CD4+CD126low/- Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases.

CD4+Foxp3+ regulatory T (Treg) cells are crucial for maintaining homeostasis and preventing autoimmune diseases. Nonetheless, we and others have previously reported that natural Treg cells are unstable and dysfunctional in the inflamed environment with a high-salt diet, limiting the Treg function in disease control. In this study, we made an innovative observation showing a high degree of heterogeneity within the Treg pool. We identified that CD126, interleukin (IL)-6 receptor alpha chain, contributed to Treg cell instability. Using a series of in vitro and in vivo experimental approaches, we demonstrated that CD126Lo/- Treg cells presented greater function and were more stable than CD126Hi nTreg cells, even in the presence of IL-6 and inflammation. Blockade of programmed death-1 (PD-1) interrupted CD126Lo/- nTreg cell stability. Additionally, CD126Lo/- Treg cells can treat colitis and established collagen-induced arthritis, while the CD126Hi cell population failed to do this. Moreover, we noted that CD126 expression of Treg cells had a positive correlation to rheumatoid arthritis (RA) severity and the stability of Treg cells. Our results strongly suggest that the manipulation of CD126Lo/- nTreg cells could be a novel strategy for the treatment of autoimmune diseases and for other conditions associated with a deficit of Treg cells.

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

BackgroundThere is no proven antiviral or immunomodulatory therapy for COVID-19. The disease progression associated with the pro-inflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. MethodsWe conducted a single pre-test, single post-test quasi-experiment in a multi-center health system in Michigan from March 12 to March 27, 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on March 20, 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of pre and post-corticosteroid groups were evaluated. A composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality was the primary outcome measure. All patients had at least 14 days of follow-up. ResultsWe analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in pre-and post-corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in post-corticosteroid group compared to pre-corticosteroid group (34.9% vs. 54.3%, p=0.005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was observed in the post-corticosteroid group (8 vs. 5 days, p < 0.001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (aOR: 0.45; 95% CI [0.25 - 0.81]). ConclusionAn early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes. SummaryIn this multi-center quasi-experimental study of 213 patients, we demonstrate early short course of methylprednisolone in moderate to severe COVID-19 patients reduced the composite endpoint of escalation of care from ward to ICU, new requirement for mechanical ventilation, and mortality.

Study design of Real World Evidence for Treatment of Hyperkalemia in the Emergency Department (REVEAL-ED): a multicenter, prospective, observational study

OBJECTIVE: Hyperkalemia affects up to 10% of hospitalized patients and, if left untreated, can lead to serious cardiac arrhythmias or death. Although hyperkalemia is frequently encountered in the emergency department (ED), and is potentially life-threatening, standard of care for the treatment is poorly defined, with little supporting evidence. The main objectives of this observational study are to define the overall burden of hyperkalemia in the ED setting, describe its causes, the variability in treatment patterns and characterize the effectiveness and safety of ED standard of care therapies used in the United States. METHODS: This is an observational study evaluating the management of hyperkalemia in the ED. Two hundred and three patients who presented to the ED with a potassium value ≥5.5 mmol/L were enrolled in the study at 14 sites across the United States. Patients were treated per standard of care practices at the discretion of the patient’s physician. In patients who received a treatment for hyperkalemia, blood samples were drawn at pre-specified time points and serum potassium values were recorded. The change in potassium over 4 hours and the adverse events after standard of care treatment were analyzed. RESULTS AND CONCLUSION: This article describes the background, rationale, study design, and methodology of the REVEAL-ED (Real World Evidence for Treatment of Hyperkalemia in the Emergency Department) trial, a multicenter, prospective, observational study evaluating contemporary management of patients admitted to the ED with hyperkalemia.