Summary Background Cirrhotic patients admitted to intensive care units (ICUs) have high mortality rates. The Chronic Liver Failure–Sequential Organ Failure Assessment (CLIF‐SOFA) score, a modified Sequential Organ Failure Assessment (SOFA) score, is a newly developed scoring system exclusively for patients with end‐stage liver disease. Aim To externally validate the efficacy of the CLIF‐SOFA score and evaluate other scoring systems for 6‐month mortality in critically ill cirrhotic patients. Methods This study prospectively recorded and analysed the data for 30 demographical parameters and some clinical characteristic variables on day 1 of 250 cirrhotic patients admitted to a 10‐bed specialised hepatogastroenterology ICU in a 2000‐bed tertiary care referral hospital during the period from September 2010 to August 2013. Results The overall in‐hospital and 6‐month mortality rate were 58.8% (147/250) and 78.0% (195/250), respectively. Liver diseases were mostly attributed to hepatitis B virus infection (32%). Multiple Cox logistic regression hazard analysis revealed that Glasgow coma scale, both the CLIF‐SOFA and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of ICU admission were independent predictors of 6‐month mortality. Analysis of the area under the receiver operating characteristic curve revealed that the CLIF‐SOFA score had the best discriminatory power (0.900 ± 0.020). Moreover, the cumulative 6‐month survival rates differed significantly for patients with a CLIF‐SOFA score ≤11 and those with a CLIF‐SOFA score >11 on the ICU admission day. Conclusion Both CLIF‐SOFA and APACHE III scores are excellent prognosis evaluation tools for critically ill cirrhotic patients.

The viral spike (S) coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human angiotensin-converting enzyme2 (ACE2) cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for Coronavirus -19 (COVID-19) in patients taking angiotensin-converting enzyme inhibitors (ACEI)/ angiotensin II type 1 receptor antagonists (ARBs). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization data-base of COVID-19 publications and ClinicalTrials.gov through Jun 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. After pooling the adjusted odds ratios (aOR) from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACEi (aOR, 0.95; 95% CI, 0.86-1.05) or ARBs (aOR, 1.05; 95% CI, 0.97-1.14). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006; 95% CI, -0.016 to 0.004)-i.e.: the use of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (< 60 years-old). The use of ACEi might not increase the susceptibility of SARS-CoV-2 infection, severity of disease and mortality in case-population and cohort studies. Additionally, we found for the first time that the use of ARBs, as opposed to ACEi, specifically augmented the risk of SARS-CoV-2 infection in younger subjects; without obvious effects on COVID-19 outcomes.

Critically ill cirrhotic patients have high mortality rates, particularly when they present with acute kidney injury (AKI) on admission. The Kidney Disease: Improving Global Outcomes (KDIGO) group aimed to standardize the definition of AKI and recently published a new AKI classification. However, the efficacy of the KDIGO classification for predicting outcomes of critically ill cirrhotic patients is unclear. We prospectively enrolled 242 cirrhotic patients from a 10-bed specialized hepatogastroenterology intensive care unit (ICU) in a 2000-bed tertiary-care referral hospital. Demographic parameters and clinical variables on day 1 of admission were prospectively recorded. The overall in-hospital mortality rate was 62.8%. Liver diseases were usually attributed to hepatitis B viral infection (26.9%). The major cause of ICU admission was upper gastrointestinal bleeding (38.0%). Our result showed that the KDIGO classification had better discriminatory power than RIFLE and AKIN criteria in predicting in-hospital mortality. Cumulative survival rates at the 6-month after hospital discharge differed significantly between patients with and without AKI on ICU admission day. In summary, we identified that the outcome prediction performance of KDIGO classification is superior to that of AKIN or RIFLE classification in critically ill cirrhotic patients.

For those patients with ECMO support, the KDIGO classification proved to be a more reproducible evaluation tool with excellent prognostic abilities than RIFLE or AKIN classification.

Protein-bound uremic toxins, indoxyl sulfate and p-cresol sulfate, increase oxidative stress and adversely affect chronic kidney disease progression and cardiovascular complications. In this study, we examined whether mitochondria are the target of indoxyl sulfate and p-cresol sulfate intoxication in vivo and in vitro. The kidneys of 10-week-old male B-6 mice with ½-nephrectomy treated with indoxyl sulfate and p-cresol sulfate were used for the animal study. Cultured human renal tubular cells were used for the in vitro study. Our results indicated that indoxyl sulfate and p-cresol sulfate impaired aerobic and anaerobic metabolism in vivo and in vitro. Indoxyl sulfate and p-cresol sulfate caused mitochondrial fission by modulating the expression of mitochondrial fission–fusion proteins. Mitochondrial dysfunction and impaired biogenesis could be protected by treatment with antioxidants. The in vitro study also demonstrated that indoxyl sulfate and p-cresol sulfate reduced mitochondrial mass by activating autophagic machinery. In summary, our study suggests that mitochondrial injury is one of the major pathological mechanisms for uremic intoxication, which is related to chronic kidney disease and its complications.

BackgroundCirrhotic patients with acute kidney injury (AKI) admitted to intensive care units (ICUs) show extremely high mortality rates. We have proposed the MBRS scoring system, which can be used for assessing patients on the day of admission to the ICU; this new system involves determination of mean arterial pressure (MAP) and bilirubin level and assessment of respiratory failure and sepsis. We had used this scoring system to analyze the prognosis of ICU cirrhotic patients with AKI in 2008, and the current study was an external validation of this scoring system.MethodsA total of 190 cirrhotic patients with AKI were admitted to the ICU between March 2008 and February 2011. We prospectively analyzed and recorded the data for 31 demographic parameters and some clinical characteristic variables on day 1 of admission to the ICU; these variables were considered as predictors of mortality.ResultsThe overall in-hospital mortality rate was 73.2% (139/190), and the 6-month mortality rate was 83.2% (158/190). Hepatitis B viral infection (43%) was observed to be the cause of liver disease in most of the patients. Multiple logistic regression analysis indicated that the MBRS and Acute Physiology and Chronic Health Evaluation III (ACPACHE III) scores determined on the first day of admission to the ICU were independent predictors of in-hospital mortality in patients. In the analysis of the area under the receiver operating characteristic (AUROC) curves, the MBRS scores showed good discrimination (AUROC: 0.863±0.032, p<0.001) in predicting in-hospital mortality.ConclusionOn the basis of the results of this external validation, we conclude that the MBRS scoring system is a reproducible, simple, easy-to-apply evaluation tool that can increase the prediction accuracy of short-term prognosis in critically ill cirrhotic patients with AKI.

Our results suggest that circulating Klotho level is a predictor of long-term macrovascular outcomes in patients with type 2 diabetes.

Background Acute kidney disease (AKD) describes acute or subacute damage and/or loss of kidney function for a duration of between 7 and 90 days after exposure to an acute kidney injury (AKI) initiating event. This study investigated the predictive ability of AKI biomarkers in predicting AKD in coronary care unit (CCU) patients. Methods A total of 269 (mean age: 64 years; 202 (75%) men and 67 (25%) women) patients admitted to the CCU of a tertiary care teaching hospital from November 2009 to September 2014 were enrolled. Information considered necessary to evaluate 31 demographic, clinical and laboratory variables (including AKI biomarkers) was prospectively recorded on the first day of CCU admission for post hoc analysis as predictors of AKD. Blood and urinary samples of the enrolled patients were tested for neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC) and interleukin-18 (IL-18). Results The overall hospital mortality rate was 4.8%. Of the 269 patients, 128 (47.6%) had AKD. Multivariate logistic regression analysis revealed that age, hemoglobin, ejection fraction and serum IL-18 were independent predictors of AKD. Cumulative survival rates at 5 years of follow-up after hospital discharge differed significantly (p < 0.001) between subgroups of patients diagnosed with AKD (stage 0A, 0C, 1, 2 and 3). The overall 5-year survival rate was 81.8% (220/269). Multivariate Cox proportional hazard analysis revealed that urine NGAL, body weight and hemoglobin level were independent risk factors for 5-year mortality. Conclusions This investigation confirmed that AKI biomarkers can predict AKD in CCU patients. Age, hemoglobin, ejection fraction and serum IL-18 were independently associated with developing AKD in the CCU patients, and urine NGAL, body weight and hemoglobin level could predict 5-year survival in these patients.