Medical Sciences Commons^™

The 2024 Think Tank On Prevention Of Sudden Cardiac Death In The Young: Pathway To Survival A Report From The Cardiac Safety Research Consortium, Jordan E Ezekian, Charles C Anderson, Peter F Aziz, Samia Baluch, Stuart Berger, Martha Lopez-Anderson, Vincent Miller, Yoshihide Mitani, Silvana Molossi, Valarie Morrow, Victoria L Vetter, Elizabeth Vickers Saarel, Bhavya Trivedi, Salim F Idriss, 2024 Think Tank Participants

Faculty, Staff and Students Publications

Sudden cardiac arrest and death in the young is a critical public health issue. It occurs in children of any age, sex, racial or ethnic demographic, or socioeconomic status. Importantly, it can affect any individual-athlete and nonathlete alike. Prevention of sudden death in the young is of high importance not only because of the loss of a young life but also because of the substantial impact to families and to society at large. This White Paper summarizes the proceedings of a third national Think Tank on prevention of sudden cardiac death in the young. The Think Tank, which convened on …

Addressing Anxiety And Depression In The Allergy Clinic Through Motivational Interviewing, Brief Cognitive Behavioral Therapy, And Curious Questions, Marylee Verdi, Dominic Candido, Juliette Madan, Jonathan A Bernstein, Don Bukstein, Aikaterini Anagnostou, Matthew Greenhawt, S Shahzad Mustafa, Julie Wang, Anna Nowak-Wegrzyn, Elissa M Abrams, John Oppenheimer, Alexandra E Conway, Andrew A White, Taylor A Doherty, Richard P Morse, Marcus Shaker

Faculty, Staff and Students Publications

Allergic diseases, particularly food allergy, can be associated with significant psychosocial impairment. Allergist-immunologists can provide evidence-based information to correct misperceptions and misunderstandings regarding food allergy that may perpetuate cycles of fear and anxiety. Whereas motivational interviewing can be an empathetic approach to empower patients to actualize health goals, cognitive behavioral therapy (CBT) aims to provide disease-state insight to facilitate an understanding of risk that can transform health beliefs and behaviors. Brief CBT is a clinical approach that can help address ineffective management paradigms through conversations that begin with curious questions. In this review, we discuss evidence supporting implementation of an …

Anaphylaxis Definition, Overview, And Clinical Support Tool: 2024 Consensus Report-A Ga2len Project, Timothy E Dribin, Antonella Muraro, Carlos A Camargo, Paul J Turner, Julie Wang, Graham Roberts, Aikaterini Anagnostou, Susanne Halken, Jay Liebermann, Margitta Worm, Torsten Zuberbier, Hugh A Sampson, Ga(2)Len Anaphylaxis Study Team

Faculty, Staff and Students Publications

Background: The 2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network anaphylaxis criteria are widely used in clinical care and research. In 2020, the World Allergy Organization published modified criteria that have not been uniformly adopted. Different criteria contribute to inconsistent care and research outcomes.

Objective: We sought to develop a consensus anaphylaxis definition, overview, and clinical support tool.

Methods: A 12-member writing group developed draft outputs modified with input from a 46-member international expert panel, 31 medical stakeholder organizations, and 15 patient advocacy organizations. The expert panel participated in a modified Delphi process to seek consensus …

Mood And Sleep In Young Adults With Type 1 Diabetes, Samantha A Carreon, Marissa N Baudino, Charles G Minard, Sarah K Lyons, Randi Streisand, Barbara J Anderson, Siripoom V Mckay, Tricia S Tang, Sara Nowakowski, Ashley M Butler, Sridevi Devaraj, Marisa E Hilliard

Faculty, Staff and Students Publications

Objective: Depression is associated with sleep problems, and both are associated with higher HbA1c in people with type 1 diabetes (T1D). However, little is known about depressed mood and sleep in young adults with T1D. The aims of this secondary analysis were to provide descriptive statistics of multiple aspects of mood and sleep in young adults with T1D and evaluate associations of depressed mood, diabetes distress, and sleep quality and duration.

Methods: At baseline of a behavioral intervention trial, young adults with T1D completed self-report measures of sleep, diabetes distress, and depressive symptoms. We described sleep metrics across racial/ethnic groups …

Privacy In Perspective: Research Participants’ Priorities And Concerns Related To Sharing Data Generated In Human Neuroscience Studies, Christi J Guerrini, Jill O Robinson, Norah L Crossnohere, Mary A Majumder, Kathryn Maxson Jones, Whitney Bash Brooks, Sameer A Sheth, Amy L Mcguire

Faculty, Staff and Students Publications

The societal benefits from sharing and reusing data collected in human neuroscience studies are widely appreciated. However, there are persistent barriers to data sharing as well as privacy concerns related to unauthorized access, misuse, and reidentification of deidentified data. Thus far, few studies have been conducted with neuroscience research participants to understand their data sharing priorities and concerns. We conducted a survey utilizing an experimental design with N=52 participants in neuroscience studies funded by the U.S. National Institutes of Health representing diverse neurotechnologies and health conditions. Respondents prioritized sharing practices that maximize reuse of data to benefit patients and reduce …

Gastrointestinal Infection Before Immune Checkpoint Inhibition Hinders Treatment Efficacy And Increases The Risk Of Colitis, Malek Shatila, Kian Abdul-Baki, Andres Urias Rivera, Kei Takigawa, Irene Jeong-Ah Lee, Andrew Sullivan, Tanvi Gupta, Linfeng Lu, Raakhi Menon, Ayesha Khan, Hamza Salim, Elliot Baerman, Carolina Colli Cruz, Cristina Natha, Varun Vemulapalli, Garrett Coleman, Krishnavathana Varatharajalu, Christopher Fan, Pablo Okhuysen, Anthony J Olszanski, Yan Zhou, Hao Chi Zhang, Mehnaz Shafi, Yinghong Wang

Faculty, Staff and Students Publications

Background: Gastrointestinal (GI) infections, which often result in or stem from intestinal dysbiosis, can affect the efficacy of immune checkpoint inhibitors (ICIs) and increase the risk of adverse effects, such as colitis. In this study, we explored the impact of GI infections before initiation of ICI therapy on the incidence and severity of immune-mediated colitis (IMC) and survival.

Methods: A single-center, retrospective review including all patients who received ICIs from January 2010 to February 2024 and subsequently developed IMC. Patients were screened for IMC and prior GI infections based on symptoms and stool tests. Patients' demographic, IMC, and GI infection-related …

Characterization Of Visual Field Loss Over 4 Years In The Rate Of Progression In Ush2a-Related Retinal Degeneration (Rush2a) Study, Jacque L Duncan, Maureen G Maguire, Lee S Mcdaniel, Nicole R Doucet, Isabelle Audo, Allison R Ayala, Janet K Cheetham, Peiyao Cheng, Todd A Durham, Rachel M Huckfeldt, Robert B Hufnagel, K Thiran Jayasundera, Naheed Khan, Brett Malbin, Ramiro S Maldonado, Michel Michaelides, Mark E Pennesi, Christina Y Weng, Alex Zmejkoski, Shobana Aravind, Hiroshi Ishikawa, David G Birch

Faculty, Staff and Students Publications

Purpose: To report visual field loss using static perimetry (SP) and kinetic perimetry (KP) over 4 years in the Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) study.

Design: Prospective, observational cohort study.

Subjects, participants, and/or controls: Participants had USH2A-related rod-cone degeneration, visual acuity ≥20/80, and KP III4e ≥10° at baseline in the study eye. Preserved cohorts with baseline visual fields sufficient to detect progression were identified.

Methods: Participants were examined annually through 4 years. Mixed-effects models were used to estimate the annual, standardized rate, and percentage rates of change.

Main outcome measures: SP measures included hill of vision (total: …

Novel Parent Survey Measures Sensory Behaviors Incorporating Sensory Modality And Stimulus Intensity, Connor Yee, Ellie Rather, Sakib Hoque, Joon Lee, Stephanie Marton, Jill Roth, Frederick L Oswald, Kenneth J Nobleza, Ankona Banerjee, Holly Harris, Ariel M Lyons-Warren

Faculty, Staff and Students Publications

Objective: Sensory behaviors are common, clinically relevant features of many neurodevelopmental disorders, including autism. However, existing assessments lack granularity in evaluating hypersensitivity and hyposensitivity, particularly in relation to stimulus intensity. We address this gap with our Sensory Response Questionnaire Phenotyper (SRQP), a parent-questionnaire that comprehensively assesses sensory behaviors across five sensory modalities. The purpose of this study was to validate the SRQP against established tools and assess its efficacy in identifying nuanced sensory processing patterns in children with autism.

Methods: A convenience sample of 317 participants (57 with autism, 260 typically developing) aged 3-17 years were enrolled in a cross-sectional …

Mechanisms Underlying Atrial Fibrillation In Chronic Kidney Disease, Jose Alberto Navarro-Garcia, Joshua A Keefe, Jia Song, Na Li, Xander H T Wehrens

Faculty, Staff and Students Publications

Chronic kidney disease (CKD) is a serious and progressive worldwide health problem affecting 15 % of the global population. CKD is associated with higher mortality rates due to secondary complications such as cardiovascular disease. Common cardiovascular complications found in CKD patients include left ventricular hypertrophy, heart failure, and cardiac arrhythmias. The most common type of cardiac arrhythmia in CKD patients is atrial fibrillation (AF). Proper management of AF is important due to its high risk of cardiovascular complications and stroke. The incidence of AF remains higher in CKD patients than in the healthy population, highlighting the need to improve our …

Sugar Functionalized Collagen Material For Local Modulation Of Innate Immunity, Francesca Taraballi, Claudia Corbo, Julia Enterria-Rosales, John Otto Martinez, Silvia Minardi, Laura Pandolfi, Xing Wang, Ennio Tasciotti, Kavindra V Singh, Cesar A Arias, Bruna Corradetti

Faculty, Staff and Students Publications

Small alterations during the early stages of the innate immune response to an implant can drive large changes in adaptive immunity. Biomaterials for regenerative purposes can be engineered to modulate this immune response in beneficial ways. This study presents an innovative patch designed and functionalized to target the innate immunity at the implant site. Mannose moieties are incorporated into collagen patches, resulting in a technology called Local Immunotuning Patch (LIP), designed to directly interact with antigen presenting cells through their mannose receptor. In vitro, LIP shows anti-inflammatory effects on bone marrow-derived macrophages and inhibitory properties even on methicillin-resistant bacterial strains. …

Minimum Core Data Elements For Evaluation Of Thoracic Aortic Disease, Andreina Carbone, Mary J Roman, Melissa L Russo, Kathryn W Holmes, Maya Brown-Zimmerman, John Elefteriades, Catherine M Otto, Nicholas S Burris, Carlos Alberto Campello Jorge, Scott C Deroo, Maral Ouzounian, Matthew D Solomon, Jay D Humphrey, Bart Loeys, Shaine A Morris, Guillaume Jondeau, Scott A Lemaire, Sherene Shalhub, Siddharth K Prakash

Faculty, Staff and Students Publications

Thoracic aortic aneurysms predisposing to aortic dissections are rare but potentially deadly conditions that can be inherited in families. Understanding the natural history and genetic causes of thoracic aortic disease (TAD) requires international collaboration. The aim of this project is to provide core data elements that can be assessed directly and summarized efficiently in research records while developing standards to harmonize data across registries and clinical trials. Ten contemporary TAD registries were analyzed to identify significant gaps in the amount and types of data that are needed for accurate, verifiable, and reproducible studies. The set of data elements recommended by …

Hospital Experiences And Medical Traumatic Stress In Adults With Spina Bifida, Ellen Fremion, Nora Deibler, Juliana Abel, Monique Ridosh

Faculty, Staff and Students Publications

Purpose

This study examined hospital and emergency department (ED) experiences of adults with spina bifida (SB), medical traumatic stress (MTS) and participant characteristics including anxiety, depression, post-traumatic stress disorder (PTSD) symptoms, and resiliency scores.

Methods

Adults with SB who had a hospital or ED encounter within the last five years were recruited from a medical home clinic and completed a structured interview and validated questionnaires. Narrative inquiry was used and descriptive analyses were conducted. MTS scores were reported per participant characteristics and emotional health questionnaire score counts and percentages.

Results

Twenty-five adults with SB representing 37% of eligible patients were …

Left Bundle Branch Area Pacing Compared With Biventricular Pacing For Cardiac Resynchronization Therapy In Patients With Left Ventricular Ejection Fraction ≤50%: Results From The International Collaborative Lbbap Study (I-Clas), Ramez Morcos, Pugazhendhi Vijayaraman, Óscar Cano, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit S Sharma, Marek Jastrzebski, Manuel Molina-Lerma, Zachary I Whinnett, Kevin Vernooy, Jiangang Zou, Girish M Nair, Rajeev K Pathak, Roderick Tung, Gaurav A Upadhyay, Karol Curila, Mihail G Chelu, Kenneth A Ellenbogen

Faculty, Staff and Students Publications

Background: Cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) is an established treatment of heart failure with reduced ejection fraction and wide QRS. Left bundle branch area pacing (LBBAP) has emerged as a physiologic alternative by directly engaging the His-Purkinje system, potentially improving electrical resynchronization and clinical outcomes.

Objective: The aim of the study was to compare the clinical outcomes between BVP and LBBAP in patients with left ventricular ejection fraction (LVEF) ≤50% undergoing CRT.

Methods: This multicenter observational study included patients with LVEF ≤50% receiving CRT with either LBBAP or BVP at 18 centers from January 2018 to June …

Effect Of Aerobic Or Resistance Exercise, Or Both On Insulin Secretion, Ciliary Neurotrophic Factor, And Insulin-Like Growth Factor-1 In Dieting Older Adults With Obesity, Georgia Colleluori, Viola Viola, Siresha Bathina, Reina Armamento-Villareal, Clifford Qualls, Antonio Giordano, Dennis T Villareal

Faculty, Staff and Students Publications

Background and aims: Obesity exacerbates age-related changes in metabolic and physical function. The effect of distinct exercise modalities combined with diet-induced weight loss on insulin secretion in older adults with obesity and frailty is unknown, and the potential mediators of the metabolic and functional improvements induced by lifestyle therapy still need to be identified. We aimed to assess the effects of various exercise therapies coupled with diet-induced weight loss on insulin secretion and sensitivity and on the levels of circulating Ciliary Neurotrophic Factor (CNTF), its receptor (CNTFRα), and Insulin-like Growth Factor-1 (IGF-1) in older adults with both obesity and frailty. …

Genetic Diversity And Expanded Phenotypes In Dystonia: Insights From Large-Scale Exome Sequencing, Mirja Thomsen, Fabian Ott, Sebastian Loens, Gamze Kilic-Berkmen, Ai Huey Tan, Shen-Yang Lim, Ebba Lohmann, Kaja M Schröder, Lea Ipsen, Lena A Nothacker, Linn Welzel, Alexandra S Rudnik, Frauke Hinrichs, Thorsten Odorfer, Kirsten E Zeuner, Friederike Schumann, Andrea A Kühn, Simone Zittel, Marius Moeller, Robert Pfister, Christoph Kamm, Anthony E Lang, Yi Wen Tay, Ana Luísa De Almeida Marcelino, Marie Vidailhet, Emmanuel Roze, Joel S Perlmutter, Jeanne S Feuerstein, Victor S C Fung, Florence Chang, Richard L Barbano, Steven Bellows, Aparna A Wagle Shukla, Alberto J Espay, Mark S Ledoux, Brian D Berman, Stephen Reich, Andres Deik, Andre Franke, Michael Wittig, Sören Franzenburg, Jens Volkmann, Norbert Brüggemann, H A Jinnah, Tobias Bäumer, Christine Klein, Hauke Busch, Katja Lohmann

Faculty, Staff and Students Publications

Objective: Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex.

Methods: Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible.

Results: We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG …

Parabolic Flight As A Research Platform To Investigate Ophthalmic Changes In Microgravity, Tuan Nguyen, Joshua Ong, Sarah Aman, Alex Weaver, Ana Garcia, Amy Song, Fatma Shakarchi, Ethan Waisberg, Andrew G Lee

Faculty, Staff and Students Publications

Parabolic flight serves as an important terrestrial analog to study acute physiological changes in microgravity without the need for space travel. During a parabolic flight, alternating hypergravity and microgravity phases, lasting up to 40 seconds, enable research into ophthalmic changes. In this review, we discuss the application of parabolic flight as a platform to study microgravity-related changes that might impact ophthalmology including intraocular pressure, intracranial pressure, choroidal blood flow, and modified eye movement patterns. We further highlight how these insights could aid our understanding of vestibulo-ocular reflexes and conditions such as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the brief duration …

Data-Driven Approach To Dynamic Resting State Functional Connectivity In Post-Traumatic Stress Disorder: An Enigma-Pgc Ptsd Study, Carissa W Tomas, Jacklynn M Fitzgerald, C Lexi Baird, Courtney C Haswell, Chadi G Abdallah, Michael Angstadt, Justin T Baker, Hannah Berg, Jennifer U Blackford, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Terri A Deroon-Cassini, Seth G Disner, Wissam El Hage, Negar Fani, Jessie L Frijling, Evan M Gordon, Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A Mclaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A Van Der Wee, Steven J A Van Der Werff, Sanne J H Van Rooij, Mirjam Van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey

Faculty, Staff and Students Publications

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven …

Sirt5 Inhibition Impairs Mitochondrial Metabolism And Enhances Venetoclax-Induced Elimination Of Acute Myeloid Leukemia Cells, Moran Wang, Ruiqi Zhu, Donald Small, Lan Lin, Li Li, Shengling Ma, Linghui Xia, Shanshan Luo, Wenjuan He, Jianming Yu, Junying Li, Ruowen Wei, Ao Zhang, Wei Shi, Yu Hu

Faculty, Staff and Students Publications

Metabolic reprogramming is a key focus of targeted therapies in acute myeloid leukemia (AML). The mitochondrial sirtuin SIRT5 removes succinyl groups from specific lysines and impacts cell metabolism, but its role in AML tumorigenesis has not been extensively explored. A recent study highlighted that SIRT5 regulates AML cell activity by modulating glutamine metabolism, but its molecular targets in AML remain unclear. This study aims to identify the substrates of SIRT5 in AML. It was found that a total of 83 proteins with 121 lysine (K) residues showed increased succinylation after SIRT5 knockdown, as determined by succinylome analysis of MOLM-13 cells. …

Cervical Cancer Outcomes In Women With Hiv In The Age Of Antiretroviral Therapy, Alison K Yoder, Rehema J Thomas, Austin Huang, Anushka Mandalapu, Dana M Roque, Kristina Bowles, Kevin Albuquerque, Christina Son, Michelle S Ludwig, Kimberly Levinson, Anna E Coghill, Elizabeth Yu Chiao, Lilie L Lin

Faculty, Staff and Students Publications

This cross-sectional study investigates the outcomes for women living with HIV and cervical cancer in the US after the emergence of antiretroviral therapy.

Endovascular Treatment Of Cirsoid Aneurysms: A Stepwise Approach To Successful Embolization, Ronak Patel, Parker Mitchell, Mohadese Ahmadzade, Mohammad Ghasemi-Rad, Ravi Kaushikkumar Shastri

Faculty, Staff and Students Publications

Cirsoid aneurysms, a subtype of arteriovenous fistulas (AVF), of the scalp are rare pathological lesions characterized by abnormal fistulous connections between superficial arteries and draining veins without intervening capillary beds. We present a case report of a cirsoid aneurysm located on the scalp, treated at our tertiary care center using percutaneous endovascular intervention with injection embolics. This report highlights the challenges posed by complex vascular anatomy and high shunt flow in the treatment of such lesions involving the head and neck. We discuss the rationale for selecting the treatment approach, emphasizing the importance of a patient-specific strategy to achieve successful …

Nephrostomy (Pcn) Versus Nephroureteral Stent (Double Jj); An Ongoing Battle, Mohammad Ghasemi-Rad, Kelly Trinh, David Wynne, Mohadese Ahmadzade, Muhammad Hamza Shamim, Omar Guerrero, Ashley Bancroft, Shreya Ranganath, David Leon

Faculty, Staff and Students Publications

In the realm of medical procedures for urinary obstructions, a distinct division of roles is evident: the vast majority of percutaneous nephrostomies (PCNs) are the domain of Interventional Radiology (IR), while the placement of double J stents (JJ stents) falls squarely under Urology. This division, however, is not without its complexities. When confronted with a patient suffering from a urinary obstruction, the decision-making process can become intricate. The underlying cause often fuels the debate: should IR intervene with a PCN, or should Urology place a JJ stent? Such decisions have profound implications for the individual patient.In this comprehensive review, we …

Rescue Use Of A Bovine Carotid Artery Xenograft For Coronary Artery Reattachment In Acute Type A Aortic Dissection, Alexis Nichols, Abraham N Katz, Scott A Weldon, Ginger M Etheridge, Susan Y Green, Anna H Xue, Vicente Orozco-Sevilla, Marc R Moon, Joseph S Coselli

Faculty, Staff and Students Publications

No abstract provided.

Explant Of An Infected Four-Vessel Fenestrated And Bilateral Iliac Branch Stent Graft In A Patient Of Jehovah’S Witness Faith, Carlotta Bugna, Lucas Ruiter Kanamori, Priscila Suguita, Ezra Koh, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Students Publications

Infection of fenestrated-branched stent graft is an uncommon but potentially catastrophic complication. The technical challenge of total stent graft explant and reconstruction of the renal-mesenteric arteries is associated with high mortality and morbidity. Among patients of Jehovah Witness faith, refusal to accept blood transfusion adds to the risk given the invasiveness of these operations. We report a Jehovah's Witness faith patient with a recurrent infection of a four-vessel fenestrated and bilateral iliac branch stent graft treated in two stages by axillofemoral bypass, followed by extra-anatomical reconstruction of the mesenteric, renal, and left internal iliac arteries and total stent graft explant …

Integrative Exome Sequencing And Machine Learning Identify Micb And Interferon Pathway Genes As Contributors To Ssc Risk, Shamika Ketkar, Hongzheng Dai, Lindsay Burrage, David Murdock, Brian Dawson, Marialbert Acosta-Herrera, Martin Kerick, Javier Martin, Kevin Wilhelm, Jennifer Kay Asmussen, Olivier Lichtarge, Regeneron Genetics Center, Shervin Assassi, Maureen D Mayes, Brendan H Lee

Faculty, Staff and Students Publications

Objectives: Systemic sclerosis (SSc) is a complex autoimmune disease with both known and unidentified genetic contributors. While genome-wide association studies (GWAS) have implicated multiple loci, many reside in noncoding regions. We aimed to identify novel protein-coding variants and pathogenic pathways using exome sequencing (ES) integrated with an Evolutionary Action-Machine Learning (EAML) framework, single-cell RNA sequencing (scRNA-seq), and expression quantitative trait locus (eQTL) analysis.

Methods: GWAS was conducted in 2,559 SSc cases and 893 controls of Caucasian ancestry, with replication in 9,846 cases and 18,333 controls of European ancestry. EAML prioritized genes with high-impact missense variants predictive of disease. Public scRNA-seq …

Molecular Maestro In The Lung: The Sphingolipid Rheostat, Joselyn Rojas-Quintero, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Glycerol Kinase Gene Variant As A Cause Of Pseudohypertriglyceridemia And Apparent Poor Response To Plozasiran, Miriam Larouche, Christie Ballantyne, Josiane Dufour, Diane Brisson, Bruce Given, Daniel Gaudet

Faculty, Staff and Students Publications

Severe hypertriglyceridemia (HTG) is characterized by plasma triglyceride (TG) levels >500 mg/dL (SI: 5.7 mmol/L) (reference range, < 150 mg/dL [SI: < 1.7 mmol/L]) and is linked to cardiovascular disease and pancreatitis risk. Treatment typically involves dietary restrictions and lipid-lowering medications. Glycerol kinase deficiency (GKD) is a rare genetic disorder that causes pseudo-HTG.

In SHASTA-2, a study of patients with severe HTG, most subjects (>90%) treated with plozasiran, an apolipoprotein C-III (APOC3) small interfering RNA (siRNA), achieved TG levels < 500 mg/dL (SI: 5.7 mmol/L), below the risk threshold for acute pancreatitis. We report herein a case study of a 65-year-old male apparently not responding to plozasiran. The patient was shown to carry a loss-of-function variant in the GK gene resulting in GKD, with high free glycerol (40.24 mg/dL or 4.37 mmol/L) (reference range, 0.03-0.13 mmol/L) that contributed to an overestimation of TG concentration. After correcting for free glycerol, the patient was noted to have had mild HTG, with plozasiran treatment decreasing real TG values by up to 71%.

This case report suggests that …

Incidence, Predictors, And Indications Of Permanent Pacemaker Implantation Following Orthotopic Heart Transplantation: A Single-Center Experience, Iriagbonse Rotimi Asemota, Siddharth Das, Michelle Nsahlai, Edward Graviss, Duc T Nguyen, Paul A Schurmann, Rayan Yousefzai

Faculty, Staff and Students Publications

In the modern era of orthotopic heart transplantation (OHT) with bicaval anastomosis, there is a paucity of data on permanent pacemaker implantation (PPI) in this population. This is a retrospective study describing the incidence, indication, and predictors in patients who underwent PPI after OHT. Using the transplant database from our institution between January 2016 and December 2022, 370 patients who had de-novo OHT were identified. The incidence of PPI post-OHT was 8.1% (n = 30 patients). The average time from OHT to PPI was 30.5 days. The most common indication for PPI was sinus node dysfunction, accounting for 83% …

Changes In Post-Transplant Serum Testosterone Levels In Men Undergoing Lung Transplantation: A Pilot Study Using The Trinetx Research Network, Austin Thompson, Danly Omil-Lima, Jaime Abraham Perez, Erin Jesse, Mohit Khera, Kenneth Chavin, Nannan Thirumavalavan

Faculty, Staff and Students Publications

Hypogonadism is understudied in men requiring solid organ transplants, particularly among lung transplant recipients. Improvement in serum testosterone levels has been reported in kidney and liver transplantation. Using the TriNetX Research Network, we performed a retrospective cohort study to evaluate the incidence of peri-transplant hypogonadism and the natural course of serum testosterone following successful lung transplantation. Men aged ≥ 18 with a lung transplant and total testosterone drawn within one year pre- and post-transplant were included. Men with receipt of testosterone therapy were excluded. A low testosterone (< 300 ng/dL) and normal testosterone (≥300 ng/dL) cohort was created before employing descriptive and analytic statistics to investigate the incidence of peri-transplant hypogonadism and the change in serum testosterone levels following lung transplantation. In our entire cohort, lung transplantation was not associated with a significant increase in post-transplant serum testosterone (329.86 ± 162.56 ng/dL pre-transplant and 355.13 ± 216.11 ng/dL post-transplant, p = 0.483). The number of men with low testosterone decreased by 9.8% following lung transplantation but was not significant, p = 0.404. In this pilot study, no significant change in the number of hypogonadal men nor serum testosterone levels was observed among men undergoing lung transplantation.

Definitions Of Cardiogenic Shock And Indications For Temporary Mechanical Circulatory Support: Joint Consensus Report Of The Perioperative Quality Initiative And The Enhanced Recovery After Surgery Cardiac Society, Michael C Grant, Charles Scott Brudney, Jaime Hernandez-Montfort, Stephanie O Ibekwe, Amanda Rea, Christian Stoppe, Alexander Zarbock, Andrew D Shaw, Daniel T Engelman, Manreet K Kanwar, Perioperative Quality Initiative (Poqi) And The Enhanced Recovery After Surgery (Eras) Cardiac Society Workgroup

Faculty, Staff and Students Publications

Background: The management of patients with cardiogenic shock (CS) is complex and resource intensive, particularly given the recent surge in temporary mechanical circulatory support (tMCS) devices. This document was created to establish an approach to the assessment of CS to provide early and targeted therapies, including tMCS.

Methods: An interdisciplinary, international panel of experts, using a structured appraisal of the literature and a modified Delphi method, derived consensus regarding the assessment of CS based on pathophysiologic severity, etiology, and phenotypic clustering to guide escalation of care as well as identify those patients who might benefit from tMCS.

Results: Key principles …

Notice-Ed: Nurse Or Technician Insights Into Cognitive Evaluations In The Emergency Department, Sarah J Nessen, Anita N Chary, Annika R Bhananker, K Jane Muir, Lauren T Southerland, Kyra O'Brien, Ari B Friedman

Faculty, Staff and Students Publications

Background: Several strategies have been proposed to increase chronic cognitive impairment (CI) screening in the emergency department (ED). Our goal was to assess the feasibility and acceptability of implementing specific CI screening tools and strategies in the ED from an ED registered nurse and technician perspective.

Methods: We performed a qualitative study using semi-structured interviews with a purposive sample of ED nurses and ED technicians (EDTs). Participants worked at an urban academic hospital and were interviewed between November 2023 and March 2024. Interviews assessed participants' opinions on the feasibility and acceptability of CI screening and the use of machine learning …