Post-Operative Increase in Serum Interleukin-6 Is Associated With Longer Hospital Stay in Children Operated on for Acute Appendicitis: A Pilot Study.

Background: Pediatric acute appendicitis (PAA) involves a substantial consumption of health and economic resources. The identification of serum biomarkers that may help predict the post-surgical evolution of these patients is a field of great interest. Patients and Methods: This was a prospective, observational substudy within the Biomarkers for the Diagnosis of Appendicitis in Pediatrics (BIDIAP) cohort aimed at evaluating the association between post-surgical increase in serum IL-6 and different outcomes related to the clinical evolution of children operated on for PAA. Sixty-nine children with a confirmed diagnosis of acute appendicitis and both pre-operative and post-operative serum IL-6 were included in the study. Three multivariable-adjusted linear regression models were fitted to analyze the association between an increase of >10% in post-operative serum IL-6 level with the length of stay, the number of post-operative emetic episodes, and the onset of oral feeding. Two multivariable-adjusted logistic regression models were fitted to assess the association of the same exposure with the indication of antibiotherapy at discharge and with positivity in peritoneal fluid culture. Results: Thirteen children showed an increase of >10% in the post-operative serum IL-6 value (group 1) whereas 56 showed only a minor increase, or no change (group 2). After accounting for potential confounders, children in group 1 had a mean of three-day longer hospital stay (difference, 3.33; 95% confidence interval [CI], 0.57-6.09) and higher odds of a positive result in peritoneal fluid culture (odds ratio [OR], 37.43; 95% CI, 1.02-1361.28) than children in group 2. Conclusions: An increase of >10% in post-operative serum IL-6 value could predict longer hospital stay and higher odds of positive peritoneal fluid culture. Future prospective studies are needed to replicate these findings and to broaden the range of biomarkers that could predict the post-operative evolution of children operated on for PAA.

Diagnostic performance of serum pentraxin-3 in pediatric acute appendicitis: a prospective diagnostic validation study.

INTRODUCTION: Pediatric acute appendicitis (PAA) is a pathology with a high rate of diagnostic error. The search for new diagnostic tools is justified by the high morbidity and healthcare costs associated with diagnostic error. METHODS: We designed a prospective study to validate serum pentraxin-3 (PTX3) as a diagnostic tool in PAA. Participants were divided into three groups: (1) patients with no underlying pathology (2) patients with non-surgical abdominal pain and (3) patients with a confirmed diagnosis of PAA. For further analyses, patients in group 3 were divided into complicated or uncomplicated PAA. Quantitative variables were expressed as medians and interquartile ranges and categorical variables as percentages. Quantitative variables were compared using the Kruskal-Wallis test and the Mann-Whitney U test. Diagnostic performance was evaluated with ROC curves. RESULTS: This study included 215 patients divided into group 1 (n = 63), group 2 (n = 53) and group 3 (n = 99). Median serum PTX3 values were 2.54 (1.70-2.95) ng/mL, 3.29 (2.19-7.64) ng/mL and 8.94 (6.16-14.05) in groups 1, 2 and 3, respectively (p = 0.001). Patients with complicated PAA showed significantly higher values than patients with uncomplicated PAA (p = 0.04). The AUC (group 2 vs. 3) was 0.77 (95% CI 0.69-0.85) and the best cut-off point was at 7.28 ng/mL, with a sensitivity of 61.3% and a specificity of 73.1%. The AUC (complicated vs. uncomplicated PAA) was 0.65 (95% CI 0.54-0.77) and the best cut-off point was 12.33 ng/mL, with a sensitivity of 51.72% and a specificity of 72.73%. CONCLUSIONS: The diagnostic ability of serum PTX3 in PAA is only moderate and therefore it cannot be considered a definitive diagnostic test. The discriminatory ability of PTX3 between complicated and uncomplicated PAA is poor. These findings, which contrast with those reported to date, should be validated with future properly designed prospective studies.

Discriminatory capacity of serum interleukin-6 between complicated and uncomplicated acute appendicitis in children: a prospective validation study.

BACKGROUND: Serum interleukin-6 (IL-6) has a moderate diagnostic performance in pediatric acute appendicitis (PAA). The evidence regarding its capacity to discern between complicated and uncomplicated PAA is scarce. METHODS: We designed a prospective observational study to validate serum IL-6 as a marker for diagnostic classification between complicated and uncomplicated PAA. This study included 205 patients divided into three groups: (1) patients who underwent major outpatient surgery (n = 57); (2) patients with non-surgical abdominal pain (NSAP) in whom the diagnosis of PAA was excluded (n = 53), and (3) patients with a confirmed diagnosis of PAA (n = 95). The PAA patients were further classified as uncomplicated or complicated PAA. IL-6 concentration was determined in all patients at diagnosis. Comparative statistical analysis was performed using the Mann-Whitney U test, the Fisher exact test and the Kruskall Wallis test. The area under the receiver operating characteristic curves (AUC) were calculated. RESULTS: Median (interquartile range, IQR) serum IL-6 values were 2 pg/mL (2.0-3.4) in group 1, 3.9 pg/mL (2.4-11.9) in group 2, and 23.9 pg/mL (11.1-61.0) in group 3 (P < 0.001). Among the participants in group 3, those with uncomplicated PAA had median (IQR) serum IL-6 values of 17.2 pg/mL (8.5-36.8), and those with complicated PAA had 60.25 pg/mL (27.1-169) serum IL-6 (P < 0.001). At the cut-off point of 19.55 pg/mL, the AUC for the discrimination between patients in group 2 vs. 3 was 0.83 [95% confidence interval (CI) 0.76-0.90], with a sensitivity of 61.3% and a specificity of 86.8. The AUC for the discrimination between patients with uncomplicated and complicated PAA was 0.77 (95% CI 0.68-0.86) and the cut-off point was 25.90 pg/mL, with a sensitivity and specificity of 84.6% and 65.6%, respectively. CONCLUSIONS: Serum IL-6 has a good performance in discerning between complicated and uncomplicated PAA. A score including clinical and radiological variables may increase the diagnostic performance of this molecule.

Serum neutrophil gelatinase-associated lipocalin (NGAL) as a diagnostic tool in pediatric acute appendicitis: a prospective validation study.

INTRODUCTION: NGAL has recently been studied as a biomarker in the diagnostic context of pediatric acute appendicitis (PAA), although existing series are scarce and have limited sample sizes. MATERIALS AND METHODS: A prospective observational study was designed to validate serum NGAL as a diagnostic tool in PAA. This study included 215 patients, divided into 3 groups: (1) patients undergoing major outpatient surgery (n = 63), (2) patients with non-surgical abdominal pain in whom a diagnosis of PAA was excluded (n = 53) and (3) patients with a confirmed diagnosis of PAA (n = 99). Patients in group 3 were divided into complicated or uncomplicated appendicitis. In 201 patients, a serum sample was obtained at the time of diagnosis and NGAL concentration was determined by ELISA. The Kolmogorov-Smirnov test was used to assess normality. Comparative statistical analyses were performed using the Mann-Whitney U test, the Kruskal-Wallis test and the Fisher's exact test. To calculate the discriminative ability of the molecule, the area under the receiver-operating characteristic curves (AUC) was calculated. A p value < 0.05 established statistical significance. RESULTS: Median (interquartile range) of serum NGAL values were 38.88 (27.15-48.04) ng/mL (group 1), 51.84 (37.33-69.80) ng/mL (group 2) and 65.06 (50.50-86.60) ng/mL (group 3). The AUC (group 2 vs 3) was 0.642 (95% CI 0.542-0.741) (p < 0.001) and the best cutoff point was found to be at 40.97 ng/mL, with a sensitivity of 89% and a specificity of 34.6%. No statistically significant differences in serum NGAL values were found between patients with uncomplicated PAA and those with complicated PAA. CONCLUSIONS: This prospective validation study with a large sample size confirms that the diagnostic yield of NGAL in the context of PAA is only moderate, and therefore, it should not be used as a unique diagnostic tool. Furthermore, NGAL is not a valid biomarker to discern between uncomplicated and complicated PAA.

Utilidad clínica de la cuantificación de infliximab y anticuerpos antiquiméricos humanos / Clinical usefulness in measuring infliximab and human anti-chimeric antibodies

Introducción: El infliximab (IFX), un anticuerpo quimérico contra el factor de necrosis tumoralalfa, es utilizado en el tratamiento de pacientes con diversas enfermedades inflamatorias, pero puede originar la formación de anticuerpos antiquiméricos humanos (HACA). La presencia de HACA y niveles séricos de IFX bajos se han asociado con falta o pérdida de respuesta y con laaparición de reacciones infusionales. Evaluamos la utilidad de la cuantificación de IFX y HACA. Material y métodos: IFX y HACA se midieron utilizando una técnica ELISA relativamente nueva en una cohorte de 110 pacientes tratados con IFX. Se recogieron muestras de suero inmediatamente antes de la siguiente infusión del fármaco. Los pacientes habían recibido una mediana de dosis de 5 mg/kg, con intervalos de dosis ajustados a la actividad de la enfermedad, habitualmente cada 8 semanas. La mediana del número de infusiones fue 17. Resultados: Los HACA se detectaron en 10 pacientes y se midieron concentraciones terapéuticas de IFX en 37 casos. Ocho de los 10 pacientes con HACA positivos tenían trastornos digestivos y en 9 de ellos el tratamiento fue suspendido. El uso concomitante de inmunosupresores no redujo el riesgo de formación de HACA. Entre los 100 pacientes sin HACA, 79 continuaron con la misma dosis, 16 requirieron un ajuste de dosis, en 2 se suspendió el tratamiento y 3 pacientes fueron cambiados a otro agente biológico. Conclusiones: Las concentraciones de IFX y HACA en sangre deberían ser monitorizadas en pacientes que reciben IFX, ya que puede ser útil para optimizar los regímenes de dosis o evitar el uso de terapias inadecuadas (AU)

Introduction: infliximab (IFX), a chimeric antibody against tumour necrosis factor-alpha, is used in the treatment of patients with several inflammatory diseases, but it can lead to the formation of human anti-chimeric antibodies (HACA). HACA and low IFX serum levels have been associated with lack or loss of response, and infusion reactions. The usefulness of measuring the IFX and HACA concentrations is evaluated. Material and methods: IFX and HACA were measured using a relatively new ELISA technique in a cohort of 110 patients treated with IFX. Serum samples were collected immediately before patients were given the next drug infusion. The patients had received a median dose of 5 mg/kg, with dose intervals adjusted to the patient’s disease activity, usually every 8 weeks. The median number of infusions was 17. Results: HACA were identified in 10 patients, and therapeutic IFX concentrations were observedin 37 patients. Eight out of 10 positive HACA patients had gastrointestinal disorders, and thetherapy was discontinued in 9 of them. The concomitant use of immunosuppressants did not reduce the risk of HACA formation. Among 100 patients with no HACA, 79 continued on the same dose, 16 required a dose adjustment, 2 discontinued treatment, and 3 were switched toanother biological agent. onclusions: Blood IFX and HACA concentrations should be monitored in patients receiving IFX, as it may be useful to optimize dose regimens or avoid use of inadequate therapy (AU)