Do low levels of alanine aminotransferase, a baseline marker of sarcopenia and frailty, associate with worse clinical outcomes among hospitalized COVID-19 patients? A Retrospective Cohort Study.

Objectives: COVID-19 geoperdize lives. Not all the risk factors for negative outcomes are known. Sarcopenia and frailty are common, negatively affecting clinical outcomes. Studies have shown that sarcopenia and frailty are associated with worse outcomes. Our objective was to examine whether low ALT (Alanine-aminotranferase), a surrogate marker for sarcopenia, is associated with worse clinical outcomes among hospitalized COVID-19 patients. Methods: We reviewed cases of COVID-19 in a tertiary hospital, during three COVID-19 waves and examined correlations between ALT and mortality using crude, univariate and multivariate analysis for age, gender, hypertension, Chronic obstructive pulmonary disease and Congestive heart failure. Results: 357 patients were included in this analysis. Median age was 69, 54% were males. Median ALT was 19 IU/L. During follow-up, 73 (20%) died. Patients with low ALT were more likely to die (HR 1.82, 95% CI 1.06-3.09, P=0.028). Other predictors for mortality were low albumin, background COPD, dyslipidemia, dementia, and malignancy. The multivariate analysis showed that low ALT was still an independent predictor of poor prognosis (HR 1.7, 95% CI 1.0-2.9, P=0.049). Conclusions: In our analysis of COVID-19 patients, low ALT levels were independently associated with increased risk of mortality, both as standalone and when incorporated into a multivariate analysis.

Hospitalized patients with positive antiphospholipid antibodies who have low complement levels are at increased risk for death-a retrospective cohort study.

PURPOSE: To investigate whether low complement levels can predict worse outcomes in patients hospitalized with positive anti-phospholipid antibodies. METHODS: This was a retrospective cohort study. We obtained demographics, laboratory, and prognostic data of all consecutive patients hospitalized between 2007 and 2021, for whatever reason, with at least one positively abnormal anti-phospholipid antibody, who were also tested for complement levels (C3 or C4). We then compared the rates of long-term mortality, 1-year mortality, deep vein thrombosis, and pulmonary emboli between groups of low complement and normal complement levels. Multivariate analysis was used to control for levels of clinical and laboratory confounders. RESULTS: We identified 32,286 patients tested for anti-phospholipid antibodies. Of those patients, 6800 tested positive for at least one anti-phospholipid antibody and had a documented complement level. Significant higher mortality rates were found in the low complement group, with an odds ratio for mortality (OR 1.93 CI 1.63-2.27 p < .001). Deep vein thrombosis and pulmonary emboli rates were similar. Multivariate analysis confirmed that low complement was an independent predictor for mortality after controlling for age, sex, dyslipidemia, chronic heart failure (CHF), chronic kidney disease (CKD), and anemia. CONCLUSIONS: Our study results indicate that low complement is associated with significantly higher mortality rates in admitted patients with elevated levels of anti-phospholipid antibodies. This finding correlates with recent literature suggesting a vital role for complement activation in anti-phospholipid syndrome.

Mortality prediction upon hospital admission - the value of clinical assessment: A retrospective, matched cohort study.

Accurate prediction of mortality upon hospital admission is of great value, both for the sake of patients and appropriate resources' allocation. A myriad of assessment tools exists for this purpose. The evidence relating to the comparative value of clinical assessment versus established indexes are scarce. We analyzed the accuracy of a senior physician's clinical assessment in a retrospective cohort of patients in a crude, general patients' population and later on a propensity matched patients' population. In one department of internal medicine in a tertiary hospital, of 9891 admitted patients, 973 (10%) were categorized as prone to death in a 6-months' duration by a senior physician. The risk of death was significantly higher for these patients [73.1% vs 14.1% mortality within 180 days; hazard ratio (HR) = 7.58; confidence intervals (CI) 7.02-8.19, P < .001]. After accounting for multiple, other patients' variables associated with increased risk of mortality, the correlation remained significant (HR = 3.25; CI 2.85-3.71, P < .001). We further performed a propensity matching analysis (a subgroup of 710 patients, subdivided to two groups with 355 patients each): survival rates were as low as 45% for patients categorized as prone to death compared to 78% in patients who weren't categorized as such (P < .001). Reliance on clinical evaluation, done by an experienced senior physician, is an appropriate tool for mortality prediction upon hospital admission, achieving high accuracy rates.

Exploring the pathways of inflammation and coagulopathy in COVID-19: A narrative tour into a viral rabbit hole.

Worldwide COVID-19 pandemic has taken a huge toll of morbidity and mortality. In selected patients, classified as severe, the overwhelming inflammatory state imposed by this infection is accompanied by a hypercoagulable state, hallmarked by a unique pattern; a marked increase in D-dimer, out of proportion to other markers of coagulopathy. In this review, we turn a spotlight to this phenomenon, offering a unified conceptual model depicting the leading hypotheses of coagulopathy in COVID-19. The key players of the coagulation cascades accompanying the COVID-19 inflammation malfunction on virtually every level; tissue factor expression is amplified, physiological anti-coagulant pathways (anti-thrombin, protein C and S, and the inhibitor of the tissue factor pathway) are impaired and fibrinolysis is inhibited. Components of autoimmunity, the complement system amongst others, further contribute to the pathology. As data continue to gather, our model offers a pathophysiological overview of COVID-19 coagulopathy, defined by the resultant histopathology: either intra-vascular or extra-vascular. We hope this review will facilitate understanding and serve as a lead point to future therapeutic directives.

Low ALT Levels Associated with Poor Outcomes in 8700 Hospitalized Heart Failure Patients.

Sarcopenia and frailty are causes for morbidity and mortality amongst heart failure (HF) patients. Low alanine transaminase (ALT) is a marker for these syndromes and, therefore, could serve as a biomarker for the prognostication of HF patients. We performed a retrospective analysis of all consecutive hospitalized HF patients in our institute in order to find out whether low ALT values would be a biomarker for poor outcomes. Our cohort included 11,102 patients, 35.6% categorized as heart failure with reduced ejection fraction. We excluded patients with ALT > 40 IU/L and cirrhosis. 8700 patients were followed for a median duration of 22 months and included in a univariate analysis. Patients with ALT < 10 IU/L were older (mean age 78.6 vs. 81.8, p < 0.001), had past stroke (24.6% vs. 19.6%, p < 0.001), dementia (7.7% vs. 4.6%, p < 0.001), and malignancy (13.4% vs. 10.2%, p = 0.003). Hospitalization length was longer in the low-ALT group (4 vs. 3 days, p < 0.001), and the rate of acute kidney injury during hospitalization was higher (19.1% vs. 15.6%; p = 0.006). The in-hospital mortality rate was higher in the low-ALT group (6.5% vs. 3.9%; p < 0.001). Long-term mortality was also higher (73.3% vs. 61.5%; p < 0.001). In a multivariate regression analysis, ALT < 10 IU/L had a 1.22 hazard ratio for mortality throughout the follow-up period (CI = 1.09-1.36; p < 0.001). Low ALT plasma level, a biomarker for sarcopenia and frailty, can assist clinicians in prognostic stratification of heart failure patients.

Frailty and Sarcopenia Assessment upon HospitalAdmission to Internal Medicine Predicts Length ofHospital Stay and Re-Admission: A ProspectiveStudy of 980 Patients.

BACKGROUND: Frailty and sarcopenia are associated with frequent hospitalizations and poor clinical outcomes in geriatric patients. Ascertaining this association for younger patients hospitalized in internal medicine departments could help better prognosticate patients in the realm of internal medicine. METHODS: During a 1-year prospective study in an internal medicine department, we evaluated patients upon admission for sarcopenia and frailty. We used the FRAIL questionnaire, blood alanine-amino transferase (ALT) activity, and mid-arm muscle circumference (MAMC) measurements. RESULTS: We recruited 980 consecutive patients upon hospital admission (median age 72 years (IQR 65-79); 56.8% males). According to the FRAIL questionnaire, 106 (10.8%) patients were robust, 368 (37.5%) pre-frail, and 506 (51.7%) were frail. The median ALT value was 19IU/L (IQR 14-28). The median MAMC value was 27.8 (IQR 25.7-30.2). Patients with low ALT activity level (<17IU/L) were frailer according to their FRAIL score (3 (IQR 2-4) vs. 2 (IQR 1-3); p < 0.001). Higher MAMC values were associated with higher ALT activity, both representing robustness. The rate of 30 days readmission in the whole cohort was 17.4%. Frail patients, according to the FRAIL score (FS), had a higher risk for 30 days readmission (for FS > 2, HR = 1.99; 95CI = 1.29-3.08; p = 0.002). Frail patients, according to low ALT activity, also had a significantly higher risk for 30 days readmission (HR = 2.22; 95CI = 1.26-3.91; p = 0.006). After excluding patients whose length of stay (LOS) was ≥10 days, 252 (27.5%) stayed in-hospital for 4 days or longer. Frail patients according to FS had a higher risk for LOS ≥4 days (for FS > 2, HR = 1.87; 95CI = 1.39-2.52; p < 0.001). Frail patients, according to low ALT activity, were also at higher risk for LOS ≥4 days (HR = 1.87; 95CI = 1.39-2.52; p < 0.001). MAMC values were not correlated with patients' LOS or risk for re-admission. CONCLUSION: Frailty and sarcopenia upon admission to internal medicine departments are associated with longer hospitalization and increased risk for re-admission.

Beneficial effect of awake prone position in hypoxaemic patients with COVID-19: case reports and literature review.

We hereby present two case reports of moderate coronavirus disease patients, suffering from profound hypoxaemia, further deteriorating later on. A schedule pre-planned awake prone position manoeuvres were executed during their hospital stay. Following this, the patients' saturation improved, later to be weaned from oxygen support. Paucity of evidence and data regarding this topic led us to review the concept of awake prone position.

Clinical Characterization of 162 COVID-19 patients in Israel: Preliminary Report from a Large Tertiary Center.

BACKGROUND: In February 2020, the World Health Organisation designated the name COVID-19 for a clinical condition caused by a virus identified as a cause for a cluster of pneumonia cases in Wuhan, China. The virus subsequently spread worldwide, causing havoc to medical systems and paralyzing global economies. The first COVID-19 patient in Israel was diagnosed on 27 February 2020. OBJECTIVES: To present our findings and experiences as the first and largest center for COVID-19 patients in Israel. METHODS: The current analysis included all COVID-19 patients treated in Sheba Medical Center from February 2020 to April 2020. Clinical, laboratory, and epidemiological data gathered during their hospitalization are presented. RESULTS: Our 162 patient cohort included mostly adult (mean age of 52 ± 20 years) males (65%). Patients classified as severe COVID-19 were significantly older and had higher prevalence of arterial hypertension and diabetes. They also had significantly higher white blood cell counts, absolute neutrophil counts, and lactate dehydrogenase. Low folic acid blood levels were more common amongst severe patients (18.2 vs. 12.9 vs. 9.8, P = 0.014). The rate of immune compromised patients (12%) in our cohort was also higher than in the general population. The rate of deterioration from moderate to severe disease was high: 9% necessitated non-invasive oxygenation and 15% were intubated and mechanically ventilated. The mortality rate was 3.1. CONCLUSIONS: COVID-19 patients present a challenge for healthcare professionals and the whole medical system. We hope our findings will assist other providers and institutions in their care for these patients.