Medical Specialties Commons^™

Rare Case Of Diffuse Spinal Arachnoiditis Following A Complicated Vertebral Artery Dissection, Elias Atallah, Md, Sophia Dang, Sage Rahm, Nohra Chalouhi, Md, Stavropoula Tjoumakaris Md, Robert H. Rosenwasswer Md, Pascal Jabbour Md

Department of Neurosurgery Posters

Spinal arachnoiditis (SA) is an extremely rare and delayed complication of intracranial subarachnoid hemorrhage (SAH). SA is an inflammatory process leading to chronic fibrosis of the spinal cord. Possible pathophysiology is a two-staged disease of initial inflammatory reaction secondary to SAH, followed by a “free interval phase” prior to delayed adhesive phase (i.e. SA). The clinical course can be complicated and is the cause of major morbidity.

Trapped As A Group, Escape As A Team: Applying Gamification To Incorporate Team-Building Skills Through An 'Escape Room' Experience, Xiao Chi Zhang, Hyunjoo Lee, Carlos Rodriguez, Joshua Rudner, Teresa M Chan, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

Teamwork, a skill critical for quality patient care, is recognized as a core competency by the Accreditation Council for Graduate Medical Education (ACGME). To date, there is no consensus on how to effectively teach these skills in a forum that engages learners, immerses members in life-like activities, and builds both trust and rapport. Recreational 'Escape Rooms' have gained popularity in creating a life-like environment that rewards players for working together, solving puzzles, and completing successions of mind-bending tasks in order to effectively 'escape the room' in the time allotted. In this regard, escape rooms share many parallels with the multitasking …

Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 1, 2018

Gibbon Surgical Review

Table of Contents

• A First Year's Perspective on JeffMD, Somnath Das, MS1
• Spotlight on TJUH's Quality and Safety Group, Samantha L. Savitch, MS1
• Medical Student Involvement in Quality Improvement Research, Tyler M. Bauer, MS3
• Global Surgery: A Shift in the Global Health Paradigm, Myles S. Dworkin, MS3
• Thomas Jefferson University Design Vault, Victor B. Hsue, MS2
• Physician Spotlight: Ernest (Gary) L. Rosato, MD, FACS, Carrie E. Andrews, MS3
• The SCALPELS Program, Emily Papai, MS1

First Report Of Nrg Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial Of Samarium-153 Followed By Salvage Prostatic Fossa Irradiation In High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy., Richard K. Valicenti, Stephanie L. Pugh, Edouard J. Trabulsi, Oliver Sartor, Eric C. Ko, Michael R. Girvigian, Seth A. Rosenthal, Mark E. Shaves, Jean Hoffman-Censits, John Schallenkamp, Howard M. Sandler

Department of Urology Faculty Papers

PURPOSE: To investigate the utility of ¹⁵³Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases.

PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) > 1.0 ng/mL; (2) PSA > 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA > 0.2 ng/mL if N1. Patients received ¹⁵³Sm (2.0 mCi/kg intravenously …

Efficacy And Safety Of Eslicarbazepine Acetate Monotherapy In Patients Converting From Carbamazepine., Ladislav Pazdera, Michael R. Sperling, Jay H. Harvey, Maria C. Sam, Laura A. Strom, David Blum, Todd Grinnell, Hailong Cheng

Department of Neurology Faculty Papers

OBJECTIVE: To evaluate the influence of prior use of carbamazepine (CBZ) and other antiepileptic drugs (AEDs) with a putatively similar mechanism of action (inhibition of voltage-gated sodium channels; VGSCs) on seizure outcomes and tolerability when converting to eslicarbazepine acetate (ESL), using data pooled from 2 controlled conversion-to-ESL monotherapy trials (studies: 093-045, 093-046).

METHODS: Adults with treatment-resistant focal (partial-onset) seizures were randomized 2:1 to ESL 1600 or 1200 mg once daily. The primary efficacy endpoint was study exit (meeting predefined exit criteria related to worsening seizure control) versus an historical control group. Other endpoints included change in seizure frequency, responder rate, …

Effects Of Adjunctive Eslicarbazepine Acetate On Serum Lipids In Patients With Partial-Onset Seizures: Impact Of Concomitant Statins And Enzyme-Inducing Antiepileptic Drugs., Scott Mintzer, Robert T. Wechsler, Joanne B. Rogin, Barry E. Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares Da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell

Department of Neurology Faculty Papers

PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.

SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.

KEY FINDINGS: In total, 426 and 1021 placebo- and ESL-treated …

Double-Row Repair Technique For Bursal-Sided Partial-Thickness Rotator Cuff Tears, Hytham Salem, Aaron Carter, Md, Fotios Tjoumakaris, Kevin Freedman

Department of Orthopaedic Surgery Faculty Papers

Rotator cuff pathology is a common cause of shoulder pain in the athletic and general population. Partial-thickness rotator cuff tears (PTRCT) are commonly encountered and can be bursal-sided, articular-sided, or intratendinous. Various techniques exist for the repair of bursal-sided PTRCTs. The 2 main distinctions when addressing these lesions include tear completion versus preservation of the intact fibers, and single- versus double-row suture anchor fixation. We present our method for addressing bursal-sided PTRCTs using an in situ repair technique with double-row suture anchors. © 2017 Arthroscopy Association of North America

Ebola Virus Localization In The Macaque Reproductive Tract During Acute Ebola Virus Disease., Donna L. Perry, Louis M. Huzella, John G. Bernbaum, Michael R. Holbrook, Peter B. Jahrling, Katie R. Hagen, Matthias J. Schnell, Reed F. Johnson

Department of Microbiology and Immunology Faculty Papers

Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, …

Temporal Trends In Incidence, Sepsis-Related Mortality, And Hospital-Based Acute Care After Sepsis., Nathaniel Meyer, Michael O. Harhay, Dylan S. Small, Hallie C. Prescott, Kathryn H. Bowles, David F. Gaieski, Mark E Mikkelsen

Department of Emergency Medicine Faculty Papers

OBJECTIVES: A growing number of patients survive sepsis hospitalizations each year and are at high risk for readmission. However, little is known about temporal trends in hospital-based acute care (emergency department treat-and-release visits and hospital readmission) after sepsis. Our primary objective was to measure temporal trends in sepsis survivorship and hospital-based acute care use in sepsis survivors. In addition, because readmissions after pneumonia are subject to penalty under the national readmission reduction program, we examined whether readmission rates declined after sepsis hospitalizations related to pneumonia.

DESIGN AND SETTING: Retrospective, observational cohort study conducted within an academic healthcare system from 2010 …

Delayed Hepatic Rupture Post Ultrasound-Guided Percutaneous Liver Biopsy: A Case Report., Jia-Yan Huang, Qiang Lu, Ji-Bin Liu

Department of Radiology Faculty Papers

RATIONALE: Hemorrhage, one of complications after liver biopsy, is often identified immediately after the procedure while delayed liver rupture is relatively rare.

PATIENT CONCERNS: A 45-year-old woman was diagnosed with undetermined liver cirrhosis and abnormal liver function. To determine the etiology and severity of liver cirrhosis, ultrasound-guided liver biopsy was arranged. The patients did not complain any pain during the procedure. Ultrasound examination on postoperative day1 (POD 1) and MRI on POD 3 showed no evidence of hematoma and ascites. On POD 7, however, the patient was taken to the hospital with a sudden onset of pain in the right …

Migraine And Vascular Disease Biomarkers: A Population-Based Case-Control Study., Gretchen E. Tietjen, Jagdish Khubchandani, Nabeel Herial, Inge H. Palm-Meinders, Hille Koppen, Gisela M. Terwindt, Mark A. Van Buchem, Lenore J. Launer, Michel D. Ferrari, Mark C. Kruit

Department of Neurosurgery Faculty Papers

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared …

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading To Cerebral Aneurysm Pathogenesis., Robert M. Starke, John W. Thompson, Muhammad S. Ali, Crissey L. Pascale, Alejandra Martinez Lege, Dale Ding, Nohra Chalouhi, David M. Hasan, Pascal Jabbour, Gary K Owens, Michal Toborek, Joshua M. Hare, Aaron S. Dumont

Department of Neurosurgery Faculty Papers

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture.

APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes …

Out Of The Straitjacket., Michael Weinstein

Department of Surgery Faculty Papers

No abstract provided.

Phosphaturic Mesenchymal Tumor Of The Nasal Cavity: Clinicopathologic Correlation Is Essential For Diagnosis, Aidan Kerr, Ryan Rimmer, Marc Rosen, James J. Evans, Madalina Tuluc, Stacey K. Mardekian

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm in which the tumor cells produce fibroblast growth factor 23 (FGF23), leading to oncogenic osteomalacia and thus a distinct clinical presentation. However, the pathologic findings of PMT are often non-specific and variable, especially in tumors occurring in the head and neck. We present a case of a 66-year-old female who presented with osteomalacia-related symptoms and was found to have a nasal cavity mass. Histopathologic examination was suggestive of PMT but certain characteristic features were lacking, requiring confirmation of the diagnosis by chromogenic in situ hybridization (CISH) assay for FGF23 mRNA. The patient's …

Tracheal Injury Detected Immediately After Median Sternotomy By Inexperienced Surgeons: Two Case Reports., Jun Takeshita, Kei Nishiyama, Atsushi Fukumoto, Suguru Ohira, Satoru Beppu, Nozomu Sasahashi, Nobuaki Shime

Department of Surgery Faculty Papers

BACKGROUND: Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery.

CASE PRESENTATION: Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our …

Submillimeter Retinoblastoma Monitoring Following Transpupillary Thermotherapy Using Hand-Held Optical Coherence Tomography, Mark Mcgarrey, Thamolwan Surakiatchanukul, Carol L. Shields

Wills Eye Hospital Papers

Background: Precise, submillimeter visualization of retinal microstructures is useful for treatment monitoring of retinoblastoma. Herein, we report the use of hand-held optical coherence tomography (HH-OCT) to document a nearly-invisible retinoblastoma and monitor tumor response to transpupillary thermotherapy (TTT). Case presentation: A 3-week-old boy was diagnosed with unilateral familial retinoblastoma in the left eye, classified as group B, and treated with intravenous chemoreduction. At 13-month follow-up, the tumor in the left eye was regressed, and evaluation of the right eye revealed a microscopic, nearly invisible tumor measuring 372 μm in thickness and 1.51 mm in basal dimension. The tumor was confirmed …

Targeting Cdk6 And Bcl2 Exploits The "Myb Addiction" Of Ph+ Acute Lymphoblastic Leukemia, Marco De Dominici, Patrizia Porazzi, Angela Rachele Soliera, Samanta A. Mariani, Sankar Addya, Paolo Fortina, Luke F. Peterson, Orietta Spinelli, Alessandro Rambaldi, Giovanni Martinelli, Anna Ferrari, Ilaria Iacobucci, Bruno Calabretta

Department of Cancer Biology Faculty Papers

Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph^þ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Ph^þ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Ph^þ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced …

Management Of Elbow Dislocations In The National Football League., Edward S. Chang, Meghan Bishop, Christopher C. Dodson, Peter F. Deluca, Michael G. Ciccotti, Steven B. Cohen, Matthew L. Ramsey

Department of Orthopaedic Surgery Faculty Papers

Background: Although much literature exists regarding the treatment and management of elbow dislocations in the general population, little information is available regarding management in the athletic population. Furthermore, no literature is available regarding the postinjury treatment and timing of return to play in the contact or professional athlete.

Purpose: To review the clinical course of elbow dislocations in professional football players and determine the timing of return to full participation.

Study Design: Case series; Level of evidence, 4.

Methods: All National Football League (NFL) athletes with elbow dislocations from 2000 through 2011 who returned to play during the season were …

Natural Progress Of D-Dimer Following Total Joint Arthroplasty: A Baseline For The Diagnosis Of The Early Postoperative Infection., Yong Seuk Lee, Young-Kyun Lee, Seung Bum Han, Chang Hyun Nam, Javad Parvizi Md, Kyung-Hoi Koo

Rothman Institute Papers

BACKGROUND: Early detection followed by prompt intervention is essential for the treatment of periprosthetic joint infection (PJI). D-dimer, a fibrin degradation product, characteristically changes rapidly during early postoperative period and has a short half-life. The aim of this prospective study was to measure postoperative change of D-dimer level after joint arthroplasty in conjunction with ESR and CRP.

METHODS: ESR, CRP, and D-dimer levels were measured on the day before surgery, postoperative days 1, 2, 3, and 5 and weeks 2 and 6 in 65 patients who underwent elective primary total hip arthroplasty (38 hips in 38 patients) or total knee …

Representing Diversity In The Dish: Using Patient-Derived In Vitro Models To Recreate The Heterogeneity Of Neurological Disease, Layla T. Ghaffari, Alexander Starr, Andrew T. Nelson, Rita Sattler

Department of Neuroscience Faculty Papers

Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic …

Closed-Loop Stimulation Of Temporal Cortex Rescues Functional Networks And Improves Memory., Youssef Ezzyat, Paul A. Wanda, Deborah F. Levy, Allison Kadel, Ada Aka, Isaac Pedisich, Michael R. Sperling, Ashwini Sharan, Bradley C. Lega, Alexis Burks, Robert E. Gross, Cory S. Inman, Barbara C. Jobst, Mark A. Gorenstein, Kathryn A. Davis, Gregory A. Worrell, Michal T. Kucewicz, Joel M. Stein, Richard Gorniak, Sandhitsu R. Das, Daniel S. Rizzuto, Michael J. Kahana

Department of Neurology Faculty Papers

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target …

Electrical Stimulation Modulates High Γ Activity And Human Memory Performance., Michal T. Kucewicz, Brent M. Berry, Vaclav Kremen, Laura R. Miller, Fatemeh Khadjevand, Youssef Ezzyat, Joel M. Stein, Paul Wanda, Michael R. Sperling, Richard Gorniak, Md, Kathryn A. Davis, Barbara C. Jobst, Robert E. Gross, Bradley Lega, S Matt Stead, Daniel S. Rizzuto, Michael J. Kahana, Gregory A, Worrell

Department of Neurology Faculty Papers

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We …

Consensus Guidelines For Newborn Screening, Diagnosis And Treatment Of Infantile Krabbe Disease., Jennifer M. Kwon, Dietrich Matern, Joanne Kurtzberg, Lawrence Wrabetz, Michael H. Gelb, David A. Wenger, Can Ficicioglu, Amy T. Waldman, Barbara K. Burton, Patrick V. Hopkins, Joseph J. Orsini

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurodegenerative genetic disorder caused by deficiency of galactocerebrosidase. Patients with the infantile form of Krabbe disease can be treated at a presymptomatic stage with human stem cell transplantation which improves survival and clinical outcomes. However, without a family history, most cases of infantile Krabbe disease present after onset of symptoms and are ineligible for transplantation. In 2006, New York began screening newborns for Krabbe disease to identify presymptomatic cases. To ensure that those identified with infantile disease received timely treatment, New York public health and medical systems took steps to accurately diagnose and rapidly …

Reassessing The Duration Of The Second Stage Of Labor In Relation To Maternal And Neonatal Morbidity., Katherine L. Grantz, Rajeshwari Sundaram, Ling Ma, Stefanie Hinkle, Vincenzo Berghella, Matthew K. Hoffman, Uma M. Reddy

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To assess the morbidity associated with continuing the second-stage duration of labor, weighing the probability of spontaneous vaginal birth without morbidity compared with birth with serious maternal or neonatal complications.

METHODS: In a retrospective cohort, we analyzed singleton, vertex births at 36 weeks of gestation or greater without prior cesarean delivery (n=43,810 nulliparous and 59,605 multiparous women). We calculated rates of spontaneous vaginal birth and composite serious maternal or neonatal complications. Results were stratified by parity (nulliparous or multiparous) and epidural status (yes or no). Competing risks models were created for 1) spontaneous vaginal birth with no morbidity, 2) …

Not Your Typical Simulation Workshop: Using Legos To Train Medical Students On The Practice Of Effective Communication., Dimitrios Papanagnou, Hyunjoo Lee, Carlos Rodriguez, Xiao Chi C Zhang, Joshua Rudner

Department of Emergency Medicine Faculty Papers

As students in the health professions transition from the classroom into the clinical environment, they will be expected to effectively communicate with their team members and their patients. Effective communication skills are essential to their ability to effectively contribute to their clinical team and the patient care they deliver. The authors propose an interactive workshop that can support students' deliberate practice of communication skills. The authors designed a simulation workshop that affords students the opportunity to practice their communication and peer-to-peer coaching skills. Using LEGOs, a one-hour workshop was conducted with medical students. Students were divided into groups of two. …

Emergency Medicine Resident Perceptions About The Need For Increased Training In Communicating Diagnostic Uncertainty., Kristin L Rising, Dimitrios Papanagnou, Danielle Mccarthy, Alexzandra Gentsch, Rhea Powell

Department of Emergency Medicine Faculty Papers

Introduction Diagnostic uncertainty is common in healthcare encounters. Effective communication is important to help patients and providers navigate diagnostic uncertainty, especially at transitions of care. This study sought to assess the experience and training of emergency medicine (EM) residents with communication of diagnostic uncertainty. Methods This was a survey study of a national sample of EM residents. The survey questions elicited quantitative and qualitative responses about experiences with and educational preparation for communication with patients in the setting of diagnostic uncertainty. Results A sample of 263 emergency medicine residents who had trained at over 87 medical schools and 37 residency …

Systematic In Vivo Evaluation Of The Time-Dependent Inflammatory Response To Steel And Teflon Insulin Infusion Catheters., Jasmin R. Hauzenberger, Julia Münzker, Petra Kotzbeck, Martin Asslaber, Vladimir Bubalo, Jeffrey I. Joseph, Thomas R. Pieber

Department of Anesthesiology Faculty Papers

Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak link of insulin pump therapy. Wear-time considerably varies between patients and the choice of catheter material is based on personal preferences rather than scientific facts. Therefore, we systematically assessed and quantified the inflammatory tissue response to steel versus Teflon CSII catheters over a maximum wear-time of 7 days in swine. Tissue surrounding catheters was analysed using histopathology and quantitative real-time PCR. The area of inflammation increased significantly over time independent of material which was confirmed by an increase in CD68 expression and an increase in mononuclear and neutrophil cell infiltrate …

Fasoracetam In Adolescents With Adhd And Glutamatergic Gene Network Variants Disrupting Mglur Neurotransmitter Signaling., Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R. Li, Walter K. Kraft, Hakon Hakonarson

Department of Pediatrics Faculty Papers

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 …

Deciphering A Case Of Pulmonary Hypertension In A Young Female: Partial Anomalous Pulmonary Venous Drainage The Culprit, Hiten R. Patel, Suchit Bhutani, Fayez Shamoon, Hartaj Virk

Abington Jefferson Health Papers

Partial anomalous pulmonary venous drainage (PAPVD) is a rare congenital cardiac defect and is associated with sinus venosus atrial septal defect. While most cases are asymptomatic, a patient can present with pulmonary hypertension (PHTN) and it can be difficult to diagnose. Here, we discuss the case of a young female with PHTN who was found to have two right-sided PAPVD. Through this case, authors try to emphasize the importance of meticulous and thorough investigation when evaluating PHTN, which allows for correct diagnosis and a timely intervention before PHTN becomes irreversible.

Erk-Mediated Phosphorylation Regulates Sox10 Sumoylation And Targets Expression In Mutant Braf Melanoma., Shujun Han, Yibo Ren, Wangxiao He, Huadong Liu, Zhe Zhi, Xinliang Zhu, Tielin Yang, Yu Rong, Bohan Ma, Timothy J. Purwin, Zhenlin Ouyang, Caixia Li, Xun Wang, Xueqiang Wang, Huizi Yang, Yan Zheng, Andrew E. Aplin, Jiankang Liu, Yongping Shao

Department of Cancer Biology Faculty Papers

In human mutant BRAF melanoma cells, the stemness transcription factor FOXD3 is rapidly induced by inhibition of ERK1/2 signaling and mediates adaptive resistance to RAF inhibitors. However, the mechanism underlying ERK signaling control of FOXD3 expression remains unknown. Here we show that SOX10 is both necessary and sufficient for RAF inhibitor-induced expression of FOXD3 in mutant BRAF melanoma cells. SOX10 activates the transcription of FOXD3 by binding to a regulatory element in FOXD3 promoter. Phosphorylation of SOX10 by ERK inhibits its transcription activity toward multiple target genes by interfering with the sumoylation of SOX10 at K55, which is essential for …