Medical Specialties Commons^™

Closing Gaps In Urban Trauma Systems: Outcomes Of An Inner-City Community Emergency Department Multidisciplinary Trauma Protocol, Kory S. London, Alan Cherney, Sulabh Neupane, H. Alex Tomlinson, Joseph Cervone, Elaine Qian, Casey Fishman, Jennifer Davis, Sean Mcgann, Varsha Goswami, George Koenig, Frederick Randolph

Department of Emergency Medicine Faculty Papers

BACKGROUND: Non-trauma center (NTC) emergency departments (EDs) play regular but underappreciated roles in the management of severely injured patients, yet many lack formal protocols to guide care. We describe the implementation and outcomes of a structured trauma evaluation and transfer protocol at an urban NTC emergency department.

METHODS: A multidisciplinary trauma protocol was implemented on April 1, 2023, at an urban NTC, supported by a Level I trauma center, 2.5 miles apart. The study period ran from January 1, 2019, to June 30, 2025. Using pre-post study design, 62 patients treated prior to implementation were compared with 49 post-intervention patients. …

Neurodevelopmental Phenotypes And Brain Anomalies In Individuals With Heterozygous Sema6a Variants, Evan Burchfiel, Xiaonan Zhao, Nichole M Owen, Tia Gordon, Mahshid S Azamian, Eric C Kao, Fan Xia, Xi Luo, Jill A Rosenfeld, Seema R Lalani, Allison P Ortega, Steven B Bleyl, Florence Petit, Sulekha Rajagopolan, Bénédicte Demeer, Meredith K Gillespie, Lijia Huang, Matthew Osmond, Kym M Boycott, Kyra E Stuurman, Marjon A Van Slegtenhorst, Haley Soller, Céline Jost, Aurore Garde, Hana Safraou, Laurence Faivre, Victor Faundes, Daryl A Scott

Faculty, Staff and Students Publications

SEMA6A is a transmembrane protein that plays a role in axon guidance and cell migration. Sema6a null mice have cerebral anatomical defects and altered social interactions and working memory. However, the phenotypes associated with loss of SEMA6A function have not been clearly defined in humans. Here we describe 11 individuals who are heterozygous for putatively damaging variants affecting SEMA6A. All of these individuals (100%) had neurodevelopmental phenotypes that included developmental delay, intellectual disability, and/or autism spectrum disorder. Abnormal behaviors were seen in 73% with oppositional defiant disorder being diagnosed in 27% and acting out, overeating, and tantrums each being described …

Language-Serving Hospitals And Seven-Day Readmission Among Patients With A Non-English Primary Language, Benjamin G Allar, Rachel E Murphy, Regan W Bergmark, Esteban F Gershanik, Alicia Fernandez, Andrea L Pusic, Gregory L Peck, David W Bates, Gezzer Ortega

Faculty, Staff and Students Publications

Objectives. To compare 7-day readmission among patients with a non-English primary language in language-serving versus non-language-serving hospitals.

Methods. We conducted a retrospective cohort study using the New Jersey State Inpatient Database (2010-2022). We identified 578 030 inpatient discharges home among patients with a non-English primary language. We used generalized linear mixed models to compare 7-day readmission between language-serving hospitals-defined as those with a higher proportion of patients with a non-English primary language-and non-language-serving hospitals.

Results. Patients with a non-English primary language were less likely to be readmitted within 7 days at language-serving versus non-language-serving hospitals (4.8% vs 9.8%; adjusted odds …

Rhino: An Integrative Multi-Omics Framework Linking Circadian Physiology To Precision Medicine, Panpan Liu, Roberto E López-Valiente, Yuan Liu, Cam Mong La, Isabella Beraldo Xavier, Sean M Hartig, Pradip Saha, Zheng Sun, Leng Han, Dongyin Guan

Faculty, Staff and Students Publications

Circadian rhythms are involved in nearly all physiological processes, and their disruption increases disease risk. Aligning drug administration timing with the body's internal clock, known as circadian medicine, holds promise for improving treatment efficacy and safety. However, systematic strategies to identify circadian‐regulated therapeutic targets remain limited. Here, we develop RHINO (RHythmic Interacting Network for multi‐Omics), an integrative multi‐omics framework for exploring circadian regulation across diverse genetic and disease contexts, and prioritizing druggable circadian targets. Applying RHINO reveals that human genetic variation broadly shapes rhythmic gene expression, with approximately 80% of FDA‐approved drug targets exhibiting genotype‐dependent rhythmicity, thereby substantially expanding the …

Association Between Estimated Time With Low Glomerular Filtration Rate And Access To Transplant Among Youth With Advanced Chronic Kidney Disease., Elaine Ku, Timothy Copeland, Charles E. Mcculloch, Jonathan D. Savant, Bradley A. Warady, Susan L. Furth, Sarah Kizilbash, Daniel I. Feig, Roshan P. George, Joseph T. Flynn, Judith Jerry-Fluker, Matthew B. Matheson, Sandra Amaral, Ckid Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation in youth has not been well studied.

METHODS: We examined the association between time spent with low eGFR (between 10-30 mL/min/1.73 m²) and odds of preemptive or living donor transplantation among youth with CKD. eGFR was estimated using the bedside Schwartz (if < 18 years) and CKD-EPI 2021 equations (if ≥ 18 years) and the CKiD U25 equation in sensitivity analysis. Time spent with low eGFR was compared by race/ethnicity.

RESULTS: Among 333 youth with CKD (median age 11 years [IQR 7,14]), median time spent with low eGFR was 28.8 months. 77% were preemptively waitlisted, and 45% received preemptive …

Prediction Model For Children With Anaphylaxis Who May Not Require Emergency Department Care: A Multicenter Retrospective Cohort Study., Timothy E. Dribin, David Schnadower, Hugh A. Sampson, Yin Zhang, Nanhua Zhang, Stephen B. Freedman, Mark I. Neuman, David C. Brousseau, Rakesh D. Mistry, Stephanie Boyd, Yonatan Wolnerman, Patrick S. Walsh, Craig Vander Wyst, Vandana Thapar, Jonathan Strutt, Geetanjali Srivastava, Nidhi V. Singh, Christopher J. Russo, Christian D. Pulcini, Thuy L. Ngo, Jo-Ann O. Nesiama, Matthew M. Moake, Ashley M. Metcalf, Tamar R. Lubell, Juhee Lee, Chari D. Larsen, Karen Y. Kwan, Curtis L. Knoles, Kajal Khanna, Julia F. Freeman, Justin R. Davis, Alicia Daggett, Joanna S. Cohen, Ari R. Cohen, Wee-Jhong Chua, Sri S. Chinta, Brittany Boswell, Kelly R. Bergmann, Paul L. Aronson, Kenneth A. Michelson

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The 2023 US Anaphylaxis Practice Parameter indicated that some patients receiving epinephrine in the community might avoid emergency department (ED) visits; however, the criteria and safety of this approach remain unproven.

OBJECTIVE: To derive and validate a clinical prediction model for identifying children at risk of receiving epinephrine after arriving at the ED.

METHODS: We conducted a 31-center retrospective cohort study of children aged 6 months to less than 18 years who received 1 prehospital dose of epinephrine for allergic reactions between 2016 and 2019. The outcome was receipt of epinephrine after ED arrival. We used least absolute shrinkage …

The Who Classification Of Genetic Tumour Syndromes: Considerations For Genetics, Erika R E Denton, Anthony J Gill, Alexander J Lazar, Ian M Frayling, Stefan M Pfister, Mark A Rubin, Katia R M Leite, Raymond Dalgleish, Elspeth A Bruford, Sharon E Plon, Ada Hamosh, Michael Francis Walsh, Gabrielle Goldman-Lévy, Harshima Wijesinghe, William D Foulkes, Dilani Lokuhetty

Faculty, Staff and Students Publications

The WHO Classification of Tumours is used widely by histopathologists and other disciplines as it provides an internationally agreed taxonomy of neoplastic disorders. Now published online and in print, it has often included genetic tumour syndromes (GTS) relevant to particular organs, as suggested by the editorial board. This highlighted the lack of a systematic classification of GTS, providing international standards for their diagnosis and a basis for research. The need for this was established by a series of meetings, leading to the adoption of a hierarchical classification of GTS based on the cellular mechanism affected, the molecular pathway involved, the …

Skin Carotenoid Scores Are A Valid Approximation Of Fruit And Vegetable Intake Among Adults With Obesity, Stephanie B Jilcott Pitts, Qiang Wu, Elizabeth Gates, Melissa N Laska, Andrew R Dinardo, Nancy E Moran

Children’s Nutrition Research Center Staff Publications

Skin carotenoid score (SCS) as measured using pressure-mediated reflection spectroscopy has been validated among adults with normal and overweight body mass index, with little validation research among adults with obesity. Therefore, the purpose of this exploratory study was to examine the validity of SCS as an approximation of fruit and vegetable intake among adults with obesity. We used samples from adults with obesity from three prior studies: The first study examined the validity of SCS among 213 adults, 34 with obesity; the second, examined sensitivity of SCS to a β-carotene-rich juice intervention among 162 adults, 14 with obesity; the third …

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

Inaccurate Interpretation Of Hypoxia Signatures From Transcriptomic Analyses In Neuro-Oncology, Marco Gallo

Faculty, Staff and Students Publications

We aim to highlight problems with the biological interpretation of computationally-derived hypoxia signatures for neuro-oncology research. By reviewing important experimental work in the field, we discuss common misinterpretations of the concepts of normoxia and hypoxia. In fact, the concentration of oxygen in the adult brain is in the range of 1-7%. Unfortunately, this oxygen concentration range is often mistakenly considered hypoxic in neuro-oncology experiments, although it should be considered physioxic. Further, given the lack of a universal hypoxic signature, we stress the importance of deriving cell type-specific hypoxic signatures using carefully-executed experiments.

Non-Hla Antibody-Associated Hyperacute Allograft Rejection Following Lung Transplantation, Justyna A Karolak, Ernestina Melicoff, Nidhy P Varghese, Przemyslaw Szafranski, Esra Yıldız Bölükbaşı, Erin E Mchugh, Sarah Nicholas, Peter Jindra, John Hicks, Eric D Austin, Paweł Stankiewicz, George B Mallory

Faculty, Staff and Students Publications

Background: Pediatric-onset pulmonary hypertension (PH) is a rare, progressive pulmonary vascular disease associated with high mortality. In cases unresponsive to pharmacological therapy with a severe cardiorespiratory phenotype, lung transplantation (LT) remains the final treatment option. Although LT for pediatric PH is considered a procedure with elevated risk, it has been successfully performed in this population.

Case presentation: A 3-year-old boy underwent uncomplicated LT for fulminant TBX4-associated PH and developed hyperacute allograft failure requiring plasmapheresis, augmentation of immunosuppression, and the use of a monoclonal complement inhibitor. Despite extensive treatment the patient died 46 days after LT. Retrospective analysis of the serum …

Diagnostic Testing After Positive Cell-Free Dna Screening For Sex Chromosome Aneuploidies: Clinical And Socioeconomic Determinants, Blair K Stevens, Sarah Araji, Mohamad Ali Maktabi, Randy Liu, Lauren Westerfield, Michael Wassef, Dejian Lai, Ignatia B Van Den Veyver, Meera Krishnan, Charlotte Lawrence, Siddharth K Prakash

Faculty, Staff and Students Publications

Objective: To assess socioeconomic and medical factors associated with prenatal confirmatory diagnostic testing after positive prenatal cell-free (cfDNA) screening for sex chromosome aneuploidies (SCA) in a diverse contemporary patient cohort.

Methods: We conducted a retrospective cohort study of patients who had abnormal prenatal cfDNA screening results indicative of SCA and were seen for genetic counseling between 2014 and 2024 at two tertiary academic medical centers. We used logistic regression analysis to evaluate the association of demographic and clinical factors with confirmatory testing.

Results: Of the 692 patients with abnormal cfDNA results, 26% (n = 180) underwent diagnostic testing. These patients …

A Small Molecule Inhibits Ebola Virus Entry Through Glycoprotein Stabilization, Bruno La Rosa, Murugesan Palaniappan, Martin M Matzuk, Damian W Young, Hailey Turner-Hubbard, Kimberly Morsheimer, Callum Owen, Katalin Toth, Michael Cameron, Robert Davey, Srinivas Chamakuri, Peter Dosa, Fang Li

Faculty, Staff and Students Publications

Ebola virus (EBOV) causes outbreaks with high fatality rates, yet potent small-molecule inhibitors targeting EBOV glycoprotein (GP) remain limited. Here, using DNA-encoded chemical libraries, we screen 4.73 billion compounds against EBOV GP and, through stereochemical optimization, identify MWAC-3634. This compound binds GP with high affinity (Kd=40.7 nM), potently neutralizes infection (IC₅₀ = 0.65 nM), shows no detectable cytotoxicity, and exhibits favorable pharmacokinetics in mice. This potency substantially exceeds that of known small-molecule inhibitors targeting EBOV GP. Cryo-EM at 2.54 Å resolution reveals that MWAC-3634 occupies a hydrophobic cavity at the GP subunit interface and stabilizes GP, supporting an entry-blocking mechanism …

Nf1 Loss In Estrogen Receptor-Positive Breast Cancer Induces Osteoclast Formation And Immunosuppression To Promote Bone Metastasis, Matthew J Baik, Yi-Hsuan Wu, Lauren K Somes, Andres F Mosquera Paternina, Omar A Harb, Owen A Chang, Fengshuo Liu, Matthew V Holt, Junkai Wang, Igor Bado, Hai Wang, George Miles, Zbigniew Gugala, Meenakshi Anurag, Ahmed Elkhanany, Yi Li, Valentina Hoyos, Xiang H-F Zhang, Eric C Chang

Faculty, Staff and Students Publications

Estrogen receptor-positive (ER+) breast cancer exhibits a marked propensity for skeletal metastasis; however, the molecular drivers of bone colonization remain incompletely defined. We investigated the tumor suppressor neurofibromin (NF1), a dual repressor for RAS and ER signaling, whose inactivation promotes endocrine therapy (ET) resistance and is associated with inferior relapse-free survival. NF1 copy number loss was detected in 62% of ER+ patients who subsequently developed metastases and was associated with an increased likelihood of bone metastases at initial diagnosis. In mouse xenograft models, NF1-depleted ER+ breast cancer cells demonstrated enhanced dissemination to skeletal sites following surgical resection of primary tumors. …

Responding To Medetomidine In Philadelphia: Narrative Summary Of The Public Health Response To A New Psychoactive Substance, Tareva Warrick-Stone, Serge-Emile Simpson, Phil Durney, Dennis Goodstein, Catherine Abrams, Raymond Bobb, Kory London, Daniel Teixeira Da Silva

Division of Internal Medicine Faculty Papers & Presentations

BACKGROUND: Despite the emergence of medetomidine as the dominant adulterant in Philadelphia's illicit opioid supply, coordinated public health responses are limited or non-existent in the literature. Thus, we summarize a recent Summit in Philadelphia of outpatient and inpatient service providers who specialize in the care of persons who use drugs to discuss medetomidine response readiness and building ongoing community readiness for potential destabilizing drug supply changes.

PURPOSE: Describe a public health intervention that distributed information about practices across health care settings and mobilized key informants to identify and address barriers to treatment.

METHODS: Descriptive summary of the in-person Summit organized …

Predictors Of Complete Obliteration And Favourable Outcome After Single-Modality Treatment For Low-Grade Arteriovenous Malformations: A Multicentre Study, Angelica Fuentes, Salem Tos, Natasha Ironside, Georgios Mantziaris, Yuki Shinya, Basel Musmar, Hamza Adel Salim, Nimer Adeeb, Christopher Ogilvy, Douglas Kondziolka, Ali Alaraj, Min Park, Adam Dmytriw, Hussein Zeineddine, Finn Mccarthy, Hussam Abou-Al-Shaar, Ahmed Abdelsalam, Mustafa Baskaya, Cagdas Ataoglu, Anthony Sanchez-Forteza, Muhammed Amir Essibayi, Abdullah Keles, Sandeep Muram, Howard Riina, Arwin Rezai, Sahin Hanalioglu, Ufuk Erginoglu, Johannes Pöppe, Davide Simonato, Yan-Lin Li, Sandeep Kandregula, Dhairya Lakhani, Christoph Griessenauer, Rahim Abo Kasem, Alejandro Spiotta, Ajit Puri, Jasmeet Singh, Anna Luisa Kuhn, Jan Karl Burkhardt, Robert Starke, Laligam Sekhar, Michael Levitt, David Altschul, Neil Haranhalli, Malia Mcavoy, Paul Foreman, Osama Zaidat, Mohammad Almajali, Hakeem Shakir, Alfred Pokmeng See, Adib Abla, Aashay Patel, Andrew Nguyen, Matthew Koch, Visish Srinivasan, Peng Roc Chen, Spiros Blackburn, Ketan Bulsara, Peter Kan, Louis Kim, Omar Choudhri, Stavropoula Tjoumakaris, Pascal Jabbour, Amey Savardekar, Hugo Cuellar, Michael Lawton, Bharat Guthikonda, Jacques Morcos, Jason Sheehan

Department of Neurology Faculty Papers

INTRODUCTION: Patient and arteriovenous malformation (AVM) characteristics that portend success after treatment for low-grade brain AVMs remain unknown.

PATIENTS AND METHODS: We utilised the MISTA multicentre registry to identify patients with Spetzler-Martin (SM) grade I or II AVMs treated with stand-alone curative-intent intervention (resection, stereotactic radiosurgery [SRS] or endovascular embolisation). Bivariate and multivariable analyses were performed to identify patient and AVM characteristics predictive of complete obliteration or favourable outcome (complete obliteration without new permanent deficit or post-treatment haemorrhage).

RESULTS: A total of 522 patients were included (292 microsurgery, 152 SRS, 78 embolisation). Complete obliteration rates differed between microsurgery (95.9%), SRS …

Variation In Meningioma Recurrence Risk Estimates Across Observational Cohorts: The Influence Of Calendar Time, Who Classifications, Geographical Settings, And Healthcare Systems, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Pedro Góes, Manoel Antonio De Paiva Neto, Ricardo Komotar, Michael E Ivan, Aria Jamshidi, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen, Andrea Daniela Maier

Duncan NRI Faculty and Staff Publications

Purpose: Recurrence risk estimates underpin meningioma research, including molecular classification and clinical trial benchmarking, yet are often based on retrospective or historical data. The aim of this study was to assess the variation of recurrence risk estimates across calendar periods, WHO classification editions, geographical settings, and healthcare systems.thetermine METHODS: We analyzed 4,111 patients with primary WHO-1/-2 meningiomas from 31 centers in 15 countries (1990-2019). Recurrence was defined according to local radiological assessment. The 5- and 10-year recurrence risks were estimated using regression standardization with inverse probability of censoring weights, adjusting for key clinical, surgical, and histopathological variables.

Results: Recurrence risk …

Endothelin Receptor Antagonists In Resistant Hypertension And Proteinuric Kidney Disease: Receptor Strategy And Volume Management, Corey Keith Goldman, Jesse M. Goldman

Division of Nephrology Faculty Papers

This narrative review examines how endothelin receptor antagonists (ERAs) can be used at the intersection of difficult-to-control hypertension, chronic kidney disease (CKD), and albuminuria or proteinuria. For clinicians, the central question is not receptor selectivity alone, but whether a specific agent, indication, dose, background therapy, and monitoring plan can deliver meaningful blood-pressure or kidney benefit without unacceptable fluid retention. Pulmonary arterial hypertension established the pharmacology and major safety liabilities of the class; the current implementation questions for hypertension and kidney specialists arise in systemic hypertension and proteinuric kidney disease. Aprocitentan is the first and only ERA approved for hypertension; in …

Allograft Tendon Pretensioning Technique Guide., Joseph R Brown, Robert W Mendicino

Surgery Articles

In foot and ankle surgery, allograft tendons are frequently used in both primary and revision cases to enhance stability and function. However, postoperative complications, such as creep, can compromise the intended correction and stability over time. This paper presents a practical guide on pretensioning techniques prior to implantation, aiming to reduce creep and improve long-term outcomes. Using two common allograft specimens, we demonstrate pretensioning methods with specific focus on tendon stitching, techniques for securing the allograft to the graft board, optimal tensioning and time parameters. We recommend pretensioning at 80 N for approximately 30 min to effectively decrease creep and …

Heritable Transgenic Schistosomes As A Living Platform For Sars-Cov-2 Neutralizing Antibody Secretion, Wannaporn Ittiprasert, Michael J Smout, Victoria H Mann, Matthew Moyle, Sean M Kinahan, Daniel N Ackerman, Danielle N Rivera, Joshua L Santarpia, Eric C Carnes, Margaret M Mentink-Kane, Marina Reis Costa, Cornelis H Hokke, Meta Roestenberg, Maria Elena Bottazzi, Bethany K Bracken, Bruce A Rosa, Sergej Djuranovic, Darren A Pickering, Paul R Giacomin, Daniel Watterson, Naphak Modhiran, Max F Moescheid, Christoph G Grevelding, Makedonka Mitreva, Alex Loukas, Paul J Brindley

Faculty, Staff and Students Publications

We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring …

Acquisition Of A Gene Cluster In Clostridioides Difficile Pcr Ribotype 023 Strains Enables Xylitol Utilization, Katherine J Wozniak, Lei Pan, Duolong Zhu, Jeroen Corver, Ed J Kuijper, Wiep Klaas Smits, Robert A Britton

Faculty, Staff and Students Publications

Hundreds of ribotypes of the gastrointestinal pathogen Clostridioides difficile have emerged over the last three decades, yet the factors driving their emergence are poorly understood. Recently, there has been an increase in infections caused by PCR ribotype 023 (RT023) strains in Europe. We profiled the growth of seven RT023 strains in 190 unique carbon sources and found they were able to grow in xylitol, a sugar alcohol used as a food additive in humans and animals. Other ribotypes of C. difficile tested (n = 19) displayed little to no growth in 0.5% xylitol and were growth-inhibited in higher …

Valvular Heart Failure Is A Distinct Heart Transplant Phenotype With Comparable Adjusted Survival To Other Heart Failure Etiologies, Devon Kelley, Varun Kathawate, Joyce Ho, Andrew Belec, Takahiro Tashima, Kazuhiro Ueno, Jessica Dominic, Pavan Atluri

Division of Cardiology Faculty Papers

PURPOSE: Valvular heart failure (VHF) accounts for 1-5% of heart transplant listings. Comparative outcomes relative to other heart failure etiologies remain poorly characterized. This study defines the VHF phenotype and compares waitlist and transplant outcomes to other heart failure recipients.

METHODS: This retrospective cohort study uses the UNOS thoracic transplant database to analyze adult, first-time, heart-only listings with a diagnosis of heart disease. Patients were grouped by diagnosis as VHF or non-VHF. The primary outcome was waitlist events; post-transplant survival and outcomes were secondary analyses. Subgroup analysis was performed in the post-2018 allocation era.

RESULTS: VHF recipients were older (55.3 …

Identification Of Potent Inhibitors Of Jun N-Terminal Kinases For Treatment Of Endometriosis And Associated Pain, Kiran L Sharma, Kurt M Bohren, Srinivas Chamakuri, Zian Liao, Feng Li, John M Hakenjos, Jian-Yuan Li, Yuji Mishina, Haichun Pan, Xuan Qin, Matthew B Robers, Banumathi Sankaran, Zhi Tan, Suni Tang, Yasmin M Vasquez, Jennifer Wilkinson, Damian W Young, Stephen S Palmer, Kevin R Mackenzie, Choel Kim, Martin M Matzuk

Faculty, Staff and Students Publications

Endometriosis, defined as the ectopic growth of endometrial tissue outside of the uterine cavity, is an inflammatory and hormone-dependent disease that causes excruciating pelvic pain, infertility, and significantly decreases quality of life in affected patients. The JUN N-terminal kinases (JNKs) are a leading class of nonhormonal therapeutic targets that have been validated in preclinical models of endometriosis and in a Phase 1/2 clinical trial. Despite their therapeutic potential, JNK inhibitors with increased potency and specificity are needed to address the inflammatory pathology of endometriosis and to prevent disease progression. Leveraging a DNA-encoded chemical library collection of ~4 billion compounds, we …

Machine Learning For Functional Outcome Prediction After Vestibular Schwannoma Surgery: A Systematic Review And Diagnostic Test Accuracy Meta-Analysis, Shiva Nischal, Shaan Patel, Musa China, Kush Kale, Yi Hein Chai, Santosh Guru, William Muirhead, Patrick Grover

Department of Neurosurgery Faculty Papers

PURPOSE: Machine learning (ML) models have been increasingly applied to predict postoperative facial nerve dysfunction and hearing preservation after vestibular schwannoma (VS) surgery. However, reported performance varies substantially, and the overall diagnostic accuracy and clinical reliability of these models remain uncertain. We conducted a systematic review and diagnostic test accuracy meta-analysis to characterise the current state and methodological readiness of ML-based prediction of these outcomes.

METHODS: PubMed, Embase, and CENTRAL were searched from inception to February 2026. Studies evaluating ML-based prediction of facial nerve function or hearing preservation following VS surgery were included. Diagnostic performance metrics were pooled using random-effects …

Redo-Transcatheter Aortic Valve Replacement With Self-Expanding Valves: A U.S. Registry Analysis., Toby Rogers, Vinayak N Bapat, Stanley J Chetcuti, Harold L Dauerman, John K Forrest, Sachin S Goel, Kendra J Grubb, Wah Wah Htun, Rishi Puri, Michael J Reardon, Gilbert H L Tang, Amit N Vora, Steven J Yakubov, Ruth Eisenberg, Guilherme F Attizzani

Heart and Vascular Articles

BACKGROUND: Redo-transcatheter aortic valve replacement (TAVR) for failed transcatheter heart valves is expected to increase, but data on outcomes with self-expanding valves remain limited.

OBJECTIVES: The aims of this study were to evaluate procedural, clinical, and quality-of-life outcomes following redo-TAVR using self-expanding Evolut valves and to compare these outcomes with those among a contemporary native TAVR cohort.

METHODS: Outcomes after redo-TAVR with Evolut R, Evolut PRO, and Evolut PRO+ valves in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry were analyzed and compared with outcomes after native-valve TAVR using the same valve platform during the …

Predictors Of Adalimumab Durability In Hidradenitis Suppurativa: A Multicenter Cohort Study, Albert T. Young, Arashleen Pannu, Alexander Velaoras, Roland Leyson, Rayad B. Shams, Alexandra Turfe, Andrea Dai, Mohsen Mokhtari, Sarah Bassett, Joshua Vazhappilly, Richard W. Hass, Iltefat Hamzavi, Christopher J. Sayed, Qing-Sheng Mi, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Adalimumab is widely used for hidradenitis suppurativa (HS), but treatment durability varies and predictors of sustained benefit remain uncertain.

OBJECTIVE: To identify clinical and laboratory factors associated with adalimumab treatment durability in HS.

METHODS: We retrospectively studied 135 adults with HS who initiated adalimumab as first biologic therapy across three academic centers from 2013 to 2023. Outcomes were categorized as primary failure (12-24 weeks), secondary failure (24 weeks-2 years), or sustained response (>2 years) based on discontinuation for inefficacy. Predictors of treatment durability were evaluated using ordinal logistic regression.

RESULTS: In univariable analyses, Hurley stage 3, higher body …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Implementation Readiness For National Cancer Survivorship Care Standards, Christiane J. El Khoury, Meera Gupta, Maryem Shirzadi, Heidi Dowst, Martha Mims, Maysa Abu-Khalaf, Hoda Badr

Kimmel Cancer Center Faculty Papers

IMPORTANCE: Cancer survivorship care is a growing public health priority, yet delivery remains variable across health systems. The National Standards for Cancer Survivorship Care provide a framework for high-quality care, but little empirical evidence exists regarding health system readiness to implement these standards in routine practice.

OBJECTIVE: To assess implementation readiness for the National Standards for Cancer Survivorship Care and identify perceived barriers to implementation.

DESIGN, SETTING, AND PARTICIPANTS: This real-time Delphi survey study was conducted from January to March 2025 at a National Cancer Institute-designated comprehensive cancer center. Participants were multidisciplinary experts involved in cancer survivorship care delivery, care …

Immune Reconstitution And Tolerance-Inducing Therapies As Promising Therapeutic Approaches In Multiple Sclerosis, Alireza Beheshti Maal, Mandana Kazem Arki, Seyed Massood Nabavi, Mostafa Rezaei-Tavirani, Elham Rismani, Massoud Vosough, Gholamreza Azizi, Nikoo Hossein-Khannazer

Department of Neurology Faculty Papers

OBJECTIVES: Multiple sclerosis (MS) is a complex, progressive neurodegenerative autoimmune disease and a major cause of neurological disability worldwide. MS affects approximately 2.8-3 million people, predominantly presenting as relapsing-remitting MS (RRMS) that frequently converts to secondary progressive disease, while effective options for progressive phenotypes remain limited.

METHODS: This review reframes MS immunotherapy through a tolerance-centric paradigm, distinguishing continuous maintenance disease-modifying therapies (DMTs) from immune reconstitution therapies (IRTs) and emerging antigen-specific tolerance strategies.

RESULTS: Classical immune reconstitution therapies, including alemtuzumab, cladribine, and autologous hematopoietic stem cell transplantation (aHSCT), have demonstrated durable disease control and prolonged periods of no evidence of disease …

Digital Markers For Passive Remote Monitoring Of Bipolar Disorder: Systematic Review, Thomas P Kutcher, Isha Chakraborty, Kristin Kostick-Quenet, Akane Sano, Nidal Moukaddam, Jeffrey A Herron, Wayne K Goodman, Sameer A Sheth, Ashutosh Sabharwal, Nicole R Provenza

Duncan NRI Faculty and Staff Publications

Background: Bipolar disorder (BD) features episodic shifts among mania, hypomania, depression, mixed states, and euthymia. Timely detection of mood transitions is difficult due to infrequent clinical touchpoints. Digital health technologies, including wearables and smartphones, offer a unique opportunity to passively and continuously monitor behavior and physiology that could reflect underlying mood dynamics in real-world settings.

Objective: This study aimed to systematically review passively collected digital markers for BD mood states, characterize devices/modalities and analytic approaches, appraise risk of bias, and identify design gaps and priorities for clinical translation.

Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) …