Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke / Rendimiento pronóstico de la razón neutrófilos/linfocitos y la razón plaquetas/linfocitos para la mortalidad en pacientes con ictus agudo

Objective: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. Design: Retrospective cohort study. Setting: Tertiary care hospital. Patients: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. Interventions: None. Main variables of interests: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. Results: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65–0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77–8.85) after adjusting for confounders. Conclusion: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients’ risk and to consider timely alternative care and management.(AU)

Objetivo: Evaluar el desempeño pronóstico de la relación neutrófilos-linfocitos (NLR) y la relación plaquetas-linfocitos (PLR) para la mortalidad en pacientes con stroke agudo tratados en un hospital peruano. Diseño: Estudio de cohorte retrospectivo. Ámbito: Hospital de atención terciaria. Participantes: Pacientes ≥18 años con diagnóstico de stroke agudo e ingresados en el hospital entre mayo de 2019 y junio de 2021. Intervenciones: Ninguna. Variables de interés principales: Razón neutrófilos/linfocitos, razón plaquetas/linfocitos y mortalidad. Resultados: Se incluyeron un total de 165 pacientes. La edad media fue de 66,1±14,2 años, y el 59,4% eran varones. Sólo el NLR tuvo un rendimiento superior a 0,7 (AUC: 0,75; IC95%: 0,65-0,85), y sus niveles elevados se asociaron con un mayor riesgo de mortalidad (RRa: 3,66; IC95%: 1,77-8,85) tras ajustar por factores de confusión. Conclusiones: La razón neutrófilos/linfocitos tiene un rendimiento pronóstico aceptable para la mortalidad en pacientes con stroke. Su uso puede ser considerado para estratificar el riesgo de los pacientes y considerar oportunamente cuidados y manejo alternativos.(AU)

Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke.

OBJECTIVE: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. INTERVENTIONS: None. MAIN VARIABLES OF INTERESTS: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. RESULTS: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65-0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77-8.85) after adjusting for confounders. CONCLUSION: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients' risk and to consider timely alternative care and management.

Exploring the impact of pharmacogenetics on personalized medicine: A systematic review.

INTRODUCTION: Pharmacogenetics evaluates how genetic variations influence drug responses. Nowadays, genetic tests have advanced, becoming more affordable, and its integration is supported by stronger clinical evidence. Guidelines such as those from CPIC (Clinical Pharmacogenetics Implementation Consortium) and resources like PharmGKB facilitate genotype-based prescribing; and organizations like the FDA promote genetic testing before initiating certain medications. Preventive pharmacogenetic panels seem promising, but further research on biomarkers and diverse populations is needed. The aim of this review is to analyze recent evidence on the genotype-drug response relationship to examine how the genetic profile of patients influences the clinical response to treatments, and analyze the areas of research that need further study to advance towards a genetic-based precision medicine. MATERIALS AND METHODS: A systematic search was conducted on PubMed to identify articles investigating the genotype-drug response relationship. The search strategy included terms such as "pharmacogenetics", "personalized treatment", "precision medicine", "dose adjustment", "individualizing dosing", "clinical routine", and "clinical practice." Clinical trials, observational studies, and meta-analyses published in English or Spanish between 2013 and 2023 were included. The initial search resulted in a total of 136 articles for analysis. RESULTS: 49 articles were included for the final analysis following review by 2 investigators. A relationship between genetic polymorphisms and drug response or toxicity was found for drugs such as opioids, GLP-1 agonists, tacrolimus, oral anticoagulants, antineoplastics, atypical antipsychotics, efavirenz, clopidogrel, lamotrigine, anti-TNFα agents, voriconazole, antidepressants, or statins. However, for drugs like metformin, quetiapine, irinotecan, bisoprolol, and anti-VEGF agents, no statistically significant association between genotype and response was found. CONCLUSION: The studies analyzed in this review suggest a strong correlation between genetic variability and individual drug responses, supporting the use of pharmacogenetics for treatment optimization. However, for certain drugs like metformin or quetiapine, the influence of genotype on their response remains unclear. More studies with larger sample sizes, greater ethnic diversity, and consideration of non-genetic factors are needed. The lack of standardization in analysis methods and accessibility to genetic testing are significant challenges in this field. As a conclusion, pharmacogenetics shows immense potential in personalized medicine, but further research is required.

Usefulness of combining inflammatory biomarkers and clinical scales in an emergency department to stratify risk in patients with infections. / Utilidad de la combinación de biomarcadores de respuesta inflamatoria y escalas clínicas para la estratificación del riesgo en pacientes atendidos en urgencias por sospecha de infección.

OBJECTIVES: To determine whether combining biomarkers of inflammatory response and clinical scales can improve risk stratification of patients with suspected infection in a hospital emergency department (ED). MATERIAL AND METHODS: Prospective observational study of ED patients treated for infections. We collected the following information on arrival: demographic and baseline clinical data, comorbidities, the focus of infection, and values for the following inflammatory biomarkers: leukocyte counts, and C-reactive protein, procalcitonin, and midregional proadrenomedullin (MR-proADM) concentrations. Scores on the following clinical scales were recorded based on the variables gathered: the SIRS (Systemic Inflammatory Response Syndrome) criteria, the qSOFA (Quick Sequential Organ Failure Assessment), and the NEWS (National Early Warning Score). The main outcome was a composite measure that included 30-day death or need for intensive care unit (ICU) admission. RESULTS: A total of 473 patients with a mean (SD) age of 70.3 (19.2) years were included. The majority were men (257, 54.3%). Thirty-one (6.6%) died within 30 days and 16 (3.4%) were admitted to the ICU. The composite outcome (death or ICU admission) occurred in 45 patients (9.5%). The MR-proADM concentration, with an area under the receiver operating characteristic curve of 0.739 (95% CI, 0671-0.809) was a better predictor than the other biomarkers or clinical scales, although the differences between MR-proADM and either lactate concentration or the NEWS were not significant in the comparisons (P = .064). Combining the MR-proADM concentration with any of the scales did not significantly improve risk prediction. CONCLUSION: Risk stratification of patients with infection is a key part of ED decision-making. MR-proADM concentration is superior to other biomarkers and clinical prediction scales for predicting short-term prognosis in the ED. Combining MR-proADM measurement with other scales or measures does not improve the yield.

OBJETIVO: Investigar si la combinación de biomarcadores de respuesta inflamatoria (BMRI) y escalas clínicas mejora la estratificación pronóstica de pacientes atendidos en servicios de urgencias hospitalarios (SUH) por sospecha de infección. METODO: Estudio analítico, observacional y prospectivo que incluyó pacientes con sospecha de infección atendidos en un SUH. Se recogieron variables demográficas, comorbilidades, datos clínicos a la llegada al SUH, foco de infección y los siguientes BMRI: leucocitos, proteína C reactiva, procalcitonina, lactato y región medial de la proadrenomodulina (MR-proADM). Se calcularon los valores de las escalas SIRS (síndrome de respuesta inflamatoria sistémica), qSOFA (quick Sequential Organ Failure Assessment) y NEWS (National Early Warning Score). La variable de resultado principal fue una compuesta que incluía mortalidad a 30 días o necesidad de ingreso en la unidad de cuidados intensivos (UCI). RESULTADOS: Se incluyeron 473 pacientes, con una edad media de 70 (DE 19) años y el 54,3% (257). Hubo 31 fallecimientos (6,6%) y 16 (3,4%) ingresos en UCI. La variable de resultado se produjo en 45 (9,5%) pacientes. La MR-proADM mostró la mejor área bajo la curva de la característica operativa del receptor (ABC-COR) en comparación con el resto de biomarcadores y escalas clínicas [0,739 (IC 95% 0,671-0,809)], aunque sin diferencias respecto a lactato (p = 0,144) ni a la escala NEWS (p = 0,064). Al combinar MR-proADM con los diferentes biomarcadores y escalas clínicas, no se obtuvo ninguna combinación que mejore significativamente la precisión pronóstica individual del MR-proADM. CONCLUSIONES: La estratificación del riesgo de los pacientes con infección es una cuestión clave para la toma de decisiones en los SUH. La determinación de MR-proADM supera a otros BMRI y escalas clínicas para la estratificación pronóstica de los pacientes a corto plazo en los SUH. La combinación con otros biomarcadores o escalas clínicas no mejora su capacidad pronóstica.

Usefulness of extended inflammatory parameters related to neutrophil activation reported by Sysmex XN-1000 hematology analyzer for predicting complicated acute appendicitis. Comparison with canonical inflammatory laboratory tests.

AIM: Accurate diagnosis of complicated appendicitis is of importance to ensure that patients receive early and effective treatment, minimizing the risk of postoperative complications to promote successful recovery. Biochemical markers are a promising tool to identify complicated appendicitis. We aimed to evaluate the potential role of novel parameters related with neutrophil activation, known as "Extended Inflammation Parameters" (EIP), included in blood cell count reported by Sysmex XN-Series analyzers, compared to other canonical biomarkers in identifying complicated appendicitis. METHOD: Prospective observational study including patients with confirmed diagnosis of acute appendicitis. C-reactive protein (CRP), procalcitonin, cell blood count, including white blood cell (WBC), absolute neutrophil (ANC) and immature granulocyte (IG) count and EIP (neutrophil reactivity [NEUT-RI] and granularity intensity [NEUT-GI]) were analyzed before surgery. Their accuracy to diagnose complicated appendicitis was tested in an ROC curve analysis. RESULTS: Our population study included 119 patients, and appendicitis was complicated in 58 (48.7%). NLR, CRP and procalcitonin levels, ANC and IG count and NEUT-RI and NEUT-GI were higher in patients with complicated appendicitis. Regarding accuracy for complicated appendicitis, CRP was the biomarker with the highest performance (ROC AUC: 0.829), with an optimal cutoff of 73.1 mg/L (sensitivity: 63.8%, specificity: 88.5%). NEUT-RI and NEUT-GI achieved both significant but poor accuracy, with ROC AUC of 0.606 and 0.637, respectively. CONCLUSIONS: Novel laboratory tests reported by Sysmex XN-Series analyzers have poor accuracy for identifying complicated appendicitis. In this study, CRP was the biomarker with the highest performance and may be useful as predictor of the severity of acute appendicitis.

Utilidad de la combinación de biomarcadores de respuesta inflamatoria y escalas clínicas para la estratificación del riesgo en pacientes atendidos en urgencias por sospecha de infección / Usefulness of combining inflammatory biomarkers and clinical scales in an emergency department to stratify risk in patients with infections

Objetivo. Investigar si la combinación de biomarcadores de respuesta inflamatoria (BMRI) y escalas clínicas mejora la estratificación pronóstica de pacientes atendidos en servicios de urgencias hospitalarios (SUH) por sospecha de infección. Método. Estudio analítico, observacional y prospectivo que incluyó pacientes con sospecha de infección atendidos en un SUH. Se recogieron variables demográficas, comorbilidades, datos clínicos a la llegada al SUH, foco de infección y los siguientes BMRI: leucocitos, proteína C reactiva, procalcitonina, lactato y región medial de la proadrenomodulina (MR-proADM). Se calcularon los valores de las escalas SIRS (síndrome de respuesta inflamatoria sistémica), qSOFA (quick Sequential Organ Failure Assessment) y NEWS (National Early Warning Score). La variable de resultado principal fue una compuesta que incluía mortalidad a 30 días o necesidad de ingreso en la unidad de cuidados intensivos (UCI). Resultados. Se incluyeron 473 pacientes, con una edad media de 70 (DE 19) años y el 54,3% (257). Hubo 31 fallecimientos (6,6%) y 16 (3,4%) ingresos en UCI. La variable de resultado se produjo en 45 (9,5%) pacientes. La MR-proADM mostró la mejor área bajo la curva de la característica operativa del receptor (ABC-COR) en comparación con el resto de biomarcadores y escalas clínicas [0,739 (IC 95% 0,671-0,809)], aunque sin diferencias respecto a lactato (p = 0,144) ni a la escala NEWS (p = 0,064). Al combinar MR-proADM con los diferentes biomarcadores y escalas clínicas, no se obtuvo ninguna combinación que mejore significativamente la precisión pronóstica individual del MR-proADM. Conclusiones. La estratificación del riesgo de los pacientes con infección es una cuestión clave para la toma de decisiones en los SUH. La determinación de MR-proADM supera a otros BMRI y escalas clínicas para la estratificación pronóstica de los pacientes a corto plazo en los SUH... (AU)

Objective. To determine whether combining biomarkers of inflammatory response and clinical scales can improve risk stratification of patients with suspected infection in a hospital emergency department (ED). Methods. Prospective observational study of ED patients treated for infections. We collected the following information on arrival: demographic and baseline clinical data, comorbidities, the focus of infection, and values for the following inflammatory biomarkers: leukocyte counts, and C-reactive protein, procalcitonin, and midregional proadrenomedullin (MR-proADM) concentrations. Scores on the following clinical scales were recorded based on the variables gathered: the SIRS (Systemic Inflammatory Response Syndrome) criteria, the qSOFA (Quick Sequential Organ Failure Assessment), and the NEWS (National Early Warning Score). The main outcome was a composite measure that included 30-day death or need for intensive care unit (ICU) admission. Results. A total of 473 patients with a mean (SD) age of 70.3 (19.2) years were included. The majority were men (257, 54.3%). Thirty-one (6.6%) died within 30 days and 16 (3.4%) were admitted to the ICU. The composite outcome (death or ICU admission) occurred in 45 patients (9.5%). The MR-proADM concentration, with an area under the receiver operating characteristic curve of 0.739 (95% CI, 0671-0.809) was a better predictor than the other biomarkers or clinical scales, although the differences between MR-proADM and either lactate concentration or the NEWS were not significant in the comparisons (P = .064). Combining the MR-proADM concentration with any of the scales did not significantly improve risk prediction. Conclusions. Risk stratification of patients with infection is a key part of ED decision-making. MR-proADM concentration is superior to other biomarkers and clinical prediction scales for predicting short-term prognosis in the ED... (AU)

Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática / Models to predict bacteremia in the emergency department: a systematic review

Objetivo. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). Métodos. Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Prediction Model/Clinical Prediction Rule/Risk Prediction Model”, “Emergencies/Emergency/Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la NewcastleOttawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). Resultados. Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja... (AU)

Objective. Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro’s model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro’s model first appeared. Methods. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). Results. Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality... (AU)

Comparación de biomarcadores inflamatorios plasmáticos en pacientes con SIM-PedS versus infecciones potencialmente graves en pacientes pediátricos / Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients

Introducción: Los biomarcadores inflamatorios se han utilizado para el diagnóstico y tratamiento del síndrome inflamatorio multisistémico en niños (SIM-PedS). Nuestro objetivo fue determinar cómo se comportan estos biomarcadores inflamatorios en pacientes con síndrome febril orientados en principio como infección bacteriana potencialmente grave y comparar los hallazgos clínicos y de laboratorio con los casos SIM-PedS. Métodos: Estudio de cohorte observacional ambispectivo unicéntrico (junio de 2020-febrero de 2022). Analizamos la demografía, los síntomas clínicos y los hallazgos de laboratorio en casos SIM-PedS y en casos de síndrome febril de otras etiologías infecciosas de pacientes menores de 15 años con ingreso hospitalario. Resultados: Incluimos a 54 pacientes con sospecha analítica de infección bacteriana y a 20 pacientes con SIM-PedS para el análisis. La fiebre (100%), los hallazgos gastrointestinales (80%) y mucocutáneos (35%) fueron más frecuentes en los pacientes con SIM-PedS, también la hipotensión (36,8%) y la taquicardia (55%). Los hallazgos de laboratorio mostraron niveles significativamente elevados de pro-BNP (70%), ferritina (35%), dímeros D (80%) así como linfopenia (55%) y trombocitopenia (27,8%) en los casos de SIM-PedS. Los valores de IL-6 fueron elevados en pacientes sin SIM-PedS (92,6%). Conclusiones: En el manejo de pacientes con SIM-PedS, la monitorización dinámica de pro-BNP, ferritina, dímero D, linfocitos y plaquetas podría ser útil para evaluar efectivamente el progreso de la enfermedad en las primeras fases. Los valores de IL-6 pueden elevarse de forma significativa en pacientes con síndrome febril de otras etiologías, así como los dímeros D. El uso de diversos biomarcadores de laboratorio podría ayudar a determinar precozmente la evolución de los pacientes con síndrome febril.(AU)

Background: Inflammatory biomarkers have been used for the diagnosis and management of multisystemic inflammatory syndrome in children (MIS-C). We aimed to compare the clinical and laboratory findings of MIS-C cases versus other febrile cases cataloged as potentially suspected bacterial infection (non-MIS-C). Methods: Unicentric ambispective observational cohort study (June 2020 to February 2022). We analyzed demographics, clinical symptoms and laboratory findings in MIS-C cases and in non-MIS-C cases with febrile processes of patients under 15 years of age admitted to hospital. Results: We enrolled 54 patients with potential suspected bacterial infection and 20 patients with MIS-C for analysis. Fever (100%), gastrointestinal (80%) and mucocutaneous findings (35%) were common in MIS-C patients, also hypotension (36.8%) and tachycardia (55%). Laboratory findings showed significantly elevated proBNP (70%), ferritin (35%), D-dimer (80%) and lymphopenia (55%) and thrombocytopenia (27.8%) in MIS-C cases. IL-6 values were high in non-MIS-C patients (92.6%). Conclusions: In the management of MIS-C patients, the dynamic monitoring of proBNP, ferritin, D-dimer, lymphocytes and platelets could be helpful to pediatricians to effectively evaluate the progress of MIS-C in the early phases, not IL-6 values. The applicability of the IL-6 level as a prognostic biomarker in MIS-C patients may require closer discussion. In addition, the optimal laboratory markers, as stated in our study, can help establish a biomarkers model to early distinguish the MIS-C versus non-MIS-C in patients who are admitted to febrile syndrome.(AU)

Utilidad de la combinación de biomarcadores de respuesta inflamatoria y escalas clínicas para la estratificación del riesgo en pacientes atendidos en urgencias por sospecha de infección / Usefulness of combining inflammatory biomarkers and clinical scales in an emergency department to stratify risk in patients with infections

Objetivo. Investigar si la combinación de biomarcadores de respuesta inflamatoria (BMRI) y escalas clínicas mejora la estratificación pronóstica de pacientes atendidos en servicios de urgencias hospitalarios (SUH) por sospecha de infección. Método. Estudio analítico, observacional y prospectivo que incluyó pacientes con sospecha de infección atendidos en un SUH. Se recogieron variables demográficas, comorbilidades, datos clínicos a la llegada al SUH, foco de infección y los siguientes BMRI: leucocitos, proteína C reactiva, procalcitonina, lactato y región medial de la proadrenomodulina (MR-proADM). Se calcularon los valores de las escalas SIRS (síndrome de respuesta inflamatoria sistémica), qSOFA (quick Sequential Organ Failure Assessment) y NEWS (National Early Warning Score). La variable de resultado principal fue una compuesta que incluía mortalidad a 30 días o necesidad de ingreso en la unidad de cuidados intensivos (UCI). Resultados. Se incluyeron 473 pacientes, con una edad media de 70 (DE 19) años y el 54,3% (257). Hubo 31 fallecimientos (6,6%) y 16 (3,4%) ingresos en UCI. La variable de resultado se produjo en 45 (9,5%) pacientes. La MR-proADM mostró la mejor área bajo la curva de la característica operativa del receptor (ABC-COR) en comparación con el resto de biomarcadores y escalas clínicas [0,739 (IC 95% 0,671-0,809)], aunque sin diferencias respecto a lactato (p = 0,144) ni a la escala NEWS (p = 0,064). Al combinar MR-proADM con los diferentes biomarcadores y escalas clínicas, no se obtuvo ninguna combinación que mejore significativamente la precisión pronóstica individual del MR-proADM. Conclusiones. La estratificación del riesgo de los pacientes con infección es una cuestión clave para la toma de decisiones en los SUH. La determinación de MR-proADM supera a otros BMRI y escalas clínicas para la estratificación pronóstica de los pacientes a corto plazo en los SUH... (AU)

Objective. To determine whether combining biomarkers of inflammatory response and clinical scales can improve risk stratification of patients with suspected infection in a hospital emergency department (ED). Methods. Prospective observational study of ED patients treated for infections. We collected the following information on arrival: demographic and baseline clinical data, comorbidities, the focus of infection, and values for the following inflammatory biomarkers: leukocyte counts, and C-reactive protein, procalcitonin, and midregional proadrenomedullin (MR-proADM) concentrations. Scores on the following clinical scales were recorded based on the variables gathered: the SIRS (Systemic Inflammatory Response Syndrome) criteria, the qSOFA (Quick Sequential Organ Failure Assessment), and the NEWS (National Early Warning Score). The main outcome was a composite measure that included 30-day death or need for intensive care unit (ICU) admission. Results. A total of 473 patients with a mean (SD) age of 70.3 (19.2) years were included. The majority were men (257, 54.3%). Thirty-one (6.6%) died within 30 days and 16 (3.4%) were admitted to the ICU. The composite outcome (death or ICU admission) occurred in 45 patients (9.5%). The MR-proADM concentration, with an area under the receiver operating characteristic curve of 0.739 (95% CI, 0671-0.809) was a better predictor than the other biomarkers or clinical scales, although the differences between MR-proADM and either lactate concentration or the NEWS were not significant in the comparisons (P = .064). Combining the MR-proADM concentration with any of the scales did not significantly improve risk prediction. Conclusions. Risk stratification of patients with infection is a key part of ED decision-making. MR-proADM concentration is superior to other biomarkers and clinical prediction scales for predicting short-term prognosis in the ED... (AU)

Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática / Models to predict bacteremia in the emergency department: a systematic review

Objetivo. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). Métodos. Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Prediction Model/Clinical Prediction Rule/Risk Prediction Model”, “Emergencies/Emergency/Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la NewcastleOttawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). Resultados. Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja... (AU)

Objective. Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro’s model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro’s model first appeared. Methods. We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). Results. Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality... (AU)

Value of the soluble urokinase-type plasminogen activator receptor as a predictor of prognosis in patients attended in hospital emergency departments. / Capacidad del biomarcador suPAR para estratificar el pronóstico en pacientes atendidos en servicios de urgencias hospitalarios.

OBJECTIVES: To determine the value of the soluble urokinase-type plasminogen activator receptor (suPAR) for predicting outcomes in emergency department (ED) patients. Secondary objectives were 1) to measure the predictive value of the usual decision points, 2) to identify patients at low risk for mortality who could be safely discharged from the ED, and 3) to measure the correlation between suPAR and other biomarkers. MATERIAL AND METHODS: Prospective observational cohort study of patients attended in the EDs of participating hospitals. We recorded sociodemographic variables, comorbidity, variables related to the acute episode, prognostic markers commonly used in EDs, and suPAR concentration. Outcome variables were the need for hospital admission during the index episode, ED revisits within 90 days, and 90-day mortality. RESULTS: A total of 990 patients with a median (interquartile range) age of 68 (53-81 years) were studied; 50.8% were men. The median suPAR concentration was 3.8 (2.8-6.0) ng/mL, and 112 patients (11.31%) required admission. At 90 days there were 276 revisits (27.9% of the cohort), and 47 patients (4.74%) had died. Mortality was lower (1%) in patients with suPAR concentrations less than 4 ng/mL (52.5%), and fewer of these patients revisited (24.4%) or required hospitalization (20.6%) than patients with suPAR concentrations higher than 6 ng/mL (mortality, 13.5%; revisits, 39.6%; admissions, 56.3%). A suPAR concentration over 6 ng/mL was associated with 90-day mortality and revisits (adjusted hazard ratios and 95% CIs of 4.61 [1.68-12.67] and 1.59 [1.13-2.10]), respectively. The high suPAR concentration was also associated with hospital admission (odds ratio, 1.62 [0.99-2.62]). CONCLUSION: A suPAR concentration of less than 4 ng/mL identifies patients at low risk of 90-day mortality and revisits or need for hospitalization, whereas a suPAR concentration higher than 6 ng/mL is associated with higher risk for these outcomes.

OBJETIVO: Determinar la capacidad del receptor soluble del activador del plasminógeno tipo uroquinasa (suPAR) para la estratificación pronóstica en pacientes atendidos en servicios de urgencias hospitalarios (SUH). Los objetivos secundarios son: 1) medir la capacidad de los `puntos de decisión habituales, 2) identificar una población de bajo riesgo de mortalidad que puede darse de alta de forma segura desde el SUH, y 3) medir la correlación entre suPAR y otros biomarcadores. METODO: Estudio observacional de cohortes prospectivo de pacientes atendidos en SUH. Se registraron variables sociodemográficas, de comorbilidad, datos del episodio agudo, biomarcadores de uso común en urgencias y suPAR. Las variables de resultado fueron la necesidad de ingreso en el episodio índice, reconsulta al SUH y mortalidad a los 90 días. RESULTADOS: Se incluyeron 990 pacientes, la edad fue de 68 (53-81) años, 50,8% eran hombres, la mediana de suPAR fue de 3,8 (2,8-6,0) ng/ml, 112 pacientes (11,31%) requirieron ingreso. En el seguimiento a 90 días hubo 276 reconsultas (27,9%) y 47 pacientes (4,74%) fallecieron. Los pacientes con suPAR 4 ng/ml (52,5%) tenían menor mortalidad (1%), menor reconsulta (24,4%) y menor necesidad de ingreso hospitalario (20,6%), que pacientes con suPAR 6 ng/ml (mortalidad 13,5%, reconsulta 39,6% e ingreso 56,3%). Un suPAR 6 ng/ml mostró una hazard ratio (IC 95%) ajustada de 4,61 (1,68-12,67) para predecir mortalidad a 90 días y de 1,59 (1,13-2,10) para la reconsulta, y una odds ratio de 1,62 (0,99-2,62) para la necesidad de ingreso hospitalario. CONCLUSIONES: Un valor de suPAR 4 ng/ml identifica pacientes con riesgo bajo de mortalidad a 90 días, de reconsulta y de necesidad de ingreso, mientras que los pacientes con suPAR 6 ng/ml tienen mayor mortalidad, reconsulta y necesidad de ingreso.

Models to predict bacteremia in the emergency department: a systematic review. / Modelos predictivos de bacteriemia en el servicio de urgencias: revisión sistemática.

OBJECTIVES: Blood cultures are ordered in emergency departments for 15% of patients with suspected infection. The diagnostic yield varies from 2% to 20%. Thirty-day mortality in patients with bacteremia is high, doubling or tripling the rate in patients with the same infection but without bacteremia. Thus, finding an effective model to predict bacteremia that is applicable in emergency departments is an important goal. Shapiro's model is the one traditionally used as a reference internationally. The aim of this systematic review was to compare the predictive power of bacteremia risk models published since 2008, when Shapiro's model first appeared. MATERIAL AND METHODS: We followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, searching in the following databases for articles published between January 2008 and May 31, 2023: PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Trip Medical Database, and ClinicalTrials.gov. No language restrictions were specified. The search terms were the following Medical Subject Headings: bacteremia/bacteraemia/blood stream infection, prediction model/clinical prediction rule/risk prediction model, emergencies/emergency/emergency department, and adults. Observational cohort studies analyzing diagnostic yield were included; case-control studies, narrative reviews, and other types of articles were excluded. The Newcastle-Ottawa Scale was used to score quality and risk of bias in the included studies. The results were compared descriptively, without meta-analysis. The protocol was included in the PROSPERO register (CRD42023426327). RESULTS: Twenty studies out of a total of 917 were found to meet the inclusion criteria. The included studies together analyzed 33 182 blood cultures, which detected 5074 cases of bacteremia (15.3%). Eleven studies were of high quality, 7 of moderate quality, and 2 of low quality. The area under the receiver operating characteristic curve (AUC) of Shapiro's model varied from 0.71 to 0.83. Sensitivity was as high as 98%, and specificity ranged from 26% to 69%. Three models with high scores for quality were also supported by both internal and external validation studies: Lee's model (AUC, 0.81; sensitivity 68%; specificity, 81%), the 5MPB-Toledo model (AUC, 0.906 to 0.946), and the MPB-INFURG-SEMES model (AUC, 0.924; sensitivity, 97%; specificity, 76%. CONCLUSION: The 5MPB-Toledo and MPB-INFURG-SEMES are useful for assessing the true risk of bacteremia in patients attended in emergency departments.

OBJETIVO: La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los servicios de urgencias (SU) con una rentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de estos pacientes con bacteriemia es elevada, doble o triple que el resto con el mismo proceso. Así, encontrar un modelo predictivo de bacteriemia eficaz y aplicable en los SU sería muy importante. Clásicamente, el modelo de Shapiro ha sido la referencia en todo el mundo. El objetivo de esta revisión sistemática (RS) es comparar la capacidad para predecir bacteriemia en los SU de los distintos modelos predictivos publicados desde el año 2008 (fecha de publicación del modelo de Shapiro). METODO: Se realiza una RS siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2008 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: "Bacteremia/Bacteraemia/Blood Stream Infection", "Prediction Model/Clinical Prediction Rule/Risk Prediction Model", "Emergencies/Emergency/Emergency Department" y "Adults". Se incluyeron estudios de cohortes observacionales (analíticos de rendimiento diagnóstico). Para valorar la calidad del método empleado y el riesgo de sesgos de los artículos incluidos se utilizó la Newcastle-Ottawa Scale (NOS). No se incluyeron estudios de casos y controles, revisiones narrativas y en otros tipos de artículos. No se realizaron técnicas de metanálisis, pero los resultados se compararon narrativamente. El protocolo de la RS se registró en PROSPERO (CRD42023426327). RESULTADOS: Se identificaron 917 artículos y se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos contienen 33.182 HC procesados con 5.074 bacteriemias (15,3%). Once estudios fueron calificados de calidad alta, 7 moderada y 2 baja. El ABC-COR conseguida por el modelo de Shapiro varía de 0,71 a 0,83, con sensibilidad (Se) hasta del 98%, con especificidad (Es) (26% a 69%). Para los tres modelos que tienen validación interna y externa y una buena calidad metodológica, el modelo de Lee consigue un ABC-COR de 0,81 con Se: 68% y Es: 81%, el modelo 5MPB-Toledo consigue un ABC-COR entre 0,91 y 0,95, y el MPB-INFURG-SEMES obtiene una ABC-COR de 0,92 con una Se: 97% y Es: 76%. CONCLUSIONES: Los modelos 5MPB-Toledo y MPB-INFURG-SEMES representan herramientas útiles para la estratificación del riesgo real de bacteriemia en los pacientes atendidos en los SU.

Carbohydrate antigen 125-guided pre-TAVI medical optimization: impact on quality of life and clinical outcomes.

INTRODUCTION AND OBJECTIVES: Carbohydrate antigen 125 (CA125), a biomarker associated with fluid overload, has proven useful in managing diuretic therapy in heart failure. We aimed to evaluate the impact of diuretic optimization guided by CA125 before transcatheter aortic valve implantation (TAVI) on outcomes. METHODS: This prospective interventional study enrolled patients scheduled for TAVI, in whom baseline CA125 was measured 2 weeks before TAVI. Patients with CA125 ≥ 20 U/mL underwent diuretic up-titration before TAVI. Three groups were included: group I) baseline CA125 <20 U/mL; IIa) CA125 ≥ 20 U/mL that decreased after treatment, and IIb) CA125 ≥ 20 U/mL that did not decrease. The primary outcome was changes in the Kansas City Cardiomyopathy Questionnaire at 3 and 12 months. The secondary endpoint was clinical events. RESULTS: The study included 184 patients (115 group I, 46 IIa, and 23 IIb). Groups I and IIa exhibited early and sustained improvements in the Kansas City Cardiomyopathy Questionnaire (group I: 18.9 points [95%CI, 15.7-22.1; P <.001] at 90 days, and 18.1 [95%CI, 14.9-21.4, P <.001] at 1 year; group IIa: 21.1 points [95%CI, 15.4-26.7; P <.001] and 19.5 [95%CI, 13.9-25.1; P <.001] respectively). In contrast, in group IIb there was no significant improvement at 90 days (P=.12), with improvement being significant only at 1 year (17.8 points, 95%CI, 5.9-29.6; P=.003). Over a median follow-up of 20.7 months, there were 63 (27.83%) deaths or heart failure admissions. Multivariate analysis showed a lower risk of events in group I vs IIb (HR, 0.28; 95%CI, 0.14-0.58; P <.001), and IIa vs IIb (HR, 0.24; 95%CI, 0.11-0.55; P <.001). CONCLUSIONS: Patients with persistently high CA125 despite diuretic therapy pre-TAVI showed slower functional recovery and poorer clinical outcomes after TAVI.

Comparison of plasma inflammatory biomarkers between MIS-C and potentially serious infections in pediatric patients.

BACKGROUND: Inflammatory biomarkers have been used for the diagnosis and management of multisystemic inflammatory syndrome in children (MIS-C). We aimed to compare the clinical and laboratory findings of MIS-C cases versus other febrile cases cataloged as potentially suspected bacterial infection (non-MIS-C). METHODS: Unicentric ambispective observational cohort study (June 2020-February 2022). We analyzed demographics, clinical symptoms and laboratory findings in MIS-C cases and in non-MIS-C cases with febrile processes of patients under 15 years of age admitted to hospital. RESULTS: We enrolled 54 patients with potential suspected bacterial infection and 20 patients with MIS-C for analysis. Fever (100%), gastrointestinal (80%) and mucocutaneous findings (35%) were common in MIS-C patients, also hypotension (36.8%) and tachycardia (55%). Laboratory findings showed significantly elevated proBNP (70%), ferritin (35%), D-dimer (80%) and lymphopenia (55%) and thrombocytopenia (27.8%) in MIS-C cases. IL-6 values were high in non-MIS-C patients (92.6%). CONCLUSIONS: In the management of MIS-C patients, the dynamic monitoring of proBNP, ferritin, D-dimer, lymphocytes and platelets could be helpful to pediatricians to effectively evaluate the progress of MIS-C in the early phases, not IL-6 values. The applicability of the IL-6 level as a prognostic biomarker in MIS-C patients may require closer discussion. In addition, the optimal laboratory markers, as stated in our study, can help establish a biomarkers model to early distinguish the MIS-C versus non-MIS-C in patients who are admitted to febrile syndrome.

Evaluation of serum placenta-specific gene 8 protein, total antioxidant capacity, interleukin-10, interleukin-17A, interleukin-21 and interleukin-33 levels in Turkish women with gestational diabetes mellitus.

PURPOSE: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or is diagnosed during pregnancy. Our study aimed to establish a correlation between proinflammatory and anti-inflammatory response in order to be able to develop treatment strategies and determine early diagnosis biomarkers in the sera of cases diagnosed with GDM. Moreover, we aimed to investigate interleukin (IL), placenta-specific gene 8 protein (PLAC8) and total antioxidant capacity (TAC) in patients with GDM. METHODS: A total of 121 patients were included in the study. These were divided into four patient groups: pregnant and diagnosed with DM (P-GDM, n=30); pregnant and not diagnosed with DM (P-NGDM, n=32); non-pregnant diagnosed with DM (NP-DM, n=29) and non-pregnant and not diagnosed with DM (NPNDM, n=30). IL-10, IL-17A, IL-21, IL-33, PLAC8 and TAC determinations from patients were evaluated by ELISA (Enzyme-Linked ImmunoSorbent Assay) method. RESULTS: IL-10 and IL-33 concentrations were found to be significantly higher in P-GDM and NP-DM patient groups compared to P-NGDM and NP-NDM groups (p<0.001). The PLAC8 level in the P-GDM patient group (20.38±5.37) was determined to be significantly higher than in the P-NGDM patient group (3.41±2.17, p<0.001). TAC in the P-NGDM and NP-NDM groups (12.42±2.31 vs. 12.96±3.78, p<0.001) was determined to be significantly higher than in the P-GDM and NP-DM groups (4.8±0.52 vs. 2.21±0.71, p<0.001). DISCUSSION: The fact that the importance of PLAC8 level and TAC in the diagnosis and follow-up of GDM in pregnancy is demonstrated for the first time in this study shows that it is unique.

Utilidad de los índices celulares y el índice neutrófilo/linfocito derivado en el diagnóstico de la apendicitis aguda pediátrica / Usefulness of cell ratios and the derived neutrophil- to-lymphocyte ratio in the diagnosis of pediatric acute appendicitis

Objetivo: Analizar la precisión de los índices celulares en el diagnóstico de la apendicitis aguda pediátrica, introduciendo uno nuevo, el índice neutrófilo/linfocito derivado (INLd). Material y métodos: Estudio retrospectivo observacional de los pacientes de 0-15 años diagnosticados de apendicitis aguda (AA) y con dolor abdominal no quirúrgico (DA) tratados en nuestro centro entre 2021-2022. Se comparó el índice neutrófilo/linfocito (INL), índice monocito/linfocito (IML), índice plaqueta/linfocito (IPL) y el INLd entre los grupos. Resultados: Se incluyeron 98 casos con AA (30% mujeres, edad 10 ± 3,3 años) y 97 pacientes con DA (53% hombres, edad 9,3 ± 3,7 años). Los valores de INL, IML, IPL e INLd fueron mayores en pacientes con AA respecto a niños con DA: 9,6 rango intercuartil (RIC) 9,5 vs. 3,3 RIC 5,3: p = < 0,0001; 0,7 RIC 0,6 vs. 0,46 RIC 0,7: p = < 0,023; 199,8 RIC 163,9 vs. 134,0 RIC 129,2: p = < 0,0001; y 5,29 RIC 3,9 vs. 2,39 RIC 2,7: p = < 0,0001; respectivamente. La sensibilidad, especificidad, valor predictivo positivo-negativo, área bajo la curva ROC y el punto de corte del INLd para el diagnóstico de AA fue de 70%, 78%, 77-72%, 0,811 y 3,98; respectivamente. Conclusiones. Los índices celulares son parámetros inflamatorios útiles y coste-efectivos que pueden contribuir al diagnóstico de la apendicitis aguda pediátrica. Los resultados de este estudio sugieren que el INLd es el de mayor precisión clínica.(AU)

Objective: To analyze the accuracy of cell ratios in the diagnosis of pediatric acute appendicitis while introducing a new one – the derived neutrophil-to-lymphocyte ratio (dNLR). Materials and methods: An observational, retrospective study of patients aged 0-15 years old diagnosed with acute appendicitis (AA) and with non-surgical abdominal pain (AP) treated in our institution from 2021 to 2022 was carried out. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and dNLR were compared between groups. Results. 98 AA patients (30% of whom were female; age: 10 ± 3.3 years) and 97 AP patients (53% of whom were male; age: 9.3 ± 3.7 years) were included. NLR, MLR, PLR, and dNLR values were higher in AA patients than in AP patients: 9.6 IQR (interquartile range) 9.5 vs. 3.3 IQR 5.3: p < 0.0001; 0.7 IQR 0.6 vs. 0.46 IQR 0.7: p < 0.023; 199.8 IQR 163.9 vs. 134.0 IQR 129.2: p < 0.0001; and 5.29 IQR 3.9 vs. 2.39 IQR 2.7; p < 0.0001, respectively. Sensitivity, specificity, positive-negative predictive value, area under the ROC curve, and dNLR cut-off point for AA diagnosis were 70%, 78%, 77-72%, 0.811, and 3.98, respectively. Conclusions. Cell ratios are useful and cost-effective inflammatory parameters in the diagnosis of pediatric acute appendicitis. The results of this study suggest dNLR has the greatest clinical accuracy.(AU)

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)

Neurodesarrollo a los 2 años en cardiopatía congénita: utilidad pronóstica de los marcadores de daño cerebral / Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury

Introducción: En la actualidad, las alteraciones del neurodesarrollo son la complicación más frecuente en los pacientes con cardiopatía congénita (CC) en edad escolar. Analizamos la incidencia de eventos neurológicos agudos (ENA) en pacientes con CC sometidos a cirugía cardiaca y la utilidad de los neuromarcadores para predecir el neurodesarrollo. Métodos: Estudio prospectivo observacional en recién nacidos (RN) con CC diagnosticada prenatalmente, y sometidos a cirugía el primer año de vida. Se evaluaron: 1) biomarcadores sanguíneos de lesión cerebral (S100B, enolasa neuronal específica) en sangre de cordón y periquirúrgicos; 2) datos clínicos y analíticos perinatales y periquirúrgicos; 3) tratamientos y complicaciones, y 4) neurodesarrollo (escala de Bayley III) a los 2 años. Resultados: Se incluyeron 84 RN con CC de diagnóstico fetal, confirmada posnatalmente, sometidos a cirugía cardiaca en el primer año de vida. Diecisiete pacientes tenían corazón univentricular, 20 pacientes obstrucción izquierda y 10 síndromes genéticos. Fallecieron en el periodo posquirúrgico 5 pacientes (5,9%) y 9 pacientes presentaron ENA (10,7%). Las puntuaciones medias en el test de Bayley III fueron normales, pero el 31% tuvieron alteración cognitiva, motora o en el lenguaje. Los pacientes con síndromes genéticos, ENA y CC univentriculares tuvieron peor neurodesarrollo. La elevación de S100B en el postoperatorio inmediato se correlacionó con peores puntuaciones. Conclusiones: Los pacientes con CC sometidos a cirugía tienen mayor riesgo de sufrir alteraciones del neurodesarrollo. Los pacientes con síndromes genéticos o corazones univentriculares presentan peores resultados. Presentar ENA posquirúrgico puede contribuir a peores resultados. Niveles de S100B elevados en el postoperatorio se correlacionan con peores resultados en los test de neurodesarrollo a los 2 años...(AU)

Introduction: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. Methods: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. Results: The study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. Conclusions: Children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years...(AU)

INFLAMMATORY IMMUNOPATHOLOGY OF COVID-19 AND ITS CORRELATION WITH THE SEVERITY OF THE DISEASE / IMUNOPATOLOGIA INFLAMATÓRIA DA COVID-19 E SUA CORRELAÇÃO COM A GRAVIDADE DA DOENÇA

SARS-CoV-2, which caused the coronavirus pandemic in 2019 (COVID-19), is a beta-coronavirus, and its infection in host cells can activate innate and adaptive immune responses through the activation of several pro-inflammatory cytokines. Thus, in this study we established the relationship between the severity and immunopathology of COVID-19 through the main inflammatory cytokines. Results show that tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukins (IL), such as IL-6, are stimulated by the activation of T cell subsets, which results in immune-mediated cellular destruction. Several cytokines reduce the immune response and predispose to a pro-inflammatory and auto-reactive state, including IL-1ß, IL-1RA, IL-7, IL-8, IL-9, IL-10, and associated inflammatory markers (LDH, GM-CSF and VEGF). These higher cytokine levels end up favoring tissue damage in multiple systems, including lungs, heart, gastrointestinal, brain, kidneys and other organs. Increasingly, a greater impact of the markers IL-6, ferritin, pro-calcitonin, lactic dehydrogenase, D-dimer and hypoalbuminemia was observed in patients with severe infection of the disease. In general, the data analyzed confirmed that COVID-19 severity is not caused simply by the viral infection, but rather by immune response and aberrant inflammation. In this way, this study allows a contribution to clinical practice, and it shows that it is essential to carry out in-depth studies about the immunopathology of COVID-19, in order to determine the severity markers involved in the pathogenesis of the viral infection.

O SARS-CoV-2, causador da doença coronavírus 2019 (COVID-19), é um beta-coronavírus, e sua infecção nas células do hospedeiro pode ativar respostas imunes inata e adaptativa, por meio da secreção de várias citocinas pró-inflamatórias. Assim, estabelecemos neste estudo a correlação da gravidade e imunopatologia da COVID-19 com as principais citocinas inflamatórias. Resultados mostram que o fator de necrose tumoral alfa (TNF-α), interferon-gama (IFN-γ) e interleucinas (IL), como a IL-6, são estimulados pela ativação de subconjuntos de células T, o que resulta em destruição celular imunomediada. Sendo que, diversas citocinas deprimem a resposta imune sadia, e predispõem a um estado pró-inflamatório e auto-reativo, dentre elas, IL-1ß, IL-1RA, IL-7, IL-8, IL-9, IL-10, e os marcadores inflamatórios associados (LDH, GM-CSF e VEGF). Isso acaba por favorecer danos teciduais em múltiplos sistemas, como no pulmonar, cardíaco, gastrointestinal, cerebral, renal, dentre outros. Acrescenta-se que foi observado um impacto maior dos marcadores IL-6, ferritina, pró-calcitonina, desidrogenase láctica, D-dímero e hipoalbuminemia em pacientes com infecção grave da doença. De forma geral, pela análise de dados, verificou-se que a gravidade da doença COVID-19 parece ser modulada não apenas pela infecção viral, mas também por respostas imunes e inflamatórias aberrantes no hospedeiro. Dessa forma, este estudo permite contribuir para o auxílio da prática clínica, sendo imprescindível a realização de estudos aprofundados acerca da imunopatologia da COVID-19, a fim de que se determine os marcadores de gravidade envolvidos na patogênese da infecção viral.

Neurodevelopmental outcomes in congenital heart disease: Usefulness of biomarkers of brain injury.

INTRODUCTION: At present, neurodevelopmental abnormalities are the most frequent type of complication in school-aged children with congenital heart disease (CHD). We analysed the incidence of acute neurologic events (ANEs) in patients with operated CHD and the usefulness of neuromarkers for the prediction of neurodevelopment outcomes. METHODS: Prospective observational study in infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. We assessed the following variables: (1) serum biomarkers of brain injury (S100B, neuron-specific enolase) in cord blood and preoperative blood samples; (2) clinical and laboratory data from the immediate postnatal and perioperative periods; (3) treatments and complications; (4) neurodevelopment (Bayley-III scale) at age 2 years. RESULTS: the study included 84 infants with a prenatal diagnosis of CHD who underwent cardiac surgery in the first year of life. Seventeen had univentricular heart, 20 left ventricular outflow obstruction and 10 genetic syndromes. The postoperative mortality was 5.9% (5/84) and 10.7% (9/84) patients experienced ANEs. The mean overall Bayley-III scores were within the normal range, but 31% of patients had abnormal scores in the cognitive, motor or language domains. Patients with genetic syndromes, ANEs and univentricular heart had poorer neurodevelopmental outcomes. Elevation of S100B in the immediate postoperative period was associated with poorer scores. CONCLUSIONS: children with a history of cardiac surgery for CHD in the first year of life are at risk of adverse neurodevelopmental outcomes. Patients with genetic syndromes, ANEs or univentricular heart had poorer outcomes. Postoperative ANEs may contribute to poorer outcomes. Elevation of S100B levels in the postoperative period was associated with poorer neurodevelopmental outcomes at 2 years. Studies with larger samples and longer follow-ups are needed to define the role of these biomarkers of brain injury in the prediction of neurodevelopmental outcomes in patients who undergo surgery for management of CHD.