Short-term neurologic outcomes in pediatric extracorporeal membrane oxygenation are proportional to bleeding severity graded by a novel bleeding scale.

Introduction: This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO.

Methods: Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies.

Charting Diagnostic Safety: Exploring Patient-Provider Discordance in Medical Record Documentation.

Background: The 21st Century Cures Act enables patients to access their medical records, thus providing a unique opportunity to engage patients in their diagnostic journey.

Objective: To explore the concordance between patients' self-reported diagnostic concerns and clinician-interpreted information in their electronic health records.

Design: We conducted a mixed-methods analysis of a cohort of 467 patients who completed a structured data collection instrument (the Safer Dx Patient) to identify diagnostic concerns while reviewing their clinician's notes.

Opposing Roles for the α Isoform of the Catalytic Subunit of Protein Phosphatase 1 in Inside-Out and Outside-In Integrin Signaling in Murine Platelets.

Platelet activation during hemostasis and thrombosis is facilitated by agonist-induced inside-out and integrin αβ-initiated outside-in signaling via protein kinases and phosphatases. Pharmacological inhibitor studies suggest that the serine/threonine protein phosphatase 1 (PP1) promotes platelet activation. However, since phosphatase inhibitors block all the isoforms of the catalytic subunit of PP1 (PP1c), the role of specific PP1c isoform in platelet signaling remains unclear.

Creating a Learning Health System for Improving Diagnostic Safety: Pragmatic Insights from US Health Care Organizations.

Objective: To identify challenges and pragmatic strategies for improving diagnostic safety at an organizational level using concepts from learning health systems METHODS: We interviewed 32 safety leaders across the USA on how their organizations approach diagnostic safety. Participants were recruited through email and represented geographically diverse academic and non-academic settings. The interview included questions on culture of reporting and learning from diagnostic errors; data gathering and analysis activities; diagnostic training and educational activities; and engagement of clinical leadership, staff, patients, and families in diagnostic safety activities.

Secretion of von Willebrand Factor and Suppression of ADAMTS-13 Activity by Markedly High Concentration of Ferritin.

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients.

Practicing Clinicians' Recommendations to Reduce Burden from the Electronic Health Record Inbox: a Mixed-Methods Study.

Background: Workload from electronic health record (EHR) inbox notifications leads to information overload and contributes to job dissatisfaction and physician burnout. Better understanding of physicians' inbox requirements and workflows could optimize inbox designs, enhance efficiency, and reduce safety risks from information overload.

Design: We conducted a mixed-methods study to identify strategies to enhance EHR inbox design and workflow.

Dietary quality and the colonic mucosa-associated gut microbiome in humans.

Background: Despite tremendous interest in modulating the microbiome to improve health, the association between diet and the colonic mucosa-associated gut microbiome in healthy individuals has not been examined.

Objective: To investigate the associations between Healthy Eating Index (HEI)-2005 and the colonic mucosa-associated microbiota.

Methods: In this cross-sectional observational study, we analyzed bacterial community composition and structure using 16S rRNA gene (V4 region) sequencing of 97 colonic mucosal biopsies obtained endoscopically from different colon segments of 34 polyp-free participants.

Recommendations for using the Revised Safer Dx Instrument to help measure and improve diagnostic safety.

The medical record continues to be one of the most useful and accessible sources of information to examine the diagnostic process. However, medical record review studies of diagnostic errors have often used subjective judgments and found low inter-rater agreement among reviewers when determining the presence or absence of diagnostic error. In our previous work, we developed a structured data-collection instrument, called the Safer Dx Instrument, consisting of objective criteria to improve the accuracy of assessing diagnostic errors in primary care.

In vitro phosphorylation of von Willebrand factor by FAM20c enhances its ability to support platelet adhesion.

Essentials Platelet adhesion to von Willebrand factor (VWF) is critical for hemostasis and thrombosis. Whether VWF can undergo phosphorylation is unknown. Family with sequence similarity 20 kinase phosphorylates VWF A2 domain at S1517 and S1613.

Cognitive and Perceptual Factors, Not Disease Severity, Are Linked with Anxiety in COPD: Results from a Cross-Sectional Study.

Purpose: Guided by the Transactional Model of Stress and Coping, the purpose of this cross-sectional study was to examine clinical factors-demographics, chronic obstructive pulmonary disease (COPD) severity, cognitive/perceptual variables (appraisal and coping)-and their relationship to clinically elevated symptoms of anxiety in a sample of veterans with COPD.

Method: Participants included a sample of veterans with COPD, with or without comorbid congestive heart failure, and clinically significant symptoms of anxiety (n = 172, mean age = 65.3, SD = 8.

The heterotrimeric G protein Gβ interacts with the catalytic subunit of protein phosphatase 1 and modulates G protein-coupled receptor signaling in platelets.

Thrombosis is caused by the activation of platelets at the site of ruptured atherosclerotic plaques. This activation involves engagement of G protein-coupled receptors (GPCR) on platelets that promote their aggregation. Although it is known that protein kinases and phosphatases modulate GPCR signaling, how serine/threonine phosphatases integrate with G protein signaling pathways is less understood.

Application of Electronic Algorithms to Improve Diagnostic Evaluation for Bladder Cancer.

Background: Strategies to ensure timely diagnostic evaluation of hematuria are needed to reduce delays in bladder cancer diagnosis.

Objective: To evaluate the performance of electronic trigger algorithms to detect delays in hematuria follow-up.

Methods: We developed a computerized trigger to detect delayed follow-up action on a urinalysis result with high-grade hematuria (>50 red blood cells/high powered field).

PAI1: a novel PP1-interacting protein that mediates human plasma's anti-apoptotic effect in endothelial cells.

Activation of apoptotic signalling in endothelial cells contributes to the detrimental effects of a variety of pathological stimuli. In investigating the molecular events underlying the anti-apoptotic effect of human plasma in cultured human endothelial cells, we unexpectedly uncovered a novel mechanism of apoptosis suppression by human plasma through an interaction between two previously unrelated proteins. Human plasma inhibited hypoxia-serum deprivation-induced apoptosis and stimulated BAD and Akt phosphorylation.

Disruption of protein complexes containing protein phosphatase 2B and Munc18c reduces the secretion of von Willebrand factor from endothelial cells.

Unlabelled: Essentials Endothelial secretion of von Willebrand factor (VWF) promotes inflammation and thrombosis. We studied the role of protein phosphatase 2B (PP2B) and Munc18c protein complex in VWF secretion. Disruption of PP2B-Munc18c complex in endothelial cells reduced agonist-induced VWF secretion.

A Novel Interaction of the Catalytic Subunit of Protein Phosphatase 2A with the Adaptor Protein CIN85 Suppresses Phosphatase Activity and Facilitates Platelet Outside-in αIIbβ3 Integrin Signaling.

The transduction of signals generated by protein kinases and phosphatases are critical for the ability of integrin αIIbβ3 to support stable platelet adhesion and thrombus formation. Unlike kinases, it remains unclear how serine/threonine phosphatases engage the signaling networks that are initiated following integrin ligation. Because protein-protein interactions form the backbone of signal transduction, we searched for proteins that interact with the catalytic subunit of protein phosphatase 2A (PP2Ac).

Relevance of low testosterone to non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a condition where there is excess accumulation of triglycerides in the liver in the absence of excess alcohol consumption. It ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NAFLD, one of the most common causes of chronic liver disease in Western populations, is the hepatic component of the metabolic syndrome (MetS) and is associated with increased visceral adipose tissue (VAT), insulin resistance, and dyslipidemia.

Esophageal COX-2 expression is increased in Barrett's esophagus, obesity, and smoking.

Background: Increased esophageal cyclooxygenase-2 (COX-2) expression has been associated with Barrett's esophagus (BE); however, it is unknown whether COX-2 expression varies among patient groups with different clinical or socio-demographic factors.

Methods: We conducted a case-control study among eligible patients scheduled for elective esophagogastroduodenoscopy and patients eligible for screening colonoscopy recruited from primary clinics. We compared 39 BE tissue samples and 47 squamous tissue samples from BE cases and 240 squamous tissue samples from controls.

Initiation of cholinesterase inhibitors in an inpatient setting.

We examined initiation of cholinesterase inhibitors (ChEIs) to determine whether ChEIs were being newly prescribed without sufficient evaluation for dementia and/or delirium and to explore whether there are differences in outcomes, such as mortality, hospital readmission rates, and duration of hospitalization, between patients newly started on ChEI and those who continued such medications prior to admission. Patients hospitalized in fiscal year 2008 and prescribed ChEI were identified. We reviewed electronic medical records.

A pilot test of videoconferencing to improve access to a stroke risk-reduction programme for Veterans.

We conducted a pilot study to determine the feasibility of using videoconferencing for a programme of self-management to prevent stroke (V-STOP). A total of 37 Veterans with a history of stroke, or with multiple risk factors for stroke, were enrolled in the study from two rural sites. The V-STOP intervention consisted of 6 weekly sessions of self-management classes and clinic visits delivered via videoconferencing, with one or two individual telephone counselling sessions.

Older adults' preferences for religion/spirituality in treatment for anxiety and depression.

Objectives: To examine patient preferences for incorporating religion and/or spirituality into therapy for anxiety or depression and examine the relations between patient preferences and religious and spiritual coping styles, beliefs and behaviors.

Method: Participants (66 adults, 55 years or older, from earlier studies of cognitive-behavioral therapy for late-life anxiety and/or depression in primary care) completed these measures by telephone or in-person: Geriatric Anxiety Inventory, Client Attitudes Toward Spirituality in Therapy, Patient Interview, Brief Religious Coping, Religious Problem Solving Scale, Santa Clara Strength of Religious Faith, and Brief Multidimensional Measure of Religiousness and Spirituality. Spearman's rank-order correlations and ordinal logistic regression examined religious/spiritual variables as predictors of preferences for inclusion of religion or spirituality into counseling.