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.

Diagnostic performance of serum CA-125 for overall and complicated acute appendicitis: a systematic review and meta-analysis.

This study aimed to analyze the diagnostic performance of serum CA-125 in acute appendicitis (AA). This review was registered in PROSPERO (CRD42023450988). We included prospective and retrospective original clinical studies evaluating the diagnostic performance of serum CA-125 in AA. A search was conducted in PubMed, Web of Science, Scopus, and OVID. Search terms and keywords were: (appendicitis OR appendectomy) AND (CA-125 OR CA125). Two independent reviewers selected the articles and extracted relevant data. Methodological quality was assessed using the QUADAS-2 index. A synthesis of the results, standardization of the metrics, and three random-effect meta-analyses were performed. Five studies with data from 533 participants (including 219 patients with a confirmed diagnosis of AA and 107 controls) were included in this review. The random-effect meta-analysis of serum CA-125 (AA vs controls) included 3 articles (125 AA and 70 controls) and resulted in a non-significant mean difference [95% CI] of - 6.80 [- 20.51, 6.92] U/mL (p = 0.33). The meta-analysis by subgroups that included only male patients resulted in a significant mean difference [95% CI] of 3.48 [0.46, 6.49] U/mL (p = 0.02). Although serum CA-125 does not appear to be a good overall marker for the diagnosis of AA, our subgroup analyses show that this marker could be useful for diagnosing AA in males. It also appears to be a potentially useful tool for discriminating complicated and uncomplicated AA. However, the limited number of included studies precludes drawing generalizable conclusions. Future prospective studies focused on males and in its potential ability to discriminate between complicated and uncomplicated AA are required.Registration. PROSPERO (CRD42023450988).

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.

Diagnostic Performance of Total Platelet Count, Platelet-to-Lymphocyte Ratio, and Lymphocyte-to-Monocyte Ratio for Overall and Complicated Pediatric Acute Appendicitis: A Systematic Review and Meta-Analysis.

Background: The aim of this study was to analyze the diagnostic performance of total platelet count (PC), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) in pediatric acute appendicitis (PAA). Methods: 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, a standardization of the metrics, and four random effect meta-analyses were performed. Results: Thirteen studies including data from 4,373 participants (2,767 patients with confirmed diagnosis of PAA and 1,606 controls) were included. Five studies compared PC, and the meta-analysis including three of them showed a non-significant mean difference of -34.47 platelets/1 × 109/L (95% confidence interval [CI], -88.10 to 19.16). Seven publications compared PLR and the meta-analysis of those studies showed significant mean differences between patients with PAA and controls (dif: 49.84; 95% CI, 25.82-73.85) as well as between patients with complicated and uncomplicated PAA (dif: 49.42; 95% CI, 25.47-73.37). Four studies compared LMR and the meta-analysis including 3 of them showed a non-significant mean difference of -1.88 (95% CI, -3.86 to 0.10). Conclusions: Although existing evidence is heterogeneous and limited, PLR appears to be a promising biomarker for the diagnosis of PAA and for the discrimination between complicated and uncomplicated PAA. Our results do not support the use of PC or LMR as biomarkers in PAA.