MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis.

Mucosal-associated invariant T (MAIT) cells are antimicrobial T cells abundant in the gut, but mechanisms for their migration into tissues during inflammation are poorly understood. Here, we used acute pediatric appendicitis (APA), a model of acute intestinal inflammation, to examine these migration mechanisms. MAIT cells were lower in numbers in circulation of patients with APA but were enriched in the inflamed appendix with increased production of proinflammatory cytokines. Using the patient-derived appendix organoid (PDAO) model, we found that circulating MAIT cells treated with inflammatory cytokines elevated in APA up-regulated chemokine receptors, including CCR1, CCR3, and CCR4. They exhibited enhanced infiltration of Escherichia coli-pulsed PDAO in a CCR1-, CCR2-, and CCR4-dependent manner. Close interactions of MAIT cells with infected organoids led to the PDAO structural destruction and death. These findings reveal a previously unidentified mechanism of MAIT cell tissue homing, their participation in tissue damage in APA, and their intricate relationship with mucosal tissues during acute intestinal inflammation in humans.

Compilation of Evidence Supporting the Role of a T Helper 2 Reaction in the Pathogenesis of Acute Appendicitis.

Despite being the most common abdominal surgical emergency, the cause of acute appendicitis (AA) remains unclear, since in recent decades little progress has been made regarding its etiology. Obstruction of the appendicular lumen has been traditionally presented as the initial event of AA; however, this is often the exception rather than the rule, as experimental data suggest that obstruction is not an important causal factor in AA, despite possibly occurring as a consequence of the inflammatory process. Type I hypersensitivity reaction has been extensively studied, involving Th2 lymphocytes, and cytokines such as IL-4, IL-5, IL-9 and IL-13, which have well-defined functions, such as a positive-feedback effect on Th0 for differentiating into Th2 cells, recruitment of eosinophils and the release of eosinophilic proteins and the production of IgE with the activation of mast cells, with the release of proteins from their granules. Cytotoxic activity and tissue damage will be responsible for the clinical manifestation of the allergy. AA histological features are similar to those found in allergic reactions like asthma. The intestine has all the components for an allergic immune response. It has contact with hundreds of antigens daily, most of them harmless, but some can potentially induce an allergic response. In recent years, researchers have been trying to assess if allergy is a component of AA, with their latest advances in the understanding of AA as a Th2 reaction shown by the authors of this article.

Comparison of miRNA profiles in the immune response of pediatric acute appendicitis and pediatric enterobiasis patients caused by Enterobius vermicularis.

BACKGROUND: The aim of this study was to determine and compare the miRNA profile in the immune response with the parasite in pediatric patients with acute appendicitis caused by Enterobius vermicularis and in pediatric patients with enterobiasis. METHODS: A total of 30 tissue samples, which were operated with the diagnosis of pediatric acute appendicitis in the last 10 y and Enterobius vermicularis was detected by histopathological findings, were analyzed. In addition, blood samples were taken from 30 pediatric patients diagnosed with enterobiasis for this study. The miRNAs that activate T and B cells were evaluated by a quantitative real-time PCR, statistically calculated within ΔΔCt values, and fold changes were evaluated by Welch's T test, in which p<0.5 was considered to be significant. RESULTS: It was found that 48 out of 136 (35.3%) miRNAs differed between the pediatric patient and healthy control groups. It was determined that 22 (57.9%) of the different miRNAs were T cell activating miRNAs and 26 (68.4%) were B cell activating miRNAs. While there was a significant difference in miRNA values activating T cells in two patient groups (p<0.01), there was no significant difference in miRNA values activating B cells (p>0.01). CONCLUSIONS: In the study, although Enterobius vermicularis was the causative agent in both patient groups, it was revealed that the immune response of patients with acute appendicitis was more affected than enterobiasis patients.

Increased IgE Deposition in Appendicular Tissue Specimens Is Compatible with a Type I Hypersensitivity Reaction in Acute Appendicitis.

BACKGROUND: IgE mediates type I hypersensitivity reaction and can be found in the mucosa of organs affected by allergy. Acute appendicitis (AA) is a common disease, but its etiology remains poorly understood. Here, we investigated IgE deposition in histological sections of AA samples to test the hypothesis that an allergic reaction may substantially contribute to the pathophysiology of AA. MATERIALS AND METHODS: In a retrospective study, we assessed the presence of IgE in appendicular specimens of histologically confirmed appendicitis and in the control group, comprised of negative appendicitis and incidental appendectomies, using a monoclonal antibody against human IgE. Samples from 134 appendectomies were included: 38 phlegmonous and 27 gangrenous appendicitis from the study group and 52 incidental appendectomies and 17 negative appendicitis from the control group. The slides were visualized by light microscopy, and a standard procedure was used to manually count the positive IgE staining cells. RESULTS: IgE staining was present in the cells of all but 5 appendicular specimens. We found a significantly increased number of IgE-positive cells in phlegmonous AA (median = 28) when compared to incidental appendectomy (median = 17) (p = 0.005; p < 0.0001 when adjusted for age and gender). No difference was found for gangrenous appendicitis. Discussion. The presence of IgE supports the contribution of an allergic reaction for the pathophysiology of phlegmonous appendicitis. The reduced number of IgE staining cells in gangrenous appendicitis can be due to tissue destruction, or, as been claimed by others, gangrenous appendicitis is a distinct entity, with different etiology. CONCLUSION: In this study, phlegmonous appendicitis had the highest number of IgE-positive appendicular cells. These findings suggest that an allergic reaction can contribute to the pathophysiology of AA, opening a novel possibility for preventive measures in a disease that typically requires surgery.

An observational study of innate immune responses in patients with acute appendicitis.

Acute appendicitis is a common surgical emergency worldwide. Exaggerated immune responses could be associated with appendicitis. This study aimed at characterizing immune responses towards a large variety of gut commensals and pathogens, and pattern recognition receptor (PRR) ligands, and investigating the course of systemic inflammation in a prospective cohort of acute appendicitis patients. PBMC responses of 23 patients of the cohort and 23 healthy controls were characterized more than 8 months post-surgery. Serum cytokine levels were measured in 23 patients at the time of appendicitis and after one month. CRP, WBC and percentage of neutrophils were analyzed in the total cohort of 325 patients. No differences in PBMC responses were found between patients and controls. Stronger IL-10 responses were found following complicated appendicitis. A trend towards lower IL-8 responses was shown following gangrenous appendicitis. Serum IL-10 and IL-6 were significantly elevated at presentation, and IL-6, IL-8 and TNF-α levels were higher in complicated appendicitis. Routine biomarkers could predict severity of appendicitis with high specificities, but low sensitivities. Cytokine responses in patients following acute appendicitis did not differ from healthy controls. Higher serum cytokine levels were found in acute complicated and gangrenous cases. Further research into discriminative biomarkers is warranted.

Markers of neutrophil activation and extracellular traps formation are predictive of appendicitis in mice and humans: a pilot study.

Appendicitis is one of the most frequent emergencies in pediatric surgery, yet current biomarkers for diagnosis are unspecific and have low predictive values. As neutrophils and extracellular traps (ETs) are an essential component of the immune defense against bacterial infections, and appendicitis is considered an inflammation reaction of the appendix, we hypothesized that neutrophil activation and NET formation play an essential role in appendicitis development and maintenance. Therefore, this pilot study aimed to establish a murine model of appendicitis and to evaluate ETs markers to diagnose appendicitis in mice and humans. The study used 20 (12 appendicitis- and 8 controls) 6-week old mice which underwent advanced appendicitis induction using a modified caecal ligation puncture procedure. During the study, cell-free DNA, neutrophil elastase (NE), myeloperoxidase (MPO), and citrullinated Histone H3 (H3cit) were assessed. Additionally, samples of 5 children with histologically confirmed appendicitis and 5 matched controls with catarrhal appendicitis, were examined for the same biomarkers. Moreover, NE, MPO, and H3cit were assessed histologically via immunofluorescence in mice and humans. All mice in the appendicitis group developed an advanced form of appendicitis with focal peritonitis. In mice and humans with appendicitis, markers of neutrophil activation and ETs formation (especially cfDNA, NE and H3cit) were significantly elevated in blood and tissue compared to controls. Ultimately, biomarkers correlated extremely well with tissue expression and thus disease severity. It appears that neutrophil activation and possibly NETs contribute to appendicitis development and biomarkers of neutrophil activation and ET formation reflect disease severity and thus could be used as biomarkers for appendicitis. However, large prospective clinical studies are needed to confirm our findings.

Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants.

The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.

Genetic polymorphism patterns suggest a genetic driven inflammatory response as pathogenesis in appendicitis.

PURPOSE: The pathogenesis of appendicitis is not well understood. Environmental factors are regarded most important, but epidemiologic findings suggest a role of inflammatory and genetic mechanisms. This study determines the association of single nucleotide polymorphisms (SNPs) of inflammatory genes with appendicitis. METHODS: As part of a larger prospective study on the diagnostic value of inflammatory variables in appendicitis, the genotype frequency of 28 polymorphisms in 26 inflammatory response genes from the appendicitis and control patients was analyzed in blood samples from 343 patients, 100 with appendicitis, and 243 with non-specific abdominal pain, using TaqMan SNP genotyping assays. RESULTS: Associations with appendicitis were found for SNPs IL-13 rs1800925 with odds ratio (OR) 6.02 (95% CI 1.52-23.78) for T/T versus C/C + T/T, for IL-17 rs2275913 with OR 2.38 (CI 1.24-4.57) for A/A vs G/G + GA, for CCL22 rs223888 with OR 0.12 (0.02-0.90), and for A/A vs G/G + GA. Signs of effect modification of age for the association with appendicitis were found for IL-13 rs1800925 and CTLA4 rs3087243. Stratified analysis showed difference in association with severity of disease for IL-17 rs2275913 and CD44 rs187115. CONCLUSIONS: The association of gene variants on risk of appendicitis and its severity suggest an etiologic role of genetically regulated inflammatory response. This may have implications for understanding the prognosis of untreated appendicitis as a possible self-limiting disorder and for understanding the inverse association of appendicitis with ulcerative colitis.

Absolute neutrophil count as a diagnostic guide for the use of MRI in the workup of suspected appendicitis in children.

BACKGROUND/PURPOSE: To assess the additive value of magnetic resonance imaging (MRI) in the setting of an equivocal US (Eq-US) with or without an elevated absolute neutrophil count (ANC). METHODS: Single-institution, retrospective review of children ages 5-18 years who presented to the ER with suspected appendicitis from 9/2015 to 8/2016. US, ANC, and MRI results were reviewed. Imaging was identified as positive/suspicious, normal, or equivocal and ANC <8000/mm3 was defined as normal. RESULTS: 738 patients with a median age of 11 years (IQR 8-14) met inclusion criteria. US was equivocal in 61.4%. Among 304 (67.1%) patients with an Eq-US and normal ANC, only 5 (1.6%) had acute appendicitis. In contrast, 28 of 149 patients (18.8%) with Eq-US and elevated ANC had appendicitis. MRI was performed in 125 patients with Eq-US and was positive/suspicious in 2.9% (2/69) with normal ANC and 25.0% (14/56) with elevated ANC. MRI had 94.7% sensitivity and 100% specificity for acute appendicitis in patients with an Eq-US. CONCLUSIONS: MRI has high sensitivity and specificity for diagnosing acute appendicitis in children. Patients with Eq-US plus a normal ANC have a very low likelihood of appendicitis and do not typically require further imaging. MRI may have utility for children with Eq-US and elevated ANC. LEVEL OF EVIDENCE: Level III.

Acute eosinophilic appendicitis simulating uncomplicated appendicitis.

Acute appendicitis is one of the most common abdominal emergencies worldwide. Uncomplicated appendicitis (UA), which does not involve perforation or peritonitis, has recently been treated with antibiotic therapy. Here, we report a case of acute eosinophilic appendicitis (AEA) that simulated UA and did not respond to antibiotic therapy. A 20-year-old Japanese woman emergently presented with the chief complaint of pain at the right iliac fossa. CT showed only swelling of the appendix. She was diagnosed with UA, and she received antibiotic therapy initially. However, the treatment was not effective and appendectomy was performed. The final histopathological diagnosis was AEA. The findings of this case suggest that AEA is likely to be diagnosed as UA. As AEA can simulate UA, the possibility of AEA should be considered when antibiotic therapy is not effective.

Role of preoperative C-reactive protein value and neutrophil ratio in the determination of conversion from laparoscopic appendectomy to open appendectomy.

BACKGROUND: In this study, we aimed to investigate the factors causing conversion from laparoscopic appendectomy (LA) to open appendectomy (OA) in patients with acute appendicitis and to investigate the role of preoperative C reactive protein (CRP) and neutrophil ratio in this conversion and determine a cut-off point for these parameters. METHODS: Records of patients who underwent LA due to acute appendicitis at our general surgery department between January 2011 and January 2017 were retrospectively evaluated. The preoperative American Society of Anesthesiology (ASA) scores, Alvarado scores, white blood cell count, C-reactive protein level, and neutrophil ratio were evaluated. RESULTS: LA was performed in 394 patients with an initial diagnosis of acute appendicitis. A conversion to OA (cOA) was performed in 17 patients (4.31%). A CRP value of ≥108.5 mg/L and a neutrophil ratio of ≥81.5% were found to be statistically significant for the cOA (p<0.001). CONCLUSION: Our study results showed that male gender, age, elevated neutrophil ratio, and CRP value were the main risk factors for cOA in patients who were scheduled for LA due to acute appendicitis.

A new and early marker in the diagnosis of acute complicated appendicitis: immature granulocytes.

BACKGROUND: The aim of this study was to investigate the effectiveness of the immature granulocyte (IG) count (IGC) and percentage (IG%) in both diagnosing acute appendicitis (AA) and discriminating between simple appendicitis (SA) and complicated appendicitis (CA). METHODS: This study was carried out using the data of 438 adult patients who underwent an appendectomy. Demographic details, the preoperative white blood cell (WBC) count, neutrophil/lymphocyte ratio (NLR), IGC and IG%, operation findings, and pathology results were assessed retrospectively. The patients were grouped as AA and normal appendix (NA) according to the pathology reports, and the AA cases were subdivided into SA and CA groups according to the intraoperative findings. RESULTS: WBC, NLR, IGC, and IG% were significant parameters in the diagnosis of AA. The area under the receiver operating characteristic curve (AUROC: 0.795), sensitivity (55.5%) and specificity (96.1%) values of IGC were higher than the other parameters. All of the parameters were also significant for a CA diagnosis; however, the value of IG% in a CA diagnosis was stronger than the other parameters (IG% AUROC: 0.979, sensitivity: 94.4%, specificity: 97.9%). CONCLUSION: The IG value is a fast, easily available, and reliable parameter in both diagnosing AA and discriminating between SA and CA.

Presentación clínica de la apendicitis aguda en pacientes inmunocomprometidos por diabetes o VIH/sida.

INTRODUCCIÓN: Los pacientes inmunocomprometidos presentan respuesta inflamatoria limitada que puede retrasar el diagnóstico de la apendicitis aguda (AA). OBJETIVO: Evaluar si el inmunocompromiso puede afectar el curso clínico y evolución de la AA. MÉTODO: Análisis retrospectivo, comparativo, de pacientes sometidos a apendicectomía por AA: con VIH, diabetes mellitus tipo 2 (DM2) y sin otra patología. RESULTADOS: Se revisaron 128 pacientes con AA intervenidos quirúrgicamente (53.6 % del sexo femenino), edad media de 42.5 años, 15 (11.7 %) tenían diagnóstico de VIH, 47 (36.7 %) de DM2 y 66 (51.6 %) no cursaban con otra enfermedad. La proporción de leucocitosis fue menor en el grupo con VIH (66.7 %; p = 0.007). En los pacientes con VIH y DM2 se registró mayor tiempo de evolución: 66.9 ± 61.2y 90.1 ± 144 horas (p ≤ 0.001), mayor tiempo de estancia hospitalaria: 11.1 ± 17.1 y 6.5 ± 4.1 días (p ≤ 0.0001), mayor tasa de complicaciones: 20 y 23.8 % (p = 0.036). La complicación más frecuente fue la infección del sitio quirúrgico superficial y profunda. La hemicolectomía derecha fue más frecuente en el grupo con VIH (20 %, p = 0.017). No se registró mortalidad. CONCLUSIONES: La inmunodepresión afecta el curso clínico y evolución de la AA. INTRODUCTION: Immunocompromised patients experience limited inflammatory response, which can delay acute appendicitis (AA) diagnosis. OBJECTIVE: To assess if immunosuppression can affect AA clinical course and evolution. METHOD: Comparative, retrospective analysis of patients with HIV or type 2 diabetes mellitus (DM2) or with no other pathology who underwent appendectomy for AA. RESULTS: A total of 128 patients with AA who were surgically intervened were assessed (53.6% were of the female gender); mean age was 42.5 years, 15 (11.7%) had been diagnosed with HIV infection, 47 (36.7%) with DM2 and 66 (51.6%) had no other disease. The proportion of leukocytosis was lower in the HIV group (66.7%; p = 0.007). Patients with HIV and DM2 had longer evolution time (HIV 66.9 ± 61.2, DM2 90.1 ± 144 hours; p ≤ 0.001), longer hospital length of stay (HIV 11.1 ± 17.1, DM2 6.5 ± 4.1 days; p ≤ 0.0001), and a higher rate of complications (HIV 20%, DM2 23.8%; p = 0.036). The most common complication was superficial and deep surgical site infection. Right hemicolectomy was more common in the HIV group (20%; p = 0.017). There was no mortality registered. CONCLUSIONS: Immunosuppression affects AA clinical course and evolution.

Association of IgE-Mediated Allergy With Risk of Complicated Appendicitis in a Pediatric Population.

Importance: Childhood appendicitis is commonly complicated by gangrene and perforation, yet the causes of complicated appendicitis and how to avoid it remain unknown. Objective: To investigate whether children with IgE-mediated allergy have a lower risk of complicated appendicitis. Design, Setting, and Participants: This retrospective cohort study included all consecutive patients younger than 15 years (hereinafter referred to as children) who underwent appendectomy for acute appendicitis at a tertiary pediatric surgery center in Sweden between January 1, 2007, through July 31, 2017. Children were stratified between those with and without IgE-mediated allergies. Main Outcome and Measures: Risk of complicated appendicitis with gangrene or perforation, with occurrence of IgE-mediated allergy as an independent variable and adjusted for age, sex, primary health care contacts, seasonal antigenic exposure, allergy medications, appendicolith, and duration of symptoms. Results: Of 605 included children (63.0% boys; median age, 10 years; interquartile range, 7-12 years), 102 (16.9%) had IgE-mediated allergy and 503 (83.1%) had no allergy. Complicated appendicitis occurred in 20 children with IgE-mediated allergy (19.6%) compared with 236 with no allergy (46.9%; adjusted odds ratio, 0.33; 95% CI, 0.18-0.59). No significant allergy effect modification by sex, seasonal antigenic exposure, or allergy medication was found. Children with IgE-mediated allergy had a shorter hospital stay (median, 2 days for both groups; interquartile range, 1-2 days vs 1-5 days; P = .004). Conclusions and Relevance: In this study, children with IgE-mediated allergy had a lower risk of complicated appendicitis. The findings suggest that immunologic disposition modifies the clinical pattern of appendiceal disease. This theory introduces novel opportunities for understanding of the pathogenesis and clinical decision making for one of childhood's most common surgical emergencies.

The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis and Appendectomy.

The appendix contains abundant lymphoid tissue and is constantly exposed to gut flora. When completed at a young age, appendicitis followed by appendectomy (AA) prevents or significantly ameliorates Inflammatory Bowel Diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn's disease and ulcerative colitis. Our murine AA model is the only existing experimental model of AA. In our unique model, AA performed in the most proximal colon limits colitis pathology in the most distal colon by curbing T-helper 17 cell activity, diminishing autophagy, modulating interferon activity-associated molecules, and suppressing endothelin vaso-activity-mediated immunopathology. In the research presented in this paper, we have examined the role of chemokines in colitis pathology with our murine AA model. Chemokines are a family of small cytokines with four conserved cysteine residues. Chemokines induce chemotaxis in adjacent cells with corresponding receptors. All 40 known chemokine genes and 24 chemokine receptor genes were examined for gene expression levels in distal colons three days post-AA and 28 days post-AA. At 28 days post-AA, the chemokine gene CCL5 was significantly upregulated. Furthermore, Gene Set Enrichment Analysis (GSEA) showed upregulation of seven CCL5-associated gene-sets 28 days post-AA in contrast to just one gene-set downregulated at the same time-point. The chemokine gene CXCL11 was significantly upregulated three days post-AA and 28 days post-AA. Evaluation using GSEA showed upregulation of six CXCL11-associated gene sets but no downregulation of any gene set. At 28 days post-AA, CCL17 gene expression was significantly downregulated. There was no expression of any chemokine receptor gene three days post-AA, but CCR10 was the only chemokine receptor gene that displayed differential gene expression (upregulation) 28 days post-AA. No CCR10-associated gene set was upregulated in GSEA in contrast to one downregulated gene set. Our analysis resulted in identifying three new therapeutic targets towards ameliorating colitis: CCL5, CXCL11, and CCL17. While CCL5 and CXCL11 are good therapeutic chemokine candidates to be exogenously administered, CCL17 is a good candidate chemokine to competitively inhibit or limit colitis pathology.

Isolated Acute Appendicitis Caused by Aspergillus in a Patient Who Underwent Lung Transplantation: A Case Report.

Invasive aspergillosis is an important cause of morbidity and mortality in patients who have undergone lung transplantation. Aspergillus infections usually involve the respiratory tract, with vascular invasion and subsequent dissemination. However, acute appendicitis associated with localized aspergillosis is rare, especially among patients who have undergone prophylaxis with voriconazole. We present a case of primary Aspergillus appendicitis diagnosed by histologic examination in a patient who underwent lung transplantation. A 51-year-old woman with dermatomyositis underwent lung transplantation for acute interstitial pneumonitis. According to our institution's protocol, the patient was treated with immunosuppressive therapy and prophylaxis with voriconazole, ganciclovir, and trimethoprim sulfamethoxazole during the post-transplantation period. Twenty-eight days after transplantation, the patient developed mild abdominal pain and paralytic ileus. There was no apparent infection sign. Abdominal computerized tomography indicated a wall defect of the appendix with multifocal fluid collection, mesenteric leave thickening, and pneumoperitoneum. These findings were consistent with perforated appendicitis, and the patient underwent an appendectomy. The histopathology examination of the resected appendix showed inflammation and abscess. Periodic acid-Schiff-positive and Grocott-Gomori methenamine silver-positive fungal hyphae with acute-angle branching were observed, demonstrating muscular invasion. A galactomannan antigen test obtained on the same day had negative results. The trough level of voriconazole was well maintained and was subsequently adjusted through monitoring of circulating drug concentration. Simultaneously, other potential sites of disseminated Aspergillus were considered and examined, but no other site of systemic Aspergillus infection was detected. Voriconazole treatment was maintained for 3 months, and no aspergillosis relapse or other invasive fungal infections were observed.

Metabolomic and inflammatory mediator based biomarker profiling as a potential novel method to aid pediatric appendicitis identification.

Various limitations hinder the timely and accurate diagnosis of appendicitis in pediatric patients. The present study aims to investigate the potential of metabolomics and cytokine profiling for improving the diagnosis of pediatric appendicitis. Serum and plasma samples were collected from pediatric patients for metabolic and inflammatory mediator analyses respectively. Targeted metabolic profiling was performed using Proton Nuclear Magnetic Resonance Spectroscopy and Flow Injection Analysis Mass Spectrometry/Mass Spectrometry and targeted cytokine/chemokine profiling was completed using a multiplex platform to compare children with and without appendicitis. Twenty-three children with appendicitis and 35 control children without appendicitis from the Alberta Sepsis Network pediatric cohorts were included. Metabolomic profiling revealed clear separation between the two groups with very good sensitivity (80%), specificity (97%), and AUROC (0.93 ± 0.05) values. Inflammatory mediator analysis also distinguished the two groups with high sensitivity (82%), specificity (100%), and AUROC (0.97 ± 0.02) values. A biopattern comprised of 9 metabolites and 7 inflammatory compounds was detected to be significant for the separation between appendicitis and control groups. Integration of these 16 significant compounds resulted in a combined metabolic and cytokine profile that also demonstrated strong separation between the two groups with 81% sensitivity, 100% specificity and AUROC value of 0.96 ± 0.03. The study demonstrated that metabolomics and cytokine mediator profiling is capable of distinguishing children with appendicitis from those without. These results suggest a potential new approach for improving the identification of appendicitis in children.

Immunoproteasome in the blood plasma of children with acute appendicitis, and its correlation with proteasome and UCHL1 measured by SPR imaging biosensors.

The aim of this study was to determinate the immunoproteasome concentration in the blood plasma of children with appendicitis, and its correlation with circulating proteasome and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1). Twenty-seven children with acute appendicitis, managed at the Paediatric Surgery Department, were included randomly into the study (age 2 years 9 months up to 14 years, mean age 9·5 ± 1 years). There were 10 girls and 17 boys; 18 healthy, age-matched subjects, admitted for planned surgeries served as controls. Mean concentrations of immunoproteasome, 20S proteasome and UCHL1 in the blood plasma of children with appendicitis before surgery 24 h and 72 h after the appendectomy were higher than in the control group. The immunoproteasome, 20S proteasome and UCHL1 concentrations in the blood plasma of patients with acute appendicitis were highest before surgery. The immunoproteasome, 20S proteasome and UCHL1 concentration measured 24 and 72 h after the operation decreased slowly over time and still did not reach the normal range (P < 0·05). There was no statistical difference between immunoproteasome, 20S proteasome and UCHL1 concentrations in children operated on laparoscopically and children after classic appendectomy. The immunoproteasome concentration may reflect the metabolic response to acute state inflammation, and the process of gradual ebbing of the inflammation may thus be helpful in the assessment of the efficacy of treatment. The method of operation - classic open appendectomy or laparoscopic appendectomy - does not influence the general trend in immunoproteasome concentration in children with appendicitis.

Retrospective review of laparoscopic versus open surgery in the treatment of appendiceal abscess in pediatric patients: Laparoscopic versus open surgery for appendiceal abscess.

Laparoscopic appendectomy (LA) has become well accepted, but the role of LA for appendicitis upon presentation with an abscess remains undefined. This study was to assess the postoperative recovery and complications following LA in pediatric patients with appendiceal abscess in comparison with open appendectomy (OA).We conducted a retrospective review of patients presented with appendiceal abscess between 2005 and 2016. Propensity score matching (PSM) was conducted to adjust for any potential selection bias for the surgical approaches. In 108 matched patients, operative outcomes and surgical complications were evaluated based on LA or OA.The patients with LA experienced prompt postoperative gastrointestinal function recovery, like first bowel movement (risk ratio [RR], 0.52; 95% confidence interval [CI], 0.44-0.69; P < .001), so spend the lower mean length of hospitalization (RR, 0.53; 95% CI, 0.41-0.76; P < .001) in comparison with patients with OA. Furthermore, the immunologic and inflammatory variable white blood cell (WBC) (RR, 0.56; 95% CI, 0.46-0.73; P < .001) and C-reactive protein (CRP) (RR, 0.58; 95% CI, 0.43-0.86; P = .011) on postoperative days (POD) 5 was reduced in patients undergone LA compared with that of OA. A lower overall postoperative complication rate, including surgical wound infection (odds ratio [OR], 0.38; 95% CI, 0.18-0.81; P = .008) and incision dehiscence (OR, 0.06; 95% CI, 0.01-0.45; P < .001) was noted in patients with LA compared with OA.LA was feasible and effective for appendicitis upon presentation with an abscess and associated with beneficial clinical effects, such as postoperative gastrointestinal function recovery and reduced postoperative complications. LA should be seriously considered as the first line procedure of choice.