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.

MR-proADM as marker of endotheliitis predicts COVID-19 severity.

BACKGROUND: Early identification of patients at high risk of progression to severe COVID-19 constituted an unsolved challenge. Although growing evidence demonstrates a direct association between endotheliitis and severe COVID-19, the role of endothelial damage biomarkers has been scarcely studied. We investigated the relationship between circulating mid-regional proadrenomedullin (MR-proADM) levels, a biomarker of endothelial dysfunction, and prognosis of SARS-CoV-2-infected patients. METHODS: Prospective observational study enrolling adult patients with confirmed COVID-19. On admission to emergency department, a blood sample was drawn for laboratory test analysis. Primary and secondary endpoints were 28-day all-cause mortality and severe COVID-19 progression. Area under the curve (AUC) and multivariate regression analysis were employed to assess the association of the biomarker with the established endpoints. RESULTS: A total of 99 patients were enrolled. During hospitalization, 25 (25.3%) cases progressed to severe disease and the 28-day mortality rate was of 14.1%. MR-proADM showed the highest AUC to predict 28-day mortality (0.905; [CI] 95%: 0.829-0.955; P < .001) and progression to severe disease (0.829; [CI] 95%: 0.740-0.897; P < .001), respectively. MR-proADM plasma levels above optimal cut-off (1.01 nmol/L) showed the strongest independent association with 28-day mortality risk (hazard ratio [HR]: 10.470, 95% CI: 2.066-53.049; P < .005) and with progression to severe disease (HR: 6.803, 95% CI: 1.458-31.750; P = .015). CONCLUSION: Mid-regional proadrenomedullin was the biomarker with highest performance for prognosis of death and progression to severe disease in COVID-19 patients and represents a promising predictor for both outcomes, which might constitute a potential tool in the assessment of prognosis in early stages of this disease.

Increased concentrations of procalcitonin in patients with paracetamol intoxication.

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

Utilidad de la hemoglobina A1c en el diagnóstico de diabetes mellitus y otras alteraciones del metabolismo glucídico en mujeres con diabetes mellitus gestacional reciente / The value of hemoglobin A1c for diagnosis of diabetes mellitus and other changes in carbohydrate metabolism in women with recent gestational diabetes mellitus

Las mujeres con diabetes mellitus gestacional (DMG) previa presentan mayor riesgo de desarrollar diabetes mellitus (DM). En estas mujeres, se recomienda realizar una reclasificación metabólica después del parto. El objetivo de este estudio fue valorar el rendimiento de la hemoglobina A1c para la evaluación postparto en mujeres con DMG reciente y evaluar la concordancia en el diagnóstico de las distintas formas de alteración de la tolerancia a la glucosa con el test de tolerancia con sobrecarga oral de 75g de glucosa (TTOG 75g), método recomendado actualmente para dicha reclasificación. Material y métodos56 mujeres con DMG reciente fueron reclasificadas tras el parto en nuestro centro según los criterios de la Asociación Americana de Diabetes (ADA). Se analizó la concordancia en el diagnóstico entre la hemoglobina A1c y el TTOG 75g y se evaluó el rendimiento de la hemoglobina A1c para el diagnóstico de DM y para la detección de cualquier forma de alteración de tolerancia a la glucosa. Resultados Se diagnosticó DM en 7 mujeres y otras formas de alteración de la tolerancia a la glucosa en 25. El índice kappa de concordancia en el diagnóstico fue de 0,22. Una hemoglobina A1c ≥ 5,7% presentó una sensibilidad de 47% y una especificidad de 71% para identificar cualquier forma de alteración de la tolerancia a la glucosa. Una hemoglobina A1c ≥ 6,5 presentó una sensibilidad de 29% y una especificidad de 100% para el diagnóstico de DM. El área bajo la curva ROC para la detección de cualquier forma de alteración de la tolerancia a la glucosa fue 0,57 y para el diagnóstico de DM de 0,81.ConclusionesLa hemoglobina A1c, empleando los puntos de corte de la ADA, no es apropiada para la reclasificación metabólica de mujeres con antecedente reciente de DMG (AU)

Women with gestational diabetes mellitus (GDM) have an increased risk for developing diabetes mellitus (DM). Their postpartum metabolic classification using a 75g oral glucose tolerance test (75g OGTT) is recommended. The purpose of this study was to assess the value of hemoglobin A1c for postpartum evaluation in women with recent gestational diabetes mellitus. Patients and methods Fifty-six women with recent GDM underwent a 75g OGTT at our center to assess postpartum changes in carbohydrate metabolism and were classified using diagnostic criteria of the American Diabetes Association (ADA). Receiver operating characteristic (ROC) curves analysis was used to assess the diagnostic performance of hemoglobin A1c, and kappa index was used to evaluate diagnostic agreement between hemoglobin A1c and 75g OGTT. Results DM was diagnosed in 7 women, and other categories of increased risk for DM in 25 women. Kappa index for diagnosis agreement was 0,22. Hemoglobin A1c ≥ 5.7% had 47% sensitivity and 71% specificity for identifying any change in carbohydrate metabolism. A hemoglobin A1c value ≥ 6.5 had 29% sensitivity and 100% specificity for diagnosis of DM. Area under the ROC curve was 0.57 for identifying any change in carbohydrate metabolism and 0.81 for diagnosis of DM. Conclusion Using ADA cutoff values, hemoglobin A1c is not appropriate for postpartum glucose tolerance evaluation in women with recent gestational diabetes mellitus (AU)

[The value of hemoglobin A1c for diagnosis of diabetes mellitus and other changes in carbohydrate metabolism in women with recent gestational diabetes mellitus]. / Utilidad de la hemoglobina A1c en el diagnóstico de diabetes mellitus y otras alteraciones del metabolismo glucídico en mujeres con diabetes mellitus gestacional reciente.

INTRODUCTION: Women with gestational diabetes mellitus (GDM) have an increased risk for developing diabetes mellitus (DM). Their postpartum metabolic classification using a 75g oral glucose tolerance test (75g OGTT) is recommended. The purpose of this study was to assess the value of hemoglobin A1c for postpartum evaluation in women with recent gestational diabetes mellitus. PATIENTS AND METHODS: Fifty-six women with recent GDM underwent a 75g OGTT at our center to assess postpartum changes in carbohydrate metabolism and were classified using diagnostic criteria of the American Diabetes Association (ADA). Receiver operating characteristic (ROC) curves analysis was used to assess the diagnostic performance of hemoglobin A1c, and kappa index was used to evaluate diagnostic agreement between hemoglobin A1c and 75g OGTT. RESULTS: DM was diagnosed in 7 women, and other categories of increased risk for DM in 25 women. Kappa index for diagnosis agreement was 0,22. Hemoglobin A1c ≥ 5.7% had 47% sensitivity and 71% specificity for identifying any change in carbohydrate metabolism. A hemoglobin A1c value ≥ 6.5 had 29% sensitivity and 100% specificity for diagnosis of DM. Area under the ROC curve was 0.57 for identifying any change in carbohydrate metabolism and 0.81 for diagnosis of DM. CONCLUSION: Using ADA cutoff values, hemoglobin A1c is not appropriate for postpartum glucose tolerance evaluation in women with recent gestational diabetes mellitus.

Evaluación del índice proteína-creatinina en orina aislada para la predicción de proteinuria significativa durante la gestación / Evaluation of spot urine protein-creatinine ratio to predict significant proteinuria during pregnancy

Introducción: El diagnóstico y seguimiento de la preeclampsia requiere de la determinación de proteinuria y la técnica de referencia para esta evaluación es la excreción en orina de 24 h. Sin embargo, su recolección es engorrosa para la gestante e implica un retraso en el diagnóstico, por el tiempo que requiere. El objetivo de este estudio es evaluar el rendimiento diagnóstico del índice proteína/creatinina (IPC), calculado en un espécimen aislado, para descartar y predecir una proteinuria significativa (≥ 300 mg/24 h) en gestantes ambulatorias con sospecha o diagnóstico previo de preeclampsia. Material y métodos: El IPC fue calculado en 106 especímenes de orina aislada, obtenidas tras la recolección del espécimen de 24 h, de 66 gestantes que acudieron de forma ambulatoria a la Unidad de Medicina Materno Fetal de nuestro hospital por hipertensión gestacional. La correlación entre el IPC y la excreción de proteína durante 24 h fue calculada. El análisis de curvas ROC fue utilizado para evaluar el rendimiento diagnóstico y establecer el punto de corte adecuado para predecir la ausencia o presencia de proteinuria significativa. Resultados: Se detectó una proteinuria significativa en 31 orinas de 22 gestantes. La correlación entre el IPC y la excreción en orina de 24 h fue significativa (rSpearman = 0,658 [p = 0,01]). El área bajo la curva ROC para el índice proteína/creatinina fue de 0,838, superior al de la tira reactiva (0,629 [IC del 95%, 0,551-62-0,707]). Ningún punto de corte fue adecuado para excluir y predecir simultáneamente una proteinuria significativa; sin embargo, el uso de la tira reactiva y del IPC, con dos puntos de corte, 120 mg/g para descartar proteinuria significativa y 240 mg/g para confirmarla, clasificó inicialmente de forma correcta el 44,3% de las orinas e hizo innecesaria la recolección de orina de 24 h en el 51% de los casos. Conclusiones: ElIPC, usado conjuntamente con la determinación de proteína urinaria mediante la tira reactiva, es una herramienta útil en la evaluación inicial de gestantes ambulatorias con hipertensión gestacional o preeclampsia para descartar o predecir una proteinuria significativa, pero no debería ser utilizada como alternativa a la excreción de 24 h en el rango intermedio de IPC, requiriendo la recolección de un espécimen de 24 h para garantizar resultados seguros (AU)

Introduction: Diagnosis and follow-up of preeclampsia requires measurement of proteinuria and the gold standard for this evaluation is the 24-hour collection. However, this collection is cumbersome, time consuming and delays clinical diagnosis. The purpose of this study is assess the diagnostic performance of the spot urine protein/creatinine (P/C) ratio to predict the absence or presence of significant proteinuria (≥ 300 mg per 24 hours) among outpatient pregnant women with suspected or previous diagnosis of preeclampsia. Material and methods: The P/C ratio was calculated in 106 single voided urine samples, obtained after the completion of the 24-hour collection, from 66 outpatient pregnant women admitted to the Maternal Fetal Care Unit at our Hospital to follow-up of hypertension gestational. Correlation between the spot urine P/C ratio with the 24-hour urine protein excretion was calculated. Receiver operator characteristic (ROC) curves analysis was used to evaluate the diagnostic performance and to determinate the best cutoff to predict the absence or presence of significant proteinuria. Results: Significant proteinuria on 24 hour collection urine was identified in 31 urines from 22 pregnant women. There was a significant correlation between the spot urine P/C and 24-hour urine protein excretion (rSpearman = 0,658, p = 0,01). ROC curves analysis revealed an area under the curve for spot P/C ratio of 0,838, greater than urine dipstick (0,629). No single P/C ratio cutoff was appropriate to rule-out or predict significant proteinuria; however, use of dipstick and spot urine P/C ratio, with two cutoffs, 120 mg/g to predict the absence of significant proteinuria and 240 mg/g to confirm it, clasiffied correctly 44,3% of urines and avoided the collection of 24 hours urine in 51% of the cases. Conclusions: Spoturine P / Cratio, in conjunction with dipstick urianalysis, is a useful test in the initial screen for rule-out and predict significant proteinuria in outpatient pregnant women with hypertensive pregnancy or preeclampsia, but it should not be used as an alternative to 24-hour total protein evaluation in midrange P/C ratio, requiring a full 24-hour urine for accurate results (AU)

Valoración de la función tiroidea durante la gestación: intervalos de referencia de tirotropina y tiroxina no unida a proteína durante el primer trimestre / Evaluation of testosterone levels through distinct analytic methods in healthy men

Objetivos Estudiar los rangos de normalidad de testosterona en varones jóvenes sanos y comparar los resultados de los distintos métodos analíticos utilizados. Material y métodos Se incluyeron 20 hombres sanos con una edad media de 24,5 años (desviación estándar (DE): 5,04), un índice de masa corporal (IMC) medio de 23,8% (DE: 3,3). Se determinaron las concentraciones de testosterona total (TT) mediante inmunoquimioluminiscencia (ICLA), de testosterona libre (TL) mediante radioinmunoensayo (RIA), y se calculó la testosterona libre calculada (TLc) y la testosterona biodisponible (TB) mediante la fórmula de Vermeulen. Se midieron las concentraciones séricas de lutropina (LH), folitropina (FSH) y proteína ligadora de hormonas sexuales (SHBG) por método inmunorradiométrico (IRMA).Resultados Las concentraciones medias de TT fueron de 20nmol/l (DE 4,96), las de TL de 0,054nmol/l (DE 0,01), los de TLc de 0,3834nmol/l (DE 0,09) y los de TB de 9,9nmol/l (DE: 2,8 ). No se encontró correlación entre las concentraciones de testosterona medidos por los distintos métodos, excepto entre TL y TLc (r=0,662; p<0,003) y entre TLc y TB (r=0,979; p<0,0001). Existe una asociación inversa entre IMC y las concentraciones de testosterona total (r: −0,52; p<0,017).Conclusiones Es necesario establecer el intervalo de normalidad para la testosterona en hombres jóvenes sanos en función del método analítico utilizado (AU)

Plasma testosterone concentrations are essential for the diagnosis of several causes of hypogonadism, including late-onset hypogonadism. Defining the normal range for testosterone concentrations poses certain difficulties due to the changes that occur with age and the variability of the different analytical methods used. Objectives To study normal ranges of testosterone in healthy young men and to compare the results of distinct analytical methods. Material and methods We recruited 20 healthy men with a mean age of 24.5 years (standard deviation (SD): 5.04) and a mean body mass index (BMI) of 23.8% (SD: 3.3). Total testosterone (TT) was measured by immunochemiluminescence (ICLA) and free testosterone (FT) by radioimmunoassay (RIA). Calculated free testosterone (FTc) and bioavailable testosterone (BT) were calculated using Vermeulen's formula. Serum lutropin (LH), follitropin (FSH) and sex hormone binding globulin (SHBG) were measured by immunoradiometric assays (IRMA).Results The mean concentrations were 20nmol/l (SD: 4.96) for TT, 0.054nmol/L (SD: 0.01) for FT, 0.3834nmol/L (SD: 0.09) for FTc and 9.9nmol/L (SD: 2.8) for BT. There was no correlation between testosterone measured by different methods other than an association between FT and FTc (r=0.662, p<0.003) and between FTc and BT (r=0.979, p<0.0001). An inverse correlation was found between BMI and TT concentrations (r: −0.52, p<0.017).Conclusions The normal range for testosterone in healthy young men should be established in each laboratory based on the analytical method used (AU)

[Evaluation of thyroid function during pregnancy: first-trimester reference intervals for thyroid-stimulating hormone and free thyroxine]. / Valoración de la función tiroidea durante la gestación: intervalos de referencia de tirotropina y tiroxina no unida a proteína durante el primer trimestre.

BACKGROUND AND OBJECTIVES: The physiological changes that occur during pregnancy affect the physiology of the thyroid gland. Consequently, interpretation of thyroid function markers during pregnancy requires trimester-specific reference intervals. The aims of our study were to: 1) establish first-trimester reference intervals for biochemical markers of thyroid function [thyroid-stimulating hormone (TSH) and free thyroxine (T4)] and 2) to establish the prevalence of autoimmune thyroid disease in pregnant women resident in Cartagena (Murcia, Spain). PATIENTS AND METHOD: A total of 441 women between weeks 11 and 13 of pregnancy were included in this study. A blood sample was extracted from all women to measure TSH, free T4 and antithyroid antibodies. Reference intervals for TSH and free T4 were determined in 400 pregnant women without autoimmune thyroid disease or known thyroid disease. RESULTS: Autoimmune thyroid disease was detected in 23 pregnant women (5.2%) who showed TSH levels higher than those in pregnant women without thyroid autoimmunity. First-trimester reference intervals were as follows: TSH: 0.130-3.710 mUI/L; free T4: 0.89-1.50 ng/dL. These reference intervals differed from the non-pregnant reference intervals used in our laboratory. CONCLUSIONS: The reference intervals established are useful to evaluate thyroid function in women between 11 and 13 weeks of pregnancy. Interpretation of thyroid function requires intervals established in a reference population without autoimmune thyroid disease and with the methodology usually used to analyze these markers.