Digital Commons Network^™

The Infected Diabetic Foot: Bacteraemia And Endocarditis Complicating Moderate And Severe Foot Infections, Mario C Reyes, Arthur N Tarricone, Mathew J Sideman, Michael C Siah, Bijan Najafi, Edgar J G Peters, Lawrence A Lavery

Center on Aging Staff Publications

To identify the incidence of blood stream infections (BSIs) and endocarditis in patients with diabetic foot infections (DFIs), risk factors and clinical outcomes. A post hoc analysis of 280 patients using pooled patient level data from three RTCs. Blood cultures were drawn at time of admission for DFI. Deep intraoperative cultures were obtained from infected foot wounds. Data from the 12-month follow-up were used to determine clinical outcomes. 77.1% (N = 216) had blood cultures of which 15.7% (n = 34) had BSI. One patient (3.3%) had endocarditis. Risk factors for BSI included Charcot Neuroarthropathy history (20.6% vs. 7.1%, p …

Prevalence And Patterns Of Opioid Use In Chronic Pancreatitis, Anna Evans Phillips, Darwin L Conwell, Shuang Li, Jami L Saloman, Phil A Hart, Evan L Fogel, Santhi Swaroop Vege, Dana K Andersen, William E Fisher, Christopher E Forsmark, Stephen Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Liang Li, Dhiraj Yadav

Faculty, Staff and Student Publications

Introduction: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aim of this study was to characterize the utilization of opioids and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis used baseline data from participants with definite CP enrolled in a cohort study in the United States (PROspective Evaluation of CP for EpidEmiologic and Translational StuDies). Data on demographics, pain medication use, healthcare utilization, disability, and pain patterns were systematically collected in case report forms while quality of life was assessed with patient-reported outcome instruments. …

Overlapping Clinical Phenotypes In Patients With Primary Ciliary Dyskinesia Or Activated Phosphoinositide 3-Kinase Delta Syndrome, Adam J Shapiro, Eveline Y Wu, Deborah J Morris-Rosendahl, Kenneth N Olivier, Sharon D Dell, Scott D Sagel, Cullen M Dutmer, Ricardo A Mosquera, Markus Rose, Michael G O'Connor, Chi A Ma, Gulbu Uzel, Timothy J Vece, Maimoona A Zariwala, Michael R Knowles, Margaret W Leigh, Stephanie D Davis, Thomas W Ferkol

Faculty, Staff and Student Publications

Primary ciliary dyskinesia and activated phosphoinositide 3-kinase delta syndrome type 1 present similarly, with recurrent respiratory infections and reduced nasal nitric oxide levels. When diagnostic confirmation of primary ciliary dyskinesia with genetic testing and/or ciliary electron microscopy is inconclusive, activated phosphoinositide 3-kinase delta syndrome type 1 and other inborn errors of immunity must be investigated.

Older Adults' Experiences Of Emergency Department Admission Decisions: A Qualitative Study In A Public Safety Net Hospital, Anita N Chary, Annika Bhananker, Beatrice Torres, Victoria Sofia Martell, Manish N Shah, Aanand D Naik

Faculty, Staff and Student Publications

Background: Hospital admission is a significant event in the healthcare trajectory of older adults (age 60 +). Numerous harms such as delirium, falls, and adverse medication events can arise that outweigh the benefits of admission. Little is known about how older adults feel about being hospitalized or what they think admission will achieve for them. These issues are particularly important to understand in socioeconomically disadvantaged patients, who have poor access to outpatient care and higher hospitalization rates.

Methods: We performed semi-structured interviews with emergency department (ED) patients aged 60 and older who were being admitted. The study site was a …

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …

The Dialysis Foot- The Impact Of Presenting Estimated Glomerular Filtration Rate On Clinical Outcomes In Patients Hospitalized With Diabetic Foot Infections, Arthur Tarricone, Tyler L Coye, Allen Gee, Bijan Najafi, Michael C Siah, Lawrence A Lavery

Center on Aging Staff Publications

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR < 30 (eGFR < 30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR < 30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR < 30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR < 30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR < 30; p <  0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

Sensitivity Of Lung Point-Of-Care Ultrasound (Pocus) To Predict Oxygen Requirements In Emerging Viral Infections, Daniel L Theodoro, Di Coneybeare, Penelope Lema, Nicholas Renz, Laura Wallace, Enyo Ablordeppey, Sean Stickles, Alek Rosenthal, Ian Holley, Sirivalli Chamarti, Josie Acuña, James Patterson, Rachel Ancona, Srikar Adhikari

2020-Current year OA Pubs

OBJECTIVES: The prognostic characteristics of lung point-of-care ultrasound (L-POCUS) to predict respiratory decompensation in patients with emerging infections remains unstudied. Our objective was to examine whether scored lung ultrasounds predict hypoxia among a nonhypoxic, ambulatory population of patients with COVID-19.

METHODS: This was a diagnostic case-control study. Three academic emergency departments across the United States collected a convenience sample of nonhypoxic subjects with COVID-19, scored subjects' hemithorax at 7 locations using lung ultrasound, and followed outcomes for 40 days. We defined cases as hypoxia (≤91% by pulse oxygenation) from 2 hours after index presentation to day 40. Follow-up was by …

Longitudinal Profiling Of Low-Abundance Strains In Microbiomes With Chronostrain, Younhun Kim, Colin J Worby, Sawal Acharya, Lucas R Van Dijk, Daniel Alfonsetti, Zackary Gromko, Philippe N Azimzadeh, Karen W Dodson, Georg K Gerber, Scott J Hultgren, Ashlee M Earl, Bonnie Berger, Travis E Gibson

2020-Current year OA Pubs

The ability to detect and quantify microbiota over time from shotgun metagenomic data has a plethora of clinical, basic science and public health applications. Given these applications, and the observation that pathogens and other taxa of interest can reside at low relative abundance, there is a critical need for algorithms that accurately profile low-abundance microbial taxa with strain-level resolution. Here we present ChronoStrain: a sequence quality- and time-aware Bayesian model for profiling strains in longitudinal samples. ChronoStrain explicitly models the presence or absence of each strain and produces a probability distribution over abundance trajectories for each strain. Using synthetic and …

Treatment Patterns And Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer, Martin W Schoen, Saira Khan, Eric M Knoche, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Combination therapy for metastatic hormone-sensitive prostate cancer (mHSPC) has been widely adopted, yet clinical use and outcomes are unknown. Furthermore, optimal therapy is uncertain due to lack of direct comparison of androgen receptor pathway inhibitors (ARPIs) and docetaxel in high-volume disease.

OBJECTIVE: To evaluate the use of combination therapy and its association with overall survival among patients with mHSPC and to compare ARPIs vs docetaxel doublet therapy by volume of disease.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study was conducted in the US Veterans Health Administration among 6216 US veterans with de novo mHSPC from January 1, 2013, …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Evaluating The Test-Negative Design For Covid-19 Vaccine Effectiveness Using Randomized Trial Data: A Secondary Cross-Protocol Analysis Of 5 Randomized Clinical Trials, Leah I B Andrews, M Elizabeth Halloran, Kathleen M Neuzil, Lars Van Der Laan, Yunda Huang, Jessica Andriesen, Mayur Patel, Leigh H Fisher, Holly Janes, Nadine Rouphael, Stephen R Walsh, Deborah A Theodore, Hong-Van Tieu, Magdalena Sobieszczyk, Hana M El Sahly, Lindsey R Baden, Ann R Falsey, Thomas B Campbell, Colleen F Kelley, Catherine Mary Healy, Lilly Immergluck, Benjamin Luft, Ian Hirsch, Guy De Bruyn, Carla Truyers, Frances Priddy, Kelsey M Sumner, Brendan Flannery, Dean Follmann, Peter B Gilbert, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

Importance: The test-negative design (TND) has been widely used to assess postmarketing COVID-19 vaccine effectiveness but requires further evaluation for this application.

Objective: To determine whether the TND reliably evaluates vaccine effectiveness against symptomatic COVID-19 using placebo-controlled vaccine efficacy randomized clinical trials (RCTs).

Design, setting, and participants: This secondary cross-protocol analysis constructed TND study datasets from study sites in 16 countries across 5 continents using the blinded phase cohorts of 5 harmonized phase 3 COVID-19 Prevention Network RCTs: COVE (Coronavirus Vaccine Efficacy and Safety), AZD1222, ENSEMBLE, PREVENT-19 (Prefusion Protein Subunit Vaccine Efficacy Novavax Trial COVID-19), and VAT00008. Participants included adults …

The Central Role Of Cytochrome P450 Reductase (Cpr) In Hyperoxic Lung Injury, Deven Narke, Bhagavatula Moorthy

Faculty, Staff and Students Publications

Introduction: Hyperoxic lung injury results from excessive supplemental oxygen therapy in conditions such as bronchopulmonary dysplasia (BPD) in preterm infants and acute respiratory distress syndrome (ARDS) in adults. This review explores the role of cytochrome P450 reductase (CPR) in hyperoxic lung injury.

Areas covered: Hyperoxia induces the production of reactive oxygen species in excessive amounts, overwhelming the body's antioxidant defenses and exacerbating lung injury in ARDS/BPD. This review examines the differential roles of CPR-dependent enzymes in the context of hyperoxic lung injury. Additionally, we highlight the potential of targeting CPR to study mechanisms of lung injury and leverage gene-editing technologies …

Functional Genomics In Age-Related Macular Degeneration: From Genetic Associations To Understanding Disease Mechanisms, Rinki Ratnapriya, Felix Grassman, Rui Chen, Alex Hewitt, Jianhai Du, Daniel R Saban, Caroline C W Klaver, John Ash, Dwight Stambolian, Santa J Tumminia, Jiang Qian, Deeba Husain, Sudha K Iyengar, Anneke I Den Hollander

Faculty, Staff and Students Publications

Genome-wide association studies have been remarkably successful in identifying genetic variants associated with age-related macular degeneration (AMD), demonstrating a strong genetic component largely driven by common variants. However, progress in translating these genetic findings into a deeper understanding of disease mechanisms and new therapies has been slow. Slow progress in this area can be attributed to limited knowledge of the functional impact of AMD-associated non-coding variants on gene function, the molecular mechanisms and cell types underlying disease. This review offers a comprehensive overview of functional genomics approaches to uncover the genetic, epigenetic, cellular and molecular mechanisms underlying AMD and outlines …

Cortical Structure In Nodes Of The Default Mode Network Estimates General Intelligence, Abhinav Yadav, Archana Purushotham

Faculty, Staff and Students Publications

Introduction: A growing number of studies implicate functional brain networks in intelligence, but it is unclear if network nodal structure relates to intelligence.

Methods: Using MRI, we studied the relationship of the general intelligence factor (g) with cortical thickness (CT), local gyrification index (LGI), and voxel-based morphometry in the nodes of the default mode network (DMN) and task-positive network (TPN) in a cohort of 44 young, healthy adults. Employing a novel strategy, we performed repeated analyses with multiple sets of g estimates to remove false positives.

Results: CT and LGI in medial and temporal nodes of the DMN were reliably …

Otolaryngology-Assisted Approach For Anterior Cervical Discectomy And Fusion, M Benjamin Larkin, Anthony K Allam, Cyrus B King, N Eddie Liou, Alexander E Ropper

Faculty, Staff and Students Publications

First introduced in 1955, anterior cervical discectomy and fusion (ACDF) surgery has seen minimal changes over the years. Its reproducibility, impressive long-term results, and minimal complication rates have established it as one of the most frequently performed cervical spinal fusion surgeries. Yet, postoperative dysphagia remains a concern with a 60% incidence rate. An otolaryngologist's expertise regarding cervical fascial anatomy can inform the spine surgeon's approach to an ACDF to potentially reduce postoperative dysphagia rates. We describe an illustrative case of a 35-year-old woman who presented with 8/10 neck and arm pain along with numbness in her fourth and fifth digits …

Challenges And Opportunities Of Acquiring Cortical Recordings For Chronic Adaptive Deep Brain Stimulation, Jeffrey Herron, Aura Kullmann, Timothy Denison, Wayne K Goodman, Aysegul Gunduz, Wolf-Julian Neumann, Nicole R Provenza, Maryam M Shanechi, Sameer A Sheth, Philip A Starr, Alik S Widge

Faculty, Staff and Students Publications

Deep brain stimulation (DBS), a proven treatment for movement disorders, also holds promise for the treatment of psychiatric and cognitive conditions. However, for DBS to be clinically effective, it may require DBS technology that can alter or trigger stimulation in response to changes in biomarkers sensed from the patient's brain. A growing body of evidence suggests that such adaptive DBS is feasible, it might achieve clinical effects that are not possible with standard continuous DBS and that some of the best biomarkers are signals from the cerebral cortex. Yet capturing those markers requires the placement of cortex-optimized electrodes in addition …

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Methods

Results

Safety, Efficacy, And Pharmacokinetics Of Oral Testosterone Undecanoate In Males With Hypogonadism, Martin Miner, Christina Wang, Jed Kaminetsky, Mohit Khera, Irwin Goldstein, Culley Carson, Nachiappan Chidambaram, Shelby King, Adrian Dobs

Faculty, Staff and Students Publications

Background: Testosterone deficiency results from insufficient testosterone production. Testosterone therapy may require dose titration to reach eugonadal serum testosterone concentrations.

Objective: The primary objective was the efficacy of oral testosterone undecanoate (TLANDO; Antares Pharma Inc.) in male patients with documented hypogonadism. Secondary objectives included a comparison of oral testosterone undecanoate safety and quality-of-life assessments to 1.62% topical testosterone gel (AndroGel 1.62%; AbbVie).

Materials and methods: In this phase 3 study, 315 patients were randomized 2:1 to oral testosterone undecanoate or 1.62% topical testosterone gel (NCT02081300). Patients received 225 mg oral testosterone undecanoate twice daily, and doses were adjusted …

Testing For Bleeding Disorders In Child Abuse: Aap Recommendation Adherence And Testing Results, Lyndsey Hultman, Angela Doswell, Henry T Puls, Shannon L Carpenter, Angela Bachim, Caitlin R Mcnamara, Farah W Brink, Lori D Frasier, Nancy S Harper, Natalie Laub, Kristine A Campbell, Daniel M Lindberg, Joanne N Wood, James Anderst

Faculty, Staff and Students Publications

Objectives: Using a multicenter child abuse pediatrics research network (CAPNET), the study objectives were to characterize the adherence to American Academy of Pediatrics (AAP) recommendations for bleeding disorder testing and the frequency of bleeding disorder identification.

Methods: We performed a descriptive study of bleeding disorder evaluations among children younger than 10 years of age who presented with bruising and/or intracranial hemorrhage (ICH) concerning for abuse from February 2021-May 2022 utilizing CAPNET. Cases were classified as bruising without ICH or ICH with or without bruising. Based on AAP guidance, testing was not recommended in cases with concomitant suspicious injuries, inflicted injury …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Expert Consensus For Key Components Of A High-Quality Ventral Hernia Repair Operative Note, Jonathan S Lall, Said Maldonado, Nicole B Lyons, Gina Adrales, Karla Bernardi, Anne P Ehlers, Hobart Harris, Julie Holihan, William Hope, Jeffrey E Janis, Michele Loor, Clayton Petro, Luke Putnam, Caroline E Reinke, John Scott Roth, Christopher Senkowski, Kendell Sowards, Shirin Towfigh, Daniel Dante Yeh, Zuhair Ali, Mike K Liang

Faculty, Staff and Students Publications

Background: Ventral hernia repair (VHR) is one of the most commonly performed procedures by surgeons; however, there remains a lack of consensus for key components of operative reporting. Prior literature has identified several key elements that are recommended for inclusion in ventral hernia repair operative notes, but it is unclear whether these details alone make for a high-quality operative note. This study sought to determine whether experts agree on what factors make a ventral hernia repair operative note high-quality.

Study design: A prospective exploratory sequential survey-based mixed-methods design was used for round 1. Conclusions via thematic analysis from survey responses …

For Girls And Women (4gw) Hpv Rct Protocol: A Crowdsourced, Pragmatic Stepped-Wedge Cluster Randomized Trial To Improve Uptake Of Hpv Vaccination And Screening Among Mother-Daughter Dyads In Nigeria, Juliet Iwelunmor, Ekenechukwu Kokelu, Temitope Ojo, Olufunto Olusanya, Titilola Gbaja-Biamila, Peter Kalulu, Angel Obiorah, Maria Afadapa, Nkiruka Obodoechina, Onyeka Anikamadu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expanding human papillomavirus (HPV) vaccination for girls and HPV self-collection for women can reduce the global burden of cervical cancer. However, HPV vaccination and self-collection services are rarely implemented simultaneously in mother-daughter dyads, leaving a critical gap in cervical cancer prevention. From 2023 to 2024, a community-engaged model for combined HPV vaccination and screening was co-designed using crowdsourcing open calls and designathons with mother-daughter teams and pilot-tested by trained research facilitators. This study explores the impact of this crowdsourced, community-engaged mother-daughter campaign and implementation strategy bundle on HPV vaccination among girls and HPV screening among their mothers in Nigeria …

Subclinical Atherosclerosis And Cardiovascular Events Among Patients With Colorectal Cancer, Julia A Levy, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

BACKGROUND: Prior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).

OBJECTIVES: To examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.

METHODS: Adults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography-CT scans at CRC diagnosis until 5 years post-diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable-adjusted …

Regulation Of Tfeb In Human Placental Cytotrophoblasts And Syncytiotrophoblasts, A Mathew, J S Trausch-Azar, C Azar, M Schuetz, M R Mahjoub, A L Schwartz

2020-Current year OA Pubs

While cellular proteins exist in a dynamic state maintained by the balance of synthesis and degradation, there is a paucity of information on these processes in placental trophoblasts, including within cytotrophoblasts which differentiate into multi-nucleate syncytiotrophoblasts. TFEB, a transcription factor with a myriad of cellular activities, is one of the most abundant genes expressed in syncytiotrophoblasts compared to cytotrophoblasts. TFEB is localized to the nucleus of human BeWo differentiated syncytiotrophoblasts and to the cytoplasm of the undifferentiated cytotrophoblasts. Within both the cytotrophoblasts and syncytiotrophoblasts, TFEB exists in subcellular compartments as both phosphorylated and unphosphorylated forms and translocates between cytoplasm and …

Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study Of Iluzanebart In Healthy Volunteers, Andreas Meier, Spyros Papapetropoulos, Andrew Marsh, Kelly Neelon, David Stiles, Ryan O'Mara, Evan A Thackaberry, Marco Colonna, Raj Rajagovindan

2020-Current year OA Pubs

OBJECTIVE: To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of iluzanebart, a fully human monoclonal antibody TREM2 (triggering receptor expressed on myeloid cells 2) agonist, after single- (SAD) and multiple-ascending-dose (MAD) administration.

METHODS: Healthy adult volunteers (N = 136) received intravenous placebo or iluzanebart 1-60 mg/kg (SAD) or 10-60 mg/kg (MAD) followed by serial pharmacokinetics and safety assessments. Safety assessments included adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory evaluations. Pharmacokinetics were assessed through noncompartmental analysis. The study also included open-label cohorts (3, 10, 20, 40, 60 mg/kg SAD; 10, 20, 40 mg/kg MAD) for cerebrospinal fluid (CSF) collection …

Elevated P16ink4a Expression Enhances Tau Phosphorylation In Neurons Differentiated From Human-Induced Pluripotent Stem Cells, Kristopher Holloway, Kashfia Neherin, Yingduo Song, Kazuhito Sato, Andrew Houston, Feng Chen, Li Ding, Hong Zhang

2020-Current year OA Pubs

Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a doxycycline-inducible system to trigger p16 up-regulation in human-induced pluripotent stem cells (iPSCs) and neurons differentiated from iPSCs. We demonstrated that up-regulated p16 expression in iPSCs reduces cell proliferation, down-regulates cell cycle genes, …

Assessing Hypersight Iterative Cbct For Dose Calculation In Online Adaptive Radiotherapy For Pelvis And Breast Patients Compared To Synthetic Ct, Jingwei Duan, Joel A Pogue, Dennis N Stanley, Sui Shen, Natalie N Viscariello, Carlos E Cardenas, Richard A Popple, Joseph Harms

2020-Current year OA Pubs

PURPOSE/OBJECTIVES: Recent technological advancements have increased efficiency for clinical deliverability of online-adaptive-radiotherapy (oART). Previous cone-beam-computed-tomography (CBCT) generations lacked the ability to provide reliable Hounsfield-units (HU), thus requiring oART workflows to rely on synthetic-CT (sCT) images derived through deformable-image-registration (DIR) between the planning CT (pCT) and the daily CBCT. These sCTs are prone to errors stemming from DIR, potentially contributing to dosimetric errors. This study aims to evaluate the capability of direct dose calculation using a novel CBCT platform, HyperSight (Varian-Medical-Systems), as an alternative for sCT.

METHODS/MATERIALS: To validate the HyperSight iterative CBCT (HS-iCBCT) HU accuracy, 125 kV and 140 kV …

Trends In Urology Residency Applications: Results From The American Urological Association Medical Student Survey From 2022 To 2024, Michael Creswell, Kirsten Greene, Lee Richstone, Simone Thavaseelan, Erica Traxel, Aaron Tverye, Casey Kowalik, Gina Badalato, Thomas Jarrett, Kate Kraft, Mathew Sorensen, Moben Mirza

2020-Current year OA Pubs

OBJECTIVE: To provide a comprehensive overview of the American Urological Association Medical Student Surveys and includes data 2022, 2023, and 2024.

METHODS: Data collected through surveys distributed prior to match day and were distributed to all medical students who submitted a rank list for urology residency. Questions consisted of various topics, including applicant demographics, application metrics, and experiences with preference signals and virtual interviews.

RESULTS: 440 (79%), 428 (84%), and 387 (77%) applicants participated in surveys for the years 2022, 2023, and 2024, respectively. Applicants continue to participate in research at a high level. Additionally, United States Medical Licensing Exam …

Functions Of Communication During Emergency Care Of Children With Medical Complexity: Caregiver Perspectives, Julia A Ciurria, Jennifer Reyes Lin, Cassandra M Pruitt, Bryan A Sisk

2020-Current year OA Pubs

OBJECTIVE: We investigated communication experiences of caregivers of children with medical complexity (CMC) during emergency care.

METHODS: Fifteen caregivers of CMC participated in semi-structured interviews regarding communication while seeking care for their child in the emergency department (ED). Thematic analysis was applied using a previously established functional communication model as an a priori framework.

RESULTS: Each of the previously established 8 core functions of communication were identified in this population. "Building relationships" manifested as clinicians soliciting caregiver input and responding to the needs of the caregiver. "Exchanging information" included clearly explaining next steps to caregivers. "Responding to emotions" acknowledged the …