CA 15-3 prognostic biomarker in SARS-CoV-2 pneumonia.

The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p < 0.001), who required intensive medical support (n = 78, 14.4%; 31.17 ± 27.83 vs. 18.68 ± 11.83; p < 0.001), and who were discharged with supplemental oxygen (n = 64, 13.3%; 22.65 ± 14.41 vs. 18.2 ± 11.7; p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22-11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37-15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.S

Utilidad de los biomarcadores en la evaluación no invasiva de la fibrosis hepática en pacientes con hepatitis crónica C y de la enfermedad de hígado graso no alcohólico en pacientes obesos

El objetivo general es evaluar la utilidad clínica de los biomarcadores ácido hialurónico (HA), péptido aminoterminal del procolágeno tipo III (PIIINP) e inhibidor tisular de la metaloproteasa-1 (TIMP-1), de forma individual y combinados mediante el algoritmo ELF, en la evaluación de la fibrosis hepática en pacientes con Hepatitis Crónica C y de la Enfermedad de Hígado Graso no Alcohólico (EHGNA) en pacientes obesos sometidos a cirugía bariátrica respectivamente. La presente tesis doctoral comprende un estudio observacional transversal que incluye dos grupos de pacientes, uno compuesto por 107 sujetos diagnosticados de hepatitis crónica C y otro formado por 57 pacientes obesos con sospecha de EHGNA sometidos a cirugía bariátrica. Los parámetros de estudio comprendieron variables clínicas, parámetros derivados del estudio radiodiagnóstico y variables de laboratorio. En ambos grupos de pacientes se evaluaron los biomarcadores directos de fibrosis HA, PIIINP y TIMP-1 y el algoritmo ELF. Se determinaron sus valores séricos en la población global y en los subgrupos de pacientes, así como su asociación con diferentes variables clínicas, del estudio radiodiagnóstico y con otras variables de laboratorio. Como estándar de referencia se utilizó la técnica Arfi en los pacientes con hepatitis crónica C y la biopsia hepática en los pacientes obesos. Las principales conclusiones obtenidas fueron: Pacientes con Hepatitis Crónica C 1- Los valores del algoritmo ELF y de los biomarcadores directos HA, PIIINP y TIMP-1 fueron más altos en los pacientes con fibrosis significativa y en aquellos que presentaban signos ecográficos de hepatopatía crónica. 2- El HA y el ELF demostraron su eficacia clínica en la identificación de fibrosis significativa y aportaron los mejores resultados de entre todas las variables estudiadas. Por otro lado, el TIMP-1 y el ELF demostraron ser las variables más eficaces en la identificación de cirrosis. 3- La combinación del algoritmo ELF con variables clínicas y biomarcadores indirectos supone una opción válida y más eficaz que cualquiera de las variables de manera individual en la identificación de fibrosis significativa. En la identificación de cirrosis hepática, la opción más eficaz es la combinación del algoritmo ELF, con variables clínicas, biomarcadores indirectos y signos ecográficos de hepatopatía crónica. La utilización de estos algoritmos resultaría muy conveniente en la evaluación del grado de fibrosis hepática en pacientes con hepatopatía crónica por VHC. Pacientes Obesos con sospecha de EHGNA 1- Los valores encontrados del algoritmo ELF y del biomarcador HA fueron significativamente más altos en el grupo de pacientes que presentaron en la biopsia, además de esteatosis, infiltrados inflamatorios, balonización hepatocitaria, hiallina de mallory o fibrosis, así como en los pacientes hipertensos. Por otro lado, los pacientes afectos de síndrome metabólico presentaron mayores valores de ELF. 2- El biomarcador HA, los algoritmos ELF y Fibrometer, y la velocidad de onda de corte demostraron su eficacia clínica en la evaluación de la hepatopatía crónica de la población de estudio. El algoritmo ELF fue, de entre estas, la variable que presentó una mejor relación sensibilidad-especificidad. 3- La combinación de los biomarcadores directos de fibrosis y la técnica Arfi representan una opción válida y más eficaz que el uso de biomarcadores o técnicas individuales, para la identificación de pacientes con EHGNA con principios de esteatohepatitis y fibrosis, por lo que su utilización resultaría muy conveniente en la evaluación y estratificación del creciente número de pacientes con sospecha de esta enfermedad. PhD Thesis: UTILITY OF BIOMARKERS IN NON-INVASIVE ASSESSMENT OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C AND OF NONALCOHOLIC FATTY LIVER DISEASE IN OBESE PATIENTS The overall objective is to evaluate the clinical utility of biomarkers hyaluronic acid (HA), aminoterminal peptide of procollagen type III (PIIINP) and tissue inhibitor of metalloproteinase-1 (TIMP-1), individually and combined by the algorithm ELF, in the assessment of liver fibrosis in patients with chronic hepatitis C and nonalcoholic fatty liver disease (NAFLD) in obese patients undergoing bariatric surgery respectively. This thesis comprises a cross-sectional observational study involving two groups of patients, one composed of 107 patients diagnosed with chronic hepatitis C and another group of 57 obese patients with suspected NAFLD underwent bariatric surgery. Study parameters understood clinical variables, parameters derived from the radiology study and laboratory variables. In both groups of patients, direct fibrosis biomarkers HA, PIIINP and TIMP-1, and ELF algorithm were evaluated. Serum concentrations were determined in the overall population and in subgroups of patients, and also their association with different clinical variables, radiology study and other laboratory variables. As reference standard, the Arfi technique was used in patients with chronic hepatitis C and liver biopsy in obese patients. The main conclusions were: Patients with Chronic Hepatitis C: 1- The values of ELF algorithm and direct biomarkers HA, PIIINP, and TIMP-1 were higher in patients with significant fibrosis and in those who had ultrasound signs of chronic liver disease. 2- HA and ELF demonstrated clinical efficacy in identifying significant fibrosis and provided the best results of all variables studied. Furthermore, TIMP-1 and ELF proved the most effective variables in identifying cirrhosis. 3- Combination of ELF algorithm with clinical variables and indirect biomarkers is a valid and more effective option than either variable individually in identifying significant fibrosis. In identifying hepatic cirrhosis, the most effective option is the combination of ELF algorithm with clinical variables, indirect biomarkers and s ultrasound signs of chronic liver disease. The use of these algorithms would be very convenient in assessing the degree of hepatic fibrosis in patients with chronic hepatitis C. Obese patients with suspected NAFLD 1- The values of ELF and HA were significantly higher in the group of patients who had in biopsy, in addition to steatosis, inflammatory infiltration, hepatocyte ballooning, Mallory´s bodys or fibrosis, and in hypertensive patients. On the other hand, patients with metabolic syndrome had higher values of ELF. 2- HA biomarker, ELF and Fibrometer algorithms and shear wave velocity showed clinical efficacy in the evaluation of chronic liver disease in the study population. ELF algorithm was, among these, the variable that showed a better combination of sensitivity and specificity. 3- The combination of direct fibrosis biomarkers and Arfi technique represent a valid option and more effective than the use of single biomarkers or techniques for identifying patients with NAFLD and early steatohepatitis or fibrosis, so that its use would be very convenient in the evaluation and stratification of the increasing number of patients with suspected disease

Value of increased soluble suppressor tumorigenicity biomarker 2 (sST2) on admission as an indicator of severity in patients with COVID-19.

BACKGROUND Soluble suppressor of tumorigenicity-2 (sST2) is a biomarker for heart failure and pulmonary injury. We hypothesize that sST2 could help predict severity of SARS-CoV-2 infections. METHODS sST2 was analyzed in patients consecutively admitted for SARS-CoV-2 pneumonia. Other prognostic markers were also measured. In-hospital complications were registered, including death, ICU admission, and respiratory support requirements. RESULTS 495 patients were studied (53% male, age: 57.6±17.6). At admission, median sST2 concentrations was 48.5ng/mL [IQR, 30.6-83.1ng/mL] and correlated with male gender, older age, comorbidities, other severity biomarkers, and respiratory support requirements. sST2 levels were higher in patients who died (n=45, 9.1%) (45.6 [28.0, 75.9]ng/mL vs. 144 [82.6, 319] ng/mL, p210ng/mL were a strong predictor of complicated in-hospital courses, with higher risk of death (OR, 39.3, CI95% 15.9, 103) and death/ICU (OR 38.3, CI95% 16.3-97.5) after adjusting for all other risk factors. The addition of sST2 enhanced the predictive capacity of mortality risk models. CONCLUSIONS sST2 represents a robust severity predictor in COVID-19 and could be an important tool for identifying at-risk patients who may benefit from closer follow-up and specific therapies.S

In Vitro Hemocompatibility and Genotoxicity Evaluation of Dual-Labeled [99mTc]Tc-FITC-Silk Fibroin Nanoparticles for Biomedical Applications

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (&sim;95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo

In Vitro Hemocompatibility and Genotoxicity Evaluation of Dual-Labeled [^99mTc]Tc-FITC-Silk Fibroin Nanoparticles for Biomedical Applications

Nuclear imaging is a highly sensitive and noninvasive imaging technique that has become essential for medical diagnosis. The use of radiolabeled nanomaterials capable of acting as imaging probes has shown rapid development in recent years as a powerful, highly sensitive, and noninvasive tool. In addition, quantitative single-photon emission computed tomography (SPECT) images performed by incorporating radioisotopes into nanoparticles (NPs) might improve the evaluation and the validation of potential clinical treatments. In this work, we present a direct method for [99mTc]Tc-radiolabeling of FITC-tagged silk fibroin nanoparticles (SFN). NPs were characterized by means of dynamic light scattering and scanning electron microscopy. In vitro studies were carried out, including the evaluation of stability in biological media and the evaluation of hemocompatibility and genotoxicity using the cytokinesis block micronucleus (CBMN) assay. The radiolabeling method was reproducible and robust with high radiolabeling efficiency (∼95%) and high stability in biological media. Hydrodynamic properties of the radiolabeled NPs remain stable after dual labeling. The interaction of SFN with blood elicits a mild host response, as expected. Furthermore, CBMN assay did not show genotoxicity induced by [99mTc]Tc-FITC-SFN under the described conditions. In conclusion, a feasible and robust dual-labeling method has been developed whose applicability has been demonstrated in vitro, showing its value for further investigations of silk fibroin NPs biodistribution in vivo

Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study).

Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p

Characteristics and laboratory findings on admission to the emergency department among 2873 hospitalized patients with COVID-19: the impact of adjusted laboratory tests in multicenter studies. A multicenter study in Spain (BIOCOVID-Spain study).

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome

Cardiac troponin and COVID-19 severity: Results from BIOCOVID study.

Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P  In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19