Utility of Enteral Contrast Protocols in Pediatric Adhesive Small Bowel Obstruction: A Prospective Multicenter Observational Study.

OBJECTIVE: Our objective was to determine the utility of enteral contrast-based protocols in the diagnosis and management of adhesive small bowel obstruction (ASBO) for children. BACKGROUND: Enteral contrast-based protocols for adults with ASBO are associated with decreased need for surgery and shorter hospitalization. Pediatric-specific data are limited. METHODS: We conducted a prospective observational study between October 2020 and December 2022 at nine children's hospitals who are members of the Western Pediatric Surgery Research Consortium. Inclusion criteria were children aged 1-20 years diagnosed with ASBO who underwent a trial of nonoperative management (NOM) at hospital admission. Comparisons were made between those children who received an enteral contrast challenge and those who did not. The primary outcome was need for surgery. RESULTS: We enrolled 136 children (71% male; median age: 12 y); 84 (62%) received an enteral contrast challenge. There was no difference in rate of operative intervention between the no contrast (34.6%) and contrast groups (36.9%; P=0.93). Eighty-seven (64%) were successfully managed nonoperatively with no difference in median length of stay (P=0.10) or rate of unplanned readmission (P=0.14). Among the 49 children who required an operation, there was no significant difference in time from admission to surgery or rate of small bowel resection based on prior contrast administration. CONCLUSIONS: The addition of enteral contrast-based protocols for management of pediatric ASBO does not decrease the likelihood of surgery or shorten hospitalization. Larger randomized studies may be needed to further define the role of radiologic contrast in the management of ASBO in children.

Outcomes of pediatric pilonidal disease treatment: excision with off-midline flap reconstruction versus endoscopic pilonidal sinus treatment.

PURPOSE: Pilonidal disease (PD) is marked by chronic inflammation and frequent recurrence which can decrease quality of life. However, debate remains regarding the optimal treatment for PD in the pediatric population. This study compares two recommended treatment approaches-excision with off-midline flap reconstruction (OMF: Bascom cleft lift flap, modified Limberg flap) and minimally invasive endoscopic pilonidal sinus treatment (EPSiT). METHODS: Single-center retrospective evaluation of patients 1-21 years of age with PD who underwent either excision with OMF reconstruction or EPSiT between 10/1/2011 and 10/31/2021. Outcomes included were disease recurrence, reoperation, and wound complication rates. Comparisons were performed using Chi-square and Mann-Whitney U tests. RESULTS: 18 patients underwent excision/OMF reconstruction and 45 patients underwent EPSiT. The excision/OMF reconstruction cohort was predominantly male (44.4% vs 17.8% p = 0.028), with history of prior pilonidal infection (33.3% vs 6.7%; p = 0.006), and longer median operative time (60 min vs 17 min; p < 0.001). The excision/OMF reconstruction cohort had a higher rate of wound complications (22.2% vs 0%; p = 0.001), but lower rates of disease recurrence (5.6% vs 33.3%; p = 0.022) and reoperation (5.6% vs 31.1%; p = 0.031). CONCLUSION: In pediatric patients with PD, excision with OMF reconstruction may decrease recurrence and reoperation rates with increased operative times and wound complication rates, compared to EPSiT.

Outcomes of Extracorporeal Life Support Utilization for Pediatric Patients With COVID-19 Infections.

Outcomes of pediatric patients who received extracorporeal life support (ECLS) for COVID-19 remain poorly described. The aim of this multi-institutional retrospective observational study was to evaluate these outcomes and assess for prognostic factors associated with in-hospital mortality. Seventy-nine patients at 14 pediatric centers across the United States who received ECLS support for COVID-19 infections between January 2020 and July 2022 were included for analysis. Data were extracted from the electronic medical record. The median age was 14.5 years (interquartile range [IQR]: 2-17 years). Most patients were female (54.4%) and had at least one pre-existing comorbidity (84.8%), such as obesity (44.3%, median body mass index percentile: 97% [IQR: 67.5-99.0%]). Venovenous (VV) ECLS was initiated in 50.6% of patients. Median duration of ECLS was 12 days (IQR: 6.0-22.5 days) with a mean duration from admission to ECLS initiation of 5.2 ± 6.3 days. Survival to hospital discharge was 54.4%. Neurological deficits were reported in 16.3% of survivors. Nonsurvivors were of older age (13.3 ± 6.2 years vs. 9.3 ± 7.7 years, p = 0.012), more likely to receive renal replacement therapy (63.9% vs. 30.2%, p = 0.003), demonstrated longer durations from admission to ECLS initiation (7.0 ± 8.1 days vs. 3.7 ± 3.8 days, p = 0.030), and had higher rates of ECLS-related complications (91.7% vs. 69.8%, p = 0.016) than survivors. Pediatric patients with COVID-19 who received ECLS demonstrated substantial morbidity and further investigation is warranted to optimize management strategies.

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury.

BACKGROUND AND AIMS: Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. APPROACH AND RESULTS: Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly >10-fold dilated peribiliary glands following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. CONCLUSIONS: We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia.

BACKGROUND AND AIMS: Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 ( Prom1 )-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1 -expressing HPC proliferation leading to profibrogenic ductular reactions in BA. APPROACH AND RESULTS: The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1 -expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1 , FN14 , and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression. CONCLUSION: TWEAK/FN14 signaling activation in Prom1 -expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.

Postoperative narcotic utilization in single incision laparoscopic-assisted extracorporeal appendectomy (SILEA): a single-institution retrospective review.

PURPOSE: Laparoscopic appendectomy for pediatric acute appendicitis is commonly performed by pediatric surgeons. A single incision approach has been investigated, but the lack of technical uniformity has resulted in conflicting data. We hypothesized that an initial single incision laparoscopic-assisted extracorporeal appendectomy (SILEA) approach is associated with similar complication rates as compared to the standard three-incision laparoscopic appendectomy (TILA). METHODS: Approximately 1300 laparoscopic appendectomies were retrospectively reviewed for acute appendicitis over a 5 year period. Patients were split into TILA or SILEA cohorts. Propensity score matching identified 102 matched cases in both cohorts. Case and control cohort comparisons were then analyzed. RESULTS: Successful SILEA was associated with no difference in post-operative complication rate. SILEA was associated with decreased postoperative narcotic dosage and shorter operative time than TILA. CONCLUSIONS: An initial SILEA approach is safe and associated with similar complication rates as TILA. Based on this data, the authors advocate adoption of the an initial SILEA approach for uncomplicated, freely mobile, acute appendicitis with seamless conversion to TILA if the appendix is not amendable to SILEA. LEVEL OF EVIDENCE: Level III.

High throughput RNA sequencing utility for diagnosis and prognosis in colon diseases.

RNA sequencing is the use of high throughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of several malignancies such melanoma, lung cancer, and colorectal cancer. RNA sequencing can identify differential expression of genes (DEG's), mutated genes, fusion genes, and gene isoforms in disease states. RNA sequencing has been used in the investigation of several colorectal diseases such as colorectal cancer, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and irritable bowel syndrome.

A low concentration of ethanol impairs learning but not motor and sensory behavior in Drosophila larvae.

Drosophila melanogaster has proven to be a useful model system for the genetic analysis of ethanol-associated behaviors. However, past studies have focused on the response of the adult fly to large, and often sedating, doses of ethanol. The pharmacological effects of low and moderate quantities of ethanol have remained understudied. In this study, we tested the acute effects of low doses of ethanol (∼7 mM internal concentration) on Drosophila larvae. While ethanol did not affect locomotion or the response to an odorant, we observed that ethanol impaired associative olfactory learning when the heat shock unconditioned stimulus (US) intensity was low but not when the heat shock US intensity was high. We determined that the reduction in learning at low US intensity was not a result of ethanol anesthesia since ethanol-treated larvae responded to the heat shock in the same manner as untreated animals. Instead, low doses of ethanol likely impair the neuronal plasticity that underlies olfactory associative learning. This impairment in learning was reversible indicating that exposure to low doses of ethanol does not leave any long lasting behavioral or physiological effects.

Olfactory conditioning in the third instar larvae of Drosophila melanogaster using heat shock reinforcement.

Adult Drosophila melanogaster has long been a popular model for learning and memory studies. Now the larval stage of the fruit fly is also being used in an increasing number of classical conditioning studies. In this study, we employed heat shock as a novel negative reinforcement for larvae and obtained high learning scores following just one training trial. We demonstrated heat-shock conditioning in both reciprocal and non-reciprocal paradigms and observed that the time window of association for the odor and heat shock reinforcement is on the order of a few minutes. This is slightly wider than the time window for electroshock conditioning reported in previous studies, possibly due to lingering effects of the high temperature. To test the utility of this simplified assay for the identification of new mutations that disrupt learning, we examined flies carrying mutations in the dnc gene. While the sensitivity to heat shock, as tested by writhing, was similar for wild type and dnc homozygotes, dnc mutations strongly diminished learning. We confirmed that the learning defect in dnc flies was indeed due to mutation in the dnc gene using non-complementation analysis. Given that heat shock has not been employed as a reinforcement for larvae in the past, we explored learning as a function of heat shock intensity and found that optimal learning occurred around 41 °C, with higher and lower temperatures both resulting in lower learning scores. In summary, we have developed a very simple, robust paradigm of learning in fruit fly larvae using heat shock reinforcement.