Medical Specialties Commons^™

Comparison Of The Effects Of Incubator And Radiant Environments On Physiological Criteria And Pain-Stress Levels During Heel Lance In Neonates In The Neonatal Intensive Care Unit: A Randomized Controlled Trial, Sezin Gürsu, Birsen Karaca Saydam, Oğuzhan Kalkanlı

Saudi Medical Journal

Objectives: To compare the effects of incubator and radiant heat on physiological criteria and pain-stress levels during heel prick procedures in newborns in the neonatal intensive care unit (NICU).

Methods: This randomized controlled quasi-experimental study was conducted between June and December 2023 with newborns diagnosed with IHB hospitalized at a NICU in Turkey. Prior to the heel prick procedure, 72 newborns (gestational age: 37–41 weeks) were randomly and equally assigned to either a radiant heater or an incubator setting. Physiological parameters (temperature, SpO₂, heart rate [HR]) and pain-stress scores of the newborns were measured and compared in both …

Etiology, Management, And Outcomes Of Hospitalized Heart Failure Patients: A Single-Center Study, Adil I. Jumani, Ghada A. Rashwan, Hadiza O. Ibrahim, Safaa M. Almohdar, Khaled M. Alfakih

Saudi Medical Journal

Objectives: To describe the clinical characteristics, etiologies, management patterns, and outcomes of hospitalized heart failure patients in a tertiary care military hospital in United Arab Emirates (UAE), and to benchmark guideline directed medical therapy (GDMT) uptake and care models against regional and international registries.

Methods: We retrospectively reviewed all consecutive patients admitted with a primary diagnosis of heart failure between January and December 2024, at Zayed Military Hospital, UAE. Clinical data were extracted from electronic medical records. The GDMT adherence was assessed according to the 2022 American Heart Association (AHA)/ American College of Cardiology (ACC) and 2023 European Society of …

Identification Of Risk Factors For Renal Insufficiency In Primary Membranous Nephropathy, Lin Qi, Bolong Fang, Xiao Fang, Yamin Yu, Yunqiang Wang

Saudi Medical Journal

Objectives: To identify possible evidence linking certain characteristics associated with primary membranous nephropathy (PMN) to renal failure progression in patients diagnosed with PMN and to establish probable evidence of an association between PMN and other risk factors leading to end-stage renal failure.

Methods: A historical investigation was carried out including 436 subjects with PMN, with or without renal insufficiency, who were treated at the No. 82 Division Defense Medical Center of the People's Liberation Army and Liaocheng People's Medical Center during January 2020 and December 2023. Binary logistic regression study was applied to determine possible hazard elements. Binary logistic regression …

Evaluation Of Raqeem Health Information System In Primary Healthcare Centers In Makkah, Saudi Arabia, Using The Delone And Mclean Information System Success Model, Ali M. Alzahrani, Holly C. Felix

Saudi Medical Journal

Objectives: To evaluate the implementation of Raqeem, a new Electronic Health Information Systems (EHIS) implemented at primary healthcare centers (PHCs) in Makkah. Implementing EHIS requires huge investments, making evaluation of systems success important.

Methods: In this cross-sectional survey design study, a developed questionnaire guided by DeLone and McLean Information System success model (D&M model) was used to collect data from PHCs' providers. Descriptive and structural equation modeling (SEM) techniques were performed to describe and examine the association between the model's constructs and assess Raqeem success.

Results: A total of 490 providers submitted completed records and were included in this study. …

Molecular Mechanisms Of Diffuse Large B-Cell Lymphoma And The Complexities Of Tumor Development, Wael I. Alzahrani

Saudi Medical Journal

Diffuse large B-cell lymphoma (DLBCL), the most prevalent aggressive non-Hodgkin lymphoma, exhibits substantial molecular heterogeneity and arises from germinal center or post-germinal center B cells through recurrent genetic and epigenetic dysregulation of critical signaling pathways. Aberrations involving BCL6, MYC, MYD88, and components of B cell receptor and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B) signaling play central roles in lymphomagenesis, treatment resistance, and clinical outcomes. Gene expression profiling has defined major molecular subgroups in DLBCL, including germinal center B cell–like and activated B cell–like tumors, that show distinct pathogenesis and prognosis. High-risk entities, such as double- and …

Integrating Traditional And Complementary Medicine Into Saudi Primary Care: A Literature Review In Light Of The Who 2025–2034 Strategy, Abeer Al Shahrani

Saudi Medical Journal

Complementary and alternative medicine (CAM) is widely practiced in Saudi Arabia, particularly for health promotion and chronic diseases management. Despite cultural acceptance and high utilization, CAM remains largely unintegrated within the formal healthcare system, particularly in primary care settings. The newly adopted World Health Organization (WHO) Traditional, complementary, and integrative medicine (TCIM) Strategy 2025–2034 offers a global framework for evidence-based, culturally appropriate integration of TCIM into national systems. This review evaluates the status of CAM in Saudi Arabia in light of strategic objectives outlined in the WHO Strategy: building the evidence base, ensuring quality and safety, integrating into health systems, …

Interleukin-6 Inhibition For Patients With Acute Myocardial Infarction: A Systematic Review And Meta-Analysis, Mohammed Y. Alasmary, Mohammed J. Almalki, Faisal H. Almalki, Waleed D. Khubzan, Mohammed H. Rajab, Mohammed S. Almalki, Hussam A. Almalki, Omar M. Alsuwat, Hussam M. Alghannami

Saudi Medical Journal

Objective: To explore the outcomes associated with interleukin-6 (IL-6) pathway blockade, using tocilizumab, in patients with ST-elevation myocardial infarction (STEMI) and non (NSTEMI). Acute myocardial infarction (AMI) denotes myocardial necrosis due to ischemia and presents in distinct electrocardiographic phenotypes. Inflammation driven by IL-6 contributes to ischemia-reperfusion injury, with tocilizumab showing promise in reducing myocardial damage and improving outcomes.

Methods: This work followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Framework and was registered in international prospective register of systematic reviews (PROSPERO). Relevant studies were identified through structured searches of PubMed, MEDLINE, the Cochrane Library, and Google Scholar up …

Effect Of Anesthetic Agents On Middle Ear Pressure: Systematic Review And Meta-Analysis, Nasser Almujaiwel, Reem Alkublan, Latifah Almakoshi

Saudi Medical Journal

Objective: To assess and compare the effects of these agents on middle ear pressure (MEP). Anesthetic agents can significantly alter MEP, which is a critical factor in middle ear surgeries that require stability to prevent complications. Different anesthetics, including inhalational and intravenous agents, have varying effects on MEP.

Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Scopus, following preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Studies that evaluated MEP changes before and after anesthesia using tympanometry were included. Relevant data, such as anesthetic type, patient demographics, MEP measurements, and reported complications, were …

The Impact Of Exercise Intervention On Pulmonary And Physical Function In Patients With Cystic Fibrosis: A Comprehensive Systematic Review, Abdullilah Alghamdi, Muroj Al-Attas, Abrar Radhi, Amnah Alfaqih, Bashair Aljabri, Rawan Alharbi, Sumayyah Alsubaie, Raneem Aljawaied, Sarah Alenazi, Ahlam Mazi, Ebtehal Qulisy

Saudi Medical Journal

Objective: To evaluate the effect of various exercise interventions on lung function, specifically forced expiratory volume in 1 second (FEV₁), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP), as well as on cardiorespiratory fitness (peak oxygen uptake [VO₂peak]), and muscle strength (handgrip strength). The review also considers factors such as patient adherence, follow-up duration, and statistical significance to inform clinical practice.

Methods: This systematic review followed preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines and was prospectively registered in international prospective register of systematic reviews. PubMed, Google Scholar, OVID, and Web of Science …

Cure Sickle Cell Initiative Recommendations On Common Data Elements For Sickle Cell Disease Gene Therapy Trials, Sophie Lanzkron, Victoria H. Coleman-Cowger, Alexis A. Thompson, C. Patrick Carroll, Traci Clemons, Michael Debaun, Julie Kanter, Punam Malik, Deepa Manwani, Francis John Pierciey, Mark C. Walters, Sherita Alai

Cardeza Foundation for Hematologic Research

The Cure Sickle Cell Initiative (CureSCi), created by the National Heart, Lung, and Blood Institute, has developed data standards to increase interoperability and meta-analysis of studies specifically investigating gene therapy for sickle cell disease (SCD). The aims of the CureSCi Common Data Elements (CDE) initiative are to facilitate the development of safe, effective, and accessible gene therapies. Five working groups (WGs) comprising people living with SCD, stakeholders, clinicians, and researchers reviewed current definitions used for SCD clinical studies, including those from the American Society of Hematology, US Food and Drug Administration, PhenX catalog of consensus measures for phenotypes and exposures, …

Text Messaging Support For Patients Diagnosed With Impaired Glucose Tolerance During Pregnancy: Nonrandomized Pre-Post Implementation Study Assessing Impact On Postpartum Transitions Of Care, Natasha R. Kumar, Whitney Bender, Celeste Durnwald

Department of Obstetrics and Gynecology Faculty Papers

BACKGROUND: Patients with impaired glucose tolerance (IGT) identified during pregnancy who do not develop gestational diabetes mellitus (GDM) often do not receive additional interventions for their long-term metabolic risks.

OBJECTIVE: This nonrandomized pre-post implementation study reports the design process and initial program evaluation for Better Follow-up of Impaired Glucose Tolerance (BRIDGE), a 12-week text-based postpartum support program promoting hemoglobin A1c (HbA1c) completion and primary care provider (PCP) visit scheduling for patients diagnosed with IGT during pregnancy, assessing improvement in desired postpartum transition milestones. The 19-month program was divided into 2 arms lasting 9.5 months each, BRIDGE- (SMS text messaging support …

Evaluation Of Corneal Infections Using A Smartphone Macro Lens For Synchronous Telemedicine, Joseph A. Anaya, Julia Yu, Marisa A. Schoen, Dilru C. Amarasekera, Cherie A. Fathy, Sophia Lam, Christopher J. Rapuano, Zeba A. Syed

Wills Eye Hospital Papers

PURPOSE: To determine the efficacy of synchronous telemedicine consultation with a corneal specialist using a macro lens attachment to a smartphone to evaluate corneal infections.

METHODS: Patients aged 18 years or older who presented to the Cornea Clinic at Wills Eye Hospital between June 2020 and March 2021 with a corneal infection were examined by two fellowship-trained cornea specialists. One examiner (CJR) performed face-to-face (FTF) slit-lamp evaluations, whereas another examiner (ZAS) performed synchronous telemedicine visit (STV) evaluations via a smartphone with a macro lens of 7× magnification (Olloclip; Foothill Ranch, CA, USA) held by trained study coordinators. Agreement between examinations …

In Vivo Orf Overexpression Screening Identifies Ccn4 As A Regulator Of Glioblastoma Growth Validated Across Multiple Models

Faculty, Staff and Students Publications

Despite current multimodal therapies for glioblastoma (GBM), its prognosis remains grim. Thus, a tremendous need exists to identify new genetic drivers that may serve as potential therapeutic targets in glioblastoma (GBM). We describe an in vivo overexpression screening strategy to identify drivers of glioblastoma where we have leveraged TCGA datasets to conduct a functional genomics screen of prioritized open reading frames (ORFs) that are overexpressed and/or amplified in GBM. To interrogate these potential drivers within a more relevant physiological context, the screening was accomplished in vivo in an orthotopic patient-derived glioma stem-like cell (GSC) model. Among 5 positive "hits" from …

Right Ventricular–Pulmonary Artery Coupling Predicts Early Myocardial Strain Improvement In Sglt2 Inhibitor-Treated Hfref, Mohammad Ali Hammad, Ramy Magdy Elgamal, Arwa Mohsen Abouelkhir, Osama Abouelfetouh Elshaer, Mohamed Shokry Fahmy, Reda Nabil Dawoud, Reda Biomy, Mohamed Kamal Salama

Journal of the Saudi Heart Association

Background: While sodium-glucose cotransporter-2 (SGLT2) inhibitors clearly benefit left ventricular recovery in heart failure with reduced ejection fraction (HFrEF), their rapid effects on right ventricular (RV) function remain poorly characterized. This prospective observational study investigated the timeline and markers of biventricular changes shortly after SGLT2 inhibitor initiation.

Methods:In this prospective observational study, 50 adults with HFrEF (LVEF

Results:After 3 months, NT-proBNP levels decreased significantly (1116.5 vs 913.5 pg/mL, P

Conclusions: In this prospective observational study without a control group, SGLT2 inhibitor initiation was associated with coordinated biventricular improvements within three months in HFrEF patients. The baseline TAPSE/PASP ratio …

Psychogastroenterology: An Introduction For Behavioral Health And Healthcare Professionals, Jerrod Brown Ph.D., M.A., M.S., M.S., M.S., M.S., M.S., Jeremiah B. Schimp Phd, Ma, Lpcc, Leanne Skehan Dcn, Msacn, Mph, Mba, Cns, Ches, Shelley Mydra Dmft, Lmft, Jonathan Ward Dc, Phd(C), Ms, Dibcn, Tiffany Flaten Cns, Ldn

Nutritional Neurocriminology Today

Although often difficult to discuss with clients, gastrointestinal (GI) issues affect an estimated 60 to 70 million Americans (American Gastroenterological Association, 2022). Yet only about 25% of those experiencing these conditions receive treatment. This is troubling because GI issues frequently co-occur with clinically significant consequences for physical health, psychological well-being, daily functioning, and overall quality of life. Designed for behavioral health and healthcare professionals, this brief article introduces the field of psychogastroenterology, with emphasis on symptoms, stigma, diagnosis, and treatment. Key topics include the gut-brain axis, common digestive health conditions, and the mental health implications associated with gastrointestinal disorders.

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Kazi M Ahmed, Kalil Saab, Defeng Deng, Jiping Wang, Xiayu Rao, Jiexin Zhang, Yuanxin Xi, Jing Wang, Zhiyi Liu, Noriaki Tanaka, David A Wheeler, Eve Shinbrot, Rami Saade, Curtis R Pickering, Tong-Xin Xie, Adel K El-Naggar, Abdullah A Osman, Kunal Rai, Patrick A Zweidler-Mckay, John V Heymach, Lauren A Byers, Faye M Johnson, Vlad C Sandulache, Jeffrey N Myers, Pedram Yadollahi, Mitchell J Frederick

Faculty, Staff and Students Publications

Inactivating NOTCH1 mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function - unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that NOTCH1 is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early …

Structured Telehealth Community Health Worker-Clinician Feedback And Diabetes Outcomes: A Randomized Clinical Trial, Aanand D Naik, Ashok Balasubramanyam, Craig A Johnston, Christi M Ballantyne, Salim S Virani, H Shelton Brown, Kristina Mena, Laura R Porterfield

Faculty, Staff and Students Publications

Importance: Community health workers (CHWs) improve chronic disease management in underserved populations, but scalable integration strategies are limited.

Objective: To evaluate whether a multidimensional intervention incorporating telementored CHWs and a structured participant-CHW-clinician feedback loop can improve diabetes outcomes.

Design, setting, and participants: This 12-month randomized clinical trial was conducted at 3 institutionally and geographically diverse community clinics in Texas between September 1, 2023, and April 30, 2025, and included low-income, uninsured White Hispanic adults with type 2 diabetes identified through clinic databases. Data were analyzed between May 1 and July 31, 2025.

Intervention: Individuals were randomized 1:1 to the intervention …

Recent Antibiotic Exposure And Response To Treatment Of Juvenile Idiopathic Arthritis: A Retrospective Cohort Study, Daniel Horton, Charu Verma, Sanika Rege, Stephen Crystal, Tobias Gerhard, Alicia Iizuka, Matthew Iozzio, Dawn Koffman, Lauren Parlett, Julianne Varga, Carlos Rose, Brian Strom

Department of Medicine Faculty Papers

BACKGROUND: Juvenile idiopathic arthritis (JIA) has been tied to microbiome disruption and antibiotic exposure. Gut microbiota may affect how adults with rheumatoid arthritis respond to methotrexate. We tested if exposure to antibiotics was associated with response to methotrexate for JIA.

METHODS: We conducted a retrospective cohort study using national US public and private insurance claims data (2001-2023). We included children ages 1-17 continuously enrolled for ≥ 10 months and diagnosed with JIA who initiated methotrexate monotherapy or, for comparison, tumor necrosis factor inhibitor (TNFi) monotherapy without prior disease-modifying antirheumatic drug (DMARD) exposure. Antibiotic exposure during the 10-month baseline period was …

Sleep-Circadian Modulation Of Autophagy And Glymphatic Function: Failure Of Coordinated Brain Clearance In Parkinson's Disease, Shamaila Zafar, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson's disease (PD) involves α-synuclein accumulation and progressive neurodegeneration. This review proposes that PD reflects failure of sleep-circadian regulated brain clearance network integrating intracellular autophagy and extracellular glymphatic transport across neurons, glia, and blood-brain-barrier. Disruption of sleep-architecture and circadian-timing desynchronizes these processes, impairing protein clearance and promoting pathology. This framework positions sleep-circadian dysfunction as an upstream mechanism, suggesting that restoring sleep-circadian regulation may improve protein clearance and support disease-modifying strategies.

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, William Saban

Faculty, Staff and Students Publications

Background: Traditional in-person neuropsychological tests for Parkinson disease (PD) lack accessibility, scalability, and PD specificity. Mobility impairments hinder access to in-person assessments, and long waiting times for expert evaluation limit scalability. Common tools for cognitive screening, such as the Montreal Cognitive Assessment, are generic and not specific to PD.

Objective: The goal of this study was to address these challenges by leveraging the internet. This study aimed to develop a sensitive tool to detect cognitive impairments in early- to mid-stage PD in an accessible and scalable manner.

Methods: We developed the Online Rapid Cognitive Assessment for Parkinson's Disease (ORCA-PD), a …

Outcomes In Single Versus Two-Stage Surgical Stabilization Of Complex Bilateral Chest Wall Injury: A Single-Center Experience., Alexis A Schweibinz, Jaya S Varre, Anna Graham, William B Devoe

Surgery Articles

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) continues to show benefit for severe chest wall injury (CWI) with improvement in morbidity and mortality following stabilization. Complex bilateral injuries pose a clinical and technical challenge. Currently, there is no formal recommendation for an approach to repair such injuries, whether that be bilateral SSRF within the index case or staged repair. We sought to describe our institutional experience with this subset of patients, identify factors that may influence the decision to pursue single- versus two-stage procedures, and assess the potential benefit of combined bilateral SSRF during the index operation.

METHODS: A retrospective, …

Inhibition Of Calpain-Mediated Hmgb1 Alleviates Cardiac Inflammation And Dysfunction Induced By Ultra-Processed Foods, Claire Ross, Sanskruti Ravindra Gare, Nasser Ho Alatawi, Oveena Fonseka, Xinyi Chen, Jiayan Zhang, Yihua Han, Andrea Ruiz-Velasco, Riham Re Abouleisa, Yingjuan Liu, Xiangjun Zhao, Han Xiao, Bernard D Keavney, Gareth J Howell, Tao Wang, Tamer Ma Mohamed, Elizabeth J Cartwright, Wei Liu

Faculty, Staff and Students Publications

Increased consumption of ultra-processed foods (UPFs) is a risk factor for metabolic disorder-associated heart failure (HF). Here, we demonstrate that UPF-induced calpain-1 aggravated oxidative stress, thereby increasing high mobility group box 1-mediated (HMGB1-mediated) myocardial inflammation, which contributes to cardiac dysfunction. After illustrating the dysregulated inflammatory pathways in human and murine hearts upon metabolic stress, we revealed an increase in calpain-1 alongside profound oxidative stress and inflammation in the failing myocardium. Mechanistically, in neonatal rat cardiomyocytes and human induced pluripotent stem cell-derived cardiomyocytes, HMGB1 was upregulated by calpain-1 and reactive oxygen species (ROS) upon stress of saturated and trans fatty acids. …

Heat Stroke Encephalopathy Without The Presence Of Distinct Imaging Findings: Case Report And Review Of Literature, Ryan Sholes, David J. Walz, Julia S. Evans, Tessa Connelly, Joseph Rigotti

Abington Jefferson Health Papers

Heat stroke is a life-threatening emergency characterized by severe hyperthermia and acute central nervous system (CNS) dysfunction. We describe a 72-year-old man who was found unresponsive in his vehicle on a day with ambient temperatures exceeding 90°F. On arrival, his core temperature was 105.8°F, and Glasgow Coma Scale (GCS) score was 5. Despite prompt initiation of active cooling and supportive care with normalization of body temperature, the patient developed persistent and fluctuating encephalopathy. Extensive metabolic, infectious, and toxicologic evaluations were unrevealing. Thyroid-stimulating hormone was normal, arterial blood gases showed no acid-base derangements, ammonia and liver function tests were within normal …

Virtual Patient-Specific 3-Dimensional Specimen Maps For Adjuvant Radiation Therapy Planning In Mucosal Head And Neck Squamous Cell Carcinoma, Whitney Jin, Michael C. Topf, Marina Aweeda, Kavita Prasad, Olivia Prosak, Sindhura Sridhar, Zachary Kohutek, Sean All, D. W. Nathan Kim, Anthony Cmelak, Ryan Whitaker, Alexander Langerman, Kyle Mannion, Melanie Hicks, Sarah Rohde, Robert Sinard, Eben Rosenthal, Natalie A. Lockney

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

PURPOSE: Adjuvant radiation therapy planning for mucosal head and neck squamous cell carcinoma is challenging due to postoperative anatomic changes, contributing to variability in clinical target volume (CTV) delineation and risk of geographic miss or unnecessary dose expansion. Patient-specific 3-dimensional (3D) specimen maps may offer a novel approach to improve the localization of high-risk margins and facilitate multidisciplinary communication.

METHODS AND MATERIALS: In this prospective, noninterventional feasibility study, 3D scanning and virtual pathologic mapping of surgical specimens were performed as part of routine pathologic processing. Annotated 3D maps were integrated into the radiation therapy planning workflow and reviewed by the …

Comments On The Letter “Bridging The Gap: The Critical Next Steps For Implementing Genetic Risk Scores In Myocardial Infarction Prevention In Saudi Arabia, Abdullah Saeed

Journal of the Saudi Heart Association

No Abstract for this article type.

Bridging The Gap: The Critical Next Steps For Implementing Genetic Risk Scores In Myocardial Infarction Prevention In Saudi Arabia, Ahmed Almohammadi

Journal of the Saudi Heart Association

No Abstract for this article type.

Imaging And Non-Imaging Approaches For The Diagnosis And Monitoring Of Necrotizing Enterocolitis-What Lies Ahead?, Indrani Bhattacharjee, Catalina Le Cacheux, Eric B. Ortigoza, Jonathan Dillman, Sherwin S. Chan, Alain Cuna

Manuscripts, Articles, Book Chapters and Other Papers

Necrotizing enterocolitis (NEC) remains one of the most serious gastrointestinal emergencies in preterm infants, and imaging plays a central role in diagnosis and clinical management. Historically, evaluation has relied primarily on abdominal radiography, which remains widely available and embedded in established diagnostic frameworks. However, the hallmark radiographic signs of NEC (i.e., pneumatosis intestinalis, portal venous gas, and free air) reflect relatively advanced manifestations of intestinal injury that indicate established mucosal disruption or transmural necrosis. Bowel ultrasound has increasingly complemented radiography by enabling real-time assessment of bowel wall integrity, perfusion, motility, and intra-abdominal fluid, providing physiologic information that may refine clinical …

Targeted Reflex Rna Sequencing For Enhanced Variant Classification On Exome And Genome Sequencing Improves Patient Outcomes, Sydney Lau, Mei Ling Chong, Jason Chibuk, Hongzheng Dai, Wilson C W Wu, Christina Peroutka, Laura Famularo, Alexander Y Kim, Bailey Hummel, Sarah Dugan, Tinsley Douglas, Linyan Meng, Fan Xia, Christine M Eng

Faculty, Staff and Students Publications

RNA sequencing (RNA-seq) has been utilized to provide functional evidence regarding the impact of splicing variants. This study explores the utility of targeted reflex RNA-seq to inform classification of predicted splicing variants identified through clinical exome sequencing (ES) and genome sequencing (GS). A retrospective analysis was conducted on consecutive ES/GS cases completed at a single center in which targeted reflex RNA-seq was performed following identification of eligible variants. There were 131 cases (4.1%) that had at least one RNA-seq eligible variant reported, with eight of these cases having two unique eligible variants. Of the 139 eligible variants, 125 were classified …

Disease-Causing Mfn2 Mutants Impair Mitochondrial Fission Dynamics By Distinct Drp1 Dysregulation, Daniel Lagos, Pamela R. De Santiago, Nicolás Pérez-Bravo, Benjamín Cartes-Saavedra, Josefa Vial-Brizzi, Diego Troncoso-Chandía, Oliver Podmanicky, Rita Horvath, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondria undergo fusion and fission. While DRP1 regulates fission, fusion is controlled by OPA1, MFN1, and MFN2. The balance between these processes and the crosstalk between machineries remains poorly understood. MFN2 mutations cause Charcot-Marie-Tooth disease type 2 A (CMT2A), affecting mitochondrial fusion and morphology. However, their role in fission is unclear. Using skin fibroblasts from CMT2A patients (L248H and M376V MFN2 mutations) and wild-type mouse embryonic fibroblasts expressing these variants, we studied how MFN2 mutations impact mitochondrial dynamics beyond fusion. We analyzed mitochondrial morphology and dynamics by live-cell confocal microscopy and tested fusion/fission protein levels, oxygen consumption rate (OCR), extracellular …

Safety And Synergy Of Finerenone And Empagliflozin In Lowering Blood Pressure, Hiddo J L Heerspink, Matthew R Weir, Janet B Mcgill, Amy K Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Muthiah Vaduganathan, Charlie Scott, Li Li, Meike Brinker, Csaba P Kovesdy, Jennifer B Green, Johannes F E Mann

Faculty, Staff and Students Publications

Background: This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions.

Methods: Participants (n=800) were stratified by baseline SBP (< 130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction.

Results: At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) …