Dataset Information

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

ABSTRACT:

Introduction

Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known.

Methods

To characterize appendiceal T cells in simple and complex appendicitis we performed in-depth immunophenotyping of appendiceal-derived T cells by flow cytometry and correlated this to appendiceal-derived microbiota analyses of the same patient.

Results

Appendix samples of twenty children with appendicitis (n = 8 simple, n = 12 complex) were collected. T cells in complex appendicitis displayed an increased differentiated phenotype compared to simple appendicitis, including a loss of both CD27 and CD28 by CD4⁺ T cells and to a lesser extent by CD8⁺ T cells. Frequencies of phenotypic tissue-resident memory CD69⁺CD4⁺ T cells and CD69⁺CD8⁺ T cells were decreased in children with complex compared to simple appendicitis, indicating disruption of local tissue-resident immune responses. In line with the increased differentiated phenotype, cytokine production of in particular IL-17A by CD4⁺ T cells was increased in children with complex compared to simple appendicitis. Furthermore, frequencies of IL-17A⁺ CD4⁺ T cells correlated with a dysregulation of the appendiceal microbiota in children with complex appendicitis.

Conclusion

In conclusion, disruption of local T cell responses, and enhanced pro-inflammatory Th17 responses correlating to changes in the appendiceal microbiota were observed in children with complex compared to simple appendicitis. Further studies are needed to decipher the role of a dysregulated network of microbiota and Th17 cells in the development of complex appendicitis in children.

SUBMITTER: The SML

PROVIDER: S-EPMC10794624 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

The Sarah-May M L SML Schreurs Renée R C E RRCE Drewniak Agata A Bakx Roel R de Meij Tim G J TGJ Budding Andries E AE Poort Linda L Cense Huib A HA Heij Hugo A HA van Heurn L W Ernest LWE Gorter Ramon R RR Bunders Madeleine J MJ

Frontiers in immunology 20240104

<h4>Introduction</h4>Appendicitis is one of the most common causes of acute abdominal surgery in children. The clinical course of appendicitis ranges from simple to complex appendicitis. The mechanisms underlying the heterogeneity of appendicitis in children remain largely unclear. Dysregulated T cell responses play an important role in several inflammatory diseases of the intestine, but the extend of T cell dysregulation in appendicitis in children is less well known.<h4>Methods</h4>To characte ...[more]

PMID: 38239362

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Project description:PurposeThe function of the appendix is largely unknown, but its microbiota likely contributes to function. Alterations in microbiota may contribute to appendicitis, but conventional culture studies have not yielded conclusive information. We conducted a pilot, culture-independent 16S rRNA-based microbiota study of paired appendix and rectal samples.MethodsWe collected appendix and rectal swabs from 21 children undergoing appendectomy, six with normal appendices and fifteen with appendicitis (nine perforated). After DNA extraction, we amplified and sequenced 16S rRNA genes and analyzed sequences using CLoVR. We identified organisms differing in relative abundance using ANOVA (p<0.05) by location (appendix vs. rectum), disease (appendicitis vs. normal), and disease severity (perforated vs. non-perforated).ResultsWe identified 290 taxa in the study's samples. Three taxa were significantly increased in normal appendices vs. normal rectal samples: Fusibacter (p = 0.009), Selenomonas (p = 0.026), and Peptostreptococcus (p = 0.049). Five taxa were increased in abundance in normal vs. diseased appendices: Paenibacillaceae (p = 0.005), Acidobacteriaceae GP4 (p = 0.019), Pseudonocardinae (p = 0.019), Bergeyella (p = 0.019) and Rhizobium (p = 0.045). Twelve taxa were increased in the appendices of appendicitis patients vs. normal appendix: Peptostreptococcus (p = 0.0003), Bilophila (p = 0.0004), Bulleidia (p = 0.012), Fusobacterium (p = 0.018), Parvimonas (p = 0.003), Mogibacterium (p = 0.012), Aminobacterium (p = 0.019), Proteus (p = 0.028), Actinomycineae (p = 0.028), Anaerovorax (p = 0.041), Anaerofilum (p = 0.045), Porphyromonas (p = 0.010). Five taxa were increased in appendices in patients with perforated vs. nonperforated appendicitis: Bulleidia (p = 0.004), Fusibacter (p = 0.005), Prevotella (p = 0.021), Porphyromonas (p = 0.030), Dialister (p = 0.035). Three taxa were increased in rectum samples of patients with appendicitis compared to the normal patients: Bulleidia (p = 0.034), Dialister (p = 0.003), and Porphyromonas (p = 0.026).ConclusionSpecific taxa are more abundant in normal appendices compared to the rectum, suggesting that a distinctive appendix microbiota exists. Taxa with altered abundance in diseased and severely diseased (perforated) samples may contribute to appendicitis pathogenesis, and may provide microbial signatures in the rectum useful for guiding both treatment and diagnosis of appendicitis.

Project description:BackgroundEducational video datasets can be an effective method for training in emergency department (ED) point-of-care ultrasound (PoCUS). A video dataset for normal appendix and appendicitis in children using ED PoCUS images was developed to assess interobserver agreement, as measured by Cohen's Kappa on key sonographic findings.MethodsThree sets of 25 ED PoCUS videos were selected and curated from pediatric patients with normal appendix and acute appendicitis. Four participant ED sonologist-physicians were trained on the first set of 25 videos showing normal appendix or normal bowel in patients without appendicitis to note if normal appendix was seen in any part or in it's entirety from tip-to-cecum. They were then tested on the second set of similar videos. A third set of 25 videos from patients who had appendicitis where participant sonologists were asked to note if appendicitis was present or absent, with and without appendicolith or perforation. Cohen's Kappa was calculated in aggregate and stratified by experience vs. novice against a senior sonologist-physician aware of all patient outcomes for visualization of: 1. any part of normal appendix, 2. normal appendix visualized from tip to cecum 3. any part of appendicitis, 4. appendicolith, 5. appendiceal perforation.ResultsCohen's Kappa for any part of normal appendix, 0.71, 95% CI (0.58-0.85); normal appendix tip-to-cecum, 0.43, 95% CI (0.19-0.67), appendicitis, 0.53, 95%CI (0.34-0.70), appendicolith, 0.63, 95%CI (0.43-0.84), perforated appendicitis, 0.46, 95%CI (0.22-0.70). Stratified by experienced vs. novice: any part of normal appendix, 0.75 vs. 0.68; normal appendix tip-to-cecum, 0.50 vs. 0.36; appendicitis, 0.78 vs. 0.31; appendicolith, 0.75 vs. 0.5; perforated appendicitis, 0.5 vs 0.42.ConclusionsThis educational video dataset may be used to train sonologist-physicians in ED PoCUS scanning for normal appendix and appendicitis in children. Sonologist experience affected interobserver agreement with respect to visualization of entire normal appendix and appendicitis.

Project description:Acute appendicitis is one of the most common causes of acute abdominal diseases seen between the ages of 10 and 19, mostly seen in males. The lifetime risk of developing acute appendicitis is 8.6% for males and 6.7% for females. We aimed to investigate the efficacy of the complete blood count parameters, C-reactive protein, and Lymphocyte-C-reactive Protein Ratio laboratory tests in the diagnosis of acute appendicitis, as well as their relationship with appendix diameter. We retrospectively examined all patients who underwent appendectomy between 1 January 2012 and 30 June 2019 in the General Surgery Clinic of Gaziosmanpasa University Faculty of Medicine. Laboratory tests, imaging findings, age, and gender were recorded. Lymphoid hyperplasia is considered as normal appendix-in other words, as negative appendicitis. The distribution of Lymphoid hyperplasia and appendicitis rates were statistically different in the groups formed according to appendix diameter (?6 and >6 mm) (p < 0.001). We found a significant correlation between appendix diameter and WBC (White blood count), Lymphocyte, Neutrophil, RDW(Red blood cell distribution width), NLR(Neutrophil to lymphocyte ratio), and PLT/L (Platelet to lymphocyte ratio), MPV (Mean platelet volume) and RDW were significantly different in patients with an appendix diameter of ?6 mm (p = 0.007, p = 0.006, respectively). WBC, Neutrophil, PDW, and NLR values were significantly different between appendicitis and hyperplasia groups in patients with an appendix diameter of >6 mm. The sensitivity of the NLR score (cutoff = 2.6057) in the diagnosis of appendicitis was 86.1% and selectivity was 50% in these patients. Complete blood count parameters evaluation with the clinical findings revealed that NLR is an important parameter that may help the diagnosis of acute appendicitis with an appendix diameter of >6 mm. In patients whose pathological results indicated acute appendicitis but who had a diameter of ?6 mm, we found an elevated MPV and low RDW values.

Dataset Information

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

Introduction

Methods

Results

Conclusion

Publications

Enhanced Th17 responses in the appendix of children with complex compared to simple appendicitis are associated with microbial dysbiosis.

Similar Datasets

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