Digital Commons Network^™

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

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 …

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 …

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. …

Underexplored Maternal Microbiomes: Immune, Metabolic, And Microbial Pathways Shaping Pregnancy Outcomes, Rafael Tomoya Michita, Nicole Jimenez, Melissa M Herbst-Kralovetz, Indira U Mysorekar

Faculty, Staff and Students Publications

Maternal microbial ecosystems play critical roles in shaping reproductive physiology and pregnancy outcomes. During the pre-conception and prenatal periods, these communities modulate maternal physiology by regulating immune tolerance, nutrient metabolism, and susceptibility to pregnancy complications such as preterm birth, hypertensive disorders, and gestational diabetes. While the gut microbiota has been extensively studied, the roles of cervicovaginal, urinary, respiratory, oral, and upper reproductive tract microbiomes remain less clear. In this minireview, we synthesize current knowledge on these underexplored maternal microbiomes, with an emphasis on the cervicovaginal and urinary microbiota and their interactions with the placenta and fetus. We discuss cross-niche microbial …

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 …

Development Of A Sustainable Blended Food Aid Product Using Local Ingredients For Nutritionally Vulnerable Populations In Haiti, Sherlie Jean Louis Dulience, Rachel Zimmerman, Michelle Dorce, Ilana Seff, Andrea Spray Bulungu, Patricia Kohl, Carolyn Lesorogol, Bazelais Dulience, Lora Iannotti

2020-Current year OA Pubs

OBJECTIVES: This study aimed to: (1) identify optimal blended food recipe options using local flours; (2) assess behaviors, attitudes, and practices around the use of blended foods among nutritionally vulnerable groups in Haiti; and (3) evaluate the nutrient composition of prototype blended food product relative to nutrient requirements for vulnerable populations.

METHODS: Blended food recipes made from local flours were identified through matrix scoring and stakeholder consensus. Focus groups (n = 7) assessed behaviors and attitudes toward blended foods. Prototype recipes were selected based on matrix scoring, program participant feedback, and feasibility of bringing to scale. Nutrient composition of the …

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 …

Immune-Mediated Necrotising Myopathy Following Semaglutide Treatment: A Contributing Factor?, Brian Lam, Eleni Tiniakou, Xinhai Robert Zhang, Shervin Assassi

Faculty, Staff and Student Publications

This report describes a female patient in her 60s with an immune-mediated necrotising myopathy (IMNM) occurring after semaglutide use. She was found to have progressive dysphagia, dysphonia, proximal muscle weakness and creatine kinase elevation over a 4-month course. Her symptoms were preceded by a single dose of semaglutide. Her work-up revealed features consistent with necrotising myopathy with inflammatory infiltrate on biopsy, and she responded to immunosuppression with corticosteroids and intravenous immunoglobulin (IVIG). She gradually improved and successfully returned to her baseline functional status while off immunosuppression for several months and with continued avoidance of glucagon-like peptide-1 (GLP-1) receptor agonists. Here, …

Proteomics Analysis Of Plasma For Risk Of Sepsis: Findings From The Atherosclerosis Risk In Communities Study, Junichi Ishigami, Xiao Hu, Pascal Schlosser, Thomas R Austin, Jingsha Chen, Bruce M Psaty, David Dowdy, Christie M Ballantyne, Morgan E Grams, Josef Coresh, James S Floyd, Kunihiro Matsushita

Faculty, Staff and Students Publications

Background: Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis.

Methods: We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses.

Results: At ARIC visit three, 669 proteins were associated with the risk …

Bi-Allelic Variants In Nrdc Cause A Neurodevelopmental Disorder Characterized By Neonatal Lethality, Microcephaly, And Brain Abnormalities, Davut Pehlivan, Abigail Sandoval, Reza Maroofian, François Lecoquierre, Aisha M Al Shamsi, Gyu S Lee, Osman Yesilbas, Preston Taylor, Matthew B Mcdougal, Vahid Bahrambeigi, Omid Aryani, Juan Felipe Ramirez, Khalid Hama Salih, Chadi Al Alam, Heba Morsy, Haytham Hussien, Tarek Omar, Ibrahim M Abdelrazek, Anne Claire Brehin, Dana Marafi, Tugba Kalayci, Jubran Abu Rahma, Jawabreh Kassem Talbeya, Husein Dabbah, Eric Verspyck, Toktam Moosavian, Jawid M Fatih, Tadahiro Mitani, Gulsen Akay, Daniel G Calame, Anne-Marie Guerrot, Wendy K Chung, Henry Houlden, James R Lupski, Adel Shalata, Wan Hee Yoon

Faculty, Staff and Students Publications

Nardilysin (NRDC) plays a role in multiple cellular functions in diverse cellular compartments, including ectodomain shedding in the plasma membrane, as well as chaperoning a key Krebs cycle enzyme in mitochondria. We had previously reported limited clinical information from two individuals with homozygous frameshift variants in NRDC. With inclusion of previously published individuals, here we report 14 individuals (10 females, four males) from nine unrelated families carrying homozygous NRDC pathogenic variants. Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), …

Smartphone-Based Ecological Momentary Assessment Of Pain In Older Adults Undergoing Auricular Point Acupressure For Chronic Low Back Pain: Secondary Analysis Of A Randomized Controlled Trial, Nada Lukkahatai, Chitchanok Benjasirisan, Xinran Huang, Hulin Wu, Jennifer Kawi, Jingyu Zhang, Claudia M Campbell, Constance M Johnson, Paul J Christo, Johannes Thrul

Faculty, Staff and Student Publications

Background: Chronic low back pain (cLBP) is a prevalent and disabling condition in older adults. Auricular point acupressure (APA), a nonpharmacologic intervention, has shown promise in managing cLBP. However, its impact on daily symptom fluctuations remains unclear. Ecological momentary assessment (EMA), which collects real-time data, offers a method to capture these fluctuations.

Objective: This secondary analysis evaluated the effects of APA on EMA-reported pain intensity and pain interference among older adults with cLBP and examined associations among APA practice patterns, recall-based assessments, and EMA engagement.

Methods: Data were drawn from a published 3-arm randomized controlled trial of 272 adults aged …

Sickle Cell Visualization In Vivo In Humans: Microvascular Occlusion Formation And Hemorheological Indices, Marisa M Morakis, Luojie Huang, Gregory N. Mckay, Sophie Lanzkron, Lydia H. Pecker, Nicholas J. Durr

Cardeza Foundation for Hematologic Research

Vaso-occlusion is a signature pathology of sickle cell disease (SCD). However, the lack of in vivo methods to observe individual blood cell dynamics in humans limits our understanding of occlusion formation mechanisms. We present a novel in vivo, noninvasive, label-free, and high-resolution imaging technique to study blood flow and sickled cell behavior in affected individuals. We used oblique back-illumination microscopy (OBM) to capture videos of 91.0 ± 42.3 sublingual capillaries in each of 10 participants with SCD before and after red cell transfusions and compared the measurements to 10 unaffected controls. With direct observation of blood cell activity, we identified …

Medial Pulvinar Nucleus As A Causal Hub For Heteromodal Naming, Oscar Woolnough, Tessy Thomas, Kathryn M Snyder, Ellery Wheeler, Jay Gavvala, Nitin Tandon

Faculty, Staff and Student Publications

Our ability to retrieve the names of objects in our environment is a fundamental aspect of everyday life. This process requires a complex, dynamic network of cortical and subcortical interactions. While the cortical constituents of this network have been extensively studied with intracranial recordings, the subcortical nodes of the naming network are unclear. We probed the role of the left medial pulvinar nucleus in naming with direct intracranial recordings and stimulation in eight humans (three male, five female) as they named objects using pictures and auditory and written descriptions. We found a spectrotemporal signature of naming in the left medial …

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 …

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, Sagar S Mukhida, Neha Venkatesh, Amishi Y Shah, 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 …