Medicine and Health Sciences Commons^™

Tofacitinib, An Oral Janus Kinase Inhibitor: Analysis Of Malignancy (Excluding Nonmelanoma Skin Cancer) Events Across The Ulcerative Colitis Clinical Program, Gary R Lichtenstein, Gerhard Rogler, Matthew A Ciorba, Chinyu Su, Gary Chan, Ronald D Pedersen, Nervin Lawendy, Daniel Quirk, Chudy I Nduaka, Andrew J Thorpe, Julian Panés

2020-Current year OA Pubs

BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]).

METHODS: Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events …

Stroma-Targeting Strategies In Pancreatic Cancer: Past Lessons, Challenges And Prospects, Faran Polani, Patrick M Grierson, Kian-Huat Lim

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is projected to emerge as the second leading cause of cancer-related death after 2030. Extreme treatment resistance is perhaps the most significant factor that underlies the poor prognosis of PDAC. To date, combination chemotherapy remains the mainstay of treatment for most PDAC patients. Compared to other cancer types, treatment response of PDAC tumors to similar chemotherapy regimens is clearly much lower and shorter-lived. Aside from typically harboring genetic alterations that to date remain un-druggable and are drivers of treatment resistance, PDAC tumors are uniquely characterized by a densely fibrotic stroma that has well-established roles in promoting …

Opportunities And Challenges In Developing A Cryptosporidium Controlled Human Infection Model For Testing Antiparasitic Agents, Rajiv S Jumani, Johanne Blais, Hanns-Christian Tillmann, Florencia Segal, Dean Wetty, Christian Ostermeier, Natko Nuber, Jay Lakshman, Natasha Aziz, Richa Chandra, Wilbur H Chen, Cynthia L Chappell, Thierry T Diagana, Ujjini H Manjunatha

Faculty, Staff and Student Publications

Cryptosporidiosis is a leading cause of moderate-to-severe diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is also strongly associated with childhood malnutrition and growth stunting. There is no vaccine for cryptosporidiosis and existing therapeutic options are suboptimal to prevent morbidity and mortality in young children. Recently, novel therapeutic agents have been discovered through high-throughput phenotypic and target-based screening strategies, repurposing malaria hits, etc., and these agents have a promising preclinical in vitro and in vivo anti-

Increased Complement Activation Is A Distinctive Feature Of Severe Sars-Cov-2 Infection, Lina Ma, Sanjaya K. Sahu, Marlene Cano, Vasanthan Kuppuswamy, Jamal Bajwa, Ja’Nia Mcphatter, Tingting Lei, Aaron Day, Daniel Reynolds, Xiaobo Wu, Rebecca Schriefer, Adriana M. Rauseo, Charles W. Goss, Jane A. O’Halloran, Rachel M. Presti, Alfred H. Kim, Andrew E. Gelman, Philip A. Mudd, John P. Atkinson, Hrishikesh S. Kulkarni, Et Al.

2020-Current year OA Pubs

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine …

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …

Implementation And Sustainability Factors Of Two Early-Stage Breast Cancer Conversation Aids In Diverse Practices, Danielle Schubbe, Mary C Politi, Julie Margenthaler, Courtney Goodwin, Et Al

2020-Current year OA Pubs

BACKGROUND: Conversation aids can facilitate shared decision-making and improve patient-centered outcomes. However, few examples exist of sustained use of conversation aids in routine care due to numerous barriers at clinical and organizational levels. We explored factors that will promote the sustained use of two early-stage breast cancer conversation aids. We examined differences in opinions between the two conversation aids and across socioeconomic strata.

METHODS: We nested this study within a randomized controlled trial that demonstrated the effectiveness of two early-stage breast cancer surgery conversation aids, one text-based and one picture-based. These conversation aids facilitated more shared decision-making and improved the …

Model Organisms Contribute To Diagnosis And Discovery In The Undiagnosed Diseases Network: Current State And A Future Vision, Dustin Baldridge, Michael F Wangler, Angela N Bowman, Shinya Yamamoto, Undiagnosed Diseases Network, Tim Schedl, Stephen C Pak, John H Postlethwait, Jimann Shin, Lilianna Solnica-Krezel, Hugo J Bellen, Monte Westerfield

2020-Current year OA Pubs

Decreased sequencing costs have led to an explosion of genetic and genomic data. These data have revealed thousands of candidate human disease variants. Establishing which variants cause phenotypes and diseases, however, has remained challenging. Significant progress has been made, including advances by the National Institutes of Health (NIH)-funded Undiagnosed Diseases Network (UDN). However, 6000-13,000 additional disease genes remain to be identified. The continued discovery of rare diseases and their genetic underpinnings provides benefits to affected patients, of whom there are more than 400 million worldwide, and also advances understanding the mechanisms of more common diseases. Platforms employing model organisms enable …

Invasive Therapies For Acute Coronary Syndromes In The Covid-19 Era, Sanket Borgaonkar, Joshua Hahn, Marilyne Daher, Waleed Kayani, Hani Jneid

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: To identify and address the challenges associated with the care of ACS patients during the coronavirus 2019 pandemic.

RECENT FINDINGS: The COVID-19 pandemic has had a considerable global impact with over 2.0 million deaths worldwide so far. There has been considerable evidence suggesting that COVID-19 increases the risk of acute coronary syndromes (ACS). We propose characterizing ACS patients into 3 distinct categories to better assist in appropriate triage and management: critically ill patients, non-critically ill ST elevation myocardial infarction (STEMI) patients, and non-critically ill non-ST elevation myocardial infarction (NSTEMI)/unstable angina (UA) patients. We thoroughly review treatments strategies, …

Neurological Diseases And Covid-19: Prospective Analyses Using The Uk Biobank, Nicola Veronese, Lee Smith, Mario Barbagallo, Gianluigi Giannelli, Maria Gabriella Caruso, Anna Maria Cisternino, Maria Notarnicola, Chao Cao, Thomas Waldhoer, Lin Yang

2020-Current year OA Pubs

COVID-19 (Coronavirus disease-19) may present with neurological signs, but whether people already affected by neurological conditions are at a higher risk of contracting COVID-19 is still not known. We, therefore, aimed to investigate the association of previously diagnosed neurological conditions with COVID-19. 502,536 community-dwelling UK Biobank participants (54.4% male, mean age 56.6 ± 10.3 years) were included. Among these, 57,463 participants had a diagnosis of neurological conditions (11.43%) and a total of 1326 COVID-19-positive cases were identified (0.26%). Neurological conditions were identified through medical history and linkage to data on hospital admissions (ICD-10 code G00-G99). COVID-19 presence was diagnosed using …

Identifying And Predicting Food Parenting Practice Profiles Among Canadian Parents, Claire N Tugault-Lafleur, Olivia De-Jongh González, Teresia M O'Connor, Sheryl O Hughes, Louise C Mâsse

Children’s Nutrition Research Center Staff Publications

Background: Food parenting practices (FPP) can affect children's eating behaviours, yet little is known about how various FPP co-occur. The primary aim was to identify profiles of FPPs use among Canadian parents. Secondary aims included examining sociodemographic correlates of FPP profiles and evaluating whether children's eating behaviours differed across FPP profiles.

Methods: Parents (n = 799) of 5-12-year-old children completed a validated FPP Item Bank and the Children's Eating Behaviour Questionnaire. Latent Class Analysis (LCA) was used to identify distinct FPP profiles. Regression analyses were used to explore associations between FPP profiles, sociodemographic variables (race, sex and education) and children's …

Protecting Sanitation Workers In Low-Middle Income Countries Amid Covid-19, Muhammad Mainuddin Patwary, Md Riad Hossain, Faysal Kabir Shuvo, Sadia Ashraf, Rabeya Sultana, Md Ashraful Alam

Faculty, Staff and Student Publications

No abstract provided.

User Testing Of A Diagnostic Decision Support System With Machine-Assisted Chart Review To Facilitate Clinical Genomic Diagnosis., Alanna Kulchak Rahm, Nephi A Walton, Lynn K Feldman, Conner Jenkins, Troy Jenkins, Thomas N Person, Joeseph Peterson, Jonathon C Reynolds, Peter N Robinson, Makenzie A Woltz, Marc S Williams, Michael M Segal

Faculty Research 2021

OBJECTIVES: There is a need in clinical genomics for systems that assist in clinical diagnosis, analysis of genomic information and periodic reanalysis of results, and can use information from the electronic health record to do so. Such systems should be built using the concepts of human-centred design, fit within clinical workflows and provide solutions to priority problems.

METHODS: We adapted a commercially available diagnostic decision support system (DDSS) to use extracted findings from a patient record and combine them with genomic variant information in the DDSS interface. Three representative patient cases were created in a simulated clinical environment for user …

Covid-19-The American Perspective., Karl Saardi, Vesna Petronic-Rosic

Dermatology Faculty Publications

No abstract provided.

Behavioral Adverse Events With Brivaracetam, Levetiracetam, Perampanel, And Topiramate: A Systematic Review., Bernhard J Steinhoff, Pavel Klein, Henrik Klitgaard, Cédric Laloyaux, Brian D Moseley, Kristen Ricchetti-Masterson, Felix Rosenow, Joseph I Sirven, Brien Smith, John M Stern, Manuel Toledo, Patricia A Zipfel, Vicente Villanueva

Neuroscience Articles

PURPOSE: To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV.

METHODS: A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of …

Mortality In Hospitalized Patients With Cancer And Coronavirus Disease 2019: A Systematic Review And Meta-Analysis Of Cohort Studies, Aakash Desai, Rohit Gupta, Shailesh Advani, Lara Ouellette, Nicole M Kuderer, Gary H Lyman, Ang Li

Library Staff Publications

BACKGROUND: Heterogeneous evidence exists on the effect of coronavirus disease 2019 (COVID-19) on the clinical outcomes of patients with cancer.

METHODS: A systematic review was performed using the Medline, Embase, and CENTRAL databases and the World Health Organization Novel Coronavirus website to identify studies that reported mortality and characteristics of patients with cancer who were diagnosed with COVID-19. The primary study outcome was mortality, defined as all-cause mortality or in-hospital mortality within 30 days of initial COVID-19 diagnosis. The pooled proportion of mortality was estimated using a random-effects model, and study-level moderators of heterogeneity were assessed through subgroup analysis and …

Global Trends In Norovirus Genotype Distribution Among Children With Acute Gastroenteritis., Jennifer L. Cannon, Joseph Bonifacio, Filemon Bucardo, Javier Buesa, Leesa Bruggink, Martin Chi-Wai Chan, Tulio M. Fumian, Sidhartha Giri, Mark D. Gonzalez, Joanne Hewitt, Jih-Hui Lin, Janet Mans, Christian Muñoz, Chao-Yang Pan, Xiao-Li Pang, Corinna Pietsch, Mustafiz Rahman, Naomi Sakon, Rangaraj Selvarangan, Hannah Browne, Leslie Barclay, Jan Vinjé

Manuscripts, Articles, Book Chapters and Other Papers

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children(genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains …

Patient-Reported Outcomes From A Randomized, Active-Controlled, Open-Label, Phase 3 Trial Of Burosumab Versus Conventional Therapy In Children With X-Linked Hypophosphatemia, Raja Padidela, Michael P Whyte, Et Al.

2020-Current year OA Pubs

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue …

The Prove Study: Us Real-World Experience With Chlormethine/Mechlorethamine Gel In Combination With Other Therapies For Patients With Mycosis Fungoides Cutaneous T-Cell Lymphoma, Ellen J Kim, Joan Guitart, Christiane Querfeld, Michael Girardi, Amy Musiek, Oleg E Akilov, James T Angello, William L Bailey, Larisa J Geskin

2020-Current year OA Pubs

BACKGROUND: Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking.

OBJECTIVE: Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting.

METHODS: This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary …

Association Of Physician Group Practice Participation In Bundled Payments With Patient Selection, Costs, And Outcomes For Joint Replacement, Karen E Joynt Maddox, E John Orav, Jie Zheng, Arnold M Epstein

2020-Current year OA Pubs

IMPORTANCE: Medicare's Bundled Payments for Care Improvement (BPCI) program, which ran from 2013 to 2018, was an important experiment in physician-focused alternative payment models. However, little is known about whether the program was associated with better quality or outcomes or lower costs.

OBJECTIVE: To determine whether participation in BPCI among physician group practices was associated with advantageous or deleterious changes in costs or patient outcomes.

DESIGN SETTING AND PARTICIPANTS: This cross-sectional study used 2013 to 2017 Medicare files and difference-in-differences (DID) models to compare the change over time in Medicare payments, patient selection, and clinical outcomes between 91 orthopedic groups …

Should Weight-Bearing Activity Be Reduced During Healing Of Plantar Diabetic Foot Ulcers, Even When Using Appropriate Offloading Devices?, Gustav Jarl, Jaap J Van Netten, Peter A Lazzarini, Ryan T Crews, Bijan Najafi, Michael J Mueller

2020-Current year OA Pubs

Physical activity is an essential part of general health and diabetes management. However, recommending weight-bearing physical activity for people with plantar diabetic foot ulcers is controversial, even when gold standard offloading devices are used, as it is commonly thought to delay healing. We aimed to narratively review relevant studies investigating the relationship between plantar diabetic foot ulcer healing and weight-bearing activity, plantar pressure and device adherence. We defined relevant studies as those from two systematic reviews, along with those identified since using a similar updated Pubmed search strategy. We identified six studies. One study found that more daily steps were …

Goals-Of-Care Course For Emergency Physicians During The Covid-19 Pandemic., Mari Siegel, Erica Westlake

Department of Emergency Medicine Faculty Papers

BACKGROUND

COVID-19 increased the need for goals of care (GOC) discussions in the Emergency Department (ED). Many Emergency Physicians (EPs) report no formal training in holding GOC discussions. COVID-19 created unique teaching challenges given social distancing requirements.

METHODS

Eight teaching sessions were held using Zoom in March and April at an urban institution in the United States. Sessions were limited to 4-8 participants. They were comprised of a 30-minute lecture and 15 minutes of role-playing, in which providers read scripts to practice communication skills. The lecture introduced vocabulary and models to shape GOC discussions. Participants were invited to complete an …

N-3 Fatty Acid Biomarkers And Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project Of 20 Prospective Cohort Studies, Frank Qian, Andres V Ardisson Korat, Fumiaki Imamura, Matti Marklund, Nathan Tintle, Jyrki K Virtanen, Xia Zhou, Julie K Bassett, Heidi Lai, Yoichiro Hirakawa, Kuo-Liong Chien, Alexis C Wood, Maria Lankinen, Rachel A Murphy, Cecilia Samieri, Kamalita Pertiwi, Vanessa D De Mello, Weihua Guan, Nita G Forouhi, Nick Wareham, Interact Consortium Frank B Hu, Ulf Riserus, Lars Lind, William S Harris, Aladdin H Shadyab, Jennifer G Robinson, Lyn M Steffen, Allison Hodge, Graham G Giles, Toshiharu Ninomiya, Matti Uusitupa, Jaakko Tuomilehto, Jaana Lindström, Markku Laakso, David S Siscovick, Catherine Helmer, Johanna M Geleijnse, Jason H Y Wu, Amanda Fretts, Rozenn N Lemaitre, Renata Micha, Dariush Mozaffarian, Qi Sun

Children’s Nutrition Research Center Staff Publications

Objective: Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

Research design and methods: For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed …

A Hindbrain Dopaminergic Neural Circuit Prevents Weight Gain By Reinforcing Food Satiation, Yong Han, Guobin Xia, Yanlin He, Yang He, Monica Farias, Yong Xu, Qi Wu

Children’s Nutrition Research Center Staff Publications

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DAcVTA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1LPBN neurons inhibits feeding, whereas genetic deletion of Drd1 within the …

Risk And Clinical Risk Factors Associated With Late Lower Cranial Neuropathy In Long-Term Oropharyngeal Squamous Cell Carcinoma Survivors, Puja Aggarwal, Ryan P Goepfert, Adam S Garden, Naveen Garg, Jhankruti S Zaveri, Xianglin L Du, Michael D Swartz, Stephen Y Lai, C David Fuller, Renata Ferrarotto, Erich M Sturgis, Linda B Piller, Katherine A Hutcheson

Faculty, Staff and Student Publications

IMPORTANCE: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors).

OBJECTIVE: to estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors.

DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, …

Intravenous Smart Pumps During Actual Clinical Use: A Descriptive Comparison Of Primary And Secondary Infusion Practices., Karen K Giuliano, Daleen Penoyer, Rebecca S. Mahuren, Melody Bennett

Parkview Pharmacy Department

This descriptive observational study was conducted to increase understanding of medication administration practices during actual clinical use between 2 commonly used, different types of intravenous (IV) smart pumps. Compliance with manufacturer-recommended setup requirements for both primary and secondary infusions and secondary medication administration delay was compared between a head-height differential system and a cassette system. A total of 301 medication administration observations were included in this study: 102 (34%) for the linear peristaltic IV smart pump (medical-surgical: N = 51; critical care: N = 51) and 199 (66%) for the cassette pump (medical-surgical: N = 88; critical care: N = …

Exercise-Induced Alterations In Phospholipid Hydrolysis, Airway Surfactant, And Eicosanoids And Their Role In Airway Hyperresponsiveness In Asthma, Ryan C Murphy, Ying Lai, James D Nolin, Robier A Aguillon Prada, Arindam Chakrabarti, Michael V Novotny, Michael C Seeds, William A Altemeier, Michael H Gelb, Robert Duncan Hite, Teal S Hallstrand

Faculty, Staff and Student Publications

The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (

Predictive Factors For Success Of Awake Proning In Hypoxemic Respiratory Failure Secondary To Covid-19: A Retrospective Cohort Study, Sujith V Cherian, Chang Li, Brad Roche, Stephan A Reyes, Siddharth Karanth, Aditya P Lal, Gabriel M Aisenberg, Rosa M Estrada-Y-Martin

Faculty, Staff and Student Publications

BACKGROUND: Awake prone positioning has been recommended as an adjunctive measure in spontaneously breathing patients with hypoxemic respiratory failure during the COVID-19 pandemic. It remains uncertain as to how long this should be implemented, what variables to follow and who would be the ideal candidates for this adjunctive therapy.

METHODS: A retrospective chart review of patients admitted from April to August 2020 within our institution with multifocal pneumonia and hypoxemic respiratory failure secondary to COVID-19 who underwent awake-proning for at least 3 hours was conducted.

RESULTS: Improvement in respiratory parameters including ROX (SpO2/Fio2/ Respiratory Rate) indices and inflammatory markers within …

Bacterial Sepsis Increases Hippocampal Fibrillar Amyloid Plaque Load And Neuroinflammation In A Mouse Model Of Alzheimer's Disease, Jacob M Basak, Aura Ferreiro, Lucy S Cohen, Patrick W Sheehan, Collin J Nadarajah, Michael F Kanan, Kimberley V Sukhum, Gautam Dantas, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sepsis, a leading cause for intensive care unit admissions, causes both an acute encephalopathy and chronic brain dysfunction in survivors. A history of sepsis is also a risk factor for future development of dementia symptoms. Similar neuropathologic changes are associated with the cognitive decline of sepsis and Alzheimer's disease (AD), including neuroinflammation, neuronal death, and synaptic loss. Amyloid plaque pathology is the earliest pathological hallmark of AD, appearing 10 to 20 years prior to cognitive decline, and is present in 30% of people over 65. As sepsis is also more common in older adults, we hypothesized that sepsis might …

Patient-Reported Barriers Are Associated With Receipt Of Hepatocellular Carcinoma Surveillance In A Multicenter Cohort Of Patients With Cirrhosis, Amit G Singal, Jasmin A Tiro, Caitlin C Murphy, James-Michael Blackwell, Jennifer R Kramer, Aisha Khan, Yan Liu, Song Zhang, Jessica L Phillips, Ruben Hernaez

Faculty, Staff and Students Publications

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt.

METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration.

RESULTS: Of 2871 patients …

Associations Of Abdominal Pain And Psychosocial Distress Measures With Health-Related Quality-Of-Life In Pediatric Healthy Controls And Irritable Bowel Syndrome, John M Hollier, Danita I Czyzewski, Mariella M Self, Yan Liu, Erica M Weidler, Miranda A L Van Tilburg, James W Varni, Robert J Shulman

Faculty, Staff and Students Publications

BACKGROUND: Children with irritable bowel syndrome (IBS) have lower health-related quality-of-life (HRQOL) than healthy controls (HC). Abdominal pain and psychosocial distress are negatively associated with HRQOL, although their relative effect is unclear.

AIM: The aim of this study was to compare the relative associations of abdominal pain and psychosocial distress with HRQOL in HC and IBS.

STUDY: Baseline abdominal pain, psychosocial distress, and HRQOL measures were obtained from HC and IBS pediatric clinical trial participants. Regression assessed which measures were most strongly associated with Physical and Psychosocial HRQOL separately by group. Interaction analyses examined group differences in the associations of …