Medicine and Health Sciences Commons^™

Eculizumab For Gemcitabine-Induced Hemolytic Uremic Syndrome: A Novel Therapy For An Emerging Condition, Raphael Karkowsky, Md, Kinjal Parikh, Md

The Medicine Forum

Introduction

Atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA), is a disease characterized by hemolytic anemia, thrombocytopenia, and renal impairment. Gemcitabine, a commonly used chemotherapy, is emerging as a cause of aHUS. Although rare, the morbidity and mortality can be significant. Few studies have explored the use of eculizumab, an anti-C5 monoclonal antibody as a potential therapy for gemcitabine-induced aHUS.

Case Presentation

A 45 year old Caucasian male with metastatic urothelial carcinoma was started on weekly gemcitabine (1000 mg/m2 per dose) to treat recurrent disease. During his seventh cycle, he was hospitalized for hypertension, acute kidney injury, and anemia. …

Chronic Idiopathic Intestinal Pseudo-Obstruction: A Working Diagnosis, Ankush Kalra, Md, Anthony Dimarino, Md

The Medicine Forum

Introduction

Chronic intestinal pseudo-obstruction (CIP) is a rare and disabling motility syndrome, yet one that demands an extensive review of digestive motility and peristaltic pathophysiology. Primarily a disorder of the small intestine, CIP was first described by Dudley and colleagues in 1958; it is defined by severe signs and symptoms of intestinal obstruction (abdominal pain and distention, nausea, vomiting, and constipation), in addition to radiographic evidence of dilated bowel in the absence of a true, mechanical obstruction. Symptoms are often slowly progressive and diagnosis requires the presence of symptoms for at least six months.1 A 2013 national survey in Japan …

Acute Respiratory Distress Syndrome From Tick-Borne Human Granulocytic Anaplasmosis Infection, Vedang Patel, Md

The Medicine Forum

Introduction

Tick-borne infections were first formally recognized over a century ago, but it was only in 1990 that the first case of human granulocytic anaplasmosis (HGA), a tick-borne infection caused by Anaplasma phagocytophilum, was identified.1,2 Like other tick-borne infections, HGA presents as a nonspecific febrile illness. The most common clinical features are fever, headache, myalgia and malaise.2 This case report presents a rare but serious complication of HGA – acute respiratory distress syndrome (ARDS).

CASE PRESENTATION

A 49-year-old female with no past medical history presented to her local emergency department with complaints of fevers, headache, neck pain, myalgia, and malaise. …

A Special Case Of A Broken Heart, Shuwei Wang, Md

The Medicine Forum

Introduction

Takotsubo cardiomyopathy (TC), also known as stress cardiomyopathy, and broken heart syndrome is characterized by transient left ventricular (LV) apical akinesis with symptoms mimicking acute coronary syndrome. The first case was described by Sato et al. in Japan.1 The Japanese word “takotsubo” translates to “octopus pot” describing the shape of the left ventricle during systole. TC can be triggered by a “broken heart” including death of a loved one, constant anxiety, surgery, or critical illness etc. Prevalence is around 2% to 3% with over 90% in postmenopausal women aged between 58 and 75. Its pathogenesis remains unclear. Some postulated …

A Case Of Ipilimumab Induced Hypophysitis, Eric Shiffrin, Md, Melinda Ukrainski, Md

The Medicine Forum

Introduction

Ipilimumab (Yervoy®) is a human monoclonal antibody that has been shown to significantly improve survival in cases of metastatic melanoma.1 Ipilimumab blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4), a protein receptor on the surface of T-cells, resulting in their activation, proliferation and an anti-tumor response.2,3,4 Commonly reported immune-related side effects of ipilimumab are enterocolitis, dermatitis, and hepatitis.5,6,7 However, different endocrinopathies, including autoimmune hypopituitarism, have become emerging clinical entities in patients taking ipilimumab. We present a case of ipilimumab induced hypophysitis in a 62-yearold male presenting with fatigue and hypotension.

Case Presentation

A 62-year-old male with a history of melanoma metastatic …

Table Of Contents

The Medicine Forum

Table of Contents for The Medicine Forum, Volume 16, 2014-2015.

From The Editors, Anusha G. Govind, Md, Loheetha Ragupathi, Md, Michael A. Valentino, Md, Phd

The Medicine Forum

We are excited to present you with the 16th annual edition of The Medicine Forum. This work is a culmination of months of effort on the part of medical students, residents, fellows and faculty to share clinical pearls from the last year of their experiences.

Amongst the greatest strengths of medical professionals and patients alike is the ability to tell stories. Stories, and how they are told form the basis of medical care. The way in which a particular patient's story unfolds has a lasting impact on physicians, trainees, other medical staff, and perhaps most importantly, on future patients. Stories …

From The Desk Of The Residency Program Director, Gretchen Diemer, Md, Facp

The Medicine Forum

It is bittersweet to write my final Message from the Program Director for the Forum. This publication is one example of the passion, talent, creativity and scientific inquisitiveness of our Jefferson residents. As a completely resident run journal, what follows in this journal helps prove to me that the future of medicine is in good hands.

In my time as program director, we have seen many changes in the healthcare landscape, both nationally and locally at Jefferson. We have launched the Milestone evaluations in the Next Accreditation System for the ACGME and are embarking on major curricular reform at the …

Trna-Derived Short Non-Coding Rna As Interacting Partners Of Argonaute Proteins., Megumi Shigematsu, Yohei Kirino, Phd

Computational Medicine Center Faculty Papers

The advent of next-generation sequencing technologies has not only accelerated findings on various novel non-coding RNA (ncRNA) species but also led to the revision of the biological significance and versatility of fundamental RNA species with canonical function, such as transfer RNAs (tRNAs). Although tRNAs are best known as adapter components of translational machinery, recent studies suggest that tRNAs are not always end products but can further serve as a source for short ncRNAs. In many organisms, various tRNA-derived ncRNA species are produced from mature tRNAs or their precursor transcripts as functional molecules involved in various biological processes beyond translation. In …

Jefferson Digital Commons Quarterly Report, April-June 2015, Daniel G. Kipnis, Msi

Jefferson Digital Commons News

The latest JDC quarterly report has been posted. Topics include:

10,000th Asset

Pennsylvania Research Commons

Faculty Day presentations

Variety of new assets in the JDC

Inside Out literary journal

What people are saying about the JDC

Clinical Utility Of Lactate Dehydrogenase In Determining The Severity Of Hemolysis In Sickle Cell Anemia., Samir K. Ballas

Cardeza Foundation for Hematologic Research

No abstract provided.

Jefferson Digital Commons Quarterly Report: April-June 2015, Daniel G. Kipnis, Msi, Kelsey Duinkerken, Msi

Jefferson Digital Commons Reports

This quarterly report includes:

• 10,000th Asset
• Pennsylvania Research Commons
• Faculty Day presentations
• Variety of new assets in the JDC
• Inside Out literary journal
• What people are saying about the JDC

Paracrine Effect Of Nrg1 And Hgf Drives Resistance To Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Mizue Terai, Ken Kageyama, Shinji Ozaki, Peter Mccue, Takami Sato, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Uveal melanoma patients with metastatic disease usually die within one year, emphasizing an urgent need to develop new treatment strategies for this cancer. MEK inhibitors improve survival in cutaneous melanoma patients but show only modest efficacy in metastatic uveal melanoma patients. In this study, we screened for growth factors that elicited resistance in newly characterized metastatic uveal melanoma cell lines to clinical-grade MEK inhibitors, trametinib and selumetinib. We show that neuregulin 1 (NRG1) and hepatocyte growth factor (HGF) provide resistance to MEK inhibition. Mechanistically, trametinib enhances the responsiveness to NRG1 and sustained HGF-mediated activation of AKT. Individually targeting ERBB3 and …

Ketamine For The Treatment Of Depression In Patients Receiving Hospice Care: A Retrospective Medical Record Review Of Thirty-One Cases., Alana Iglewicz, Katherine Morrison, Richard A. Nelesen, Tingting Zhan, Boris Iglewicz, Nathan Fairman, Jeremy M. Hirst, Scott A. Irwin

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Depression is prevalent in patients receiving hospice care. Standard antidepressant medications do not work rapidly enough in this setting. Evidence suggests that ketamine rapidly treats treatment refractory depression in the general population. Ketamine׳s role for treating depression in the hospice population warrants further study.

METHODS: A retrospective medical record review of 31 inpatients receiving hospice care who received ketamine for depression on a clinical basis was conducted. The primary outcome measure was the Clinical Global Impression Scale, which was used retrospectively to rate subjects׳ therapeutic improvement, global improvement, and side effects from ketamine over 21 days. Additionally, time to …

Surgeon Radiation Exposure In Hip Arthroscopy: A Prospective Analysis, John P. Salvo, Jake Zarah

Rothman Institute Papers

Objectives: Hip arthroscopy is an established field within orthopaedic surgery. The majority of the procedures involve repairs of the acetabular labrum and arthroscopic treatment of femoroacetabular impingement (FAI). The procedures are being performed with increasing frequency annually. Fluoroscopic guidance is recommended during these procedures, and radiation exposure to the surgeon, staff, and patient remains a valid concern. The purpose of this study is to measure radiation exposure to the surgeon during hip arthroscopy and determine if this exposure remains below recommended annual occupational radiation exposure thresholds recommended by the International Committee on Radiological Protection (IRCP). Methods: Prospectively, radiation exposure was …

Medial Opening Wedge High Tibial Osteotomy: A Retrospective Review Of Patient Outcomes Over 10 Years, Fotios P. Tjoumakaris, Nicholas J. Lombardi, Bradford Tucker, Matthew D. Pepe

Rothman Institute Papers

Objectives: High tibial osteotomy (HTO) has become a well-established treatment for unicompartmental osteoarthritis of the knee. Over the last 30 years, various techniques have been introduced to advance this procedure. The purpose of this study is to review the outcomes of patients who received medial opening wedge HTO over the last ten years (2002-2012) using a modern, low profile, medially based fixation device. In addition, we sought to determine if obese patients had a less favorable outcome than their non-obese counterparts. Methods: Ninety-three patients were identified from a surgical database as having undergone a HTO for medial compartment osteoarthritis of …

Current Management Of Heart Failure: When To Refer To Heart Failure Specialist And When Hospice Is The Best Option., Behnam Bozorgnia, Paul J. Mather

Division of Cardiology Faculty Papers

Heart failure is a common syndrome caused by different abnormalities of the cardiovascular system that result in impairment of the ventricles in filling or ejecting blood. It is one of the most common causes of hospitalization in the United States, with a very high cost to the health care system. This article focuses on the causes of left ventricle dysfunction and the presentation and management of heart failure, both acute and chronic.

Development And Implementation Of A Clinical Pathway Approach To Simulation-Based Training For Foregut Surgery., Kiyoyuki W. Miyasaka, Joseph Buchholz, Denise Lamarra, Giorgos C. Karakousis, Rajesh Aggarwal

Student Papers, Posters & Projects

INTRODUCTION: Contemporary demands on resident education call for integration of simulation. We designed and implemented a simulation-based curriculum for Post Graduate Year 1 surgery residents to teach technical and nontechnical skills within a clinical pathway approach for a foregut surgery patient, from outpatient visit through surgery and postoperative follow-up.

METHODS: The 3-day curriculum for groups of 6 residents comprises a combination of standardized patient encounters, didactic sessions, and hands-on training. The curriculum is underpinned by a summative simulation "pathway" repeated on days 1 and 3. The "pathway" is a series of simulated preoperative, intraoperative, and postoperative encounters in following up …

Strategies For Searching The Internet For Orthopedic Surgeons: Tips And Tricks, Fatih Küçükdurmaz, Md, Terry Whipple, Md, Murat Bozkurt, Md, Daniel G. Kipnis, Msi

Academic Commons and Scott Memorial Library Staff Papers and Presentations

Internet provides access to large amounts of information quickly, provides a flexible learning platform, and is easily accessible from anywhere, especially with new technologies. Web-based search engines and bibliographic databases, have already become part of a doctor's everyday life. However, even well-published researchers often fail to appreciate the background knowledge required to conduct a good literature search on the internet. Using the right techniques can improve the ability to search for relevant information This chapter briefly outlines the internet as an information resources such as Google, Google Scholar, PubMed, Cochrane for orthopedic surgeons. Also the subsequent sections of the chapter …

Long-Term Oncological Outcomes Of A Phase Ii Trial Of Neoadjuvant Chemohormonal Therapy Followed By Radical Prostatectomy For Patients With Clinically Localised, High-Risk Prostate Cancer., Jonathan L. Silberstein, Stephen A. Poon, Daniel D. Sjoberg, Alexandra C. Maschino, Andrew J. Vickers, Aaron Bernie, Badrinath R. Konety, William Kevin Kelly, James A. Eastham

Department of Urology Faculty Papers

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer.

PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only.

RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. …

Kinase Independent Oncogenic Cyclin D1., Mathew C Casimiro, Andrew Arnold, Richard Pestell

Kimmel Cancer Center Faculty Papers

No abstract provided.

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

Pain Management Strategies In Hand Surgery., Constantinos Ketonis, Md, Phd, Asif M Ilyas, Frederic Liss

Department of Orthopaedic Surgery Faculty Papers

Modern anesthetic agents have allowed for the rapid expansion of ambulatory surgery, particularly in hand surgery. The choice between general anesthesia, peripheral regional blocks, regional intravenous anesthesia (Bier block), local block with sedation, and the recently popularized wide-awake hand surgery depends on several variables, including the type and duration of the procedure and patient characteristics, coexisting conditions, location, and expected length of the procedure. This article discusses the various perioperative and postoperative analgesic options to optimize the hand surgical patients' experience.

Role Of Phenol-Soluble Modulins In Formation Of Staphylococcus Aureus Biofilms In Synovial Fluid., Sana S Dastgheyb, Amer E Villaruz, Katherine Y Le, Vee Y Tan, Anthony C Duong, Som S Chatterjee, Gordon Y C Cheung, Hwang-Soo Joo, Noreen J Hickok, Michael Otto

Department of Orthopaedic Surgery Faculty Papers

Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such …

Understanding Infection Prevention And Control In Nursing Homes: A Qualitative Study., Patricia W. Stone, Carolyn T.A. Herzig, Monika Pogorzelska-Maziarz, Eileen Carter, Ragnhildur I. Bjarnadottir, Patricia K. Semeraro, Catherine C. Cohen, Jasmine Travers, Steven Schweon

College of Nursing Faculty Papers & Presentations

Infections have been identified as a priority issue in nursing homes (NHs). We conducted a qualitative study purposively sampling 10 NHs across the country where 6-8 employees were recruited (N = 73). Semi-structured, open-ended guides were used to conduct in-depth interviews. Data were audiotaped, transcribed and a content analysis was performed. Five themes emerged: 'Residents' Needs', 'Roles and Training' 'Using Infection Data,' 'External Resources' and 'Focus on Hand Hygiene.' Infection prevention was a priority in the NHs visited. While all sites had hand hygiene programs, other recommended areas were not a focus and many sites were not aware of available …

Functional Neuroimaging Distinguishes Posttraumatic Stress Disorder From Traumatic Brain Injury In Focused And Large Community Datasets., Daniel G Amen, Cyrus A Raji, Kristen Willeumier, Derek Taylor, Robert Tarzwell, Andrew B. Newberg, Md, Theodore A Henderson

Department of Radiology Faculty Papers

BACKGROUND: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are highly heterogeneous and often present with overlapping symptomology, providing challenges in reliable classification and treatment. Single photon emission computed tomography (SPECT) may be advantageous in the diagnostic separation of these disorders when comorbid or clinically indistinct.

METHODS: Subjects were selected from a multisite database, where rest and on-task SPECT scans were obtained on a large group of neuropsychiatric patients. Two groups were analyzed: Group 1 with TBI (n=104), PTSD (n=104) or both (n=73) closely matched for demographics and comorbidity, compared to each other and healthy controls (N=116); Group 2 …

Nrg Oncology/Rtog 0921: A Phase 2 Study Of Postoperative Intensity-Modulated Radiotherapy With Concurrent Cisplatin And Bevacizumab Followed By Carboplatin And Paclitaxel For Patients With Endometrial Cancer., Akila N. Viswanathan, Jennifer Moughan, Brigitte E. Miller, Ying Xiao, Anuja Jhingran, Lorraine Portelance, Walter R. Bosch, Ursula A. Matulonis, Neil S. Horowitz, Robert S S. Mannel, Luis Souhami, Beth A. Erickson, Kathryn A. Winter, William Small, David K. Gaffney

Department of Radiation Oncology Faculty Papers

BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.

METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 …

Treatment For Inclusion Body Myositis, Michael R. Rose, Katherine Jones, Kevin Leong, Maggie C. Walter, James Miller, Marinos Dalakas, Ruth Brassington, Robert Griggs

Department of Neurology Faculty Papers

Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects …

Selective Impact Of Cdk4/6 Suppression On Patient-Derived Models Of Pancreatic Cancer., Agnieszka K Witkiewicz, Nicholas A Borja, Jorge Franco, Jonathan Brody, Md, Charles Yeo, John Mansour, Michael A Choti, Peter Mccue, Erik S Knudsen

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDA) harbors an exceedingly poor prognosis, and is generally considered a therapy-recalcitrant disease due to poor response to conventional chemotherapy coupled with non-actionable genetic drivers (e.g. KRAS mutations). However, PDA frequently loses p16ink4a, thereby leading to deregulation of CDK4/6. Surprisingly, in established cell models and xenografts, CDK4/6 inhibition has a modest effect on proliferation and resistance develops rapidly. To determine if such weak response was an intrinsic feature of PDA, we developed primary tumor explants that maintain the tumor environment and recapitulate feuture of primary PDA. The CDK4/6 inhibitor PD-0332991 was highly efficient at suppressing proliferation in …

Novel Cross Talk Between Igf-Ir And Ddr1 Regulates Igf-Ir Trafficking, Signaling And Biological Responses., Roberta Malaguarnera, Maria Luisa Nicolosi, Antonella Sacco, Alaide Morcavallo, Veronica Vella, Concetta Voci, Michela Spatuzza, Shi-Qiong Xu, Renato V Iozzo, Riccardo Vigneri, Andrea Morrione, Antonino Belfiore

Kimmel Cancer Center Faculty Papers

The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression.Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. …