Digital Commons Network^™

Conventional Versus Advanced Imaging Selection For Endovascular Treatment Of Basilar Artery Occlusion Strokes., Huanwen Chen, Marco Colasurdo, Hidetoshi Matsukawa, Conor Cunningham, Ilko Maier, Sami Al Kasab, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M. Starke, Marios-Nikos Psychogios, Edgar A. Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Jonathan A. Grossberg, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G. Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Roberto Crosa, Charles Matouk, Min S. Park, Michael R. Levitt, Waleed Brinjikji, Mark Moss, Travis Dumont, Ergun Daglioglu, Richard Williamson, Pedro Navia, Reade De Leacy, Shakeel Chowdhry, David J. Altschul, Alejandro M. Spiotta, Peter Kan

Department of Medicine Faculty Papers

INTRODUCTION: Endovascular thrombectomy (EVT) is an effective treatment for basilar artery occlusion (BAO) stroke in select patients. While there is a growing body of literature suggesting that advanced imaging modalities such as computed tomography perfusion (CTP) and magnetic resonance (MR) may not be necessary for selecting anterior circulation large vessel occlusion stroke patients for EVT, whether advanced imaging may be superior to conventional imaging (non-contrast CT and CT angiography) in identifying good treatment candidates among BAO patients is less clear.

PATIENTS AND METHODS: This was a multicenter retrospective cohort study of BAO EVT patients treated from 2013 to 2022 in …

External Multicenter Validation Of The Esah Score For Predicting Outcomes After Subarachnoid Hemorrhage, Natália Vasconcellos De Oliveira Souza, Rohan Sharma, Otavio Frederico De Toledo, Ingrid Pereira Marques, Salvador F. Gutierrez-Aguirre, Lara-Velazquez Montserrat, Eric Sauvageau, Naval Neeraj, Amin Aghaebrahim, Feres Chaddad Neto, Ricardo A. Hanel, Gisele Sampaio Silva, William David Freeman

Jefferson Hospital Staff Papers and Presentations

Reliable assessment of prognosis after aneurysmal subarachnoid hemorrhage (SAH) is essential to inform clinical decision-making and prevent premature assumptions of poor outcome. The enhanced SAH (eSAH) score combines three routinely available variables-age, Glasgow Coma Scale (GCS), and subarachnoid hemorrhage blood volume (SAHV)-to provide an objective framework for early outcome stratification. SAHV is estimated using the ABC/2-derived ellipsoid method applied across five major cisternal compartments on non-contrast CT. While the eSAH score has shown promise in initial derivation studies, its external performance and calibration have not yet been validated across diverse healthcare settings. We conducted a retrospective cohort study using consecutive …

Membrane Il-18 Identifies A Human Macrophage Subset With Distinct Proteomic And Functional Traits, Chiara Vitale, Marco Colonna, Et Al.

2020-Current year OA Pubs

This study contributes to the characterization of human macrophages in normal and pathological conditions such as cancer. We characterized a macrophage population expressing membrane-associated IL-18 (mIL-18) that shows peculiar proteomic, phenotypic, ultrastructural, and functional properties. mIL-18+ macrophages exhibit increased levels of key proteins involved in pathogen recognition, activation, migration, and endocytosis. They also display specialized functions in vesicle and actin filament transport and lipid metabolism, and have typical mitochondrial traits. Importantly, mIL-18+ cells dominate the peritoneal fluid of adult cancer patients and are present in the bone marrow of children with neuroblastoma. They express high levels of TREM2 but display …

Co-Developing Strategies For Leprosy Management In Malaysia: A Transdisciplinary Research Approach Involving Individuals Affected By Leprosy And Other Stakeholders, Norana Abdul Rahman, Vaikunthan Rajaratnam, Ruth Mh Peters, Marjolein Bm Zweekhorst, Pamela Wright Phd, Ms, Med, Rn, Cen, Karen Morgan, Mohamed Rusli Abdullah

Publications

Despite Malaysia's low leprosy prevalence, new cases continue to emerge in rural and Indigenous communities. National strategies often prioritise elimination and surveillance, while overlooking the needs and challenges of individuals affected by leprosy and those managing their care. This study employed a transdisciplinary research approach, guided by the Dialogue Model, to co-develop context-specific strategies to improve the lives of those affected through participatory engagement with both groups. Conducted across three high-burden states in Peninsular Malaysia, the research involved a desk review and stakeholder mapping, followed by 40 in-depth interviews with affected individuals and other stakeholders. These were complemented by a …

Speeding Up Interval Estimation For R2-Based Mediation Effect Of High-Dimensional Mediators Via Cross-Fitting, Zhichao Xu, Chunlin Li, Sunyi Chi, Tianzhong Yang, Peng Wei

Faculty, Staff and Student Publications

Mediation analysis is a useful tool in investigating how molecular phenotypes such as gene expression mediate the effect of exposure on health outcomes. However, commonly used mean-based total mediation effect measures may suffer from cancellation of component-wise mediation effects in opposite directions in the presence of high-dimensional omics mediators. To overcome this limitation, we recently proposed a variance-based R-squared total mediation effect measure that relies on the computationally intensive nonparametric bootstrap for confidence interval estimation. In the work described herein, we formulated a more efficient two-stage, cross-fitted estimation procedure for the R2 measure. To avoid potential bias, we performed …

Nutrition Support Adequacy In Children With Biliary Atresia After Liver Transplant, Nicole Knebusch, Manpreet Virk, Moreshwar S Desai, Marwa Mansour, Stacey Beer, Brittany Pearo, Kelby Fuller, Krupa Mysore, John Goss, Thomas Fogarty, Fernando Stein, Jorge A Coss-Bu

Faculty, Staff and Students Publications

No abstract provided.

The Impact Of Pasifikas In Medicine On Pacific Islander Medical Student Experiences, Devon Hori Harvey, Micah Ngatuvai, Siale Vaitohi, Paige E. Faasuamalie, Maegan Tupinio, Lisa H. Smith

Student Papers, Posters & Projects

BACKGROUND: Pacific Islanders experience significant health disparities. One contributing aspect to these disparities is the lack of racial concordance as Pacific Islanders are underrepresented in the U.S. physician work force. Several factors contribute to this underrepresentation including lack of support systems for Pacific Islander premed and medical students. Pasifikas in Medicine (PiM) is a recently established national student organization founded to provide support for Pacific Islander premed students, medical students, residents, fellows and attending physicians. This study seeks to understand the impact of PiM on medical student experiences.

METHODS: An anonymous survey was distributed to the PiM listserv and to …

Gender, Mental Health Symptoms, Loss To Clinic, And Viral Non-Suppression 6 Months After Hiv Care Initiation Among A Cohort Of People With Hiv In Cameroon, Angela M Parcesepe, Lindsey M Filiatreau, Peter Vanes Ebasone, Anastase Dzudie, Marcel Yotebieng, Kathryn Anastos, Eric Pefura-Yone, Annereke Nyenti, Denis Nash

2020-Current year OA Pubs

BACKGROUND: People with HIV (PWH) experience high levels of mental health or substance use disorders (MSDs) which may compromise HIV treatment outcomes. Differences in the relationship between MSDs and HIV treatment outcomes by gender remain understudied.

METHODS: We conducted interviews with 426 PWH aged ≥ 21 years initiating HIV care in Cameroon between June 2019 and March 2020. Clinic data and laboratory results were used to ascertain loss to clinic and viral non-suppression six months after HIV care initiation. We used log binomial regression models to assess the relationship between symptoms of depression (PHQ-9 scores > 9), anxiety (GAD-7 scores > 9), …

Chemotherapy-Induced Adipo-Lineage Cell Senescence Drives Bone Loss, Ganesh Kumar Raut, Taylor Malachowski, Anupama Melam, Renata Ramalho-Oliveira, Taylor Holt, Xianmin Luo, Zhangting Yao, Douglas V Faget, Qihao Ren, David G Denardo, Sheila A Stewart

2020-Current year OA Pubs

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to significant bone loss. Notably, we find that inhibition of the p38MAPK-MK2 pathway suppresses the senescence-associated secretory phenotype (SASP), including RANKL production abrogating bone loss. Furthermore, treatment with the senolytic combination dasatinib and quercetin (D + Q) selectively eliminates …

Low Utilization Of Intracavernosal Injection And Penile Doppler Ultrasound In The Evaluation Of Erectile Dysfunction And Peyronie's Disease, Joon Yau Leong, Tyler Gaines, Zachary J. Prebay, David Ebbott, Paul H. Chung

Department of Urology Faculty Papers

INTRODUCTION: Despite the diagnostic value of intracavernosal injections (ICI) and penile Doppler ultrasound (PDUS), there remain barriers to widespread clinical adaptation of these methods. The study aimed to evaluate the practice patterns of utilization of ICI and PDUS in the assessment of erectile dysfunction (ED) and Peyronie's disease (PD).

METHODS: Using the TriNetX database (Cambridge, MA, USA), adult (≥18 years) male patients with a diagnosis of ED on oral phosphodiesterase-5 (PDE5) inhibitors were identified. Current Procedural Terminology codes were utilized to identify patients who underwent further evaluation with ICI or PDUS, as well as penile prosthesis placement after PDUS. A …

Mental Health And Beliefs About Abortion Access Following Changes To Reproductive Healthcare Laws In 2022: Findings From Oklahoma, Munjireen Sifat, Laili K. Boozary, Tina N. Le, Julia Mcquoid, Brittany Zaring-Hinkle, Sarah Tonkin, Lizbeth Benson, Bingjing Mao, Motolani Ogunsanya, Ruosi Shao, Amy M. Cohn, Allyson Shortle, Darla E. Kendzor

Department of Medical Oncology Faculty Papers

INTRODUCTION: A secondary analysis of cross-sectional survey data was conducted to characterize beliefs about abortion access in Oklahoma, measure stress associated with the overturn of Roe vs. Wade (2022), and evaluate the potential relationship between post-Roe stress (PR stress) and mental health.

METHODS: From August through September 2022, adult Oklahomans (N = 1793) were surveyed about their sociodemographic characteristics, beliefs about abortion access, frequency of past-month stress related to the overturn of Roe vs. Wade, and mental health. Beliefs about abortion access were characterized overall and within sociodemographic groups. The relationship between PR stress and mental health was evaluated, and …

Subgroup Analyses Of The Phase 3 Focus Study Of Melphalan/Hepatic Delivery System In Patients With Unresectable Metastatic Uveal Melanoma, Jonathan S. Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan S. Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia M. Beasley, Anja Gesierich, Martin Gschnell, Reinhard Dummer, Ana Arance, Stephen William Fenwick, Joseph J. Sacco, Johnny John, Matthew Wheater, Christian H. Ottensmeier

Department of Medical Oncology Faculty Papers

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS: 102 patients with mUM were enrolled; treatment was attempted …

Sex Differences In Bile Acid Homeostasis And Excretion Underlie The Disparity In Liver Cancer Incidence Between Males And Females, Megan E Patton, Sherwin Kelekar, Lauren J Taylor, Angela E Dean, Qianying Zuo, Rhishikesh N Thakare, Sung Hwan Lee, Emily C Gentry, Morgan Panitchpakdi, Pieter Dorrestein, Yazen Alnouti, Zeynep Madak-Erdogan, Ju-Seog Lee, Milton J Finegold, Sayeepriyadarshini Anakk

Faculty, Staff and Student Publications

Hepatocellular carcinoma (HCC), the common liver cancer, exhibits higher incidence in males. Here, we report that mice lacking bile acid (BA) regulators, Farnesoid X Receptor (FXR also termed NR1H4) and Small Heterodimer Partner (SHP also termed NR0B2), recapitulate the sex difference in liver cancer risk. Since few therapeutic options are available, we focused on understanding the intrinsic protection afforded to female livers. Transcriptomic analysis in control and NR1H4 and NR0B2 double knockout livers identified female-specific changes in metabolism, including amino acids, lipids, and steroids. To assess translational relevance, we examined if transcriptomic signatures obtained from this murine HCC model correlate …

Batf2 Is A Glutamine-Responsive Tumour Suppressor Required For Type-I Interferon-Dependent Anti-Tumour Immunity, Wang Gong, Hülya F Taner, Yuesong Wu, Yumin He, Xingwu Zhou, Zaiye Li, Xin Hu, Charisse Ursin, Kala Chand Debnath, Kohei Okuyama, Qiang Hu, Christopher R Donnelly, Felipe Nör, Chamila D Perera, Emily Bellile, Arash Yunesi, Zhiqian Zhai, Mei Zhao, Wanqing Cheng, Zackary R Fitzsimonds, Luke Broses, Jiaqian Li, Shadmehr Demehri, Deepak Nagrath, Gregory T Wolf, Andrew G Sikora, Yanbao Yu, Haitao Wen, Lei Wei, Steven B Chinn, Jeffrey N Myers, Shizuo Akira, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Recent evidence highlights the significance of a new type of tumour suppressors, which are not frequently mutated but inhibited by metabolic cues in cancers. Here, we identify BATF2 as a tumour suppressor whose expression is epigenetically silenced by glutamine in Head and Neck Squamous Cell Carcinomas (HNSCC). BATF2 correlates with type-I interferon and Th1 signatures in human HNSCC, with correlation coefficients even stronger than those of the positive control, STING. The phosphorylation of BATF2 at serine 227 promotes the oligomerization of STING. BATF2 deficiency or high glutamine levels result in higher oxygen consumption rates and metabolic profiles unfavorable for …

Real-World Outcomes Of Talimogene Laherparepvec As Salvage Therapy For Advanced Melanoma, Melissa M Yamada, Smitha Chandrasekhar, Ted A Gooley, Rita E Chen, Coley Doolittle-Amieva, George Ansstas, Shailender Bhatia, Evan T Hall, Paul T Nghiem, Song Y Park, David Y Chen

2020-Current year OA Pubs

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic herpes simplex virus therapy approved for treatment of unresectable and metastatic melanoma. However, real-world use often occurs in heavily pretreated patients, where evidence of effectiveness remains limited. This study evaluates treatment responses and clinical factors influencing T-VEC outcomes in patients with diverse treatment histories.

METHODS: We analyzed patients with metastatic melanoma treated with T-VEC between 2015 and 2024. Objective responses (OR), complete response (CR) and partial response were assessed using univariate and multivariate Cox regression models. Durability of responses, progression-free survival (PFS), and overall survival (OS) were evaluated using Kaplan-Meier estimates.

RESULTS: Among …

Stimulant Medications Affect Arousal And Reward, Not Attention Networks, Benjamin P Kay, Muriah D Wheelock, Ryan V Raut, Roselyne J Chauvin, Athanasia Metoki, Aishwarya Rajesh, Andrew Eck, Jim Pollaro, Anxu Wang, Vahdeta Suljic, Babatunde Adeyemo, Noah J Baden, Kristen M Scheidter, Julia S Monk, Forrest I Whiting, Nadeshka Ramirez-Perez, Samuel R Krimmel, Anita Randolph, Jarod L Roland, Ginger E Nicol, Timothy O Laumann, Scott Marek, Evan M Gordon, Marcus E Raichle, Deanna M Barch, Nico U F Dosenbach, Et Al.

2020-Current year OA Pubs

Prescription stimulants (e.g., methylphenidate) are thought to improve attention, but evidence from prior fMRI studies is conflicted. We utilized resting-state fMRI data from the Adolescent Brain Cognitive Development Study (n = 11,875; 8-11 years old) and validated the functional connectivity findings in a precision imaging drug trial with highly sampled (n = 5, 165-210 min each) healthy adults (methylphenidate 40 mg). Stimulant-related connectivity differences in sensorimotor regions matched fMRI patterns of daytime arousal, sleeping longer at night, and norepinephrine transporter expression. Taking stimulants reversed the effects of sleep deprivation on connectivity and school grades. Connectivity was also changed in salience …

Using A Heuristic Tool To Improve Symptom Self-Management In Adolescents And Young Adults With Cancer: Protocol For A Randomized Controlled Trial., Suzanne Ameringer, Grace Hodges, R K Elswick, Lauri Linder, Catherine Fiona Macpherson, Kristin Stegenga

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Adolescents and young adults (AYAs) with cancer experience multiple distressing symptoms during treatment, yet few developmentally relevant resources have been developed to help them self-manage their symptoms. Empowering patients to have a more active role in self-management during cancer treatment may lessen their symptom severity and distress.

OBJECTIVE: The aim of this study is to test an intervention designed to improve symptom self-management, the Computerized Symptom Capture Tool (C-SCAT), by helping AYAs understand their unique symptom experience and discuss it with their health care providers.

METHODS: We are conducting a multisite, 2-group randomized controlled trial to evaluate the effects …

Association Of Shock Index And Variants With Mortality In Acute Pulmonary Embolism, Cameron P Upchurch, Kristen Sanfilippo, Daphne Lew, Maanasi Samant, Rachel Mcdonald

2020-Current year OA Pubs

INTRODUCTION: Pulmonary embolism (PE) is common with potential for morbidity and mortality. Several PE risk-stratification tools exist; however, more granular and patient-specific indicators of potential decompensation or short-term mortality that can be easily obtained are needed for the bedside clinician to further sub-stratify risk and inform management decisions. We sought to determine the association of early emergency department (ED) measurement of the shock index (SI) and SI variants (modified SI, SI to peripheral oxygen saturation ratio, age-adjusted SI, respiratory-adjusted SI, and double product) and mortality among patients with acute PE.

METHODS: This was an observational case-control study of adult patients …

Soluble Urokinase Plasminogen Activator Receptor And Acute Kidney Injury In Hematopoietic Cell Transplantation, Bhavna Bhasin-Chhabra, Tao Wang, John E Levine, Shalini Shenoy, Miguel-Angel Perales, Asad Bashey, Hershel Raff, Wael Saber

2020-Current year OA Pubs

Acute kidney injury (AKI) frequently follows hematopoietic cell transplantation (HCT). Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker of AKI in the general population. We evaluated suPAR and its association with AKI requiring dialysis (AKI-D) in patients undergoing allogeneic HCT (alloHCT). Performance of suPAR was compared with serum creatinine (sCr) and neutrophil gelatinase-associated lipocalin (NGAL). Data were obtained from the Blood and Marrow Transplant Clinical Trials Network 1202 cohort, an observational study of 1709 alloHCT recipients. Adults aged ≥18 years with AKI-D after HCT were included. Adults who did not develop AKI were included as controls and matched 1:1. …

Predictive Modeling Of Hematoma Expansion From Non-Contrast Computed Tomography In Spontaneous Intracerebral Hemorrhage Patients, Natasha Ironside, Shinjini Kundu, Et Al.

2020-Current year OA Pubs

Hematoma expansion is a consistent predictor of poor neurological outcome and mortality after spontaneous intracerebral hemorrhage (ICH). An incomplete understanding of its biophysiology has limited early preventative intervention. Transport-based morphometry (TBM) is a mathematical modeling technique that uses a physically meaningful metric to quantify and visualize discriminating image features that are not readily perceptible to the human eye. We hypothesized that TBM could discover relationships between hematoma morphology on initial Non-Contrast Computed Tomography (NCCT) and hematoma expansion. 170 spontaneous ICH patients enrolled in the multi-center international Virtual International Trials of Stroke Archive (VISTA-ICH) with time-series NCCT data were used for …

Synergistic Effects Of Gfap With Tnfr1 And Tnfr2 On Conversion To Ad Dementia And Overall Survival Across The Alzheimer’S Disease Spectrum, Laura Alejandra Ramirez Tirado, Ann D. Cohen, C. Elizabeth Shaaban, Cristy Matan, Brian J. Lopresti, Milos D. Ikonomovic, Thomas K. Karikari, Victor L. Villemagne, Oscar L. Lopez

Department of Neurology Faculty Papers

Background: We recently reported synergistic effects of TNFR1 and TNFR2 with
astrogliosis resulting in greater vascular burden and neurodegeneration, particularly in
Aβ+ participants. Here, we aimed to assess the interactions of peripheral inflammation
and astrogliosis on incidence of AD dementia and mortality. We hypothesized
synergistic effects with astrogliosis resulting in increased incidence of dementia, and
mortality, particularly in Aβ+ participants.
Methods: Participants of the Gingko evaluation of memory (GEM) study underwent
PiB-PET scans between 2009-2018. GFAP and peripheral inflammatory markers were
measured in 2009 by immunoassay. We evaluated the relationship of peripheral
markers of inflammation (TNFR1,TNFR2) and astrogliosis (GFAPdementia incidence …

Simultaneous Initiation Of Finerenone And Empagliflozin Across The Spectrum Of Kidney Risk In The Confidence Trial, Muthiah Vaduganathan, Jennifer B Green, Hiddo J L Heerspink, Sung Gyun Kim, Johannes F E Mann, Janet B Mcgill, Amy Mottl, Masaomi Nangaku, Julio Rosenstock, Peter Rossing, Li Li, Na Li, Katja Rohwedder, Charlie Scott, Rajiv Agarwal

2020-Current year OA Pubs

BACKGROUND: The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and type 2 diabetes using a UACR Endpoint) trial investigated the safety and efficacy of simultaneously initiating finerenone and empagliflozin for patients with chronic kidney disease (CKD) and type 2 diabetes. This prespecified analysis aimed to determine if the predicted risk of kidney disease progression, based on KDIGO risk categories, influenced the benefits and safety of this combination therapy.

METHODS: The double-blind, double-dummy trial randomized 818 adults with CKD and type 2 diabetes [urine albumin-creatinine ratio (UACR) ≥100 to < 5000 mg/g] to receive once-daily finerenone plus empagliflozin, finerenone alone or empagliflozin alone, all in addition to a renin-angiotensin system inhibitor. The relative change in UACR from baseline to day 180 (primary endpoint) and a >30% reduction in UACR (secondary endpoint) across KDIGO …

Liberal Or Restrictive Postoperative Transfusion In Patients At High Cardiac Risk: The Top Randomized Clinical Trial, Panos Kougias, Sherene E Sharath, Min Zhan, Jeffrey L Carson, L Erin Norman, Zhibao Mi, Rupsi Pal, Hasan Dosluoglu, J Gregory Modrall, George A Sarosi, Peter Nelson, Shipra Arya, Alexandra Scrymgeour, Jade Ollison, Lawrence A Calais, Vijay Nambi, L Parker Gregg, Shuaib M Abdullah, Shirling Tsai, Natasha Becker, Justin C Choi, Louisa Chiu, Salvatore Scali, Neal R Barshes, Samir Awad, Mohammed Moursi, Matthew C Koopmann, Mitchell Sally, Daniel Ihnat, Archana Ramaswamy, Warren Gasper, Edith Tzeng, Mark A Wilson, Gale Tang, Grant Huang, Kousick Biswas

Faculty, Staff and Students Publications

Importance: Postoperative red blood cell transfusion guidelines recommend transfusion for hemoglobin levels less than 7 g/dL. However, the safety of this strategy in patients at high risk of cardiac events undergoing major operations remains unclear.

Objective: To evaluate the risk of death or major ischemic events within 90 days after a liberal transfusion strategy compared with a restrictive transfusion strategy in patients at high risk of cardiac events who had undergone major vascular or general surgery operations and developed postoperative anemia.

Design, setting, and participants: This parallel, single-blind, randomized clinical superiority trial included 1428 veterans (≥18 y) at high cardiac …

Titin-Related Familial Dilated Cardiomyopathy: Factors Associated With Disease Onset, Renee Johnson, Robert A Fletcher, Stacey Peters, Monique Ohanian, Magdalena Soka, Andrei Smolnikov, Katherine E Abihider, Michael J Ackerman, Flavie Ader, Mohammed M Akhtar, Ahmad S Amin, Euan A Ashley, John J Atherton, Rachel Austin, Annette F Baas, Richard D Bagnall, Samantha Barratt Ross, Jean-Louis Blouin, Emily E Brown, Henning Bundgaard, Douglas Cannie, Przemyslaw Chmielewski, Gemma Correnti, Maria Generosa Crespo-Leiro, Matteo Dal Ferro, Lisa M Dellefave-Castillo, Fernando Dominguez, Dennis Dooijes, Anne M Dybro, Youssef Ed Demri, Mohamed El Hachmi, Luis Escobar-Lopez, Sarah Jajesnica Foye, Maria Franaszczyk, Marta Gigli, Esther Gonzalez Lopez, Adeline Goudal, Sharon Graw, Michel Guipponi, Eric Haan, Jan Haas, Daniel J Hammersley, Frederikke G Hansen, Christopher S Hayward, Thomas Morris Hey, Stephane Heymans, Carolyn Y Ho, Arjan C Houweling, Jodie Ingles, Angela Ingrey, Andrew Jabbour, Paul A James, Joeri A Jansweijer, Jan D H Jongbloed, Anne M Keogh, Jose M Larrañaga-Moreira, Ronald H Lekanne Deprez, Ivan Macciocca, Peter S Macdonald, Nicolas Mansencal, Julia Mansour, Cristina Martinez-Veira, Barbara Mcdonough, Julie Mcgaughran, Kristen Medo, Marco Merlo, Ewa Michalak, Lorenzo Monserrat, Helen Mountain, Steven A Muller, Anne M Murphy, Brittney Murray, Emily C Oates, Elizabeth Ormondroyd, Nicholas Pachter, Alessia Paldino, Aurélien Palmyre, Naveen L Pereira, Kermshlise C Picard, Nicola Poplawski, Sanjay Prasad, Julie Proukhnitzky, Jean-Francois Pruny, Patricia Reant, Pascale Richard, Anne Ronan, Farbod Sedaghat-Hamedani, Christopher Semsarian, Garrett Storm, Sophie Stroeks, Petros Syrris, Matthew R G Taylor, Kate Thomson, Tina Thompson, J Peter Van Tintelen, Christoffer Rasmus Vissing, Kathryn E Waddell-Smith, Mathew Wallis, Dominica Zentner, Clare Arnott, Ali J Marian, Jaewon Oh, Siv Fokstuen, Cynthia A James, Roberto Barriales-Villa, Benjamin Meder, Karim Wahbi, John R Giudicessi, Victoria N Parikh, James S Ware, Nicolas Piriou, Caroline Rooryck, Neal K Lakdawala, Luisa Mestroni, Gianfranco Sinagra, Perry M Elliott, Hugh Watkins, Elizabeth M Mcnally, Philippe Charron, Karin Y Van Spaendonck-Zwarts, Pablo Garcia-Pavia, Maria Luisa Peña-Peña, Jens Mogensen, Alex Hoerby Christensen, Zofia T Bilińska, Torsten B Rasmussen, Jonathan G Seidman, Christine E Seidman, Anneline S J M Te Riele, Job A J Verdonschot, Yigal M Pinto, Imke Christiaans, Diane Fatkin

The Brown Foundation: Institute of Molecular Medicine

Background and aims: Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv.

Methods: An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM.

Results: A total of 3158 subjects in 1043 …

Investigating Chronic Toxicity, Diet, Patient-Reported Outcomes And The Microbiome In Immunotherapy-Treated Metastatic Melanoma Survivors: A New Frontier, Margaux Robert, Satabdi Saha, Nazli Dizman, Michelle Rohlfs, Elizabeth Sirmans, Julie Simon, Rodabe N Amaria, Isabella C Glitza Oliva, Hussein A Tawbi, Michael A Davies, Alexandra Ikeguchi, Karen Basen-Engquist, Keri Schadler, Michael E Roth, Wenye Song, Xiaotao Zhang, Nadim J Ajami, Lorenzo Cohen, Jennifer A Wargo, Christine B Peterson, Jennifer L Mcquade, Carrie R Daniel

Faculty, Staff and Student Publications

Background/Objectives: Immune checkpoint blockade (ICB) therapies have significantly improved outcomes in metastatic melanoma. However, immune-related adverse events (irAEs) and persistent chronic toxicities (CTs) among this emerging survivor population likely influence different facets of quality of life. This study characterized CT, patient-reported outcomes (PROs), diet, physical activity and gut microbiome features in a cohort of long-term survivors with a history of ICB-treated metastatic melanoma.

Methods: Forty-eight patients with a history of metastatic melanoma who initiated ICB treatment at least 3 years earlier and were not currently on treatment were prospectively enrolled from a melanoma survivorship clinic. Participants completed screening …

Implementation Of Single-Pill Combination Medication For Hypertension Treatment By Nonphysician Health Care Workers At Primary Healthcare Facilities In Nigeria: An Explanatory Mixed Methods Study, Emmanuel I Okpetu, Chisom Obiezu-Umeh, Boni M Ale, Abigail S Baldridge, Rosemary C B Okoli, Grace J Shedul, Gabriel L Shedul, Nanna R Ripiye, Ikechukwu A Orji, Lisa R Hirschhorn, Dike B Ojji, Mark D Huffman, Hypertension Treatment In Nigeria Program Investigators

2020-Current year OA Pubs

BACKGROUND: Single-pill combination (SPC) therapy improves hypertension control; however, its implementation in primary care settings remains limited. In Nigeria, there is insufficient evidence on factors influencing SPC uptake, particularly from the perspective of healthcare workers (HCWs). This study examined the implementation of SPC medications for hypertension treatment by nonphysician HCWs at primary healthcare facilities (PHCs) in Nigeria.

METHODS: An explanatory sequential mixed methods study was conducted, building on a cluster randomized controlled trial embedded within the Hypertension Treatment in Nigeria Program. The trial compared SPC medications with free-equivalent combination therapies across 60 PHCs (January-June 2021). A subsequent qualitative component (September-December …

Discovery Of Small Molecules And A Druggable Groove That Regulate Dna Binding And Release Of The Ap-1 Transcription Factor Δfosb, Sean Mcneme, Yun Young Yim, Ashwani Kumar, Yi Li, Brandon Hughes, Corey Peyton St Romain, Galina Aglyamova, Jianping Chen, Nghi D Nguyen, Shanghua Fan, Gabriel S Stephens, Wen-Ning Zhao, Samantha Kruzshak, Molly Estill, Corrine Brener, Solange Tofani, Anil Kumar, Earnest P Chen, Nadeen Takatka, Alfred J Robison, Haiying Chen, Reid T Powell, Stephen J Haggarty, Clifford Stephan, Eric J Nestler, Jeannie Chin, Mischa Machius, Jia Zhou, Gabby Rudenko

Faculty, Staff and Students Publications

ΔFOSB, a member of the AP-1 family of transcription factors, mediates long-term neuroadaptations underlying drug addiction, seizure-related cognitive decline, dyskinesias, and several other chronic conditions. AP-1 transcription factors are notoriously difficult to modulate pharmacologically due to the absence of well-defined binding pockets. Here, we identify a novel site on ΔFOSB, located outside the DNA-binding cleft, that accommodates small molecules. We show that sulfonic acid-containing compounds bind to this site via an induced-fit mechanism, reorienting side chains critical for DNA binding, and that they may hinder the ΔFOSB bZIP α-helix from binding to the major groove of DNA. In vivo, direct …

The Common Cold Is Associated With Protection From Sars-Cov-2 Infections, Camille M Moore, Katherine Rivera-Spoljaric, Et Al.

2020-Current year OA Pubs

BACKGROUND: Adults and children often respond differently to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with adults facing a higher risk of symptomatic and severe illness. We hypothesize that children's protection from symptomatic SARS-CoV-2 may be due to more frequent respiratory viral infections, which prime their airway antiviral defenses.

METHODS: Using case-cohort and case-control analyses in the Human Epidemiology and Response to SARS-CoV-2 cohort, we evaluated whether infection with common respiratory viruses protects against SARS-CoV-2 infections and investigated airway molecular mechanisms by which this protection is achieved. We tested 10 493 longitudinal nasal swabs from 1156 participants for 21 …

Updating The Epidemiology Of Blastomycosis And Histoplasmosis In The United States, Using National Electronic Health Record Data, 2013-2023., Juliana G E Bartels, Simon K. Camponuri, Theo T. Snow, Brittany L Morgan Bustamante, Natalie J. Kane, Rose Reynolds, Aidan Lee, Mark A. Hoffman, Theodore C. White, Justin V. Remais, Jennifer R. Head

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Where surveillance data are limited, nationally representative electronic health records allow for geographic, temporal, and demographic characterization of the fungal diseases blastomycosis and histoplasmosis.

METHODS: We identified incident blastomycosis and histoplasmosis cases from 2013 to 2023 within Oracle EHR Real-World Data, which comprises 1.6 billion healthcare encounters nationally. To characterize spatiotemporal incidence trends, we used generalized estimating equations weighted for nonrepresentativeness of electronic health record-reporting facilities. We computed standardized incidence rate ratios (sIRRs), which relay relative differences in standardized incidence rates between regions, race/ethnicity, gender, and age subgroups and the national population.

RESULTS: National incidence rates in 2023 were …

Trait-Like Visual Cortical Hyperactivity In Trait Anxiety, Zhaohan Wu, Yuqi You, Joshua A Brown, Raymond J Dolan, Wen Li

Faculty, Staff and Student Publications

Sensory processing varies across individuals, with some traits-particularly sensory hypersensitivity to basic non-valenced stimuli-linked to emotional traits and psychiatric risk. Traditional accounts attribute this sensory-emotion linkage to limbic or prefrontal modulation, but empirical support is limited. Growing evidence suggests sensory cortex itself flexibly encodes value beyond labeled-line analysis. Across four high-density EEG experiments with multi-wave assessments, we identified reliable visual cortical hyperactivity in high trait anxiety. The effect emerged as early as 46 ms, localized to V1/V2, and was specific to the parvocellular pathway. It was reproducible across arousal states, stimulus valence, extended intervals, and paradigms, and evident for both …