Microbiota Assessment of Pediatric Simple and Complex Acute Appendicitis.

Background and Objectives. The aim of this study is to determine the prevailing microbiota in samples from pediatric patients with acute appendicitis, as well as evaluate the antibacterial sensitivity of the isolated microorganisms, comparing the data obtained with the clinic's antibacterial therapy guidelines. Materials and Methods. The study group consisted of 93 patients between the ages of 7 and 18. All patients underwent a laparoscopic or conventional appendectomy. The children were hospitalized with signs and symptoms suggestive of acute appendicitis. Microbiological cultures from the appendix and abdominal cavity were collected intraoperatively. Results. E. coli was identified in most cases irrespective of the clinical presentation of acute appendicitis. Most strains were susceptible to ampicillin and amoxicillin/clavulanic acid. Five strains of E. coli produced extended spectrum beta-lactamase (ESBL). Pseudomonas aeruginosa (P. aeruginosa) was the second most commonly isolated causative agent. Furthermore, it was common in cases of acute complex appendicitis. Most strains of P. aeruginosa were resistant to amoxicillin/clavulanic acid, ertapenem, ampicillin and cefotaxime, yet were susceptible to ceftazidime. Regardless of the clinical presentation, the samples yielded mixed isolates. Conclusion. E. coli is the main causative agent of acute appendicitis in the pediatric population displaying susceptibility to various antibiotics. P. aeruginosa was more prevalent in cases of acute complex appendicitis. P. aeruginosa isolates were susceptible to ceftazidime; however, they were resistant to cefotaxime, which should, therefore, be removed from guidelines for empirical antibacterial treatment of acute appendicitis due to phenotypic resistance of P. aeruginosa. We recommend antibiotics with distinct implementation to avoid antibiotic resistance.

Case Series of Variable Acute Appendicitis in Children with SARS-CoV-2 Infection.

This case series study consists of six children, aged 5-16 years, admitted to a centralized tertiary paediatric hospital serving a population of 1.9 million with acute appendicitis in the setting of SARS-CoV-2 infection. From the beginning of the pandemic in March 2020 until August 2021, 121 COVID-19-positive children were admitted to the hospital. A total of 49 (40.5%) of these patients presented with gastrointestinal symptoms, of which six were diagnosed with acute appendicitis. Five underwent an appendectomy, while one was treated conservatively. To date, it has been reported that appendicitis may have a plausible association with SARS-CoV-2 infection in children. With COVID-19 cases rising, every medical specialist, including all paediatric surgeons, must be ready to treat common acute diseases with SARS-CoV-2 infection as a comorbidity. Providers should consider testing for this infection in paediatric patients with severe gastrointestinal symptoms. Non-surgical treatment of acute appendicitis in children may gain new importance during and after the COVID-19 pandemic. Further studies are needed to prove the link of causality between COVID-19 and acute appendicitis in children.

Gallbladder Interleukins in Children with Calculous Cholecystitis.

Calculous cholecystitis connects to inflammation and various complications. It is a common disease in the paediatric population, yet it is still uncertain how inflammation factors are involved in its morphopathogenesis. Twenty calculous cholecystitis surgery tissue samples were obtained from 20 children. As a control, seven unaffected gallbladders were used. Tissues were immunohistochemically stained for IL-1α, IL-4, IL-6, IL-7, IL-8, IL-10, and IL-17A, and the slides were inspected by light microscopy. To evaluate statistical differences and correlations between interleukins, Mann-Whitney U and Spearman's tests were used. Statistically significant difference between patient and control gallbladder epithelium was for IL-1α and IL-17A, but connective tissue-IL-1α, IL-4, IL-6, IL-7, IL-8, and IL-17A positive structures. A strong positive correlation in patients was detected between epithelial IL-1α and IL-1α in connective tissue, epithelial IL-6 and IL-7, IL-6 and IL-17A, IL-7 and IL-10, IL-7 and IL-17A, as well as between IL-6 and IL-7, IL-7 and IL-10 in connective tissue. The increase of IL-1α, IL-4, IL-6, IL-7, IL-8 and IL-17A positive structures suggests their role in the morphopathogenesis of calculous cholecystitis. The correlations between interleukins in epithelium and in connective tissues prove that the epithelial barrier function and inflammatory response in deeper layers are sustained through intercellular signalling pathways.

Serum and Urine Biomarker Leucine-Rich Alpha-2 Glycoprotein 1 Differentiates Pediatric Acute Complicated and Uncomplicated Appendicitis.

PURPOSE: This prospective, single-center cohort study analyzes the potential of inflammatory protein mediator leucine-rich alpha-2 glycoprotein 1 (LRG1) for the early and accurate diagnosis of acute appendicitis (AA), and differentiation of acute complicated (AcA) from uncomplicated appendicitis (AuA). METHODS: Participants were divided into the AcA, AuA, and control groups, and their serum (s-LRG1) and urine LRG1 (u-LRG1) levels were assayed preoperatively on the second and fifth postoperative days. RESULTS: 153 patients participated, 97 had AA. Preoperative u-LRG1 with a cut-off value of 0.18 µg/mL generated an area under the receiver operated characteristic (AUC) curve of 0.70 (95% CI 0.62-0.79) for AA versus control (p < 0.001), while the results for AcA versus AuA were not significant (AUC 0.60, 95% CI 0.49-0.71, p = 0.089). The s-LRG1 levels of AA versus the control with a cut-off value of 51.69 µg/mL generated an AUC of 0.94 (95% CI 0.91-0.99, p < 0.001). The cut-off value of s-LRG1 was 84.06 µg/mL for diagnosis of AcA from AuA, and therefore, significant (AUC 0.69, 95% CI 0.59-0.80, p = 0.001). CONCLUSIONS: LRG1 exhibited excellent diagnostic performance as an inexpensive, non-invasive, rapid, and accurate biomarker able to reflect the pathogenesis of AA. LRG1 has the potential to replace advanced imaging to diagnose clinically ambiguous AA cases.

Determining acute complicated and uncomplicated appendicitis using serum and urine biomarkers: interleukin-6 and neutrophil gelatinase-associated lipocalin.

PURPOSE: The study aim is to determine whether serum and urine interleukin-6 (IL-6) and neutrophil gelatinase-associated lipocalin (NGAL) can be included in the early diagnostic algorithm for pediatric appendicitis. METHODS: Prospective single-center cohort study included 92 children divided into control, acute complicated appendicitis (AcA) and acute uncomplicated appendicitis (AnA) groups. Serum and urine samples were assayed for IL-6 and NGAL preoperatively, and on the second and fifth postoperative days. Intraoperative and bacteriological findings divided the appendicitis patients. RESULTS: Average serum biomarker levels were higher in appendicitis patients versus the control, and the following values were produced via receiver operating characteristic (ROC) analysis. NGAL and IL-6 cutoff values were 113.95 ng/ml and 24.64 pg/ml, respectively, NGAL had 68.3% sensitivity and 65.5% specificity, while IL-6 had 72.6% and 86.2%. Comparing AcA and AnA, IL-6 was the only biomarker of significance yielding 77.4% sensitivity and 58.1% specificity with a 26.43 pg/ml cutoff value. Urine biomarkers were non-specific in differentiation appendicitis severity and ultimately, between infectious and non-infectious disease. CONCLUSION: Although NGAL provided measurable useful diagnostic information in evaluating children for appendicitis, its values were not sufficient for appendicitis severity. Serum IL-6 remains a strong biomarker for suspected acute appendicitis and has promising results predicting its severity.

Moxifloxacin in Pediatric Patients With Complicated Intra-abdominal Infections: Results of the MOXIPEDIA Randomized Controlled Study.

BACKGROUND: This study was designed to evaluate primarily the safety and also the efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal infections (cIAIs). METHODS: In this multicenter, randomized, double-blind, controlled study, 451 pediatric patients aged 3 months to 17 years with cIAIs were treated with intravenous/oral MXF (N = 301) or comparator (COMP, intravenous ertapenem followed by oral amoxicillin/clavulanate; N = 150) for 5 to 14 days. Doses of MXF were selected based on the results of a Phase 1 study in pediatric patients (NCT01049022). The primary endpoint was safety, with particular focus on cardiac and musculoskeletal safety; clinical and bacteriologic efficacy at test of cure was also investigated. RESULTS: The proportion of patients with adverse events (AEs) was comparable between the 2 treatment arms (MXF: 58.1% and COMP: 54.7%). The incidence of drug-related AEs was higher in the MXF arm than in the COMP arm (14.3% and 6.7%, respectively). No cases of QTc interval prolongation-related morbidity or mortality were observed. The proportion of patients with musculoskeletal AEs was comparable between treatment arms; no drug-related events were reported. Clinical cure rates were 84.6% and 95.5% in the MXF and COMP arms, respectively, in patients with confirmed pathogen(s) at baseline. CONCLUSIONS: MXF treatment was well tolerated in children with cIAIs. However, a lower clinical cure rate was observed with MXF treatment compared with COMP. This study does not support a recommendation of MXF for children with cIAIs when alternative more efficacious antibiotics with better safety profile are available.

Role of serum cytokines in acute appendicitis and acute mesenteric lymphadenitis among children.

BACKGROUND AND OBJECTIVE: The diagnostic role of serum cytokines depends on the etiology and pathogenesis of acute appendicitis (AA) and acute mesenteric lymphadenitis (AML). The aim of this study was to evaluate differences in cytokine levels between AA and AML. MATERIALS AND METHODS: Data of 7- to 18-year-old children were collected prospectively from October 2010 to October 2013. There were 31 patients with AA (AA group), 26 with AML (AML group), and 17 with elective non-inflammatory surgical disease (control group). Serum levels of IL-10, IL-12(p70), IL-1ß, IL-4, IL-6, IL-8, IL-17, MCP-1, EGF, TNF-α and white blood count (WBC) were measured three times consecutively in each group. RESULTS: The level of IL-6 and IL-10 was significantly higher in the AA group than the AML group at the first measurement (8pg/mL vs. 3.2pg/mL, P=0.000; 6.1pg/mL vs. 3.2pg/mL, P=0.005, respectively). There was a significant difference observed in time dynamics of concentration of IL-6 and MCP-1 for AA and AML. The area under the curve (AUC) was 0.77 (95% CI 0.64-0.89; P=0.001) for IL-6 with a cut-off value of 4.3pg/mL (67.7% sensitivity and 76.9% specificity) for AA 1h before surgery. The AUC for WBC was 0.72 (95% CI 0.58.4-0.85; P=0.005) with a cut-off value of 10.7×103/µL (sensitivity 71.0% and specificity 46.2%). CONCLUSIONS: Serum IL-6 with a cut-off value of 4.3pg/mL and WBC with a cut-off value of 10.7×103/µL assessed together will yield more sensitivity for AA.

BCG-SSI(®) vaccine-associated lymphadenitis: Incidence and management.

BACKGROUND AND OBJECTIVE: There is a high incidence of childhood tuberculosis in Latvia, including children aged less than 1 year, while BCG-associated lymphadenitis is one of the most frequent adverse events requiring surgical treatment. The aim of this study was to analyze the incidence of purulent BCG adenitis through-out the population of Latvia after the introduction of BCG-SSI(®) vaccine and to evaluate the treatment results. MATERIAL AND METHODS: The study included 194 patients. All patients had received the BCG-SSI(®) vaccine during the first week of life routinely or at a later time according to the indications. The indications for surgical treatment were lymph node destruction also affecting the skin. All patients in this study received surgical treatment - the affected lymph node extirpation. RESULTS: The mean age of the patients was 5.12±0.96 months. A total of 172 patients had purulent axillar lymphadenitis, 14 had purulent supraclavicular lymphadenitis, 8 patients had lymphadenitis at both localizations. During the whole study period the incidence of BCG adenitis varied from 0.02% to 0.36%, while the mean rate was 0.11%±0.08% from 184,068 vaccinated children during the study period. We observed an increasing trend in the incidence of BCG lymphadenitis during the study period. The primary and complete healing rate at the end of period was 99.5% (n=193) following an affected lymph node extirpation. The mean hospitalization time after the operation was 3.71±0.18 days. CONCLUSIONS: The incidence of BCG-SSI(®) vaccine associated purulent lymphadenitis varied widely with an increasing trend, followed by the return to the product characteristic limits. Indications for the surgical treatment should not be changed. Extirpation of the purulent BCG adenitis is a safe treatment method and leads to the primary wound healing in the majority of cases.

Re-evaluation of histological findings of nonparasitic splenic cysts.

OBJECTIVE: The pathogenesis of nonparasitic splenic cysts (NPSCs) has not been clarified completely. The aim of this multinational and multicentre retrospective study was to further elucidate the origin of NPSCs. METHODS: From 1980 to 2006, 50 children and adolescents were surgically treated for NPSC at six paediatric surgical centres in four European countries. The initial histology report of 35 NPSCs, 22 epidermoid cysts, 11 pseudocysts or post-traumatic cysts and two mesothelial cysts was available. Additional re-evaluation, including immunohistochemistry, to detect cytokeratin, carcino-embrionic antigen and mesothelioma antibody in the inner surface of the cysts was carried out. Special attention was given to the possibility of preceding trauma to the splenic area and whether it played a role in the genesis of NPSC. RESULTS: The pathological re-evaluation showed 30 epidermoid cysts, four mesothelial cysts and one pseudocyst. Immunohistology revealed eight epidermoid and two mesothelial linings of the cysts in those 11 patients in whom pseudocyst was diagnosed originally. No pseudocyst was documented in those patients who had a history of previous blunt abdominal trauma but was not proved by ultrasound and computed tomography scan. CONCLUSION: In contrast with the prevailing belief, it has been demonstrated that NPSCs are congenital in origin, and there is no clinically proven evidence that trauma does play a role in their genesis.