-

growing communities in the nation, keeping our

low ‘door-to-doc’ time is a priority we take very

seriously.”

■ Study tests new treatment for high-risk patients with aortic stenosisRobert Stoler, MD, FACC, FSCAI, director

of the cardiac catheterization lab at Baylor

Baylor news 413October 2013

Heart and Vascular Hospital (BHVH) and co-

medical director, Division of Cardiology, is

leading Baylor’s participation in a clinical

trial to research a new treatment option for

patients with aortic stenosis. BHVH is one

of 45 national sites researching the use of

the Medtronic CoreValve transcatheter aor-

tic valve replacement system as a treatment

alternative to open-heart surgery. “Every

research division in the country would like

to have this study. We’re proud that we can

offer this opportunity to our patients,” said

Dr. Stoler.

The procedure, which is minimally inva-

sive, takes approximately 2 hours to com-

plete. It is performed by making an incision

in the femoral artery and delivering the new

aortic valve via a catheter threaded up to the

heart. The artificial valve is made of natural

tissue with “leaflets” that control the flow of

blood secured to a flexible, self-expanding

frame for support. Patients who have re-

ceived the system report an immediate im-

provement in their ability to breathe deeply,

and typical recovery time is between 4 and

7 days. Dr. Stoler has high hopes that the

CoreValve clinical trial will result in its Food

and Drug Administration approval for use in

high-risk or inoperable patients within the

next 1 to 2 years. He also anticipates that a

successful trial will lead to new generations

of valves from Medtronic and other device

companies coming to trial as advances in

the understanding of this treatment con-

tinue.

UPCOMING CME PROGRAMSThe A. Webb Roberts Center for Continuing Education of Baylor Health Care System is

offering the following programs:

40th Annual Williamsburg Conference on Heart Disease, December 8–10, 2013

17th Annual Tyler Breast Cancer Conference, March 21–22, 2014

Cardiac Innovations, May 8, 2014

Fifth Annual Latest Advances in Ischemic and Hemorrhagic Stroke Therapy, May 17, 2014

For more information, call 214-820-2317 or visit www.cmebaylor.org.

PHILANTHROPY NOTES■ NFL lineman goes on the offense for

the 14th annual Celebrating Women luncheonThe 14th annual Baylor Health Care System

Foundation Celebrating Women luncheon will be

held on Wednesday, October 23, at 11:45 AM

at the Hilton Anatole Hotel in Dallas. The event,

presented for the ninth consecutive year by Tom

Thumb, has raised more than $19 million to

fight breast cancer throughout BHCS. In the past

13 years, donations to Celebrating Women have

supported expanded technology, community

outreach, innovative clinical research, educa-

tion, and programmatic needs for the men and

women fighting this disease.

This year’s speaker, Chris Spielman, is an

ESPN college football analyst with a remarkable

athletic record. An 11-year veteran in the NFL, he

is a member of the College Football Hall of Fame,

a four-time Pro Bowl linebacker, and a two-time

defensive MVP for the Detroit Lions. He discov-

ered after his late wife Stefanie’s diagnosis that

his biggest opponent in life wasn’t a hard-hitting

football player but the difficult fight against breast

cancer. Through his awareness and fundraising

work, Chris remains committed to continuing

Stefanie’s legacy of hope and to finding a cure.

For information about underwriting oppor-

tunities and tickets to Celebrating Women, call

214-820-4500 or e-mail CelebratingWomen@

BaylorHealth.edu. Sponsorship and underwriting

opportunities are still available; individual tickets

start at $250 and table prices start at $2500.

■ Grand Rounds® Golf Tournament to raise money for medical education D. A. Weibring will be the guest speaker at

the VIP celebrity reception for the 12th annual

Grand Rounds® Golf Tournament. Golfer, de-

signer, and businessman, D. A. is the founder

and chairman of Weibring-Wolfard Golf Design

and a full-time player on the PGA Champions

Tour. In a career that spans 35 years, D. A. has

13 victories worldwide, including several on

the PGA Tour and Champions Tour.

The event, presented by Bank of Texas and

held Monday, October 7, at Dallas’ Northwood

Club, raises funds to provide medical educa-

tion to both undergraduate medical students

and graduate physicians at BUMC. Last year,

more than 200 golfers and 50 sponsors raised

a record $305,000 for the medical education

program at BUMC.

BUMC trains nearly 220 residents and fel-

lows in 30 specialty and subspecialty programs.

With donor support, BHCS Foundation plans to

fund 30 residents and fellows at a cost of more

than $2.2 million this fiscal year. Playing spots

and sponsorships for this year’s tournament are

now available. For more information, contact

Lindsay Nahoum at 214-820-7734 or Lindsay.

[email protected].

■ Walk your way to better health at fourth annual DHWI Healthy Harvest eventJoin us and be a part of the fourth annual

Diabetes Health and Wellness Institute (DHWI)

Healthy Harvest Fun Walk/5K Run & Diabetes Expo

on Saturday, October 26, 2013. The event will bring

more than 1000 walkers and runners together at

DHWI headquarters to promote awareness and

raise funds for the programs at DHWI.

The event’s keynote speaker is Sherri

Shepherd. The host of The View, New York

Times best-selling author, and former Dancing

with the Stars contestant is dedicated to shar-

ing her passion for staying healthy.

DHWI is the area’s first and only diabetes

health and wellness facility addressing the re-

gion’s health care needs relative to diabetes.

The goal of the center is to weave diabetes

prevention into the fabric of the community so

that it is a natural and convenient part of life

in the neighborhood. The mission: To improve

the care and save lives of people with diabetes

through a new care model focused on health

care, education, and research.

For more information, contact Courtney

Brown at 214-820-7410 or Courtney.Brown@

baylorhealth.edu.


■ Baylor expands low-dose CT scan program for those at high risk of developing lung cancerFor people at high risk of developing lung

cancer, the most effective screening may be

a low-dose CT scan, according to the latest

research published from the National Lung

Screening Trial in The New England Journal

of Medicine. People who are referred by their

physician for being at high risk for lung can-

cer can take advantage of the low-dose CT

lung cancer screening at Baylor Charles A.

Sammons Cancer Centers at Dallas, Irving,

and Plano. Candidates for the screening in-

clude current and former smokers over the

age of 55, people over 50 years old who have

smoked the equivalent of one pack per day for

30 years or three packs a day for 10 years,

and people with occupational exposure to other

carcinogenic agents, including asbestos and

diesel fumes. An important consideration for

screening is whether the level of individual risk

is high enough for screening to be of benefit.

A physician referral is required.

■ Baylor Endocrine Center begins recruiting for long-term diabetes drug studyBaylor Endocrine Center is looking for vol-

unteers to take part in a study to compare the

long-term benefits and risks of four widely used

diabetes drugs in combination with metformin,

the most common first-line medication for treat-

ing type 2 diabetes. The study—called GRADE:

Glycemia Reduction Approaches in Diabetes: A

Comparative Effectiveness Study—will compare

drug effects on glucose levels, adverse effects,

diabetes complications, and quality of life over

an average of nearly 5 years.

GRADE aims to enroll about 5000 patients

around the country. Investigators at Baylor

Endocrine Center and 36 other study sites are

seeking people diagnosed with type 2 diabetes

within the past 5 years. They may be taking

metformin but not any other diabetes medica-

tions. During the study, all participants will take

metformin along with a second medication

randomly assigned from among four classes of

medications approved for use with metformin by

the US Food and Drug Administration.

■ EPA awards area’s first Energy Star to Baylor Fort Worth Baylor All Saints Medical Center at Fort

Worth recently became the first hospital in the

Dallas–Fort Worth metroplex to earn Energy

Star certification from the US Environmental

Protection Agency. Energy Star certification rec-

ognizes the hospital for its leadership in energy

management and conservation efforts.

Key elements of Baylor Fort Worth’s energy

management strategy included upgrading older

HVAC equipment to improve efficiency; replac-

ing parking garage light fixtures with new, more

efficient lighting; creating an operational effi-

ciency scorecard for engineering focusing on

identifying, implementing, and measuring en-

ergy improvements in daily facility operations;

and launching an employee energy awareness

program.

Results of the program since July 2010 in-

clude $825,000 in energy project savings; a

12.4% year-over-year reduction in total energy

consumption; a 9.5% year-over-year reduction

in water consumption; an 11.1% commingled

recycle rate; and a 52% overall improvement

in first-year operational energy scorecard per-

formance.

■ Providing a new dimension to medical care: the Integrative Medicine Program at Baylor Charles A. Sammons Cancer Center at DallasThe Integrative Medicine Program at

Baylor Charles A. Sammons Cancer Center at

Dallas—the first hospital-based program in

North Texas—offers different therapies that

work together with traditional medicine to help

patients. The program focuses on each pa-

tient’s concerns from a holistic viewpoint and

addresses nutritional, physical, emotional, and

spiritual aspects of their lives.

“Every patient is unique, and individual

recommendations are tailored for the patient’s

own set of circumstances and concerns,” said

Carolyn Matthews, MD, a gynecologic oncolo-

gist on the medical staff at BUMC and medical

director of the Integrative Medicine Program. “In

the last year, we have helped patients fine-tune

their lifestyles to address such issues as weight

loss, hypertension, and chronic back pain, in

addition to helping those patients being treated

for cancer.” Dr. Matthews is board certified in

integrative and holistic medicine, medical acu-

puncture, and palliative medicine.

Therapies include nutritional guidance, with

a focus on special diets and botanical supple-

ments, as well as mind-body techniques such

as acupuncture. Guided imagery, breathing for

stress relief and relaxation, and personalized

exercise programs are also offered as part of

integrative therapies. Music and art classes

also add dimension to customized care plans.

Cooking classes focusing on the nutritional

needs of patients during treatment are of-

fered in an on-site demonstration kitchen, a

program that is unique to Baylor Sammons

Cancer Center. The integrative medicine pro-

gram works in conjunction with the Virginia

R. Cvetko Patient Education and Support

Center.

“Integrative medicine contributes to all the

incredible advances made in traditional medi-

cine,” said Dr. Matthews. “This is a way to sup-

plement or integrate existing treatment options

with ‘low-tech’ approaches, some of which have

been around for thousands of years.”

■ Two Baylor hospitals recognized among best in nation for heart surgery Baylor Heart and Vascular Services at Dallas

and The Heart Hospital Baylor Plano have earned

the coveted 3-star rating from the Society of

Thoracic Surgeons (STS). The rating—the high-

est honor bestowed by STS—is for both aortic

valve replacement surgery and heart bypass

surgery. Less than 3% of the nation’s hospitals

have earned 3-star ratings. The STS National

Cardiac Database, which the STS rating system

is based upon, measures outcomes for more

than 90% of the 1100 cardiac surgery programs

in the United States.

“Only 24 hospitals in the US are STS 3-star

hospitals in both procedures. Baylor is home to

two of them,” says Michael Mack, MD, FACS,

medical director of cardiovascular disease for

BHCS. “I think that’s an exclamation point on

our long-standing commitment to improving the

quality of care for patients with heart disease

and striving to offer a level of medical excellence

that just isn’t available everywhere.”

415October 2013 Baylor news

416

Clinical research studies enrolling patients through

Baylor Research Institute

Currently, Baylor Research Institute is conducting more than 800 research projects. Studies open to enrollment are listed in the Table. To learn more about a study or to enroll patients, please call or e-mail the contact person listed.

Table. Clinical research studies conducted through Baylor Research Institute that are enrolling patients

Research area Specific disease/condition Contact information (name, phone number, and e-mail address)

Asthma and pulmonary disease

Chronic obstructive pulmonary disease, asthma (adult) Rose Boehm, CCRC, RRT, RCP 214-820-9772 [email protected]

Cancer

Breast, ovarian, endometrial, prostate, brain, lung,

bladder, colorectal, pancreatic, and head and neck

cancer; hematological malignancies, leukemia, multiple

myeloma, non-Hodgkin’s lymphoma; melanoma vaccine

Grace Townsend 214-818-8472 [email protected]

Diabetes (Dallas)Type 1 and type 2 diabetes, cardiovascular events Kris Chionh 214-820-3416 [email protected]

Pancreatic islet cell transplantation for type I diabetics Kerri Purcell, RN 817-922-4640 [email protected]

Diabetes (Fort Worth)Type 2; cardiac events Trista Bachand, RN 817-922-2587 [email protected]

Pancreatic islet cell transplantation for type I diabetics Kerri Purcell, RN 817-922-4640 [email protected]

Gastroenterology Crohn’s disease Dallas Clinical Trials Office 214-820-9626 [email protected]

Heart and vasculardisease (Dallas)

Aortic aneurysms, coronary artery disease,

hypertension, poor leg circulation, heart attack, heart

disease, congestive heart failure, angina, carotid artery

disease, familial hypercholesterolemia, surgical renal

denervation for hypertension, diabetes in heart disease,

cholesterol disorders, heart valves, thoracotomy pain,

stem cells, critical limb ischemia, cardiac surgery

associated with kidney injury

Merielle Boatman 214-820-2273 [email protected]

Heart and vascular disease (Fort Worth)

Atrial fibrillation, carotid artery stenting Deborah Devlin 817-922-2575 [email protected]

Heart and vasculardisease (Plano)

Aneurysms; coronary artery disease; surgical renal

denervation, or stent, for uncontrolled hypertension;

poor leg circulation; heart attack; heart disease; heart

valve repair and replacement; critical limb ischemia;

repair of AAA, TAA, and dissections with endografts;

thoracic surgery leak repair; atrial fibrillation; carotid

artery disease; congestive heart failure; left atrial

appendage and stroke; gene profiling

Natalie Settele, PA-C 469-814-4712 [email protected]

Hepatology Liver disease Cheryl Sandbach 214-820-6267 [email protected]

Infectious diseaseHIV/AIDS Bryan King, LVN 214-823-2533 [email protected]

Hepatitis C, hepatitis B Cheryl Sandbach 214-820-6267 [email protected]

NephrologyHomocysteine and kidney disease, dialysis fistulas,

urine/protein disorders in cancer patientsDallas Clinical Trials Office 214-820-9626 [email protected]

NeurologyStroke Dion Graybeal, MD 214-820-4561 [email protected]

Multiple sclerosis Annette Okai, MD 214-820-4655 [email protected]

Neurosurgery Cerebral aneurysms Kennith Layton, MD 214-827-1600 [email protected]

Rheumatology (9900 N. Central Expressway)

Rheumatoid arthritis, psoriatic arthritis, lupus, gout,

ankylosing spondylitis

John J. Cush, MD

Kathryn Dao, MD

214-987-1253

214-987-1249

[email protected]

[email protected]

TransplantationBone marrow, blood stem cells Grace Townsend 214-818-8472 [email protected]

Solid organs Jonnie Edwards 214-820-6243 [email protected]

Weight management Obesity Kris Chionh 214-820-3416 [email protected]

Women’s health (Fort Worth)Endometriosis and endometrial ablation; interstitial

cystitis/bladder pain syndrome Theresa Cheyne, RN 817-922-2579 [email protected]

Baylor Research Institute is dedicated to providing the support and tools needed for successful clinical research. To learn more about Baylor Research Institute, please contact Kristine Hughes at 214-820-7556 or [email protected].


417417

The very existence of ethics consultation reflects both the increasing com-

plexity of modern medicine’s ethical questions and our discomfort with the

prospect of answering them alone. Two developments in the past century

were instrumental in driving the development of ethics consultation—

organ replacement therapy and intensive care. With the proliferation of

extreme life-prolonging measures came the thorny difficulties in the with-

drawal of such services or rationing when resources were poor. Insofar as

“someone must,” lamented Dr. Karen Teel (a pioneer of ethics consultation),

the physician “is charged with the responsibility of making ethical judg-

ments which we are sometimes ill-equipped to make.” More than anything,

ethics consultation has come to best satisfy a central desire of American

health care—sharing the responsibility for tough decisions.

Today, ethics consultants are an important component of American health care delivery. Th ey are found in 81% of hospitals and 100% of those with more than 400 beds. In one year (2006), 29,000 individuals performed 36,000

consultations, devoting 314,000 hours (1). By one account, ethics consultations are performed for 0.16% of all hospital admissions (2). In a relatively short time, a novel discipline has emerged and thrived in American hospital wards.

Born to serve the dual and reinforcing fears of futile care and medicolegal liability, the ethics consult has come to refl ect both the increasing complexity of medicine’s ethical questions and our discomfort with the prospect of answering them alone. Th e practice of ethics consultation developed slowly in the 1970s and 1980s, was essentially fully formed by 1987, and has proliferated since. It is now nearly ubiquitous (1). Th en, as now, the matters of standards, credentials, and how we evaluate consultation are very controversial. Yet, despite the lack of clarity about funda-mental aspects of this enterprise, ethics consultation fl ourishes. More than anything, ethics consultation has come to best satisfy a central desire of American health care—sharing the responsi-bility for tough decisions. Herein, this historical study of ethics consultation examines the practice’s roots, the forces that shaped it, and the people responsible for its development.

MEDICAL ETHICSClinical ethics consultation is a relatively novel service

that developed within the broader history of medical ethics.

From the Department of Gastroenterology, Beth Israel Deaconess Medical Center,

Boston, Massachusetts.

Corresponding author: Elliot B. Tapper, MD, Department of Gastroenterology, Beth

Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 (e-mail:

[email protected]).

Th e history of contemporary medical ethics—rich, broad, and mostly outside the bounds of this inquiry—began in 1802. Th omas Percival, an English physician, coined the term “medical ethics” in a widely circulated pamphlet wherein he unilaterally codifi ed the professional ethic of doctors. Th e Percivillian code—which formed the basis for the American Medical Association’s code of ethics—asserted the moral au-thority and independence of physicians in service to others, affi rmed the profession’s responsibility to care for the sick, and emphasized individual honor (3). Th e rigorous study of how this code translated to practice began in earnest as recently as the 1950s. Joseph Fletcher’s Morals and Medicine (1954) was the fi rst major work to closely examine the “knotty issues” of medicine, old (e.g., euthanasia) or new (e.g., artifi cial insemi-nation) (3, 4). Fifteen years later, Paul Ramsey, a theologian, was the fi rst to lay out a systematic approach to these issues that became known as bioethics. As he wrote in his seminal work, Th e Patient as a Person (1970), “I could put my questions to experts in many fi elds of medicine, overhear discussions among them, and begin to learn how teachers of medicine . . . themselves understand the moral aspects of their practice” (5, 6). Meanwhile, the discussion that Paul Ramsey began in the academy was slowly developing in the clinic. In 1949, Catholic hospitals began forming “medicomoral committees” to discuss and maintain Catholic values in health care delivery (7). Th e concept of an ethics committee, however, was slow to take a widespread hold.

THE PHYSICIAN’S DILEMMA AND THE ETHICS COMMITTEENotwithstanding the infancy of medical ethics, medi-

cal technology—and with it the scope and reach of medical interventions—was advancing spectacularly. By the mid 20th century, there were several signs that medical technology had outstripped the capacity of individual physicians to confi dently navigate clinical medicine’s ethical quandaries. Two develop-ments were instrumental—organ replacement therapy and

Consults for conflict: the history of ethics consultationElliot B. Tapper, MD


intensive care. Together, they led directly to the formation of ethics committees and, later, ethics consultation.

In 1960, Belding Scribner’s Tefl on arteriovenous shunt en-abled outpatient hemodialysis for the fi rst time. Immediately, there was far more demand for this procedure than supply. Concerned about fairness in rationing, the Seattle Artifi cial Kidney Center founded an “Admissions and Policy Committee.” Composed of a minister, a lawyer, a businessman, a homemaker, a labor leader, and two physicians, this committee chose the pa-tients who received the available dialysis slots. Shana Alexander, the journalist who immortalized the so-called “God-Squad” in her blockbuster Life magazine article, declared that “they decide who lives, who dies.” A central theme in her interviews was the need to share in the responsibility of such weighty decisions. Indeed, Alexander sympathized with the hospital, arguing that “the medical fraternity should share the burden [of these deci-sions] . . . otherwise society would be forcing the doctors alone to play God” (8).

Dialysis and, later, the advent of renal transplantation raised the stakes on medical decisions at the end of life, for both those patients with and without a chance for survival. Accordingly, in 1968, Harvard famously commissioned a committee to provide a “defi nition of irreversible coma” (9). Th e fact of this report on “brain death” spoke not only to the problem of organ supply and determining from which bodies it is appropriate to har-vest organs but also generalized diffi culties in knowing when to terminate “life support.” As they wrote, “Obsolete criteria for the defi nition of death can lead to controversy in obtain-ing organs for transplantation.” At the same time, intensive care or “improvements in resuscitative and supportive measures have led to increased eff orts to save those who are desperately injured.” Th ese eff orts place a diffi cult burden on patients, “on their families, on the hospitals and on those in need of hospital beds already occupied by these comatose patients” (9).

Indeed, the linchpin in this history is the intensive care unit (ICU) and the technical advancements thereof. With the proliferation of extreme life-prolonging measures came the diffi culties in the withdrawal of such services. In the con-text of a litigious society, a worry quickly developed about the consequences in withdrawing life support. Th ere was a pervasive sense that physicians were duty bound to provide universal cardiopulmonary resuscitation and support. Th ese were procedures whose benefi t was a given, and thus the failure to provide them “might invite civil suits or criminal prosecu-tion” (10). It was easy to start life support but stopping it or withholding it proved trickier. Patients were just as uneasy with life support. In 1969, the fi rst “living will” emerged and slowly gained popularity (11).

End-of-life decisions in the ICU took on a fundamentally legalistic character which, in turn, led to the creation of ethics committees. Dr. Karen Teel, a pediatrician at the Children’s Hospital of Austin, saw physicians “faced with the reality of a no-win situation.” Insofar as “someone must,” the physician “is charged with the responsibility of making ethical judgments which we are sometimes ill-equipped to make.” “In good faith, he acts,” “assuming a civil and criminal liability.” Teel referred to

the “God Squad” (as Seattle’s committee was known colloqui-ally) and argued that all hospitals ought to provide a mechanism to share in the responsibility of such tough decisions, one that would “provide a regular forum for more input and dialogue in individual situations and . . . allow the responsibility for these judgments to be shared.” Crucially, she published these thoughts in a 1975 article entitled “A Physician’s Dilemma” in a law review journal (12).

As it happens, shortly thereafter, the Karen Ann Quinlan legal saga was coming to a close. As a frail college student in New Jersey, Ms. Quinlan aspirated after an accidental over-dose of benzodiazepines and alcohol, resulting in a persistent vegetative state. Her parents eventually decided to terminate ventilation. Her doctors, however, worried about the impli-cations and resisted. Th e result was a defi nitive, landmark legal battle. Judge Richard J. Hughes presided and ruled the extubation legally sound. And in setting this precedent, he cited Teel, urging all hospitals to adopt her proposal for an ethics committee (13).

Ethics committees appeared around the country but were not successful in addressing their motivating concerns. Th e Beth Israel Hospital in Boston was a leader, forming an ad hoc com-mittee of physicians and nurses to help treating physicians de-termine if a “do-not-resuscitate” order was appropriate for those patients who were competent to choose and not “irreversibly and irreparably ill” (14). It could be left to the physician alone to discuss the order with the committee, if the patient was, in fact, irreparably ill. Th is committee indirectly addressed the fear of litigation by sharing responsibility. Above all, it served to mitigate for treating physicians the feelings of guilt and un-certainty bound up in forgoing resuscitative measures (personal correspondence, Dr. Rabkin). Across town, the Massachusetts General Hospital organized the “Optimum Care Committee” to address the care of the hopelessly ill patient and the utilization of critical care resources. Its mandate, far more expansive than Beth Israel’s, was to determine “what would be the best thing to do for the patient” (15). Controversy followed with many unanswered philosophical questions: To what end? In whose service? Who joins? What sort of background was required for membership? (16, 17).

No one had satisfactorily addressed the concerns of confl ict of interest and authority before the fact of the committee, let alone what an ethics committee would actually do on a day-to-day basis. Th is had practical consequences. For example, the ethics committee at Montefi ore Medical Center was established in 1977, quickly became a “discussion group,” and fl oundered “because of lack of clear direction well into the 1980s” (18). Furthermore, there remained a widespread concern that the removed committee was an inappropriate mechanism to solve the dilemmas of the bedside (17). Five years into the committee era, the fear of legal liability had only worsened. One observer remarked, “It has become almost impossible for some classes of patient to die without a court order” (19). Hospitals began deliberately choosing to not start new committees (20). In 1982, only 1% of US hospitals had adopted ethics committees (21). Th e physician’s dilemma persisted.


419

“PSYCHIATRIC CONSULTATION MASKING MORAL DILEMMAS IN MEDICINE”

Confronting modern ethical dilemmas alone at the bedside, clinicians yearned for support. For this, they often turned to psychiatrists, asking consultants to weigh in on what turned out to be fundamentally ethical troubles. Clinicians began using the accessible language of psychiatry to frame their dilemmas. Dr. Mark Perl, a psychiatrist, exposed this practice with a case series in the New England Journal of Medicine. One patient with metastatic osteosarcoma refused treatment. Her oncologist consulted Perl for the management of “depression.” Another case involved a brain-dead patient whose wife refused organ donation, preferring to take him home on a ventilator. Th e neurosurgeon consulted Perl, again to manage her depression. Perl argued that the mechanism of psychiatric consultation was inappropriate for these confl icts and therefore declined to “lend authority to another physician in infl uencing a patient’s decisions (so as to conform to that physi-cian’s desires)” (22). Th ere was a growing demand for a consultant to sort out clinical ethical questions.

THE ETHICISTSAcross the country, a small group of “ethicists” began to off er

consultations. Professional ethicists—academics trained in various disciplines of the humanities—were increasingly available on hos-pital campuses. Largely, they were teachers of medical students, asked to guide students through the ethical questions engendered by the modern physician’s dilemma. Indeed, the proliferation of ethicists occurred concomitantly with the above developments during the 1970s: in 1972, 4.2% of medical schools had formal medical ethics curricula, and by 1982, 72.8% did; that percent-age has remained about the same (78% in 2004) (23, 24). Th e pioneers of the fi eld at this time included John Fletcher (philoso-pher; National Institutes of Health), William Winslade (lawyer and psychoanalyst; University of California at Los Angeles), John Golensky (minister; California), Ruth Macklin (philosopher; Albert Einstein), among many others. Foremost in this group was the philosopher Albert Jonsen. It is likely that he was the fi rst ethicist at the bedside sometime in the early 1970s at the Uni-versity of California at San Francisco, where he taught ethics to medical students when Dr. William Tooley (neonatologist) asked Jonsen to initiate bedside teaching in the neonatal ICU (personal correspondence, Dr. Jonsen). Jonsen is also responsible for train-ing many of the most important fi gures in the fi eld, including Bernard Lo (University of California at San Francisco) and John Golensky. Golensky, in turn, was responsible for developing eth-ics consultation services in countless hospitals across the nation, including those within the Kaiser Permanente system (personal correspondence, Dr. Golensky). Th ese ethicists were busy and they were in demand.

Th e fi rst ethics consultation in the published record was conducted by such an ethicist. Dr. Ruth Purtilo, a professor of ethics and physical therapy at the University of Nebraska, published her case in the New England Journal of Medicine. Th e patient was a critically ill neonate with gastroschisis. Her con-sultation “entailed an in-depth analysis of the moral obligations, rights, responsibilities, and considerations of justice that bear

on the infant’s situation” (25). She helped the physicians work through their thoughts, ultimately providing “reassurance that the clinicians had all the pertinent ethical data needed for as-sessing the ethical problem.” Confi rming the problem with committees, she lamented that “in our hospital, most cases in which a clinician can benefi t from a sympathetic and skilled ethicist never reach the committee” (25). Consulting ethicists provided one solution to the physician’s dilemma.

CLINICAL ETHICS Meanwhile, in Chicago, Dr. Mark Siegler became the direc-

tor of the University of Chicago’s new medical ICU in 1972. Quickly he found that “there was no place to send my housestaff and students to fi nd answers” to the troubling questions engen-dered by intensive care (26). He was not alone. While increasing numbers of nonmedical academics were specializing in medi-cal ethics, starting journals (Hastings Center Report, 1971) and departments (Kennedy Center at Georgetown, 1971), these people were predominantly concerned with theory. Th ere was a critical gap for practicing clinicians seeking guidance in eth-ics. Th e Kennedy Center began off ering immersion courses in medical ethics. However, in the words of one observer, they were “long discussions on rather esoteric, theoretical and philosophi-cal problems, at the expense of more practical topics of interest to the average physician” (27). Th e fi eld of biomedical ethics often had little to do with day-to-day medicine. Its “language of theory was not helpful in resolving the dilemmas of practice” (26). Disturbed by “the lack of involvement by physicians” in biomedical ethics, Siegler brought a refocus on physicians and their training to tackle the dilemma (28). Th is was revolution-ary. “It is clear by now,” he observed, “that medicine has merely reacted to, rather than anticipated or participated in, most major developments in biomedical ethics” (28). Th e medical establish-ment was trying to divide the clinical from ethical by fostering a class of ethical arbiters. Siegler spoke out against this. “Th e distinction that is to be made between clinical decisions and ethical ones is an invidious, but unfortunately misguided, one.” Th e treating physician, ultimately accountable to the patient, cannot “rely on the false courage of the noncombatant” (28). Medicine, more “than a technical service delivered like auto-repair or plumbing,” has inextricably linked technical and ethi-cal dimensions (29).

In 1978, Siegler coined the phrase “clinical ethics” in a paper where he argued that “whatever else medical ethics is, it must have something to do with the practice of clinical medicine” (30). Siegler’s clinical ethics is an approach to the diffi cult ques-tions of patient care that is a fundamentally bedside procedure, aimed at bedside clinicians. He saw the solution to the “physi-cian’s dilemma” in education and training. He was, from the outset, inspired by the words of Sir William Osler:

In what may be called the natural method of teaching, the student begins with the patient, continues with the patient, and ends his study with the patient, using books and lectures as tools, as means to an end. . . . Th e best teaching is that taught by the patient himself (30).

Consults for conflict: the history of ethics consultationOctober 2013

Siegler’s model of clinical ethics begins and ends with the patient, its aims derivative of and guided by the patient-doctor relationship. Th is puts Siegler at odds with the pre-vailing concept of medical ethics, wherein nonphysicians were providing the bulk of the consultations. Siegler’s vision involves training physicians to conduct ethical medicine and, perhaps, to involve trained physicians as ethics consultants where needed. Th is confl ict has never been resolved but com-promises have been made. Th us, in 1980, Siegler joined with Albert Jonsen and William Winslade to draft a pocket guide for clinical ethics aimed at all clinicians. Over 2 weeks, in Jonsen’s house overlooking the San Francisco Bay, they de-veloped the famous “four box method” that importantly orients all ethical discussions to consider fi rst the medical indications, followed by patient preferences, quality of life, and other contingencies. Clinical Ethics (1982) is actually a step-by-step guide to the ethics of medicine organized by clinical scenario. Cases are presented—e.g., “Th e Problem Patient: Critically Ill”—the ethical dimensions are dissected, and recommendations are made (31). Clinical ethics con-sultation, provided by a physician or not, now had a process and a manual.

THE SOCIETY FOR BIOETHICS CONSULTATIONBy 1985, far from having practice standards, it was still

not even clear who should consult or what a consult should look like. To unite the pioneers of consultation, John Fletcher convened a conference on ethics consultation at the National Institutes of Health. Sixty-one people were in attendance; 31 (51%) had PhDs, 8 (13%) had MDs, 8 (13%) had JDs, and 14 had other degrees. Th irty-eight consultants participated in a survey on their practices. Nineteen (53%) kept records in the chart of their consultations, 8 (21%) made medical rounds, and only 11 (29%) were employed by hospitals with ethics committees (32). Th e most frequent issue encountered was “removal of life support in terminal cases.” Th irty-nine consultants participated in another survey about the confer-ence itself. Th e group praised the conference for its “sharing of diverse experiences and ideas” and being “the beginning of attention to ethical consultants.” However, there were many criticisms, including a “lack of a formal discussion on what participants actually do with regard to consultation—their roles and aims.” One participant even asked, “Should this breed of technician be encouraged?” Th e most contentious issue was credentials. Indeed, the attendees were split across this fault line. John Golensky argued that consultants “needed credentials and defi ned skills,” while Siegler and his fellow, Dr. John La Puma, disagreed. La Puma emerged as the strongest advocate of the physician-as-consultant position. In the end, no compromise could be struck at this meeting (personal cor-respondence, Dr. Golensky).

Eleven of the participants gathered at the National Insti-tutes of Health in early 1986 and agreed to found the Society for Bioethics Consultation (SBC), the fi rst organization dedi-cated to consultation. It had three aims: to sponsor confer-ences, raise funds for training grants, and help organizations

develop their own training programs. John Fletcher lamented in a memorandum that interested graduate students and pro-fessionals had no one to guide them, that “no organized body is working on the problem. . . . Why not us?” Th e SBC planned three conferences across the nation between September 1987 and March 1988. However, interest was very weak. Th e lack of cohesiveness at the prior meeting had dampened general enthusiasm for the society. So few had registered, including three of the 61 attendees of the 1985 conference, that all conferences were cancelled (archived memoranda, Moody Medical Library).

THE CLINICAL ETHICISTIn the mid 1980s, a young resident at the West Los Angeles

Veteran’s Administration attended a grand rounds on clinical ethics by Dr. Bernie Lo. Th at resident was Dr. John La Puma. Today he is the “Chef MD.” At the time, he was an ethically minded resident invited to have lunch with Lo. At that lunch, Lo told him about a brand new sort of fellowship getting started up for people like him at the University of Chicago led by Mark Siegler. La Puma left for Chicago after residency as a member of the fi rst class of fellows at Siegler’s MacLean Center for Clinical Ethics (personal correspondence, Dr. La Puma).

During his fellowship, La Puma set up in a community hospital a weekly case conference to discuss clinical ethics with the ward clinicians and covertly promoted and developed his own consult service. Despite his work being informed at every level by Siegler, Siegler himself thought—at least at the time—that ethics consults were intrusive and potentially harmful to the core relationship between the primary doctor and patient. Siegler believed that the primary doctor was the rightful tar-get of clinical ethics education and interventions. Meanwhile, La Puma was working hard to legitimize the practice to his mentor. He collected 27 experiences which dealt, by and large, with fi nality and the do-not-resuscitate discussion. Th en, un-beknownst to Siegler, he published them in the Western Journal of Medicine (33).

Perhaps owing to the strength of its foundations, the method that La Puma employed and reported for his consultations re-mains essentially unchanged to this day. Two features of the La Puma-Siegler method ought to be highlighted. First, La Puma made sure to expand the social history, asking not how many packs per day but deeper questions about worldview to get at where the patient was coming from. Second, and crucially, unlike Jonsen and Purtilo before him, the consultant would do a physical exam and review laboratory values. True to the “four box method,” La Puma began by reviewing the chart and grounded his recommendations in the medical indications. Bor-rowing the style and structure of a traditional medical consult, the La Puma-Siegler method lent immediate credibility to the ethics consult.

STANDARDS AND EVALUATIONBy 1987, ethics consultation had matured. Th ere was a

manual, a published record of experiences, a series of journals devoted to the subject, and a growing number of textbooks.


421

Little has changed since. Since 1992, the Joint Commission on the Accreditation of Healthcare Organizations has required all of its approved hospitals to construct means for resolving ethical confl icts. In 1996, a consensus statement was preparing describing the aims of consultation:

. . . a service provided by an individual consultant, team, or committee to address the ethical issues involved in a specifi c clinical case. Its central purpose is to improve the process and outcomes of patient care by helping to identify, analyze, and resolve ethical problems (34).

In 2000, a joint task force of the SBC and Society for Health and Human Values published the recommendations that nearly crushed the society in 1985. Th ey compromised, recommending that “individual consultants, teams, or committees should have the core competencies for ethics consultation,” that an “evalu-ation of process, outcomes, and competencies is needed,” but that there “ought not to be any requirement for the certifi cation of individuals and accreditation of programs” (35).

Despite roughly 30 years of service, the issues addressed have not changed, with goals of care and medical futility rep-resenting 54%, and withholding or withdrawing measures the focus of 52% of consultations at one center (36). And despite the task force recommendations, only 15% of all con-sultations had any form of external review of their services (1). Meanwhile, 45% of consultants in one survey reported receiving only informal, on-the-job training, while 73% of consultants at pediatric hospitals reported informal training and 40% worked in hospitals without formal guiding policies (37). Th e literature still sees calls for studies to identify “indica-tors that lead to ethics consultation . . . and the enumeration of the various ethical skills, such as dispute resolution, utilized during ethics consultation” (38).

We are still trying to fi gure out how to evaluate ethics con-sultation. In the past two decades, owing to amazing concerted eff orts, ethics consultation has been involved in two ambitious multicenter clinical trials, one of which was even randomized. Only one, however, showed that ethics consultation had any eff ect, measured by resource utilization in patients who would not survive to discharge (39, 40). It is not clear that ethics con-sultation or committees can or even ought to be evaluated by a randomized trial (41). After all, it is possible that the greatest role of the ethics consultant is the sharing of responsibility, an eff ect that cannot be measured in patient outcomes.

CONCLUSIONTh e history of ethics consultation refl ects the developments

of modern medicine. Ethics consultation is a hospital service providing support for clinicians that developed in response to the practical bedside diffi culties inherent to the era of organ replacement/transplantation and brain death. Th e credibility of ethics consultants will be adjudicated less on the basis of their credentials than on their ability to address Karen Teel’s physician’s dilemma—to soothe the anxiety and share the responsibility for diffi cult medical decisions.

1. Fox E, Myers S, Pearlman RA. Ethics consultation in United States hos-pitals: a national survey. Am J Bioeth 2007;7(2):13–25.

2. Tapper EB, Vercler CJ, Cruze D, Sexson W. Ethics consultation at a large urban public teaching hospital. Mayo Clin Proc 2010;85(5):433–438.

3. Bean W. Th omas Percival (1740–1804): codifi er of medical ethics. JAMA 1965;194(12):1319–1320.

4. Fletcher J. Morals and Medicine. Princeton, NJ: Princeton University Press, 1954.

5. Ramsey P. Th e Patient as a Person. New Haven, CT: Yale University Press, 1970.

6. Jonsen A. Th e Birth of Bioethics. Oxford, UK: Oxford University Press, 1998.

7. May WW. Th e composition and function of ethical committees. J Med Ethics 1975;1(1):23–29.

8. Alexander S. Th ey decide who lives, who dies. Life, November 9, 1962.9. Ad Hoc Committee of the Harvard Medical School to Examine the

Defi nition of Brain Death. A defi nition of irreversible coma. JAMA 1968;205(6):337–340.

10. Burns JP, Edwards J, Johnson J, Cassem NH, Truog RD. Do-not-resus-citate order after 25 years. Crit Care Med 2003;31(5):1543–1550.

11. Bok S. Personal directions for care at the end of life. N Engl J Med 1976;295(7):367–369.

12. Teel K. Th e physician’s dilemma: a doctor’s view: what the law should be. Baylor Law Review 1975;27:6–10.

13. In the Matter of Quinlan. 70 N.J. 10, 355 A.2d.647, 1976.14. Rabkin MT, Gillerman G, Rice NR. Orders not to resuscitate. N Engl J

Med 1976;295(7):364–366.15. Brennan TA. Ethics committees and decisions to limit care. Th e experi-

ence at the Massachusetts General Hospital. JAMA 1988;260(6):803–807.

16. Veatch RM. Hospital ethics committees: is there a role? Hastings Cent Rep 1977;7(3):22–25.

17. Levine C. Hospital ethics committees: a guarded prognosis. Hastings Cent Rep 1977;7(3):25–27.

18. Rosner F. Hospital medical ethics committees: a review of their develop-ment. JAMA 1985;253(18):2693–2697.

19. Morison RS. Refl ections on morality and medicine: bioethics after two decades. Hastings Cent Rep 1981;11(2):8–12.

20. Esqueda K. Hospital ethics committees: four case studies. Hosp Med Staff 1978;7(11):26–30.

21. Youngner SJ, Jackson DL, Coulton C, Juknialis BW, Smith EM. A national survey of hospital ethics committees. Crit Care Med 1983;11(11):902–905.

22. Perl M, Shelp EE. Psychiatric consultation masking moral dilemmas in medicine. N Engl J Med 1982;307(10):618–621.

23. Fletcher J, Quist N, Jonsen AR, eds. Ethics Consultation in Health Care. Ann Arbor, MI: Health Administration Press, 1989:53.

24. Lehmann LS, Kasoff WS, Koch P, Federman DD. A survey of medi-cal ethics education at U.S. and Canadian medical schools. Acad Med 2004;79(7):682–689.

25. Purtilo RB. Ethics consultations in the hospital. N Engl J Med 1984;311(15):983–986.

26. Siegler M. Th e contributions of clinical ethics to patient care. Forum: Trends in Experimental and Clinical Medicine 1997;7:244–253.

27. Moore CB. Th is is medical ethics? Hastings Cent Rep 1974;4(5):1–3.28. Siegler M. Clinical ethics and clinical medicine. Arch Intern Med

1979;139(8):914–915.29. Kass LR. Ethical dilemmas in the care of the ill. I. What is the physician’s

service? JAMA 1980;244(16):1811–1816.30. Siegler M. A legacy of Osler. Teaching clinical ethics at the bedside. JAMA

1978;239(10):951–956.31. Jonsen A, Winslade W, Siegler M. Clinical Ethics: A Practical Approach to

Ethical Decisions in Clinical Medicine. New York: MacMillan, 1982.32. Bermel J. Ethics consultants: a self-portrait of decision makers. Hastings

Cent Rep 1985;15(6):2.

Consults for conflict: the history of ethics consultationOctober 2013

33. La Puma J. Consultations in clinical ethics—issues and questions in 27 cases. West J Med 1987;146(5):633–637.

34. Fletcher JC, Siegler M. What are the goals of ethics consultation? A con-sensus statement. J Clin Ethics 1996;7(2):122–126.

35. Aulisio MP, Arnold RM, Youngner SJ. Health care ethics consultation: na-ture, goals, and competencies. A position paper from the Society for Health and Human Values-Society for Bioethics Consultation Task Force on Stan-dards for Bioethics Consultation. Ann Intern Med 2000;133(1):59–69.

36. Swetz KM, Crowley ME, Hook C, Mueller PS. Report of 255 clini-cal ethics consultations and review of the literature. Mayo Clin Proc 2007;82(6):686–691.

37. Kesselheim JC, Johnson J, Joff e S. Ethics consultation in children’s hospitals: results from a survey of pediatric clinical ethicists. Pediatrics 2010;125(4):742–746.

38. Nilson EG, Acres CA, Tamerin NG, Fins JJ. Clinical ethics and the quality initiative: a pilot study for the empirical evaluation of ethics case consulta-tion. Am J Med Qual 2008;23(5):356–364.

39. SUPPORT Principal Investigators. A controlled trial to improve care for seriously ill hospitalized patients. Th e study to understand prognoses and preferences for outcomes and risks of treatments (SUPPORT). JAMA 1995;274(20):1591–1598.

40. Schneiderman LJ, Gilmer T, Teetzel HD, Dugan DO, Blustein J, Cran-ford R, Briggs KB, Komatsu GI, Goodman-Crews P, Cohn F, Young EW. Eff ect of ethics consultations on nonbenefi cial life-sustaining treat-ments in the intensive care setting: a randomized controlled trial. JAMA 2003;290(9):1166–1172.

41. Chen YY, Chen YC. Evaluating ethics consultation: randomised controlled trial is not the right tool. J Med Ethics 2008;34(8):594–597.



Dental education has gone through numerous changes since World War II. Th ese changes have had, and con-tinue to have, a major impact on the practice of den-tistry in the United States and Texas.

NATIONAL TRENDSDental schools

In 1950, there were 42 dental schools in the US, 60% of which were affi liated with private universities (Figure 1). With some government assistance and support from a growing ap-plicant pool, the number of dental schools increased to 60 by 1978. Most of this growth was in schools that were affi liated with public universities; they represented 58% of the schools at that time. However, not all these schools were destined to survive. Beginning in the mid 1970s, the dental school applicant pool began a steep decline. By 1989, the number of applicants to dental school had decreased by two thirds. As a direct or indirect result, six of the dental schools closed—all affi liated with private universities. New dental schools began to open shortly after the turn of the century. By fall 2013, the number of fully operational schools had increased to 64. In addition, several universities around the country are in various stages of planning to open a new dental school, although there is a great deal of uncertainty as to the number of these plans that will come to fruition.

Dental school enrollmentAs might be expected, dental school enrollment follows a

pattern similar to the trend in the number of dental schools. Between 1950 and 1971, there was a steady increase in fi rst-year enrollment in dental schools, totalling 47.1%, or 2.2% per year (Figure 2). Th e fi rst-year enrollment growth rate then more than doubled between 1971 and 1978—increasing by 32.8%, or 4.7% per year. A signifi cant amount of this growth can be attributed to a federal capitation program that began in 1972. Th rough this program, the federal government gave dental schools approximately $251.5 million to build new den-tal schools, renovate existing schools, and increase enrollment. If this amount were adjusted for infl ation, it be would close to a billion dollars today. Th ese funds played a crucial role in updating the dental education infrastructure. As enrollment increased, dental school graduates followed (Figure 2). Between

From Texas A&M Baylor College of Dentistry, Dallas, Texas.

Corresponding author: Eric S. Solomon, DDS, MA, Professor and Executive

Director for Institutional Research, Texas A&M Baylor College of Dentistry, 3302

Gaston Avenue, Dallas, TX 75246 (e-mail: [email protected]).

1950 and 1975, the number of dental school graduates increased by 2506 (88.6%).

Enrollment trends generally follow applicant trends; thus, the decline of applicants during the late 1970s and the 1980s had a direct impact on enrollment. First-year enrollment in

What’s going on in dental education?Eric S. Solomon, DDS, MA

Figure 1. Dental schools by type. Source: American Dental Association, Survey

of Dental Education.

Figure 2. Dental first-year enrollment (FYE) and graduates. Source: American

Dental Association, Survey of Dental Education; projection by E. Solomon.

dental school peaked in 1978 at 6301 and then dropped to 3979 in 1989, a decrease of 36.9%. Because of the enrollment build-up, dental school graduates did not begin to fall off until the mid 1980s. Between 1975 and 1984, dental schools graduated more than 5000 dentists a year. By 1990 the number of dental school graduates had dropped to <4000 (3995).

Th e trend in the number of applicants to dental school reversed, and the number of applicants began to increase in 1990. As a result, between 1989 and 2010, fi rst-year enrollment increased from 3979 to 5171—a 30% increase. Dental school graduates increased by more than 1000, from 3701 in 1994 to 4496 in 2010 (35%). With new schools coming on line and some existing schools increasing their class size, it is likely that enrollments and graduates will continue to increase until at least the middle of the decade.

TRENDS IN TEXASIn 1970, the University of Texas Health Science Center

at San Antonio’s dental school accepted its fi rst class. Th e University of Texas Dental Branch at Houston and the Baylor College of Dentistry had been around since the turn of the past century (1901). Since 1970, these three schools have been the only dental schools in Texas. During the 1970s and 1980s, enrollment trends in Texas schools mirrored the na-tional trends (Figure 3). During the decade of the 1970s, fi rst-year enrollment in Texas schools almost doubled, increasing from 221 to 417 in 1979. Th en, as in the national trend, fi rst-year enrollment fell to 246 in 1993. First-year enrollment levels were relatively fl at for the next 10 years; however, since 2004, enrollment has crept up to almost 300. Class sizes at


the three schools are currently fairly similar, with each school having a class size of about 100 students. Naturally, the num-ber of graduates of Texas dental schools follows the fi rst-year enrollment trend. Th e number of graduates increased from 191 in 1970 to 384 in 1985 and then decreased to 228 in 1996. Since then, the number of graduates has remained fairly consistent, increasing to only 258 in 2010. Enrollment levels at the Texas dental schools are unlikely to change much over the remainder of the decade. Dental enrollments are limited by the size of facilities. Signifi cant increases in dental school enrollments can only occur if new or expanded clinical facili-ties are developed.

Figure 3. Texas dental first-year enrollment (FYE) and graduates. Source:

American Dental Association, Survey of Dental Education.

425425

In the spring of 1961, during my sophomore year of medical school at Johns Hopkins, I had an elective quarter at Guy’s Hospital in London along with my roommate, Larry Kirkland. Shortly before that, I had encountered an old friend of mine

at Davidson College, Don Stewart (now a neurosurgeon), who explained that he had spent a wonderful year at London at St. Th omas Hospital (Figure 1).

Don suggested that in London I should immediately contact John Ormsby-Gore at the “St. Th omas Club.” I found that the St. Th omas Club was a club for medical students that had a bar and was across from the hospital, which was on Lambeth Palace Road and Southwark on the Th ames River. After a few weeks in London, I decided to call John; it was fairly late, around 9:30 pm. He talked to me shortly on the phone, asked about my location, and immediately said, “I will send a taxi to you soon!”

About 30 minutes later, I found John at the St. Th omas Club enthralling several medical students with continual stories. John was also a medical student but seemed somewhat older, in his mid 30s. He was an excellent host, off ering several beers (English “pints of bitter”). Th e time of midnight came shortly, and I was invited to go to an Indian restaurant with the group. Th ey explained their custom: “We English never have dinner before midnight!”

I discovered that John Ormsby-Gore had been a medical stu-dent at St. Th omas for a long time—perhaps as long as 15 years—after serving in World War II as a military offi cer. John’s father was a “lord,” a former member of Parliament, and an authority

Corresponding author: S. Robert Lathan, MD, 122 Old Ivy Road, #17, Atlanta,

GA 30342 (e-mail: [email protected]).

on archeology. John’s brother was said to be the ambassador to the United States and a close friend of President John F. Kennedy. John had also met “JFK” but was not really in the “same circle” and called himself the “black sheep” of his family.

When I asked John about his medical school activities, he talked about spending almost every night at the St. Th omas Club and serving as manager of the St. Th omas rugby and cricket squads. He did not talk much about his experiences in his medical school courses and clinical work. When I asked about his plans for fi nishing medical school and the required “qualifi cation tests,” he said: “Oh, I’ve considered the ‘qualifi cations,’ but it’s very tough and takes about 6 months’ work before the test, and every time I seem to think about the test, it’s at the same time as the Royal Ascot, to which I always go!” Th e Royal Ascot (Figure 2) is traditionally held during the third week in June and is England’s annual display of horse racing and hat pageantry. It is also closely associated with the British royal family.

John Ormsby-Gore was always hospitable to me during my several weeks in London. He was an encyclopedia of all the important events in London and also suggested the best travel places in England, Scotland, and Wales. I recalled a special Satur-day in mid June with John showing me and Larry the “Trooping the Colours” annual parade (Figure 3) in London, in which the

An unforgettable, perpetual medical student, 1961S. Robert Lathan, MD


Figure 1. St. Thomas Hospital: (a) in the past and (b) now.

a b

queen’s personal troops honor her offi cial birthday. Th is display of pageantry dates back to the time of Charles II in the 17th century. Not many tourists could fi nd this unique event.

More than 40 years after my wonderful 10-week stay in London, I continued to try to fi nd what had happened to John Ormsby-Gore. I contacted St. Th omas to fi nd his address with-out success. Finally I decided to use the Internet and found very unusual facts about the Ormsby-Gore family.

John Ormsby-Gore (1816–1876) was the fi rst Baron Harlech and was a British Conservative member of Parliament. He was elected to the House of Commons for Carnarvonshire in 1837. William Ormsby-Gore (1885–1964), the fourth Baron Harlech, was the father of our friend, John Ormsby-Gore. He was also a Conservative member of Parliament. David Ormsby-Gore (1918–1985) was the fi fth Baron Harlech and a British diplo-mat and Conservative member of Parliament from Oswestry in Shropshire. He was John’s older brother and had been educated at Eton College and Oxford University. David knew John F. Kennedy well from Kennedy’s time in London while his father, Joseph P. Kennedy, had served as the American ambassador. After Kennedy’s election as president, David was appointed Brit-

ish ambassador to the United States from 1961 to 1965. In 1965 he took his seat in the House of Lords as Lord Harlech. He also had a successful career as a television executive.

The family later had several tragedies. Of David’s fi ve chil-dren, one son died of gunshot wounds, an apparent suicide, and one daughter was en-gaged to rock guitarist Eric Clapton in 1969 and later died of a heroin overdose. (An-other daughter had an aff air with Mick Jagger during the 1960s.) Lady Harlech died in a car accident in 1967, and Lord Harlech died in a car crash near his home in 1985.

David was succeeded in the barony by his second son, Francis Ormsby-Gore, the sixth Baron Harlech. However, in 2011, this Lord Harlech and his daughter were involved in a dangerous driving incident in North Wales. He had lived in Brogyntyn Hall near Oswestry in Shropshire, England, close to the Welch border.

In the past few years I have read of several Ormsby-Gore family celebrities and also tragedies and accidents. Despite this, I was able to fi nd very little about my good friend John Ormsby-Gore. Internet sources provided only four lines about him recently:

Capt. Th e Hon. John Julian Staff ord Ormsby-Gore, late of the Coldstream Guards, and educated from Eton College and Oxford University, who died in 18 April, 2008, after a short illness, age 83, a son of the 4th Baron Harlech.

Unfortunately, there was no information concerning his medi-cal experience at St. Th omas Medical School, although he was cited as a “British nobility.”

My roommate, Dr. Larry Kirkland, and I still remember our kind, hospitable English medical friends. We especially re-member Dr. Dick Squires, who was also in medical school at St. Th omas and invited us to spend a weekend with him in his home in Wantage, Oxfordshire, England, only a few feet away from the statue of King Alfred the Great (871–899) (Figure 4). I have had the fortune of visiting Dr. Dick Squires two other times and most recently saw his restored Lains Barn dating in part from 1750, which is now used for community and edu-cational functions. Dick is now a member of the Order of the British Empire.

Figure 2. Royal Ascot.

Figure 3. Trooping the Colours.

Figure 4. Statue of Alfred the Great in Wantage.


427427Proc (Bayl Univ Med Cent) 2013;26(4):427

For the Love of Wild Places by Greg and Mary Beth Dimijian

Dallas, TX: Brown, 2013.

Hardcover, 167 pp., $29.95.

Reviewed by Daniel E. Polter, MD

or the Love of Wild Places is a memoir of Greg and Mary Beth Dimijian’s travels to remote

parts of our planet, relating an extensive knowledge of the wild-life, natural history, biology, geology, and ecology of the sites they visited. Th ey documented their adventures with unique and artistic photographs of life in some of the most interesting places on earth.

Greg is an unusual personality. He is a modern-day poly-math, a psychiatrist with special expertise in addiction, a self-taught biologist and ecologist, a photographer and artist with his camera, and a former pilot. As a teenager he considered a career as a concert pianist. Th is multitude of interests became wedded to a love of nature and adventure during a summer as a young park ranger in Glacier National Park.

Chapters cover life in tropical rainforests; African wild-life in the Serengeti and the Okavango Delta of Botswana; Antarctica and the magical South Georgia Island; active volcanoes in Costa Rica, Hawaii, and Iceland; the under-water world of coral reefs; and remote and beautiful places in America. Th is work contains many scientifi c tidbits, il-lustrating the tremendous complexity of nature. A typical example is the Leafcutter. Leafcutter ants in the tropics bring leaf fragments back to their nest, which provides food for a type of soil fungus. Th e fungus then secretes a substance that serves as food for the ants. Th is is termed mutualism. Another example of mutualism is the fi g wasp-fi g relation-ship. Most tropical fi gs are dependent on a tiny wasp for pollination. Th e wasp itself relies on the fi g fruit for its own reproduction. Th e wasp burrows into the unripe fi g, which interestingly is part fl ower and part fruit. Th e wasps depart before the fi g ripens.

Th is book is a delightful treat for travelers who have visited some of the places described by the authors. For those who plan to travel to any of these sites it is a helpful introduction, and for those who enjoy learning about our natural world it is informative and entertaining. Th e photographs are stunning and the narrative is well written. It is a worthy homage to our beautiful and amazing planet.

The reviewer, Daniel E. Polter, MD, is a gastroenterologist on the medical staff

of Baylor University Medical Center at Dallas.

Book Review

428

Sifting Shades by Amanullah Khan, MD, PhD

Indianapolis, IN: Dog Ear Publishing, 2013.

90 pp.: Hardcover, $26.00; paperback,

$9.99.

Reviewed by Harbans Lal, PhD, DLitt(hons)

As an academic medical scientist, I do not tra-ditionally write reviews of poetry. However, in

Dr. Khan’s poetry, I found his heart speaking to my heart. Such a conversation elicited a drive to share and urge others to experience the same energy.

Dr. Khan is a medical oncologist and scientist who is itching to apprehend the secrets of immortality being so well perfected by the cancer cells. For years I have been enjoying his associa-tion, along with that of his poetry composed in our mother tongue. Frankly, I did not expect a book from him written in the language we adopted in our new home country. Th at certainly proves that poetry is a language of the heart without recognizing any frontier.

Th ere are a string of spiritual and reforming poets that we remember as enlightened souls of the Sufi tradition. Guru Nan-ak, Baba Farid, Baba Waris Shah, Mian Mir, and BabaBulleh Shah, among them, lived in the more recent past. Th ey were humanists, pluralists, and philosophers. Guru Nanak was the founder of the Sikh religion. Mian Mir laid the foundation stone of the Golden Temple Sikh Shrine. In Dr. Khan’s poetry, I sensed the Sufi wisdom and belief traditions that were for the fi rst time expressed, and not just translated, by a scientist in the English language.

Th e fi rst thing that strikes the reader of Dr. Khan’s book is its coverage of life aspects that are diverse and vast. Th e book consists of 80 poems divided into six chapters and an introduc-tion. He starts the book with “Let me paint my roses; Let me

share my thorns” and ends with “Let me chase infi nity. Let the ideas soar.” Th ose statements say a lot about the wide coverage he undertakes.

He begins with a poem on River Ravi, which divides the Punjab State of India and the Punjab State of Pakistan. Th e only bridge on the river connecting the two states was built by the British and was destroyed by bombs in the wars between India and Pakistan. Th e banks of this river witnessed a rich history of prophets who were born and lived on its banks and the sad history of political upheavals and fi ghts. Presently this river separates the sacred shrine of Guru Nanak from his followers. Here Guru Nanak spent the last 18 years of his life establishing the Sikh religion. His followers, now in the millions, live on the other side of the river bank and come twice a day to gaze at their sacred shrine for prayer from a distance. Dr. Khan rightfully describes Ravi River as the “book of time.”

Th en Dr. Khan goes on to grab the human soul: “Th e issue of the soul have many pondered, But the trail turned up cold.” Longevity to Dr. Khan is a “cruel bargain”: “Plum is bartered for a prune.” Th e readers will appreciate both the humor and the imagery.

Dr. Khan is disturbed over wars of religion—both wars of worship and wars among worshipers. He expressed his anguish in a poem on page 58: “A mosque on the north, a church on the south, And tranquil path lay between the two. . . . Belief was nestled at a chosen place. Not on forehead but the altar of heart.” I am going to refrain from describing every poem. Readers must have the opportunity to take their own dip and let their listening heart meet Dr. Khan’s speaking heart.

We live in a multifaceted environment, which asks for easily understandable imagery. In his poems, Dr. Khan has succeeded in simplifying complex issues of life in a way that a lay person may appreciate. I recommend this book for professional audi-ences and the public alike. Every reader will fi nd Sifting Shades an engaging experience.

The reviewer, Harbans Lal, PhD, DLitt(hons), is emeritus professor and chair,

pharmacology and neuroscience, at the University of North Texas Health Science

Center. He can be reached at [email protected].

Book Review


Reader comments

Cardiac rehabilitation in firefightersWe read the case series, “High-intensity, occupation-specifi c

training in a series of fi refi ghters during phase II cardiac rehabili-tation” by Adams et al (1) with great interest. We applaud the authors’ eff orts to bring greater attention to the cardiovascular hazards of fi refi ghting. However, we are extremely concerned that this article’s anecdotal report on six fi refi ghters with a his-tory of coronary revascularization provides physicians with the false impression that most fi refi ghters should return to unre-stricted fi re department emergency duties after acute myocardial infarction, angioplasty, or cardiac surgery if they completed a similar cardiac rehabilitation program. Furthermore, the report fails to provide clinicians with the most relevant epidemiologic data regarding the risk of sudden cardiac death (SCD) during fi re suppression and other fi re emergency duties that would assist them to make more informed and evidence-based decisions on return to work in this dangerous occupation.

While the authors correctly note that SCD due to coro-nary heart disease (CHD) is the leading cause of death in US fi refi ghters (2), they do not mention key facts that drive this observation. First, fi refi ghters with an established diagnosis of CHD (like the six patients reported on here) unnecessarily ac-count for 25% to 30% of all on-duty CHD events and SCD (3, 4). Second, not only is a recurrent on-duty CHD event more likely, but the odds of case fatality during a fi refi ghting CHD event are four times higher for those with a prior diagnosis of CHD after adjustment for other risk factors (5). Th e relative risk of on-duty SCD death for such individuals is 35 times that of their colleagues without a CHD history. In fact, even after accounting for all other comorbid cardiovascular disease risk factors, the relative risk of on-duty SCD remains about 15-fold higher (4). Clinicians almost never face risks of such magnitude and then decide that it is still acceptable for the individual to engage in such a strenuous occupational activity.

Th ere are other major problems with this report. Th e authors fail to state how the patients were selected or medically cleared to participate in this program and do not mention or do not have any inclusion/exclusion criteria based on disease severity. At what point would they determine that a fi refi ghter is not safe to enter the program? To the authors’ credit, they mention the CHD return to work criteria developed by the National Fire Protec-tion Agency (NFPA) (6). From the data presented, however, the participants did not meet these criteria because of their persistent cardiovascular disease risk factors. Moreover, the authors do not describe how and when they determined that a cardiac rehabilita-tion program participant was eligible to return to work.

Th e authors mention that the NFPA standard recom-mends >12 METS aerobic capacity for safe return to fi re-fi ghting activities, and the authors’ own previous paper on this

subject showed that healthy fi refi ghters required an average of 12 METS and >85% of their age-predicted max heart rate to complete a fi re obstacle course (7). Clearly then, a safe cardiac rehabilitation program would need to address those aerobic capacity criteria as one of the many necessary require-ments for determining safety to return to work. However, the rehabilitation subjects have no peak METS reported after completing the program. In addition, the peak heart rates dur-ing the cardiac rehabilitation program were uniformly below 150 bpm (and below 85% age-predicted heart rate max in 5/7 cases). Th is strongly suggests that even though they mimicked fi re suppression activities in terms of muscular activities, the self-paced nature of the program allowed the participants to perform below the 12 MET threshold.

Published studies of various fi refi ghter activities and condi-tions consistently demonstrate peak heart rates of >160–180 (8–11). Th erefore, the intensity of a cardiac rehabilitation pro-gram targeting fi refi ghters would need to be higher than the one reported by Adams et al to meet this demand. While beta blockade is off ered as a reason for the low peak heart rates during exertion, such a confounding factor would make it even more imperative to objectively demonstrate participants’ aerobic ca-pacities in a quantitative fashion. Accordingly, while the cardiac rehabilitation program the authors present is unique, it by no means simulates or approximates the cardiovascular stressors of actual fi re suppression duties for all of the reasons above. To the authors’ credit, they acknowledge that the program has no element of shift work, heat stress, dehydration, low oxygen tension, or exposure to inhalational toxins, which are additional cardiac stressors and part of the essential job duties that the returning cardiac patient would face (12, 13). Again, however, they fail to explain how they would infer from such limited data in a safe and controlled environment the participants’ ability to safely return to work under complex, unpredictable, and dangerous conditions.

An even more serious fl aw of the paper is that the method-ology cannot support any of the claims made by the authors about their proposed cardiac rehabilitation regimen. Th ere is no pres entation of pre- and post-rehabilitation exercise data (e.g., peak exercise heart rate and blood pressure response, electrocardiographic patterns during exertion, or aerobic capacity) to show that the fi refi ghters were more fi t and had better cardiovascular responses to exertion after completing the program. Firefi ghters did not complete a standard fi re service Physical Abilities Test and did not (or it was not reported) achieve 12 METS as a more standardized surrogate measure of the ability to safely perform essential fi refi ghting duties. Finally, no longitudinal follow-up was provided to document that the patients had indeed “safely” returned to unrestricted duties without further incidents. Th us, while we agree that

Proc (Bayl Univ Med Cent) 2013;26(4):429–431 429

a single treadmill exercise stress test is inadequate to deter-mine ability to safely return to work (6, 13), the proposed rehabilitation program described in the present report lacks objective evaluation criteria and does not provide clinicians or patients with the additional information required to make an informed life or death decision regarding the safe resumption of unrestricted fi refi ghting duties.

—Stefanos N. Kales, MD, MPH ([email protected])

Harvard School of Public Health and the Cambridge Health Alliance

—Dorothee M. Baur, MD, MScHarvard School of Public Health and

Endokrinologikum ULM—David Hostler, PhD

State University of New York, University at Buffalo—Denise L. Smith, PhD

Skidmore College and University of Illinois Fire Service Institute

1. Adams J, Cheng D, Berbarie RF. High-intensity, occupation-specifi c train-ing in a series of fi refi ghters during phase II cardiac rehabilitation. Proc (Bayl Univ Med Cent) 2013;26(2):106–108.

2. Kales SN, Soteriades ES, Christophi CA, Christiani DC. Emergency duties and deaths from heart disease among fi refi ghters in the United States. N Engl J Med 2007;356(12):1207–1215.

3. Holder JD, Stallings LA, Peeples L, Burress JW, Kales SN. Firefi ghter heart presumption retirements in Massachusetts 1997–2004. J Occup Environ Med 2006;48(10):1047–1053.

4. Kales SN, Soteriades ES, Christoudias SG, Christiani DC. Firefi ghters and on-duty deaths from coronary heart disease: a case control study. Environ Health 2003;2(1):14.

5. Geibe JR, Holder J, Peeples L, Kinney AM, Burress JW, Kales SN. Predic-tors of on-duty coronary events in male fi refi ghters in the United States. Am J Cardiol 2008;101(5):585–589.

6. National Fire Protection Association. NFPA 1582: Standard on Compre-hensive Occupational Medical Program for Fire Departments. Quincy, MA: NFPA, 2007.

7. Adams J, Roberts J, Simms K, Cheng D, Hartman J, Bartlett C. Mea-surement of functional capacity requirements to aid in development of an occupation-specifi c rehabilitation training program to help fi refi ghters with cardiac disease safely return to work. Am J Cardiol 2009;103(6):762–765.

8. Horn GP, Blevins S, Fernhall B, Smith DL. Core temperature and heart rate response to repeated bouts of fi refi ghting activities. Ergonomics 2013 Jul 22 [Epub ahead of print].

9. Smith DL, Manning TS, Petruzzello SJ. Eff ect of strenuous live-fi re drills on cardiovascular and psychological responses of recruit fi refi ghters. Er-gonomics 2001;44(3):244–254.

10. Hostler D, Gallagher M Jr, Goss FL, Seitz JR, Reis SE, Robertson RJ, Northington WE, Suyama J. Th e eff ect of hyperhydration on physiologi-cal and perceived strain during treadmill exercise in personal protective equipment. Eur J Appl Physiol 2009;105(4):607–613.

11. Colburn D, Suyama J, Reis SE, Morley JL, Goss FL, Chen YF, Moore CG, Hostler D. A comparison of cooling techniques in fi refi ghters after a live burn evolution. Prehosp Emerg Care 2011;15(2):226–232.

12. Smith DL, Barr DA, Kales SN. Extreme sacrifi ce: sudden cardiac death in the US Fire Service. Extrem Physiol Med 2013;2(1):6.

13. Soteriades ES, Smith DL, Tsismenakis AJ, Baur DM, Kales SN. Car-diovascular disease in US fi refi ghters: a systematic review. Cardiol Rev 2011;19(4):202–215.

Th e authors respond:

We appreciate the opportunity to respond to the letter by Kales et al regarding our article published in BUMC Proceedings (1). We would fi rst like to emphasize that the high-intensity, occupation-specifi c training (HIOST) program described in our case series was never meant to be used to clear fi refi ghters for return to active duty. Th e National Fire Protection Association’s own guidelines (2) recommend a single exercise stress test to help physicians decide whether fi refi ghters with coronary heart disease (CHD) can return to work. In our opinion, this is inadequate. Our HIOST cardiac rehabilitation program is intended to make available more detailed information than a single exercise stress test may provide.

Kales et al explain the facts that drive CHD as the leading cause of sudden cardiac death (SCD) in US fi refi ghters. Th e authors’ previous report (3) is cited as evidence of increased risk of SCD in fi refi ghters with prior CHD. However, the study grouped patients together and labeled them with a diagnosis of previous CHD if they had any of the following: a previous abnormal exercise or radionu-clide stress test or a history of coronary artery bypass grafting, coro-nary angioplasty, myocardial infarction, angina pectoris, carotid stenosis, or peripheral arterial disease. Th is is an extremely varied patient population. Our point is that the individual fi refi ghter, not a single diagnosis, should be considered when determining whether the patient should be allowed to return to work.

Kales et al correctly point out that there is a selection bias in our case series, as fi refi ghters themselves determined if they wanted to participate. We readily acknowledge that not all fi refi ghters would be able to participate in HIOST following coronary revascular-ization events. However, as reported by the authors previously, many fi refi ghters have uncontrolled cardiovascular risk factors (3) and have undiagnosed CHD. It is noted that 75% of fi refi ghters with CHD-related deaths had no recent fi re department medical examination (3). We are concerned that many fi refi ghters may not seek medical attention and cardiovascular risk stratifi cation because receiving a diagnosis of CHD may not allow a return to work. We also believe that the availability of structured post–coronary revascularization programs like HIOST in a cardiac rehabilita-tion setting will encourage fi refi ghters to seek cardiovascular risk stratifi cation.

Kales et al also are concerned that we have not reported whether participants were eligible to return to work and that no longitudinal follow-up was provided. Tracking return to work in this patient population can be misleading. Th ere are many confounding factors that may be used in the fi nal decision about return to work that have nothing to do with the exercise training in cardiac rehabilita-tion. Examples include workplace and/or physician denial, spouse refusal, fear, department policies, and current existing guidelines.

Kales et al cite concerns that our report has not simulated suffi ciently the aerobic capacity requirements of fi refi ghting activi-ties (4). We would again acknowledge that beta-blockade therapy likely explains the blunted heart rates. In addition, the activities completed by the fi refi ghters in our report mirrored the 12-MET activities from our prior study (4).

To reiterate, we did not intend for the information in this report to be used for clearing individuals to return to active fi refi ghting


duties. We believe this is an individual decision that should be made with as much clinical information as possible and not solely because of the presence or absence of a particular diagnosis. Limited data exist on fi refi ghters’ ability to perform fi refi ghting tasks following successful coronary revascularization procedures. We hope that ours is the fi rst of many reports to explore fi refi ghter safety following coronary revascularization.

—Rafic Berbarie, MD, Jenny Adams, PhD, and Tim Bilbrey, BS

Cardiac Rehabilitation Department, Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, Texas

1. Adams J, Cheng D, Berbarie RF. High-intensity, occupation-specifi c training in a series of fi refi ghters during phase II cardiac rehabilitation. Proc (Bayl Univ Med Cent) 2013;26(2):106–108.

2. National Fire Protection Association. NFPA 1582: Standard on Comprehensive Occupational Medical Program for Fire Departments. Quincy, MA: NFPA, 2007.

3. Kales SN, Soteriades ES, Christoudias SG, Christiani DC. Firefi ghters and on-duty deaths from coronary heart disease: a case control study. Environ Health 2003;2(1):14.

4. Adams J, Roberts J, Simms K, Cheng D, Hartman J, Bartlett C. Measurement of functional capacity requirements to aid in develop-ment of an occupation-specifi c rehabilitation training program to help fi refi ghters with cardiac disease safely return to work. Am J Cardiol 2009;103(6):762–765.

Reader commentsOctober 2013 431

432

Facts and ideas from anywhere

From the Editor

ALTERNATIVE MEDICINETh at includes everything from

herbal supplements to crystal healing and acupuncture. About 50% of Americans use alternative medicine and 10% use it on their children, according to Paul Offi t, the author of Do You Believe in Magic? Th e Sense and Nonsense of Alternative Medicine (1). Consum-ers of alternative medicine range from healthy people who pop the

occasional supplement, hoping to ward off a cold, for example, to the seriously ill, who turn over their life savings to gurus promising miracles. Offi t indicates that alternative medicine is a $34 billion a year industry whose key players are adept at using lawsuits, lobbyists, and legislation to protect their market. More than 54,000 varieties of supplements are on the market. Th ere is a Congressional Dietary Supplement Caucus of legis-latures who look favorably on the industry. One congressman indicated that the alternative medicine industry is as tough as any industry lobbying in Washington. Th ey want as little legislation as possible.

Alternative medicine proponents say it is popular because people want more control over their health. While some supple-ments are just high-priced placebos, others carry serious risks. Dietary supplements can be prescription medications in dis-guise. Th e most common off enders tend to be the “natural” supplements claiming to melt fat, build muscles, or boost sexual performance. Th e Food and Drug Administration (FDA) has found that hundreds of brands actually contain real drugs, including anabolic steroids and the active ingredient in Viagra. In April 2013, the FDA indicated that it had received 86 reports of illness and death due to body-building supplements that illegally contained a stimulant called DMAA, which is especially risky when combined with caff eine because it can raise the blood pressure with its consequences. Th e FDA in 2012 estimated that supplements cause 50,000 adverse reactions a year.

Some patients with serious illnesses delay proper therapy as they opt for alternative medicine. Apple founder Steve Jobs’ faith in alternative medicine may have cost him his life. Jobs was diagnosed with pancreatic cancer in 2003, and although revered

for his brilliant mind, chose to delay surgery for 9 months in favor of acupuncture, herbs, and special diets. Jobs eventually had surgery and, later, a liver transplant, but it was too late. He died in 2011, 8 years after diagnosis. According to his physi-cian he had the only kind of pancreatic cancer that is treatable and curable.

According to Offi t, consumers are often taken in by the outrageous claims of the supplement producers or because they fall victim to hucksters’ charismatic personalities.

Many Americans also are unaware that supplements, unlike drugs, do not need to be approved by the FDA or tested for safety before going on the market! During all these years the FDA has banned only one supplement, namely Ephedra, which was taken off the market in 2004 after it was found to increase the risk of heart problems and death. Th e FDA’s authority with supplements is mostly “reactive.” Th e agency must wait for people to get hurt or die before it can remove an unsafe supplement from the market.

Beware of supplements!

MEDICAL SPASA piece by Melinda Beck indicates that states are tighten-

ing regulations on medical spas and wading into some disputes over where beauty treatments stop and the practice of medicine starts (2). Medical spas are fast-growing hybrids between day spas and doctors’ offi ces. Th ey typically off er Botox injections, facial peels, laser skin treatments, and other minimally invasive cosmetic procedures. Some even add breast implants, tummy tucks, and chin, face, brow, and eyelid lifts. Th e International Spa Association now counts 1750 medical spas across the US, up from 471 in 2003. Some of the growth comes from dermatolo-gists and plastic surgeons adding such services and amenities to their practices. But physicians trained in unrelated specialties, such as obstetrics or orthopedics, also are supplementing their incomes with the lucrative procedures that rarely are covered by insurance. Most of the services are performed by nonphysi-cians.

State regulations vary widely. Only a few require medical spas to be licensed. In some states, procedures from laser hair removal to liposuction can be performed by nonphysicians. Most require physician oversight, though the physician does not necessarily have to be on site or even in the same state.

William C. Roberts, MD.


Some serious injuries have prompted crackdowns. Florida now requires that liposuctions removing >2 pounds of fat be performed in a state-licensed surgical center with emergency equipment on hand. A new state law in Maryland requires the state health department to oversee cosmetic surgery facilities. Pennsylvania is presently weighing tighter rules on who can provide laser treatments. Some of the push for more regulation is being driven by dermatologists who say allowing nonphysicians to perform cosmetic procedures puts physicians at risk. Only a few states require medical spas to report injuries.

Laws requiring physicians to perform procedures do not guarantee confi dence either. Several groups have sprung up to teach cosmetic procedures to physicians from other fi elds. Th e National Society of Cosmetic Physicians, for example, advertises 2-day workshops on laser liposuction, breast augmentation, and tummy tucks. Th e proposed medical spa law in New York would require physicians advertising themselves as “board certifi ed” to specify which board. Th is kind of medical business is obviously quite profi table to those who do it.

THE REAL CHOLESTEROL-LOWERING MAGIC BULLETMy friend, cardiologist Robert L. Rosenthal, sent me a

New York Times piece entitled “Rare mutation ignites race for cholesterol drug” (3). Th e article by Gina Kolata describes the development and early testing of a monoclonal antibody, made in living cells, with the ability to lower the low-density lipopro-tein (LDL) cholesterol (the bad one) to levels lower than they were at birth, to as low as 12 mg/dL. Th e story began about a decade ago when some French researchers published a note in Nature Genetics describing three generations of a family with extremely high LDL levels—up to 466—and a strong history of coronary heart disease. Th e researchers found that the family had a mutation in a gene called PCSK9, which slowed the body’s ability to rid itself of LDL. Th e mutated gene leads to the soaring cholesterol levels.

Th e French study gave Jonathan C. Cohen and Helen H. Hobbs of the University of Texas Southwestern Medical Center in Dallas an idea. If a mutation in PCSK9 could lead to high LDL levels, perhaps there were mutations that did the oppo-site, namely lead to very low levels of LDL and protect against atherosclerosis. Cohen and Hobbs found in data from a Dallas study that about 2.5% of blacks had a single mutated PCSK9 gene that no longer functioned, and about 3.2% of whites had a less powerful mutation that hampered the gene but did not destroy it. Because people have two copies of every gene, one inherited from each parent, those with the newly discovered mutation did not have two mutated genes, but instead had one fully functioning PCSK9 gene and one that was disabled. Blacks with the mutation ended up with LDL levels averaging 100 instead of the usual 138, a 28% reduction; whites with a less powerful mutation had LDL levels averaging 117, about 15% lower than average. Th e people with one disabled gene had lower than normal LDL levels for their entire lives. Hobbs and Cohen found that blacks aged 45 to 64 with a single mutated gene seemed almost immune to coronary heart disease during a 15-year follow-up, and whites, who had the less powerful

mutation, had a 46% reduction in the incidence of coronary heart disease. Th ese fi ndings led them to search for a mother and father who each carried the single mutated gene. Th ey found one such couple and tested their daughter who had the rare double inheritance. Th e daughter was a 32-year-old aerobics instructor living in a Dallas suburb with her two young children. She was healthy. Her LDL was 14, a level unheard of in healthy adults. Th is aerobics instructor was only 1 of 2 people thus far found on planet Earth with the rare gene mutation inherited from both parents; the other person, a young healthy Zimbabwean woman, had an LDL of 15.

Th e discovery of the mutation and the two women with their extremely low LDL levels has set off one of the greatest medical chases ever among three pharmaceutical companies, Amgen, Pfi zer, and Sanofi , to test and win approval for a drug that mimics the eff ects of the mutation, drives LDL levels to new lows, and prevents coronary heart disease and other forms of atherosclerotic disease. All three companies now have drugs in clinical trials and report that the results so far are exciting. Each company’s drug is a biologic. Th e drugs will be injected, probably twice a month. Th is is great news on the horizon for our most frequent cardiovascular disease, namely atherosclero-sis, and its most frequent form, coronary heart disease (heart attack).

PREVENTING HEART ATTACKS WHEN MOUNTAIN CLIMBINGNovice mountaineers may lower their risk of having a fatal

heart attack if they acclimate themselves before a high-altitude recreational hiking or skiing expedition according to a study published in the American Heart Journal (4). Th e risk of dying of a heart attack on the fi rst day of vigorous mountain exercise was more than 5 times as high in individuals who had slept at lower elevations on the previous evening compared with those who had slept at higher elevations. Th e study from mountainless Dallas analyzed 301 sudden cardiac deaths occurring during weeklong expeditions in the Austrian mountains from 1985 to 1993. Of the 301 victims, 149 died on the fi rst day of climb-ing and 152, on a subsequent day; 29% of the deaths occurred around noon after 2.5 hours of activity. Sleeping altitude was the only signifi cant predictor of sudden cardiac death on the fi rst day. Th ose individuals who died on the fi rst day slept at an altitude about 1000 feet lower than those who died on a subse-quent day. Deaths in both groups occurred at altitudes of 5354 to 5899 feet. Try to spend the fi rst night at a higher altitude.

EXERCISE AND WEIGHT LOSSTh rough the years I have heard many people talk about

their desire to lose weight. Many have commented that they needed to exercise more. Dwyer-Lindgren and colleagues (5) in a recent article provide evidence that, although exercise can provide many health benefi ts, weight loss is usually not one of them. US obesity levels have risen over the past decade despite an increase in physical activity. For every 1% increase in physical activity, obesity rates declined by only one tenth of a percent. Th e researchers concluded that exercise alone is not enough to lose much weight.

Facts and ideas from anywhereOctober 2013 433

COWS, NUMBERS, DROUGHT, AND PRICESWholesale beef prices rose in 2013 (6). Th e meatpackers

have been paying more for cows after droughts the past two summers in Texas, Oklahoma, and other big cattle-ranching states. Th e dry weather parched pastures and drove up feed costs, forcing many ranchers to cull their herds. Th e nation’s cattle herd shrunk by 2% at the end of 2012 from a year earlier to under 90 million cows, the lowest level since 1952. Th at means fewer beef carcasses are making it through the industries’ supply chain. In 2012, Americans spent $288 per person on beef, a 4.2% rise from $277 a year earlier, as retail prices rose. US beef sales in 2012 reached $91 billion, up from $86 billion in 2011. Th e sales of beef in the fi rst half of 2013 fell 1.7% from a year earlier. In contrast, pork volumes rose 3% and chicken volumes were fl at. As beef prices rise, less beef is consumed. Because most Americans devour bovine muscle, an increase in price may be the only way to really decrease its consumption. Th e same happened with cigarettes: as the price rose, the number of smokers declined. It continues to be true: we kill the cows and then the cows kill us.

E-CIGARETTESTh ese are the battery-powered devices that turn heated

nicotine-laced liquid into vapor (7). Th e market for this type of cigarette presently is small but growing rapidly, in part because it is increasingly seen as less harmful than conventional cigarettes. E-cigarettes, unlike traditional smokes, currently are not feder-ally regulated. Th e FDA warned consumers in 2009 that the new technology could pose its own health risks and stressed the need for more study. Th e agency has said it is planning regula-tions that would treat e-cigarettes as tobacco products, but has provided no details thus far. More than a dozen states have banned e-cigarette sales to minors, and others have outlawed their use in enclosed public spaces.

Th e long-term impact of inhaling e-cigarette vapor, which contains other substances such as propylene glycol, has yet to be determined. But, could e-cigarettes, which currently off er fl avors such as chocolate, strawberry, and pina colada, serve as a gateway to traditional cigarettes for young people? What kind of age restrictions and warnings should e-cigarettes carry? What about advertising? E-cigarette sellers are not currently allowed to make health or smoking cessation claims. Nevertheless, the potential market for e-cigarettes is huge. Industry experts say US retail sales of e-cigarettes could reach $1 billion in 2013, just 1% of the country’s cigarette market but twice that of 2012. It’s better not to use a-, b-, c-, d-, or e-cigarettes!

CARE GIVING FOR THE ELDERLYKelly Greene (8) discussed the problem of overseeing home

health care for elderly patients. In 2011 alone, the most recent data available, so-called informal caregivers provided at least 11.2 billion hours of unpaid care to family members and friends. Th at commitment is expected to escalate. In 2010, about 4% of adults under age 65 were providing unpaid care to relatives or friends who were 65 and older. By 2050, demand for informal caregivers could double to 8% as the younger

population shrinks relative to the elderly population. Elderly people and their families also spent at least $3 billion on their own in 2011 on long-term care in the community, mainly at home, in addition to $36 billion on nursing homes and other long-term care facilities. And those fi gures do not necessarily include drugs not covered by Medicare and other unreim-bursed expenses, such as food for special diets, increased utility costs, home renovations, and special supplies. One third of adults 65 or older and two thirds of those who have reached their mid 80s have functional limitations, needing help with tasks ranging from eating and bathing to preparing meals or paying bills. Four out of fi ve older adults who fi t that descrip-tion still are living in the community rather than in a nursing home.

Greene provided suggestions for helping families cope with paying for more care at the same time they are stretched by the unpaid time they are spending providing it themselves:1. Hire your own homecare professional or become one yourself. 2. Take the tax breaks. Many elder-care expenses qualify for

a medical expense deduction from federal income taxes. It is still 7.5% for people 65 and older. If you hire paid caregivers on your own, rather than working through an agency, the parent has to report the caregivers’ income, either on a W-2 or 1099 form, to be able to deduct the expense. Th e adult child can take deductions only if the parent is a dependent and the child pays. Home im-provements made with a physician’s prescription are tax deductible also. Such remodeling could include adding an elevator, swimming pool, central air conditioning, or ramps. Th e key is getting the physician’s note and de-ducting only the amount “over and above the amount it increases the home’s value.” One other possible medical expense deduction is entrance fees to a continuing-care retirement community, which provides care ranging from independent living to skilled nursing. Th e fees can run to >$100,000.

3. Designate a bookkeeper. People planning for later life should decide who should handle their fi nances in a health crisis, including designating who in the family should take control of the parents’ fi nances when needed, taking inventory of the parents’ resources, making sure the parents’ will and power of attorney are current, and pinpointing resources to pay for care costs.

4. Remember the veterans. Th e “aid and attendance” benefi t of wartime veterans pays up to $2054 a month to married vet-erans who qualify. Single veterans and surviving spouses can qualify for smaller amounts. To qualify, veterans generally must have served at least 90 days of active military service, including at least one day during a war. Th e income limits are met after deducting unreimbursed medical expenses, including any long-term care expenses.

5. Embrace respite care. Respite care is short-term care designed to give the regular caregiver a break. One person who cared for her mother sometimes would take her mother to a hos-pital facility for a week for what was called respite care. Th ese respite programs are available nationwide through

434 Baylor University Medical Center Proceedings Volume 26, Number 4

social service agencies, nonprofi t groups, and long-term care providers (eldercare.gov).

6. Know when to consider a permanent facility. Home care works best if you need a visiting nurse 3 or 4 times a week. But dementia requires round-the-clock care, and in these cir-cumstances a nursing home or assisted living facility can be considerably less expensive.

As George Burns said, “Getting old is not for sissies.”

HOSPITAL CACOPHONYHospital noise is constant: the beeping of a heart monitor;

the opening of doors by a nurse to take vital signs; changing shift conversations; overhead pagers; a visitor’s cell phone conversa-tion; television; rattling dishes in a moving cart; an alarm going off when an intravenous medication is fi nished (9). Noise reduc-tion eff orts began gaining momentum in 2012 when Medicare began basing a portion of hospital reimbursement on quality measurements, including patient ratings of the quality of care. (Noise consistently gets the worst marks on patient surveys!) Th e latest data from the federal program for the year ending June 2012 showed that only 60% of patients said the area out-side their room was quiet at night, the lowest satisfaction score among 27 questions about the hospital experience.

Several hospital administrators have cited changing behavior and culture as the biggest challenge to reducing hospital noise. Many hospitals now have only private rooms. Noise remains harder to control in shared rooms. A complicating factor is hospitals’ increasing openness, including more liberal visiting hours and policies that permit cell phones and other devices. Some hospitals have formed “quiet teams” to identify ways to reduce noise. Some are reducing the frequency and intensity of medical alarms, dimming lights in the evenings, and replacing nurses’ pagers and walkie-talkies with mobile headsets. Patients are getting Quiet Kits, white-noise machines and headsets for TVs and iPads. Some hospitals have hired consultants off ering “sound scrapping” solutions, including architectural changes and the use of ambient sound.

Some consultants apparently suggest that hospitals “stop chasing silence” and increase the ratio of good sounds to bad sounds. Complete silence can actually be worrisome and isolat-ing. Th e sickest patients may want quality sleep, but they also want to feel connected to their caregivers and know that they are not far away in case of an emergency. Some hospitals are asking staff ers to use “library” voices because quiet murmurs can be more comforting than normal speaking tones. A recent study at Baylor Health Care System’s Heart Hospital in Plano found that white-noise machines made no diff erence in patients’ perception of noises in rooms. Terri Nuss has indicated that smooth hard surfaces enhance noise but they are easy to clean and help fi ght infection. Ms. Nuss indicates that Baylor University Medical Center at Dallas is trying to fi gure out what is an acceptable sound level. We can all be a little quieter.

END-OF-LIFE PREFERENCESEllen Goodman, a favorite of mine, retired as a widely syndi-

cated columnist about a year ago and founded the Conversation

Project (theconversationproject.org), a national campaign to encourage conversations about our wishes for end-of-life care (10). Dying is not easy today. Too often, of course, feeding tubes and life support abound. A fractious family may play out its contentious relationships. Every day in this country, Ellen Goodman opines, thousands of families face these crises without being able to call on the voice of the person they love. It is a familiar drama in an era when death is no longer likely to be natural. How do we know when medical technology extends life and when it prolongs suff ering? Goodman indicates that the thousands of people who have used the Conversation Starter Kit on the website state that with help these talks can be far more intimate than intimidating. Goodman indicates that since she launched the project it seems as if everyone has a story to tell of a good death or a hard death. Th e diff erence often hinged on whether people they loved had expressed their wishes and, in turn, had those wishes respected. It is clear that too many people are dying in a way they would not choose. Surveys indi-cate that 70% of Americans want to die at home, yet 70% end up dying in hospitals and institutions. At home, one is at least surrounded by loved ones in comfort and in peace. Too many survivors are left not just mourning but feeling guilty, depressed, and uncertain of whether they have done the right thing—done what their mother, father, husband, friend would have wanted, if he or she had said. Have you had the conversation?

GUIDELINES ON FOOD IMPORTED TO THE USIn July 2013, the FDA proposed new steps to ensure that

fresh produce, cheeses, and other foods imported to the US are safe (11). Th e proposed rules, required by a sweeping Food Safety Law passed by Congress 2 years ago, are meant to es-tablish better checks on what has long been a scattershot eff ort to guard against unsafe food imported from >150 countries. Only around 2% of that food is inspected by the US govern-ment at ports and borders. About 15% of the food Americans eat is imported, including about 50% of fruits and 20% of vegetables. An estimated 3000 people die from food-related illnesses in the US every year.

Th e proposed guidelines require US food importers to verify that the foreign companies they are importing from are achiev-ing the same levels of food safety required in the USA. Th e rules, which would also improve audits of food facilities abroad, could cost the food industry up to $470 million annually.

Since Congress passed the Food Safety Law in December 2010, several outbreaks have been caused by imported foods, including an occurrence of Listeria in imported Italian cheese in 2012 that killed 4 people. Other illnesses were linked to tainted papayas, mangoes, and nuts and spices used as ingredients. Like rules for domestic farmers and food companies released in early 2013, the idea of the new guidelines is to make businesses more responsible for the food they sell or import by proving that they are using good food safety practices. Currently, the government does little to ensure that companies are trying to prevent food safety problems rather than waiting and responding to outbreaks after they happen. Requiring better prevention was the intent when Congress passed the bill. Since then, however, the law


has run into several obstacles, including FDA delays in issuing the guidelines, a lack of congressional funding, and increasing opposition from some rural members of Congress who represent worried farmers. FDA regulators say the new rules are necessary as the food system becomes more complex and more global. Food often stops in several locations and passes through several diff erent hands in a matter of days before it hits grocery shelves. A lack of funding also has given the FDA little oversight over what is produced. Th e agency inspects most food companies in the US only once every 5 to 10 years, and it does even fewer inspections abroad. Th e Food Safety Law requires the agency to step up those inspections. In 2012, the FDA inspected about 1300 facilities in foreign countries, up from 300 in 2010. Th at is still just a fraction of the companies that import to the USA. Sounds reasonable.

DESTROYING CHINA’S EARTHJosh Chin and Brian Spegele (12) recently described some

experiences of farmers in central China’s Hunan province. Th ey highlight an emerging and critical front in China’s intensifying battle with pollution. For years, the focus was on the choking air and contaminated water that plagued China’s ever-expanding cities. A series of recent events, however, has highlighted the spread of pollution outside of urban areas, now encompassing vast swaths of countryside, including the agricultural heartland. Estimates from state-affi liated researchers indicate that anywhere from 10% to 20% of arable land, some 25 to 60 million acres, may be contaminated with heavy metals. A loss of even 5% could be disastrous, taking China below the “red line” of 296 million acres of arable land currently needed, according to its government, to feed the country’s 1.35 billion people.

Rural China’s toxic turn is largely a consequence of two trends: the expansion of polluting industries into remote areas a safe distance from population centers and heavy use of chemi-cal fertilizers to meet the country’s mounting food needs. Both changes have been driven by the rapid pace of urbanization in a country that in 2012 for the fi rst time had more people living in cities than outside of them. Yet, the eff ort to keep urbanites comfortable and well fed has also led to the poisoning of parts of the food chain, and some of that pollution is traveling back to the cities in a diff erent guise. Judith Shapiro, the US-based author of the recent book China’s Environmental Challenges, indicates that pollution can be displaced only to an extent and that it cannot be walled off . She among others has warned that pollution poses an existential threat to the current regime. Shapiro says that the single most signifi cant determinant of whether the Communist Party will maintain its legitimacy in coming years will be its ability to control that pollution.

China has sought to industrialize its countryside for the last 50 years when it began urging peasants to set up backyard steel furnaces at the expense of agricultural output. Th e cumulative impact of decades of building up rural industry is now taking an environmental toll, particularly as industrial growth surges forward in China’s breadbasket. In some cases, factories are mov-ing to the countryside to take advantage of cheaper land, often made available with the help of local offi cials who want to boost

growth. In other cases, urban leaders want factories to move out of crowded cities. Th e ensuing problems of rural pollution are exacerbated by the fact that many small-town governments have less capacity to properly regulate complex industrial activities than their counterparts in big cities. Th e consequences of this shift catapulted to national attention in February 2013 when China’s Ministry of Environmental Protection refused to release the results of a multiyear nationwide soil-pollution survey, call-ing the data a “state secret.” Th e decision sparked an outcry. Many farmers who farmed lands adjacent to various factories now cannot eat what they grow but by still farming the land they receive payments from the factory owners to compensate for polluting the ground. Bad deal!

US MEDICAL COSTSAs nearly everyone knows, Americans pay more for almost

every interaction with the medical system than do people re-siding in other developed nations (13). Th ey are typically pre-scribed more expensive procedures and tests than people in other countries, regardless of whether those nations operate a private or national health system. A list of drug, scan, and procedure prices compiled by the International Federation of Health Plans, a global network of health insurers, found that the US came out the most costly in all 21 categories and often by a huge margin. Americans pay, on average, about 4 times as much for a hip replacement as patients in Switzerland or France and >3 times as much for a Cesarean section as those in New Zealand or the UK. Th e costs of hospital stays in the US are about triple those in other developed countries, even though they last no longer. While the US medical system is famous for use of drugs costing hundreds of thousands of dollars and heroic care at the end of life, a much more signifi cant factor in the nation’s $2.7 trillion annual health care bill is not the use of extraordinary services but the high price tag of ordinary ones. Th e US pays providers of health care much more for everything. Colonoscopies are the most expensive screening test that healthy Americans routinely undergo. Th ey often cost more than childbirth or appendectomy in most other developed countries. Th eir numbers have increased many fold over the last 15 years, and data from the Centers for Disease Control and Prevention suggest that more than 10 million people get them each year, adding up to more than $10 billion in annual costs. Largely an offi ce procedure when widespread screening was fi rst recommended, colonoscopies have moved into surgery centers where they are billed like a quasi-operation.

As Elisabeth Rosenthal writes, “Hospitals, drug companies, device makers, physicians, and other providers can benefi t by charging infl ated prices, favoring the most costly treatment op-tions, and curbing competition that could give patients more and cheaper choices. And almost every interaction can be an opportunity to send multiple, often opaque bills with long lists of charges.”

Th e United States spends about 18% of its gross domestic product (GDP) on health care—nearly twice as much as most other developed countries. While the rise in health care spend-ing in the US has slowed in the past 4 years—to about 4%


annually from about 8%—it is still expected to rise faster than the GDP. Aging baby boomers and tens of millions of patients newly insured under the Aff ordable Care Act are likely to add to the burden.

Consumers of medical care, the patients, do not see prices until after a service is provided, if they see them at all. Patients with insurance pay a tiny fraction of the bill, providing scant disincentive for spending. Physicians often do not know the cost of the tests and procedures they order. Without posted prices, how can one make an intelligent decision? Th is situation is unique to medicine, where payments are often determined in countless negotiations between a physician, hospital or phar-macy, and an insurer, with the result often depending on their relative negotiating power. Insurers have limited incentive to bargain forcefully since they can raise premiums to cover costs. How medicine got into this situation is a bit unclear to me, and determining a reasonable solution will be a challenge for all.

TEXAS DEBTAccording to Steven Malanga (14), Texas’ combined state

and local debt as of 2011 is just over $233 billion! While state government debt stands at $40 billion, or $1577 per resi-dent, local government debt is >4 times as high: $192 billion, or $7505 per person, the second highest sum in the nation behind only New York’s municipalities and far ahead of third place California. During the last 10 years local debt in Texas has increased 144%, much faster than the rate of population increase plus infl ation.

Where is all this debt coming from? One place is the huge expenditures by local school districts on athletic facilities. Allen, for example, just spent $60 million on its new high school sta-dium, and its population is only 83,000. Th e 18,000-seat facility, which boasts a massive high-defi nition TV screen, was built from funds generated by a $119 million bond off ering. More than 100 new high school stadiums have opened in Texas during the last 5 years, and that does not include pricey upgrades in several.

Debt owed by public school districts constitutes the big-gest chunk of the state’s soaring local obligations. Over the last decade, it has increased 155%, even as the state’s student popu-lation has grown just 21%. Interest payments on these school debts now constitute 10% of school spending ($5.5 billion).

Debt is also growing rapidly among the state’s 81 retire-ment systems for local government workers. Th ese systems are underfunded. A result of this underfunding means that the con-tributions to pension systems that municipalities must make each year are rising, eating up large portions of local budgets. Additionally, employee costs are rising locally, going from 15% of city budgets to 30%. Th ose cost increases are partly to blame for sharp increases in property taxes: 38% in the last decade. I thought California, New York, and Illinois were the big debt states, but that seems not to be the entire story.

HIGHEST-PAID STATE EMPLOYEESMy friend, Robert Doroghazi of Columbia, Missouri, a retired

cardiologist who writes a wonderful biweekly investor newsletter, Th e Physician Investor Newsletter (www.thephysicianinvestor.com/

members), to which I have subscribed for several years, recently had a piece on the highest-paid state employees in the USA (15). Th ey were as follows: football coach, 27; basketball coach, 11; football/basketball coach, 1; hockey coach, 1; college president, 4; medical school dean/administrator, 5; and law school dean, 1. Th us, our society, as Doroghazi comments, rewards sport coaches more than university presidents and medical school deans. Our society also rewards the average Major League Baseball play-ers 5 times more than the average physician ($1.3 million vs. $241,000) (16).

TOP CITIES FOR JOBSBetween 2009 and the end of 2011, Texas added 428,000

jobs to restore the Lone Star State to its prerecession employ-ment level, which it achieved faster than any other state (17). Of the top 10 US cities for jobs, four are in Texas, including Fort Worth, #4; Houston, #5; Dallas, #6; and Austin, #10. Since 2001, employment in Houston has expanded 20%; in Fort Worth, 16%; in Dallas, 11%; and in Austin, 27%. Th e oil and gas boom has been a big factor, particularly in Houston, but growth has also been strong in technology, manufacturing, and business services. Good for Texas!

STEM JOBSTh ey are jobs that require some knowledge of science, tech-

nology, engineering, or math. A June 2013 report from the Brookings Institution disclosed that the number of US jobs that now require STEM knowledge is 26 million as of 2011, or 20% of all jobs (18). In Dallas–Fort Worth, STEM jobs also make up 20% of all jobs. Pay and employment rates are higher for all STEM workers compared to non-STEM workers. For all STEM jobs in the Dallas–Fort Worth area, the average pay is $70,000, whereas for non-STEM jobs, it is $40,000. For jobs requiring a bachelor’s degree or higher, the average STEM salary is $88,000 and the average non-STEM salary is $68,000. Study hard, young folks, particularly in science, technology, engineering, and math courses.

SMARTPHONE ADDICTIONIn-Soo Nam (19) described smartphone addiction in high

school students in South Korea. She defi ned this addiction as spending >7 hours a day using the phone and experiencing symptoms such as anxiety, insomnia, and depression when cut off from the device. She indicated that roughly 1 in 5 students in South Korea are addicted to the smartphone. In July 2013, the South Korean government said it plans to provide nationwide counseling programs for youngsters by the end of the year and train teachers on how to deal with students with addiction. Taxpayer-funded counseling treatments already exist in South Korea for adults addicted to smartphones.

South Korea, home of the world’s biggest smartphone maker, Samsung Electronics, prides itself on being the global leader in high-speed Internet and advanced mobile technology. Koreans are some of the fi rst adopters of new digital devices. Th eir mobile phone penetration rate is more than 100%, mean-ing that some individuals carry more than one handset, and


smartphones are nearly two thirds of those devices. In contrast, the smartphone penetration rate in the US was 50% as of June 2013. (Korea also has had problems with online game addiction among teenagers for years thanks to widespread availability of high-speed Internet services.) Th e smartphone penetration rate in children aged 6 to 19 tripled to 65% in 2012 from a year earlier. Th e smartphone addiction rate among teens was 18%, double the addiction rate of 9% for adults. In the US in 2012, 37% of teens had smartphones.

Th e same problem appears to be surfacing also in other tech-savvy places such as Japan and Taiwan. According to experts, in addition to distracting students from their studies, smartphones are damaging their interpersonal skills. Students today, for example, are poor at reading facial expressions. One professor commented, “When you spend more time texting people instead of talking to them, you don’t learn how to read nonverbal language.” In Taiwan, the phenomenon of constantly checking e-mail or social media has led to the label “heads-down tribes.” Th e number of people in Taiwan accessing the Internet via laptops, tablets, or smartphones in the past 6 months has doubled to a record of 5.35 million from a year earlier.

It is now standard practice in Korean schools for teachers to collect mobile devices from their students during school hours. One teacher there commented that smartphones are often the most important possession for a young person.

POWER-GENERATING WIND TURBINES AND BIRDSWind turbines may exceed 400 feet in height, a space

extending into bird fl ight paths (20). Th e spinning rotors can cover an area >1 acre. Birds scanning the ground for prey fl ying at night or gliding with the wind may fl y directly into the path of a wind turbine, slamming into spinning blades, metal towers, or other structures. Th e blade tips can travel more than 150 miles per hour. A recent study estimates that approximately 575,000 birds, including species protected by federal law, are killed each year by collisions with power-generating wind turbines. Th at number could reach 1 million a year by 2030 as utilities install more wind farms. No matter what the power source, be it coal, oil, gas, water, or wind, there is suff ering, be it from humans or salmon or birds or other species. Th ere is really no such thing as “clean energy” despite what some of us might like to think.

BASEBALL DOWNTIMEMy friend, Baylor surgeon G. Ken Hempel, recently

took me and two others to a Texas Rangers baseball game. It was a wonderful evening. Ken picked me up at 5:15 pm, the game started at 7:05, and Ken dropped me back home about 11:00 pm. Th at nearly 6-hour period produced a great deal of relaxation and a few minutes of excitement. Th e Wall Street Jour-nal recently had a piece on baseball downtime (21). During an average 3-hour Major League Baseball game, the inaction amounts to 2 hours 40 minutes, and the action about 20 min-utes. Th e inaction provided much time to talk. During the game David Murphy hit a home run over the centerfi eld fence, which stands 425 feet from home plate. Th e question arose as to the longest home run ever hit. It was by Mickey Mantle, who hit one

634 feet—200 feet longer than David Murphy’s big blast and over two football fi elds in length.

In any given year, roughly 70 million people attend a Major League Baseball game. One thing every one of those fans sees is a bunch of grown men standing in a fi eld doing absolutely nothing “about 90% of the time.” Baseball is known for its moments of action, but they are fl eeting. Nevertheless, it is clear why this game is known as our “national pastime.”

TURNING NIGHT INTO DAYDarkness was, for all of human existence, a universal obstacle

to human happiness. In the late 19th century, the yearning for more light became more urgent. Many forms of work in the new industrial age, both in factories and offi ces, made more demands on the eyes, requiring greater attention to detail. At the same time, the urban world had grown darker, as tall buildings cast their shade and burning coal belched its smothering pall, blocking sunlight and coating windows with grime.

My father was born into this darkness when he entered the world in 1878; no city in the US was lit at that time. Although Th omas A. Edison had started working on the incandescent bulb in 1877, a year later there was still no reliable bulb. Although Edison made no claim that he had invented the fi rst working light bulb, what he did create was a complete lighting system that linked his powerful and effi cient dynamo, through a central main, to feeders and switches to his incandescent bulb of superior de-sign. His system delivered a steady supply of current to hundreds of lights, at varying distances from the source of power, and used parallel circuits to maintain the current even when some of his lights burned out or were turned off . His bulbs used a fi lament of high resistance, a crucial innovation that saved money by using a relatively small amount of current for each lamp. In the 14-week light exposition in Paris in 1881, Edison showed that electric light not only worked but could be distributed some distance from a central station, a system with the potential to become large and economical enough to challenge the gas companies. Other inventors had shown that they could light a house, but Edison was on his way to lighting an entire city.

Ernest Freeberg recently published Th e Age of Edison: Electric Light and the Invention of Modern America, and what follows comes from his book (22). From the start, all recognized electric light as an agent of creative destruction that would only survive and thrive by stealing away gas customers. Th e gas compa-nies were among the most heavily capitalized companies in the Western world. Right away, however, people saw that electric light was preferable to gas.

Th e fi rst American showcase for street lighting (23 arc lamps) was a three-quarter mile stretch of Broadway in New York City installed by Charles Brush in 1880. Leaders in other cities sent delegations to see “the Great White Way” for themselves and to investigate the claims of the various lighting systems. Elec-tric light’s fi rst entrance into each new town was always a cause for civic celebration. Th e market for electric light grew rapidly in part because Americans embraced the idea that their town standing could be measured by its ability to provide residents with the latest technological conveniences. My hometown, Atlanta,


Georgia, was called by Henry Clay, the great editor of the Atlanta Constitution, “the poorest lighted city of her size in the country.” Th at changed in 1883, just over 4 years after my father’s birth in Oxford, Georgia, a small town 20 miles from Atlanta where Emory University originated, with the arrival of a shipment of light poles. “Let us have light,” the newspaper urged.

Th e dark cities of the Gilded Age were dangerous and lighting companies marketed their product as nothing less than a police force on a pole. After nightfall, urban parks became notorious danger zones, a haven for the cities’ dregs and a playground of indecency. Now all that could end by harnessing light’s power of exposure. Th e mayor of Baltimore remarked, “An electric light is a nocturnal joy to an honest man, but a scarecrow to a thief.” One British reformer remarked, “Each electric light is as good as a policeman.” Gas light was only half as powerful as electric and thus only half as eff ective in fi ghting crime. Th e link between strong light and safe streets became so axiomatic that some worried that a prolonged blackout would produce a crime wave.

While electric light made the urban night less dangerous, it also made it less private, exposing behavior that was not illegal but illicit. Everyone understood that in a world of crowded tenements, city parks provided a place not only for breathing but also for courting. By the middle of the 1880s, most town dwellers in America lived with a new light on a daily basis. Most, however, experienced the new light on the town’s main boulevard or park, in a department store, theater, or hotel lobby, and perhaps in the offi ce or factory where they worked. But at the end of the evening, most returned to houses still lit by gas, kerosene, or oil lamps. Gas had not been driven from the fi eld in the fi rst decades of the electric light.

In the months following his 1881 triumph in Paris, Edison worked with his team to introduce improvements and effi cien-cies in every aspect of his invention, as he prepared to install his fi rst central power station in downtown New York. He won per-mission to dig up the city streets and had the technical challenge of running 18 miles of copper mains and wires along with the fuses, meters, switches, and fi xtures to serve >1000 customers. All of these elements were connected to his six 30-ton dynamos powered by coal housed in a 4-story building on a rundown block centrally located to reach downtown Manhattan custom-ers for half a mile in every direction. By September 1882, Edison fi red up thousands of lamps in a square mile of lower Manhat-tan. After years of painstaking preparation and a half million dollars of invested capital, the system turned on without a hitch. In place of the usual dim fl icker of gas, the bamboo fi laments of the new lamps provided a steady glare, bright and mellow, which illuminated interiors and showed through windows. Th e Edison bulb would become so ubiquitous, so mundane, that it would become invisible. Th ose using the fi rst ones marveled that they were simplicity itself—a glass globe shaped like a dropping tear, enclosing a slender horseshoe of glowing carbon. Th ere was no nauseous smell, no fl icker, and little heat. Each light socket contained a key whereby the lamp may be turned on or off at pleasure. Oil lamps and candles in contrast required wick trimming and soot cleaning, while gas burners demanded even more technical skills from customers, who had to adjust meters

and burners in addition to regular cleaning. Th e electric light required no maintenance while the source of power hummed out of sight, sometimes many city blocks away. Th e bulb worked for about 600 hours until it either broke or began to blacken and dim. Th en an electric company worker could replace the expired bulb in a minute or two. Th e light bulb was safe enough for a child and simple enough for all to use. Th e functioning light bulb represented the culmination of decades of scientifi c insight, inventive genius, and technical skill.

Both Edison and his rival electricians sold standalone systems, single dynamos that fi red a string of lamps, enough for a large house, store, or ship. But after the successful test of his Pearl Street station, Edison hoped to move forward with his much grander vision for an electrical grid, installing his central system in the urban core of every major city. Each territory off ered a potential market of tens of thousands of lamps for offi ce buildings, theaters, and the private residences of the elite. Edison’s company planned to sell its equipment to a local utility which would pay royalties and assume responsibility for fi nding and serving its customers. Once free from the obligation to oversee the daily operation of his New York power station, Edison devoted his time and resources to improving every aspect of his system. He founded a series of interlocking companies. He supervised their work in developing and manufacturing dynamos, underground conduits, fi xtures, and bulbs. Edison set out to apply this strategy not only to the US, but around the world. He arranged similar partnerships with local utility operators in major cities in Europe, Asia, Central and South America, and Australia.

As the popularity of electric lights grew, the electric compa-nies strung numerous high-tension wires along streets already thick with wires for telephones, telegraphs, fi re and police alarms, and stock tickers. At dense urban intersections a pole might carry as many as 200 diff erent wires. Th ose wires were unsightly. Initially, those wires used only a moderate current that posed no danger. All that changed when electric companies added their powerful and fully insulated high pressure arc wires to the mix. Th ese often broke loose and fell across the web of other over-head wires. Traffi c stopped and crowds gathered as wires burned and sparked. Once in contact with broken or sagging arc wires, harmless telegraph, fi re alarm, and telephone wires delivered awful, even deadly shocks. At other times, they burned and melted, causing numerous fi res. Th e fi remen who came to the rescue faced not only the risk of the blaze but also the danger of electrocution.

For late 19th-century city dwellers, the sky overhead became increasingly ominous, thick with wires that might pour down a lightning bolt without warning. One medical journal declared that “the overhead system is a standing menace to life and health.” Every week the newspapers ran stories of this very modern form of sudden death. A Memphis man tied his mule to an iron lamp post that had been accidently electrifi ed; the powerful current knocked the screaming mule off its feet and when its owner came to the rescue he leaned against the post himself and was instantly killed. Similar stories multiplied.

Most electric light victims worked for the companies, at a time when the properties of powerful currents were barely


understood and safety standards for the industry were just be-ing invented. Many more were struck down while working around the dynamos, accidently completing a circuit that sent the powerful current through their bodies. At a time when prison reformers were exploring the use of electricity to execute prisoners, one editor suggested that death row inmates should simply be apprenticed to work for an electric light company because sooner or later the job would carry them off .

For all of human history, the rhythm of night and day exerted a powerful infl uence on how people arranged their lives. Nature seemed to intend the daylight hours for toil and the night for rest. Th is rough rule of thumb made sense in early America’s agricultural society but came under challenge during the 19th century’s illumination revolution. Although gas light and the new pressures of industrial production had already begun to blur the line between day and night, the more powerful electric light threatened to erase the distinc-tion entirely. Th e electric light particularly complicated the primordial bifurcation by adding a third option—illuminating evening that mixed elements of brilliance and shadow, looking and feeling like nothing any human had experienced before. Th ese lit hours between sundown and bedtime became a new piece of time. In many industries owners embraced electric lights’ economic potential, eager to keep their factories, mills, and shops open and their goods moving. Th eir workshops had required an enormous outlay of capital for expensive machinery and expanded facilities. To earn the best return on that invest-ment, owners needed to keep those machines running as much as possible. As Henry Ford said some years later, “Expensive tools cannot remain idle. Th ey ought to work 24 hours a day.” Th us, electricity would make possible the perpetual workday.

In the early days of the Industrial Revolution, workers relied on sunlight as their primary light source, often setting their benches as close as possible to the factories’ tall windows. Th e introduction of gas off ered a stronger light for night work, but gas light was expensive, still caused fi res and explosions, and, since it was not portable, proved useless in many work situa-tions. Workers immediately noted the advantages of electric lights. Th e new light relieved them from the nasty smell and oppressive atmosphere of burning gas or oil lamps. In addition to having clearer heads, they enjoyed clear vision, no longer deceived by the fl ame’s yellow fl icker. In some trades the more powerful light proved a useful tool of production, making work not only safer and faster, but also more accurate. Newspapers became early adopters of the new technology and often its greatest fans.

Th e transportation industry was another early adopter of the electric light, using it to extend the reach and value of the era’s powerful new railroads and steam ships, culminating by the early 20th century in a 24-hour per day distribution network. Lighthouses became popular.

Electricity was changing not only the way goods were produced but also how they were sold. Over time, merchants became sophisticated masters of light’s power to seduce customers. Stores installing electric lights were believed to have nothing to hide.

Physicians immediately recognized the potential value that the new light might provide to the healing arts, another fi eld profoundly improved by its ability to illuminate a once invisible world. Th e electric light amplifi ed the power and consistency of the microscope, which in turn helped to confi rm the germ theory of disease. Th e conventional microscope had long re-vealed minuscule creatures in water and organic matter. Th e British scientist John Tyndall used a beam of electric light to demonstrate that the air itself carried an organic swarm of spores, bacteria, and other minute solid particles, a startling discovery that unsettled many but added support to Louis Pasteur’s germ theory. Electric lights powered to reveal this hidden world proved valuable to health offi cials as they tried to publicize these radical new ideas about the source and preven-tion of devastating urban scourges, such as cholera and typhus. Even as 19th-century science asked the public to accept its claims about a world beyond human senses, the new technology gave some of this a tangible reality. A drop of water presented the most extraordinary monsters imaginable, one reported after seeing one of these germ slides.

Surgeons embraced electric light technology almost im-mediately, another part of the late 19th-century revolutionary improvement in medical practice. Over the centuries, physi-cians had tried using candles and mirrors to refl ect light into the body’s darkest corners and performed operations under skylights. Experts had recommended using the “cold north light” whenever possible since it cast less heat on the surgeon and fewer shadows on the patient. Physicians also had rigged devices to concentrate the beam of a candle or oil light, using it to illuminate translucent fl esh and reveal the shadows casts by tumors and abscesses. Th e incandescent bulbs were cooler, fl exible, and much brighter, and physicians used them almost immediately to provide the fi rst clear look at the living tissues of the throat, nasal passages, urinary bladder, and other portions of the body. Within a few years, instrument makers had crafted a series of specialized surgical lights, each adapted for the unique challenges posed by the various surgical procedures. Physicians improved their power of diagnosis, sending the focused light of incandescent bulbs into every opening in the body. Dentists benefi ted as well, fi nding the light cool enough to use right against the teeth and gums, illuminating defects otherwise hidden beneath the surface. Along with the development of anesthetics and aseptic practices, electric light laid the founda-tion for modern surgery.

Still others explored the idea that the electric light itself might be good medicine. Patients with nervous diseases and depres-sion were advised to replace their clear glass window panes with blue glass, and a Southern dentist swore by the use of an electric blue light for “the painless extraction of teeth.” Dr. John Harvey Kellogg pioneered the medical use of plain white electric light in his “laboratory of hygiene,” experimenting with the tonic eff ects of electric light. If the new urban environment disrupted sleep patterns and frayed nerves, producing a generation of Ameri-cans who retreated to sanitariums looking for a cure, then it was fortuitous for Kellogg to discover that the electric light, which had done so much to create these modern maladies, could also be


used to cure them. Kellogg thought that electric light was “noth-ing more nor less than a form of resuscitated sunshine.” Kellogg delivered light to thousands of patients, using what he called the “electric light bath.” Th e bather sat in a small cabinet, its interior lined with mirrors and studded with 60 incandescent bulbs. In this way patients dipped themselves into a healing “sea of light.” Kellogg claimed, “Shed upon the nude surface of the body the rays will enliven the nerves with renewed force and will dissipate and destroy the enumerable malefi c infl uences which imperil health and life.” His electric light cabinet proved a good place to work up a sweat, stimulating the skin, accelerating respiration, and somehow encouraging the internal organs in their eliminative work. Saturating the body in the warm glow of incandescent light, Kellogg claimed, would prevent disease, heal skin conditions, nourish the body, and was the most agreeable means of reducing fl esh, especially when the bather followed the electric bath with a brisk rubdown with salt or ice cold mittens.

And now the incandescent bulbs, in wide use since Th omas Edison received a patent for his version in 1880, are being phased out (23). A federal law passed in 2007 will end incandescent manufacturing and importing in the USA by the end of 2014, although stores will be allowed to keep them on the shelves until the inventory is gone. In their place will be the energy-effi cient replacements (Halogen, CFL [compact fl uorescent lamp], LED [light-emitting diode]), which are more expensive but last longer and require much less energy. Mr. Edison, thank you for the long and good run!

William Clifford Roberts, MD12 August 2013

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Morning News, June 10, 2013.19. Nam IS. Rising addiction among teens: smartphones. Wall Street Journal,

July 23, 2013.20. Cappiello D. Unprotected species. Dallas Morning News, May 15, 2013.21. Moyer S. Play ball . . . please! Wall Street Journal, July 13, 2013.22. Freeberg E. Th e Age of Edison: Electric Light and the Invention of Modern

America. New York: Penguin Group, 2013 (354 pp.).23. Lights out for old bulbs. Dallas Morning News, March 8, 2013.


442

Selected published abstracts of Baylor researchers

AMERICAN JOURNAL OF CARDIOLOGY

Natural history of unoperated aortic stenosis during a 50-year period of cardiac valve replacement

Roberts WC, Vowels TJ, Filardo G, Ko JM, Mathur RP, Shirani J

Am J Cardiol 2013;112(4):541–553. Reprinted with permission from Elsevier.

Although a number of publications have described the natural his-tory of patients with aortic stenosis (AS), the defi nition of “natural history” varies widely. Th ose describing a large number of patients with AS without operative therapy with necropsy fi ndings are rare. Two hundred sixty patients >15 years of age with AS were studied at necropsy over a 50-year period by the same investigator. Of the 260 patients, the valve in 37 (14%) was congenitally unicuspid, in 123 (47%), congenitally bicuspid, and in 100 (38%), tricuspid. Aortic valve structure varied with age of death (in years; unicuspid 52 ± 17, bicuspid 63 ± 12, and tricuspid 70 ± 14 years); gender (men/women: unicuspid 95%/5%, bicuspid 78%/22%, and tricuspid 63%/37%), and frequency of calcium in the mitral valve annulus and epicardial coronary arteries. Th e patients with cardiac-related symptoms com-pared with those without were more likely to have a congenitally malformed valve (unicuspid 17% vs 12%; bicuspid 51% vs 29%; tricuspid 31% vs 60%; unadjusted P = 0.013), to die from cardiac disease (86% vs 54%; unadjusted P = 0.001), and to have larger hearts (mean cardiac weight 606 ± 138 g vs 523 ± 121 g; unadjusted P = 0.009) and a larger quantity of calcium in the aortic valve cusps. In conclusion, the length of survival in adults with AS is related to valve structure, gender, presence of cardiac-related symptoms, cardiac mass, and quantity of calcium in the aortic valve cusps.

Comparison of total 12-lead QRS voltage in a variety of cardiac conditions and its usefulness in predicting increased cardiac mass

Roberts WC, Filardo G, Ko JM, Siegel RJ, Dollar AL, Ross EM,

Shirani J

Am J Cardiol 2013 Jun 14 [Epub ahead of print]. Reprinted with permission from Elsevier.

Echocardiography provides a more accurate method to determine increased cardiac mass than does electrocardiography. Nevertheless, most offi ces of physicians do not possess echocardiographic machines, but many possess electrocardiographic machines. Many electrocardio-graphic criteria have been used to determine increased cardiac mass, but few of the criteria have been measured against cardiac weight determined at necropsy or after cardiac transplantation. Such was the purpose of the present study. Cardiac weight at necropsy or af-ter transplantation was determined in 359 patients with 11 diff erent cardiac conditions, and total 12-lead electrocardiographic QRS volt-age (from the peak of the R wave to the nadir of either the Q or the S wave, whichever was deeper) was measured in each patient. Even in hearts with massively increased cardiac mass (>1,000 g), the total 12-lead QRS voltage was clearly increased (>175 mm) in only 94%,

but this criterion was superior to that of previously described electro-cardiographic criteria for “left ventricular hypertrophy.” Hearts with excessive adipose tissue infrequently had increased total 12-lead QRS voltage despite increased cardiac weight. Likewise, patients with fatal cardiac amyloidosis had hearts of increased weight but quite low total 12-lead QRS voltage. In conclusion, 12-lead QRS voltage is useful in predicting increased cardiac mass, but that predictability is dependent in part on the cause of the increased cardiac mass.

ANESTHESIA AND ANALGESIA

The accuracy, precision and reliability of measuring ventilatory rate and detecting ventilatory pause by rainbow acoustic monitoring and capnometry

Ramsay MA, Usman M, Lagow E, Mendoza M, Untalan E, De Vol E

Anesth Analg 2013;117(1):69–75. Reprinted with permission from Wolters Kluwer Health.

Background: Current methods for monitoring ventilatory rate have limitations including poor accuracy and precision and low patient tolerance. In this study, we evaluated a new acoustic ventilatory rate monitoring technology for accuracy, precision, reliability, and the ability to detect pauses in ventilation, relative to capnometry and a reference method in postsurgical patients.

Methods: Adult patients presenting to the postanesthesia care unit were connected to a Pulse CO-Oximeter with acoustic monitoring technology (Rad-87, version 7804, Masimo, Irvine, CA) through an adhesive bioacoustic sensor (RAS-125, rev C) applied to the neck. Each subject also wore a nasal cannula connected to a bedside capnometer (Capnostream20, version 4.5, Oridion, Needham, MA). Th e acous-tic monitor and capnometer were connected to a computer for con-tinuous acoustic and expiratory carbon dioxide waveform recordings. Recordings were retrospectively analyzed by a trained technician in a setting that allowed for the simultaneous viewing of both waveforms while listening to the breathing sounds from the acoustic signal to determine inspiration and expiration reference markers within the ventilatory cycle without using the acoustic monitor- or capnometer-calculated ventilatory rate. Th is allowed the automatic calculation of a reference ventilatory rate for each device through a software program (TagEditor, Masimo). Accuracy (relative to the respective reference) and precision of each device were estimated and compared with each other. Sensitivity for detection of pauses in ventilation, defi ned as no inspiration or expiration activity in the reference ventilatory cycle for ≥30 seconds, was also determined. Th e devices were also evaluated for their reliability, i.e., the percentage of the time when each displayed a value and did not drop a measurement.

Results: Th irty-three adults (73% female) with age of 45 ± 14 years and weight 117 ± 42 kg were enrolled. A total of 3712 minutes of monitoring time (average 112 minutes per subject) were analyzed across the 2 devices; reference ventilatory rates ranged from 1.9 to 49.1 bpm. Acoustic monitoring showed signifi cantly greater accuracy (P = 0.0056) and precision (P = 0.0024) for respiratory rate as compared with capnometry. On average, both devices displayed data over 97%


of the monitored time. Th e (0.95, 0.95) lower tolerance limits for the acoustic monitor and capnometer were 94% and 84%, respectively. Acoustic monitoring was marginally more sensitive (P = 0.0461) to pauses in ventilation (81% vs 62%) in 21 apneic events.

Conclusions: In this study of a population of postsurgical patients, the acoustic monitor and capnometer both reliably monitored ventilatory rate. Th e acoustic monitor was statistically more accurate and more precise than the capnometer, but diff erences in performance were modest. It is not known whether the observed diff erences are clini-cally signifi cant. Th e acoustic monitor was more sensitive to detecting pauses in ventilation. Acoustic monitoring may provide an eff ective and convenient means of monitoring ventilatory rate in postsurgical patients.

ASAIO JOURNAL

Case series using the ROTAFLOW system as a temporary right ventricular assist device after HeartMate II implantation

Khani-Hanjani A, Loor G, Chamogeorgakis T, Shafii A, Mountis M,

Hanna M, Soltesz E, Gonzalez-Stawinski GV

ASAIO J 2013;59(4):456–460. Reprinted with permission from Wolters Kluwer Health.

Th e purpose of this study was to investigate the outcomes of using the ROTAFLOW as a temporary right ventricular assist device (RVAD) support in patients who develop right ventricular dysfunction (RVD) at the time of left ventricular assist device (LVAD) implantation with the HeartMate (HM) II. We conducted a retrospective chart review of patients in whom the ROTAFLOW system was used for RV support during HM II implantation from October 2009 to September 2011. Twelve patients received a ROTAFLOW as an RVAD at the time of HM II implantation; 83% had preoperative echocardiography evidence of either moderate or severe RVD. Th e most common complications in the postoperative period were the need for tracheostomy because of respiratory failure (45%) and mediastinal bleeding requiring explora-tion (36%). Ninety-one percent of patients survived to discharge, and all were alive at 1 year follow-up. Our results show that temporary RVAD support with the ROTAFLOW system in the setting of RVD at the time of HM II implantation is feasible and eff ective.

CLINICAL NUCLEAR MEDICINE

Diffuse FDG uptake due to fat necrosis following transverse rectus abdominus myocutaneous (TRAM) flap reconstruction

Dobbs NB, Latifi HR

Clin Nucl Med 2013;38(8):652–654. Reprinted with permission from Wolters Kluwer Health.

We report a case of a 57-year-old female patient with right breast invasive ductal carcinoma. Bilateral mastectomy and TRAM fl ap re-constructions were performed. Postoperatively, a palpable focus was identifi ed within the left breast. PET/CT showed hypermetabolism throughout the reconstructed left breast, correlating with mixed fat attenuation and infl ammatory soft tissue. MRI showed extensive fat necrosis/oil cyst formation in the left breast. As a TRAM fl ap recon-struction with fat-rich tissue can be damaged intraoperatively due to surgical manipulation, abnormal FDG uptake in this setting is more likely related to fat necrosis than recurrent tumor.

CONTEMPORARY CLINICAL TRIALS

Chronic obstructive pulmonary disease self-management activation research trial (COPD-SMART): design and methods

Ashmore J, Russo R, Peoples J, Sloan J, Jackson BE, Bae S, Singh

KP, Blair SN, Coultas D

Contemp Clin Trials 2013;35(2):77–86. Reprinted with permission from Elsevier.

Background: Treatment of COPD requires multiple pharmacological and non-pharmacological intervention strategies. One target is physical inactivity because it leads to disability and contributes to poor physical and mental health. Unfortunately, less than 1% of eligible patients have access to gold-standard pulmonary rehabilitation.

Methods: A single-site parallel group randomized trial was designed to determine if a self-management lifestyle physical activity intervention would improve physical functioning and dyspnea. During the fi rst 6 weeks after enrollment, patients receive COPD self-management education delivered by a health coach using a workbook and weekly telephone calls. Patients are then randomized to usual care or the physical activity intervention. Th e 20-week physical activity interven-tion is delivered by the health coach using a workbook supported by alternating one-on-one telephone counseling and computer assisted telephone calls. Th eoretical foundations include social cognitive theory and the transtheoretical model.

Results: Primary outcomes include change in Chronic Respiratory Questionnaire (CRQ) dyspnea domain and 6-minute walk distance measured at 6, 12, and 18 months after randomization. Secondary out-comes include other CRQ domains (fatigue, emotion, and mastery), SF-12, and health care utilization. Other measures include process outcomes and clinical characteristics.

Conclusions: Th is theory-driven self-management lifestyle physical activity intervention is designed to reach patients unable to complete center-based pulmonary rehabilitation. Results will advance knowledge and methods for dissemination of a potentially cost-eff ective program for patients with COPD.

FOOT AND ANKLE INTERNATIONAL

Prospective study of the treatment of adult primary hallux valgus with scarf osteotomy and soft tissue realignment

Choi JH, Zide JR, Coleman SC, Brodsky JW

Foot Ankle Int 2013;34(5):684–690. Reprinted with permission from Sage Publications.

Background: Th e scarf osteotomy has been a widely practiced bunion operation, but relatively limited prospective data on its outcomes have been reported. Th e purpose of this investigation was to prospectively evaluate the clinical and radiographic results of treatment of adult primary hallux valgus using the scarf osteotomy of the fi rst metatarsal with soft tissue realignment.

Methods: Hallux valgus corrections were performed on 51 patients (53 feet), who were followed for at least 1 year with an average follow-up of 24 months. Mean age at the time of surgery was 59 years, and subjects included 3 male and 48 female patients. Pro-spective clinical data collected included the American Orthopaedic Foot & Ankle Society (AOFAS) hallux-interphalangeal scale score,

Selected published abstracts of Baylor researchers 443October 2013

the SF-36 scores, and the visual analogue scale (VAS) for pain. Data were collected preoperatively and postoperatively. Prospective radiologic data were also collected including hallux valgus angle (HVA), fi rst-second intermetatarsal angle (IMA), and medial sesa-moid position (MSP). Clinical data were collected on complications and reoperations.

Results: Mean AOFAS hallux-interphalangeal score increased from 52 preoperatively to 88 postoperatively. Mean preoperative and last follow-up SF-36 physical component summary increased from 46 preoperatively to 52 postoperatively, whereas mean VAS pain scores decreased from 5.8 preoperatively to 1.1 postoperatively. All the changes in clinical outcomes were statistically signifi cant, except the Mental Component Summary of the SF-36. Mean preoperative HVA decreased from 29 degrees preoperatively to 10.7 degrees in the initial postoperative period and was maintained at last follow-up at 10.6 degrees. Th e mean preoperative IMA decreased from 13.6 degrees preoperatively to 5.6 degrees in the initial postoperative period and regressed mildly at last follow-up to 7.8 degrees. Th e mean preopera-tive MSP grade of 2.3 decreased to 0.5 in the initial postoperative period and regressed mildly to 0.9 at last follow-up. All radiographic changes were statistically signifi cant. Th e overall complication rate was 15% (8/53), attributable to 4 feet with symptomatic hardware, 2 feet with hallux varus, and 2 feet with progression of fi rst MTP arthritis. Reoperations were performed in 4 feet (8%) for removal of symptomatic hardware.

Conclusion: Scarf osteotomy was a reliable technique for correction of moderate to severe hallux valgus and had low rates of complication or recurrence.

Level of evidence: Level IV, case series.

Hindfoot motion following STAR total ankle arthroplasty: a multisegment foot model gait study

Brodsky JW, Coleman SC, Smith S, Polo FE, Tenenbaum S

Foot Ankle Int 2013 Jun 17 [Epub ahead of print]. Reprinted with permission from Sage Publications.

Background: One of the rationales for total ankle arthroplasty (TAA) is that it may retard the changes of hypermobility and accelerated arthritis in the hindfoot after ankle arthrodesis. Until recently, it has not been possible to quantify or even objectively demonstrate biomechanical fi ndings to substantiate the theory that postsurgical biomechanical changes in the ankle produce changes in the kinematics of the hind-foot. Standard gait analysis has treated the foot as a single biomechani-cal unit. Th is study was undertaken to describe the hindfoot motion following Scandinavian Total Ankle Replacement (STAR) TAA by using multisegment foot model gait analysis.

Methods: Forty-six patients with a mean age of 66 years underwent a 3D gait analysis following TAR. Mean interval between surgery and gait analysis was 4.9 years (range 2 to 9). Th e contralateral limb was used as control for each patient. Temporospatial variables and kine-matic parameters were studied.

Results: Temporospatial results showed statistically signifi cant dif-ferences. Stance time on the aff ected side was 61.1% ± 2.2% of the gait cycle compared to 63.2% ± 2.1% for the unaff ected side. Step length was 55.6 cm ± 10 on the aff ected side compared to 53.9 cm ± 10 for the unaff ected side. Kinematics results were statistically signifi cant: Ankle range of motion (ROM) on the arthroplasty side

was 16.8 ± 4.5 degrees compared to 23.6 ± 5.0 on the unaff ected side. Sagittal plane ROM was 12.7 ± 4.2 degrees on the arthro-plasty side and 17.3 ± 3.5 degrees on the unaff ected side. Coronal plane ROM was 4.7 ± 2.4 degrees on the arthroplasty side and 7.5 ± 2.4 degrees on the unaff ected side. Transverse plane ROM on the arthroplasty side was 4.1 ± 1.5 degrees and 4.9 ± 1.6 on the unaff ected side.

Conclusion: Th is study showed that, in addition to previously docu-mented diminution in sagittal plane motion and gait velocity, some of the residual abnormalities of gait following TAR were comprised of diff erences in hindfoot function. Th ese results relate to the growing recognition of the importance of understanding hindfoot mechanics apart from those of the tibiotalar joint.

Level of evidence: Level III, comparative case series.

GUT

Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis

Hur K, Cejas P, Feliu J, Moreno-Rubio J, Burgos E, Boland CR, Goel A

Gut 2013 May 23 [Epub ahead of print]. Reprinted with permission from BMJ Publishing Group Ltd.

Objective: Hypomethylation of LINE-1 elements has emerged as a distinguishing feature in human cancers. Limited evidence indicates that some LINE-1 elements encode an additional internal antisense promoter, and increased hypomethylation of this region may lead to inadvertent activation of evolutionarily methylation-silenced down-stream genes. However, the signifi cance of this fundamental epige-netic mechanism in colorectal cancer (CRC) has not been investigated previously.

Design: We analysed tissue specimens from 77 CRC patients with matched sets of normal colonic mucosa, primary CRC tissues (PC), and liver metastasis tissues (LM). LINE-1 methylation levels were determined by quantitative bisulfi te pyrosequencing. MET, RAB3IP and CHRM3 protein expression was determined by western blotting and IHC. MET proto-oncogene transcription and 5-hydroxymethyl-cytosine (5-hmc) were evaluated by quantitative real-time PCR.

Results: Global LINE-1 methylation levels in LM were signifi cantly lower compared with the matched PC (PC = 66.2% vs LM = 63.8%; P < 0.001). More importantly, we observed that specifi c LINE-1 sequences residing within the intronic regions of multiple proto-oncogenes, MET (P < 0.001), RAB3IP (P = 0.05), and CHRM3 (P = 0.01), were signifi cantly hypomethylated in LM tissues compared with corresponding matched PC. Furthermore, reduced methylation of specifi c LINE-1 elements within the MET gene inversely correlated with induction of MET expression in CRC metastases (R = –0.44; P < 0.0001). Finally, increased 5-hmc content was associated with LINE-1 hypomethylation.

Conclusions: Our results provide novel evidence that hypomethyla-tion of specifi c LINE-1 elements permits inadvertent activation of methylation-silenced MET, RAB3IP, and CHRM3 proto-oncogenes in CRC metastasis. Moreover, since 5-hmc content inversely corre-lated with LINE-1 hypomethylation in neoplastic tissues, our results provide important mechanistic insights into the fundamental processes underlying global DNA hypomethylation in human CRC.


IMMUNITY

Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines

Obermoser G, Presnell S, Domico K, Xu H, Wang Y, Anguiano E,

Thompson-Snipes L, Ranganathan R, Zeitner B, Bjork A, Anderson

D, Speake C, Ruchaud E, Skinner J, Alsina L, Sharma M, Dutartre H,

Cepika A, Israelsson E, Nguyen P, Nguyen QA, Harrod AC, Zurawski

SM, Pascual V, Ueno H, Nepom GT, Quinn C, Blankenship D, Palucka

K, Banchereau J, Chaussabel D

Immunity 2013;38(4):831–844. Reprinted with permission from Elsevier.

Systems immunology approaches were employed to investigate in-nate and adaptive immune responses to infl uenza and pneumococcal vaccines. Th ese two non-live vaccines show diff erent magnitudes of transcriptional responses at diff erent time points after vaccination. Software solutions were developed to explore correlates of vaccine effi cacy measured as antibody titers at day 28. Th ese enabled a fur-ther dissection of transcriptional responses. Th us, the innate response, measured within hours in the peripheral blood, was dominated by an interferon transcriptional signature after infl uenza vaccination and by an infl ammation signature after pneumococcal vaccination. Day 7 plasmablast responses induced by both vaccines were more pronounced after pneumococcal vaccination. Together, these results suggest that comparing global immune responses elicited by diff erent vaccines will be critical to our understanding of the immune mechanisms underpin-ning successful vaccination.

JOURNAL OF SPINAL DISORDERS AND TECHNIQUES

Retrospective study of anterior interbody fusion rates and patient outcomes of using mineralized collagen and bone marrow aspirate in multilevel adult spinal deformity surgery

Hostin R, O’Brien M, McCarthy I, Bess S, Gupta M, Klineberg E;

International Spine Study Group

J Spinal Disord Tech 2013 Apr 3 [Epub ahead of print]. Reprinted with permission from Wolters Kluwer Health.

Design: Retrospective, single-center analysis of multilevel anterior fu-sion rates and health-related quality-of-life (HRQOL) outcomes of mineralized collagen and bone marrow aspirate (BMA) in anterior interbody fusion cages for spine fusion surgery.

Objective: To determine the ability and eff ectiveness of mineralized collagen and BMA to achieve multilevel anterior spinal fusion in adult spinal deformity patients when placed in carbon fi ber reinforced poly-mer cages.

Summary of background data: High rates of post-operative pain and non-union can result from spine fusion procedures. Factors that af-fect the success of fusion include patient co-morbidities, position of implant, and mechanical and biologic defi ciencies, as well as the choice of bone graft replacement.

Methods: Analysis of radiographic images and HRQOL outcomes was performed for a consecutive series of 22 prospectively enrolled adult spinal deformity patients with 104 total anterior fusion levels. Fusions were graded by 3 blinded surgeons not involved in the opera-tive procedure; each fusion was graded on a 1–4 scale based on fusion

mass appearance. Levels with an average fusion grade of 1–2.4 were classifi ed as fused; levels with an average grade >2.5 were classifi ed as not fused.

Results: Th e mean patient age was 51.5 years (range 38–61) with 21 females; 95% of anterior operative levels were graded as fused based on fl exion/extension and full length biplane radiographs at one year. CT grading showed a reduced fusion rate at 87% overall. Th ere was a statistically signifi cant improvement in the Oswestry Disability Index and Scoliosis Research Society 22-item questionnaire scores at one year and two years following index surgery.

Conclusions: Fusion rates in multilevel anterior spinal fusion using mineralized collagen and BMA are relatively low compared to fusion rates of 95% or more reported in the existing literature on long fu-sions with BMP.

LIVER TRANSPLANTATION

Preformed class II donor-specific antibodies are associated with an increased risk of early rejection after liver transplantation

O’Leary JG, Kaneku H, Jennings LW, Bañuelos N, Susskind BM,

Terasaki PI, Klintmalm GB

Liver Transpl 2013 Jun 18 [Epub ahead of print]. Reprinted with permission from John Wiley and Sons.

Preformed donor-specifi c human leukocyte antigen antibodies (DSAs) are considered a contraindication to the transplantation of most solid organs other than the liver. Confl icting data currently exist on the importance of preformed DSAs in rejection and patient survival after liver transplantation (LT). To evaluate preformed DSAs in LT, we retrospectively analyzed prospectively collected samples from all adult recipients of primary LT without another organ from January 1, 2000 to May 31, 2009 with a pre-LT sample available (95.8% of the pa-tients). Fourteen percent of the patients had preformed class I and/or II DSAs with a mean fl uorescence intensity (MFI) > 5000. Preformed class I DSAs with an MFI > 5000 remained persistent in only 5% of patients and were not associated with rejection. Preformed class II DSAs with an MFI of 5000 to 10,000 remained persistent in 23% of patients, and this rate increased to 33% for patients whose MFI was >10,000 (P < 0.001). Preformed class II DSAs in a multivariate Cox proportional hazards modeling were associated with an increased risk of early rejection [hazard ratio (HR) = 1.58]. In addition, multivariate modeling showed that in comparison with no DSAs (MFI < 1000), preformed class I and/or II DSAs with an MFI > 5000 were indepen-dently correlated with the risk of death (HR = 1.51).

MOLECULAR GENETICS AND METABOLISM

Quantitation of gamma-hydroxybutyric acid in dried blood spots: Feasibility assessment for newborn screening of succinic semialdehyde dehydrogenase (SSADH) deficiency

Forni S, Pearl PL, Gibson KM, Yu Y, Sweetman L

Mol Genet Metab 2013;109(3):255–259. Reprinted with permission from Elsevier.

Objective: SSADH defi ciency, the most prevalent autosomal recessive disorder of GABA degradation, is characterized by elevated gamma-hydroxybutyric acid (GHB). Neurological outcomes may be improved with early intervention and anticipatory guidance. Morbidity has been

Selected published abstracts of Baylor researchers 445October 2013

compounded by complications, e.g. hypotonia, in undiagnosed infants with otherwise routine childhood illnesses. We report pilot methodol-ogy on the feasibility of newborn screening for SSADH defi ciency.

Method: Dried blood spot (DBS) cards from patients aff ected with SSADH defi ciency were compared with 2831 archival DBS cards for gamma-hydroxybutyric acid content. Following extraction with methanol, GHB in DBS was separated and analyzed using ultra high-performance liquid chromatography tandem mass spectrometry.

Results: Methodology was validated to meet satisfactory accuracy and reproducibility criteria, including intra-day and inter-day validation. Archival refrigerated dried blood spot samples of babies, infants, and children (N = 2831) were screened for GHB, yielding a mean ± S.D. of 8 ± 5 nM (99.9%-tile 63 nM) (Min 0.0 Max 78 nM). Th e measured mean and median concentrations in blood spots derived from seven SSADH defi cient patients were 1182 nM and 699 nM respectively (Min 124, Max 4851 nM).

Conclusions: GHB concentration in all 2831 dried blood spot cards was well below the lowest concentration of aff ected children. Th ese data provide proof-of-principle for screening methodology to detect SSADH defi ciency with applicability to newborn screening and earlier diagnosis.

WORLD JOURNAL OF SURGERY

Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors

Landry CS, Lin HY, Phan A, Charnsangavej C, Abdalla EK, Aloia T,

Nicolas Vauthey J, Katz MH, Yao JC, Fleming JB

World J Surg 2013;37(7):1695–1700. Reprinted with permission from Springer.

Background: Neuroendocrine tumors of the small intestine commonly metastasize to regional lymph nodes (LNs). Single-institution reports suggest that removal of LNs improves outcome, but comprehensive data are lacking. We hypothesized that the extent of lymphadenectomy reported in a large administrative database would be associated with overall survival for jejunal and ileal neuroendocrine tumors.

Methods: A search of the Surveillance Epidemiology and End Results database was performed for patients with jejunal and ileal neuroendo-crine tumors from 1977 to 2004. Descriptive patient characteristics were collected to include age at diagnosis, sex, race, grade, primary tumor size, LN status, number of LNs resected, presence of distant metastasis, and the type of operation. Statistical analyses were limited to patients with only one primary tumor to exclude patients with other malignancies. Univariate and multivariate analyses were performed to analyze the number of LNs resected and the LN ratio (number of positive LNs/total number of LNs removed) to determine the eff ect on cancer-specifi c survival.

Results: Altogether, 1,364 patients were included in this analysis. Re-moval of any LNs was associated with improved cancer-specifi c survival when compared to patients with no LN removal reported (P = 0.0027) on univariate analysis. Among those who had any LNs removed, a me-dian of eight LNs were identifi ed in resection specimens with a median LN ratio of 0.29 (range 0–1). On multivariate analysis (adjusting for age and tumor size), patients with >7 LNs removed experienced bet-ter cancer-specifi c survival than those with ≤7 LNs removed (median survival not reached vs. 140 months): hazard ratio and 95% confi dence interval were 0.573 (0.402, 0.817) (P = 0.002).

Conclusions: Th is review of a large number of surgical patients demon-strates that regional mesenteric lymphadenectomy in conjunction with resection of the primary tumor is associated with improved survival of patients with small bowel neuroendocrine tumors.

If you are a Baylor researcher and would like your published abstract to be included in this section, please e-mail the PubMed citation to [email protected].


447

Instructions for authors

Baylor University Medical Center Proceedings welcomes re-search articles, review articles, case studies, and editorials from Baylor and non-Baylor authors. Manuscripts contain-ing Baylor data are particularly desired. Send all manuscripts

and editorial correspondence to William C. Roberts, MD, Editor in Chief, Baylor Scientifi c Publications Offi ce, 3500 Gaston Avenue, Dal-las, Texas 75246; phone: 214-820-9996; fax: 214-820-4064; e-mail: [email protected].

MANUSCRIPT SUBMISSIONSubmit the word processing document by e-mail to cynthiao@Bay-

lorHealth.edu. Large fi les may be sent using YouSendIt or SendNow. Cover letter and attachments: According to journal policies outlined

below, list suggested reviewers and discuss potential confl icts of interest in your cover letter and provide as attachments copies of institutional review board approval or exemption, written permission for reprinting tables or fi gures, copies of any published material that could be considered duplicative, and release authorization forms for photographs.

Schedule: Deadlines for submission are as follows: January is-sue, September 1; April issue, December 1; July issue, March 1; and October issue, June 1. Th e editorial offi ce cannot guarantee that any manuscript submitted by these deadlines will be published in the specifi ed issue; variables include the peer review and revision process and the number of articles already accepted.

ARTICLE TYPESIn addition to multipatient studies (original research articles),

Proceedings publishes several other article types. Case studies: Include an abstract, a single-paragraph introduction

(optional with short reports), a case description of 0.5 to 2 double-spaced pages, and a discussion of 1 to 5 double-spaced pages. Up to 25 references are acceptable (although many case reports have 5 to 10). Th e maximum number of fi gures and tables (combined) is 6.

Historical studies: Abstracts are recommended. Th ere is no word limit, but most historical studies are 1500 to 3500 words.

Editorials: Th ere is no word limit, but most editorials are 800 to 1600 words.

Book reviews: See past issues for format. Th ere is no word limit, but most book reviews are 800 to 1600 words.

Avocations: Submit an image fi le for your painting or photograph or a discussion of your hobby for a maximum of 300 words.

Reader comments (letters to the editor): Both responses to previously published material and brief reports or observations are considered for this section. Th e limit is 1200 words.

MANUSCRIPT PREPARATIONFormat: Type manuscripts double spaced, leaving 1-inch margins.

Number all pages, including the title page. Title page: Include on the fi rst page the article’s title; the authors’

names, highest degree(s), and affi liations; and the name, address, e-mail

address, and phone number of the corresponding author. Acknowledge any grant support.

Abstract: Provide a one-paragraph double-spaced abstract of 150 to 250 words. Abstracts are required for original articles and case stud-ies and are recommended for reviews and long historical articles.

Conclusions: Conclusion paragraphs at the end of the discussion section are rarely needed and are often cut if included.

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Journal article: O’Shaughnessy J, Osborne C, Pippen JE, Yoff e M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 2011;364(3):205–214.Book chapter: Ramsay M. Liver transplantation and portopul-monary hypertension. In Milan Z, ed. Cardiovascular Diseases and Liver Transplantation. New York: Nova Biomedical Books, 2011:83–97.Book: Gulati G, Filicko-O’Hara J, Krause JR. Case Studies in Hematology and Coagulation. Chicago, IL: American Society for Clinical Pathology Press, 2012.Authors using Endnote can access Proceedings’ reference style by

downloading an EndNote style fi le, available at http://www.baylor-health.edu/Research/Proceedings/SubmitaManuscript/Pages/Manu-scriptPreparation.aspx. Personal communications and unpublished data should not be used as references; they should be identifi ed in parentheses in the text.

Tables and fi gures: Number tables and fi gures in the order in which they are discussed in the text. Include call-outs in the text and place the tables at the end of the document as Word fi les using the Word table function. Figures can be embedded in the text at the end of the document or provided as separate fi les, with legends in the Word fi le. Provide enough details in titles, footnotes, and legends so that the tables and fi gures can be understood apart from the text. Submit photographs as 350-ppi tiff or jpeg fi les. Submit graphs and diagrams as electronic fi les (EPS format preferred).

Use of color: Color is used in articles only when clinically re-quired (as with certain pathology and radiology images). Avoid using color when creating charts and graphs. If photographs (such as those in interviews) are originally in color, they can be con-verted to black and white during journal production. Articles that use color are generally grouped together in the issue to decrease overall printing expenses.

Style issues: Use generic names for drugs; capitalize any trade names when they are used. Limit the number of abbreviations in a manuscript to fi ve, and do not abbreviate single words, such as intravenous. Spell out all abbreviations on fi rst usage. Proceedings

Proc (Bayl Univ Med Cent) 2013;26(4):447–448 447

follows the style guide of the American Medical Association. As further guidance, prospective authors are encouraged to consult the “Authors’ submission toolkit” (1) and an article on medical publishing by the editor in chief (2).

MANUSCRIPT PROCESSINGPeer review: All manuscripts are subject to peer review by editorial

board members or other selected reviewers; however, the fi nal decision as to which articles are published will be made by the editor in chief. At the time of manuscript submission, authors are encouraged to suggest reviewers, within or outside the Baylor Health Care System, and to list any reviewers they feel should not be used because of potential bias. If a manuscript was previously reviewed by another journal, authors should submit those reviews and clearly indicate any revisions that have been made. Such manuscripts will receive expedited processing, since they usually will not be sent out for re-review.

Editing: All manuscripts will be edited for clarity and conformity to Proceedings’ style. Th e corresponding author will have the opportu-nity to review editing either before or at the page proof stage.

Reprints: Authors can order reprints using the form provided through an e-mail link from the printer. Reprints are delivered ap-proximately 4 weeks after the issue comes out. All authors receive a copy of the printed journal, and PDF fi les of articles are freely available to the authors and the general public.

JOURNAL POLICIESDuplicate publication: When submitting the manuscript, pro-

vide a copy of any published or submitted article that is similar to what is being submitted to Proceedings, so that the editor can judge whether the manuscript in question would be a duplicate publication. Once manuscripts are accepted, authors transfer copyright to Baylor University Medical Center at Dallas.

Authorship: All authors listed in the manuscript must have par-ticipated in the design or analysis of the project. In addition, all authors must review the fi nal text and be prepared to take public responsibility for its content.

Ethical treatment of research subjects: For reports of experimen-tal investigations of human or animal subjects, indicate institutional review board approval or exemption within the manuscript. Authors should also explain in the Methods section the procedures followed to obtain informed consent.

Confl ict of interest: Grant support for a particular study must be indicated on the title page. In addition, authors must commu-nicate to the editor in the cover letter any affi liations that could be perceived as potential confl icts of interest. Examples include honoraria, educational grants, participation in speakers’ bureaus, expert testimony, patent licensing arrangements, consultancies, and stock ownership.

Use of protected health information: Authors should not refer to patients by name or initials or provide other specifi c identifying information, such as Social Security number or medical record number. Authors are further encouraged to avoid including extraneous social details about patients. Patient authorization forms are required for all identifying photographs. For a copy of Proceedings’ full privacy policy, contact the managing editor.

Permissions: Permission is required for reproduction of any mate-rial, including fi gures and tables, that has been published elsewhere. When submitting manuscripts, provide written documentation that permission has been obtained or notify the editorial staff of the need to request permission (providing all necessary source information). For photographs in which the subject can be recognized, submit release authorizations at the time of manuscript submission.

For additional information, please contact Cynthia Orticio, man-aging editor, at 214-820-9996 or [email protected].

1. Chipperfi eld L, Citroma L, Clark J, David FS, Neck R, Evangelista M, Gonzalez J, Groves T, Magan J, Mansa B, Miller C, Mooney LA, Murphy A, Shelton J, Wilson PD, Weigl A. Authors’ submission toolkit: a practical guide to getting your research published. Cur Med Res Open 2010;26(8):1967–1982.

2. Roberts WC. Formulating an answerable question, displaying data, il-lustrating, writing, reviewing, and editing manuscripts for publication in medical journals. Am J Cardiol 2012;110(2):290–306.

MANUSCRIPT SUBMISSION CHECKLIST— Th e entire manuscript is double-spaced and in one Word fi le, in

the following order: title page, abstract, text, references, tables, fi gures (either fi gure legends only or fi gures embedded plus leg-ends). Page numbers appear on the bottom of each page.

— Th e title page has required elements: title, authors (with full names and degrees), affi liations, and address for corresponding author.

— A single-paragraph abstract of 150 to 250 words is included.— For case studies: After the abstract, the manuscript includes

a single-paragraph introduction (optional), a case discussion of 0.5 to 2 double-spaced pages, and a discussion of 0.5 to 5 double-spaced pages. Th e manuscript does not exceed the limit of 25 references or 6 fi gures and tables.

— Figures are high-resolution. Photographs are 350-ppi tiff or jpeg fi les.

— References include all authors, the full article title, the journal abbreviation from Index Medicus, the volume and issue number, and inclusive page numbers. References in the text appear in pa-rentheses, rather than in superscript or footnotes or endnotes.

— All authors have approved the version to be submitted.

Manuscripts that do not meet these requirements may be returned to authors before peer review is initiated.


Volume 26

Number 4

October 2013

To access Baylor’s physicians, clinical services, or

educational programs, contact the Baylor Physician

ConsultLine: 1-800-9BAYLOR (1-800-922-9567)

Baylor University Medical Center, Dallas, Texas

Baylor University Medical Center Proceedings

Volume 26, N

umber 4 • October 2013

Pages 361–448

www.BaylorHealth.edu/Proceedings

Indexed in PubMed, with full text available through PubMed Central

405 Fibromuscular dysplasia of the renal artery as a cause of secondary hypertension

A. Y. Hundae, C. A. Hebert, and J. M. Schussler

407 Slow group beating D. L. Glancy and V. N. Lathia

408 Continuous murmur and cardiac failure in a 53-year-old woman

D. L. Glancy and E. B. Hanna

410 Amlodipine overdose T. Patel, D. Tietze, and A. N. Mehta

Historical Studies 417 Consults for confl ict: the history of ethics consultation Elliot B. Tapper

Editorials 423 What’s going on in dental education? Eric S. Solomon

425 An unforgettable, perpetual medical student, 1961 S. Robert Lathan

Book Reviews 427 Review of For the Love of Wild Th ings (Dimijian) Daniel E. Polter

428 Review of Sifting Shades (Khan) Harbans Lal

From the Editor 432 Facts and ideas from anywhere William C. Roberts

Miscellany

386 Avocations: Photograph by Dr. Rosenthal

412 Baylor news

416 Clinical research studies enrolling patients

429 Reader comments: Cardiac rehabilitation in fi refi ghters (S. N. Kales, D. M. Baur, D. Hostler, and D. L. Smith; author reply: R. Berbarie, J. Adams, and T. Bilbrey)

442 Selected published abstracts of Baylor researchers

447 Instructions for authors

Multipatient Studies 363 Migraine disability, healthcare utilization, and

expenditures following treatment in a tertiary headache center

F. G. Freitag, H. Lyss, and G. R. Nissan

368 Advance care planning knowledge and documentation in a hospitalized cancer population

A. Barakat, S. A. Barnes, M. A. Casanova, M. J. Stone, K. M. Shuey,

and A. M. Miller

373 Incidence and severity of respiratory insuffi ciency detected by transcutaneous carbon dioxide monitoring after cardiac surgery and intensive care unit discharge

E. E. Lagow, B. Leeper, L. W. Jennings, and M. A. E. Ramsay

376 Outcome assessment of 603 cases of concomitant inferior turbinectomy and Le Fort I osteotomy

R. Movahed, C. Morales-Ryan, W. R. Allen, S. Warren, and L. M. Wolford

Single-Patient Studies 382 Copper defi ciency (hypocupremia) and pancytopenia

late after gastric bypass surgery S. D. Robinson, B. Cooper, and T. V. Leday

387 Isolated atrial amyloidosis and the importance of molecular classifi cation

V. Podduturi, D. R. Armstrong, M. A. Hitchcock, W. C. Roberts,

and J. M. Guileyardo

390 Th e Heerfordt-Waldenström syndrome as an initial presentation of sarcoidosis

M. C. Denny and A. D. Fotino

393 Unusual dermal pleomorphic calcifi cations in a case of infl ammatory breast carcinoma

A. R. Yactor, M. Zarghouni, J. C. Wang, R. R. Hamilton, and J. J. Spigel

396 Basal cell adenoma of the breast M. Van Vrancken, M. Mir, and W. Herlihy

398 Critical lower limb ischemia from an embolized Angio-Seal closure device

C. Cianci, R. C. Kowal, G. Feghali, S. Hohmann, R. C. Stoler,

and J. W. Choi

401 Th e myth of the Bernheim syndrome M. S. Chung, J. M. Ko, T. Chamogeorgakis, S. A. Hall, and W. C. Roberts

baylor university medical center, dallas, texas proceedings/2013 vol...volume 26 number 4 october...

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