Medical Specialties Commons^™

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 …

Acute And Late Toxicities Of Concurrent Chemoradiotherapy For Locally-Advanced Non-Small Cell Lung Cancer., Vivek Verma, Charles B 2nd Simone, Maria Werner-Wasik

Department of Radiation Oncology Faculty Papers

For patients with unresectable locally-advanced non-small cell lung cancer (LA-NSCLC), concurrent chemoradiotherapy improves overall survival as compared to sequential chemotherapy and radiation therapy, but is associated with higher rates of toxicities. Acute, clinically significant esophagitis or pneumonitis can occur in one in five patients. The risks of esophagitis and pneumonitis can impact the decision to deliver concurrent therapy and limit the total dose of radiation therapy that is delivered. Hematologic toxicities and emesis are common toxicities from systemic therapies for LA-NSCLC and can result in delaying chemotherapy dosing or chemotherapy dose reductions. Late treatment morbidities, including pulmonary fibrosis and cardiac …

Serum D-Dimer Test Is Promising For The Diagnosis Of Periprosthetic Joint Infection And Timing Of Reimplantation., Alisina Shahi, Michael M. Kheir, Majd Tarabichi, Hamid R.S. Hosseinzadeh, Timothy L. Tan, Javad Parvizi

Rothman Institute Papers

BACKGROUND: Despite the availability of a battery of tests, the diagnosis of periprosthetic joint infection (PJI) continues to be challenging. Serum D-dimer assessment is a widely available test that detects fibrinolytic activities that occur during infection. We hypothesized that patients with PJI may have a high level of circulating D-dimer and that the presence of a high level of serum D-dimer may be a sign of persistent infection in patients awaiting reimplantation.

METHODS: This prospective study was initiated to enroll patients undergoing primary and revision arthroplasty. Our cohort consisted of 245 patients undergoing primary arthroplasty (n = 23), revision for …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On The Use Of Methylprednisolone Sodium Succinate, Michael G. Fehlings, Jefferson R. Wilson, Lindsay A. Tetreault, Bizhan Aarabi, Paul A. Anderson, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory W. Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark R. Kotter, Shekar N. Kurpad, Brian Kwon, Ralph J. Marino, Allan R. Martin, Eric M. Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Andrea C. Skelly, Anoushka Singh, Eve Tsai, Alexander R. Vaccaro, Albert Yee, James S. Harrop

Department of Rehabilitation Medicine Faculty Papers

Introduction: The objective of this guideline is to outline the appropriate use of methylprednisolone sodium succinate (MPSS) in patients with acute spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MPSS in acute SCI. A multidisciplinary Guideline Development Group used this information, in combination with their clinical expertise, to develop recommendations for the use of MPSS. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: The main conclusions …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On The Role Of Baseline Magnetic Resonance Imaging In Clinical Decision Making And Outcome Prediction, Michael G. Fehlings, Allan R. Martin, Lindsay A. Tetreault, Bizhan Aarabi, Paul Anderson, Paul M. Arnold, Darrel Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark Kotter, Shekar Kurpad, Brian K. Kwon, Ralph J. Marino, Eric Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Anoushka Singh, Andrea C. Skelly, Eve C. Tsai, Alexander R. Vaccaro, Jefferson R. Wilson, Albert Yee, James Harrop

Department of Rehabilitation Medicine Faculty Papers

Introduction: The objective of this guideline is to outline the role of magnetic resonance imaging (MRI) in clinical decision making and outcome prediction in patients with traumatic spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions related to the use of MRI in patients with traumatic SCI. This review focused on longitudinal studies that controlled for baseline neurologic status. A multidisciplinary Guideline Development Group (GDG) used this information, their clinical expertise, and patient input to develop recommendations on the use of MRI for SCI patients. Based on GRADE (Grading of Recommendation, Assessment, …

A Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury: Recommendations On The Type And Timing Of Anticoagulant Thromboprophylaxis, Michael G. Fehlings, Lindsay A. Tetreault, Bizhan Aarabi, Paul Anderson, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark Kotter, Shekar Kurpad, Brian K. Kwon, Ralph J. Marino, Allan R. Martin, Eric Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Anoushka Singh, Andrea C. Skelly, Eve C. Tsai, Alexander R. Vaccaro, Jefferson R. Wilson, Albert Yee, James Harrop

Department of Rehabilitation Medicine Faculty Papers

Introduction: The objective of this study is to develop evidence-based guidelines that recommend effective, safe and cost-effective thromboprophylaxis strategies in patients with spinal cord injury (SCI). Methods: A systematic review of the literature was conducted to address key questions relating to thromboprophylaxis in SCI. Based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation), a strong recommendation is worded as “we recommend,” whereas a weaker recommendation is indicated by “we suggest.” Results: Based on conclusions from the systematic review and expert panel opinion, the following recommendations were developed: (1) “We suggest that anticoagulant thromboprophylaxis be offered routinely to reduce the …

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 Clinical Practice Guideline For The Management Of Patients With Acute Spinal Cord Injury And Central Cord Syndrome: Recommendations On The Timing (≤24 Hours Versus >24 Hours) Of Decompressive Surgery, Michael G. Fehlings, Lindsay A. Tetreault, Jefferson R. Wilson, Bizhan Aarabi, Paul Anderson, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Furlan, Gregory Hawryluk, Langston T. Holly, Susan Howley, Tara Jeji, Sukhvinder Kalsi-Ryan, Mark Kotter, Shekar Kurpad, Ralph J. Marino, Allan R. Martin, Eric Massicotte, Geno J. Merli, James W. Middleton, Hiroaki Nakashima, Narihito Nagoshi, Katherine Palmieri, Anoushka Singh, Andrea C. Skelly, Eve C. Tsai, Alexander R. Vaccaro, Albert Yee, James S. Harrop

Department of Rehabilitation Medicine Faculty Papers

Objective: To develop recommendations on the timing of surgical decompression in patients with traumatic spinal cord injury (SCI) and central cord syndrome. Methods: A systematic review of the literature was conducted to address key relevant questions. A multidisciplinary guideline development group used this information, along with their clinical expertise, to develop recommendations for the timing of surgical decompression in patients with SCI and central cord syndrome. Based on GRADE, a strong recommendation is worded as “we recommend,” whereas a weak recommendation is presented as “we suggest.” Results: Conclusions from the systematic review included (1) isolated studies reported statistically significant and …

Crossed Aphasia In A Patient With Anaplastic Astrocytoma Of The Non-Dominant Hemisphere, Stephanie Prater, Neil Anand, Lawrence Wei, Neil Horner

Student Papers, Posters & Projects

Aphasia describes a spectrum of speech impairments due to damage in the language centers of the brain. Insult to the inferior frontal gyrus of the dominant cerebral hemisphere results in Broca's aphasia - the inability to produce fluent speech. The left cerebral hemisphere has historically been considered the dominant side, a characteristic long presumed to be related to a person's "handedness". However, recent studies utilizing fMRI have shown that right hemispheric dominance occurs more frequently than previously proposed and despite a person's handedness. Here we present a case of a right-handed patient with Broca's aphasia caused by a right-sided brain …

A Multi-Institutional Consensus On How To Perform Endoscopic Ultrasound-Guided Peri-Pancreatic Fluid Collection Drainage And Endoscopic Necrosectomy., Jintao Guo, Adrian Saftoiu, Peter Vilmann, Pietro Fusaroli, Marc Giovannini, Girish Mishra, Surinder S. Rana, Sammy Ho, Jan-Werner Poley, Tiing Leong Ang, Evangelos Kalaitzakis, Ali A. Siddiqui, Jose G. De La Mora-Levy, Sundeep Lakhtakia, Manoop S. Bhutani, Malay Sharma, Shuntaro Mukai, Pramod Kumar Garg, Linda S. Lee, Juan J. Vila, Everson Artifon, Douglas G. Adler, Siyu Sun

Division of Gastroenterology and Hepatology Faculty Papers

There is a lack of consensus on how endoscopic ultrasound (EUS)-guided pseudocyst drainage and endoscopic necrosectomy should be performed. This survey was carried out amongst members of the EUS Journal Editorial Board to describe their practices in performing this procedure. This was a worldwide multi-institutional survey amongst members of the EUS Journal Editorial Board in May 2017. The responses to a 22-question survey with respect to the practice of EUS-guided pseudocyst drainage and endoscopic necrosectomy were obtained. Twenty-two endoscopists responded to the questionnaire as follows: 72.7% (16/22) were of the opinion that lumen-apposing metal stents (LAMS) should be the standard …

Comparison Of The Diagnostic Accuracy Of Three Current Guidelines For The Evaluation Of Asymptomatic Pancreatic Cystic Neoplasms., Ming-Ming Xu, Shi Yin, Ali A. Siddiqui, Ronald R. Salem, Beth Schrope, Amrita Sethi, John M. Poneros, Frank G. Gress, Jeanine M Genkinger, Catherine Do, Christian A. Brooks, John A. Chabot, Michael D. Kluger, Thomas E. Kowalski, David E. Loren, Harry Aslanian, James J. Farrell, Tamas A. Gonda

Division of Gastroenterology and Hepatology Faculty Papers

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine …

A Clinical Practice Guideline For The Management Of Patients With Degenerative Cervical Myelopathy: Recommendations For Patients With Mild, Moderate, And Severe Disease And Nonmyelopathic Patients With Evidence Of Cord Compression, Michael G. Fehlings, Lindsay A. Tetreault, K. Daniel Riew, James W. Middleton, Bizhan Aarabi, Paul M. Arnold, Darrel S. Brodke, Anthony S. Burns, Simon Carette, Robert Chen, Kazuhiro Chiba, Joseph R. Dettori, Julio C. Ferlan, James S. Harrop, Langston T. Holly, Sukhvinder Kalsi-Ryan, Mark Kotter, Brian K. Kwon, Allan R. Martin, James Milligan, Hiroaki Nakashima, Narihito Nagoshi, John Rhee, Anoushka Singh, Andrea C. Skelly, Sumeet Sodhi, Jefferson R. Wilson, Albert Yee, Jeffrey C. Wang

Department of Neurosurgery Faculty Papers

Study Design: Guideline development. Objectives: The objective of this study is to develop guidelines that outline how to best manage (1) patients with mild, moderate, and severe myelopathy and (2) nonmyelopathic patients with evidence of cord compression with or without clinical symptoms of radiculopathy. Methods: Five systematic reviews of the literature were conducted to synthesize evidence on disease natural history; risk factors of disease progression; the efficacy, effectiveness, and safety of nonoperative and surgical management; the impact of preoperative duration of symptoms and myelopathy severity on treatment outcomes; and the frequency, timing, and predictors of symptom development. A multidisciplinary guideline …

Efficacy, Safety, And Timing Of Anticoagulant Thromboprophylaxis For The Prevention Of Venous Thromboembolism In Patients With Acute Spinal Cord Injury: A Systematic Review, Paul M. Arnold, James S. Harrop, Geno J. Merli, Lindsay G. Tetreault, Brain K. Kwon, Steve Casha, Katherine Palmieri, Jefferson R. Wilson, Michael G. Fehlings, Haley K. Holmer, Daniel C. Norvell

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objectives: The objective of this study was to answer 5 key questions: What is the comparative effectiveness and safety of (1a) anticoagulant thromboprophylaxis compared to no prophylaxis, placebo, or another anticoagulant strategy for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) after acute spinal cord injury (SCI)? (1b) Mechanical prophylaxis strategies alone or in combination with other strategies for preventing DVT and PE after acute SCI? (1c) Prophylactic inferior vena cava filter insertion alone or in combination with other strategies for preventing DVT and PE after acute SCI? (2) What is the optimal timing to …

Impact Of Baseline Magnetic Resonance Imaging On Neurologic, Functional, And Safety Outcomes In Patients With Acute Traumatic Spinal Cord Injury, Shekar N. Kurpad, Allan R. Martin, Lindsay A. Tetreault, Dena J. Fischer, Andrea C. Skelly, David J. Mikulis, Adam E. Flanders, Bizhan Aarabi, Thomas E. Mroz, Eve Tsai, Michael G. Fehlings

Department of Radiology Faculty Papers

Study Design: Systematic review. Objective: To perform a systematic review to evaluate the utility of magnetic resonance imaging (MRI) in patients with acute spinal cord injury (SCI). Methods: An electronic search of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar was conducted for literature published through May 12, 2015, to answer key questions associated with the use of MRI in patients with acute SCI. Results: The literature search yielded 796 potentially relevant citations, 8 of which were included in this review. One study used MRI in a protocol to decide on early surgical decompression. The MRI-protocol group showed improved …

Efficacy And Safety Of Methylprednisolone Sodium Succinate In Acute Spinal Cord Injury: A Systematic Review, Michael G. Fehlings, Jefferson R. Wilson, James S. Harrop, Brian Kwon, Lindsay A. Tetreault, Paul M. Arnold, Jeffrey M. Singh, Gregory W.J. Hawryluk, Joseph R. Dettori

Department of Neurosurgery Faculty Papers

Study Design: Systematic review and meta-analysis. Objective: The objective of this study was to conduct a systematic review to assess the comparative effectiveness and safety of high-dose methylprednisolone sodium succinate (MPSS) versus no pharmacological treatment in patients with traumatic spinal cord injury (SCI). Methods: A systematic search was performed in PubMed and the Cochrane Collaboration Library for literature published between January 1956 and June 17, 2015. Included studies were critically appraised, and Grades of Recommendation Assessment, Development and Evaluation methods were used to determine the overall quality of evidence for primary outcomes. Previous systematic reviews on this topic were collated …

A Clinical Practice Guideline For The Management Of Acute Spinal Cord Injury: Introduction, Rationale, And Scope, Michael G. Fehlings, Lindsay A. Tetreault, Jefferson R. Wilson, Brian K. Kwon, Anthony S. Burns, Allan R. Martin, Gregory Hawryluk, James S. Harrop

Department of Neurosurgery Faculty Papers

Acute spinal cord injury (SCI) is a traumatic event that results in disturbances to normal sensory, motor, or autonomic function and ultimately affects a patient’s physical, psychological, and social well-being. The management of patients with SCI has drastically evolved over the past century as a result of increasing knowledge on injury mechanisms, disease pathophysiology, and the role of surgery. There still, however, remain controversial areas surrounding available management strategies for the treatment of SCI, including the use of corticosteroids such as methylprednisolone sodium succinate, the optimal timing of surgical intervention, the type and timing of anticoagulation prophylaxis, the role of …

Timing Of Decompression In Patients With Acute Spinal Cord Injury: A Systematic Review, Jefferson R. Wilson, Lindsay A. Tetreault, Brian Kwon, Paul M. Arnold, Thomas E. Mroz, Christopher I. Shaffrey, James S. Harrop, Jens R. Chapman, Steven Casha, Andrea C. Skelly, Haley K. Holmer, Erika D. Brodt, Michael G. Fehlings

Department of Neurosurgery Faculty Papers

Study Design: Systematic review. Objective: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (≤24 hours) versus late decompression (>24 hours) in adults with acute spinal cord injury (SCI). Methods: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of …

Intracranial Eeg Fluctuates Over Months After Implanting Electrodes In Human Brain., Hoameng Ung, Steven N. Baldassano, Hank Bink, Abba M. Krieger, Shawniqua Williams, Flavia Vitale, Chengyuan Wu, Dean Freestone, Ewan Nurse, Kent Leyde, Kathryn A. Davis, Mark Cook, Brian Litt

Department of Neurosurgery Faculty Papers

OBJECTIVE: Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings.

APPROACH: Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for …

Bilateral Retinal Problem In A Patient With Alport Syndrome., Sundeep K. Kasi, Murtaza K Adam, David S Ehmann

Wills Eye Hospital Papers

No abstract provided.

Characterization Of Health Care Utilization In Patients Receiving Implantable Cardioverter-Defibrillator Therapies: An Analysis Of The Managed Ventricular Pacing Trial., John Rickard, David J. Whellan, Lou Sherfesee, Brett J. Peterson, Tara Nahey, Anthony S. Tang, Kenneth A. Ellenbogen, Alan Cheng

Division of Cardiology Faculty Papers

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are effective in terminating lethal arrhythmias, but little is known about the degree of health care utilization (HCU) after ICD therapies.

OBJECTIVE: Using data from the managed ventricular pacing trial, we sought to identify the incidence and types of HCU in ICD patients after receiving ICD therapy (shocks or antitachycardia pacing [ATP]).

METHODS: We analyzed HCU events (ventricular tachyarrhythmia [VTA]-related, heart failure-related, ICD implant procedure-related, ICD system-related, or other) and their association with ICD therapies (shocked ventricular tachycardia episode, ATP-terminated ventricular tachycardia episode, and inappropriately shocked episode).

RESULTS: A total of 1879 HCUs occurred in 695 …

Strain Specific Effects Of Low Level Lead Exposure On Associative Learning And Memory In Rats., Megha Verma, J. S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Exposure to lead (Pb) remains a significant public health concern. Lead exposure in early life impairs the normal development of numerous cognitive and neurobehavioral processes. Previous work has shown that the effects of developmental Pb exposure on gene expression patterns in the brain are modulated by various factors including the developmental timing of the exposure, level of exposure, sex, and genetic background. Using gene microarray profiling, we previously reported a significant strain-specific effect of Pb exposure on the hippocampal transcriptome, with the greatest number of differentially expressed transcripts in Long Evans (LE) rats and the fewest in Sprague Dawley (SD) …

The Rna-Binding Protein Hur Contributes To Neuroinflammation By Promoting C-C Chemokine Receptor 6 (Ccr6) Expression On Th17 Cells., Jing Chen, Jennifer L. Martindale, Carole Cramer, Myriam Gorospe, Ulus Atasoy, Paul D. Drew, Shiguang Yu

Department of Neurology Faculty Papers

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA …

Ibrutinib Unmasks Critical Role Of Bruton Tyrosine Kinase In Primary Cns Lymphoma., Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S. Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Dan Rohle, Marc Rosenblum, Agnes Viale, Viviane S. Tabar, Cameron W. Brennan, Igor T. Gavrilovic, Thomas J. Kaley, Craig P. Nolan, Antonio Omuro, Elena Pentsova, Alissa A. Thomas, Elina Tsyvkin, Ariela Noy, M. Lia Palomba, Paul Hamlin, Craig S. Sauter, Craig H. Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C. Lallana, Vaios Hatzoglou, Anne S. Reiner, Philip H. Gutin, Jason T. Huse, Katherine S. Panageas, Thomas G. Graeber, Nikolaus Schultz, Lisa M. Deangelis, Ingo K. Mellinghoff

Department of Neurology Faculty Papers

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated …

National Football League Skilled And Unskilled Positions Vary In Opportunity And Yield In Return To Play After An Anterior Cruciate Ligament Injury., Jaewon Yang, Jonathan D. Hodax, Jason T. Machan, Eric S. Secrist, Wesley M. Durand, Brett D. Owens, Adam E.M. Eltorai, Christopher C. Dodson

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions.

PURPOSE: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to …

Amlexanox Enhances Premature Termination Codon Read-Through In Col7a1 And Expression Of Full Length Type Vii Collagen: Potential Therapy For Recessive Dystrophic Epidermolysis Bullosa., Velina S. Atanasova, Qiujie Jiang, Marco Prisco, Christina Gruber, Josefina Piñón Hofbauer, Mei Chen, Cristina Has, Leena Bruckner-Tuderman, John A. Mcgrath, Jouni Uitto, Andrew P. South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by the lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. A total of 46% of patients with RDEB harbor at least one premature termination codon (PTC) mutation in COL7A1, and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing "read-through" and incorporation of an amino acid at the PTC site. However, aminoglycoside toxicity will likely prevent widespread clinical application. Here the FDA-approved drug amlexanox was tested for its ability …

Debate On Human Aging And Lifespan, Mohammad Rafi, Abass Alavi

Department of Neurology Faculty Papers

The issue of human lifespan has long been a matter of controversy among scientists. In spite of the recent claim by Dong et al that human lifespan is limited to 115 years, with the mounting improvements in biotechnology and scientific understanding of aging, we may be confident that aging will slow down over the course of the current century extending human longevity much longer than 115 years.

Integrated Results From The Copernicus And Galileo Studies., Amelie Pielen, W. Lloyd Clark, David S. Boyer, Yuichiro Ogura, Frank G. Holz, Jean-Francois Korobelnik, Brigitte Stemper, Friedrich Asmus, Kay D. Rittenhouse, Christiane Ahlers, Robert Vitti, Namrata Saroj, Oliver Zeitz, Julia A. Haller

Wills Eye Hospital Papers

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO.

PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52.

RESULTS: At week 24, mean gain in best-corrected …

Cabazitaxel In The Treatment Of Metastatic Castration-Resistant Prostate Cancer: Patient Selection And Special Considerations., Sheel Patel, Jean Hoffman-Censits

Department of Medical Oncology Faculty Papers

Cabazitaxel is an effective chemotherapeutic agent used in the treatment of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel. With the advent of new antiandrogen therapies, immune-based treatments, and radioactive-targeted therapy, there are now multiple effective and approved agents for this disease state. The optimal sequencing of these agents is unclear as there are no large-scale head-to-head comparisons. Clinicians must familiarize themselves with the most recent studies as well as drug toxicities to determine the best treatment option for their patients. In this review, we focus on the development of cabazitaxel for mCRPC, evaluate its efficacy, and highlight key strategies …

A Prospective Randomized Study Analyzing Preoperative Opioid Counseling In Pain Management After Carpal Tunnel Release Surgery., Todd H. Alter, Asif M Ilyas

Rothman Institute Papers

PURPOSE: Prescription opioid misuse has become increasingly prevalent in the United States. Preoperative opioid counseling has been proposed to decrease opioid consumption after surgery. This study aimed to evaluate the effect of preoperative opioid counseling on patients' pain experience and opioid consumption after carpal tunnel release (CTR) surgery.

METHODS: A prospective comparison of consecutive patients scheduled to undergo CTR surgery was conducted. Patients were randomized to receive either formal preoperative opioid counseling or no counseling. All operations were performed with the same miniopen CTR surgical technique, and the same number of opioids were prescribed after surgery. Daily opioid pill consumption, …

Tia1 Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia Promote Phase Separation And Alter Stress Granule Dynamics., Ian R. Mackenzie, Alexandra M. Nicholson, Mohona Sarkar, James Messing, Maria D. Purice, Cyril Pottier, Kavya Annu, Matt Baker, Ralph B. Perkerson, Aishe Kurti, Billie J. Matchett, Tanja Mittag, Jamshid Temirov, Ging-Yuek R. Hsiung, Charles Krieger, Melissa E. Murray, Masato Kato, John D. Fryer, Leonard Petrucelli, Lorne Zinman, Sandra Weintraub, Marsel Mesulam, Julia Keith, Sasha A. Zivkovic, Veronica Hirsch-Reinshagen, Raymond P. Roos, Stephan Züchner, Neill R. Graff-Radford, Ronald C. Petersen, Richard J. Caselli, Zbigniew K. Wszolek, Elizabeth Finger, Carol Lippa, David Lacomis, Heather Stewart, Dennis W. Dickson, Hong Joo Kim, Ekaterina Rogaeva, Eileen Bigio, Kevin B. Boylan, J. Paul Taylor, Rosa Rademakers

Department of Neurology Faculty Papers

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 10