Prognostic Value of Hypochloremia in Critically Ill Patients With Decompensated Cirrhosis.

OBJECTIVES: Cirrhosis is frequently complicated by electrolyte disturbances, with prior studies primarily focused on the importance of hyponatremia. Emerging evidence on patients with chronic heart failure and chronic kidney disease has identified hypochloremia as an independent predictor for mortality. This study aimed to investigate the prognostic value of serum chloride and its association with mortality in cirrhotic patients. DESIGN: Retrospective cohort study. SETTING: The medical ICU at Parkland Memorial Hospital, a tertiary care public health system in Dallas, Texas. PATIENTS: Adult patients with confirmed diagnosis of decompensated cirrhosis who were admitted to the ICU between March 2015 and March 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Kaplan-Meier analysis and multivariable Cox proportional hazard ratio models were performed to determine the impact of hypochloremia on 180-day mortality. Of the 389 enrolled patients, 133 (34.2%) died within 180 days of ICU admission. Patients with hypochloremia had higher 180-day mortality than those with normochloremia (45.2% vs 26.7%; p < 0.0001). Cumulative survival via the Kaplan-Meier method was significantly lower in the hypochloremic group. Serum chloride was independently associated with 180-day mortality with multivariable adjustment (hazard ratio, 0.95; 95% CI, 0.93-0.98; p = 0.001) or after adjusting for Model for End-stage Liver Disease or Sequential Organ Failure Assessment. Contrarily, the inverse association between serum sodium and mortality no longer existed in all multivariable models. CONCLUSIONS: Serum chloride is independently and inversely associated with short-term mortality in critically ill cirrhotic patients. Hypochloremia, but not hyponatremia, remained associated with mortality with multivariable analyses, suggesting that hypochloremia may account for the mortality risk previously attributed to hyponatremia. These findings signify the prognostic value of serum chloride and potential inclusion of chloride into future cirrhosis prognostic scores.

Cell type-specific immune dysregulation in severely ill COVID-19 patients.

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.