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Platelet Distribution Width (PDW) as a Significant Correlate of COVID-19 Infection Severity and Mortality
No full textSARS-CoV-2 infection may cause a wide spectrum of symptoms, from asymptomatic, to mild respiratory symptoms and life-threatening sepsis. Among the clinical laboratory biomarkers analyzed during COVID-19 pandemic, platelet indices have raised great interest, due to the critical involvement of platelets in COVID-19-related thromboinflammation. Through an electronic literature search on MEDLINE, CINAHL, PubMed, EMBASE, Web of Science, and preprint servers we performed and updated a systematic review aimed at providing a detailed analysis of studies addressing the potential clinical utility of platelet distribution width, platelet distribution width (PDW), in laboratory medicine, exploring the possible association between increased PDW levels, disease severity, and mortality in COVID-19. Our systematic review revealed a wide heterogeneity of COVID-19 cohorts examined and a lack of homogenous expression of platelet indices. We found that 75 % of studies reported significantly elevated PDW values in COVID-19 infected cohorts compared to healthy/non-COVID-19 controls, and 40 % of studies reported that patients with severe COVID-19 showed increased PDW values than those with less-than-severe illness. Interestingly, 71.4 % of studies demonstrated significant increased PDW values in non survivors vs. survivors. Overall, these results suggest that platelets are critically involved as major players in the process of immunothrombosis in COVID-19, and platelet reactivity and morphofunctional alterations are mirrored by PDW, as indicator of platelet heterogeneity. Our results confirm that the use of PDW as prognostic biomarkers of COVID-19 sepsis still remains debated due to the limited number of studies to draw a conclusion, but new opportunities to investigate the crucial role of platelets in thrombo-inflammation are warranted
Permissive Role of Vascular Endothelium in Fibrosis: Focus on the Kidney
No full textFibrosis, the morphologic end-result of a plethora of chronic conditions and the scorch for organ function, has been thoroughly investigated. One aspect of its development and progression, namely the permissive role of vascular endothelium, has been overshadowed by studies into (myo)fibroblasts and TGF-β; thus, it is the subject of the present review. It has been established that tensile forces of the extracellular matrix acting on cells are a prerequisite for mechanochemical coupling, leading to liberation of TGF-β and formation of myofibroblasts. Increased tensile forces are prompted by elevated vascular permeability in response to diverse stressors, resulting in the exudation of fibronectin, fibrinogen/fibrin, and other proteins, all stiffening the extracellular matrix. These processes lead to the development of endothelial cells dysfunction, endothelial-to-mesenchymal transition, premature senescence of endothelial cells, perturbation of blood flow, and gradual obliteration of microvasculature, leaving behind string vessels. The resulting microvascular rarefaction is not only a constant companion of fibrosis but also an adjunct mechanism of its progression. The deepening knowledge of the above chain of pathogenetic events involving endothelial cells, namely increased permeability-stiffening of the matrix-endothelial dysfunction-microvascular rarefaction-tissue fibrosis, may provide a roadmap for therapeutic interventions deemed to curtail and reverse fibrosis
Surgery Clerkship Directors\u27 Perceptions of the COVID-19 Pandemic\u27s Impact on Medical Student Education
No full textBACKGROUND: This study assessed the national impact of the coronavirus disease 2019 (COVID-19) pandemic on the education of medical students assigned to surgery clerkship rotations, as reported by surgery clerkship directors (CDs). STUDY DESIGN: In the spring of 2020 and 2021, the authors surveyed 164 CDs from 144 Liaison Committee on Medical Education-accredited US medical schools about their views of the pandemic\u27s impact on the surgery clerkship curriculum, students\u27 experiences, outcomes, and institutional responses. RESULTS: Overall survey response rates, calculated as number of respondents/number of surveyed, were 44.5% (73 of 164) and 50.6% (83 of 164) for the spring 2020 and 2021 surveys, respectively. Nearly all CDs (more than 95%) pivoted to virtual platforms and solutions. Most returned to some form of in-person learning by winter 2020, and prepandemic status by spring 2021 (46%, 38 of 83). Students\u27 progression to the next year was delayed by 12% (9 of 73), and preparation was negatively impacted by 45% (37 of 83). Despite these data, CDs perceived students\u27 interest in surgical careers was not significantly affected (89% vs 77.0%, p = 0.09). During the 1-year study, the proportion of CDs reporting a severe negative impact on the curriculum dropped significantly (p \u3c 0.0001) for most parameters assessed except summative evaluations (40.3% vs 45.7%, p = 0.53). CDs (n = 83) also noted the pandemic\u27s positive impact with respect to virtual patient encounters (21.7%), didactics (16.9%), student test performance (16.9%), continuous personal learning (14.5%), engagement in the clerkship (9.6%), and student interest in surgery as a career (7.2%). CONCLUSIONS: During the pandemic, the severe negative impact on student educational programs lessened, and novel virtual curricular solutions emerged. Student interest in surgery as a career was sustained. Measures of student competency and effectiveness of new curriculum, including telehealth, remain areas for future investigation
Impact of Sarcoidosis on In-Hospital Outcomes Among Patients with Atrial Fibrillation: A Nationwide Readmissions Database Analysis
No full textSarcoidosis is a disease that involves multiple organs, including the cardiovascular system. While cardiac sarcoidosis has been increasingly recognized, the impact of sarcoidosis on atrial fibrillation (AF) is not well established. This study aimed to analyze the impact of sarcoidosis on in-hospital outcomes among patients who were admitted for a primary diagnosis of AF. Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged ≥18 years who were admitted for AF between 2017-2020. We stratified the cohort into two groups depending on the presence of sarcoidosis diagnosis. The in-hospital outcomes were assessed between the two groups via propensity score analysis. A total of 1031 (0.27%) AF patients with sarcoidosis and 387,380 (99.73%) AF patients without sarcoidosis were identified in our analysis. Our propensity score analysis of 1031 (50%) patients with AF and sarcoidosis and 1031 (50%) patients with AF but without sarcoidosis revealed comparable outcomes in early mortality (1.55% vs. 1.55%
Lack of Genotoxicity Potential and Safety Assessment of 4-(2-Hydroxyethyl) Morpholine Present as an Impurity in Pharmaceuticals and Nutritional Supplements
No full text4-(2-Hydroxyethyl) morpholine (HEM) is widely used as a building block of macromolecules in the manufacture of pharmaceuticals and dietary supplements and could remain as an impurity in the finished products. An evaluation of HEM was conducted to identify endpoints that could be used to determine the point-of-departure (POD) for use in assessing the potential risk from exposure to HEM. No oral repeated dose toxicological studies of appropriate duration were found for HEM. Therefore, suitable analogue(s) were identified. Although oral repeated dose studies were available for the analogues, the studies were not of sufficient duration for use in the assignment of a POD for risk evaluation. Accordingly, the Threshold of Toxicological Concern (TTC) approach, which proposes that a de minimis value can be derived to qualitatively assess risk, was considered for HEM. To determine the appropriate TTC approach (genotoxic or non-genotoxic), the genotoxicity of HEM and its analogues were evaluated. The weight of the evidence indicated that HEM, and the appropriate analogues, are not genotoxic. Considering the chemical structure of HEM, the non-genotoxic Cramer class III TTC value of 1.5 μg/kg bw/day was determined to be appropriate for use in safety assessment of HEM as an impurity in products intended for human consumption
