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Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan Mcreynolds, Yuzhou Chang, Fangfang Qi, William Tauer, Cassandra Rosenberg, Melissa Wren, Tadafumi C Ikezu, Yuka A Martens, Minghui Wang, Bin Zhang, Gregory W Carter, Michael Sasner, David M Holtzman, Junmin Peng, Long-Jun Wu, Takahisa Kanekiyo, Chia-Chen Liu, Guojun Bu

The Brown Foundation: Institute of Molecular Medicine

Background

Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms.

Methods

We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …

Synthetic Lethality Between Rb-Loss And E2f3 Inhibition In Small Cell Cancers Targeted By Pyrimidine Synthesis Blockade, Evan R. Abt, Liang Wang, Grigor Varuzhanyan, Jack Freeland, Tian He, Guadalupe M. Peña-Garcia, Lauryn Ruegg, Jami Mclaughlin, Donghui Cheng, Nikolas G. Balanis, Chia-Chun Chen, Yang Xu, Yi Xing, Sanaz Memarzadeh, Caius G. Radu, Thomas G. Graeber, Owen N. Witte

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Small cell carcinoma is a highly lethal cancer variant often found with neuroendocrine (NE) features, as exemplified by small cell lung cancer and small cell NE prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3. E2F3 dependency is linked to RB inactivation, a near universal occurrence across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung, and adnexa. In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of …

Cystic Fibrosis And Sickle Cell Disease Associated With Nonadministration Of Vte Prophylaxis In Hospitalized Adults, Kiera Caparon, Matthew J. Lankiewicz, Jessica Crow, Jennifer C. Yui, John Lindsley, Brandyn D. Lau, Michael B. Streiff, Rakhi P. Naik, Sophie Lanzkron, Lydia H. Pecker, Peggy Kraus, Elliott R. Haut, Jiangxia Wang, Kathryn E. Dane

Cardeza Foundation for Hematologic Research

Cystic fibrosis (CF) and sickle cell disease (SCD) are associated with an increased risk of venous thromboembolism (VTE), and this risk is exacerbated by hospitalization. VTE prophylaxis nonadministration is a VTE risk factor. The objective of this study was to characterize VTE prophylaxis nonadministration among patients with either CF or SCD compared with medically ill patients without CF or SCD. We conducted a single-center retrospective cohort study of hospitalized patients who were prescribed at least 2 doses of pharmacologic VTE prophylaxis. The primary outcome was the proportion of nonadministered VTE prophylaxis doses by cohort. Multivariable logistic regression was used to …

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

Associations Between Reported Use Of Nutritional Labels And Calorie Intake In Us Adults: Findings From Nhanes 2017–2020, Ariana M. Chao, Nancy Greene, Alexandra Paul, Paule V. Joseph

College of Nursing Faculty Papers & Presentations

Objective: Caloric information is commonly displayed on nutritional fact labels and food menus. Yet evidence is limited on whether label use is associated with a reduced-calorie diet. This study examined the associations between the use of caloric information on nutritional facts and menu labels and daily caloric intake. Methods: We used data from adults in the National Health and Nutrition Examination Survey (NHANES) 2017–2020 to conduct a cross-sectional study. Calorie label use on nutritional labels and menus was assessed using the Flexible Consumer Behavior Survey telephone interview. Caloric intake was evaluated using the mean of two 24-h diet recalls implemented …

Therapeutic Plasma Exchange For Uncontrollable Bleeding After Platelet Inhibition With Ticagrelor: A Report Of 2 Cases, Amanda Herrmann, Brenda Mai, Yu Bai, Brian Castillo, Biswajit Kar, Kimberly Klein, Ismael A Salas De Armas, Eric Salazar, Hlaing Tint, Igor D Gregoric

Faculty, Staff and Student Publications

Case series

Patients: Male, 52-year-old Male, 66-year-old

Final Diagnosis: Uncontrolled bleeding following ticagrelor associated with cardiac surgery

Symptoms: Bleeding

Clinical Procedure: —

Specialty: Cardiology Critical Care Medicine Pathology

Objective: Unusual clinical course

Background

Acute coronary syndrome is the most common cause of death in the United States. Successful intervention often requires a multi-therapeutic approach, including percutaneous coronary intervention (PCI) and antiplatelet agents such as ticagrelor. However, the use of antiplatelet agents can cause life-threatening bleeding, particularly during emergency procedures. Therapeutic plasma exchange (TPE) is a procedure that selectively removes the patient’s plasma to eliminate harmful substances. Here, we present 2 …

Photobiomodulation In Treatment Of Head And Neck Cancer-Related Chronic Lymphedema: A Pilot Randomized Controlled Trial, Jie Deng, John N. Lukens, Barbara A. Murphy, Erin Mcmenamin, Karthik Rajasekaran, Ryan J. Quinn, Joy C. Cohn, Wendy Schlessinger, Lucy P. Andersen, Bryan A. Spinelli, Alexander Lin

Department of Physical Therapy Faculty Papers

BACKGROUND: Chronic lymphedema is a common late effect after completion of head and neck cancer (HNC) treatment, contributing to substantial symptom burden and negatively impacting quality of life. No effective approaches are available to treat this progressive condition. This study aimed to evaluate the preliminary efficacy of photobiomodulation (PBM) therapy for chronic lymphedema in HNC survivors.

METHODS: This was a pilot, randomized, wait-list controlled trial. Eligible HNC survivors included those with chronic lymphedema after completion of complete decongestive therapy. Participants were randomized (1:1) to 1 of 2 arms: intervention group (active) or wait-list control group (control). The active group received …

Targeting Cardiomyocyte-Derived Extracellular Vesicle Mir-574-5p Protects Against Cognitive Impairment Induced By Ischemia-Reperfusion, Erya Chen, Xiaoyu Zhu, Haiqing Chang, Qi Li, Zhenkun Zhao, Changteng Zhang, Yu Cao, Yajing Wang, Xinliang Ma, Tao Zhu, Shu Zhang, Lu Gan, Jin Liu, Chan Chen

Department of Emergency Medicine Faculty Papers

BACKGROUND:  Acute myocardial ischemia/reperfusion (MI/R) increases risk for cognitive decline, yet the underlying mechanisms mediating heart-brain communication remain poorly understood. Small extracellular vesicles (sEVs) have emerged as novel long-range signaling mediators and may play a critical role.

METHODS: MI/R was induced by transient ligation of the left anterior descending artery. Cognitive performance was assessed using multiple behavioral tests. sEVs derived from cardiomyocytes were labeled to track their distribution and cellular uptake in the brain. Heart and brain tissues were analyzed for microRNAs (miRNAs) expression using bioinformatics, qPCR, and RNAScope. The role of specific miRNAs was investigated through genetic inhibition of …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Patient Perceptions And Knowledge Of Corticosteroid Injections: A Cross-Sectional Survey Study, Juliet Chung, Sina Ramtin, Philip Koehler, Stephen Stache, Charles Langman, Bryan Hozack, Asif M. Ilyas

Rothman Institute Papers

INTRODUCTION: Although cortisone injections are commonly used, patient understanding of cortisone is variable and often affected by misconceptions. This study explores patient perspectives, identifies misconceptions, and emphasizes the importance of improved patient education to enhance patient-centered care.

METHODS: A cross-sectional survey study was conducted from April to August 2024 among patients aged 18 and older presenting to an orthopedic physicians' office. Patients completed a novel anonymous questionnaire designed to assess their knowledge and perceptions of cortisone injections. A total of 246 patients participated, with responses collected electronically via SurveyMonkey.

RESULTS: Among 246 respondents, individuals with history of prior cortisone infections …

Impact Of Long-Term Nitrogen Scavenger Therapy On Clinical Outcome In Individuals With Urea Cycle Disorders, Roland Posset, Friederike Epp, Sven F Garbade, Florian Gleich, Andrea L Gropman, Sandesh C S Nagamani, Georg F Hoffmann, Stefan Kölker, Matthias Zielonka

Faculty, Staff and Students Publications

Principles of long-term medical management in individuals with urea cycle disorders (UCDs) encompass (1) a low protein diet, (2) supplementation of arginine and/or citrulline along with essential amino acids, nutrients, vitamins and trace elements, and (3) use of nitrogen scavenging agents to reduce recurrent hyperammonemic events (HAEs). These principles aim at providing metabolic stability, elimimation of chronic complications, and achievement of normal development as well as growth. A retrospective comparative analysis was performed by studying 138 individuals with male ornithine transcarbamylase deficiency (mOTC-D), citrullinemia type 1 (CTLN1) and argininosuccinic aciduria (ASA) based on in vitro residual enzymatic activity for severity-adjustment. …

Development And Validation Of The Emergency Department Transitions Measure, Sara Beachy, Danielle M. Mccarthy, Julianna Lenoir, Alexzandra Gentsch, Richard W. Hass, Marissa Witmer, Paula Ostroff, Melissa Tupas, Lindsey Shughart, Hailey Shughart, Kristin L. Rising

Jefferson Center for Connected Care Faculty Papers

BACKGROUND: Transitions of care are high-risk periods for patient safety in the emergency department (ED), particularly for patients who are still in the diagnostic process and are discharged with diagnostic uncertainty. Care transitions must be improved for these patients, as one third of discharged ED patients have diagnostic uncertainty. Yet there are no validated measures that assess the quality of care transitions from the ED, limiting the ability to assess the impact of interventions. Thus, we developed and validated the ED Transitions (EDT) measure.

METHODS: This mixed methods study was conducted across a large healthcare system in three phases: item …

Fungal Meningitis In Us Patients Who Received Epidural Anesthesia In Matamoros, Mexico, Dallas J Smith, Elizabeth Misas, Jeremy A W Gold, Nicole Evert, Thi Dang, Emilie Prot, Simone Godwin, Julieanna Rivas, Jessica Pearson, Lori Koenecke, Nirma D Bustamante, Maria Julia Marinissen, Gabriel Garcia Rodriquez, Irma López-Martínez, Caitlyn Lutfy, Samantha Williams, Axel A Vazquez Deida, Katrina M Byrd, Julian A Villalba, Sarah Reagan-Steiner, Lindsay Parnell, Lalitha Gade, Romney M Humphries, Nathan P Wiederhold, Charles Y Chiu, Joshua A Lieberman, Anastasia P Litvintseva, Tom Chiller, Luis Ostrosky-Zeichner, Fungal Meningitis Response Team

Faculty, Staff and Student Publications

Background: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in US patients who received epidural anesthesia in Matamoros, Mexico.

Methods: Early epidemiological information suggested US patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in 2 Matamoros clinics. US patients known to have received surgery at these clinics during 1 January-13 May 2023 (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, …

Factors Associated With Telemedicine Use By Cardiologists For Medicare Beneficiaries In 2022 To 2023: An Observational Study, Samantha Harris, R J Waken, Fengxian Wang, Khavya C Avula, Rishi K Wadhera, Jose F Figueroa, E John Orav, Uchenna Ofoma, Karen E Joynt Maddox

2020-Current year OA Pubs

BACKGROUND: During the COVID-19 pandemic, the Centers for Medicare and Medicaid Services created a waiver to reimburse telemedicine services. It is important to understand factors that facilitate incorporation of telemedicine into ongoing cardiovascular practice.

METHODS: This was a retrospective cohort study of telemedicine and office visits delivered by cardiologists between January 1, 2022, and December 31, 2023, for Medicare beneficiaries. We calculated the adjusted incidence rate ratio (aIRR) of telemedicine visits, representing the proportion of a physician's visits delivered by telemedicine, to identify factors associated with telemedicine use.

RESULTS: There were 23 334 physicians in our cohort; they were predominantly …

High Dietary Fiber Is Associated With Improved Outcomes In Patients With Melanoma And Sarcoma Treated With Immunotherapy Regardless Of Gut Microbiome Dysbiosis And Social Vulnerability, Brittany C Fields, Raymond S Traweek, Kai Jiang, Russell G Witt, Ashish Damania, Yi-Ju Chiang, Nadim Ajami, Elise Nassif-Haddad, Emily Z Keung, Manoj Chelvanambi, Xiaotao Zhang, Christine B Peterson, Jennifer A Wargo, Carrie R Daniel, Christina L Roland, Ashley M Holder

Faculty, Staff and Student Publications

Background: Social vulnerability, dietary fiber, and the gut microbiome have been individually implicated in clinical outcomes for melanoma and sarcoma patients. This study hypothesized that increasing social vulnerability is associated with insufficient dietary fiber intake and negatively associated with microbiome composition and clinical outcomes.

Methods: Clinicopathologic data, baseline fiber intake, and gut microbiome profiles were assessed in 153 patients with melanoma or sarcoma treated with immune checkpoint blockade (ICB) and prospectively followed. Patients' social vulnerability index (SVI) and fiber intake were evaluated for associations with microbiome composition, treatment response, and overall survival (OS).

Results: SVI percentile was 0.4 (interquartile ratio …

Radiation Doses To Cardiac Substructures Predict Elevation In High-Sensitivity Cardiac Troponin T Levels In Radiation Therapy For Lung Cancer, Xinru Chen, Xiaodong Zhang, Ting Xu, Radhe Mohan, Ruitao Lin, Mei Chen, Rachel C Maguire, Yao Zhao, Efstratios Koutroumpakis, Nicolas L Palaskas, Anita Deswal, Ali Ajdari, Joshua S Niedzielski, Sanjay S Shete, Laurence E Court, Jinzhong Yang, Zhongxing Liao

Faculty, Staff and Student Publications

Purpose: Cardiotoxicity is a major concern for patients undergoing thoracic radiation therapy. This study compared the predictive power of radiation dose-volume histogram (DVH) parameters and radiomic/dosiomic features of the whole heart (WH) and cardiac substructures for elevated circulating high-sensitivity cardiac troponin T (hs-cTnT), a biomarker for early detection of cardiac adverse events.

Methods and materials: A retrospective cohort of 160 patients with non-small cell lung cancer (NSCLC) from a completed prospective trial and a prospective cohort of 57 patients with NSCLC enrolled in an ongoing trial were analyzed. The endpoint was hs-cTnT elevation, indicated by an increase of ≥5 ng/L …

Pimicotinib Versus Placebo For Tenosynovial Giant Cell Tumour (Maneuver): An International, Randomised, Placebo-Controlled, Phase 3 Trial, Hairong Xu, Xiaohui Niu, Vinod Ravi, Javier Martin-Broto, Albiruni Abdul Razak, Ramy Saleh, Yong Zhou, Jingnan Shen, Tang Liu, Kamlesh Kumar Sankhala, César Serrano, Silvia Stacchiotti, Jing Wang, Giacomo G Baldi, Yi Feng, Yingqi Hua, Tao Li, Piotr Rutkowski, Xiaojing Zhang, Gabriel Tinoco, Qingping Zou, Boyao Shan, Xiangyu Zhu, Hans Gelderblom

Faculty, Staff and Student Publications

Background: Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods: MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 …

Gastrointestinal Symptoms After Sport-Related Concussion In Irish Athletes, Emma Finnegan, Ed Daly, Katherine Hunzinger, Lisa Ryan

Department of Exercise Science Faculty Papers

Background/Objectives: Sport-related concussion (SRC) elicits multi-systemic symptoms, including nausea, fatigue, and cognitive changes. Gastrointestinal (GI) symptoms are not well captured in current concussion assessments and may be under-recognised in clinical follow-up. GI disturbances may influence intake tolerance and day-to-day fuelling during post-SRC recovery. This study investigated the prevalence and severity of self-reported GI symptoms in Irish athletes after their most recent SRC, examined sex-based patterns, and evaluated the rationale for integrating GI symptom checks into standard concussion tools (e.g., SCAT6) and post-injury monitoring. Methods: An online survey was completed by recreational, competitive, and elite athletes who retrospectively self-reported concussion history, …

Cannabis Stigma And Symptom Management Considerations In Cancer Survivors: A Mixed-Methods Exploration Of Patient Perspectives, Sera Levy, Salimah Meghani, Brooke Worster, Colleen Kilanowski, Danielle Smith, Amy A. Case, Rebecca L. Ashare

Department of Medical Oncology Faculty Papers

PURPOSE: This study aims to assess for indications of stigma and attitudes toward cannabis among cancer survivors (CS) who use or consider the use of cannabis.

METHODS: This study employed a convergent, parallel mixed methods design utilizing focus group and questionnaire data to assess the presence of stigma among a sample of CS (n = 23) who use (n = 10) and do not use (n = 13) cannabis to manage symptoms. CS were recruited from a multi-site observational study in the Northeast U.S. region that assesses cannabis use among oncology patients.

RESULTS: A total of 23 CS participated in …

Glycative Stress Disrupts The Mitochondrial-Lysosome Axis And Promotes Geroconversion In Aging Cardiomyocytes, Diana Bou-Teen, Simonas Valiuska, Elisabet Miro-Casas, Chiara Rubeo, Elena Bonzon-Kulichenko, Zuzana Nichtova, Celia Fernandez-Sanz, Javier Inserte, Antonio Rodriguez-Sinovas, Begoña Benito, Eduard Ródenas-Alesina, Jesús Vázquez, Ignacio Ferreira-González, Marisol Ruiz-Meana

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Aging is a major risk factor for heart failure, yet the molecular mechanisms linking cardiac aging to the inflammatory pathophysiology of heart failure remain elusive. Mitochondrial dysfunction and defective organelle quality control are emerging hallmarks of the aging heart, but their biochemical underpinnings are poorly defined. Using comprehensive glycomics, we found that cardiac mitochondria from physiologically aged mice (≥ 20 months) are the major intracellular reservoirs of advanced glycation end products (AGEs), derived primarily from the chemical attack of some α-oxoaldehydes on proteins. This was associated with mild mitochondrial dysfunction and structural remodeling. Lysosomes in aged hearts were enlarged, more …

Gut Microbiota Modulation Via Repeated Donor Fecal Transplantation Improves Motor And Gastrointestinal Symptoms In Drug-Naïve Parkinson’S Disease: A Randomized Phase 2 Trial, Rui Zhang, Renyi Feng, Jiuqi Wang, Yongkang Chen, Han Liu, Qingyong Zhu, Haiyan Tian, Chi Qin, Junfang Teng, Beisha Tang, Min Wu, Jinsheng Zeng, Erxi Wu, Xuebing Ding, Xuejing Wang

Faculty, Staff and Students Publications

The gut-brain axis is increasingly recognized as a critical contributor to Parkinson's disease (PD) pathogenesis, yet the therapeutic impact of microbiota modulation remains unclear due to lack of clinical trials in drug-naïve patients. We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety, tolerability, and efficacy of repeated donor fecal microbiota transplantation (dFMT) in de novo PD. FMT was administered for seven days (200 mL on days 1-3; 50 mL on days 4-7) per 4-week cycle. Seventy-two patients were randomized 1:1 to receive dFMT or autologous FMT (aFMT), and 66 completed the trial. At 35 weeks, the …

Virtual Reality For The Management Of Postoperative Pain And Anxiety In Children And Adolescents Undergoing Nuss Repair Of Pectus Excavatum: Randomized Controlled Trial, Charlotte M. Walter, Dillon Froass, Nora Bell, Lauren Haack, Chloe Boehmer, Claudia Bruguera Torres, Rachel Spivak, Max Chou, Kristie Geisler, Keith O'Conor, Sara E. Williams, Lili Ding, Christopher D. King, Vanessa A. Olbrecht

Department of Medicine Faculty Papers

BACKGROUND: Virtual reality (VR) is a novel technology with implications for pain and sensory processing. VR may serve as a novel, scalable method to deliver clinically validated therapy for pain management as an alternative or adjunct to opioids for acute pain. Given that psychological factors and pain perception are both components of postoperative pain, it may also be beneficial to incorporate modalities that decrease anxiety, such as active relaxation and guided meditation with VR. Unfortunately, these therapies are not widely available due to multiple barriers. VR has the potential to deliver pain-reducing, psychologically based therapy to children, thereby enhancing multimodal …

Hematopoietic Cell Transplantation For Wiskott-Aldrich Syndrome: A Pidtc Report, Jessie L Alexander, Blachy J Dávila Saldaña, Ruta Brazauskas, Sravya Gethika Dammalapati, Linda M Griffith, Ami J Shah, Kristin A Shimano, Hans D Ochs, Jack J Bleesing, Christen L Ebens, Malika Kapadia, Andrea Bauchat, Neena Kapoor, Joseph H Oved, Hesham Eissa, Hannah Lust, Michael D Keller, Hilary Haines, Shanmuganathan Chandrakasan, Julie-An Talano, Ahmad Rayes, Lisa Madden, Evan Shereck, Holly K Miller, Lisa Forbes Satter, Caridad Martinez, Jacob Rozmus, Jeffrey J Bednarski, Lolie C Yu, Deepakbabu Chellapandian, Victor M Aquino, Alan Knutsen, Hey Chong, Ashley Chopek, Alfred P Gillio, Avni Joshi, Hemalatha Rangarajan, Theodore B Moore, Jeffrey R Andolina, Kenneth B Desantes, Mark Vander Lugt, Susan E Prockop, David C Shyr, Kathleen E Sullivan, Suhag Parikh, Katja G Weinacht, Troy R Torgerson, Rebecca Marsh, Christopher C Dvorak, Alice Y Chan, Elie Haddad, Jennifer R Heimall, Michael A Pulsipher, Jennifer W Leiding, Donald B Kohn, Jennifer M Puck, Luigi D Notarangelo, David J Rawlings, Morton J Cowan, Aleksandra Petrovic, Sung-Yun Pai, Lauri M Burroughs

Faculty, Staff and Students Publications

Wiskott-Aldrich syndrome (WAS), an X-linked disorder characterized by immunodeficiency, thrombocytopenia, autoimmunity, and malignancy, can be effectively treated with allogeneic hematopoietic cell transplantation (HCT). Older age at HCT and mismatched donors are known to affect overall survival (OS). However, the influence of specific clinical manifestations or WAS variant class on OS and factors associated with event-free survival (EFS) remain incompletely defined. We analyzed outcomes of 308 patients with WAS who underwent HCT at 37 institutions of the Primary Immune Deficiency Treatment Consortium from 1990 to 2018. With a median follow-up of 5.3 years, the 5-year OS and EFS were 87.2% and …

Incarcerated Geriatric Patients’ Experiences Of Aging And Healthcare, Michelle I Suh, Stephen Chen, Megan Benavides, Sumin Yoon, Nia Lucas, Josiah D Rich, Marc David Robinson, Anita N Chary

Faculty, Staff and Students Publications

Older adults comprise the fastest growing demographic in correctional facilities in the United States. Studies have shown older adults in prison report difficulty accessing healthcare and navigating the prison environment. Little is known about how older adults navigate aging and access healthcare in the jail setting. We sought to explore experiences of older adults incarcerated in a county jail. We conducted semi-structured qualitative interviews with 20 older adults (> 50 years old) who were incarcerated at a local county jail and were referred to the emergency department for acute care needs. Interviews focused on experiences of aging while incarcerated and …

Emapalumab Use In Malignancy-Associated Hemophagocytic Lymphohistiocytosis In The United States: The Real-Hlh Study, Adi Zoref-Lorenz, Carl E Allen, Edward M Behrens, Shanmuganathan Chandrakasan, May Chien, Michelle L Hermiston, Ashley P Hinson, Stefanos Intzes, Michael S Isakoff, Jennifer W Leiding, Abiola Oladapo, Arun Panigrahi, Sachit A Patel, Priti Pednekar, Anish K Ray, Jennifer A Rothman, Blachy Dávila Saldaña, Kelly J Walkovich, Joanna Weinstein, John D Yee, Michael B Jordan, Joanna Weinstein, Ashley P Hinson, Carl E Allen, Olive S Eckstein, Nitya Gulati, Shanmuganathan Chandrakasan, Hilary Haines, Taizo A Nakano, Sachit A Patel, Edward M Behrens, Stefanos Intzes, Allyson Hays, Blachy Dávila Saldaña, Michael B Jordan, Adi Zoref-Lorenz, Rabi Hanna, Michael Isakoff, Anish K Ray, Jennifer A Rothman, Anand Tandra, Robert Cooper, Jennifer W Leiding, May Chien, Susmita Sarangi, Vinod K Gidvani-Diaz, Prakash Satwani, John Carter, Michael Henry, Nicholas Gloude, Sima Bhatt, Deepika Bhatla, Lauren Draper, Arun Panigrahi, Michelle L Hermiston, Renee Modica, Mona Riskalla, Ashley Baker, Brant Ward

Faculty, Staff and Students Publications

Malignancy-associated hemophagocytic lymphohistiocytosis (mHLH), a hyperinflammatory syndrome, has poor prognosis and no standard therapy. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved for treating primary hemophagocytic lymphohistiocytosis (pHLH). REAL-HLH, a retrospective chart review conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. Data are presented for the subset of patients with mHLH. Overall, 51 of 105 (48.6%) patients were categorized as having secondary HLH, of which 17 of 51 patients had HLH associated with an …

Bacterial Fecal Microbiome Composition Associated With Hiv Stage Among Rural And Peri-Urban Adults Living With Hiv In Uganda, Bożena M Morawski, Elise R Morton, Miya Yunus, Claudia Muñoz-Zanzi, Rojelio Mejia, Ran Blekhman, David R Boulware, Sarah M Lofgren

Faculty, Staff and Students Publications

Background

Gut microbiome composition in HIV-infection provides insight into HIV pathogenesis and potentially offers avenues to adjunctive HIV therapies. Although two-thirds of people living with HIV (PLHIV) are in Africa, studies of the gut microbiome PLHIV have focused on non-African populations. Additionally, social, cultural, and environmental factors influence the gut microbiome and differ substantially between African and Western and urban and rural communities. Here, we quantify the relationships between immune status and fecal microbiome composition in 175 rural Ugandan PLHIV.

Methods

In 2013, 175 Ugandan PLHIV contributed a single fecal sample as part of a cohort study of 202 participants. …

A Case Of Autosomal Dominant Polycystic Kidney Disease With Multiple Bilateral Spontaneous Retroperitoneal Hemorrhages, Masato Mizuta, Tatsuya Suwabe, Yuki Oba, Akinari Sekine, Masayuki Yamanouchi, Hiroki Mizuno, Eiko Hasegawa, Takehiko Wada, Makoto Fukuda, Motoaki Miyazono, Naoki Sawa, Yoshifumi Ubara

Children’s Nutrition Research Center Staff Publications

We experienced a 45-year-old male with ADPKD who developed spontaneous retroperitoneal hemorrhages with hypertension in the right subcapsular renal space without trauma. After his condition worsened with conservative management, he was treated by renal transarterial embolization (TAE). Over the next eight years, he experienced bilateral bleeding at three different sites and underwent repeated endovascular treatment with renal TAE to stop the bleeding. After the fourth occurrence, the patient underwent hemodialysis. Although renal cysts and urinary tract bleeding occur frequently in ADPKD, retroperitoneal hemorrhage is rare; however, TAE is both effective and a good way to preserve renal function.

Penile Prosthetic Infections: What Can Be Learned From Orthopedics?, Kenneth B Mathis, Alisina Shahi

Faculty, Staff and Student Publications

No abstract provided.

Multi-Stakeholder Perspectives On Barriers To Mental Health Support For Informal Caregivers, Maria Lizette Rangel, Donaji Stelzig, Cassandra Martinez Enriquez, Hoda Badr

Department of Medical Oncology Faculty Papers

BACKGROUND: Informal caregivers experience elevated psychological distress but face substantial challenges in accessing mental health support. Prior research has focused primarily on individual or interpersonal determinants, with less attention to how organizational, community, and policy contexts shape access and contribute to inequities in service availability.

METHODS: Fifty-one stakeholders, including 17 informal caregivers, 23 community health workers (CHWs), and 11 mental health professionals, completed a demographic survey and 60-90-min semi-structured interviews in English or Spanish. Data were analyzed using thematic analysis, combining deductive coding guided by the Socioecological Model with inductive identification of emergent themes.

RESULTS: Participants identified both barriers and …

Identification Of De Novo Variants From Parent-Proband Duos Via Long-Read Sequencing, Leandros Boukas, Emmanuèle C. Délot, Georgia Pitsava, Christine Lambert, Cairbre Fanslow, Primo Baybayan, Sami Belhadj, Bojan Losic, John Harting, Krista Bluske, Jonathan Lotempio, Huda B. Al-Kouatly, Rachid Karam, William J. Rowell, Changrui Xiao, Eric Vilain, Seth I. Berger

Department of Obstetrics and Gynecology Faculty Papers

While de novo variants cause many Mendelian disorders, their detection currently requires sequencing of the proband and both biological parents. This is not feasible when only one parent is available, a limitation for millions of families. Here, we develop duoNovo, which identifies de novo variants from parent-proband duos using long-read sequencing followed by haplotype reconstruction and detection of identical-by-descent haplotype blocks. We sequenced 104 trios with PacBio HiFi sequencing and applied duoNovo to each of the 208 duos constructed by masking one parent, classifying over 55 million variants according to their de novo status. We evaluated duoNovo's performance against classifications …