Predictive factors for adverse outcomes in patients with COVID-19 are urgently needed. Data related to the applicability of the Clinical Frailty Scale (CFS) for risk stratification in patients with COVID-19 are currently lacking. We investigated the ability of CFS to predict need for mechanical ventilation and the duration of hospital stays in European patients with COVID-19. In total, 42 patients with confirmed COVID-19 infection admitted to the University Medical Center Mainz between March 3 and April 15 2020 were included into this validation study and data were retrospectively analyzed. CFS was assessed at admission in all patients. Patients were followed for need for mechanical ventilation and time to hospital discharge. At admission, the median CFS was 3 (range: 1–7) and 14 (33.3%) patients were considered as at least pre-frail (CFS >3). 24 (57.1%) patients were discharged from hospital after a median time of 7 days (IQR 4–8). 12 (28.6%) patients developed acute respiratory distress syndrome and required mechanical ventilation. In multivariable Cox regression analyses, higher CFS scores (HR 1.659, 95% CI 1.090 to 2.525, p=0.018) were an independent predictor for a higher risk of mechanical ventilation after adjusting for age, Charlson Comorbidity Index and quick sepsis-related organ failure score. Additionally, lower CFS scores (HR 0.554, 95% CI 0.312 to 0.983, p=0.043) were associated with earlier discharge from hospital. In conclusion, this report demonstrates the usefulness of the CFS for risk stratification at hospital admission in patients with COVID-19.

Background: Diabetes mellitus may lead to increased serum ammonia and systemic inflammation thereby promoting hepatic encephalopathy (HE). Aim: To investigate the potential association between diabetes mellitus/glycaemic control and the presence of covert HE as well as the development of overt HE in a prospective setting. Methods: A total of 240 patients with liver cirrhosis were included into this prospective cohort study and followed for a median of 17 months. Covert HE was diagnosed by pathological results in the Portosystemic Hepatic Encephalopathy Score. Predictors for the presence of covert HE or the development of overt HE were analysed using logistic regression or Cox-regression models. Results: At study inclusion, 65 patients (27.1%) presented with diabetes mellitus and covert HE was detected in 33.3%. Patients with diabetes mellitus had a more preserved liver function as compared to patients without diabetes mellitus (MELD 9 vs 10; P = 0.043). In regression analyses after adjustment for confounders, diabetes mellitus was independently associated with the presence of covert HE at study inclusion and the development of overt HE during follow-up. These associations were confirmed in separate propensity-score-weighted regression models. In subgroup analyses, patients with worse glycaemic control (HbA1c >= 6.5%) had a pronounced risk for covert HE (OR 2.264, 95% CI 1.002-5.118) and overt HE (HR 4.116, 95% CI 1.791-9.459). Conclusions: Diabetes mellitus may associate with higher risk for the presence of covert HE and the development of overt HE in patients with liver cirrhosis. Adequate glycaemic control may be a potential target to attenuate this important complication. How to cite this article: Labenz C, Nagel M, Kremer WM, et al. Association between diabetes mellitus and hepatic encephalopathy in patients with cirrhosis.

Background Assessment of muscle quantity by sonographic muscle indices could help identify patients at risk for fatal outcome during coronavirus disease-2019 . The aim of this study was to explore sonographic muscle indices as predictors of COVID-19 outcome and to test the feasibility of sonographic muscle measurement in an isolation context. Methods Muscle indices, derived from the psoas muscle or thigh muscles, were quantified by sonography in a cohort of patients without COVID-19 to obtain reference values for low muscle quantity. Gender-specific median of different muscle indices were defined as threshold value for low muscle quantity. The prognostic relevance of low muscle quantity, was prospectively explored in two cohorts of hospitalized COVID-19 patients. Optimal muscle index cutoff values predictive for 30 day mortality during COVID-19 were determined by receiver operating characteristic-area under the curve and Youden index calculation. Muscle quantity and known prognostic factors of COVID-19 were analysed by multivariable log-regression. Results Compared with other muscle indices, the psoas muscle area index (PMAI) showed the most favourable characteristics to predict outcome of COVID-19 disease. Sonographic morphometry of patients without COVID-19 (n = 136) revealed a gender-specific median for PMAI (male: 291.1 mm 2 /m 2 , female 260.6 mm 2 /m 2 ) as threshold value of low muscle quantity. Subsequently, COVID-19 patients (Cohort I: n = 58; Cohort II: n = 55) were prospectively assessed by bedside sonography. The studied COVID-19 patients developed a critical course of disease in 22.4% (Cohort I: n = 13/58) and 34.5% (Cohort II: n = 20/55). Mortality rate reached 12.1% (Cohort I: n = 7/58) and 20.0% (Cohort I: n = 11/55) within 30 days of follow up. COVID-19 patients with a PMAI below the gender-specific median showed a higher 30 day mortality in both COVID-19 cohorts (log rank, P < 0.05). The optimal PMAI cutoff value (206 mm 2 /m 2 ) predicted 30 day mortality of hospitalized COVID-19 patients with a sensitivity of 72% and specificity of 78.5% (receiver operating characteristic-area under the curve: 0.793, 95% confidence interval 0.671-0.914, P = 0.008). Multivariable log-regression analysis of PMAI, age, gender, BMI and comorbidities confirmed an independent association of low PMAI with 30 day mortality of COVID-19 patients (P = 0.018). Conclusions Sonographic morphometry provides reliable muscle quantification under hygienic precautions and allows risk stratification of patients with COVID-19.

INTRODUCTION: Frailty is a common but often underestimated complication in patients with liver cirrhosis. The Clinical Frailty Scale (CFS) allows the assessment of frailty within a short period of time but has only been investigated in a Canadian cohort of outpatients. The aim of the current study was to evaluate the ability of the CFS to predict mortality in outpatients and nonelectively hospitalized German patients. METHODS: Two hundred outpatients and 99 nonelectively hospitalized patients with liver cirrhosis were prospectively enrolled. Outpatients/inpatients were followed for a median of 364/28 days regarding the primary outcome of death or liver transplantation. Eighty-seven patients of the outpatient cohort and 64 patients of the inpatient cohort had available computed tomography-scans for the quantification of muscle mass. RESULTS: Median CFS was 3 in the outpatient and the inpatient cohort. Twenty-one (10.5%) outpatients were at least prefrail (CFS > 3) and 26 (26.3%) inpatients were frail (CFS > 4). For every one-unit increase, there was an independent association between the CFS and mortality in the outpatient cohort (hazard ratio 1.534, P = 0.007). This association remained significant after controlling for muscle mass in the subcohort with available computed tomography scans. In the inpatient cohort, frailty (CFS > 4) was an independent predictor for 28-day mortality after controlling for acute-on-chronic liver failure, albumin, and infections (odds ratio 4.627, P = 0.045). However, this association did not reach significance in a subcohort after controlling for muscle mass. DISCUSSION: Especially in outpatients, CFS is a useful predictor regarding increased mortality independent of the muscle mass.

Background and aim Body composition has emerged as a prognostic factor for end-stage liver disease. We therefore investigated muscle mass, body fat and other clinical–pathological variables as predictors of posttransplant survival. Methods A total of 368 patients, who underwent orthotopic liver transplantation (OLT) at our institution, were assessed prior to OLT and followed for a median of 9.0 years (range 2.0–10.0 years) after OLT. Psoas, erector spinae and the combined paraspinal muscle area, as well as the corresponding indices normalized by body-height squared, were quantified by a lumbar (L3) cross-sectional computed tomography. In addition, absolute body fat and bone density were estimated by the same computed tomography approach. Results Paraspinal muscle index (PSMI) (hazard ratio 0.955, P = 0.039) and hepatitis C (hazard rati 1.498, P = 0.038) were independently associated with post-OLT mortality. In contrast, body fat and bone density did not significantly affect post-OLT outcome (P > 0.05). The PSMI also predicted one-year posttransplant mortality with a receiver operating characteristics-area under the curve of 0.671 [95% confidence interval (CI) 0.589–0.753, P < 0.001) in male patients and outperformed individual psoas and erector spinae muscle group assessments in this regard. In male patients, a defined PSMI cutoff (<18.41 cm2/m2) was identified as suitable determinant for sarcopenia and posttransplant one-year mortality. In female OLT-recipients, however, sarcopenia was not predictive for patient survival und a women-specific cutoff could not be derived from this study. Conclusions Taken together this analysis provides evidence, which PSMI is a relevant marker for muscle mass and that sarcopenia is an independent predictor of early post-OLT survival in male patients.