Vitamin D Status Is Associated With In-Hospital Mortality and Mechanical Ventilation: A Cohort of COVID-19 Hospitalized Patients.

OBJECTIVE: To explore the possible associations of serum 25-hydroxyvitamin D [25(OH)D] concentration with coronavirus disease 2019 (COVID-19) in-hospital mortality and need for invasive mechanical ventilation. PATIENTS AND METHODS: A retrospective, observational, cohort study was conducted at 2 tertiary academic medical centers in Boston and New York. Eligible participants were hospitalized adult patients with laboratory-confirmed COVID-19 between February 1, 2020, and May 15, 2020. Demographic and clinical characteristics, comorbidities, medications, and disease-related outcomes were extracted from electronic medical records. RESULTS: The final analysis included 144 patients with confirmed COVID-19 (median age, 66 years; 64 [44.4%] male). Overall mortality was 18%, whereas patients with 25(OH)D levels of 30 ng/mL (to convert to nmol/L, multiply by 2.496) and higher had lower rates of mortality compared with those with 25(OH)D levels below 30 ng/mL (9.2% vs 25.3%; P=.02). In the adjusted multivariable analyses, 25(OH)D as a continuous variable was independently significantly associated with lower in-hospital mortality (odds ratio, 0.94; 95% CI, 0.90 to 0.98; P=.007) and need for invasive mechanical ventilation (odds ratio, 0.96; 95% CI, 0.93 to 0.99; P=.01). Similar data were obtained when 25(OH)D was studied as a continuous variable after logarithm transformation and as a dichotomous (<30 ng/mL vs ≥30 ng/mL) or ordinal variable (quintiles) in the multivariable analyses. CONCLUSION: Among patients admitted with laboratory-confirmed COVID-19, 25(OH)D levels were inversely associated with in-hospital mortality and the need for invasive mechanical ventilation. Further observational studies are needed to confirm these findings, and randomized clinical trials must be conducted to assess the role of vitamin D administration in improving the morbidity and mortality of COVID-19.

Characteristics and Significance of Tricuspid Valve Prolapse in a Large Multidecade Echocardiographic Study.

BACKGROUND: Characteristics of tricuspid valve prolapse (TVP) on transthoracic echocardiography are not well defined. As tricuspid valve interventions are increasingly considered, information on the definition and clinical significance of TVP is needed. METHODS: At the authors' institution, between January 26, 2000, and September 20, 2018, 410 patients (0.3%) were determined to have suspected TVP. These transthoracic echocardiograms and those of 97 age- and sex-matched normal control subjects were reviewed. Interrater agreement on TVP by visual inspection was assessed in a blinded subset. Leaflet atrial displacement (AD) > 2 SDs above the mean in normal control subjects was used to identify an empiric definition of TVP Features of patients meeting this definition were evaluated. RESULTS: Three hundred twelve transthoracic echocardiograms with available and interpretable images (76.1%) were included. Interrater agreement on TVP diagnosis by visual inspection was moderate. Normal values of AD were up to 4 mm in the right ventricular inflow view and 2 mm in all other views. AD > 2 mm in the parasternal short-axis view had the best accuracy against suspected TVP to identify TVP. Those with TVP by this definition more frequently had 3 to 4+ tricuspid regurgitation (22.2% vs 3.1%; P < .001), mitral valve prolapse (MVP; 75.0% vs 3.1%; P < .001), and more clinically significant MVP (greater prevalence of 3 to 4+ mitral regurgitation). No difference in mortality was observed in those with isolated TVP versus TVP and MVP (log-rank P = .93). CONCLUSIONS: In the largest study of TVP to date, interrater agreement on TVP diagnosis by visual inspection was moderate. A cutoff of >2-mm AD in the parasternal short-axis view was optimal to define TVP. Those with TVP by this definition had more significant tricuspid regurgitation, larger right ventricles, and more clinically significant MVP. Overall, these results suggest an increased role for surveillance for TVP and the need for clear diagnostic criteria in updated guidelines.

Usefulness of Circulating Caspase-3 p17 and Caspase-1 p20 Peptides and Cardiac Troponin 1 During Cardioplegia to Gauge Myocardial Preservation.

Evidence is accumulating that cardiac apoptosis occurs and contributes to myocyte cell death during myocardial ischemia. Cardioplegia, defined as the temporary cessation of cardiac activity during cardiac surgery, is a clinically controlled condition with myocardial ischemia and reperfusion. Our goal was to determine whether the apoptotic biomarker caspase-3 p17 is elevated in the coronary sinus (CS) during cardioplegia and if any elevations were reflected in the peripheral venous (PV) blood. Levels of the necrotic biomarker cardiac troponin I (cTnI) and the inflammatory marker caspase-1 p20 were also quantified in CS and PV. Blood was drawn before and at the end of cardioplegia in PV and CS and levels of p20, p17, and cTnI were measured. cTnI, p20, and p17 PV levels were significantly elevated compared with the control population before and at the end of cardioplegia. PV levels of all 3 markers increased after cardioplegia. CS levels were higher than PV levels for all 3 markers at both time points. Our data are consistent with the occurrence of cardiac apoptosis and inflammation during cardioplegia, in addition to necrosis. The heart-derived markers contributed to the peripheral levels and suggest that measurement of PV biomarker concentrations can be used to gauge cardiac preservation.

Identification of the substrate recruitment mechanism of the muscle glycogen protein phosphatase 1 holoenzyme.

Glycogen is the primary storage form of glucose. Glycogen synthesis and breakdown are tightly controlled by glycogen synthase (GYS) and phosphorylase, respectively. The enzyme responsible for dephosphorylating GYS and phosphorylase, which results in their activation (GYS) or inactivation (phosphorylase) to robustly stimulate glycogen synthesis, is protein phosphatase 1 (PP1). However, our understanding of how PP1 recruits these substrates is limited. Here, we show how PP1, together with its muscle glycogen-targeting (GM) regulatory subunit, recruits and selectively dephosphorylates its substrates. Our molecular data reveal that the GM carbohydrate binding module (GM CBM21), which is amino-terminal to the GM PP1 binding domain, has a dual function in directing PP1 substrate specificity: It either directly recruits substrates (i.e., GYS) or recruits them indirectly by localization (via glycogen for phosphorylase). Our data provide the molecular basis for PP1 regulation by GM and reveal how PP1-mediated dephosphorylation is driven by scaffolding-based substrate recruitment.