Potential biomarkers of perforated appendicitis show association with severe sepsis

Machine learning enabled researchers to identify genetic biomarkers to predict perforated appendicitis in children with suspected appendicitis, according to a single-center prospective exploratory diagnostic study.

Whole blood transcriptome analysis of 71 children reveals four genetic signatures that predict perforated rather than simple appendicitis with 85.7% accuracy, says Dr. Robert Hancock of the University of British Columbia in Vancouver. (95% CI 72.8-94.1).colleague of JAMA Pediatrics.

The small test set used for internal validation had high sensitivity with an accuracy of 72.7%, and all cases of perforated appendicitis were so identified, but specificity was low.

Although appendicitis is the most common childhood disease requiring emergency surgery, its severity varies widely, with perforated appendicitis resulting in longer hospital stays and much higher morbidity and morbidity, the authors say. Pointed out. Although surgery is the standard treatment for both simple appendicitis and perforated appendicitis, “important differences in management include alternative strategies, including different antibiotic choices, surgical priorities, and nonsurgical approaches.” “possibly,” the researchers wrote.

However, the symptoms of both are similar, and the data collected from ultrasound examinations, laboratory tests, and clinical scoring systems such as the Alvarado score and Pediatric Appendicitis score are sufficient to provide appropriate and timely treatment. is often insufficient to distinguish between different conditions.

Maurizio Pacilli, MD, MBBS, of Monash University and Monash Children’s Hospital in Melbourne, Australia, and Rishikesan Kamaleswaran, MD, of Emory University School of Medicine and Georgia Institute of Technology in Atlanta, explain that other imaging options each have their own problems. did.of accompanying editorial.

CT has variable accuracy in children compared to adults and involves radiation exposure. MRI has similar accuracy to CT, but is “limited by cost, availability, and the need for sedation or general anesthesia in young children,” Pasiri and Kamaleswaran write.

“Therefore, an accurate preoperative diagnosis of acute appendicitis, ideally a test that allows for the differentiation of simple appendicitis from perforated appendicitis, is highly desirable, and allows for improved counseling and personalized guidance for the management of individual patients. approach,” the researchers added.

With this goal in mind, the study authors identified four gene expression signatures in which ANXA3, S100A8, S100A12, and PLBD1 were all significantly upregulated in patients with perforated appendicitis. Previous research by the same group found that the first three of these predicted sepsis, especially the most severe type of sepsis.

Patients with perforated appendicitis had different proportions of various immune cell types and increased numbers of white blood cells and neutrophils, and these differences may explain the gene expression changes identified in these patients. I couldn’t explain it completely. Hancock et al. compared these gene expression signatures to a previously published dataset of sepsis signatures. They found that 11 of 14 patients with perforated appendicitis had signs consistent with high sepsis severity, whereas 35 patients with simple appendicitis did not show high sepsis severity. It turns out.

In addition, 9 of the 14 patient signs corresponded to the most severe sepsis phenotype (neutrophil-suppressed endotype). The researchers concluded that signs of sepsis in patients with perforated appendicitis “may be a clear indicator of severity and may also be relevant for the diagnosis of severe appendicitis.”

Pasiri and Kamaleswaran write, “The assumption underlying these findings is that the complex functional responses of innate inflammation may arise from crosstalk between other inflammatory diseases, such as sepsis, and that they may be present in whole blood as well.” This means that it may be reflected in the

The study authors write that their findings “have the potential to help clinicians stratify patients by disease severity and recognize the onset of sepsis early, ideally at the time of onset.” wrote that it has the potential to inform medical management decisions and “advance the evidence.” Based on strategies for antibiotic stewardship. ”

However, they also noted that the biomarker’s low specificity makes it “not particularly useful for diagnostic purposes.” Additionally, “the authors have not yet assessed its feasibility as a diagnostic tool in a clinical scenario in terms of analysis time and cost,” and will test the gene signature’s accuracy, sensitivity, and specificity in a larger study. He added that it was necessary to do so. Finally, the authors stated that they “limited their investigation to inflammatory processes rather than potential confounders that may contribute to these factors, such as obesity.”

For this study, Professor Hancock and his team used peripheral whole blood transcriptomics to examine 71 children (average age We analyzed blood samples taken before surgery from patients aged 11.8 years, 67.6% of whom were boys. Blood was drawn before antibiotic administration in all but five children, and from 5 minutes to 11 hours after antibiotic administration.

The researchers defined perforated appendicitis as “perforation of the appendix due to pathology, surgery, or imaging reports (in that order).” Of the 71 participants, 35 had simple appendicitis, 14 had perforated appendicitis, and 22 controls had no confirmed appendicitis but had abdominal pain.

Genetic analysis of children with perforated appendicitis showed altered gene expression in the blood compared to children with simple appendicitis or no appendicitis. Hancock and his team found that patients with simple appendicitis and abdominal pain without appendicitis had “virtually indistinguishable” gene expression, whereas patients with perforated appendicitis had “various immune system and signaling “They had between 1,200 and 3,000 significantly differentially expressed genes, including transmission and tissue overexpression.” damage or repair, and homeostatic pathways. ”