George Washington University Medical Center Research Articles

Invited Commentary: FIGO Staging Classification for Cervical Cancer-Behold the Big Picture.

Invited Commentary: FIGO Staging Classification for Cervical Cancer-Behold the Big Picture.

Losing a Radiant Star—Dr. Edward C. De Fabo (1937–2019)

On December 24, 2019, the pigment, melanoma, and photobiology research communities lost a treasure. Dr. Edward De Fabo passed away peacefully after a valiant 5-year battle against advanced colon cancer. He was 82. He is survived by his wife of 33 years, Dr. Frances Noonan, who had also been his scientific partner. Together, they were a remarkable team, seeking and finding answers to critical scientific questions that had plagued researchers for decades.

APA Condemns Use of Therapy Records in Immigration Cases

APA Condemns Use of Therapy Records in Immigration Cases

Our Future Selves: Unprecedented Opportunities.

Carole B. Lewis, PT, DPT, GTC, PhD, has focused throughout her career on the continuous improvement of clinical care provided to older adults. Dr Lewis is an adjunct professor at the George Washington University Medical Center Department of Health Care Services and continues to work in private practice. She serves as president of Great Seminars and Books and Great Seminars Online and for 33 years has been editor-in-chief of Topics in Geriatric Rehabilitation , which won the Association of American Publishers' Award for the Most Outstanding Issue of a Scientific Journal. She earned a DPT from MGH Institute of Health Professions, a PhD in health education from the University of Maryland, an MS in gerontology from the University of Southern California Leonard Davis School, an MPA in health care management from the University of Southern California, and a BS in physical therapy from The Ohio State University. Dr Lewis has held 24 consultation positions in clinics and workplaces and with third-party payers. One of the first researchers to determine that older adults are able to exercise safely and can realize major improvements in outcomes when prescribed appropriate exercise, Dr Lewis has published extensively in the field of aging, with research published in journals such as Archives of Physical Medicine and Rehabilitation and the New England Journal of Medicine. She is author of more than 20 textbooks on aging, including what may be the first text on aging and rehabilitation and one of the first on functional assessment ( Aging: Health Care's Challenge: Interdisciplinary Assessment and Treatment of the Geriatric Patient , now in its fourth edition; Geriatric Clinical Strategies ; Geriatric Physical Therapy ; Orthopedic Assessment and Treatment of the Geriatric Patient ; The Geriatric Exercise Kit ; The Functional Toolbox I & II ; The Balance Book and Osteoporosis Exercise …

ABO phenotype and sepsis in very low birth infants

An association between infection and an individual's blood group has been reported in the adult medical literature. This association has so far not been investigated in the neonate, and may be reflected in the differences in susceptibilities of neonates to bacterial sepsis. The aim of this study is to investigate the association between ABO phenotype and the incidence of sepsis in very low birth weight infants. This is a retrospective data analysis. All very low birth weight infants admitted to The George Washington University Medical Center between November 1997 and March 2003 were classified according to blood groups into group 1: Phenotype O and A (possible B-antibody (ab)); and group 2: Phenotype B and AB (without B-ab). Multivariate regression analysis was performed to determine statistically significant differences in sepsis between the two groups. Data on 164 infants was analyzed. One hundred and twenty five infants (76.2%) had blood group A or O and 39 infants (23.8%) had blood group B or AB. Mean gestational age was 27.6 ± 2.4 weeks and mean birth weight was 984.5 ± 295 g. Groups were not significantly different in gestational age, birth weight, gender, and race. After controlling for confounding variables, there was no difference between the groups in the incidence of sepsis (34% vs. 33%, P = 0.24). ABO blood group phenotype was not correlated with sepsis in the very low birth weight infants in our unit.

English

HIV treatment has been greatly impacted by transmitted resistance to antiretrovirals (ARV). Several studies have documented resistance in naive individuals and estimates of transmitted drug resistance mutations range from <5% to as high as 25%. Washington, D.C. has one of the highest human immunodeficiency virus (HIV) prevalence rates in the United States (3.2% in 2009), but local data regarding the frequency of major mutations and antiretroviral (ARV) resistance has been limited. Medical records of HIV positive, ARV-naive adults at two facilities in Washington, D.C., The George Washington University Medical Center and the Veterans Affairs Medical Center, were retrospectively analyzed in subjects who had genotypic resistance testing from 2007 to 2010. Of 407 ARV-naive patients, at least one transmitted drug resistance mutation was detected in 17% of our patients, with non-nucleoside reverse transcriptase (NNRTI) mutations observed in 15%. Among patients with at least one reverse transcriptase (RT) or major protease region (Pr) resistance mutation, 85% had resistance against a single ARV class. Dual and triple class resistance mutations were seen in 8 patients (2%) and 3 patients (0.7%), respectively. Most of the multiple class resistance was seen in 2010. A gradual increase in NNRTI resistance was noted during 2008 to 2010. Our prevalence of transmitted RT, major Pr mutations (17.4%) and ARV resistance (8.6%) were high but similar to rates reported by others within the United States. Given the high HIV prevalence in the District of Columbia, this has important implications for treatment of these ARV-naive patients. Key words: HIV, Washington D.C., naive to antiretrovirals, transmitted drug resistance, transmitted drug resistance mutations, antiretroviral mutations.

Median Arcuate Ligament Release

Department of Surgery, The George Washington University Medical Center, Washington, DC *Correspondence address: Fred Brody, MD, FACS, MBA, The George Washington University Medical Center, 2150 Pennsylvania Ave, NW, Suite 6B, Washington, DC 20037. E-mail: [email protected] Received May 2, 2014; accepted July 9, 2014. Disclosure Information: Nothing to disclose.

Patient With Acquired Immunodeficiency Syndrome Presenting With Pancytopenia and Disseminated Intravascular Coagulation

From the *Department of Medicine, Jefferson University Hospital, Philadelphia, PA and †Division of Infectious Diseases, George Washington University Medical Center, Washington, DC. Correspondence to: Lillian C. Man, MD, Department of Medicine, Jefferson University Hospital, 1025 Walnut St, Room 805, Philadelphia, PA 19107. E-mail: [email protected]. The authors have no funding or conflicts of interest to disclose. The authors have read and complied with the policy of the journal on ethical consent as stated in the Guide to Authors.

Targeting the Androgen Receptor in Metastatic Castration-Resistant Prostate Cancer

*Department of Medicine, Division of Hematology & Oncology, George Washington University Medical Center, 2150 Pennsylvania Avenue, NW, Washington, DC 20037, USA; Tel.: +1 202 741 2478; Fax: +1 202 741 2487; jaragonching@mfa.gwu.edu Androgen deprivation therapy (ADT) has been the cornerstone of treatment for metastatic prostate cancer. Since the emergence of castration resistance, attempts to define mechanisms of resistance has led the field into a search for non-androgen receptor (AR)-driven targets. This brought on an era of investigation that began with the use of chemotherapy for prostate cancer. While chemotherapy has been one of the earliest established treatments for men with symptomatic prostate cancer, based on the TAX327 and SWOG 9916 trials, it has only recently been established that the role of chemotherapy may not be limited to microtubule inhibition alone, but also inhibition of AR nuclear translocation [1,2]. The perception that the AR ceases to become a therapeutic target also heralded a generation of agents targeting alternative nonandrogen-dependent pathways that showed promising results in Phase II trials, but failed to provide survival benefit when tested in larger prospective Phase III trials. The landscape of treatment was truly revolutionized when further AR manipulation via the use of androgen biosynthesis inhibitors and novel antiandrogens came into fruition. The traditional concept of testicular androgen suppression was considered insufficient when increased intraprostatic and intratumoral androgens were considered contributors to further testosterone production, which brought about the concept of CYP17 enzyme inhibition that would later give rise to the development and approval of abiraterone acetate in 2011 and 2012 for both postchemotherapy metastatic castration-resistant prostate cancer (CRPC) patients [3], as well as prechemotherapy-naive patients [4], respectively. Similarly, peripheral androgen blockade with novel second-generation enzalutamide provided a unique profile as it was selected from a library of compounds for its AR inhibition of cells overexpressing the AR, which is far more potent than bicalutamide and was approved in 2012 for postchemotherapy metastatic CRPC patients. In addition, the more recently concluded PREVAIL trial has been reported [5] and enzalutamide has been shown to statistically improve overall survival in men who were chemotherapy-naive compared with patients receiving placebo (p < 0.0001). Enzalutamide provided a 30% reduction in risk of death compared with placebo (hazard ratio: 0.70; 95% CI: 0.59–0.83). Jeanny B Aragon-Ching* “The discovery of novel androgen biosynthesis inhibitors and second-generation antiandrogens are only the beginning of a host of agents that can circumvent the androgen receptor machinery.”

End-of-life electrical surges

We read the study by Borjigin et al. about postcardiac arrest electrical activity and the possible explanation for near death experiences (NDEs) with great interest (1). Our research group at The George Washington University Medical Center published an observation of end-of-life electrical surges (ELES) in 2009 (2). In that study, we proposed that ELES could be responsible for NDEs, and this new study largely confirms that hypothesis. However, it is important to recognize that nothing has been definitively proven. Nonetheless, the findings of multiple research groups confirm that organized electrical activity can emanate from the brain at the time of death (3, 4). Our ongoing research here at The George Washington University Medical Center suggest that about half of patients who succumb in the intensive care unit display an ELES, and the waveform is at a higher frequency than that observed in animals. The significance of ELES remains unknown and is the source of significant controversy.

Pulmonary Infiltrates and Eosinophilia in a 25-Year-Old Traveler

A 25-year-old Spanish male travelled to Senegal in September 2009, where he swam near the Dindefelo fresh-water falls. Five weeks later, he presented with fever, myalgia, and dry cough. His complete blood count showed a hemoglobin level of 157 g/L, platelet count of 123.000 platelets/mL, and a leukocyte count of 8.670 cells/mL, with 9% eosinophils. Malaria smear, blood cultures, and serologies for common viral and bacterial infections were negative. Titers of an indirect hemagglutination test for Schistosoma mansoni were 1:80. The patient was treated with a single dose of praziquantel (40 mg/kg) and prednisone (30 mg) for three days. After treatment, the dry cough increased and he developed moderate dyspnea, with increasing malaise and myalgia. A second blood sample revealed eosinophilia of 1.200 cells/mL. A chest Xray showed patchy infiltrates in both lungs (Figure 1), and a CT Editor: David Joseph Diemert (The George Washington University Medical Center, United States of America)

THU0016 Deep Sequencing Transcriptome Analysis of Traumeel Therapeutic Action in Wound Healing

Background: BackgroundRecent developments in genomics have laid the foundation for a growing understanding of Systems Biology, which explores the complex interrelationship between physiological processes and biological networks underlying human disease...

Role(s) of androgens in breast cancer biology and treatment

Hironobu Sasano has been involved in the translational research of various human neoplasms for nearly 20 years and has published more than 150 articles, including original, review and case reports, of breast cancer. In particular, his groups have established the details of intracrinology, or intracrine steroid production in the human sex steroid-dependent neoplasm. Sasano is also currently serving as an associate editor of the Journal of Steroid Biochemistry and Molecular Biology, Cancer Science and Pathology International. He graduated from Tohoku University School of Medicine (Japan) in 1982 and his postgraduate training included a clinical and research fellowship in New York Hospital, The Cornel Medical Center (NY, USA) as a Fulbright Scholar and pathology resident at The George Washington University Medical Center and Armed Forces Institute of Pathology (Washington, DC, USA).

“World Health”

From the George Washington University Medical Center, Washington, DC. Received July 8, 2011. Accepted for publication July 8, 2011. Address correspondence and reprint requests to Glenn W. Geelhoed, MD, FACS, George Washington University Medical Center, Washington, DC; E-mail: [email protected] The author was the recipient of the 2009 International Volunteer Award from the American College of Surgeons. The author reports no conflicts of interest.

The Challenge Of Deriving Health Policy Lessons From Abroad

The Challenge Of Deriving Health Policy Lessons From Abroad

CD4 Counts in Patients Diagnosed With HIV Through Routine HIV Screening in Two Urban Emergency Departments

CD4 Counts in Patients Diagnosed With HIV Through Routine HIV Screening in Two Urban Emergency Departments

Surgery in the Horn of Africa

To describe the 1-year experience of a unique postgraduate medical education program set in Eritrea, a recently war-torn country. The Partnership for Eritrea, a cooperative between The George Washington University Medical Center, Physicians for Peace, and the Eritrean Ministry of Health, formed a surgical residency program, launched January 2, 2008, in Asmara, Eritrea, to train native Eritrean surgeons. No prior residency program (to our knowledge) had existed in Eritrea. Eritrea, a country in the Horn of Africa. Five Eritrean physicians participated in the surgical residency. The number of operations performed, length of stay, antibiotic use, and intravenous fluid use. The number of operations increased and resource use decreased because of improved and standardized clinical management. The Partnership for Eritrea established a general surgical residency program that improved clinical care in a resource-poor country that previously had lacked postgraduate training. The program experience suggests a model that can be reproduced in other developing countries.

Abstract 889: Evaluating the case definition of inflammatory breast cancer

Abstract Background: Inflammatory breast cancer (IBC) is recognized as an aggressive form of breast cancer requiring neoadjuvant chemotherapy. Although IBC affects only a small percentage of breast cancer patients, the estimated 4,810 new cases for 2009 exceeds the number of women diagnosed with other cancers, such as acute lymphocytic leukemia and chronic myelocytic leukemia (as reported by the American Cancer Society). Research on IBC is hampered by the absence of an agreed upon case definition. While the American Joint Committee on Cancer (AJCC) relies on clinical features (more than half of the breast being involved with redness, warmth and edema), the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program focuses on pathologic confirmation. This study was undertaken to determine whether the outcome of IBC differs among patients who meet IBC criteria by AJCC, SEER, and private practitioners to try to improve the case definition for research purposes. Methods: This is a retrospective study of 121 patients in The George Washington University Medical Center IBC Registry who were classified as an IBC case by AJCC, SEER or private practitioners. We grouped these IBC cases into four epidemiological categories: (1) clinical-pathologic presentation of disease involving more than half of the breast, (2) clinical-only presentation of disease involving more than half of the breast, (3) clinical-pathologic presentation of disease involving less than half of the breast, and (4) clinical-only presentation of disease involving less than half of the breast. Note that Categories 1 and 2 meet AJCC criteria, while Categories 1 and 3 meet SEER criteria for IBC. We used an unadjusted Cox proportional hazards model to test the homogeneity of the progression-free survival (PFS) curves among these four epidemiological categories. Results: Of the 121 IBC cases, 33.1% (n=40) were classified as Category 1, 16.5% (n=20) were Category 2, 25.6% (n=31) were Category 3, and 24.8% (n=30) were Category 4. Using Category 4 as the reference group, the Cox proportional hazards model yielded insignificant hazard ratios (95% CI) of 1.69 (0.82, 3.51), 0.80 (0.28, 2.28), and 1.98 (0.95, 4.12) for Categories 1, 2, and 3, respectively. Applying the Score test, we found no significant difference in the PFS curves among the four epidemiological categories (χ2=5.87, p=0.12). Conclusions: The case definitions of IBC as proposed by the AJCC and SEER are inadequate. This study suggests that IBC as identified by private practitioners not meeting these criteria have the same poor prognosis as those meeting the case definitions of these national organizations. Preliminary laboratory studies support the conclusion that women with clinical evidence of IBC not involving half of the breast and with no documentation of involvement of the dermal lymphatics have the same disease as those meeting AJCC and SEER diagnostic criteria. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 889.

A randomized, controlled crossover study to discern the value of 360-degree versus traditional, faculty-only evaluation for performance improvement of anesthesiology residents

360-degree evaluation, or multi-rater feedback, is a means of providing evaluation from a variety of stakeholders. The Accreditation Council for Graduate Medical Education (ACGME) lists 360-degree feedback as a recommended method for evaluating residents. Our study determines if 360-degree evaluation, as compared to traditional evaluation, affords anesthesiology residents greater potential for performance improvement. After IRB exemption and resident consent to participate, sixteen anesthesiology residents of various training levels at The George Washington University Medical Center were randomly assigned to receive either 360-degree evaluation or traditional evaluation. Mid-way through the study, the groups were crossed over. Three faculty members blinded to which type of evaluation each resident received evaluated all residents pre-study, midway, and at the conclusion of the study according the six core competencies set forth by the ACGME. The 360-degree study included evaluations by faculty (traditional), self, medical students, nursing staff and patients. Performance improvement in all core competencies demonstrated a trend toward greater scoring for residents who received early exposure to 360-degree evaluation compared to later exposure. Paired t-Tests demonstrated significance for resident performance improvement with early 360-degree evaluation versus early traditional evaluation for the Interpersonal and Communication Skills core competency over the entire study. Systems-based Practice and Practice-Based Learning and Improvement suggested improvements, but failed to reach statistical significance (P = 0.09, 0.07 respectively). Does a 360-degree evaluation, as compared to traditional, faculty-only evaluation afford anesthesiology residents greater potential for performance improvement? Sixteen residents were exposed to a prospective, single-blinded, crossover design study to determine the answer. For 360-degree evaluations, residents were rated according to the ACGME core competencies after adjusting to Program Director review of evaluations from self, faculty, nursing staff, medical students and patients.

Pathologic analysis of capsular and incisional denudation and positive margin status in the development of a robot-assisted laparoscopic prostatectomy program.

The aim of this study is to explore the use of pathologically confirmed capsular incision and denudation as a measure of adequacy of extirpation following robot-assisted laparoscopic prostatectomy (RALP). All patients who underwent RALP at the George Washington University Medical Center during the first 2years of inception of the robotic prostatectomy program were included. All pathologic specimens were reviewed by a single pathologist. One hundred twenty-eight men who underwent RALP during the first 2years were identified. Sixty-four patients underwent RALP during the first year (group1) and all pathologic specimens were reviewed retrospectively. Sixty-four patients underwent RALP during the second year (group2) after revision of our operative technique and all pathologic specimens were reviewed prospectively. Of patients in group1, 18 (28%) had a positive surgical margin (PSM), and 18 (28%) with negative surgical margins were found to have capsular incision or denudation. In group1, 32 (50%) patients had evidence of iatrogenic capsular violation. Group2 consisted of 13 (20%) patients with a PSM and 9 (14%) margin-negative patients with capsular incision or denudation. Group2 had a total of 22 (34%) patients with evidence of iatrogenic capsular violation. Overall reduction in positive margins was not statistically significant between the groups. Improvement in capsular incision/denudation rate and overall capsular violation between the two groups was statistically significant (P<0.03 and <0.0055). Surgical margin status alone underestimates the overall quality of surgical resection after RALP because not all capsular violations result in a PSM. Surgeon-guided pathologic review in addition to intraoperative experience may improve oncologic success during the RALP learning curve.