Circulating levels of calprotectin, a signature of neutrophil activation in prediction of severe respiratory failure in COVID-19 patients: a multicenter, prospective study (CalCov study).

OBJECTIVE: Severe COVID-19 is characterized by a dysregulated immune response in which neutrophils play a critical role. Calprotectin reflects neutrophil activation and is involved in the self-amplifying thrombo-inflammatory storm in severe COVID-19. We aimed to evaluate the role of calprotectin in early prediction of severity in COVID-19 patients. METHODS: This was a multicenter prospective observational study enrolling consecutive adult COVID-19 patients. On arrival to emergency department, blood samples were collected for laboratory tests, including serum calprotectin. The primary outcome was severe respiratory failure requiring invasive mechanical ventilation and the secondary outcome was need for Intensive Care Unit (ICU) admission. RESULTS: Study population included 395 patients, 57 (14.4%) required invasive mechanical ventilation and 100 (25.3%) were admitted to ICU. Median serum calprotectin levels were significantly higher in intubated (3.73 mg/L vs. 2.63 mg/L; p < 0.001) and ICU patients (3.48 mg/L vs. 2.60 mg/L; p = 0.001). Calprotectin showed a significant accuracy to predict the need for invasive mechanical ventilation (ROC AUC 0.723) and ICU admission (ROC AUC 0.650). In multivariate analysis, serum calprotectin was an independent predictor of invasive mechanical ventilation (OR 1.161) and ICU admission (OR 1.068). CONCLUSION: Serum calprotectin can be used as an early predictor of severity in COVID-19 patients.

Role of Pancreatic Stone Protein as an Early Biomarker for Risk Stratification of Acute Pancreatitis.

BACKGROUND: Early risk stratification of acute pancreatitis is crucial to improve clinical outcomes. The objective of this study was to evaluate the ability of pancreatic stone protein (PSP) to predict acute pancreatitis severity and to compare it with the biomarkers and severity scores currently used for that purpose. PATIENTS AND METHODS: Prospective single-center observational study enrolling 268 adult patients with acute pancreatitis. Biomarkers including PSP were measured upon admission to the Emergency Department and severity scores as SOFA, PANC-3, and BISAP were computed. Patients were classified into mild-moderate (non-severe) and severe acute pancreatitis according to the Determinant-Based Classification Criteria. Area under the curve (AUC) and regression analysis were used to analyze the discrimination abilities and the association of biomarkers and scores with severity. RESULTS: Two hundred and thirty-five patients (87.7%) were classified as non-severe and 33 (12.3%) as severe acute pancreatitis. Median [IQR] PSP was increased in patients with severe acute pancreatitis (890 µg/L [559-1142] vs. 279 µg/L [141-496]; p < 0.001) and it was the best predictor (ROC AUC: 0.827). In multivariate analysis, PSP and urea were the only independent predictors for severe acute pancreatitis and a model combining them both ("biomarker model") showed an AUC of 0.841 for prediction of severe acute pancreatitis, higher than the other severity scores. CONCLUSIONS: PSP is a promising biomarker for predicting the severity of acute pancreatitis upon admission. A model combining PSP and urea might further constitute a potential tool for early risk stratification of this disease.

Mortality prediction model from combined serial lactate, procalcitonin and calprotectin levels in critically ill patients with sepsis: A retrospective study according to Sepsis-3 definition.

OBJECTIVE: 1) To evaluate the ability of baseline and on 24 h serum calprotectin, in comparison to canonical biomarkers (lactate and procalcitonin), for prognosis of 28-day mortality in critically ill septic patients; and 2) To develop a predictive model combining the three biomarkers. DESIGN: A single-center, retrospective study. SETTING: Intensive Care Unit of a university hospital. PATIENTS OR PARTICIPANTS: One hundred and seventy three septic pacientes were included. INTERVENTIONS: Measurement of baseline lactate, procalcitonin and calprotectin level and procalcitonin and calprotectin levels on 24 h. MAIN VARIABLES OF INTEREST: Demographics and comorbidities, SOFA score on ICU admission, baseline lactate, procalcitonin and calprotectin on admission and on 24 h and 28-day mortality. RESULTS: 1) On ICU admission, lactate was the only biomarker achieving a significant accuracy (AUC: 0.698); 2) On 24 h, no differences were found on procalcitonin and calprotectin levels. Procalcitonin and calprotectin clearances were significantly lower in non-survivors and both achieved a moderate performance (AUCs: 0.668 and 0.664, respectively); 3) A biomarker based-model achieved a significant accuracy (AUC: 0.766), trending to increase (AUC: 0.829) to SOFA score alone; y 4) Baseline lactate levels and procalcitonin and calprotectin clearance were independent predictors for the outcome. CONCLUSIONS: 1) Baseline and on 24 h calprotectina and procalcitonin levels lacked ability in predicting 28-day mortality; 2) Accuracy of clearance of both biomarkers was moderate; and 3) Combination of SOFA score and the predictive biomarker based-model showed a high prognostic accuracy.

Increased concentrations of procalcitonin in patients with paracetamol intoxication.

Objectives: Paracetamol intoxication is one of the causes of elevated procalcitonin concentrations unrelated to infection. We report a case series of two patients intoxicated with paracetamol whose laboratory data revealed a significant elevation of serum procalcitonin concentrations without clinical, radiological and/or biological evidence of infection. The underlying mechanism by which paracetamol triggers an increase in procalcitonin concentrations is still unclear. Case presentation: We report two cases of paracetamol intoxication. Both patients were admitted to the Emergency Department (ED) and subsequently transferred to the Intensive Care Unit (ICU). The patients exhibited elevated procalcitonin levels during the first hours of admission without clinical and/or microbiological evidence of infection that could explain such increase. Notably, only Case 1 developed liver injury, with alterations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and esterified bilirubin concentrations, which were not observed in Case 2. Conclusions: The two patients showed elevated procalcitonin concentrations resulting from paracetamol intoxication, although only a patient exhibited signs of liver injury. These findings suggest that increased procalcitonin levels induced by a paracetamol overdose cannot be fully explained by hepatocyte injury alone, but other mechanisms involving other organs and tissues may also be associated. In any case, although this mechanism is not well understood, it is important to be aware of this limitation when using procalcitonin as a biomarker of infection in patients intoxicated with paracetamol.

Influence of the matrix type over the concentration of GDF-15.

Growth differentiation factor 15 (GDF-15) has been suggested as a prognostic biomarker for bleeding and mortality in atrial fibrillation (AF). To date, serum and EDTA matrices are standardized for the GDF-15 assay but it is unclear if it can be measured also in citrate. In this study, we aim to investigate if the Elecsys GDF-15 assay (Roche Diagnostics, Mannheim, Germany) can be determined accurately in citrate samples in a cohort of 10 patients with AF and 10 healthy controls. From January 2018 to March 2018, we included healthy controls and patients with AF under vitamin K antagonists in a tertiary hospital. Blood samples were drawn in both groups. We included 10 controls (50% males, mean age 36.4±8.9 years) and 10 patients with AF (80% males, mean age 76.5±16.6 years). The mean GDF-15 levels were increased in patients with AF in comparison to healthy controls, as expected by the presence of a heart-related condition and the higher age of this population. In healthy controls, GDF-15 levels showed an optimal correlation between EDTA-serum (r=0.975; p<0.001), EDTA-citrate (r=0.972; p<0.001), and serum-citrate (r=0.997; p<0.001) samples. This was also observed in patients with AF: EDTA-serum (r=0.975; p<0.001), serum-citrate (r=0.835; p=0.003), and EDTA-citrate (r=0.768; p=0.009). Our results demonstrate that citrate samples may be used for the determination of GDF-15 in AF given the positive and good correlation with EDTA and serum matrices. Further studies should validate these observations.