Medical Sciences Commons^™

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

The Effect Of Hunger On The Likelihood Of Glucose Excursions In Adults With Overweight Or Obesity: Continuous Glucose Monitoring And Ecological Momentary Assessment Observational Study, Byunggul Lim, Phrashiah Githinji, Yue Liao, Jacob Szeszulski, Alexandra L Macmillan Uribe, Rebecca A Seguin-Fowler, Jane Anderson, Chad D Rethorst

Faculty, Staff and Students Publications

Background: Maintaining stable glucose levels is important for metabolic health. Glucose excursions (GEs), which are marked increases in glucose following food intake, have been associated with a higher risk for cardiovascular disease and metabolic dysfunction. Individuals with overweight or obesity who do not have diabetes may still show impaired glucose regulation, as reflected in increased glucose variability. Hunger, as a real-time physiological cue, may be associated with subsequent glucose changes and represents a potential target for just-in-time adaptive interventions.

Objective: This study aimed to investigate the temporal relationship between self-reported hunger and subsequent glucose dynamics, including the likelihood of GE …

Rare Pediatric Venolymphatic Malformations: Pericardial Cyst Mimickers, Shelby E Walcott, Joseph Burns, Juan Pablo Sandoval Jones, Neil Cambronero, David Brennen, Thomas M Glenn, Betul Yilmaz Furtun

Faculty, Staff and Students Publications

Background: Pericardial cystic masses are rare, and exceedingly so in pediatrics. The clinical course of such masses in children is poorly described.

Case summary: We report 2 cases in 3- and 7-year-old children. Both were initially thought to represent pericardial cysts on imaging, but surgical excision and histopathology confirmed diagnoses of a venolymphatic malformation and an epicardial cyst, respectively. The first patient presented with abdominal pain, and the second patient was asymptomatic. Both recovered well after an uncomplicated surgical intervention.

Discussion: A small number of patients with pericardial masses will have symptoms thought to be related to compression of adjacent …

Prevalence Of Hyperprolactinemia And Its Association With Menstrual Abnormalities And Hypothyroidism Among Infertile Women: A Cross-Sectional Study From Saudi Arabia, Aseel Y. Alwahhabi, Rahaf H. Labban, Maryam Y. Alshaikh, Amal M. Alanazi, Samaher S. Alfaraj, Fahad M. Alsalman, Hayat A. Alrabiea

Saudi Medical Journal

Objectives: To determine the prevalence of hyperprolactinemia among infertile women and assess its association with menstrual irregularities and hypothyroidism in a tertiary-care setting in Riyadh, Saudi Arabia.

Methods: A cross-sectional study was conducted between September 2022 and August 2023 at the Reproductive Endocrinology and IVF Unit, King Abdulaziz Medical City, Riyadh. Electronic medical records of 480 infertile women who met the inclusion criteria were reviewed. Data on demographic characteristics, infertility type, thyroid status, and serum prolactin levels were collected and analyzed using SAS version 9.4. Statistical significance was set at p < 0.05.

Results: Hyperprolactinemia was identified in 27.7% of infertile women, …

Polysomnographic And Clinical Characteristics Of Narcolepsy In Saudi Arabia: A 12-Year Retrospective Study, Banan Almalki, Omar Kanbr, Ghufran Bin Afeef, Shaimaa Hawsawi, Ranya Alshumrani, Faris Alhejaili, Siraj Wali

Saudi Medical Journal

Objective: To evaluate the clinical features, polysomnographic findings, and therapeutic outcomes of narcolepsy type 1 and type 2 patients in Kingdom of Saudi Arabia (KSA). Narcolepsy is a neurological condition marked by excessive daytime sleepiness (EDS) and associated symptoms, including cataplexy and disrupted nighttime sleep. Data on narcolepsy in KSA are still limited.

Methods: Forty-three patients diagnosed with narcolepsy from 2012 to 2024 were included in this retrospective study. Diagnosis followed the International Classification of Sleep Disorders criteria and incorporated clinical features, the epworth sleepiness scale (ESS), overnight polysomnography (PSG), and multiple sleep latency testing (MSLT). Data on demographics, clinical …

Lived Experiences And Perceptions Of People With Knee Osteoarthritis In Saudi Arabia: A Qualitative Study, Sultan A. Alanazi, Amjad S. Alhabishi, Rana O. Alawafi, Samia A. Alamrani

Saudi Medical Journal

Objectives: To explore how people with knee osteoarthritis (OA) in Kingdom of Saudi Arabia (KSA) perceive and live with their condition, how they self-manage symptoms, and how they experience physiotherapy and rehabilitation services.

Methods: A descriptive qualitative study was conducted using semi-structured interviews. Interviews were undertaken with individuals with knee OA who are aged ≥ 45 years. Interviews were audio-recorded, transcribed verbatim, de-identified and analyzed using reflexive thematic analysis with investigator triangulation.

Results: Twenty-seven (19 females) participants aged 45–74 years (mean = 61) from different regions of KSA shared lived experiences of knee OA. Four themes describing participants' experiences …

Prevalence And Risk Factors Of Surgical Site Infections In Hospitals Across Al Madinah Al Munawwarah, Saudi Arabia: A Retrospective Cohort Study, Atheer M. Aljohani, Danah O. Sandaqji, Rana A. Alahmadi, Raha Z. Ishqi, Manal A. Alanazi, Shouq N. Aloufi, Husain I. Sandugji

Saudi Medical Journal

Objectives: To determine the prevalence of surgical site infection (SSI) and identify associated risk factors in hospitals in Al Madinah Al Munawwarah, Saudi Arabia.

Methods: We conducted a retrospective cohort study of 363 adult surgical patients from major hospitals in Madinah between 2023 and 2024. We analyzed medical records using descriptive statistics, bivariate analysis, and multivariable logistic regression.

Results: The overall SSI rate was 5.2% (95% confidence interval [CI]: 3.3–7.9%). Infection types comprised superficial incisional (57.9%), deep incisional (36.8%), and organ/space infections (5.3%). Significant risk factors included younger age (adjusted odds ratio [aOR] = 0.94 per year, p = 0.014), …

A Predictive Model For Cytomegalovirus Infection Using Routine Hematological And Biochemical Parameters: A Pilot Study, Ahmad A. Shaikh, Mofareh H. Alabdaly, Nabil A. Ageeli, Sultan Z. Alasmari, Adel M. Abo Mansour, Mohammed H. Makkawi

Saudi Medical Journal

Objective: To examine whether hematological and biochemical parameters assist in diagnosing cytomegalovirus (CMV) infections and differentiating between CMV-G and CMV-M. Cytomegalovirus causes distinct hematological changes that can serve as markers for diagnosis.

Methods: A retrospective analysis was conducted on 54 patients infected with CMV (25 CMV-G and 29 CMV-M) and 82 healthy controls. Age, gender, and routine hematological and biochemical parameters were evaluated. Receiver operating characteristics (ROC) analysis and logistic regression were used for data analysis.

Results: In comparison to controls, laboratory findings of patients with CMV-G revealed characteristic decreases in red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), and …

Safety And Efficacy Of Adalimumab Biosimilar In Psoriasis And Hidradenitis Suppurativa: A Clinical Experience, Raneem H. Najjar, Sarah O. Alrashid, Rnda F. Almahfouz, Hadeel T. Alzahrani, Majed Y. Aleissa, Alanoud R. Hakami

Saudi Medical Journal

Objectives: To evaluate the clinical experience, safety, and effectiveness of adalimumab biosimilars in patients with psoriasis and hidradenitis suppurativa.

Methods: We conducted a retrospective, single-center observational study between March and September 2024 using electronic medical records from King Abdulaziz Medical City and King Abdullah Specialized Children's Hospital, Riyadh, Saudi Arabia. Pediatric and adult patients with psoriasis or hidradenitis suppurativa who switched to adalimumab biosimilars between 2016 and 2022 were included. Variables included demographics, disease characteristics, prior therapies, biosimilar use, and adverse events.

Results: A total of 57 (93% adults; 50.9% female) patients were included. Obesity was present in 35.1%, and …

Immunoinformatic Based Development Of A Multi-Epitope Precision Vaccine Targeting Glycoprotein And Rdrp Of Oropouche Virus: An Innovative Approach To Counter Emerging Public Health Threats, Mohammed Alissa, Muhammad Suleman

Saudi Medical Journal

Objectives: To design high immunogenic vaccine against the Oropouche virus (OROV). The OROV is a neglected arbovirus endemic to Central and South America, causes oropouche fever, which can progress to severe complications such as meningitis and hemorrhagic symptoms.

Methods: We utilized immunoinformatic and molecular dynamic simulation approaches to design highly immunogenic vaccines against OROV. This observational study, carried out between January and August 2024 in Saudi Arabia. As it involves an in-silico method, ethical consent was not required.

Results: Docking analysis confirmed the stable interaction of the designed vaccines with human toll-like receptors (TLR)-3, producing binding scores of –300.78, –306.19, …

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 Kalkanl\I

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 …

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

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 …

Notch1 Acts As A Tumor Suppressor That Induces Early Differentiation In Head And Neck Cancer, Chenfei Huang, Shhyam Moorthy, Qiuli Li, 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, Elizabeth M Vaughan, Xiaoying Yu, Amber B Amspoker, 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 …

Development And Preliminary Validation Of Orca-Pd, An Online Rapid Cognitive Assessment For Parkinson Disease: Mixed Methods Study, Avigail Lithwick Algon, Sarah Brisman, Chi-Ying R Lin, 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 …

Intouch Week Of June 8, 2026, New York Medical College

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• As COPD Rates Rise in Women, Clinical Trial Representation Lags
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Behavioural Activation For The Prevention Of Poststroke Depression In Low-Income Older Stroke Survivors (Live Wel): Protocol For A Randomised Controlled Trial, Jennifer E S Beauchamp, Sean I Savitz, Anjail Sharrief, Belinda M Reininger, Ronald Acierno, Robert Suchting, Jason Burnett, Lauren Rosales, Jenan Ahmed Albaqali, Rinitha Rajan, Namkee G Choi

Faculty, Staff and Student Publications

Introduction: Poststroke depression (PSD) affects approximately 33% of stroke survivors and is associated with worse outcomes, poor quality of life (QOL) and mortality. Despite its prevalence and consequences, there is no consensus on the most effective strategy for PSD prevention. Behavioural activation (BA) is an effective intervention for depression across diverse populations and is considered safer, better tolerated and a longer-lasting alternative to antidepressant medications. This study aims to test the effectiveness of a remotely delivered BA intervention to prevent PSD (Tele-BA-S).

Methods and analysis: We will conduct a randomised effectiveness trial of 350 low-income adults (≥ 55 years) within …

Patterns Of Language And Visuospatial Lateralisation In Three-Year-Old Children, Josephine E. Quin-Conroy, Donna M. Bayliss, Stephanie J. Bovell, Debra Eamer, Georgina H.M. Earl, Simon E. Fisher, Clyde Francks, Murray T. Maybery, Sarah Pillar, Desiree Silva, Andrew J.O. Whitehouse, Nicholas A. Badcock

Research outputs 2022 to 2026

Little is known about how or when language and visuospatial processing lateralise in the brain, and if individual differences in lateralisation are related to early language or visuospatial abilities. We explored if patterns of language and visuospatial lateralisation are related to cognitive skills in young children. A large sample of 3-year-olds (n = 136) attempted two functional transcranial Doppler ultrasound (fTCD) tasks to estimate language and visuospatial lateralisation. At the group level, language was lateralised to the left hemisphere, but visuospatial processing was weakly lateralised to the right hemisphere. The relationship between patterns of lateralisation and cognitive skills was investigated …

Targeted Reflex Rna Sequencing For Enhanced Variant Classification On Exome And Genome Sequencing Improves Patient Outcomes, Xiaonan Zhao, Robert Rigobello, Morgan Driver, 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 …

Safety And Synergy Of Finerenone And Empagliflozin In Lowering Blood Pressure, Rajiv Agarwal, Ricardo Correa-Rotter, Sankar D Navaneethan, 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%) …

Histone Deacetylase Enzyme Activity Is Not The Universal Anticancer Target Of Hdac Inhibitors, Chaitra Rai, Hang Ruan, Xue Li, Wenbo Li, Hyun-Hwan Jeong, Chengchuang Song, Panpan Liu, Yingjie Chang, Hao Fang, Udhaya Kumar S, Yuxiang Sun, M James You, Dongyin Guan, Zhandong Liu, Leng Han, Xuben Hou, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase inhibitors (HDIs) are approved for treating hematologic cancers and are currently being evaluated in hundreds of clinical trials for various cancers and other diseases, although their mechanisms of action remain poorly understood. Here, our unbiased bioinformatics analyses found that, for most cancer types, expression levels or genetic variants of histone deacetylase (HDACs) do not consistently correlate with carcinogenesis, do not predict cancer patient survival, and do not associate with cellular responses to HDIs. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs. Overexpression of dominant-negative Class I HDACs causes similar protein hyperacetylation …

Monoclonal Antibodies Targeting Pcdh7 Inhibit Tumor Growth And Enhance Immune Responses In Kras-Mutant Non-Small Cell Lung Cancer, Nicole Novaresi, Poorva Ghosh, Shayna Thomas-Jardin, Hui Deng, Xuejun Fan, Zhiqiang Ku, Wei Xiong, Xiaorong Zhou, Jingfei Zhu, Huiyu Li, Mahesh S Padanad, Bethany Smith, Chul Ahn, John D Minna, Zhiqiang An, Ningyan Zhang, Kathryn A O'Donnell

The Brown Foundation: Institute of Molecular Medicine

We identified an important oncogenic role for protocadherin 7 (PCDH7), a cell surface protein frequently overexpressed in lung adenocarcinoma and associated with poor clinical outcome. Pcdh7 depletion reduces tumor burden and prolongs survival in KrasLSL-G12D; Tp53fl/fl mice. These findings nominate this cell surface protein as an actionable therapeutic target and highlight the therapeutic potential of PCDH7 inhibition for non–small cell lung cancer. We report the development and characterization of high-affinity anti-PCDH7 monoclonal antibodies (mAbs) that inhibit downstream mitogen-activated protein kinase (MAPK) pathway activation and suppress tumor growth in multiple mutant KRAS–driven models. A lead mAb (mAb7) sensitized tumors …