How to select patients for anti-reflux surgery? The ICARUS guidelines (International Consensus regarding preoperative examinations and clinical characteristics assessment to select adult patients for AntiReflUx Surgery)

Objective: Anti-reflux surgery can be proposed in patients with gastro-esophageal reflux disease, especially when proton pump inhibitor use leads to incomplete symptom improvement. However, to date, international consensus guidelines on the clinical criteria and additional technical examinations used in patient selection for anti-reflux surgery are lacking. We aimed at generating key recommendations in the selection of patients for anti-reflux surgery. Design: We included 35 international experts (gastroenterologists, surgeons and physiologists) in a Delphi process and developed 37 statements that were revised by the Consensus Group, to start the Delphi process. Three voting rounds followed where each statement was presented with the evidence summary. The panel indicated the degree of agreement for the statement. When 80% of the Consensus Group agreed (A+/A) with a statement, this was defined as consensus. All votes were mutually anonymous.Results: Patients with heartburn with a satisfactory response to PPIs, patients with a hiatal hernia (HH), patients with esophagitis LA grade B or higher and patients with Barrett’s esophagus are good candidates for anti-reflux surgery. An endoscopy prior to anti-reflux surgery is mandatory and a barium swallow should be performed in patients with suspicion of a HH or short esophagus. Esophageal manometry is mandatory to rule out major motility disorders. Finally, esophageal pH (+/- impedance) monitoring off PPI is mandatory to select patients for anti-reflux surgery, if endoscopy is negative for unequivocal reflux esophagitis. Conclusion: With the ICARUS guidelines, we generated key recommendations for selection of patients for anti-reflux surgery

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis