Diagnostic performance of urinary 5-Hydroxyindoleacetic Acid in acute appendicitis: a systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVES: This study aimed to analyze the diagnostic performance of urinary 5-Hydroxyindoleacetic Acid (5-HIAA) in acute appendicitis (AA). METHODS: This review was registered in PROSPERO (CRD42023399541). We included prospective or retrospective original clinical studies evaluating the diagnostic performance of 5-HIAA in AA. A search was conducted in PubMed, Web of Science, Scopus and OVID. Search terms and keywords were: (appendicitis OR acute appendicitis) AND (5-HIAA OR 5-Hydroxyindoleacetic acid OR serotonin metabolite). Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics, and a random-effect meta-analysis were performed. Additionally, a coupled forest plot and a diagnostic test accuracy meta-analysis (DTA) were performed. RESULTS: Twelve studies with data from 1467 participants (724 patients with a confirmed diagnosis of AA and 743 controls) were included in this review. The random-effect meta-analysis of urinary 5-HIAA (AA vs controls) included 7 articles (352 AA and 258 controls) and resulted in a significant mean difference [95% CI] of 23.30 [15.82-30.77] µmol/L (p < 0.001). The DTA meta-analysis of urinary 5-HIAA included 8 articles and resulted in a pooled sensitivity [95% CI] of 68.6 [44.1-85.9]% and a pooled specificity [95% CI] of 82 [54.7-94.5]%. CONCLUSIONS: Although the evidence is heterogeneous and limited, urinary 5-HIAA emerges as a potential non-invasive diagnostic tool for AA. Urinary 5-HIAA does not seem to be a useful biomarker to distinguish between NCAA and CAA. Future prospective studies with a large sample size and a rigorous design are necessary to validate these findings. TRIAL REGISTRATION: PROSPERO (CRD42023399541).

Leucine-Rich Alpha-2-Glycoprotein as a non-invasive biomarker for pediatric acute appendicitis: a systematic review and meta-analysis.

The aim of this study was to analyze the diagnostic performance of Leucine-Rich Alpha-2-Glycoprotein (LRG1) in pediatric acute appendicitis (PAA). We conducted a systematic review of the literature in the main databases of medical bibliography. Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS2 index. A synthesis of the results, standardization of the metrics and 4 random-effect meta-analyses were performed. Eight studies with data from 712 participants (305 patients with confirmed diagnosis of PAA and 407 controls) were included in this review. The random-effect meta-analysis of serum LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 46.76 µg/mL (29.26-64.26). The random-effect meta-analysis for unadjusted urinary LRG1 (PAA vs control) resulted in a significant mean difference (95% CI) of 0.61 µg/mL (0.30-0.93). The random-effect meta-analysis (PAA vs control) for urinary LRG1 adjusted for urinary creatinine resulted in a significant mean difference (95% CI) of 0.89 g/mol (0.11-1.66).   Conlusion: Urinary LRG1 emerges as a potential non-invasive biomarker for the diagnosis of PAA. On the other hand, due to the high between-study heterogeneity, the results on serum LRG1 should be interpreted with caution. The only study that analyzed salivary LRG1 showed promising results. Further prospective studies are needed to confirm these findings. What is Known: • Pediatric acute appendicitis continues to be a pathology with a high rate of diagnostic error. • Invasive tests, although useful, are a source of stress for patients and their parents. What is New: • LRG1 emerges as a promising urinary and salivary biomarker for the noninvasive diagnosis of pediatric acute appendicitis.

Discriminatory capacity of serum total bilirubin between complicated and uncomplicated acute appendicitis in children: a systematic review and a diagnostic test accuracy meta-analysis.

This study aimed to examine the ability of serum total bilirubin (STB) to discriminate between complicated and uncomplicated paediatric acute appendicitis (PAA). 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, OVID, Scopus, Cochrane Library). Two independent reviewers selected the relevant articles based on the previously defined inclusion and exclusion criteria. Methodological quality of the selected articles was assessed using the QUADAS2 index. Data extraction was performed by two independent reviewers. A synthesis of the results, a standardization of the metrics and a random-effect meta-analysis were performed. Between-study heterogeneity was assessed in subgroup analysis by study design. In addition, a diagnostic test accuracy (DTA) meta-analysis was performed. This review included 8 studies with data from 3634 participants aged between 0 and 18 years (2230 with uncomplicated PAA and 1404 with complicated PAA). The random-effects meta-analysis showed significantly higher mean STB in the complicated PAA group than in the uncomplicated PAA group (difference = 0.27; 95% CI 0.06-0.48) and high heterogeneity (I2 = 96%). In subgroup analyses by study design, the difference remained significant in prospective studies. The DTA meta-analysis resulted in an AUC of 0.83 (95% CI 0.79-0.86) and pooled sensitivity and specificity of 68.53% (95% CI 48.35%-83.51%) and 81.12% (95% CI 67.76%-89.78%), respectively. Mean values of STB are higher in children with complicated than uncomplicated acute appendicitis, and the diagnostic yield of STB seems to be high. Due to the high heterogeneity between studies, these results must be interpreted with caution.

Pop-off mechanisms as renoprotective mediators in children with posterior urethral valves: A systematic review and meta-analysis.

BACKGROUND: Pop-off mechanisms are potential pressure-relieving mediators in patients diagnosed with posterior urethral valves (PUV). This systematic review aimed to synthesize the existing evidence regarding the protective effect of pop-off mechanisms on renal function in children with PUV. METHODS: We conducted a systematic review of the literature that involved an extensive search in the main databases of the medical bibliography. Three independent reviewers selected the relevant articles. Methodological quality was rated using the Newcastle Ottawa Scale index. We used random meta-analyses to compare different outcomes (serum creatine, Nadir serum creatinine, and Chronic Kidney Disease) between children with PUV and pop-off mechanisms and those with PUV without pop-off mechanisms. RESULTS: 10 studies with data from 896 participants were included in this review. Seven articles reported serum creatinine values for each group and 3 of them found significant differences between groups. The random-effects meta-analysis for serum creatinine showed significant lower mean (diff = -52.88 µmol/L [95 % CI -73.65 to -32.11]) in the group of children with pop-off mechanisms, and the random-effects meta-analysis for Nadir serum creatinine showed a marginally significantly lower mean in the group of children with pop-off mechanisms (diff = -12.00 µmol/L [95 % CI -24.04 to 0.04]). The random-effect meta-analysis for Chronic Kidney Disease resulted in a significant risk reduction for the group of children with pop-off mechanisms (odds ratio = 0.48 [95 % CI 0.23 to 0.98]). CONCLUSIONS: Children with PUV and pop-off mechanisms show better renal function and lower risk of Chronic Kidney Disease than those with PUV without pop-off mechanisms suggesting these mechanisms may act as renoprotective mediators. The high heterogeneity between studies in the assessment of renal function and long-term outcomes calls for a cautious interpretation of these findings. Future studies that stratify by different types of pop-off mechanisms and use standardized metrics, such as Nadir creatinine, are needed.