Flow cytometric characterization of cecal appendix lymphocyte subpopulations in children: a pilot study.

INTRODUCTION: Scientific literature regarding the characterization of lymphocyte subpopulations of the cecal appendix is sparse, with few precedents limited to immunohistochemical techniques. METHODS: We conducted a prospective pilot study to characterize lymphocyte subpopulations of the cecal appendix in children. Participants were divided into three groups: (1) patients without histological acute appendiceal inflammation, (2) patients with histological uncomplicated acute appendicitis, and (3) patients with histological complicated acute appendicitis (gangrenous, perforated). A fresh sample of the base of the appendix was taken from all patients and a flow cytometric study was performed. Quantitative variables were compared using Kruskal-Wallis test and Mann-Whitney U test. RESULTS: This study included 57 patients divided into Group 1 (n = 5), Group 2 (n = 37), and Group 3 (n = 15). Median values (IQR) of the percentage of B-lymphocytes were 67.8 [66.8-68.1] in group 1, 61.15 [53.74-66.4] in group 2, and 52.1 [33-62.02] in group 3 (p = 0.02). Median values (IQR) of the percentage of NK-lymphocytes were 0.26 [0.2-0.3] in group 1, 0.55 [0.37-0.66] in group 2, and 0.84 [0.35-1.45] in group 3 (p = 0.008). Median values (IQR) of the percentage of T-lymphocytes were 31.9 [31.7-33.1] in group 1, 37.68 [32.15-45.69] in group 2, and 46.9 [37.03-67] in group 3 (p = 0.02). Pair comparisons of groups 2 and 3 also showed significant differences in the percentage of B lymphocytes (p = 0.03) and NK-lymphocytes (p = 0.02). CONCLUSIONS: Significant differences in lymphocyte subpopulations were identified according to the histologic grade of the cecal appendix. More specifically, a lower percentage of B-lymphocytes and a higher percentage of T- and NK-lymphocytes were observed in cases of acute appendicitis. These findings must be confirmed and their etiopathogenic, diagnostic, and prognostic implications elucidated in future studies with larger sample sizes.

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.

The BIDIAP index: a clinical, analytical and ultrasonographic score for the diagnosis of acute appendicitis in children.

BACKGROUND: Pediatric acute appendicitis (PAA) continues to be a diagnostic challenge today. The diagnostic performance of classical indices is only moderate, especially in pediatric population. This study aimed to define a clinical, radiological and analytical index for the diagnosis of PAA. MATERIALS AND METHODS: This prospective study included 151 patients divided into two groups: (1) 53 patients with non-surgical abdominal pain (NSAP) and (2) 98 patients with a confirmed PAA. Sociodemographic and clinical characteristics were compared between groups using the Mann-Whitney U test and the Fisher exact test. To identify the predictors of PAA, we performed a multivariable logistic regression using a forward stepwise analysis and we assigned multiples of integer values to the selected variables. The diagnostic performance of the index was assessed by calculating the area under the receiver operating characteristic curve. Intra-cohort calibration was assessed with the Hosmer-Lemeshow test. RESULTS: We developed the BIDIAP index (BIomarkers for the DIagnosis of Appendicitis in Pediatrics), which included three variables that independently predicted higher odds of PAA: appendiceal caliber (≥ 6.9 mm), systemic immune-inflammation index (≥ 890) and peritoneal irritation, which scored 4, 3 and 2 points, respectively. Mean (SD) score of the participants was 2.38 (2.06) in group 1 and 7.89 (1.50) in group 2. The area under the ROC was 0.97 (95% CI 0.95-0.99). The cut-off point was established at 4 points, resulting in a sensitivity of 98.98% and a specificity of 77.78%. CONCLUSIONS: The BIDIAP index has an exceptional diagnostic performance in PAA. The importance of these results lies in its novelty and in the simplicity of the index. Although external validation will be necessary, initial results look promising.

Coagulation Profile: Alterations and Diagnostic Yield in Pediatric Acute Appendicitis: A Prospective Validation Study.

Background: The literature regarding alterations in the coagulation profile in pediatric acute appendicitis (PAA) is scarce and mainly limited to retrospective studies. Evidence on the diagnostic yield of coagulation parameters is limited to fibrinogen. Patients and Methods: This is a prospective study with 151 patients divided into two groups: patients with nonsurgical abdominal pain (NSAP) in whom the diagnosis of PAA was excluded (n = 53) and patients with a confirmed diagnosis of PAA (n = 98). In 93 patients (62%), a coagulation study was obtained at the time of diagnosis and international normalized ratio (INR), activated partial thromboplastin time (aPTT), d-dimer, platelets, mean platelet volume, and platelet-to-lymphocyte ratio were analyzed. The PAA group was further classified into complicated (n = 19) and non-complicated PAA (n = 40). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of the coagulation profile was evaluated with the area under the receiver operating characteristic (ROC) curves. Results: Patients with NSAP had lower median levels of INR, fibrinogen and d-dimer than those with PAA. Moreover, patients with complicated PAA had higher median values of INR and fibrinogen. None of the patients needed specific treatment for the correction of coagulopathy. Fibrinogen was the parameter with the highest diagnostic yield for distinguishing between NSAP and PAA (area under the curve [AUC], 0.74; 95% confidence interval [CI], 0.65-0.85), as well as between complicated versus non-complicated PAA (AUC, 0.71; 95% CI, 0.57-0.86). Conclusions: This study found a moderate extrinsic pathway coagulopathy in patients with PAA, especially in complicated PAA. Fibrinogen is a parameter with moderate diagnostic yield for the diagnosis of PAA.

Diagnostic performance of calprotectin and APPY-1 test in pediatric acute appendicitis: a systematic review and a meta-analysis.

BACKGROUND: Pediatric acute appendicitis (AA) is a challenging pathology to diagnose. In the last decades, multiple biomarkers have been evaluated in different human biological samples to improve diagnostic performance. This study aimed to examine the diagnostic performance of serum, fecal and urinary calprotectin as well as the role of the APPY-1 biomarker panel in pediatric acute appendicitis. METHODS: We conducted a systematic review of the literature that involved an extensive search in the main databases of medical bibliography (Medline, PubMed, Web of Science and SciELO). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected article was rated using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and two random-effect meta-analyses, one for serum calprotectin and one for APPY-1, were performed. RESULTS: The research resulted in 173 articles. Thirty-eight duplicates were removed. Among the remaining 135 articles, we excluded 125 following the inclusion and exclusion criteria, resulting in the 10 studies included in this review. This systematic review included data from of 3901 participants (1276 patients with confirmed diagnosis of AA and 2625 controls). The age of the participants ranged from 0 to 21 years. Four of the studies compared serum calprotectin values and reported significant differences between groups, but inconsistent results regarding cutoff points, sensitivity and specificity. Two publications compared urinary values of calprotectin and presented inconsistent results regarding sensitivity and specificity as well. One publication evaluated the diagnostic performance of fecal calprotectin, but it did not provide data on measured values. Four studies evaluated the diagnostic performance of APPY-1 test in pediatric acute appendicitis. The calculated pooled sensitivity and specificity of those studies were 97.37 (95% CI 95.60-98.44) and 36.74 (95% CI 32.28-41.44), respectively, and the calculated pooled NLR, 0.0714 (95% CI 0.041-0.115). CONCLUSION: Serum calprotectin has limited diagnostic yield in pediatric acute appendicitis. Its performance seems to increase with the hours of clinical evolution and in advanced AA, although the evidence is limited. There is not enough evidence on the usefulness of urinary or fecal calprotectin in the diagnosis of pediatric acute appendicitis. On the other hand, the APPY-1 is a reliable test to exclude the diagnosis of AA in patients at low or moderate risk according to PAS and Alvarado Score.

Glans Penis Ischemia after Circumcision in a 15-Year-Old Patient Managed with Intravenous Pentoxifylline: A Case Report and a Diagnostic-Therapeutic Guideline Proposal.

Glans ischemia is an extremely infrequent complication characterized by a total or partial compromise in the penile arterial perfusion. A 15-year-old male patient suffered an episode of ischemia in the glans penis post-circumcision 24 h after surgery. Intravenous treatment with continuous perfusion of pentoxifylline was started for 4 days, with favorable evolution. Complete resolution was observed with no sequelae. There is no consensus on the best therapeutic management. The favorable evolution reported in most of the cases despite different therapeutic approaches leads us to think that the role of the treatments proposed so far is probably less than we believe. Additionally, we present a proposal for a diagnostic and therapeutic guide for this entity. Although the evidence in the literature is scarce and this guideline should be interpreted with caution, we believe that it can constitute a support resource for cases similar to ours.

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.

Alterations and diagnostic performance of capillary ketonemia in pediatric acute appendicitis: a pilot study.

INTRODUCTION: The diagnostic performance of capillary ketonemia (CK) has been previously evaluated in context of pediatric acute gastroenteritis. To our knowledge, there is no literature on its performance in the setting of pediatric acute appendicitis (PAA). MATERIALS AND METHODS: In this study, 151 patients were prospectively included and divided into two groups: (1) patients with non-surgical abdominal pain in whom the diagnosis of PAA was excluded (n = 53) and (2) patients with a confirmed diagnosis of PAA (n = 98). In 80 patients (Group 1, n = 23 and group 2, n = 57) a CK was measured at the time of diagnosis. The PAA group was further classified into complicated (n = 18) and uncomplicated PAA (n = 39). Quantitative variables were compared between groups using the Mann-Whitney U test. Diagnostic performance of CK was evaluated with ROC curves. RESULTS: CK values were 0.3 [0.1-0.9] mmol/L in group 1 and 0.7 [0.4-1.4] mmol/L in group 2 (p = 0.01). Regarding the type of PAA, CK values were 0.6 [0.4-0.9] mmol/L in uncomplicated PAA and 1.2 [0.8-1.4] mmol/L in complicated PAA (p = 0.02). The AUC for the discrimination between groups 1 and 2 was 0.68 (95% IC 0.53-0.82) (p = 0.24) and the AUC for the discrimination between uncomplicated PAA and complicated PAA was 0.69 (95% IC 0.54-0.85) (p = 0.04). The best cut-off point (group 1 vs group 2) resulted in 0.4 mmol/L, with a sensitivity of 80.7% and a specificity of 52.2%. The best cut-off point (non-complicated vs complicated PAA) resulted in 1.1 mmol/L, with a sensitivity of 61.1% and a specificity of 76.9%. CONCLUSIONS: This study found significantly higher levels of CK in patients with PAA than in those with NSAP. Similarly, significantly higher levels were observed in patients with complicated than in those with uncomplicated PAA. Nevertheless, the diagnostic performance of CK was only moderate in the two settings analyzed. The potential usefulness of CK determination as a tool to guide the preoperative rehydration regimen of patients with PAA to prevent postoperative hyporexia and vomiting is a promising line of research and should be evaluated in future 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.

Pseudoaneurismas postraumáticos pediátricos: nuestra experiencia / Paediatric post-traumatic pseudoaneurysm: Our experience

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