Krebs von den Lungen 6 levels in COVID-19 ICU Patients are Associated with Mortality

RationaleKrebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Elevated circulating levels of KL-6 may denote disorder of the alveolar epithelial lining. ObjectiveAim of this study was to verify if KL-6 values may help to risk stratify and triage severe COVID-19 patients. MethodsWe performed a retrospective prognostic study on 110 COVID-19 ICU patients, evaluating the predictive role of KL-6 for mortality. Measurements and Main ResultsThe study sample was divided in two groups related according to the median KL-6 value [Group A (KL-6 lower than the log-transformed median (6.73)) and Group B (KL-6 higher than the log-transformed median)]. In both linear and logistic multivariate analyses, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (P/F) was significantly and inversely related to KL-6. Death rate was higher in group B than in group A (80.3 versus 45.9%) (p<0.001), Accordingly, the Cox regression analysis showed a significant prognostic role of KL-6 on mortality in the whole sample as well as in the subgroup with SOFA lower than its median value. ConclusionsAt ICU admission, KL-6 serum level was significantly lower in the survivors group. Our findings shown that, in severe COVID19 patients, elevated KL-6 was strongly associated with mortality in ICU.

Methodological aspects of superiority, equivalence, and non-inferiority trials.

Depending on the scientific hypothesis to be addressed, randomized-controlled trials (RCT) are accordingly designed. RCTs that aim to determine whether a novel, experimental therapeutic intervention (either a drug or a treatment) is superior to a placebo or control intervention, are called superiority trials. Less common are the non-inferiority RCTs, designed to assess whether a new intervention is not unacceptably worse than an already existing reference intervention. An equivalence RCT is designed to investigate whether a novel treatment is equivalently effective to another, already existing, control intervention. In equivalence and non-inferiority RCTs, the efficacy of the reference intervention (active comparator) is already established, and therefore, an untreated control group would not be ethical. In this review, using a series of examples derived from equivalence and non-inferiority/superiority RCTs, we describe the main differences and methodological aspects among these three different types of RCTs.

Prevalence of renal artery stenosis in patients undergoing cardiac catheterization.

To investigate the prevalence of significant renal artery stenosis (RAS ≥50%), and to identify clinical predictors for significant RAS in patients with an elevated cardiovascular risk, such as those affected by ischemic heart disease. In patients with an elevated cardio-vascular risk, both atherosclerotic renovascular disease and coronary artery disease (CAD) are likely to occur. Prospectively from April 2007 to March 2008, all consecutive patients with ischemic heart disease undergoing non-emergent cardiac catheterization were also evaluated for atherosclerotic RAS by renal arteriography. A RAS ≥50% was considered as significant. A total of 1,298 patients underwent cardiac and renal angiography. Significant RAS was found in 70 out of 1,298 patients (5.4%). The presence of peripheral vascular disease, eGFR <67 ml/min/1.73 m(2), age >66 years, dyslipidemia, CAD severity and pulse pressure >52 mmHg were independent clinical predictors of significant RAS, and jointly produced a ROC AUC of 0.79 (95% CI 0.73-0.85, P < 0.001). Based on these data, a prediction rule for significant RAS was developed, and it showed an adequate predictive performance with 64% sensitivity and 82% specificity. In a large cohort of patients undergoing coronary angiography, significant RAS is a relatively rare comorbidity (5.4%). A model based on simple clinical variables may be useful for the clinical identification of high CV risk patients who may be suitable for renal arteriography at the time of cardiac catheterization.