Digital Commons Network^™

Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al

Open Access Publications

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned …

Pathways To Post-Traumatic Stress Disorder And Alcohol Dependence: Trauma, Executive Functioning, And Family History Of Alcoholism In Adolescents And Young Adults, Stacey Subbie-Saenz De Viteri, Andrey Anokhin, Vivia Mccutcheon, Kathleen Bucholz, Et Al

Open Access Publications

INTRODUCTION: Family history (FH) of alcohol dependence is likely to increase the risk of trauma exposure, post-traumatic stress disorder (PTSD), and alcohol dependence. FH of alcohol dependence and trauma has been separately shown to adversely affect planning/problem-solving aspects of executive function. However, few studies have examined these risk factors in an integrated model.

METHODS: Using data from trauma-exposed individuals from the Collaborative Study on the Genetics of Alcoholism prospective cohort (N = 1,860), comprising offspring from alcohol-dependent high-risk and comparison families (mean age [SE] = 21.9 [4.2]), we investigated associations of trauma (nonsexual assaultive, nonassaultive, sexual assaultive) with DSM-IV PTSD …

The Perceived Challenge Of Everyday Technologies In Sweden, The United States And England: Exploring Differential Item Functioning In The Everyday Technology Use Questionnaire, Sarah Wallcook, Camilla Malinowsky, Louise Nygård, Georgina Charlesworth, Jenica Lee, Ryan Walsh, Sophie Gaber, Anders Kottorp

Open Access Publications

No abstract provided.

Rate Of Surgery And Baseline Characteristics Associated With Surgery Progression In Young Athletes With Prearthritic Hip Disorders, Reid W Collis, Andrea B Mccullough, Chris Ng, Heidi Prather, Graham A Colditz, John C Clohisy, Abby L Cheng

Open Access Publications

Background: Prearthritic hip disorders (PAHD), such as femoroacetabular impingement (FAI), acetabular dysplasia, and acetabular labral tears, are a common cause of pain and dysfunction in adolescent and young adult athletes, and optimal patient-specific treatment has not been defined. Operative management is often recommended, but conservative management may be a reasonable approach for some athletes.

Purpose: To identify (1) the relative rate of progression to surgery in self-reported competitive athletes versus nonathletes with PAHD and (2) baseline demographic, pain, and functional differences between athletes who proceeded versus those who did not proceed to surgery within 1 year of evaluation.

Study Design: …

Short-Term Clinical Outcomes Of Hip Arthroscopy Versus Physical Therapy In Patients With Femoroacetabular Impingement: A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Maria T Schwabe, John C Clohisy, Abby L Cheng, Cecilia Pascual-Garrido, Marcie Harris-Hayes, Devyani M Hunt, Michael D. Harris, Heidi Prather, Jeffrey J Nepple

Open Access Publications

Background: Both physical therapy (PT) and surgery are effective in treating femoroacetabular impingement (FAI), but their relative efficacy has not been well established until recently. Several randomized controlled trials (RCTs) comparing the early clinical outcomes of these treatments have been published, with contradictory results.

Purpose/Hypothesis: The purpose of this study was to perform a meta-analysis of RCTs that compared early patient-reported outcomes (PROs) of hip arthroscopy versus PT in patients with symptomatic FAI. The hypothesis was that surgical treatment of FAI leads to better short-term outcomes than PT.

Study Design: Systematic review; Level of evidence, 1.

Methods: In March 2019, …

The Impact Of Direct-To-Consumer Wearables In Pediatric Electrophysiology Telehealth Clinics: A Real-World Case Series, Lisa Roelle, Aarti S Dalal, Nathan Miller, William B Orr, George Van Hare, Jennifer N Avari Silva

Open Access Publications

No abstract provided.

The Cost Of A Single Concussion In American High School Football: A Retrospective Cohort Study, Aaron M. Yengo-Kahn, Patrick D. Kelly, David C. Liles, Lydia J. Mckeithan, Candace J. Grisham, Muhammad Saad Khan, Timothy Lee, Andrew M. Kuhn, Christopher M. Bonfield, Scott L. Zuckerman

Open Access Publications

Aim: The potential financial burden of American football-related concussions (FRC) is unknown. Our objective was to describe the healthcare costs associated with an FRC and determine factors associated with increased costs.

Methodology/results: A retrospective cohort study of concussed high school football players presenting between November 2017 and March 2020 was undertaken; 144 male high school football players were included. Total costs were about $115,000, for an average direct healthcare cost of $800.10/concussion. Visiting the emergency department (β = 502.29, 95% CI: 105.79-898.61; p = 0.01), the initial post-concussion symptom scale score (β = 0.39, 95% CI: 0.11-0.66; p = 0.01) …

Sarm1 Depletion Rescues Nmnat1-Dependent Photoreceptor Cell Death And Retinal Degeneration, Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron Diantonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt

Open Access Publications

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD

Use And Awareness Of The Community Guide In State And Local Health Department Chronic Disease Programs, Emily Rodriguez Weno, Stephanie Mazzucca, Renee G Parks, Margaret Padek, Peg Allen, Ross C Brownson

Open Access Publications

INTRODUCTION: The Community Guide (Guide) is a user-friendly, systematic review system that provides information on evidence-based interventions (EBIs) in public health practice. Little is known about what predicts Guide awareness and use in state health departments (SHDs) and local health departments (LHDs).

METHODS: We pooled data from 3 surveys (administered in 2016, 2017, and 2018) to employees in chronic disease programs at SHDs and LHDs. Participants (n = 1,039) represented all 50 states. The surveys asked about department practices and individual, organizational, and external factors related to decisions about EBIs. We used χ

RESULTS: Eighty-one percent (n = 498) of …

Performance Of The Lateral Flow Assay And The Latex Agglutination Serum Cryptococcal Antigen Test In Cryptococcal Disease In Patients With And Without Hiv, Matthew A Hevey, Ige A George, Adriana M Rauseo, Lindsey Larson, William Powderly, Andrej Spec

Open Access Publications

Cryptococcal epidemiology is shifting toward HIV-negative populations who have diverse presentations. Cryptococcal antigen (CrAg) testing is also changing, with development of the lateral flow assay (LFA) having reported increased sensitivity and specificity, but with minimal knowledge in the HIV-negative population. In this study, we evaluate the real-life performance of CrAg testing in patients with cryptococcal disease. We conducted a retrospective review of patients with cryptococcosis from 2002 to 2019 at Barnes-Jewish Hospital. Latex agglutination (LA) was used exclusively until April 2016, at which point LFA was used exclusively. Demographics, presentations, and testing outcomes were evaluated. Serum CrAg testing was completed …

Role Of Endothelial Nitric Oxide Synthase In Isoflurane Conditioning-Induced Neurovascular Protection In Subarachnoid Hemorrhage, Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel

Open Access Publications

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic …

Burst Mitofusin Activation Reverses Neuromuscular Dysfunction In Murine Cmt2a, Antonietta Franco, Xiawei Dang, Emily K. Walton, Joshua N. Ho, Barbara Zablocka, Cindy Ly, Timothy M. Miller, Robert H. Baloh, Michael E. Shy, Andrew S. Yoo, Gerald W. Dorn

Open Access Publications

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal

The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski

Open Access Publications

The closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are …

Walking School Bus Programs: Implementation Factors, Implementation Outcomes, And Student Outcomes, 2017-2018, Jordan A Carlson, Chelsea Steel, Carolina M Bejarano, Marshall T Beauchamp, Ann M Davis, James F Sallis, Jon Kerner, Ross Brownson, Sara Zimmerman

Open Access Publications

PURPOSE AND OBJECTIVES: Walking school bus programs increase children's physical activity through active travel to school; however, research to inform large-scale implementation of such programs is limited. We investigated contextual factors, implementation outcomes, and student outcomes in existing walking school bus programs in the United States and internationally.

INTERVENTION APPROACH: Walking school bus programs involve a group of children walking to school together with an adult leader. On the trip to school, these adults provide social support, address potential traffic and interpersonal safety, and serve as role models to the children while children increase their physical activity levels.

EVALUATION METHODS: …

Zanubrutinib Monotherapy For Patients With Treatment Naïve Chronic Lymphocytic Leukemia And 17p Deletion, Constantine S. Tam, Brad S. Kahl, Et Al

Open Access Publications

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma whose tumors carry deletion of chromosome 17p13.1 [del(17p)] have an unfavorable prognosis and respond poorly to standard chemoimmunotherapy. Zanubrutinib is a selective next-generation Bruton tyrosine kinase inhibitor. We evaluated the safety and efficacy of zanubrutinib 160 mg twice daily in treatment-naïve patients with del(17p) disease enrolled in a dedicated, nonrandomized cohort (Arm C) of the phase 3 SEQUOIA trial. A total of 109 patients (median age, 70 years; range, 42 - 86) with centrally confirmed del(17p) were enrolled and treated. After a median of 18.2 months (range, 5.0 - 26.3), seven …

Acute Kidney Injury Pathology And Pathophysiology: A Retrospective Review, Joseph P. Gaut, Helen Liapis

Open Access Publications

Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

A Prognostic Gene Expression Signature For Oropharyngeal Squamous Cell Carcinoma, Xinyi Liu, Ping Liu, Rebecca D Chernock, Krystle A Lang Kuhs, James S Lewis, Jingqin Luo, Hiram A Gay, Wade L Thorstad, Xiaowei Wang

Open Access Publications

BACKGROUND: Robust prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is important for developing individualized treatment plans. This study was conducted to develop and validate a clinically feasible prognostic classifier based on transcriptome-wide gene expression profiles.

METHODS: Tumor tissues were collected from 208 OPSCC patients treated at Washington University in St. Louis and 130 OPSCC patients treated at Vanderbilt University, used for model training and validation, respectively. OPSCC patients (n = 70) from the TCGA cohort were also included for independent validation. Based on RNA-seq profiling data, Cox proportional hazards regression analysis was performed to identify genes associated …

Proceedings From The Fourth International Symposium On Sigma-2 Receptors: Role In Health And Disease, Nicholas J Izzo, Martí Colom-Cadena, Aladdin A Riad, Jinbin Xu, Meharvan Singh, Carmen Abate, Michael A Cahill, Tara L Spires-Jones, Wayne D Bowen, Robert H Mach, Susan M Catalano

Open Access Publications

The sigma-2 receptor (S2R) complex has been implicated in central nervous system disorders ranging from anxiety and depression to neurodegenerative disorders such as Alzheimer's disease (AD). The proteins comprising the S2R complex impact processes including autophagy, cholesterol synthesis, progesterone signaling, lipid membrane-bound protein trafficking, and receptor stabilization at the cell surface. While there has been much progress in understanding the role of S2R in cellular processes and its potential therapeutic value, a great deal remains unknown. The

Delirium Prevention And Treatment In The Emergency Department (Ed): A Systematic Review Protocol, Elijah Blue Dahlstrom, Jin Ho Han, Heather Healy, Maura Kennedy, Glenn Arendts, Jacques Lee, Chris Carpenter, Sangil Lee

Open Access Publications

INTRODUCTION: Delirium is a dangerous syndrome of acute brain dysfunction that is common in the emergency department (ED), especially among the geriatric population. Most systematic reviews of interventions for delirium prevention and treatment have focused on inpatient settings. Best practices of effective delirium care in ED settings have not been established. The primary objective of this study is to identify pharmacologic and non-pharmacologic interventions as applied by physicians, nursing staff, pharmacists and other ED personnel to prevent incident delirium and to shorten the severity and duration of prevalent delirium in a geriatric population within the ED.

METHODS AND ANALYSIS: Searches …

Upper Extremity Pain And Overuse Injuries In Fly-Fishing: A North American Cross-Sectional Survey And Implications For Injury Prevention, Andrew W Kuhn, John E Kuhn

Open Access Publications

Background: Fly-fishing requires rhythmic, coordinated movements to successfully cast a fly line. Previous studies have shown that the biomechanical demands of fly-casting may cause some individuals to develop upper extremity pain or injuries.

Purpose: To report the rates, trends, and contributing factors of upper extremity pain and overuse injuries in a sample of North American recreational fly-fishers.

Study Design: Descriptive epidemiology study.

Methods: Participants were reached via 3 popular online fly-fishing forums in April 2019. Each consenting North American participant over 18 years of age was given a link to a unique survey that recorded his or her demographic and …

It's Complicated: The Relationship Between Sleep And Alzheimer's Disease In Humans, Brendan P Lucey

Open Access Publications

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an asymptomatic period of amyloid-β (Aβ) deposition as insoluble extracellular plaque, intracellular tau aggregation, neuronal and synaptic loss, and subsequent cognitive dysfunction and dementia. A growing public health crisis, the worldwide prevalence of AD is expected to rise from 46.8 million individuals affected in 2015 to 131.5 million in 2050. Sleep disturbances have been associated with increased future risk of AD. A bi-directional relationship is hypothesized between sleep and AD with sleep disturbances as either markers for AD pathology and/or a mechanism mediating increased risk of AD. In this review, …

Mechanisms Underlying Familial Aggregation Of Exceptional Health And Survival: A Three-Generation Cohort Study, Kaare Christensen, Mary K Wojczynski, Jacob K Pedersen, Lisbeth A Larsen, Susanne Kløjgaard, Axel Skytthe, Matt Mcgue, James W Vaupel, Michael A Province

Open Access Publications

The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes …

Does The Presence Of Chondral Lesions Negatively Affect Patient-Determined Outcomes After Arthroscopic Rotator Cuff Repair?, Keith M Baumgarten, Peter S Chang, Will E Schweinle

Open Access Publications

Background: There are limited data available to guide patients to their prognosis when glenohumeral chondral lesions are found during arthroscopic rotator cuff repair.

Hypothesis: The primary hypothesis was that patients with glenohumeral chondral lesions will have inferior outcomes after arthroscopic rotator cuff repair compared with patients without chondral lesions. The secondary hypothesis was that patients with concomitant chondral lesions will have more severe preoperative symptoms compared with those without chondral lesions.

Study Design: Cohort study; Level of evidence, 3.

Methods: A retrospective analysis was performed of patients who underwent arthroscopic rotator cuff repair between 2008 and 2012. We examined the …

A Molecular Understanding Of Alphavirus Entry, Autumn C. Holmes, Katherine Basore, Daved H. Fremont, Michael S. Diamond

Open Access Publications

Alphaviruses cause severe human illnesses including persistent arthritis and fatal encephalitis. As alphavirus entry into target cells is the first step in infection, intensive research efforts have focused on elucidating aspects of this pathway, including attachment, internalization, and fusion. Herein, we review recent developments in the molecular understanding of alphavirus entry both in vitro and in vivo and how these advances might enable the design of therapeutics targeting this critical step in the alphavirus life cycle.

Classifying Complications: Assessing Adult Spinal Deformity 2-Year Surgical Outcomes, Eric O. Klineberg, Munish Chandra Gupta, Et Al.

Open Access Publications

STUDY DESIGN: Retrospective review of prospective database.

OBJECTIVE: Complication rates for adult spinal deformity (ASD) surgery vary widely because there is no accepted system for categorization. Our objective was to identify the impact of complication occurrence, minor-major complication, and Clavien-Dindo complication classification (Cc) on clinical variables and patient-reported outcomes.

METHODS: Complications in surgical ASD patients with complete baseline and 2-year data were considered intraoperatively, perioperatively (<6 weeks), and postoperatively (>6 weeks). Primary outcome measures were complication timing and severity according to 3 scales: complication presence (yes/no), minor-major, and Cc score. Secondary outcomes were surgical outcomes (estimated blood loss [EBL], length of stay [LOS], …

Economic Evaluation Of The Specialized Donor Care Facility For Thoracic Organ Donor Management, Jason M. Gauthier, Maria B. Majella Doyle, William C. Chapman, Gary Marklin, Chad A. Witt, Elbert P. Trulock, Derek E. Byers, Ramsey R. Hachem, Michael K. Pasque, Bryan F. Meyers, G. Alexander Patterson, Ruben G. Nava, Benjamin D. Kozower, Daniel Kreisel, Su-Hsin Chang, Varun Puri

Open Access Publications

Background: Over the last decade two alternative models of donor care have emerged in the United States: the conventional model, whereby donors are managed at the hospital where brain death occurs, and the specialized donor care facility (SDCF), in which brain dead donors are transferred to a SDCF for medical optimization and organ procurement. Despite increasing use of the SDCF model, its cost-effectiveness in comparison to the conventional model remains unknown.

Methods: We performed an economic evaluation of the SDCF and conventional model of donor care from the perspective of U.S. transplant centers over a 2-year study period. In this …

Spontaneous Restoration Of Functional Β-Cell Mass In Obese Sm/J Mice, Mario A Miranda, Caryn Carson, Celine L St Pierre, Juan F Macias-Velasco, Jing W Hughes, Marcus Kunzmann, Heather Schmidt, Jessica P Wayhart, Heather A Lawson

Open Access Publications

Maintenance of functional β-cell mass is critical to preventing diabetes, but the physiological mechanisms that cause β-cell populations to thrive or fail in the context of obesity are unknown. High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we characterize insulin homeostasis, islet morphology, and β-cell function during SM/J's diabetic remission. As they resolve hyperglycemia, obese SM/J mice dramatically increase circulating and pancreatic insulin levels while improving insulin sensitivity. Immunostaining of pancreatic sections reveals that obese SM/J mice selectively increase β-cell mass but not α-cell mass. Obese SM/J …

Genetic Mutations In Young Nonsmoking Patients With Oral Cavity Cancer: A Systematic Review, Rohini R Bahethi, Katelyn O Stepan, Rachel Pinotti, Ryan Li, Nishant Agrawal, Sidharth V Puram, Brett A Miles, Brittany Barber

Open Access Publications

OBJECTIVE: This investigation aims to review the known genetic mutations associated with oral cavity squamous cell carcinoma (OCSCC) in young adults with limited environmental risk factors (YLERs).

DATA SOURCES: A comprehensive search strategy was designed to identify studies in MEDLINE (Ovid), Embase (Ovid), and Scopus from database inception to May 2017 that included adults ≤50 years of age with OCSCC and minimal tobacco use history (≤10 pack-years) who had their tumors genetically sequenced or mutational profiles analyzed.

REVIEW METHODS: Identified articles were screened by 2 reviewers. Quality of evidence was graded by the MINORS criteria for case-control studies; other studies …

Adaptation Of Arginine Synthesis Among Uropathogenic Branches Of The Escherichia Coli Phylogeny Reveals Adjustment To The Urinary Tract Habitat, Michael E Hibbing, Karen W Dodson, Vasilios Kalas, Swaine L Chen, Scott J Hultgren

Open Access Publications

Urinary tract infections (UTIs) are predominantly caused by uropathogenic

Five Years Of Ocrelizumab In Relapsing Multiple Sclerosis: Opera Studies Open-Label Extension, Stephen L Hauser, Robert T Naismith, Et Al

Open Access Publications

OBJECTIVE: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.

METHODS: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), …