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 < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I. CONCLUSION: 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.

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.

Prognostic performance of pancreatic stone protein in critically ill patients with sepsis.

Aim: To assess the prognostic value for 28-day mortality of PSP in critically ill patients with sepsis. Material & methods: 122 consecutive patients with sepsis were enrolled in this study. Blood samples were collected on admission and day 2. Results: On admission, the combination of PSP and lactate achieved an area under the receiver operating characteristic (AUC-ROC) of 0.796, similar to sequential organ failure assessment score alone (AUC-ROC: 0.826). On day 2, PSP was the biomarker with the highest performance (AUC-ROC: 0.844), although lower (p = 0.041) than sequential organ failure assessment score (AUC-ROC: 0.923). Conclusion: The combination of PSP and lactate and PSP alone, on day 2, have a good performance for prognosis of 28-day mortality and could help to identify patients who may benefit most from tailored intensive care unit management.

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department.

INTRODUCTION: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. MATERIALS AND METHODS: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. RESULTS: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. CONCLUSION: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia.

Analyzing the capability of PSP, PCT and sCD25 to support the diagnosis of infection in cancer patients with febrile neutropenia.

Background Early diagnosis of infection is essential for the initial management of cancer patients with chemotherapy-associated febrile neutropenia (FN). In this study, we have evaluated two emerging infection biomarkers, pancreatic stone protein (PSP) and soluble receptor of interleukin 2, known as soluble cluster of differentiation 25 (sCD25), for the detection of an infectious cause in FN, in comparison with other commonly used infection biomarkers, such as procalcitonin (PCT). Methods A total of 105 cancer patients presenting to the emergency department were prospectively enrolled. We observed 114 episodes of chemotherapy-associated FN. At presentation, a blood sample was collected for the measurement of PCT, PSP and sCD25. In order to evaluate the discriminatory ability of these markers for the diagnosis of infection, the area under the curve (AUC) of the receiver operating characteristic curves was calculated. Results Infection was documented in 59 FN episodes. PCT, PSP and sCD25 levels were significantly higher in infected patients. PCT was the biomarker with the highest diagnostic accuracy for infection (AUC: 0.901), whereas PSP and sCD25 showed a similar performance, with AUCs of 0.751 and 0.730, respectively. In a multivariable analysis, PCT and sCD25 were shown to be independently associated with infection. Conclusions Two novel biomarkers, PSP and sCD25, correlated with infection in cancer patients with chemotherapy-associated FN, but neither PSP nor sCD25 improved the performance of PCT. Based on the results obtained, the introduction of these novel biomarkers as a tool for the diagnosis of infection in this patient group is not recommended.

Identificación de líquidos biológicos de origen desconocido / Identification of body fluids of unknown origin

Los laboratorios clínicos son frecuentemente requeridos para la identificación de líquidos corporales de los que se desconoce su origen. La información bibliográfica con respecto a la identificación de líquidos biológicos de procedencia incierta es escasa. El objetivo de este documento es actualizar los conocimientos sobre aquellos constituyentes útiles como marcadores para la identificación y diferenciación de estos líquidos. Se abordan aspectos como la identificación de una punción lumbar traumática o de líquido cefalorraquídeo en fístulas, la identificación de un derrame quiloso o pseudoquiloso, de secreción biliar, pancreática, gastroesofágica o de orina en las cavidades serosas así como del líquido amniótico

Clinical laboratories are regularly requested to analyze unusual body fluids of unknown origin. There is little in the literature about the identification of body fluids of uncertain origin. The purpose of this document is to perform an updated review on those constituents that may be useful as markers for identifying and diferentiating these unusual fluids. A review is presented on aspects such as the identification of a traumatic lumbar puncture or a cerebrospinal fluid leakage, the identification of a chylous or pseudochylous effusion, leakage of bile, pancreatic fluid, gastroesophageal fluid, or urine, in the serous cavities, as well as the amniotic fluid

Diagnostic accuracy of lipopolysaccharide-binding protein for sepsis in patients with suspected infection in the emergency department.

Background Biomarkers can facilitate the diagnosis of sepsis, enabling early management and improving outcomes. Lipopolysaccharide-binding protein (LBP) has been reported as a biomarker for the detection of infection, but its diagnostic value is controversial. In this study, we assessed the diagnostic accuracy of LBP for sepsis in the emergency department (ED) patients, comparing it with more established biomarkers of sepsis, including procalcitonin (PCT) and C-reactive protein (CRP). Methods LBP and other sepsis biomarkers, including PCT and CRP, were measured on admission in 102 adult patients presenting with suspected infection . Classification of patients was performed using the recently updated definition for sepsis (Sepsis-3). The diagnostic accuracy of LBP, CRP and PCT for sepsis was evaluated by using receiver operating characteristic curve (ROC) analysis. Results A total of 49 patients were classified as having sepsis. In these patients, median (interquartile range) LBP (41.8 [41.1] µg/dL vs. 26.2 [25] µg/dL), CRP (240 [205] mg/L vs. 160 [148] mg/dL) and PCT (5.19 [13.68] µg/L vs. 0.39 [1.09] µg/L) were significantly higher than in patients classified as not having sepsis ( P < 0.001 for all three biomarkers). ROC curve analysis and area under curve (AUC) revealed a value of 0.701 for LBP, similar to CRP (0.707) and lower than that for PCT (0.844) ( P = 0.012). Conclusion In adult ED patients with suspected infection, the diagnostic accuracy for sepsis of LBP is similar to that of CRP but lower than that of PCT.

Biomarcadores empleados en sepsis / Sepsis biomarkers: A review

Las enfermedades infecciosas, como la sepsis, constituyen un grave problema de salud en el mundo, asociándose con una elevada morbilidad y mortalidad en todos los ámbitos de la asistencia sanitaria. Se trata de enfermedades tiempo dependientes en las que la aplicación precoz de una serie de medidas diagnostico terapéuticas mejoran de forma significativa la supervivencia y el pronóstico del paciente. Para ello se disponen de herramientas como los biomarcadores que nos ayudan tanto en el diagnóstico como pronóstico de estas patologías; biomarcadores clásicos y ampliamente utilizados como la PCR, procalcitonina o citocinas y otros menos conocidos como presepsina, pro-adrenomedulina (pro-ADM), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen activator receptor (suPAR), Pancreatic Stone Protein (PSP) o sCD25 (AU)

Infectious diseases, such as sepsis, are a serious health problem in the world, associated with high morbidity and mortality in all areas of health care. These are time dependent diseases in which the early application of diagnostic therapeutic actions, significantly improve patient survival and prognosis. To carry out this, we have tools such as biomarkers that help us in the diagnosis and prognosis of these pathologies; There are biomarkers widely used such as PCR, Procalcitonin or cytokines, and others that are less known as pro-adrenomedullin (pro-ADM), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen activator receptor (SuPAR), Pancreatic Stone Protein (PSP) or sCD25 (AU)

Pancreatic stone protein and soluble CD25 for infection and sepsis in an emergency department.

BACKGROUND: Infection is a common problem in emergency departments (EDs) and is associated with high mortality, morbidity and costs. Identifying infection in ED patients can be challenging. Biomarkers can facilitate its diagnosis, enabling an early management and improving outcomes. In the critical care setting, two emerging biomarkers, pancreatic stone protein (PSP) and soluble CD25 (sCD25), have demonstrated to be useful for diagnosis of sepsis. We aimed to assess the diagnostic value of these biomarkers, in comparison with procalcitonin (PCT), for infection and sepsis in an ED population with suspected infection. MATERIALS AND METHODS: Through a prospective, observational study, we investigated the utility of serum PCT, PSP and sCD25 levels, measured on admission, for diagnosis of infection and sepsis, defined according to the recently updated for sepsis (Sepsis-3), in patients presenting to the ED for suspected infection. Diagnostic accuracy was evaluated by using receiver operating characteristic curves (ROC) analysis. RESULTS: Of the 152 patients enrolled in this study, 129 had a final diagnosis of infection, including 82 with noncomplicated infection and 47 with sepsis. Median PCT, PSP and sCD25 levels were significantly higher in patients with infection and sepsis. The ROC curve analysis revealed a similar diagnostic accuracy for infection (ROC area under the curve (AUC) PCT: 0·904; sCD25: 0·869 and PSP: 0·839) and for sepsis (ROC AUC: PCT: 0·820; sCD25: 0·835 and PSP: 0·872). CONCLUSIONS: Pancreatic stone protein and sCD25 perform well as infection and sepsis biomarkers, with a similar performance than PCT, in ED patients with suspected infection. Further larger studies investigating use of PSP and sCD25 are needed.

Magnitudes biológicas que tiene interés medir de modo urgente / Biological markers in emergency laboratory

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Value of lipopolysaccharide binding protein as diagnostic marker of infection in adult cancer patients with febrile neutropenia: comparison with C-reactive protein, procalcitonin, and interleukin 6.

PURPOSE: Early detection of infection is essential for initial management of cancer patients with chemotherapy-associated febrile neutropenia in the emergency department. In this study, we evaluated lipopolysaccharide binding protein (LBP) as predictor for infection in febrile neutropenia and compared with other biomarkers previously studied: C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. METHODS: A total of 61 episodes of chemotherapy-associated febrile neutropenia in 58 adult cancer patients were included. Serum samples were collected on admission at emergency department and CRP, LBP, PCT, and IL-6 were measured. Patients were classified into fever of unknown origin and infection, including microbiologically and clinically documented infection, groups. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker for the diagnosis of infection. RESULTS: Thirty-two of the 61 episodes were classified as infection. On admission, CRP, PCT, IL-6, and LBP were significantly increased in patients with infection compared to fever of unknown origin group. Area under the ROC curve (AUC ROC) of CRP, PCT, IL-6, and LBP for discriminating both groups was 0.77, 0.88, 0.82, and 0.82, respectively, without significant difference between them. The combination of IL-6 and PCT or LBP did not lead to a significant improvement of the diagnostic accuracy of PCT or LBP alone. CONCLUSIONS: On admission, LBP has a similar diagnostic accuracy than PCT or IL-6 for the diagnosis of infection and might be used as additional diagnostic tool in adult cancer patients with chemotherapy-associated febrile neutropenia.

The value of lipopolysaccharide binding protein for diagnosis of late-onset neonatal sepsis in very low birth weight infants.

OBJECTIVE: To assess the accuracy of lipopolysaccharide binding protein (LBP) for diagnosing late-onset neonatal sepsis (LONS) in very low birth weight (VLBW) infants. STUDY DESIGN: Observational, prospective study. We assessed the diagnostic performance of LBP in 26 suspected LONS episodes among 54 patients. Proven and probable LONS episodes were recorded according to established criteria. Receiver operating characteristic curve analysis was performed to evaluate LBP's ability to predict LONS. RESULTS: LONS was diagnosed in 17 of 26 episodes. LBP levels were significantly higher in confirmed LONS episodes (P<0.001). The area under the curve of LBP was 0.89. A cut-off of 17.5 µg/mL had a sensitivity of 94.1%, a specificity of 77.8%, a positive predictive value of 88.9% and a negative predictive value of 87.5%. CONCLUSIONS: Serum LBP measurement may be useful as an additional tool in the evaluation of suspected LONS in VLBW infants.

Utilidad de la procalcitonina para predecir bacteriemia en pacientes oncológicos con fiebre / Usefulness of procalcitonin for predicting bacteremia in cancer patients with fever

Introducción. La bacteriemia es una de las principales causas de morbimortalidad en el paciente con cáncer. El objetivo de este estudio es evaluar la utilidad de la procalcitonina como marcador predictor de bacteriemia en pacientes oncológicos y oncohematológicos que acudieron al Servicio de Urgencias de nuestro hospital. Material y métodos. Se incluyeron en el estudio 152 episodios de fiebre en 134 pacientes adultos oncológicos. Al ingreso en el Servicio de Urgencias una muestra de sangre fue extraída para la medida de proteína C reactiva (PCR) y procalcitonina (PCT). Los episodios febriles se clasificaron en dos grupos en función de los resultados del hemocultivo: bacteriémicos (n = 22) y no bacteriémicos (n = 130). El rendimiento diagnóstico de los biomarcadores como predictores de bacteriemia fue calculado mediante el análisis del área bajo la curva Receiver Operating Characteristic. Resultados. Las concentraciones de PCT y PCR fueron significativamente más altas en los episodios febriles con bacteriemia que en los no bacteriémicos. La PCT presentó un rendimiento diagnóstico más alto que la PCR como predictor de bacteriemia (área bajo la curva Receiver Operating Characteristic: PCT 0,781 (IC 95%: 0,667 - 0,895) vs. PCR: 0,632 (IC 95%: 0,493 - 0,771); p = 0,02). Un punto de corte de 0,20 ng/mL presentó un valor predictivo negativo de 95,8% para descartar bacteriemia. Conclusión. En el Servicio de Urgencias, la medida de PCT en pacientes oncológicos con fiebre es una herramienta útil para descartar bacteriemia y puede contribuir a la toma inicial de decisiones terapéuticas y a racionalizar la solicitud del hemocultivo (AU)

Aim. Bacteraemia is one of the most important causes of morbidity and mortality in cancer patients. The aim of this study was to evaluate the usefulness of procalcitonin for predicting bacteraemia in febrile oncology and oncohaematology patients admitted to the Emergency Department of our hospital. Material and methods. The study included a total of 152 febrile episodes in 134 adult cancer patients. A blood sample was collected on admission to the Emergency Department to measure C-reactive protein (CRP) and procalcitonin (PCT). Febrile episodes were classified into two groups according to the blood culture results: bacteraemia episodes (n = 22) and non-bacteraemia episodes (n = 130). Receiver Operating Characteristic curve analysis was performed for each biomarker as a predictor of bacteraemia. Results. PCT and CRP levels were significantly higher in the bacteraemia episodes group when compared with non-bacteraemia episodes group. PCT showed a diagnostic accuracy higher than CRP for predicting bacteraemia (AUC Receiver Operating Characteristic: PCT 0,781 (95% CI: 0,667 - 0,895) vs. CRP: 0,632 (95% CI: 0,493 - 0,771); p = 0,02). A cut-off value of 0,20 ng/mL was associated with a negative predictive value of 95,8% to rule-out bacteraemia. Conclusion. PCT measurement in febrile cancer patients in the Emergency Department is a useful tool to rule-out bacteraemia, and may contribute in initial therapeutic decision making and rationalise the request for blood culture (AU)