Medicine and Health Sciences Commons^™

Association Of Pathogenic/Likely Pathogenic Inherited Cardiomyopathy Variants With Heart Failure: A Topmed Multiancestry Analysis, Naman S Shetty, Mokshad Gaonkar, Akhil Pampana, Nirav Patel, April P Carson, Bernhard Haring, Bruce M Psaty, Charles Kooperberg, Eric Boerwinkle, Jerome I Rotter, João A C Lima, Jorge R Kizer, Lisa Warsinger Martin, Kent D Taylor, Michael E Hall, Myriam Fornage, Sanjiv J Shah, Stephen S Rich, Ramachandran S Vasan, Rami Nassir, Peng Li, Garima Arora, Pankaj Arora

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the prevalence of pathogenic/likely pathogenic inherited cardiomyopathy variants and their association with heart failure in the (TOPMed) TransOmic for Precision of Medicine cohorts.

METHODS: A retrospective cohort study using the TOPMed cohorts, including multi-ancestry US adults (≥18 years of age) with sequencing data, was conducted. Pathogenic/likely pathogenic inherited cardiomyopathy variant carrier status was determined based on ClinVar variants classified with two or more stars of evidence. Individuals without pathogenic/likely pathogenic variants were used as the reference group. The primary outcome was heart failure , adjudicated by an expert panel. Cox proportional hazards models assessed the association between …

Microbial Signals In Primary And Metastatic Brain Tumors, Golnaz Morad, Ashish V Damania, Brenda Melendez, Bharat B Singh, Fabiana J Veguilla, Rebecca A Soto, Yasmine M Hoballah, Pranoti V Sahasrabhojane, Matthew C Wong, Mona M Ahmed, Rene N Rico, Kaitlyn N Lewis, Khalida Wani, Diana D Shamsutdinova, Rossana N Lazcano Segura, Davis R Ingram, Eric A Goethe, Abderrahman Day, Ivonne I Flores, Lauren K Mcdaniel, Manoj Chelvanambi, Sarah B Johnson, Florentia Dimitriou, Pravesh Gupta, Shivangi Oberai, M Anna Zal, Phoebe Doss, Mohamed A Jamal, Eiko Hayase, Chetna Wathoo, Lisa M Norberg, Stephanie L Jenkins, Sara Nass, Joy Gumin, Lihong Long, Jing Yang, Gina R Bradley, Mahesh Prasad Bekal, Antonio G Dono, Pavel S Pichardo-Rojas, Samuel W Andrewes, Leomar Y Ballester, Jillian S Losh, Jiyong Liang, Longfei Huo, Douglas C Nielsen, Brittany C Parker Kerrigan, Priscilla K Brastianos, Natalie Wall Fowlkes, Chia-Chi Chang, Robert R Jenq, Candelaria Gomez-Manzano, Jason T Huse, Michael A Davies, Alexander J Lazar, Krishna P Bhat, Nitin Tandon, Yoshua Esquenazi, Christine B Peterson, Vinay K Puduvalli, Frederick F Lang, Christopher D Johnston, Susan Bullman, Nadim J Ajami, Sherise D Ferguson, Jennifer A Wargo

Faculty, Staff and Student Publications

Gliomas and brain metastases are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. Although our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intratumoral microbiota emphasize the importance of rigorous, orthogonal validation. This prospective, multi-institutional study included a total of 243 samples from 221 patients, comprising 168 glioma and brain metastases samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescence in situ hybridization, immunohistochemistry and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and brain metastases …

Ocular Bacterial Microbiome Analysis By Next-Generation Sequencing In Patients With Stevens-Johnson Syndrome And Sjögren’S Disease: Associations With Dry Eye Indices, Luciana Frizon, Talita Trevizani Rocchetti, André Frizon, Rafael Jorge Alves De Alcântara, Ana Luisa Hofling-Lima, Cintia S De Paiva, José Álvaro Pereira Gomes

Faculty, Staff and Students Publications

The ocular surface microbiome plays a crucial role in maintaining immune homeostasis, and its disruption may contribute to mucosal inflammation and autoimmunity. This pilot exploratory study investigated and compared the ocular surface bacterial microbiome in patients with Stevens-Johnson syndrome (SJS), Sjögren's disease (SjD), and healthy controls using next-generation sequencing (NGS) and correlated these findings with dry eye parameters. Conjunctival swabs were collected from sixteen individuals: ten with SJS, three with SjD, and three healthy controls. Dry eye parameters were employed to evaluate the dry eye disease. Microbiome profiles were determined by the NGS of the 16S V3-V4 region and analyzed …

Depression Polygenicity And Disease Activity And Disability Worsening In Multiple Sclerosis, Ali Manouchehrinia, Kathryn C Fitzgerald, Amber Salter, Ruth Ann Marrie, Lars Alfredsson, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Lesley A Graff, Carol A Hitchon, Jan Hillert, Ingrid Kockum, Yi Lu, Fred D Lublin, Kyla Mckay, Tomas Olsson, Scott Patten, Amit Patki, Hayley Riel, Klementy Shchetynsky, Pernilla Stridh, Hemant K Tiwari, Jerry S Wolinsky, Kaarina Kowalec

Faculty, Staff and Student Publications

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes. We computed the depression polygenic score (PGS) and …

Colorectal-Specific Radiation Dose And Chemotherapy Risk For Subsequent Colorectal Malignancies In Childhood Cancer Survivors: A Childhood Cancer Survivor Study (Ccss) Report, Constance A Owens, Ethan B Ludmir, Qi Liu, Weiyu Qiu, Aashish C Gupta, Susan A Smith, Bastien Rigaud, Kristy K Brock, James E Bates, Taylor G Meyers, Arnold C Paulino, Christine B Peterson, Stephen F Kry, Jop C Teepen, Cécile M Ronckers, Joseph P Neglia, Wendy M Leisenring, Kevin C Oeffinger, Paul C Nathan, Lucie M Turcotte, David C Hodgson, Melissa M Hudson, Leslie L Robison, Chaya S Moskowitz, Gregory T Armstrong, Tara O Henderson, Yutaka Yasui, Rebecca M Howell

Faculty, Staff and Student Publications

Purpose: Among childhood cancer survivors, we evaluated not previously explored relationships between colorectal subsequent malignant neoplasm (SMN) incidence and colorectum-specific radiation dose metrics currently used in radiation therapy (RT) planning and expanded upon previously reported chemotherapy associations.

Methods: The Childhood Cancer Survivor Study (CCSS) includes 5-year survivors of childhood cancer diagnosed between 1970 and 1999. RT was assessed as mean colorectal dose (MCD) and the percent volume (VX Gy) receiving ≥5, 10, 20, 30, and 40 Gy. Chemotherapy was assessed as cumulative doses for procarbazine and platinum agents, cyclophosphamide-equivalent doses for alkylating agents, and doxorubicin-equivalent doses for anthracyclines. Piecewise-exponential models …

Probabilistic Template Matching For Detecting Resting-State Functional Mri Language Network In Brain Tumor Patients, Jian Ming Teo, Vinodh A Kumar, Alexander M Khalaf, Kyle R Noll, Sherise D Ferguson, Chibawanye I Ene, Sujit S Prabhu, Max Wintermark, Ho-Ling Liu

Faculty, Staff and Student Publications

Background: Intersubject variation among patients with brain tumors complicates the template matching process for detecting the resting-state (rs) functional MRI (fMRI) language network when using independent component analysis (ICA).

Purpose: This study aimed to develop methods that use a probabilistic language atlas to incorporate intersubject variation in brain tumor patients into the template matching process.

Methods: This retrospective study included 79 patients with brain tumors (average age, 50 ± 15 years) who underwent presurgical task-based (tb)-fMRI and rs-fMRI at clinical 3T scanners. At varying template generation thresholds (τ), binary and probabilistic templates were obtained from the language atlas. A binary …

Parental Psychosocial Outcomes After A Positive Newborn Screen For A Lysosomal Storage Disorder., Courtney D. Berrios, Randi N. Gadea, Meghan Strenk, Twisha Nadella, Jennifer L. Gannon, Janelle R. Noel-Macdonnell Phd

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: This study explores the psychosocial impact of a positive newborn screen (NBS) result for four lysosomal storage disorders (LSDs) (Fabry disease, Krabbe disease, Mucopolysaccharidosis Type I, Pompe disease) across confirmatory results.

METHODS: Parents whose child who had a positive NBS for one of the included LSDs were recruited for a retrospective cohort (n = 80) or prospective, longitudinal cohorts (n = 50). Surveys assessed uncertainty, anxiety, intrusive or avoidant thoughts, and perceived vulnerability of their child's health. In-depth interviews explored the NBS experience and psychosocial response.

RESULTS: Participants experienced uncertainty and anxiety during confirmatory testing that improved as parents …

Using Video Ethnography And Stimulated Recall Interviews To Describe The Diagnostic Process In The Emergency Department, Milisa Manojlovich, Caitlin Cassady, Sarah J Parker, Ellie Davis, Charlotte Ahr, David Ryamukuru, Anna Wang, Kalyan Pasupathy, Hardeep Singh, Prashant Mahajan

Faculty, Staff and Students Publications

Objectives: Understanding how physicians make diagnoses is challenging because cognitive processes are unobservable and partly unconscious, making it difficult for physicians to describe how they arrived at a diagnosis. Physicians who work in emergency departments (EDs) are especially vulnerable to making diagnostic errors because the ED is a fast-paced, dynamic setting where complex decision-making occurs under severe time, information, and resource constraints. The purpose of our study was to describe how the diagnostic process evolves for ED clinicians in both pediatric and adult ED settings.

Methods: We used a qualitative, video ethnography study design to capture in situ, real-time ED …

Priming With Transcutaneous Spinal Direct Current Stimulation Followed By Robotic Exoskeleton Gait Training In Individuals With Spinal Cord Injury: A Case Series, Marcie Kern, Catherine Velasquez-Ignacio, Taimoor Afzal, Shih-Chiao Tseng, Gerard E Francisco, Shuo-Hsiu Chang

Faculty, Staff and Student Publications

Objectives: To investigate the safety and feasibility of repeated transcutaneous spinal direct current stimulation (tsDCS) as priming strategy during exoskeleton-assisted locomotor training in individuals with SCI and evaluate potential neurophysiologic and functional gait changes.

Study design: Case series experimental design.

Setting: Research laboratory at a post-acute rehabilitation hospital.

Participants: Four participants with chronic incomplete SCI.

Interventions: Four participants with chronic incomplete SCI received three weeks of training consisting of two types of interventions after baseline (A): 20-minute tsDCS (anode or cathode) applied over the spinous processes of T10 followed by 20-minute exoskeleton-assisted locomotor training (B, B1, B2) and 20-minute exoskeleton-assisted …

Basal Cell Carcinoma Risk Prediction In Survivors Of Childhood Cancer, Cindy Im, Christina Boull, Zhe Lu, Kenneth Liao, Hasibul Hasan, Linwan Xu, Yadav Sapkota, Rebecca M Howell, Michael A Arnold, Miriam R Conces, Ashley J Housten, Judith Gebauer, Thorsten Langer, Jop C Teepen, Leontien C M Kremer, Louis S Constine, Yutaka Yasui, Melissa M Hudson, Kirsten K Ness, Gregory T Armstrong, Joseph P Neglia, Yan Yuan, Lucie M Turcotte

Faculty, Staff and Student Publications

Background: Survivors of childhood cancer face excess risk of developing basal cell carcinoma. Age-specific basal cell carcinoma risk prediction models for survivors may support targeted screening recommendations.

Methods: We developed models predicting basal cell carcinoma risk by ages 40 and 50 years featuring detailed cancer treatment predictors, utilizing statistical and machine-learning algorithms and data from 23 166 five-year survivors in the Childhood Cancer Survivor Study, a multi-institutional retrospective cohort study. Selected models were externally validated in 5314 survivors in the St Jude Lifetime Cohort. Model discrimination and precision were evaluated using the area under the receiver operating characteristic curve (AUROC) …

Surgical Outcomes With Neoadjuvant Durvalumab Plus Chemotherapy Followed By Adjuvant Durvalumab In Resectable Nsclc, Tetsuya Mitsudomi, John V Heymach, Martin Reck, Janis M Taube, Shugeng Gao, Yoshitsugu Horio, Jian You, Gaofeng Li, Dinh Van Luong, Somcharoen Saeteng, Fumihiro Tanaka, Stefan B Watzka, Laszlo Urban, Zsuzsanna Szalai, Hiroaki Akamatsu, Jin Hyoung Kang, Francisco J Orlandi, Guzel Z Mukhametshina, Andreas Pircher, Carlos Henrique Andrade Teixeira, Mike Aperghis, Gary J Doherty, Ruth Doake, Tamer M Fouad, David Harpole

Faculty, Staff and Student Publications

Introduction: In AEGEAN, perioperative durvalumab plus neoadjuvant chemotherapy, versus neoadjuvant chemotherapy alone, significantly improved event-free survival (p = 0.004) and pathologic complete response (p < 0.001; primary end points; modified intention-to-treat [mITT] population, which excluded patients with known EGFR or ALK aberrations) with a manageable safety profile in patients with resectable (R)-NSCLC. Here, we report surgical outcomes from AEGEAN.

Methods: Patients with treatment-naive R-NSCLC (stage II-IIIB [N2]) and Eastern Cooperative Oncology Group performance status 0 or 1 were randomized (1:1) to platinum-based chemotherapy plus durvalumab or placebo intravenously (every 3 wk, 4 cycles) before surgery, followed by durvalumab or placebo (every 4 wk, 12 cycles). Surgical outcomes were summarized for the mITT population using descriptive statistics.

Results: A total of 737 out of 740 mITT patients received treatment, 366 and 371 in the durvalumab and …

Can Interpersonal Trust Predict And Account For Symptom Change During Group Cognitive Processing Therapy For Ptsd? An Investigation Of The Iterated Trust Game, M Wright Williams, Christopher Hunt, David P Graham, Matt Estey, Lia Smith, Katherine Mccurry, Brooks King-Casas, Pearl Chiu

Faculty, Staff and Students Publications

Objective: Group cognitive processing therapy (GCPT) is frequently utilized to treat PTSD within the VA healthcare system, but its mechanisms are not well understood. Interpersonal trust could be an important change process in GCPT given its relevance to group-based therapy and its role in CPT, but self-report measures are inadequate for capturing the dynamic interplay that defines interpersonal trust. Here, we examined the degree to which interpersonal could predict and account for PTSD symptom change in GCPT using the iterated trust game (ITG)-a behavioral task used to approximate real-world trust behavior.

Methods: Participants were Veterans with PTSD who participated in …

Predictors Of Decannulation Success In Tracheostomy: A 10-Year Analysis Of The Global Tracheostomy Collaborative Database, Charissa J Zaga, Carly E Milliren, Brendan A Mcgrath, Christina J Yang, Bradley A Schiff, Stephen J Warrillow, Jennifer K Henningfeld, Prudence A Gregson, Joshua R Bedwell, Karen M Beaudet, Michael J Brenner, Vinciya Pandian

Faculty, Staff and Students Publications

Objective: Decannulation is a critical milestone in functional recovery after tracheostomy, but standardized guidelines are lacking. This study examined factors associated with tracheostomy decannulation success, comparing hospital utilization, adverse events, and survival outcomes between decannulated and non-decannulated patients.

Study design: Retrospective, observational study.

Setting: Data were collected from 25 hospitals participating in the Global Tracheostomy Collaborative (GTC) in the United States, Australia, and the United Kingdom.

Methods: Prospectively collected data from adult patients who underwent tracheostomy from 2013 to 2022 were analyzed. Outcomes included decannulation success, hospital utilization metrics (intensive care unit [ICU] admissions, mechanical ventilation use, tracheostomy duration, and …

Neural Signatures And Personalized Neuromodulation In A Subject Experiencing Context-Dependent Inhibitory Control Deficits, Layth S Mattar, Shraddha Shah, Lily S Chamakura, Denise Oswalt, Yue Zhang, Davin Devara, Jung Uk Kang, Zahra Jourahmad, Ryan Jafri, Geoffrey Liu, Joshua Adkinson, Isabel A Danstrom, Xiaoxu Fan, Yvonne Y Reed, Kelly R Bijanki, Alica Goldman, Lu Lin, Vaishnav Krishnan, Nicole R Provenza, Andrew J Watrous, Sameer A Sheth, Sarah R Heilbronner, Garrett P Banks, Eleonora Bartoli

Faculty, Staff and Students Publications

The ability to override prepotent actions is critical to control impulses and adjust behavior depending on goals and contextual needs. In this study, we investigate the inhibitory control abilities of a patient diagnosed with Klüver-Bucy Syndrome following a left temporal resection. The patient presented with disruptive hypersexuality symptoms akin to compulsions, leading to the inability to control and suppress inappropriate actions. The patient was recruited for the current research study while undergoing intracranial monitoring for epilepsy, to investigate the cognitive and neural processes underlying the patient's inhibitory control symptoms. We formulated the hypothesis that a reactive inhibitory control deficit emerges …

Beyond Seizures As An Outcome Measure: A Global Severity Scoring System For Cdkl5 Deficiency Disorder, Peter Jacoby, Eric D Marsh, Scott Demarest, Jacinta M Saldaris, Helen Leonard, Heather E Olson, Joni N Saby, Elia Pestana-Knight, Rajsekar Rajaraman, Dana Price, Judith Weisenberg, Bernhard Suter, Jenny Downs, Tim A Benke

Faculty, Staff and Students Publications

Background: CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated.

Methods: The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance …

Clonal Hematopoiesis And Subsequent Venous Thromboembolism Among Survivors Of Autologous Transplantation For Lymphoma, Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Alysia Bosworth, Elizabeth Ross, Liton Francisco, Purnima Singh, Melissa A Richard, Chengcheng Yan, Rashi Kalra, Changde Cheng, Saro H Armenian, Stephen J Forman, Ravi Bhatia, Smita Bhatia

Faculty, Staff and Students Publications

Clonal hematopoiesis is associated with increased risk of venous thromboembolism (VTE). The risk of VTE is high in patients with lymphoma and after autologous peripheral blood stem cell transplantation, and clonal hematopoiesis is present in many patients with lymphoma at autologous peripheral blood stem cell transplantation. We examined whether clonal hematopoiesis increases posttransplant VTE risk in patients with lymphoma. Our study included 557 patients with lymphoma who had survived 2 or more years after receiving autologous peripheral blood stem cell transplantation between 1999 and 2014. Clonal hematopoiesis was measured by targeted sequencing of cryopreserved peripheral blood stem cell product. Median …

Characterization Of Educational And Executive Leadership In University-Based General Surgery Programs: Demographics, Training Backgrounds, And Institutional Ties, Nicole M Santucci, Daniel Alligood, Sabrina Madrigal, Ariana Naaseh, Jonathan Davies, Hannah M Phelps, Paul E Wise, Jennifer Yu, Jesse D Vrecenak, Colin A Martin

2020-Current year OA Pubs

INTRODUCTION: Despite longstanding homogeneity in surgical leadership at academic institutions, promoting diversity in leadership positions is increasingly recognized as critical to fostering inclusion, mentorship, and improved patient outcomes. This study aims to further characterize and compare educational and executive leaders within academic general surgery (GS) programs.

METHODS: A cross-sectional study was conducted using publicly accessible online resources to collect program characteristics and leadership demographics for Accreditation Council for Graduate Medical Education-accredited, university-based GS residency programs for the 2024-25 academic year. Leadership roles included Program Directors (PDs), Associate Program Directors (APDs), Clerkship Directors (CDs), Vice Chairs of Education (VCE), and Department …

Episodic Memory Involves Transient And Sparse Connectivity Aligned To Both Internal And External Events, Adam J. O. Dede, Peter Brunner, Jarod L. Roland, Et Al.

2020-Current year OA Pubs

Episodic memory depends on the coordination of local processing, indexed by high-frequency broadband (HFB) activity, with global organization, indexed by theta oscillations. However, theta and HFB exhibit asynchronous timing, raising the question of how results of local processing are communicated. Using intracranial EEG in patients performing a recognition memory task, we examined this coordination across medial temporal (MTL) and prefrontal (PFC) regions. HFB peaks occurred earlier in the MTL than in the PFC. Contrasting analyses were anchored either to these internally driven HFB peaks or to the external event of stimulus presentation. We discovered three key results. First, the role …

Real-World Effectiveness And Safety Of Upadacitinib In Crohn's Disease: A Multicenter Study, Jalpa Devi, Katherine Huang, Fnu Jaiprada, Julia Huecker, Parakkal Deepak, Et Al.

2020-Current year OA Pubs

BACKGROUND & AIMS: We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor, in patients with Crohn's disease (CD).

METHODS: A retrospective analysis was conducted across 9 centers in the United States, focusing on adults with CD treated with UPA, 45 mg, as induction therapy for active luminal disease. The coprimary end points were clinical remission at 12 weeks (Harvey Bradshaw Index ≤4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (Simplified Endoscopic Mucosal Assessment for Crohn's Disease score of 0-1 or absence of ulcers). Secondary …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

The Impact Of Social Determinants Of Health On Outcomes Of Brexucabtagene Autoleucel In Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia, Timothy E O'Connor, Chenyu Lin, Gregory W Roloff, Amy Zhang, Katharine Miller, Ibrahim Aldoss, Noam E Kopmar, Simone E Dekker, Vishal K Gupta, Nikeshan Jeyakumar, Ibrahim N Muhsen, Yannis Valtis, Naveed Ahmed, Katherine Sutherland, Kaitlyn C Dykes, Mohamed Ahmed, Evan Chen, Hector Zambrano, Danielle Bradshaw, Santiago Mercadal, Marc Schwartz, Sean Tracy, Matthew P Connor, Michal Kubiak, Akash Mukherjee, Navneet Majhail, Minoo Battiwalla, Luke Mountjoy, Shahbaz A Malik, John Mathews, Paul Shaughnessy, Betsy Blunk, Aaron C Logan, Abdullah Ladha, Anjali S Advani, Maryann Stefan, Caitlin Guzowski, Rasmus T Hoeg, Talal Hilal, Jozal Moore, Kristen M O'Dwyer, Laquisa C Hill, Joshua Sasine, Caspian Oliai, Melhem M Solh, Catherine J Lee, Vamsi K Kota, Divya Koura, Muthu V Kumaran, Jessica T Leonard, Noelle V Frey, Jae H Park, Marlise R Luskin, Veronika Bachanova, Ahmed Galal, Vinod Pullarkat, Michael R Bishop, Wendy Stock, Ryan D Cassaday, Bijal D Shah, Rawan Faramand, Lori S Muffly, Stephanie B Tsai, Bhagirathbhai Dholaria

Faculty, Staff and Students Publications

Brexucabtagene autoleucel (brexu-cel) is a chimeric antigen receptor T (CAR T) cell therapy approved for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We studied the impact of social determinants of health (SDoH) on outcomes of adults with B-ALL receiving brexu-cel. This retrospective analysis included adults (≥18 years) with R/R B-ALL treated with brexu-cel between 2021 and 2023. Cox proportional hazards models evaluated the association of race, ethnicity, and SDoH with progression-free survival (PFS) and overall survival (OS). 189 patients received brexu-cel and 57% were male. 55% were non-Hispanic White, 30% Hispanic, 7% non-Hispanic Black, 6% Asian/Pacific …

Real-World Effectiveness And Safety Of Upadacitinib In Crohn's Disease: A Multicenter Study, Jalpa Devi, Anthony Xu, Molly Stone, Anish Patel, Abdul Khan, Nikhil Reddy, Jeremy Klein, Navreet Chowla, Caroline Benson, Bryan Christopher Luu, Katherine Huang, Fnu Jaiprada, Marc Fenster, Ryan Ungaro, Joel Pekow, Amanda M Johnson, Andres J Yarur, Richa Shukla, Julia Huecker, Shrinivas Bishu, Reboot Ibd Consortium, Parakkal Deepak

Faculty, Staff and Students Publications

Background & aims: We aimed to describe the real-world effectiveness and safety of upadacitinib (UPA), an oral Janus kinase 1 inhibitor, in patients with Crohn's disease (CD).

Methods: A retrospective analysis was conducted across 9 centers in the United States, focusing on adults with CD treated with UPA, 45 mg, as induction therapy for active luminal disease. The coprimary end points were clinical remission at 12 weeks (Harvey Bradshaw Index ≤4 or absence of symptoms on physician's global assessment) and endoscopic remission at 6 months (Simplified Endoscopic Mucosal Assessment for Crohn's Disease score of 0-1 or absence of ulcers). Secondary …

Centrally Inserted Central Catheter Placement Using A Novel, Handheld, Image-Guided, Robotic Device: Results Of Initial Feasibility Trial In Patients, James P Herlihy, William E Cohn, Adrian Ebner

Faculty, Staff and Students Publications

Background: Central venous access devices (CVADs) are an essential and widely used tool for the treatment of the critically ill, patients undergoing major surgery, and for many patients requiring hemodialysis. Automation of centrally inserted central catheters (CICCs) could potentially make CVAD placement safer, more effective, and more accessible. A new device that uses ultrasound image-guided, robotic needle placement, in addition to traditional Seldinger technique, to place a CICC is described.

Objective: The device was used in a small, first-in-human, trial for placing non-tunneled hemodialysis catheters (NTHDCs), in order to determine feasibility of clinical use.

Methods: Consecutive patients requiring a NTHDC, …

Physician Perceptions Of The Evaluation And Management Of Incarcerated Patients In The Emergency Department, Michelle Suh, Anita N Chary, Melanie F Molina, Caitlin M Farrell, Mark B Mycyk, Vidya Eswaran

Faculty, Staff and Students Publications

Background: Incarcerated patients in the United States are frequently seen in the emergency department. Although other specialties have reported differential care for patients who are incarcerated, little is known about the emergency physicians' evaluation and management of patients who are incarcerated.

Objective: The aim of our study was to characterize emergency physician (EP) perceptions of the emergency department (ED) care of incarcerated patients.

Methods: We surveyed emergency medicine resident and attending physicians at three academic safety-net EDs that regularly treat incarcerated patients from May to June 2023. We conducted thematic analysis of responses about perceptions of ED evaluation and management …

Mutations In The Key Autophagy Tethering Factor Epg5 Link Neurodevelopmental And Neurodegenerative Disorders Including Early-Onset Parkinsonism, Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri, Franciska Baur, Lea Hentrich, Birgit Gerisch, Mina Zamani, Cesar Alves, Ata Siddiqui, Haidar S Dafsari, Mehri Salari, Anthony E Lang, Michael Harris, Alice Abdelaleem, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Gholamreza Shariati, Alireza Sedaghat, Jawaher Zeighami, Daniel Calame, Dana Marafi, Ruizhi Duan, Adrian Boehnke, Gary D Clark, Jill A Rosenfeld, Carrie A Mohila, Dora Steel, Saurabh Chopra, Suvasini Sharma, Nicolai Kohlschmidt, Steffi Patzer, Afshin Saffari, Darius Ebrahimi-Fakhari, Büşra Eser Çavdartepe, Irene J Chang, Erika Beckman, Renate Peters, Andrew Paul Fennell, Bernice Lo, Luisa Averdunk, Felix Distelmaier, Martina Baethmann, Frances Elmslie, Kairit Joost, Sheela Nampoothiri, Dhanya Yesodharan, Hanna Mandel, Amy Kimball, Antonie D Kline, Cyril Mignot, Boris Keren, Vincent Laugel, Katrin Õunap, Kalpana Devadathan, Frederique M C Van Berkestijn, Arpana Silwal, Saskia Koene, Sumit Verma, Mohammed Yousuf Karim, Chahynez Boubidi, Majid Aziz, Gehad Elghazali, Lauren Mattas, Mohammad Miryounesi, Farzad Hashemi-Gorji, Shahryar Alavi, Nayereh Nouri, Mehrdad Noruzinia, Saeideh Kavousi, Arveen Kamath, Sandeep Jayawant, Russell Saneto, Nourelhoda A Haridy, Pinar Ozkan Kart, Ali Cansu, Madeleine Joubert, Claire Beneteau, Kyra E Stuurman, Martina Wilke, Tahsin Stefan Barakat, Homa Tajsharghi, Annarita Scardamaglia, Sadeq Vallian, Semra Hız, Ali Shoeibi, Reza Boostani, Narges Hashemi, Meisam Babaei, Norah Saleh Alsaleh, Julie Porter, Tania Attié-Bitach, Pauline Marzin, Dorota Wicher, Jessica I Gold, Elisabeth Schuler, Amna Kashgari, Rakan F Alanazi, Wafaa Eyaid, Marc Engelen, Mirjam Langeveld, Burkhard Stüve, Yun Li, Gökhan Yigit, Bernd Wollnik, Mariana H G Monje, Dimitri Krainc, Niccolò E Mencacci, Somayeh Bakhtiari, Michael Kruer, Emanuela Argilli, Elliott Sherr, Yalda Jamshidi, Ehsan Ghayoor Karimiani, Yiu Wing Sunny Cheung, Ivan Karin, Giovanni Zifarelli, Peter Bauer, Wendy K Chung, James R Lupski, Manju A Kurian, Jörg Dötsch, Jürgen-Christoph Von Kleist-Retzow, Thomas Klopstock, Matias Wagner, Calvin Yip, Andreas Roos, Rita Carsetti, Carlo Dionisi-Vici, Mathias Gautel, Michael R Duchen, Adam Antebi, Henry Houlden, Manolis Fanto, Heinz Jungbluth

Faculty, Staff and Students Publications

Objective: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Methods: We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.

Results: Through worldwide collaboration, we identified 211 patients, 97 …

Understanding The Effects Of Real-Time Head Position Feedback On Postural Sway In Terms Of Changes In Underlying Deterministic And Stochastic Dynamical Processes, Steven J. Harrison, Benjamin De Bari, Ryan Poutre, Jeffrey M. Kinsella-Shaw

College of Humanities and Sciences Faculty Papers

Our perceptual systems detect information about how our body is moving relative to the surrounding environment. Such information is essential to our ability to maintain upright standing balance. Real-time postural feedback systems are technologies that appear to enhance our ability to detect information about the movements of our body, and as a consequence improve our capacity to control the posture of our body. Here we examine a system in which real-time measurements of head position were "felt" as changes in the intensity of vibration of tactors in a headband. Using this system, participants were able to stabilize their body posture, …

Sexual Activity And Functioning After Breast Cancer Treatment: Perspectives On The Importance Of Pleasure From A Radiotherapy Cohort, Melanie Besculides, Lauren Carney, Ksenia Gorbenko, Sheryl Green, Melissa Brito, Jezelle Lynch, Carly Feldman, Cindy Munoz, Madhu Mazumdar, Deborah C. Marshall

Student Papers, Posters & Projects

BACKGROUND: Breast cancer affects millions of women and while treatment can be lifesaving, it also has numerous side effects, including those related to sexual function, which often impact the ability to experience pleasure from sex. This study aimed to understand how breast cancer survivors define sexual activity, identify important aspects, and ascertain perceived impacts of treatment on sexual activity and function, particularly related to pleasure.

METHODS: Semi-structured interviews were conducted with women who were breast cancer survivors at least one-year post-radiation. Priority populations were oversampled (racial/ethnic/sexual/gender minorities, those aged over 65 or under 45). The sample included 23 participants: 11 …