Digital Commons Network^™

Circulating Ketone Bodies And Incident Cardiovascular Outcomes And Mortality: Insights From The Uk Biobank, Parag Anilkumar Chevli, Saeid Mirzai, Richard Kazibwe, Jeff Kingsley, Alexis C Wood, Joseph Yeboah, Leandro Slipczuk, Anurag Mehta, Harpreet S Bhatia, Ambarish Pandey, Michael D Shapiro

Children’s Nutrition Research Center Staff Publications

Background: Ketone bodies (KB) are endogenous energy sources synthesized by the liver in response to metabolic stress. Their associations with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality and their potential beneficial or harmful effects have yet to be determined. This study aimed to examine the association between KB and incident cardiovascular outcomes and mortality in a large general population cohort free from ASCVD and HF at baseline.

Methods: This analysis included 90 987 participants (mean age 56.4 ± 8.1 years; 54.7% women) from the UK Biobank without prevalent ASCVD or HF. KB were measured by nuclear magnetic resonance …

Post-Traumatic Stress Disorder And Risk Of All-Cause And Cause-Specific Mortality: A Nationwide Population And Sibling-Controlled Cohort Study In Taiwan, Chih-Wei Hsu, Yang-Chieh Brian Chen, Liang-Jen Wang, Mu-Hong Chen, Yao-Hsu Yang, Chih-Sung Liang, Edward Chia-Cheng Lai

Children’s Nutrition Research Center Staff Publications

Aims: Post-traumatic stress disorder (PTSD) may shorten life expectancy, but evidence for Asian populations and cause-specific mortality remains limited. The aim of this study is to investigate the association between PTSD and mortality risk in an Asian population.

Methods: We used Taiwan's National Health Insurance Research Database (2000-2022) to assemble a cohort of 28,777 individuals with incident PTSD and 115,108 age- and sex-matched unexposed individuals, plus a sibling cohort of 13,305 affected patients and 22,030 unaffected siblings. Cox models estimated adjusted hazard ratios (AHRs) for all-cause, unnatural-cause (suicide and accidents) and natural-cause mortality, with progressive adjustment for sociodemographic factors, comorbidity …

Single-Layer Spherical (Sls) Vs Single-Layer (Sl) Woven Endobridge (Web) Device In The Treatment Of Narrow-Neck Intracranial Aneurysms: A Propensity Score-Matched Analysis, Hamza Adel Salim, Vivek Yedavalli, Fathi Milhem, Nimer Adeeb, Basel Musmar, Muhammed Amir Essibayi, Motaz Daraghma, Mahmoud Dibas, Nicole M. Cancelliere, Jose Danilo Bengzon Diestro, Oktay Algin, Sherief Ghozy, Sovann V. Lay, Adrien Guenego, Leonardo Renieri, Joseph Carnevale, Guillaume Saliou, Panagiotis Mastorakos, Kareem El Naamani, Eimad Shotar, Markus Möhlenbruch, Michael Kral, Charlotte Chung, Mohamed M. Salem, Ivan Lylyk, Paul M. Foreman, Hamza Shaikh, Vedran Župančić, Muhammad U. Hafeez, Joshua Catapano, Muhammad Waqas, Muhammet Arslan, Onur Ergun, James D. Rabinov, Julian Maingard, Clemens M. Schirmer, Mariangela Piano, Anna L. Kühn, Caterina Michelozzi, Robert M. Starke, Ameer Hassan, Mark Ogilvie, Anh Nguyen, Jesse Jones, Waleed Brinjikji, Marie T. Nawka, Marios Psychogios, Christian Ulfert, Bryan Pukenas, Jan-Karl Burkhardt, Thien Huynh, Juan Carlos Martinez-Gutierrez, Sunil A. Sheth, Diana Slawski, Rabih Tawk, Benjamin Pulli, Boris Lubicz, Pietro Panni, Ajit S. Puri, Guglielmo Pero, Eytan Raz, Christoph J. Griessenauer, Hamed Asadi, Adnan Siddiqui, Elad I. Levy, Neil Haranhalli, David Altschul, Andrew F. Ducruet, Felipe C. Albuquerque, Robert W. Regenhardt, Christopher J. Stapleton, Peter Kan, Vladimir Kalousek, Pedro Lylyk, Srikanth Boddu, Jared Knopman, Stavropoula I. Tjoumakaris, Hugo H. Cuellar-Saenz, Pascal M. Jabbour, Frédéric Clarençon, Nicola Limbucci, Vitor Mendes Pereira, Aman B. Patel, Max Wintermark, Adam A. Dmytriw

Department of Neurosurgery Faculty Papers

Data on the use of Woven EndoBridge (WEB) devices in the treatment of narrow-neck intracranial aneurysms (NNA) are limited. We compared the efficacy and safety of single-layer (SL) and single-layer spherical (SLS) WEB devices in treating NNA. We conducted a multicenter retrospective analysis of adult patients with NNA (neck ≤ 4 mm and width-to-neck ratio ≥ 2) treated with SL or SLS WEB devices between January 2011 and December 2022. Patients with fusiform or blister aneurysms, adjunctive treatments, or devices other than SL or SLS were excluded. Propensity score matching was used to adjust for confounding variables. Outcomes included procedural …

Ten Years Real-World Experience With Sacubitril/Valsartan In Patients With Heart Failure With Reduced Ejection Fraction, Antoni Bayes-Genis, Seok Min Kang, Byung-Su Yoo, Carlos Eid, Biykem Bozkurt, Javed Butler

Faculty, Staff and Students Publications

Introduction: Sacubitril/valsartan (Sac/Val) represents a cornerstone of heart failure (HF) with reduced ejection fraction (HFrEF) management. This systematic review provides a comprehensive overview of real-world evidence (RWE) regarding the implementation, clinical effectiveness, and safety of Sac/Val in patients with HFrEF.

Methods: A systematic literature search of PubMed was conducted through March 2024 following PRISMA guidelines.

Results: The review included 45 manuscripts from 30 different studies, primarily from Europe (44%) and the US (30%). RWE confirmed that Sac/Val was associated with a lower risk of cardiovascular mortality (10%-16%), HF hospitalization (10%-38%), and all-cause mortality (10%-25%). Sac/Val was significantly associated with cardiac …

Influence Of Body Composition On The Efficacy Of Nivolumab Plus Ipilimumab For Metastatic Clear Cell Renal Cell Carcinoma, Kabir Grewal, Maria Julia Moura Nascimento Santos, Pankaj Kumar Chauhan, Kai Yu, Nizar M Tannir, Neha Venkatesh, Amado J Zurita, Andrew C Johns, Matthew T Campbell, Sangeeta Goswami, Jianjun Gao, Eric Jonasch, Jennifer L Mcquade, Omar Alhalabi, Pavlos Msaouel, Andrew W Hahn

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors influence the tumor microenvironment and response to ICI. Although higher body mass index (BMI) has been associated with improved outcomes in several malignancies, BMI is an imprecise surrogate for underlying adipose and muscle compartments. We evaluated the association between body composition and outcomes with 1L nivolumab+ipilimumab in metastatic ccRCC.

Methods: We retrospectively analyzed patients with mccRCC treated with 1L nivolumab+ipilimumab at MD Anderson Cancer Center between June 2015 and …

Proteomic Profiling Of Pulmonary Function And Cardiovascular Disease Risk In The Atherosclerosis Risk In Communities Study, Yura Lee, Astrid M Manuel, Ngoc Quynh H Nguyen, Christine Ladd-Acosta, Alanna C Morrison, Eric Boerwinkle, Zhongming Zhao, Stephanie J London, Bing Yu

Faculty, Staff and Student Publications

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of …

Examining The Relationship Between Academic Excellence And Clinical Productivity In Orthopedic Surgery, Mohamad Y. Fares, Xiaoran Zhang, Harry H. Liu, Ana Paula Beck Da Silva Etges, Krishna Chopra, Brian Zhou, Ira Sivaram, Chrishaun Alexander, Peter Boufadel, Porter Jones, Derek A. Haas, Adam Z. Khan, Eric Wagner, Joseph A. Abboud

Rothman Institute Papers

Background/Objectives: The relationship between clinical volume and academic performance in orthopedic surgery remains understudied. The purpose of this study is to explore the characteristics of high-achieving academic orthopedic surgeons in an attempt to extrapolate patterns and trends that govern the relationship between clinical performance and academia in orthopedic surgery. Methods: The 2023 National Plan and Provider Enumeration System and Medicare claims data (2021–2022) databases were used to include all active orthopedic surgeons of different subspecialties. A publication score, based on publication volume, journal impact, and authorship position, was calculated for each included surgeon, and surgeons who scored in the top …

Depression Due To Combined Dexamethasone And Cyproheptadine Abuse For Weight Gain, Sanjana Sateesh, Jatin Kumar, Dhananjay Ardawatia, Kishor M, Shashidhara Kc, Srikanth Ms

Digital Journal of Clinical Medicine

Cyproheptadine, an H1 antihistamine, and Dexamethasone, a long-acting steroid, are often misused in combination for addressing self-perceived body image issues and have become a popular but dangerous ‘weight gain cocktail’, often available over the counter without any prescription. This case describes a 25-year-old man who had self-prescribed the above-mentioned drugs in combination to address his self-perceived lean physique. This resulted in a significant weight gain, followed by an abnormal increase in appetite, which affected his daily life. Upon cessation, it resulted in rebound weight changes, depressive features, along with features of corticosteroid withdrawal, which required multidisciplinary management.

This case highlights …

Which Repair Technique, Bone Tunneling Or Suture Anchors, Is Superior When Performing Lesser Tuberosity Osteotomy At The Time Of Stemless Total Shoulder Arthroplasty?, Jared M. Mahylis, Stephaine J. Muh, Mahdi Mazeh, Emil Espinal Nunez, Daniel Oravec, Johnny Kasto, Chimdindu Obinero, Kai Zhu, Yener N. Yeni, Shariff K. Bishai

Conference Presentation Abstracts

INTRODUCTION: Total shoulder arthroplasty (TSA) has evolved as a treatment for advanced shoulder osteoarthrosis, with stemless implants gaining popularity due to reduced risks of stress shielding and complications associated with stemmed designs. However, the optimal technique for repairing the subscapularis during TSA remains under investigation. This study evaluates the biomechanical performance of two repair techniques—bone tunneling and suture anchors—used for Lesser Tuberosity Osteotomy (LTO) in the context of stemless TSA.  
METHODS: Ten shoulders from six cadaveric specimens (3 male, 3 female; aged 58–93) were prepared and allocated to bone tunneling or suture anchor repair groups. Cyclic loading tests were performed, …

Comparison Of Integrated 3d Electroanatomic Mapping And Conventional Mapping Systems For Pentaspline Pulsed Field Ablation Of Atrial Fibrillation., Auroa Badin, Andrea K Robinson, Allyson Farrah, Saanvi Billakanty, David M Nemer, Ankur N Shah, Jaret D Tyler, Eugene Y Fu, Nagesh Chopra, Anish K Amin

Heart and Vascular Articles

INTRODUCTION: Pulsed field ablation (PFA) is an established therapy for atrial fibrillation (AF), yet optimal mapping strategies during pentaspline PFA remain uncertain. We compared procedural characteristics and material costs of an integrated 3D electroanatomic mapping (EAM) platform with conventional mapping systems.

METHODS AND RESULTS: In a multicenter observational study of 448 consecutive AF ablations done using pentaspline catheter (62 integrated mapping; 386 conventional mapping) performed between February 2024 and August 2025, baseline characteristics were similar between groups. Compared with conventional mapping, the integrated platform was associated with shorter total procedure time (49 ± 16 vs. 66 ± 26 min, p …

Activin A Secretion By Muscle-Repairing Macrophages Induces Heterotopic Ossification In Mice, Warunee Pluemsakunthai, Takehito Ono, Taku Ito-Kureha, Shizuo Akira, Yoshinobu Hashizume, Roland Baron, Satoshi Ueha, Kouji Matsushima, Martin M Matzuk, Yuji Mishina, Hiroshi Takayanagi

Faculty, Staff and Students Publications

The immune system is not only essential for host defense, but it is also involved in tissue maintenance and disease pathogenesis. Macrophages play a key role in tissue repair, fibrosis, and tumorigenesis, but the mechanisms underlying their multifunctionality have not been fully explored. Here, we identified Mrep (Ly6ChiCX3CR1loPDPN+CD9+) as a crucial subset of macrophages for muscle regeneration after muscle injury. Muscle regeneration required Mrep-derived activin A, which was produced via the TLR4/TIR domain-containing adapter-inducing interferon-β/TANK-binding kinase 1/interferon regulatory factor 3/7 signaling pathway in response to muscle injury. Mrep exerted pathological effects by secreting activin A in a model of genetically …

Medial Meniscus Root Repair Demonstrates Superior Radiographic And Clinical Outcomes At Long-Term Follow-Up Compared To Partial Medial Meniscetomy, Robert Dean, Ryan Mcnassor, Aaron John Krych, Brian R. Waterman

Conference Presentation Abstracts

INTRODUCTION: Posterior medial meniscus root tears (PMMRTs) are frequently observed injuries that lead to alterations in tibiofemoral biomechanics. Few long-term reviews have considered the long term clinical and radiographic outcomes of management of these injuries. This study sought to perform a systematic review and meta-analysis of the current literature on long term clinical and radiographic outcomes of PMMRTs. METHODS: Using PRISMA guidelines, a systematic review was performed with inclusion criteria of English language studies, diagnosis of PMMRT on MRI with confirmation on arthroscopy if managed operatively, studies with minimum 5-year radiographic or patient reported outcome metrics. Data including management strategy, …

Population Analysis And Immunologic Landscape Of Melanoma In People Living With Hiv, Lindsay Barger, Derek Wang, Ashley Saravia, Valeria Mezzano, Gyles Ward, Cynthia Loomis, Carly Feldman, Madalina Tuluc, Rino Seedor, Peter Gaskill, Anna Coghill, Gita Suneja, Iman Dehzangi, Jennifer Hope, George Jour, Gabriele Romano

Department of Medical Oncology Faculty Papers

PURPOSE: To dissect the clinical and immunologic features of people living with human immunodeficiency virus (HIV; PLWH) diagnosed with melanoma, who have consistently shown worse outcomes than HIV-negative individuals (PLw/oH) with the same cancer.

EXPERIMENTAL DESIGN: We analyzed electronic health records from 1,087 PLWH and 394,437 PLw/oH with melanoma. Demographic and clinical characteristics were compared. Spatial immune transcriptomics (72 immune-related genes) was performed on melanoma tumor samples (n = 11), with downstream validation using multiplex immunofluorescence (mIF; n = 15 PLWH, n = 14 PLw/oH).

RESULTS: PLWH were diagnosed at a younger age, had a greater representation of Hispanic and …

Editorial: Clinical Imaging, Neurophysiological, Neuropathology And Neuroethics Studies On Disorders Of Consciousness, Coma Mechanisms, And Theories Of Consciousness: A Unifying Attempt, Diego Iacono, Manuel Trachsel, Thanh Phan, Charlène Aubinet

Department of Neurology Faculty Papers

No abstract provided.

Mechanometabolism Instructs Hematopoietic Stem Cell Specification, Paulina D Horton, Alina Syed, Michelle Winkler, Abishek B Vaidya, Michael Rariden, Yong Zhou, Momoko Yoshimoto, Hyun Jung Lee, Hyun-Eui Kim, John P Hagan, Catherine Denicourt, Travis I Moore, Pamela L Wenzel

Faculty, Staff and Student Publications

Mechanical force generated by blood flow stimulates emergence of the first hematopoietic stem cells (HSCs) that populate the blood system. Force drives the transition of HSC precursors from an endothelial to hematopoietic identity, yet the molecular regulation of this fate switch remains poorly understood. We report that shear stress triggers adaptation in mitochondrial composition, ultrastructure, and function, which are essential for hematopoietic fate and engraftment potential. Shear stress remodels mitochondria in hemogenic endothelium by promoting mitochondrial gene transcription and protein synthesis. Laminar flow selectively initiates translation of 5' terminal polypyrimidine (5'TOP) motif-containing transcripts, which commonly encode ribosome and translation machinery. …

Poly(Adp-Ribose) Glycohydrolase Enforces P21 Degradation Via Deparylation To Promote Gastric Cancer Progression, Yangchan Hu, Qimei Bao, Yixing Huang, Yan Wang, Xin Zhao, Yuxin Meng, Yuancong Li, Zirui Zhuang, Hanyi He, Dan Zu, Yuke Zhong, Chunkai Zhang, Bing Wang, Ran Li, Yanhua He, Qihan Wang, Min Liu, John A Tainer, Yin Shi, Xiangdong Cheng, Ji Jing, Zu Ye

Faculty, Staff and Student Publications

Dysregulation of cell cycle checkpoints is a cancer hallmark, with ubiquitination-controlled protein stability playing a pivotal role. Although p21, a key cyclin-dependent kinase inhibitor, is tightly regulated by ubiquitin-mediated degradation, the key upstream modulators of its ubiquitination remain incompletely defined. Here, we identify poly(ADP-ribose) glycohydrolase (PARG) as a regulator of p21 stability in gastric cancer (GC) cells. We show that PARG expression is markedly upregulated in GC tissues and correlates with poor patient prognosis. Functional assays revealed that genetic depletion of PARG triggers G2/M phase arrest and impairs GC cell proliferation. Mechanistically, we demonstrate that PARG loss enhances p21 PARylation, …

Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage Via Mif-Cd74/Cxcr4 And Interferon Signaling, Sheng Yang, Hang Zhang, Lu-Lu Xu, Luo-Qi Zhou, Yun-Hui Chu, Xiao-Wei Pang, Li-Fang Zhu, Ming-Hao Dong, Ke Shang, Jun Xiao, Long-Jun Wu, Wei Wang, Dai-Shi Tian, Chuan Qin

Faculty, Staff and Student Publications

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells …

The 'Golden Hour': A Geospatial Analysis Of Travel Time To Public Emergency Departments In Kenya, Tushara Surapaneni, Nancy Kinyua, Benjamin Wachira

Emergency Medicine, East Africa

Introduction In Kenya and many other low- and middle-income countries, prehospital care systems are underdeveloped or entirely non-existent, leaving emergency departments (EDs) as the primary point of care for medical emergencies. The aim of this cross-sectional observational study was to use a geographic information system (GIS) to comprehensively analyse access to public EDs in Kenya within 1-hour and 2-hour travel times.

Methods Using open-source GIS software, population, land cover, elevation and road network data were analysed to create maps of 1-hour and 2-hour travel time catchment areas around public EDs in Kenya. Travel time analysis was calculated using AccessMod with …

Pharmacokinetic Profiles Of Sertraline In Pregnancy As A Predictor Of Postpartum Depressive Symptoms, Sílvia M. Illamola, Zachary N. Stowe, Marc L. Kalin, Michael D. Evans, Catherine M.T. Sherwin, Maged M. Costantine, D. Jeffrey Newport, James C. Ritchie, Angela K. Birnbaum

Pediatrics Faculty Publications

Aim: To characterize pharmacokinetic changes of sertraline and its metabolite during pregnancy and postpartum, and their relationship to maternal postpartum depressive symptoms. Methods: This was a prospective observational, longitudinal study of pregnant women with a major depressive disorder treated with sertraline (N = 185 women, 205 pregnancies). Women were enrolled at <16 weeks' gestation and followed at 4-8 week intervals throughout pregnancy and the first postpartum year. Baseline measures included structured clinical interviews and demographic information. Drug and metabolite concentrations and psychometric measures (study outcomes) (ie, Hamilton Rating Scale for depression - 17 item, Beck Depression Inventory, Edinburgh Postnatal Depression Scale [EPDS], Clinical Global Impression [CGI]) were measured at follow-up visits. Serum sertraline and N-desmethylsertraline exposure were reported asstandardized 24-h concentration-to-dose (C/D) and parent to metabolite (P/M) ratios. Linear mixed-effects and latent trajectory models were used to characterize longitudinal patterns in concentration measures across pregnancy and postpartum, and their association with study outcomes. Results: Mean 24-h C/D ratios showed high variability throughout pregnancy and postpartuM.T.hat were characterized by three trajectories for sertraline and five for N-desmethylsertraline and P/M ratio corresponding to different sertraline pharmacokinetic profiles. At postpartum, sertraline drug exposure was inversely associated with higher EPDS score (P < .05), while N-desmethylsertraline exposure was associated with higher scores for all measured depression scales (P < .001). Higher P/M ratios had higher CGI scores (P < .05) postpartum. Conclusion: Sertraline pharmacokinetic profiles varied across pregnant women and were associated with postpartum depressive symptoms. The use of therapeutic monitoring may provide clinical insight that can be useful for identifying patients with a potential toward depressive symptoms.

Early Insights From A Multi-Centre National Stroke Surveillance Initiative In Tanzania, Sarah Shali Matuja, Azan Nyundo, Emmanuel Assey, Joel Bwelemo, Marieke Dekker, Sarah Urasa, Emanuel Makarius, Peter Kishimbo, Philip Adebayo, Paschal Ruggajo

Internal Medicine, East Africa

Background: Stroke is a leading cause of death and disability globally, with sub-Saharan Africa, bearing the greatest burden. Tanzania has only one active stroke registry, limiting evidence-based care and policy development. We aimed to expand the registry into a multi-centre study across eight major tertiary hospitals to generate baseline data for a national stroke registry.

Methods: From January to August 2024, we analysed de-identified data from adults (≥18 years) admitted with a World Health Organisation defined stroke. Data collected included demographics, risk factors, imaging, and in-hospital mortality. Logistic regression identified predictors of mortality.

Results: A total of 1000 patients were …

Disseminated Iatrogenic Upper Gastrointestinal Kaposi Sarcoma Following Prolonged Steroid Use In A Patients With Crohn's Disease: A Case Report, Glory Makupa, Furaha Serventi, Leila Mwakipunda, Godwin Nnko, Edwin Liwa, Salum Lidenge, Ayesiga Herman, Lilian Gasper, Amos Mwasamwaja, Beatrice Kombole

Internal Medicine, East Africa

Background Kaposi sarcoma is a malignant vascular neoplasm caused by human herpesvirus-8. It is mostly seen in immunocompromised individuals, particularly those with human immunodeficiency virus/acquired immunodeficiency syndrome or organ transplants. Cutaneous and mucosal Kaposi sarcoma manifestation is common; however, Kaposi sarcoma may involve the visceral organs. Iatrogenic or drug-induced Kaposi sarcoma may develop in immunocompromised patients undergoing immunosuppressive medication. It is quite uncommon for patients with inflammatory bowel diseases on immunosuppressive medication to develop intestinal Kaposi sarcoma. This case report describes the clinical presentation of steroid-induced disseminated upper gastrointestinal Kaposi sarcoma in a patient with underlying Crohn’s disease and examines …

Did A.T. Still, Do, Have An Md Degree?, David B. Fuller

PCOM Scholarly Works

A.T. Still, DO (1828–1917), founder of osteopathic medicine, was a licensed physician practicing in late 19th- and early 20th-century America. Although many assume he held an MD degree, the reality is more complex. Examining whether Dr. Still earned an MD degree provides important insight into the origins of osteopathic medicine and the profession that followed.

The Emerging Role Of Tertiary Lymphoid Structures As Predictive And Prognostic Biomarkers Of Immunotherapy In Cancer, Lidia B. Medhin, Rodas Amanuel, Lydia Warburton, Leslie Calapre, Benhur Amanuel, Elin S. Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes across several cancers, yet many patients do not respond, highlighting the need for robust predictive biomarkers. Tertiary lymphoid structures (TLS), ectopic lymphoid aggregates that support local antigen presentation and adaptive immune activation, have emerged as potential indicators of favourable prognosis and immunotherapy responsiveness. Methods: This review summarises current clinical and translational evidence examining the prognostic and predictive value of TLS in solid malignancies. Studies assessing TLS presence, organisation, and biological function were identified through searches of major scientific databases and evaluated with respect to their association with patient outcomes and responses to …

Skeletal Muscle Health In Childhood Cancer Survivors: A Systematic Review And Meta-Analysis, Anna Maria Markarian, Dennis R. Taaffe, Daniel A. Galvão, Carolyn J. Peddle-Mcintyre, Jodie Cochrane Wilkie, Francesco Bettariga, Nicholas G. Gottardo, Mayank Dhamija, Santosh Valvi, Catriona M. Buchanan, Kerrie Graham, Robert U. Newton

Research outputs 2022 to 2026

Purpose: Childhood cancer survivors (CCS) are at risk of long-term skeletal muscle deficits following intensive therapies during critical periods of growth. This review aimed to synthesize approaches for assessing muscle quantity, quality, and function in CCS and to quantify deficits relative to healthy peers. Methods: A systematic search was conducted in CINAHL, Embase, PubMed, SPORTDiscus, and Web of Science from inception to June 2024, with an update in November 2025. Studies including CCS who had completed cancer treatment and reported measures of muscle quantity, quality, or physical function were eligible. A three-level mixed-effects model meta-analysis was conducted. Associations between muscle …

Vibostolimab Coformulated With Pembrolizumab Versus Pembrolizumab Alone As Adjuvant Therapy For High-Risk Stage Iib–Iv Melanoma (Keyvibe-010): A Randomised, Double-Blind, Phase 3 Study, Reinhard Dummer, Jun Guo, Jason J. Luke, Matteo S. Carlino, Dirk Schadendorf, Muhammad A. Khattak, Axel Hauschild, Paolo A. Ascierto, Yu Chen, Sang Joon Shin, Piotr Rutkowski, Zhiguo Luo, Jing Chen, Gareth Rivalland, Corlia Coetzee, Antoni Ribas, Karmele Mujika, Gal Markel, Rodrigo U. Villarroel, Omer Dizdar, Christian Caglevic, Dmitri Grebennik, Kevin Donovan, Clemens Krepler, Georgina V. Long

Research outputs 2022 to 2026

Background Combination therapy with vibostolimab plus pembrolizumab has previously shown promising antitumor activity in melanoma. We aimed to evaluate the efficacy and safety of vibostolimab coformulated with pembrolizumab as adjuvant therapy for high-risk resected melanoma. Methods This randomised, double-blind, phase 3 study was done at 205 global sites (hospitals and cancer centres). Participants aged 12 years or older with surgically resected, stage IIB–IV cutaneous melanoma per the American Joint Committee on Cancer Cancer Staging Manual 2017 (8th edition), with no evidence of metastatic disease after resection, were randomly assigned (1:1) to receive vibostolimab 200 mg coformulated with pembrolizumab 200 mg …

Transcatheter Aortic Valve Replacement In Systemic Sclerosis: A Case Series And Review Of Short- And Long-Term Outcomes, Chris T. Derk, Ahmadreza Badali, Esra Mehmetoglu, Anvitha Mummadisetty, Amit Syal, Konstantinos Parperis

Student Papers, Posters & Projects

Objectives: A higher frequency of valvular heart disease is seen among Systemic Sclerosis (SSc) patients. Advanced aortic valve stenosis leads to significant morbidity in these patients with multiple other comorbidities. In this study, we aim to define the short- and long-term outcomes of transcatheter aortic valve replacement (TAVR) procedures in SSc patients. Methods: We undertook a retrospective chart review of all patients with SSc who underwent a TAVR procedure at our institution over a defined 11-year period. Demographics as well as short- and long-term outcomes were identified. Results: Fourteen SSc patients underwent a TAVR procedure between 2012 and 2023. They …

Evaluation Of Pulse Oximetry Alarm Fatigue And The Impact Of Spo2 Thresholds On Clinical Workflow: A Prospective Observational Study In A Kenyan Neonatal Unit, Bazil Masabo, Augustine Waswa, Jesse Coleman, Morris Ogero, Grace Irimu, Dorothy Chomba, Millicent Parsimei, Cynthia Shitote, Ferdinand Okwaro, William Macharia

Paediatrics and Child Health, East Africa

Introduction: Effective pulse oximetry monitoring in a newborn unit requires clinician action. However, if thresholds are not adapted to each neonate, frequent alarms cause alarm fatigue, which impacts the quality of patient monitoring, staff workload and clinical workflow.

Methods: We conducted an observational study from October 2021 to December 2022 in a Kenyan newborn unit which enrolled neonates through convenience sampling. Data were analysed in R using default thresholds of 85% to 96% for SpO2 and 90 to 200 bpm for PR.

Results: Among the 49 neonates enrolled, median hourly alarms per patient were 12 visual and …

Defining The Society Of Pediatric Liver Transplantation (Split) Research Agenda: A Delphi Consensus Project., Sharad I. Wadhwani, Pooja Reddy Spector, Amy G. Feldman, Katryn N. Furuya, Kayla Hartjes, Chaowapong Jarasvaraparn, Beau Kelly, Stacee M. Lerret, Krupa Mysore, Arti Pawaria, Philip Rosenthal, Amy Shui, Voytek Slowik, Sarah Taylor, Jennifer Vittorio, Pamela L. Valentino, Society Of Pediatric Liver Transplantation (Split)

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite major advances in surgical and medical management, only one-third of pediatric liver transplant (LT) recipients remain morbidity-free at 10 years. The Society of Pediatric Liver Transplantation (SPLIT) published a research agenda over 10 years ago, and much progress has been made since then. An updated consensus-driven SPLIT research agenda could guide future research and funding priorities. We aimed to identify and prioritize key research needs across the continuum of pediatric LT care using a modified Delphi consensus approach.

METHODS: We conducted a three-round modified Delphi process among SPLIT members. In round 1, participants submitted open-ended research priorities. In …

Pharmacogenetics Of Cyp3a5 In Pediatric Patients With Eosinophilic Esophagitis., Janelle R. Noel-Macdonnell Phd, Norah Almahbub, Erin C. Boone, Wendy Y. Wang, Dilyara Cheranova, Lisa Harvey, Valentina Shakhnovich, Rachel Chevalier

Manuscripts, Articles, Book Chapters and Other Papers

Eosinophilic esophagitis (EoE) is an atopic inflammatory disease with limited treatment options. Though swallowed topical steroids are commonly used, they are not effective in all patients. We investigated the presence of CYP3A4/5 and ABCB1 (P-glycoprotein) mRNA in esophageal tissue and its differential expression by genotype in pediatric patients. Esophageal tissue biopsies were obtained from pediatric patients undergoing standard of care endoscopy. Levels of CYP3A4, CYP3A5, and ABCB1 mRNA were measured using droplet digital PCR and compared across patients with and without EoE. Genotypes for common, clinically relevant CYP3A5 variants were evaluated in a cohort of individuals with and without EoE. …

Complications Leading To Reoperation After Pediatric Tibial Spine Fracture Fixation., Benjamin R. Caruso, Suzanna M. Ohlsen, Keinan Agonias, Robert L. Van Pelt, Michelle M. Son, Michael G. Saper, Jason Rhodes, J Marc Cardelia, Jay C. Albright, Shital N. Parikh, Kevin G. Shea, Henry B. Ellis, Philip L. Wilson, Members Of The Score Quality Improvement Registry, Sheila Algan, Jennifer J. Beck, Richard E. Bowen, Jennifer M. Brey, Matthew J. Brown, Christian Clark, Allison Crepeau, Eric W. Edmonds, Matthew Ellington, Peter D. Fabricant, Jeremy Frank, Theodore J. Ganley, Daniel W. Green, Benton Heyworth, Ryan Koehler, Alfred A. Mansour, Stephanine Mayer, Scott D. Mckay, Molly C. Meadows, Matthew Milewski, Emily L. Niu, Donna M. Pacicca, Stephanie S. Pearce, Matthew R. Schmitz, Stephen Storer, Curtis Vandenberg, Yi-Meng Yen, Gregory A. Schmale

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tibial spine fractures (TSFs) are uncommon injuries in pediatric patients, often requiring operative fixation. While complications such as arthrofibrosis and anterior cruciate ligament (ACL) insufficiency have been previously reported, the risk factors associated with unplanned reoperation remain incompletely understood.

PURPOSE: To identify the most common complications leading to reoperation and to evaluate associated risk factors, using a multicenter quality improvement registry.

STUDY DESIGN: Case-control study; Level of evidence, 3.

METHODS: A multicenter registry of operatively treated pediatric TSFs was retrospectively reviewed from July 2018 to March 2025 across 27 institutions. Grade 3 complications were defined as complications resulting in …