Reduction in Nosocomial Infections in Patients With Cirrhosis During the COVID-19 Era Compared with Pre-COVID-19: Impact of Masking and Restricting Visitation.

Nosocomial infections (NIs) in critically ill patients with cirrhosis result in higher death and transplant delisting. NIs are promoted by staff, visitors, and the environment, all of which were altered to reduce pathogen transmission after COVID-19. Two cohorts of intensive care unit patients with cirrhosis from March 2019 to February 2020 (pre-COVID, n = 234) and March 2020 to March 2021 (COVID era, n = 296) were included. We found that despite a higher admission MELD-Na, qSOFA, and WBC count and requiring a longer intensive care unit stay, COVID-era patients developed lower NIs (3% vs 10%, P < 0.001) and had higher liver transplant rates vs pre-COVID patients. COVID-era restrictions could reduce NIs in critically ill patients with cirrhosis.

Patient- and provider-level factors that underlie alcohol use disorder treatment offer and acceptance in veterans with cirrhosis.

BACKGROUND: Untreated alcohol use disorder (AUD) is associated with poor cirrhosis outcomes. We evaluated factors associated with AUD treatment discussions and initiation in the Veterans Health Administration. METHODS: Chart reviews were conducted for veterans with International Classification of Diseases codes for both cirrhosis and AUD who were receiving care at one of three large medical centers in 2020. Factors associated with a 1-year offer of AUD treatment and its acceptance were assessed using regression models, which included as covariates demographic characteristics, comorbidities, and depression, as measured by the patient health questionnaire (PHQ-2) from the electronic health record. RESULTS: The cohort included 654 veterans, 68 of whom were engaged in AUD treatment at baseline and 174 who were documented as being in AUD remission. Treatment was offered to 264 (64%) of the 412 veterans with opportunities to initiate it. AUD treatment discussions were most often documented by practitioners in primary care (n = 162), hepatology (n = 45), or both (n = 41). Multivariable logistic regression modeling revealed that treatment was significantly more likely to be offered to patients with co-occurring bipolar disorder (OR 2.94, p = 0.03) or depression (1.50, p = 0.05) or who were younger (0.97, p = 0.01). Of the 264 patients offered AUD treatment, 107 (40%) agreed to initiate it. Acceptance of an offer of treatment was significantly associated with hospitalization in the prior year (OR 1.74, p = 0.05), prior AUD treatment (9.92, p < 0.0001), and a higher PHQ-2 depression score (2.85, p = 0.004). CONCLUSIONS: We identified factors associated with an offer of AUD treatment and its initiation among veterans with cirrhosis. Application of these findings could increase the likelihood that veterans with alcoholic cirrhosis initiate AUD treatment.

Timing of valproic acid in acute lung injury: prevention is the best therapy?

BACKGROUND: Acute lung injury and respiratory distress syndrome is characterized by uncontrolled inflammation of the lungs after a severe inflammatory stimulus. We have previously demonstrated an ameliorated syndrome and improved survival in mice with early administration of valproic acid (VPA), a broad-spectrum histone deacetylase inhibitor, while studies in humans have shown no benefit when anti-inflammatories are administered late. The current study tested the hypothesis that early treatment would improve outcomes in our gram-negative pneumonia-induced acute lung injury. MATERIALS AND METHODS: Mice (C57BL/6) had 50 × 106 Escherichia coli (strain 19,138) instilled endotracheally and VPA (250 mg/kg) administered intraperitoneally 3, 4, 6, and 9 h (n = 12/group) later. Six hours after VPA administration, the animals were sacrificed, and bronchoalveolar lavage (BAL) fluid interleukin-6 (IL-6), tumor necrosis factor, neutrophils and macrophages as well as the E coli colony-forming units were quantified. Plasma IL-6 was also measured. A separate group of mice (n = 12/group) were followed prospectively for 7 days to assess survival. RESULTS: BAL IL-6 and tumor necrosis factor as well as plasma IL-6 were significantly lower in the animals administered VPA within 3 h (P < 0.05) but not when administered later (4, 6, 9 h). There was no difference in the BAL E coli colony-forming units, macrophage, or neutrophil numbers at any time point. Survival improved only when VPA was administered within 3 h. CONCLUSIONS: A narrow therapeutic window exists in this murine model of gram-negative pneumonia-induced acute lung injury and likely explains the lack of response in studies with late administration of anti-inflammatory therapies in clinical studies.