IMPORTANCE The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. OBJECTIVES To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. EXPOSURES Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. MAIN OUTCOMES AND MEASURES The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. RESULTS A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (Ն80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (Ն40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (PaO 2 :FIO 2 <100 vs Ն300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs Ն100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. CONCLUSIONS AND RELEVANCE This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

IMPORTANCE Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. OBJECTIVE To test whether tocilizumab decreases mortality in this population. DESIGN, SETTING, AND PARTICIPANTS The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. EXPOSURES Treatment with tocilizumab in the first 2 days of ICU admission. MAIN OUTCOMES AND MEASURES Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. RESULTS Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). CONCLUSIONS AND RELEVANCE Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

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Diabetes is a worldwide epidemic that has led to a rise in diabetic kidney disease (DKD). Over the past two decades, there has been significant clarification of the various pathways implicated in the pathogenesis of DKD. Nonetheless, very little has changed in the way clinicians manage patients with this disorder. Indeed, treatment is primarily centered on controlling hyperglycemia and hypertension and inhibiting the renin-angiotensin system. The purpose of this review is to describe the current understanding of how the hemodynamic, metabolic, inflammatory, and alternative pathways are all entangled in pathogenesis of DKD and detail the various therapeutic targets that may one day play a role in quelling this epidemic.

for the STOP-COVID investigators † Background: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 .Objective: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.Design: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used.Setting: 67 hospitals in the United States.Participants: Adults with COVID-19 admitted to a participating ICU.Measurements: Time to death, censored at hospital discharge, or date of last follow-up.Results: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]).Limitation: Observational design. Conclusion:Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation.

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The use of cooled dialysate temperatures first came about in the early 1980s as a way to curb the incidence of intradialytic hypotension (IDH). IDH was then, and it remains today, the most common complication affecting chronic hemodialysis patients. It decreases quality of life on dialysis and is an independent risk factor for mortality. Cooling dialysate was first employed as a technique to incite peripheral vasoconstriction on dialysis and in turn reduce the incidence of intradialytic hypotension. Although it has become a common practice amongst incenter hemodialysis units, cooled dialysate results in up to 70% of patients feeling cold while on dialysis and some even experience shivering. Over the years, various studies have been performed to evaluate the safety and efficacy of cooled dialysate in comparison to a standard, more thermoneutral dialysate temperature of 37 ℃. Although these studies are limited by small sample size, they are promising in many aspects. They demonstrated that cooled dialysis is safe and equally efficacious as thermoneutral dialysis. Although patients report feeling cold on dialysis, they also report increased energy and an improvement in their overall health following cooled dialysis. They established that cooling dialysate temperatures improves hemodynamic tolerability during and after hemodialysis, even in patients prone to IDH, and does so without adversely affecting dialysis adequacy. Cooled dialysis also reduces the incidence of IDH and has a protective effect over major organs including the heart and brain. Finally, it is an inexpensive measure that decreases economic burden by reducing necessary nursing intervention for issues that arise on hemodialysis such as IDH. Before cooled dialysate becomes standard of care for patients on chronic hemodialysis, larger studies with longer follow-up periods will need to take place to confirm the encouraging outcomes mentioned here. Core tip: Cooled dialysate is commonly employed to reduce the incidence of intradialytic hypotension (IDH) in patients on chronic dialysis. The studies to date that have evaluated cooled dialysate are limited by small sample size and it has not become the standard of care for managing IDH. However, the small studies that exist are promising and suggest that cooling dialysate improves hemodynamic tolerability of dialysis, minimizes IDH, and exerts a protective effect over major organs including the heart and brain. More studies are needed to assess the long-term effects of cooling dialysate in this population.Toth-Manikowski SM, Sozio SM. Cooling dialysate during incenter hemodialysis: Beneficial and deleterious effects. World J Nephrol 2016; 5(2): 166-171 Available from:

The association of residual kidney function (RKF) with improved outcomes in peritoneal dialysis and hemodialysis patients is now widely recognized. RKF provides substantial volume and solute clearance even after dialysis initiation. In particular, RKF provides clearance of nonurea solutes, many of which are potential uremic toxins and not effectively removed by conventional hemodialysis. The presence of RKF provides a distinct advantage to incident dialysis patients and is an opportunity for nephrologists to individualize dialysis treatments tailored to their patients' unique solute, volume, and quality of life needs. The benefits of RKF present the opportunity to personalize the management of uremia.