Medicine and Health Sciences Commons^™

Targeting Oncogenic Gαq/11 In Uveal Melanoma, Dominic Lapadula, Jeffrey L Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Uveal melanoma is the most common intraocular cancer in adults and arises from the transformation of melanocytes in the uveal tract. While treatment of the primary tumor is often effective, 36–50% of patients develop metastatic disease primarily to the liver. While various strategies have been used to treat the metastatic disease, there remain no effective treatments that improve survival. Significant insight has been gained into the pathways that are altered in uveal melanoma, with mutually exclusive activating mutations in the GNAQ and GNA11 genes being found in over 90% of patients. These genes encode the alpha subunits of the hetetrotrimeric …

Reduced Risk Of Reoperations With Modern Deep Brain Stimulator Systems: Big Data Analysis From A United States Claims Database, Chengyuan Wu, Sean J Nagel, Rahul Agarwal, Monika Pötter-Nerger, Wolfgang Hamel, Ashwini Sharan, Allison T Connolly, Binith Cheeran, Paul S Larson

Department of Neurosurgery Faculty Papers

Objective: There have been significant improvements in the design and manufacturing of deep brain stimulation (DBS) systems, but no study has considered the impact of modern systems on complications. We sought to compare the relative occurrence of reoperations after de novo implantation of modern and traditional DBS systems in patients with Parkinson's disease (PD) or essential tremor (ET) in the United States.

Design: Retrospective, contemporaneous cohort study.

Setting: Multicenter data from the United States Centers for Medicare and Medicaid Services administrative claims database between 2016 and 2018.

Participants: This population-based sample consisted of 5,998 patients implanted with a DBS system, …

The Transition To Peer Learning, C. G. Roth, H. V. Naringrekar, A. E. Flanders

Department of Radiology Posters

Problem Description: Historically, peer review has been compelled by regulatory and legislative mandates, such as the Joint Commission Ongoing Professional Practice Evaluation (OPPE) requirement and the Health Care Quality Improvement Act (HCQIA) enacted by Congress in 1986. [1] However, these external mandates were focused on quality assurance, generally carrying punitive connotations and practically translated into rote compliance without the benefit of learning and improvement. In fact, the lack of quality improvement focus prompted the Institute of Medicine (IOM) to release its 2015 report, “Improving Diagnosis in Health Care,” stating that a “critical type of error in health care—diagnostic error—has received …

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Association Between Sex And Immune Checkpoint Inhibitor Outcomes For Patients With Melanoma., Se Ryeong Jang, Nikita Nikita, Joshua Banks, Scott W. Keith, Jennifer M. Johnson, Melissa Wilson, Grace Lu-Yao

Kimmel Cancer Center Faculty Papers

Importance: Immune checkpoint inhibitors (ICIs) have revolutionized melanoma treatment and are now standard of care. Although sex is associated with immune function and immune-related diseases, the interaction between sex and ICIs is understudied.

Objective: To examine whether cancer immunotherapy effectiveness varies between female and male patients with advanced melanoma treated with either nivolumab plus ipilimumab combination therapy or anti-programmed cell death protein 1 (PD-1) therapy (namely, pembrolizumab or nivolumab).

Design, Setting, and Participants: The study population consisted of 1369 older adults (aged ≥65 years) with a record of melanoma diagnosis from January 1, 1991, to December 31, 2015, in the …

In Response: Neuraxial And Peripheral Misconnection Events Leading To Wrong-Route Medication Errors, Eugene R. Viscusi, Vincent Hugo, Klaus Hoerauf, Frederick S Southwick

Department of Anesthesiology Faculty Papers

No abstract provided.

A Word From The Writing Team (December 2021), Pam Walter, Mfa

A Word From the Writing Team (Newsletter)

This issue includes:

• New Writing Specialist, Liz Declan
• Saying Farewell to Jen Wilson
• Coming Soon -- Find the Time: Time Management

Augmentation Of Pedicle Screws Using Bone Grafting In Patients With Spinal Osteoporosis, Andrey Evgenievich Bokov, Anatoliy Bulkin, I S. Bratsev, Svetlana Ya Kalinina, Sergey G. Mlyavykh, David G. Anderson

Department of Neurosurgery Faculty Papers

The aim of the study was to develop a new method of vertebral augmentation based on autologous and allogeneic bone chips to be used in pedicle screw fixation and to compare this method with the technique based on polymethyl methacrylate (PMMA). Materials and Methods. This prospective non-randomized study included 164 patients with degenerative pathologies or traumatic injuries of the lumbar spine and transitional thoracolumbar segments; 153 of the operated patients were followed up for 18 months. In these patients, radiodensity of the cancellous bone tissue was below 110 HU by the Hounsfield scale. Patients with degenerative spinal disorders underwent pedicle …

Stem Signatures Associating Sox2 Antibody Helps To Define Diagnosis And Prognosis Prediction With Esophageal Cancer, Zi-Yang Peng, Qing-Shi Wang, Kai Li, Si-Si Chen, Xiang Li, Guo-Dong Xiao, Shou-Ching Tang, Hong Ren, Zhe Wang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: esophageal cancer is one of the deadliest diseases worldwide. Due to the ineffectual screening methods referring to early diagnosis, most people have lost their chance of radical resection when diagnosed with esophageal cancer. This aim of this study was designed to evaluate the latent values of the stem signatures-associated autoantibodies (AABS) in predicting the early diagnosis, and particularly seeking the precise predictive outcomes with sensitive SOX2. We also studied the potential immunotherapeutic targets and prospective long-term prognosis predicators of esophageal cancer.

Methods: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of …

The Effects Of Molecular Crowding And Cpg Hypermethylation On Dna G-Quadruplexes Formed By The C9orf72 Nucleotide Repeat Expansion., Kadir A. Ozcan, Layla T. Ghaffari, Aaron R. Haeusler

Farber Institute for Neuroscience Faculty Papers

A nucleotide repeat expansion (NRE), (G₄C₂)_n, located in a classically noncoding region of C9orf72 (C9), is the most common genetic mutation associated with ALS/FTD. There is increasing evidence that nucleic acid structures formed by the C9-NRE may both contribute to ALS/FTD, and serve as therapeutic targets, but there is limited characterization of these nucleic acid structures under physiologically and disease relevant conditions. Here we show in vitro that the C9-NRE DNA can form both parallel and antiparallel DNA G-quadruplex (GQ) topological structures and that the structural preference of these DNA GQs can be dependent …

Clinical Applications Of Magnetic Resonance Imaging Based Functional And Structural Connectivity, Chengyuan Wu, Francisca Ferreira, Michael Fox, Noam Harel, Jona Hattangadi-Gluth, Andreas Horn, Saad Jbabdi, Joshua Kahan, Ashwini Oswal, Sameer A Sheth, Yanmei Tie, Vejay Vakharia, Ludvic Zrinzo, Harith Akram

Department of Neurosurgery Faculty Papers

Advances in computational neuroimaging techniques have expanded the armamentarium of imaging tools available for clinical applications in clinical neuroscience. Non-invasive, in vivo brain MRI structural and functional network mapping has been used to identify therapeutic targets, define eloquent brain regions to preserve, and gain insight into pathological processes and treatments as well as prognostic biomarkers. These tools have the real potential to inform patient-specific treatment strategies. Nevertheless, a realistic appraisal of clinical utility is needed that balances the growing excitement and interest in the field with important limitations associated with these techniques. Quality of the raw data, minutiae of the …

Giant Abdominal Aortic Aneurysms, Joshua I Ng, Tuong Nguyen, Anand Tarpara, Dawn Salvatore, Paul J Dimuzio, Babak Abai

Department of Surgery Faculty Papers

Giant abdominal aortic aneurysms (AAAs) are defined as AAAs >10 to 13 cm in the maximum transverse diameter. We have described a case of a patient who had presented for open repair of an 18-cm AAA and a review of reported cases of giant AAAs >10 cm in the maximum transverse diameter. Forty cases were compiled. The average maximum AAA diameter was 14.5 ± 4.1 cm. The AAA was ruptured on presentation in 12 patients (30%). Of the 40 cases, 34 (85%) were repaired with open surgery. The reported mortality was 15%. Despite the case complexity, five endovascular repairs were …

Contrast-Enhanced Ultrasound Of Muscle Perfusion May Indicate Patient Response To Left Ventricular Assist Device Therapy., Lauren J. Delaney, Kathleen Fitzgerald, Maria Stanczak, Priscilla Machado, John W..C. Entwistle, Flemming Forsberg, Gordon R. Reeves

Department of Radiology Faculty Papers

PURPOSE: Left ventricular assist device (LVAD) support is associated with peripheral vascular abnormalities beyond those associated with heart failure (HF). These abnormalities are associated with persistent functional impairments that adversely impact quality of life (QoL). Methods for measuring peripheral vascular function in this population are needed.

METHODS: This pilot study investigated the use of contrast-enhanced ultrasound (CEUS) using standardized protocols to estimate changes in peripheral (quadriceps) muscle perfusion among patients with HF (INTERMACS profile 3) undergoing LVAD implantation (n = 7). Patients were then stratified by those who did ("responders", n = 4) and did not ("nonresponders", n = 3) …

Narrative Review-Drug Delivery In Age-Related Macular Degeneration, Rachel Israilevich, Raziyeh Mahmoudzadeh, Mirataollah Salabati, David Xu

Wills Eye Hospital Papers

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration (AMD). AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7% of blindness worldwide. Advanced AMD can be classified into two subtypes: late-stage dry AMD [known as geographic atrophy (GA)] and neovascular AMD (nAMD). GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium. Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium (RPE) or retina, a process known as choroidal neovascularization …

Micro-Computed Tomographic Analysis Of The Shaping Ability Of Xp-Endo Shaper In Oval-Shaped Distal Root Canals Of Mandibular Molars, Ane Poly, Wei-Ju Louis Tseng, Fernando Marques, Frank Carsten Setzer, Bekir Karabucak

Center for Translational Medicine Faculty Papers

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals.

Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer's instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan …

Disparities In Delaware Caregiver Beliefs About The Covid-19 Vaccine For Their Children, Thao-Ly Phan, Paul T Enlow, Michael K. Wong, Amanda M. Lewis, Anne E Kazak, Jonathan M. Miller

Department of Pediatrics Faculty Papers

Objective: To describe sociodemographic disparities in caregiver beliefs about the COVID-19 vaccine for their children. Methods: This was a cross-sectional study, linking caregiver-reported data to geocoded sociodemographic data from child EHRs. Caregivers of children receiving care in a Delaware pediatric healthcare system were invited to complete a survey about COVID-19 vaccine beliefs from March 19 to April 16, 2021. Results: 1499 caregivers participated (18% Black, 11% Hispanic, 32% public insurance, 12% rural). 54% of caregivers intended to vaccinate their children, while 34% were unsure and 12% would not. Caregivers of younger children (aOR 3.70, CI 2.36-5.79), Black children (aOR 2.11, …

Metabolic Syndrome And Acute Respiratory Distress Syndrome In Hospitalized Patients With Covid-19, Joshua L Denson, Aaron S Gillet, Yuanhao Zu, Margo Brown, Thaidan Pham, Yilin Yoshida, Franck Mauvais-Jarvis, Ivor S Douglas, Mathew Moore, Kevin Tea, Andrew Wetherbie, Rachael Stevens, John Lefante, Jeffrey G Shaffer, Donna Lee Armaignac, Katherine Belden, Margit Kaufman, Smith F Heavner, Valerie C Danesh, Sreekanth R Cheruku, Catherine A St Hill, Karen Boman, Neha Deo, Vikas Bansal, Vishakha K Kumar, Allan J Walkey, Rahul Kashyap, Society Of Critical Care Medicine Discovery Viral Infection And Respiratory Illness Universal Study (Virus): Covid-19 Registry Investigator Group

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome.

Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19.

Design, setting, and participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined …

Commentary: Zoom Into The Coronary Anastomosis During Coronavirus Disease 2019 (Covid-19), Danial Ahmad, Vakhtang Tchantchaleishvili

Division of Cardiology Faculty Papers

No abstract provided.

Prevalence Of Chronic Disease In Older Adults In Multitier Eye-Care Facilities In South India: Electronic Medical Records-Driven Big Data Analytics Report, Umesh Chandra Behera, Brooke Salzman, Anthony Vipin Das, Gumpili Sai Prashanthi, Parth Lalakia, Richard Derman, Bharat Panigrahy

Department of Family & Community Medicine Faculty Papers

Purpose: To study the prevalence of systemic conditions in older adults, either self-reported or discovered during routine eye examinations, at multitier eye-care facilities over the past decade, and to explore their association with vision and common ocular disorders, including cataract, glaucoma, and retinopathy.

Methods: Retrospective review of a large data set compiled from the electronic medical records of patients older than 60 years who presented to an eye facility of a multitier ophthalmology network located in 200 different geographical locations that included urban and rural eye-care centers spread across four states in India over a 10-year period.

Results: 618,096 subjects …

Combination Intrathecal Drug Therapy Strategies For Pain Management, Jay Karri, Mani Singh, Devas J Modi, Vwaire Orhurhu, Caleb Seale, Michael Saulino, Anuj Marathe, Darrell Vydra, Jonathan M Hagedorn, Brian Bruel, Alaa Abd-Elsayed

Department of Rehabilitation Medicine Faculty Papers

Background: Numerous combination intrathecal drug therapy (CIDT) strategies exist and are utilized for varying pain syndromes, typically when monotherapy dose escalation or medication alternation is deemed untenable or unfeasible. Unfortunately, the supportive evidence basis for the use of these strategies and specific drug combinations is generally lacking and unclear, with many medications being used for off-label indications.

Objective: In this manuscript, we provide a robust exploration and analysis of the literature to provide an evidence-based narrative for the use of CIDT strategies in regard to clinical indications, pharmacologic parameters, specific drug combinations, safety profiles, and future directions.

Study design: Narrative …

Reactive Granulomatous Dermatitis Associated With Ovarian Cancer And A Review Of Its Role As A Harbinger For Malignancy, Alexander Sherban, Jisun Cha, Elizabeth Jones

Department of Dermatology and Cutaneous Biology Faculty Papers

Reactive granulomatous dermatitis (RGD) is a rare dermatosis with a variety of cutaneous manifestations unified by a dermal granulomatous infiltrate on histology. Rheumatoid arthritis and autoimmune disease are classic associations, but an increasing number of cases have been attributed to covert malignancy. Only 41 cases of paraneoplastic RGD have been documented to our knowledge and we present an additional case that manifested eight months prior to the diagnosis of ovarian cancer and clinically mimicked morphea. Histopathologic examination identifying palisaded CD68+ cells and collagen degeneration are helpful in diagnosing this entity which may mimic a host of other cutaneous processes, including …

Assessment Of Temporal Variations In Adherence To Nrp Using Video Recording In The Delivery Room, Amy J Sloane, Kaitlin M Kenaley, Michael T Favara

Department of Medicine Faculty Papers

INTRODUCTION: Video recording and video evaluation tools have been successfully used to evaluate neonatal resuscitation performance. The objective of our study was to evaluate differences in Neonatal Resuscitation Program (NRP) adherence at time of birth between three temporal resuscitative periods using scored video recordings.

METHODS: This is a retrospective review of in-situ resuscitation video recordings from a level 3 perinatal center between 2017 and 2018. The modified Neonatal Resuscitation Assessment (mNRA) scoring tool was used as a surrogate marker to assess NRP adherence during daytime, evening, and nighttime hours.

RESULTS: A total of 260 resuscitations, of which 258 were births …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Gut Permeability And Osteoarthritis, Towards A Mechanistic Understanding Of The Pathogenesis: A Systematic Review, Giorgio Guido, Guido Ausenda, Veronica Iascone, Emanuele Chisari

Rothman Institute Faculty Papers

Osteoarthritis (OA) is the most common condition affecting human joints. Along with mechanical and genetic factors, low-grade inflammation is increasingly supported as a causal factor in the development of OA. Gut microbiota and intestinal permeability, via the disruption of tight junction competency, are proposed to explain a gut-joint axis through the interaction with the host immune system. Since previous studies and methods have underestimated the role of the gut-joint axis in OA and have only focussed on the characterisation of microbiota phenotypes, this systematic review aims to appraise the current evidence concerning the influence of gut permeability in the pathogenesis …

Vte And Anticoagulation In Menstruating Women, Ida Micaily, Bethany T. Samuelson Bannow

Department of Medicine Faculty Papers

Women of childbearing potential have a high prevalence of venous thromboembolism (VTE) due to high estrogen states, such as pregnancy and the use of estrogen-containing contraceptives. Abnormal uterine bleeding (AUB) affects up to two-thirds of menstruating women on anticoagulation (AC), and can severely impair a woman's quality of life. Rates of heavy menstrual bleeding (HMB) and other forms of AUB including inter-menstrual and postmenopausal bleeding are consistently underreported in the original clinical trials utilizing AC. VTE can occur at any time in a woman's life, and the aim of this review article is to discuss the current landscape of literature …

Dysregulation Of Mir-21-Associated Mirna Regulatory Networks By Chronic Ethanol Consumption Impairs Liver Regeneration., Austin Parrish, Ankita Srivastava, Egle Juskeviciute, Jan B Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Impaired liver regeneration has been considered as a hallmark of progression of alcohol-associated liver disease. Our previous studies demonstrated that in vivo inhibition of the microRNA (miRNA) miR21 can restore regenerative capacity of the liver in chronic ethanol-fed animals. The present study focuses on the role of microRNA regulatory networks that are likely to mediate the miR-21 action. Rats were chronically fed an ethanol-enriched diet along with pair-fed control animals and treated with AM21 (anti-miR-21), a locked nucleic acid antisense to miR-21. Partial hepatectomy (PHx) was performed and miRNA expression profiling over the course of liver regeneration was assessed. Our …

Predicting Risk Factors For Thromboembolic Complications In Patients With Sickle Cell Anaemia - Lessons Learned For Prophylaxis, Salam Alkindi, Anwaar R Al-Ghadani, Samah R Al-Zeheimi, Said Y Alkindi, Naglaa Fawaz, Samir K. Ballas, Anil V Pathare

Cardeza Foundation for Hematologic Research

Objective: To assess the clinical and laboratory predictors of venous thromboembolism (VTE) in patients with sickle cell anaemia (SCA) and its relationship to morbidity and mortality.

Methods: This retrospective case-control study analysed data from patients with SCA that experienced VTE compared with matched control patients with SCA but no VTE (2:1 ratio).

Results: A total of 102 patients with SCA were enrolled (68 cases with VTE and 34 controls). Amongst the 68 cases (median age, 29.5 years), 26 (38.2%) presented with isolated pulmonary embolism (PE). A higher prevalence of splenectomy (73.5% versus 35.3%) was observed in the cases compared with …

Outcomes Of Mechanical Thrombectomy For Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score In The Early And Extended Window, Eyad Almallouhi, Sami Al Kasab, Zachary Hubbard, Eric C Bass, Guilherme Porto, Ali Alawieh, Reda Chalhoub, Pascal Jabbour, Robert M Starke, Stacey Q Wolfe, Adam S Arthur, Edgar Samaniego, Ilko Maier, Brian M Howard, Ansaar Rai, Min S Park, Justin Mascitelli, Marios Psychogios, Reade De Leacy, Travis Dumont, Michael R Levitt, Adam Polifka, Joshua Osbun, Roberto Crosa, Joon-Tae Kim, Walter Casagrande, Shinichi Yoshimura, Charles Matouk, Peter T Kan, Richard W Williamson, Benjamin Gory, Maxim Mokin, Isabel Fragata, Osama Zaidat, Albert J Yoo, Alejandro M Spiotta

Department of Neurosurgery Faculty Papers

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct.

Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5.

Design, setting, and participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid …

Looking Upstream: Promoting Health Equity In Philadelphia Through Novel Partnership Strategies, Adrea Cope, David B. Nash, Sandra E Brooks, David Platt

College of Population Health Faculty Papers

No abstract provided.

Activation Of Crtc2/Creb1 In Skeletal Muscle Enhances Weight Loss During Intermittent Fasting, Nelson E Bruno, Jerome C Nwachukwu, David C Hughes, Sathish Srinivasan, Richard Hawkins, David Sturgill, Gordon L Hager, Stephen Hurst, Shey-Shing Sheu, Sue C Bodine, Michael D Conkright, Kendall W Nettles

Department of Medicine Faculty Papers

The Creb-Regulated Transcriptional Coactivator (Crtc) family of transcriptional coregulators drive Creb1-mediated transcription effects on metabolism in many tissues, but the in vivo effects of Crtc2/Creb1 transcription on skeletal muscle metabolism are not known. Skeletal muscle-specific overexpression of Crtc2 (Crtc2 mice) induced greater mitochondrial activity, metabolic flux capacity for both carbohydrates and fats, improved glucose tolerance and insulin sensitivity, and increased oxidative capacity, supported by upregulation of key metabolic genes. Crtc2 overexpression led to greater weight loss during alternate day fasting (ADF), selective loss of fat rather than lean mass, maintenance of higher energy expenditure during the fast and reduced binge-eating …