Diseases Commons^™

Emerging Issues In Probiotic Safety: 2023 Perspectives, Daniel Merenstein, Bruno Pot, Gregory Leyer, Arthur C Ouwehand, Geoffrey A Preidis, Christopher A Elkins, Colin Hill, Zachery T Lewis, Andi L Shane, Niv Zmora, Mariya I Petrova, Maria Carmen Collado, Lorenzo Morelli, Gina A Montoya, Hania Szajewska, Daniel J Tancredi, Mary Ellen Sanders

Faculty, Staff and Students Publications

Probiotics are used for both generally healthy consumers and in clinical settings. However, theoretical and proven adverse events from probiotic consumption exist. New probiotic strains and products, as well as expanding use of probiotics into vulnerable populations, warrants concise, and actionable recommendations on how to work toward their safe and effective use. The International Scientific Association for Probiotics and Prebiotics convened a meeting to discuss and produce evidence-based recommendations on potential acute and long-term risks, risks to vulnerable populations, the importance for probiotic product quality to match the needs of vulnerable populations, and the need for adverse event reporting related …

Cholestasis Impairs Gut Microbiota Development And Bile Salt Hydrolase Activity In Preterm Neonates, Lauren E Lynch, Amy B Hair, Krishnakant G Soni, Heeju Yang, Laura A Gollins, Monica Narvaez-Rivas, Kenneth D R Setchell, Geoffrey A Preidis

Faculty, Staff and Students Publications

Cholestasis refers to impaired bile flow from the liver to the intestine. In neonates, cholestasis causes poor growth and may progress to liver failure and death. Normal bile flow requires an intact liver-gut-microbiome axis, whereby liver-derived primary bile acids are transformed into secondary bile acids. Microbial bile salt hydrolase (BSH) enzymes are responsible for the first step, deconjugating glycine- and taurine-conjugated primary bile acids. Cholestatic neonates often are treated with the potent choleretic bile acid ursodeoxycholic acid (UDCA), although interactions between UDCA, gut microbes, and other bile acids are poorly understood. To gain insight into how the liver-gut-microbiome axis develops …

Insulin-Like Growth Factor 1 Supplementation Supports Motor Coordination And Affects Myelination In Preterm Pigs, Line I Christiansen, Gemma C Ventura, Bo Holmqvist, Karoline Aasmul-Olsen, Sandy E H Lindholm, Matthew D Lycas, Yuki Mori, Jan Bojsen-Møller Secher, Douglas G Burrin, Thomas Thymann, Per T Sangild, Stanislava Pankratova

Faculty, Staff and Students Publications

INTRODUCTION: Preterm infants have increased risk of impaired neurodevelopment to which reduced systemic levels of insulin-like growth factor 1 (IGF-1) in the weeks after birth may play a role. Hence, we hypothesized that postnatal IGF-1 supplementation would improve brain development in preterm pigs, used as a model for preterm infants.

METHODS: Preterm pigs delivered by cesarean section received recombinant human IGF-1/IGF binding protein-3 complex (rhIGF-1/rhIGFBP-3, 2.25 mg/kg/day) or vehicle from birth to postnatal day 19. Motor function and cognition were assessed by monitoring of in-cage and open field activities, balance beam test, gait parameters, novel object recognition and operant conditioning …

Determinants Of Retention In Care Of Newborns Diagnosed With Sickle Cell Disease In Liberia: Results From A Mixed-Methods Study Of Caregivers, Kanagasabai Udhayashankar, Patience D Franklin, Cecelia J Nuta, Adolphus K Cherue, Heather Haq, Debbe Thompson, Venée N Tubman

Faculty, Staff and Students Publications

High-income nations have established that early diagnosis and preventive treatment reduces early deaths in sickle cell disease (SCD). However, in low-/middle-income countries where SCD is common, attrition from clinical care is common. Reasons for poor retention in care are multi-factorial and poorly understood. The objective of this study was to identify factors that influence caregiver decision-making around chronic health care needs of a child with SCD. We conducted an exploratory sequential mixed methods study of caregivers of children diagnosed with SCD during a newborn screening program in Liberia. Caregivers completed questionnaires and semi-structured interviews designed to identify drivers of health …

Impact Of The Covid Pandemic On Mental Health And Training Opportunities Of Public Health Residents From 4 European Countries: A Cross-Sectional Study, Giovanna Failla, Marta Caminiti, José Chen-Xu, Giuseppina Lo Moro, Nausicaa Berselli, Madalena Cabral Ferreira, Filipa Malcata, David Peyre-Costa, Roberto Croci, Giorgia Soldà, Angelo Capodici, Caterina Morcavallo, Francesco Traglia, Fabrizio Cedrone, Ilaria Storti, Alfonso Alonso Jaquete, Martina Antinozzi, Anca Vasiliu

Faculty, Staff and Students Publications

OBJECTIVES: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic.

METHODS: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors.

RESULTS: Among the 443 respondents, many showed symptoms of depression …

The Epidemiology Of Cephalosporin Allergy Labels In Pediatric Primary Care, Torsten Joerger, Margaret G Taylor, Debra L Palazzi, Jeffrey S Gerber

Faculty, Staff and Students Publications

BACKGROUND: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting.

METHODS: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis …

Review Of Acute Kidney Injury And Progression To Chronic Kidney Disease In Pediatric Patients Undergoing Hematopoietic Cell Transplant, Kim T Vuong, Catherine Joseph, Joseph R Angelo

Faculty, Staff and Students Publications

While acute kidney injury (AKI) after hematopoietic cell transplant (HCT) has been well-described in pediatric patients, literature regarding the long term renal consequences of HCT-related AKI, the development of chronic kidney disease (CKD), and CKD care in pediatric patients post-HCT is limited. CKD affects almost 50% of patients after HCT with multifactorial etiology including infection, nephrotoxic medications, transplant-associated thrombotic microangiopathy, graft-versus-host disease, and sinusoidal obstruction syndrome. As renal function declines in CKD, eventually progressing to end stage kidney disease (ESKD), mortality increases and is more than 80% among patients requiring dialysis. Using society guidelines and current literature, this review summarizes …

Cefepime Dosing In A Critically Ill Neonate Receiving Continuous Renal Replacement Therapy With The Cardio-Renal Pediatric Dialysis Emergency Machine (Carpediem), Cynthia Toy, Grant Stimes, Megan Moore, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

We report on a former 27-week gestational age infant who was placed on the Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM) at 4 months post-menstrual age while receiving cefepime treatment for an Enterobacter cloacae bacteremia and persistent peritonitis secondary to an infected peritoneal dialysis catheter. Using therapeutic drug monitoring while assessing the clearance of cefepime on continuous renal replacement therapy (CRRT), we were able to successfully treat this patient's infection while also minimizing the risk of side effects from this medication. Current literature supports dosing in adult patients on all modalities of CRRT with effluent flow rates of 20 to 25 …

Clinical Correlates Of Cholestasis In Preterm Infants With Surgical Necrotizing Enterocolitis, Parvesh Mohan Garg, Isabella Pittman, Joe Yi, Victoria G Weis, Ricardo Jorge Rodriguez, Mitchell R Ladd, Jessica L Rauh, Anna Greene Mcdonald, Cherrie Welch, Muralidhar Hebbur Premkumar, Padma P Garg, Akhil Maheshwari

Faculty, Staff and Students Publications

BACKGROUND: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC).

METHODS: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not.

RESULTS: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%;

CONCLUSION: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer …

Multiomics, Artificial Intelligence, And Precision Medicine In Perinatology, Mohan Pammi, Nima Aghaeepour, Josef Neu

Faculty, Staff and Students Publications

Technological advances in omics evaluation, bioinformatics, and artificial intelligence have made us rethink ways to improve patient outcomes. Collective quantification and characterization of biological data including genomics, epigenomics, metabolomics, and proteomics is now feasible at low cost with rapid turnover. Significant advances in the integration methods of these multiomics data sets by machine learning promise us a holistic view of disease pathogenesis and yield biomarkers for disease diagnosis and prognosis. Using machine learning tools and algorithms, it is possible to integrate multiomics data with clinical information to develop predictive models that identify risk before the condition is clinically apparent, thus …

A Rapid, Low-Cost, And Highly Sensitive Sars-Cov-2 Diagnostic Based On Whole-Genome Sequencing, Per A Adastra, Neva C Durand, Namita Mitra, Saul Godinez Pulido, Ragini Mahajan, Alyssa Blackburn, Zane L Colaric, Joshua W M Theisen, David Weisz, Olga Dudchenko, Andreas Gnirke, Suhas S P Rao, Parwinder Kaur, Erez Lieberman Aiden, Aviva Presser Aiden

Faculty, Staff and Students Publications

Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably ( …

Mass Spectrometry Imaging As An Emerging Tool For Studying Metabolism In Human Brain Organoids, Gerarda Cappuccio, Saleh M Khalil, Sivan Osenberg, Feng Li, Mirjana Maletic-Savatic

Faculty, Staff and Students Publications

Human brain organoids are emerging models to study human brain development and pathology as they recapitulate the development and characteristics of major neural cell types, and enable manipulation through an in vitro system. Over the past decade, with the advent of spatial technologies, mass spectrometry imaging (MSI) has become a prominent tool for metabolic microscopy, providing label-free, non-targeted molecular and spatial distribution information of the metabolites within tissue, including lipids. This technology has never been used for studies of brain organoids and here, we set out to develop a standardized protocol for preparation and mass spectrometry imaging of human brain …

The Role Of Supervised School Therapy In Poorly Controlled Asthma In Children, Muppala Raju, Malvika Sagar, Andrew Bush, Eugene Quaye, Shekhar Ghamande, Sonal Malhotra, Mercedes E Arroliga

Faculty, Staff and Students Publications

BACKGROUND: In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications.

METHODS: We evaluated the benefit from initiation of ICS administration once daily at school. We retrospectively chose patients from our pediatric pulmonary clinic who had poorly controlled asthma and prescribed ICS daily. For the study period, we examined the number of corticosteroid courses, emergency room visits, hospital admissions, symptom history, and pulmonary function tests.

RESULTS: Thirty-four patients who satisfied the inclusion criteria began the intervention. Preintervention, there were a mean number of 2.6 oral corticosteroid courses compared to 2 courses in the year following …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

Prevalence Of Trypanosoma Cruzi, The Etiologic Agent Of Chagas Disease, Infection In Texas Skunks (Mammalia: Mephitidae), Bonnie E Gulas-Wroblewski, Rodion Gorchakov, Rebecca B Kairis, Robert C Dowler, Kristy O Murray

Faculty, Staff and Students Publications

Background:

Chagas disease is one of the world's most neglected tropical diseases, infecting over six million people across the Americas. The hemoparasite Trypanosoma cruzi is the etiological agent for the disease, circulating in domestic, peridomestic, and sylvatic transmission cycles that are maintained by triatomine vectors and a diversity of wild and synanthropic hosts. Public health and wildlife management interventions targeting the interruption of T. cruzi transmission rely on an understanding of the dynamics driving the ecology of this zoonotic pathogen. One wildlife host that purportedly plays a role in the transmission of Chagas disease within the southern United States is …

Immunomodulatory Proteins From Hookworms Reduce Cardiac Inflammation And Modulate Regulatory Responses In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Kathryn M Jones, Bin Zhan, Keenan J Ernste, Maria Jose Villar, Nalini Bisht, Duc Nguyen, Li-Yen Chang, Cristina Poveda, Gonteria J Robinson, Akshar J Trivedi, Colby J Hofferek, William K Decker, Vanaja Konduri

Faculty, Staff and Students Publications

Introduction

Hookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased …

Risk Factors Of Local Control In Adrenal Metastases Treated By Stereotactic Body Radiation Therapy – A Systematic Review And Meta-Analysis, Xuehong Liao, Kazushi Kishi, Kaixin Du, Ritsuko Komaki, Junetsu Mizoe, Gosuke Aikawa, Wei Zheng, Chao Pan

Faculty, Staff and Students Publications

PURPOSE: This study is aimed to explore risk factors affect the therapy outcomes of adrenal metastases (AM) for stereotactic body radiation therapy (SBRT) and guide clinical dose selection.

METHODS AND MATERIALS: PubMed, Embase and Web of Science were searched in September 22, 2022 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Subgroup analysis and meta-regression were used to search for sources of heterogeneity and identify risky outcomes factors. Publication bias test and sensitivity analysis were also conducted.

RESULTS: Thirty-three studies with full text from 2009 to 2022 about AM with SBRT on 1483 patients were …

Development Of A Clinical Prediction Model For Diabetes In Chronic Pancreatitis: The Predict3c Study, Christie Jeon, Phil A Hart, Liang Li, Yunlong Yang, Eleanor Chang, Melena D Bellin, William E Fisher, Evan L Fogel, Christopher E Forsmark, Walter G Park, Stephen K Van Den Eeden, Santhi Swaroop Vege, Jose Serrano, David C Whitcomb, Dana K Andersen, Darwin L Conwell, Dhiraj Yadav, Mark O Goodarzi

Faculty, Staff and Students Publications

OBJECTIVE: Diabetes that arises from chronic pancreatitis (CP) is associated with increased morbidity and mortality. Methods to predict which patients with CP are at greatest risk for diabetes are urgently needed. We aimed to examine independent risk factors for diabetes in a large cohort of patients with CP.

RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 645 individuals with CP enrolled in the PROCEED study, of whom 276 had diabetes. We conducted univariable and multivariable regression analyses of potential risk factors for diabetes. Model performance was assessed by area under the receiver operating characteristic curve (AUROC) analysis, and accuracy was …

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …

Inotropic Score And Vasoactive Inotropic Score As Predictors Of Outcomes In Congenital Diaphragmatic Hernia: A Single Center Retrospective Study, Srirupa Hari Gopal, Cynthia L Toy, Morcos Hanna, Betul Yilmaz Furtun, Joseph L Hagan, Ahmed A Nassr, Caraciolo J Fernandes, Sundeep Keswani, Sharada H Gowda

Faculty, Staff and Students Publications

BACKGROUND: Neonates with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction. These neonates frequently require vasoactive support and are at high risk for mortality and morbidity, including prolonged ventilator support, need for extracorporeal membrane oxygenation (ECMO), prolonged length of stay, and need for tracheostomy. However, identifying which infants are at increased risk can be challenging. In this study, we sought to investigate the utility of the inotropic score (IS) and vasoactive inotropic score (VIS) as tools to predict significant clinical outcomes and overall survival in patients with CDH. Additionally, we evaluated the …

Peyronie's Disease: An Outcomes-Based Guide To Non-Surgical And Novel Treatment Modalities, Amit G Reddy, Michelle C Dai, Jeffrey J Song, Hudson M Pierce, Sagar R Patel, Larry I Lipshultz

Faculty, Staff and Students Publications

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. …

Smart Offloading Boot System For Remote Patient Monitoring: Toward Adherence Reinforcement And Proper Physical Activity Prescription For Diabetic Foot Ulcer Patients, Catherine Park, Ramkinker Mishra, Davide Vigano, Maurizio Macagno, Stefano Rossotti, Karen D'Huyvetter, Jason Garcia, David G Armstrong, Bijan Najafi

Center on Aging Staff Publications

Background: A critical factor in healing diabetic foot ulcers is patient adherence to offloading devices. We tested a smart offloading boot (SmartBoot) combined with a smartwatch app and cloud dashboard to remotely monitor patient adherence and activity. In addition, the impact of SmartBoot on balance, gait, and user experience was investigated.

Methods: Fourteen volunteers (31.6±8.7 years; 64% female) performed natural activities (eg, sitting, standing, walking) with and without the SmartBoot for approximately 30 minutes. All participants completed balance tests, 10-meter walking tests at slow, normal, and fast pace while wearing the SmartBoot, and a user experience questionnaire. The accuracy of …

Mitral Valve Surgery In Patients With An Implanted Amplatzer Septal Occluder: A Review Of 2 Cases, Ufuk Sayar, Nurel Ertürk

The Texas Heart Institute Journal

Surgical approaches for mitral valve exploration vary, with the preferred approach being via the interatrial groove. Data on whether the interatrial groove approach can be used for mitral valve surgery in patients with a previously implanted Amplatzer septal occluder (ASO) (St Jude Medical, an Abbott company) are extremely limited. The authors performed mitral valve surgery using the transatrial septal approach on 2 patients following explantation of an ASO, which significantly impedes the interatrial groove approach. Concomitant surgical procedures with mitral valve replacement, removal of the ASO, and closure of an atrial septal defect with a patch significantly prolonged the cross-clamp …

Surgical Reconstruction Of The Anomalous Left Coronary Artery From The Pulmonary Artery, Slobodan Micovic, Petar Milacic, Miroslav Milicic, Milica Brkovic, Petar Vukovic, Igor Zivkovic

The Texas Heart Institute Journal

The anomalous left coronary artery from the pulmonary artery is a rare congenital disease. Early surgical reconstruction is mandatory to prevent adverse cardiac events. Direct coronary button transfer, vein graft interposition, ligation, and coronary artery bypass construction are the most commonly used techniques. This case report presents a modified technique of Dacron graft interposition and reimplantation anomalous left coronary artery from the pulmonary artery on the ascending aorta.

Is It Time To Switch To Bivalirudin For Ecmo Anticoagulation?, Amir Navaei, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

For decades, unfractionated heparin (hereafter, heparin) has been the primary anticoagulant used for extracorporeal membrane oxygenation (ECMO) support. More recently, however, bivalirudin, a direct thrombin inhibitor, has emerged as an alternative. This systematic review based on PRISMA guidelines, aims to summarize 16 comparative studies and 8 meta-analysis and review articles published from January, 2011 till May, 2023 which directly compares ECMO courses using heparin versus bivalirudin as the anticoagulant. While this comparison is complicated by the lack of a standardized definition of major bleeding or thrombosis, our overall findings suggest there is no statistical difference between heparin and bivalirudin in …

A Rare Case Of Pancreatic Actinomyces, Marguerite Poche, Kyle Liu, Codey Pham, Shilpa Jain, Robert Sealock

Faculty, Staff and Students Publications

Actinomyces israelii is a filamentous, gram-positive anaerobic bacterium commonly found in the upper gastrointestinal tract, colon, and female genital tract. Rarely, actinomycosis can infect the pancreas most commonly after pancreatic instrumentation, often mimicking malignancy. We describe a case of a 26-year-old woman who presented with epigastric abdominal pain and nausea without prior pancreatic instrumentation. Abdominal imaging demonstrated a mass in the pancreatic head with fine-needle biopsy revealing Actinomyces. The patient was successfully treated with long-term antibiotic therapy resulting in resolution of the mass. Our case emphasizes the importance of considering nonmalignant etiologies in the differential diagnosis of pancreatic masses.

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

Early Detection Of Mandible Osteoradionecrosis Risk In A High Comorbidity Veteran Population, David Chamberlayne Wilde, Sagar Kansara, Logan Banner, Rickey Morlen, David Hernandez, Andrew Tsao Huang, Weiyuan Mai, Clifton David Fuller, Stephen Lai, Vlad Constantin Sandulache

Faculty, Staff and Student Publications

OBJECTIVE: Osteoradionecrosis (ORN) of the mandible is a devastating complication of external beam radiation therapy (EBRT) for head and neck squamous cell carcinoma (HNSCC). We sought to ascertain ORN risk in a Veteran HNSCC population treatment with definitive or adjuvant EBRT and followed prospectively.

STUDY DESIGN: Retrospective analysis of prospective cohort.

SETTING: Tertiary care Veterans Health Administration (VHA) medical center.

METHODS: Patients with HNSCC who initiated treatment at the Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) are prospectively tracked for quality of care purposes through the end of the cancer surveillance period (5 years post treatment completion). We retrospectively …

Trends In Disease Severity Among Critically Ill Children With Severe Acute Respiratory Syndrome Coronavirus 2: A Retrospective Multicenter Cohort Study In The United States, Catherine E Ross, Jeffrey P Burns, Anne V Grossestreuer, Pallav Bhattarai, Christine A Mckiernan, Jennifer D Franks, Sonja Lehmann, Jill L Sorcher, Matthew P Sharron, Kitman Wai, Haitham Al-Wahab, Konstantinos Boukas, Mark W Hall, George Ru, Anita I Sen, Hariprem R Rajasekhar, Lawrence C Kleinman, John K Mcguire, Amy S Arrington, Flor Munoz-Rivas, Christopher M Osborne, Lara S Shekerdemian

Faculty, Staff and Student Publications

OBJECTIVES: To describe trends in critical illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children over the course of the COVID-19 pandemic. We hypothesized that PICU admission rates were higher in the Omicron period compared with the original outbreak but that fewer patients needed endotracheal intubation.

DESIGN: Retrospective cohort study.

SETTING: This study took place in nine U.S. PICUs over 3 weeks in January 2022 (Omicron period) compared with 3 weeks in March 2020 (original period).

PATIENTS: Patients less than or equal to 21 years old who screened positive for SARS-CoV-2 infection by polymerase chain reaction or …