Background and objectivesHypernatremia is common in hospitalized, critically ill patients. Although there are no clear guidelines on sodium correction rate for hypernatremia, some studies suggest a reduction rate not to exceed 0.5 mmol/L per hour. However, the data supporting this recommendation and the optimal rate of hypernatremia correction in hospitalized adults are unclear.Design, setting, participants, & measurementsWe assessed the association of hypernatremia correction rates with neurologic outcomes and mortality in critically ill patients with hypernatremia at admission and those that developed hypernatremia during hospitalization. We used data from the Medical Information Mart for Intensive Care-III and identified patients with hypernatremia (serum sodium level >155 mmol/L) on admission (n=122) and hospital-acquired (n=327). We calculated different ranges of rapid correction rates (>0.5 mmol/L per hour overall and >8, >10, and >12 mmol/L per 24 hours) and utilized logistic regression to generate adjusted odds ratios (aOR) with 95% confidence intervals (95% CIs) to examine association with outcomes.ResultsWe had complete data on 122 patients with severe hypernatremia on admission and 327 patients who developed hospital-acquired hypernatremia. The difference in in-hospital 30-day mortality proportion between rapid (>0.5 mmol/L per hour) and slower (≤0.5 mmol/L per hour) correction rates were not significant either in patients with hypernatremia at admission with rapid versus slow correction (25% versus 28%; P=0.80) or in patients with hospital-acquired hypernatremia with rapid versus slow correction (44% versus 40%; P=0.50). There was no difference in aOR of mortality for rapid versus slow correction in either admission (aOR, 1.3; 95% CI, 0.5 to 3.7) or hospital-acquired hypernatremia (aOR, 1.3; 95% CI, 0.8 to 2.3). Manual chart review of all suspected chronic hypernatremia patients, which included all 122 with hypernatremia at admission, 128 of the 327 hospital-acquired hypernatremia, and an additional 28 patients with ICD-9 codes for cerebral edema, seizures and/or alteration of consciousness, did not reveal a single case of cerebral edema attributable to rapid hyprnatremia correction.ConclusionsWe did not find any evidence that rapid correction of hypernatremia is associated with a higher risk for mortality, seizure, alteration of consciousness, and/or cerebral edema in critically ill adult patients with either admission or hospital-acquired hypernatremia.

IMPORTANCE Geriatric (aged Ն80 years) patients are historically underrepresented in cancer clinical trials. Little is known about the efficacy of immune checkpoint inhibitors (ICIs) in geriatric patients. These agents are associated with immune-related adverse events (irAEs), which may be particularly associated with morbidity in this population.OBJECTIVE To provide insight into the clinical outcomes and safety of ICIs among geriatric patients (aged Ն80 years) with cancer. DESIGN, SETTING, AND PARTICIPANTSA Multicenter, international retrospective study of 928 geriatric patients with different tumors treated with single-agent ICIs between 2010 to 2019 from 18 academic centers in the US and Europe. Analyses were conducted from January 2021 to April 2021. MAIN OUTCOMES AND MEASURESClinical outcomes and irAE patterns in geriatric patients treated with single-agent ICIs.RESULTS Median (range) age of the 928 patients at ICI initiation was 83.0 (75.8-97.0) years. Most patients (806 [86.9%]) were treated with anti-programmed cell death 1 therapy. Among the full cohort, the 3 most common tumors were non-small cell lung cancer (NSCLC, 345 [37.2%]), melanoma (329 [35.5%]), and genitourinary (GU) tumors (153 [16.5%]). Objective response rates for patients with NSCLC, melanoma, and GU tumors were 32.2%, 39.3%, and 26.2%, respectively. Median PFS and OS, respectively, were 6.7 and 10.9 months (NSCLC), 11.1 and 30.0 months (melanoma), and 6.0 and 15.0 months (GU). Within histologically specific subgroups (NSCLC, melanoma, and GU), clinical outcomes were similar across age subgroups (aged <85 vs Ն85 years). Among all 928 patients, 383 (41.3%) experienced Ն1 irAE(s), including 113 (12.2%) that were reported to be grade (G) 3 to 4 based on Common Terminology Criteria for Adverse Events (version 5.0). The median time to irAE onset was 9.8 weeks; 219 (57%) occurred within the first 3 months after ICI initiation. Discontinuation of treatment with ICIs owing to irAEs occurred in 137 (16.1%) patients. There was no significant difference in the rate of irAEs among patients aged younger than 85, 85 to 89, and 90 years or older. Despite the similar rate of G3 or higher irAEs, ICIs were discontinued due to irAEs more than twice as often among patients aged 90 years or older compared with patients younger than 90 years (30.9% vs 15.1%, P = .008). CONCLUSIONS AND RELEVANCEThe findings of this international cohort study suggest that treatment with ICIs may be effective and generally well tolerated among older patients with cancer, though ICI discontinuation owing to irAEs was more frequent with increasing age.

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BackgroundSensitive and specific biomarkers are needed to provide better biologic insight into the risk of incident and progressive CKD. However, studies have been limited by sample size and design heterogeneity.MethodsIn this assessment of the prognostic value of preclinical plasma and urine biomarkers for CKD outcomes, we searched Embase (Ovid), MEDLINE ALL (Ovid), and Scopus up to November 30, 2020, for studies exploring the association between baseline kidney biomarkers and CKD outcomes (incident CKD, CKD progression, or incident ESKD). We used random-effects meta-analysis.ResultsAfter screening 26,456 abstracts and 352 full-text articles, we included 129 studies in the meta-analysis for the most frequently studied plasma biomarkers (TNFR1, FGF23, TNFR2, KIM-1, suPAR, and others) and urine biomarkers (KIM-1, NGAL, and others). For the most frequently studied plasma biomarkers, pooled RRs for CKD outcomes were 2.17 (95% confidence interval [95% CI], 1.91 to 2.47) for TNFR1 (31 studies); 1.21 (95% CI, 1.15 to 1.28) for FGF-23 (30 studies); 2.07 (95% CI, 1.82 to 2.34) for TNFR2 (23 studies); 1.51 (95% CI, 1.38 to 1.66) for KIM-1 (18 studies); and 1.42 (95% CI, 1.30 to 1.55) for suPAR (12 studies). For the most frequently studied urine biomarkers, pooled RRs were 1.10 (95% CI, 1.05 to 1.16) for KIM-1 (19 studies) and 1.12 (95% CI, 1.06 to 1.19) for NGAL (19 studies).ConclusionsStudies of preclinical biomarkers for CKD outcomes have considerable heterogeneity across study cohorts and designs, limiting comparisons of prognostic performance across studies. Plasma TNFR1, FGF23, TNFR2, KIM-1, and suPAR were among the most frequently investigated in the setting of CKD outcomes.

Simultaneous liver‐kidney allocation protocols allocate dual organs based on a sustained eGFR of 30 mL/min or less. A 2017‐UNOS update includes CKD3 as dual organ candidates but only when the listing eGFR is <30 mL/min while recommending a "safety net" for prioritized kidney listing post‐LT. We retrospectively reviewed adult LTs examine whether the UNOS proposal captured the LT population at highest risk for developing post‐LT ESRD. Among 290 LT recipients, 67 had pre‐LT CKD3, 141 had AKI, of whom 47 required dialysis (<4 weeks). During follow‐up, 25 (8.62%) developed ESRD, while 70 (24.1%) died. In adjusted Cox models, CKD3 had an independent association with post‐LT ESRD (adjusted HR 4.8; P = 0.001), independent of AKI. Interestingly, CKD3 with listing GFR >30 mL/min was still significantly associated with post‐LT ESRD. AKI was associated with reduced post‐LT survival (adjusted HR 1.9; P = 0.02), albeit only in the first‐year post‐LT. Severe AKI‐D was associated with post‐LT ESRD and mortality. The safety net would have captured only 60% of all post‐LT ESRD cases in our cohort. Pre‐LT CKD3 was associated with increased risk of post‐LT ESRD above the recommended cutoff for listing GFR. These findings, if generalizable in larger cohorts have important implications for dual organ allocation.