Medical Specialties Commons^™

Sickle Cell Disease: Classification Of Clinical Complications And Approaches To Preventive And Therapeutic Management., Samir K. Ballas

Department of Medicine Faculty Papers

Sickle cell disease (SCD) is an inherited disorder of hemoglobin structure that has no established cure in adult patients. Cure has been achieved in selected children with sickle cell anemia (SCA) using allogeneic bone marrow transplantation or cord blood transplantation. SCD is essentially a triumvirate of (1) pain syndromes, (2) anemia and its sequelae and (3) organ failure, including infection. Pain, however, is the hallmark of SCD and dominates its clinical picture throughout the life of the patients. The prevalence of these complications varies with age from infancy through adult life. However, pain, infections and anemia requiring blood transfusion occur …

Blood Rheological Abnormalities In Sickle Cell Anemia., Philippe Connes, Céline Renoux, Marc Romana, Manouk Abkarian, Philippe Joly, Cyril Martin, Marie-Dominique Hardy-Dessources, Samir K. Ballas

Department of Medicine Faculty Papers

This review focuses on the contribution of abnormal blood rheology in the pathophysiology of sickle cell anemia (SCA). SCA is characterized by a reduction of red blood cell (RBC) deformability but this reduction is very heterogeneous among patients. Recent works have shown that patients with the lowest RBC deformability (measured by ektacytometry) have enhanced hemolysis and would be more prone to develop several complications such as priapism, leg ulcers and glomerulopathy. In contrast, patients with the highest deformability, and not under hydroxyurea therapy, seem to develop more frequently vaso-occlusive like events. Although less studied, RBC aggregation properties are very different …

Changes In The 2017 Pediatric Hypertension Clinical Guidelines., Bonita Falkner

Department of Medicine Faculty Papers

The clinical practice guidelines on diagnosis and management of high blood pressure in children and adolescents have been periodically modified and updated since the original publication in 1977.1 Since the last pediatric blood pressure guideline was published in 2004, known as the Fourth Report,2 the literature on child BP and hypertension has expanded considerably. There has been a recognized need to update the Fourth Report for several years. However, the National Heart, Lung, and Blood Institute (NHLBI) who sponsored previous pediatric BP guidelines announced that NHLBI would no longer sponsor development of new clinical guidelines.3 Subsequently, in 2014 the American …

Plekhg5-Regulated Autophagy Of Synaptic Vesicles Reveals A Pathogenic Mechanism In Motoneuron Disease., Patrick Lüningschrör, Beyenech Binotti, Benjamin Dombert, Peter Heimann, Angel Perez-Lara, Carsten Slotta, Nadine Thau-Habermann, Cora R. Von Collenberg, Franziska Karl, Markus Damme, Arie Horowitz, Isabelle Maystadt, Annette Füchtbauer, Ernst-Martin Füchtbauer, Sibylle Jablonka, Robert Blum, Nurcan Üçeyler, Susanne Petri, Barbara Kaltschmidt, Reinhard Jahn, Christian Kaltschmidt, Michael Sendtner

Department of Medicine Faculty Papers

Autophagy-mediated degradation of synaptic components maintains synaptic homeostasis but also constitutes a mechanism of neurodegeneration. It is unclear how autophagy of synaptic vesicles and components of presynaptic active zones is regulated. Here, we show that Pleckstrin homology containing family member 5 (Plekhg5) modulates autophagy of synaptic vesicles in axon terminals of motoneurons via its function as a guanine exchange factor for Rab26, a small GTPase that specifically directs synaptic vesicles to preautophagosomal structures. Plekhg5 gene inactivation in mice results in a late-onset motoneuron disease, characterized by degeneration of axon terminals. Plekhg5-depleted cultured motoneurons show defective axon growth and impaired autophagy …

Oral Apolipoprotein A-I Mimetic D-4f Lowers Hdl-Inflammatory Index In High-Risk Patients: A First-In-Human Multiple-Dose, Randomized Controlled Trial., Richard L. Dunbar, Rajesh Movva, Leanne T. Bloedon, Danielle Duffy, Robert B. Norris, Mohamad Navab, Alan M. Fogelman, Daniel J. Rader

Department of Medicine Faculty Papers

A single dose of the apolipoprotein (apo)A-I mimetic peptide D-4F rendered high-density lipoprotein (HDL) less inflammatory, motivating the first multiple-dose study. We aimed to assess safety/tolerability, pharmacokinetics, and pharmacodynamics of daily, orally administered D-4F. High-risk coronary heart disease (CHD) subjects added double-blinded placebo or D-4F to statin for 13 days, randomly assigned 1:3 to ascending cohorts of 100, 300, then 500 mg (n = 62; 46 men/16 women). D-4F was safe and well-tolerated. Mean ± SD plasma D-4F area under the curve (AUC, 0-8h) was 6.9 ± 5.7 ng/mL*h (100 mg), 22.7 ± 19.6 ng/mL*h (300 mg), and 104.0 ± …

Dabigatran Reversal With Idarucizumab., Charles V. Pollack, Paul A Reilly, Jeffrey I Weitz

Department of Medicine Faculty Papers

No abstract provided.

Intravesical Rad-Ifnα/Syn3 For Patients With High-Grade, Bacillus Calmette-Guerin-Refractory Or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase Ii Randomized Study., Neal D Shore, Stephen A Boorjian, Daniel J Canter, Kenneth Ogan, Lawrence I Karsh, Tracy M Downs, Leonard G Gomella, Ashish M Kamat, Yair Lotan, Robert S Svatek, Trinity J Bivalacqua, Robert L Grubb, Tracey L Krupski, Seth P Lerner, Michael E Woods, Brant A Inman, Matthew I Milowsky, Alan Boyd, F Peter Treasure, Gillian Gregory, David G Sawutz, Seppo Yla-Herttuala, Nigel R Parker, Colin P N Dinney

Department of Medicine Faculty Papers

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 10(11) viral particles (vp)/mL or 3 × 10(11) vp/mL). Patients who responded at months 3, …

Effect Of Oral Semaglutide Compared With Placebo And Subcutaneous Semaglutide On Glycemic Control In Patients With Type 2 Diabetes: A Randomized Clinical Trial., Melanie Davies, Thomas R. Pieber, Marie-Louise Hartoft-Nielsen, Oluf K.H. Hansen, Serge Jabbour, Julio Rosenstock

Department of Medicine Faculty Papers

Importance: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection.

Objectives: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes.

Design, Setting, and Patients: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and …

Clinical Characteristics, Management, And Outcomes Of Suspected Poststroke Acute Coronary Syndrome., Sylvia Marie Biso, Marvin Lu, Toni Anne De Venecia, Supakanya Wongrakpanich, Mary Rodriguez-Ziccardi, Sujani Yadlapati, Marina Kishlyansky, Harish Seetha Rammohan, Vincent M. Figueredo

Department of Medicine Faculty Papers

Background: Acute coronary syndrome (ACS) can complicate acute ischemic stroke, causing significant morbidity and mortality. To date, literatures that describe poststroke acute coronary syndrome and its morbidity and mortality burden are lacking.

Methods: This is a single center, retrospective study where clinical characteristics, cardiac evaluation, and management of patients with suspected poststroke ACS were compared and analyzed for their association with inpatient mortality and 1-year all-cause mortality.

Results: Of the 82 patients, 32% had chest pain and 88% had ischemic ECG changes; mean peak troponin level was 18, and mean ejection fraction was 40%. The medical management group had older …

Patient-Reported Outcome Assessment Of Inflammatory Arthritis Patient Experience With Intravenously Administered Biologic Therapy, Norman B. Gaylis, Joanne Sagliani, Shawn Black, Kezhen L. Tang, Raphael J. Dehoratius, Wesley A. Kafka, Dennis Parenti

Department of Medicine Faculty Papers

Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA). Methods: This was a single-center, non-interventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using …

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As A Graft Source For T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide., Asad Bashey, Mei-Jie Zhang, Shannon R Mccurdy, Andrew St Martin, Trevor Argall, Claudio Anasetti, Stefan O Ciurea, Omotayo Fasan, Sameh Gaballa, Md, Mehdi Hamadani, Pashna Munshi, Monzr M Al Malki, Ryotaro Nakamura, Paul V O'Donnell, Miguel-Angel Perales, Kavita Raj, Rizwan Romee, Scott Rowley, Vanderson Rocha, Rachel B Salit, Melhem Solh, Robert J Soiffer, Ephraim Joseph Fuchs, Mary Eapen

Department of Medicine Faculty Papers

Purpose T-cell-replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil …

Efficacy And Safety Of Spironolactone In Acute Heart Failure: The Athena-Hf Randomized Clinical Trial., Javed Butler, Kevin J. Anstrom, G. Michael Felker, Michael M. Givertz, Andreas P Kalogeropoulos, Marvin A. Konstam, Douglas L. Mann, Kenneth B. Margulies, Steven E Mcnulty, Robert J. Mentz, Margaret M. Redfield, W.H. Wilson Tang, David J. Whellan, Monica Shah, Patrice Desvigne-Nickens, Adrian F. Hernandez, Eugene Braunwald

Department of Medicine Faculty Papers

Importance: Persistent congestion is associated with worse outcomes in acute heart failure (AHF). Mineralocorticoid receptor antagonists administered at high doses may relieve congestion, overcome diuretic resistance, and mitigate the effects of adverse neurohormonal activation in AHF.

Objective: To assess the effect of high-dose spironolactone and usual care on N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels compared with usual care alone.

Design, Setting, and Participants: This double-blind and placebo (or low-dose)-controlled randomized clinical trial was conducted in 22 US acute care hospitals among patients with AHF who were previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone and had …

A Review Of Neurogenic Stunned Myocardium., Sylvia Biso, Supakanya Wongrakpanich, Akanksha Agrawal, Sujani Yadlapati, Marina Kishlyansky, Vincent M. Figueredo

Department of Medicine Faculty Papers

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective …

Evaluating The Relationship Between Participation In Student-Run Free Clinics And Changes In Empathy In Medical Students., Anita Modi, Michele Fascelli, Zachary Daitch, Mohammadreza Hojat Professor

Department of Medicine Faculty Papers

PURPOSE: We explored differences in changes in medical student empathy in the third year of medical school between volunteers at JeffHOPE, a multisite medical student-run free clinic of Sidney Kimmel Medical College (SKMC), and nonvolunteers.

METHOD: Volunteerism and leadership experience at JeffHOPE were documented for medical students in the Class of 2015 (n = 272) across their medical educations. Students completed the Jefferson Scale of Empathy at the beginning of medical school and at the end of the third year. Students who reported participation in other Jefferson-affiliated clinics (n = 44) were excluded from this study. Complete data were available …

Disseminated Nocardia Cyriacigeorgia Causing Pancreatitis In A Haploidentical Stem Cell Transplant Recipient., Jason Chen, Md, Jonathan Pan, Md, Joanne Filicko-O'Hara, Margaret Kasner, Phyllis Flomenberg

Department of Medicine Faculty Papers

We report the first published case of acute pancreatitis secondary to disseminated nocardiosis in a hematopoietic stem cell transplant (HSCT) recipient on chronic immunosuppression for graft-versus-host disease (GVHD). Nocardiosis in the HSCT population is relatively rare, and has not yet been described in haploidentical HSCT recipients. Our patient is a 28-year-old male with a history of haploidentical HSCT and GVHD of the skin and lung who was admitted to the hospital with acute pancreatitis. The workup for the etiology of his pancreatitis was initially unrevealing. He subsequently developed worsening sepsis and respiratory failure despite broad spectrum antimicrobials. After multiple bronchoscopies …

Effect Of Oral Iron Repletion On Exercise Capacity In Patients With Heart Failure With Reduced Ejection Fraction And Iron Deficiency: The Ironout Hf Randomized Clinical Trial., Gregory D Lewis, Rajeev Malhotra, Adrian F Hernandez, Steven E Mcnulty, Andrew Smith, G Michael Felker, W H Wilson Tang, Shane J Larue, Margaret M Redfield, Marc J Semigran, Michael M Givertz, Peter Van Buren, David J Whellan, Kevin J Anstrom, Monica R Shah, Patrice Desvigne-Nickens, Javed Butler, Eugene Braunwald

Department of Medicine Faculty Papers

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown.

Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency.

Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (

Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. …

The Nephrotoxicity Of Vancomycin., Edward J. Filippone, Walter K. Kraft, John L. Farber

Department of Medicine Faculty Papers

No abstract provided.

The Value Of Cancer Immunotherapy Summit At The 2016 Society For Immunotherapy Of Cancer 31st Anniversary Annual Meeting, Howard L. Kaufman, Michael B. Atkins, Adam Dicker Md, Phd, Heather S. Jim, Louis P. Garrison, Roy S. Herbst, William T. Mcgivney, Steven Silverstein, Jon M. Wigginton, Peter P. Yu

Department of Medicine Faculty Papers

As healthcare costs continue to rise, there has been great interest in understanding and defining the value of current therapeutic strategies for the treatment of cancer. Cancer immunotherapy has emerged as a clinically beneficial alternative to conventional therapies for a variety of malignancies. Characterized by broad clinical activity, durable response rates, distinct side effects, and unique response kinetics, immune-based agents are vastly different compared with traditional cytotoxic or targeted therapies. To date, however, value assessments in oncology have not focused on the unique aspects of cancer immunotherapy, which has resulted in a lack of understanding of the true value of …

Discordance In Investigator-Reported And Adjudicated Sudden Death In Tiospir., Robert A. Wise, Peter R. Kowey, George Austen, Achim Mueller, Norbert Metzdorf, Andy Fowler, Lorcan P Mcgarvey

Department of Medicine Faculty Papers

Accurate and consistent determination of cause of death is challenging in chronic obstructive pulmonary disease (COPD) patients. TIOSPIR (N=17 135) compared the safety and efficacy of tiotropium Respimat 5/2.5 µg with HandiHaler 18 µg in COPD patients. All-cause mortality was a primary end-point. A mortality adjudication committee (MAC) assessed all deaths. We aimed to investigate causes of discordance in investigator-reported and MAC-adjudicated causes of death and their impact on results, especially cardiac and sudden death. The MAC provided independent, blinded assessment of investigator-reported deaths (n=1302) and assigned underlying cause of death. Discordance between causes of death was assessed descriptively (shift …

Influence Of Sex/Gender And Race On Responses To Raltegravir Combined With Tenofovir-Emtricitabine In Treatment-Naive Human Immunodeficiency Virus-1 Infected Patients: Pooled Analyses Of The Startmrk And Qdmrk Studies., Kathleen E. Squires, Linda-Gail Bekker, Christine Katlama, Yazdan Yazdanpanah, Yan Zhou, Anthony J Rodgers, Mark J Dinubile, Peter A Sklar, Randi Y Leavitt, Hedy Teppler

Department of Medicine Faculty Papers

BACKGROUND: Antiretroviral therapy in human immunodeficiency virus (HIV)-infected women and blacks merits particular scrutiny because these groups have been underrepresented in clinical trials.

METHODS: To document the effects of raltegravir across sex and racial lines, we conducted a pooled subgroup analysis of the efficacy and safety of raltegravir 400 mg BID plus tenofovir-emtricitabine by sex (women vs men) and self-identified race (black vs non-black) using phase 3 studies in treatment-naive patients.

RESULTS: Study participants included 42 black women, 102 non-black women, 48 black men, and 477 non-black men. Clade B infections were less common in women (43.8%) than men (84.6%) …

The Humoral Theory Of Transplantation: Epitope Analysis And The Pathogenicity Of Hla Antibodies., Edward J Filippone, John Farber

Department of Medicine Faculty Papers

Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA …

Stimulation Of Transforming Growth Factor-Β1-Induced Endothelial-To-Mesenchymal Transition And Tissue Fibrosis By Endothelin-1 (Et-1): A Novel Profibrotic Effect Of Et-1., Peter J. Wermuth, Zhaodong Li, Fabian A. Mendoza, Sergio A. Jimenez

Department of Medicine Faculty Papers

TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. …

Postoperative Intussusception In 10-Year-Old Presenting As Decreased Intestinal Motility, Arielle Spellun, Loren Berman, Stephen Murphy

Department of Medicine Faculty Papers

No abstract provided.

Parental And Staff Perspectives Of Nicu Research Procedures., Christina Freibott, Ursula Guillen, Amy Mackley, Robert Locke

Department of Medicine Faculty Papers

BACKGROUND: There are limited data on parental perception of infant participation in minimal risk and minor increase above minimal risk research focusing on the NICU population. The study objective was to assess parental and NICU staff perceptions concerning minimal risk and minor increase above minimal risk in the NICU setting.

METHODS: Parents of infants and NICU staff were presented with a combination of 4 infant scenarios and 5 hypothetical research procedures. These assessed participants' willingness to allow their infant to participate in research and their attitude towards obligation to assist future children. Linear and hierarchal linear models analyzed the association …

Utilization Of Hiv-1 Envelope V3 To Identify X4- And R5-Specific Tat And Ltr Sequence Signatures., Gregory C Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R Nonnemacher, Jeffrey M Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Gregory Schwartz, Uri Hershberg, Fred C Krebs, Brian Wigdahl

Department of Medicine Faculty Papers

BACKGROUND: HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures …

Childhood Psychosocial Determinants Of Cardiovascular Health, Samuel S. Gidding, Erica D. Sood

Department of Medicine Faculty Papers

Understanding risk and protective factors that impact cardiovascular health is of utmost importance. There is ample evidence that cardiovascular health begins in childhood, tracks over time, and is subject to adverse social influences. This paper reviews key studies examining the relations of psychosocial factors in childhood to cardiovascular health in adulthood. The existing literature provides evidence for both individual and cumulative effects of childhood psychosocial factors on adult cardiovascular health across the population, although the specific mechanisms underlying these relationships are not yet fully understood. This paper also includes a discussion of evidence-based strategies for prevention and treatment of childhood …

Hospitalized Patients At High Risk For Obstructive Sleep Apnea Have More Rapid Response System Events And Intervention Is Associated With Reduced Events., Sunil Sharma, Md, Anindita Chowdhury, Lili Tang, Leslee Willes, Brian Glynn, Stuart F Quan

Department of Medicine Faculty Papers

BACKGROUND: Rapid response system (RRS) is a safety tool designed for early detection and intervention of a deteriorating patient on the general floor in the hospital. Obstructive sleep apnea (OSA) has been associated with significant cardiovascular complications. We hypothesized that patients with high-risk of OSA have higher rate of RRS events and intervention with positive airway pressure therapy in these patients can mitigate the RRS events.

METHODS: As part of a clinical pathway, during a 15 month period, patients with BMI ≥ 30 kg/m2 in select medical services were screened with a validated sleep questionnaire. Patients were characterized as high …

Cell-Free Circulating Mitochondrial Dna Content And Risk Of Hepatocellular Carcinoma In Patients With Chronic Hbv Infection., Ling Li, Hie-Won Hann, Shaogui Wan, Richard Hann, Chun Wang, Yinzhi Lai, Xishan Ye, Alison Evans, Ronald E. Myers, Phd, Dsw, Zhong Ye, Bingshan Li, Jinliang Xing, Hushan Yang

Department of Medicine Faculty Papers

Recent studies have demonstrated a potential link between circulating cell-free mitochondrial DNA (mtDNA) content and cancers. However, there is no study evaluating the association between circulating mtDNA as a non-invasive marker of hepatocellular carcinoma (HCC) risk. We conducted a nested case-control study to determine circulating mtDNA content in serum samples from 116 HBV-related HCC cases and 232 frequency-matched cancer-free HBV controls, and evaluate the retrospective association between mtDNA content and HCC risk using logistic regression and their temporal relationship using a mixed effects model. HCC cases had significantly lower circulating mtDNA content than controls (1.06 versus 2.47, P = 1.7 …

Evaluation Of Polymorphic Locus Sequence Typing For Candida Glabrata Epidemiology., Santosh Katiyar, Eric Shiffrin, Md, Celeste Shelton, Kelley Healey, John-Paul Vermitsky, Tom Edlind

Department of Medicine Faculty Papers

The opportunistic yeastCandida glabratais increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care-associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole-genome sequencing are impractical for routine use. A commercial sequence-based typing service forC. glabratathat targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of …

A 22-Year-Old Man With Pleural Tuberculosis Associated Hydropneumothorax: Case Report And Literature Review., Lauren A Sharan, Thea Price, Md, Boyd Hehn, David Manoff, Md, Scott W. Cowan, Md

Department of Medicine Faculty Papers

A 22-year-old Asian male presented with fever, non-productive cough, right-sided pleuritic chest pain and was found to have a large right hydropneumothorax. A chest tube was placed. Pleural fluid analysis revealed a lymphocytic predominant exudate and he was subsequently started on four-drug daily anti-tuberculosis therapy (isoniazid, ethambutol, rifampin, pyrazinamide). Pleural biopsy revealed acid-fast bacilli. Given his persistent pleural effusion, he was given four doses of intrapleural tissue plasminogen activator (tPA) and dornase alpha (DNase) via his chest tube over a period of 6 days resulting in clinical and radiologic improvement. Pleural biopsy and pleural fluid culture specimens later revealed Mycobacterium …