Procalcitonin and C-reactive protein to rule out early bacterial coinfection in COVID-19 critically ill patients.

PURPOSE: Although the prevalence of community-acquired respiratory bacterial coinfection upon hospital admission in patients with coronavirus disease 2019 (COVID-19) has been reported to be < 5%, almost three-quarters of patients received antibiotics. We aim to investigate whether procalcitonin (PCT) or C-reactive protein (CRP) upon admission could be helpful biomarkers to identify bacterial coinfection among patients with COVID-19 pneumonia. METHODS: We carried out a multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish intensive care units (ICUs). The primary outcome was to explore whether PCT or CRP serum levels upon hospital admission could predict bacterial coinfection among patients with COVID-19 pneumonia. The secondary outcome was the evaluation of their association with mortality. We also conducted subgroups analyses in higher risk profile populations. RESULTS: Between 5 February 2020 and 21 December 2021, 4076 patients were included, 133 (3%) of whom presented bacterial coinfection. PCT and CRP had low area under curve (AUC) scores at the receiver operating characteristic (ROC) curve analysis [0.57 (95% confidence interval (CI) 0.51-0.61) and 0.6 (95% CI, 0.55-0.64), respectively], but high negative predictive values (NPV) [97.5% (95% CI 96.5-98.5) and 98.2% (95% CI 97.5-98.9) for PCT and CRP, respectively]. CRP alone was associated with bacterial coinfection (OR 2, 95% CI 1.25-3.19; p = 0.004). The overall 15, 30 and 90 days mortality had a higher trend in the bacterial coinfection group, but without significant difference. PCT ≥ 0.12 ng/mL was associated with higher 90 days mortality. CONCLUSION: Our study suggests that measurements of PCT and CRP, alone and at a single time point, are not useful for ruling in or out bacterial coinfection in viral pneumonia by COVID-19.

Minimal invasive fluorescence methods to quantify advanced glycation end products (AGEs) in skin and plasma of humans.

Advanced glycation end products (AGEs) are non-enzymatic modifications of proteins and lipids, which are spontaneously produced in the body in relation with several human diseases. Their relevance on protein functions alteration, either structural or enzymatic is under study, but their value as biomarkers or predictors of disease progression and clinical outcomes is unquestionable. The heterogeneity and amplitude of these modifications make their analysis difficult, although, different methods have been developed for specific AGEs based on colorimetric reactions, immunoassays or chromatography. However, for a massive application on human population, methods based on the autofluorescence of some AGEs stand out. Several qualities of these methods such as label-free measurement, rapidity, cost-effectiveness, and minimal invasiveness make them very useful for periodic measurements in critically ill patients and for the analysis of large populations. Here we explain the rationale of these methods, and we present a step-by-step protocol and the equipment requirements to carry out the estimation of AGE content in skin and plasma. AGE plasma content and skin accumulation are temporally related, so AGE plasmatic levels are a possible predictor of skin AGE content. On the other hand, AGE skin accumulation is a surrogate or an indicator of past AGE levels in plasma and in the rest of the body. AGE levels or their variations have shown to be related with prognosis of several diseases, so they can be used as predictor biomarkers for clinicians.

First-Days Reduction of Plasma and Skin Advanced Glycation End Products is Related to Outcome in Septic Patients.

BACKGROUND: Advanced glycation end products (AGEs) are a result of nonenzymatic glycation of proteins and lipids, which can attach to either their cell surface receptor (RAGE) or its soluble form (sRAGE). Evidence exists for the implication of AGE-RAGE axis in sepsis, but data are still insufficient and conflicting. We aimed to analyze the kinetics of plasma and skin AGEs and sRAGE during sepsis, and their association with outcome in septic patients. METHODS: We performed a prospective observational study. We enrolled 90 consecutive patients with severe sepsis or septic shock, within the first 24 h of Intensive Care Unit admission. During the first 5 days of sepsis, we measured plasma autofluorescence (PAF) and skin autofluorescence (SAF) as surrogates of circulating and skin AGEs, respectively. sRAGE was measured on days 1, 3, and 5. Delta values were defined as the difference between the PAF, SAF, or sRAGE on a specific day and the value on day 1. RESULTS: 28-day mortality was 18%. Bivariate analysis found that ΔPAF3-1, ΔPAF4-1, ΔPAF5-1, and ΔSAF5-1 were significantly associated with 28-day mortality. Additionally, sRAGE1 was inversely correlated to ΔPAF4-1 (r = -0.250, P = 0.019) and ΔPAF5-1 (r = -0.246, P = 0.024), and significantly associated with 28-day mortality. In an adjusted multivariate logistic regression analysis, ΔPAF2-1, ΔPAF3-1, ΔPAF4-1, ΔPAF5-1, and ΔSAF5-1 were associated with 28-day mortality. CONCLUSIONS: Kinetics of plasma and skin AGEs during the first days of sepsis are independently associated with mortality, where a decrease of plasma and skin AGEs are related to higher mortality.

Cystatin C provides more information than other renal function parameters for stratifying risk in patients with acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: The protein cystatin C has a stable plasma concentration and is eliminated exclusively by the kidneys. The aim of this study was to determine the prognostic value of cystatin C in patients with acute coronary syndrome (ACS). METHODS: The prospective study included 203 hospitalized ACS patients. Clinical evaluation during the first 24 hours of hospitalization included a hemogram and measurement of creatinine, cystatin C, total and fractionated cholesterol and markers of myocardial necrosis. The glomerular filtration rate (GFR) was estimated using the MDRD (Modification of Diet in Renal Disease) equation. A comparison was made between two groups of patients divided according to a serum cystatin-C level above or below 0.95 mg/L. The mean follow-up period was 151 days. RESULTS: In total, 90 patients (44.3%) had a cystatin-C level < or =0.95 mg/L and 113 (55.7%) had a level >0.95 mg/L. Those with a cystatin-C level >0.95 mg/L had poorer in-hospital outcomes, including more frequent heart failure (51.3% vs. 13.3%; P=.001) and higher in-hospital mortality (17.6% vs. 3.3%; P=.001), as well as higher mortality throughout follow-up (22.0% vs. 5.6%; P=.001). Multivariate analysis adjusted for age, ejection fraction and troponin-I and high-sensitivity C-reactive protein concentrations showed that cystatin C was the most powerful independent predictor of a cardiovascular event (relative risk=1.91; 95% confidence interval, 1.03-3.53). Patients with a GFR >60 mL/1.73 m(2) and a cystatin-C level >0.95 mg/L had higher in-hospital mortality (10.2% vs. 3.9%; P=.001). CONCLUSIONS: Measurement of cystatin C in high-risk ACS patients may be clinically useful for risk stratification during hospitalization, particularly in those with a normal GFR.