Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation.

The tuft cell-ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca 2+ flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutive Il25 expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basal Il25 expression. Suboptimal ILC2 stimulation by IL-25 resulting from tuft cell Il17rb -deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.

Surgical Treatment of Short Bowel Syndrome-The Past, the Present and the Future, a Descriptive Review of the Literature.

Short bowel syndrome (SBS) is a devastating disorder with both short- and long-term implications for patients. Unfortunately, the prevalence of SBS has doubled over the past 40 years. Broadly speaking, the etiology of SBS can be categorized as congenital or secondary, the latter typically due to extensive small bowel resection following diseases of the small intestine, e.g., necrotizing enterocolitis, Hirschsprung's disease or intestinal atresia. As of yet, no cure exists, thus, conservative treatment, primarily parenteral nutrition (PN), is the first-line therapy. In some cases, weaning from PN is not possible and operative therapy is required. The invention of the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure in 1980 was a major step forward in patient care and spawned further techniques that continue to improve lives for patients with severe SBS (e.g., double barrel enteroplasty, serial transverse enteroplasty, etc.). With this review, we aim to provide an overview of the clinical implications of SBS, common conservative therapies and the development of operative techniques over the past six decades. We also provide a short outlook on the future of operative techniques, specifically with respect to regenerative medicine.

Open Versus Laparoscopic Pyloromyotomy for Pyloric Stenosis-A Systematic Review and Meta-Analysis.

INTRODUCTION: Infantile hypertrophic pyloric stenosis is treated by either open pyloromyotomy (OP) or laparoscopic pyloromyotomy (LP). The aim of this meta-analysis was to compare the open versus laparoscopic technique. METHODS: A literature search was conducted from 1990 to February 2021 using the electronic databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Primary outcomes were mucosal perforation and incomplete pyloromyotomy. Secondary outcomes consisted of length of hospital stay, time to full feeds, operating time, postoperative wound infection/abscess, incisional hernia, hematoma/seroma formation, and death. RESULTS: Seven randomized controlled trials including 720 patients (357 with OP and 363 with LP) were included. Mucosal perforation rate was not different between groups (relative risk [RR] LP versus OP 1.60 [0.49-5.26]). LP was associated with nonsignificant higher risk of incomplete pyloromyotomy (RR 7.37 [0.92-59.11]). There was no difference in neither postoperative wound infections after LP compared with OP (RR 0.59 [0.24-1.45]) nor in postoperative seroma/hematoma formation (RR 3.44 [0.39-30.43]) or occurrence of incisional hernias (RR 1.01 [0.11-9.53]). Length of hospital stay (-3.01 h for LP [-8.39 to 2.37 h]) and time to full feeds (-5.86 h for LP [-15.95 to 4.24 h]) were nonsignificantly shorter after LP. Operation time was almost identical between groups (+0.53 min for LP [-3.53 to 4.59 min]). CONCLUSIONS: On a meta-level, there is no precise effect estimate indicating that LP carries a higher risk for mucosal perforation or incomplete pyloromyotomies compared with the open equivalent. Because of very low certainty of evidence, we do not know about the effect of the laparoscopic approach on postoperative wound infections, postoperative hematoma or seroma formation, incisional hernia occurrence, length of postoperative stay, time to full feeds, or operating time.

Minimally Invasive Total Extraperitoneal Varicocele Repair: First Description in Children.

Introduction: The aim of this study was to report the first pediatric case series treated with minimally invasive total extraperitoneal varicocele (MITEV) repair using the total extraperitoneal (TEP) approach. Materials and Methods: Five male adolescents (12-17 years) were included in this study, all with left-sided Grade III varicoceles. A 5 mm camera port was inserted just below the umbilicus and two 5 mm working ports were used, one above the symphysis in the midline and the other in the left lateral hemiabdomen just below the arcuate line. Results: Operation time ranged from 47 to 61 minutes (mean: 53 minutes). There were no intra- or postoperative complications. The peritoneum was not perforated, and the abdominal cavity was not entered. Two patients had resolution from varicoceles on follow-up clinical examination and ultrasonography was performed 6 months after surgery. In 3 patients, long-term follow-up was pending. Conclusion: MITEV repair reflects a new minimally invasive access to the retroperitoneum in children with varicocele.