ERBB3 deficiency causes a multisystemic syndrome in human patient and zebrafish.

The Erb-B2 receptor tyrosine kinase 3 (ERBB3) gene was first identified as a cause of lethal congenital contracture syndrome (OMIM 607598), while a recent study reported six additional patients carrying ERBB3 variants which exhibited distinct clinical features with evident intestinal dysmotility (OMIM 243180). The potential connection between these phenotypes remains unknown, and the ERBB3-related phenotype spectrum needs to be better characterized. Here, we described a patient presenting with a multisystemic syndrome including skip segment Hirschsprung disease, bilateral clubfoot deformity, and cardiac defect. Trio-whole exome sequencing revealed a novel compound heterozygous variant (c.1914-7C>G; c.2942_2945del) in the patient's ERBB3 gene. RT-PCR and in vitro minigene analysis demonstrated that variant c.1914-7C>G caused aberrant mRNA splicing. Both variants resulted in premature termination codon and complete loss of ERBB3 function. erbb3b knockdown in zebrafish simultaneously caused a reduction in enteric neurons in the distal intestine, craniofacial cartilage defects, and micrognathia, which phenotypically mimics ERBB3-related intestinal dysmotility and some features of lethal congenital contracture syndrome in human patients. These findings provide further patient and animal evidence supporting that ERBB3 deficiency causes a complex syndrome involving multiple systems with phenotypic variability among distinct individuals.

Alterations of gut microbiota in a mouse model with partial small intestinal obstruction.

Introduction: Changes in the gut microbiota of patients with partial small intestinal obstruction (PSIO) have not been widely clarified. We aimed to explore bacterial diversity in a PSIO mouse model. Methods: A PSIO mouse model was established using male C57BL/6 mice, and feces samples from the distal ileum and ileum epithelium tissues were collected. MiSeq sequencing of the 16S rRNA gene was conducted to characterize microbiota diversity and composition. RNA sequencing for differences in transcriptomic programming of the ileum tissue was performed between the PSIO and (Control) Ctrl groups. Results: Bacterial diversity in the PSIO group was significantly lower than that in the controls. Pseudomonadota was predominant in the feces of the PSIO group. Unclassified_Muribaculaceae (p = 0.008) and Akkermansia (p = 0.007) were more abundant in the Ctrl group than those in the PSIO group. Furthermore, Escherichia_Shigella (p = 0.008) was more predominant in the feces of the PSIO group. The Kyoto Encyclopedia of Genes and Genomes pathways related to metabolism were depleted in the PSIO group. Pathways associated with intestinal fibrosis, including extracellular matrix-receptor interaction, focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt signaling pathway and transforming growth factor (TGF)-beta signaling pathway, which were enriched in ileum epithelial tissue in the PSIO group. Conclusion: PSIO can lead to changes in the predominant intestinal bacterial groups. Depleted functional profiles of the gut microbiota were identified in the PSIO group. Functional pathways associated with intestinal fibrosis were activated by PSIO. The potential regulation by the microbiota needs to be explored in the future.

Histopathology of Ganglion Cells in the Proximal Resected Bowel Correlates With the Clinical Outcome in Hirschsprung Disease: A Pilot Study.

INTRODUCTION: Intraoperative leveling biopsy by identifying ganglion cells is crucial to determine surgical margin during surgery for Hirschsprung disease (HSCR). The anastomosis should be performed at least 5 cm proximal to the ganglionic segment to prevent transition zone pull-through. However, the length of the transition zone could be much longer than expected and the histological evaluation of the entire circumference of the proximal margin is recommended, which is time-consuming and not applicable for leveling biopsy. We found that the histopathologic features of ganglion cells varied in the examined bowel specimens and demonstrated a pattern similar to immature and degenerated neuron cells. We assumed that the histopathologic features of ganglion cells in the proximal resected bowel were associated with the clinical outcome and might guide the leveling biopsy. In this study, we described a histopathologic grade of ganglion cells based on the degree of maturity and degeneration. We assessed the correlation between the histopathological grade of ganglion cells in the proximal surgical margin and clinical outcome. METHODS: Three hundred fifty seven patients with HSCR treated between 2013 and 2020 were included. The ganglion cells were divided into six grades based on the histopathologic features in frozen sections. Medical records and detailed histopathologic results of intraoperative frozen sections were reviewed. Follow-up data were collected to evaluate clinical outcomes. The pediatric incontinence and constipation scoring system was used to predict bowel function. RESULTS: The histopathologic results of proximal resected bowel from 357 HSCR patients were presented as follows: Grade I in 52 patients (14.6%), Grade II in 186 patients (52.1%), Grade III in 107 patients (30.0%), and Grade IV in 12 patients (3.4%). The median follow-up time was 46.8 mo (13.0-97.6 mo). The histopathologic grade of ganglion cells from the proximal resected margin was significantly related to postoperative constipation problems and the incidence of Hirschsprung-associated enterocolitis. The results from the pediatric incontinence and constipation scoring system indicated a positive correlation between better postoperative bowel function and lower histopathologic grade of ganglion cells. CONCLUSIONS: This pilot study showed an association between the histopathologic features of ganglion cells in the proximal surgical margin and the clinical outcome. It may provide additional information for intraoperative pathologic consultation in leveling biopsy to prevent insufficient resection of the affected colon. A prospective study is warranted to validate these findings before clinical application.

Corrigendum: Sacral Curvature in Addition to Sacral Ratio to Assess Sacral Development and the Association With the Type of Anorectal Malformations.

[This corrects the article DOI: 10.3389/fped.2021.732524.].

Sacral Curvature in Addition to Sacral Ratio to Assess Sacral Development and the Association With the Type of Anorectal Malformations.

Introduction: Sacral ratio (SR) is currently the only measurement to quantitatively evaluate sacral development in patients with anorectal malformations (ARM). This study proposes sacral curvature (SC) as a new indicator to qualitatively assess the sacrum and hypothesizes that sacral development, both quantitatively and qualitatively, can be an indicator to predict the type of ARM. The study aims to investigate the difference of SR and SC between ARM types and the association with the type of ARM. Methods and Materials: This study was retrospectively conducted between August 2008 and April 2019. Male patients with ARMs were enrolled and divided into three groups based on the types of ARM: (1) rectoperineal fistulae, (2) rectourethral-bulbar fistulae, and (3) rectourethral-prostatic or rectobladder-neck fistulae. SC was measured in the sagittal views of an MRI or a lateral radiograph of the sacrum. Results: Included in the study were 316 male patients with ARMs. SRs were 0.73 ± 0.12, 0.65 ± 0.12, and 0.57 ± 0.12 in perineal, bulbar, and prostatic/bladderneck fistula, respectively (p < 0.01). The SCs in perineal fistulae and bulbar fistulae were significantly higher than that in prostatic/bladderneck fistulae (0.25 ± 0.04, 0.22 ± 0.14, and 0.14 ± 0.18, p < 0.01). When SR ≥ 0.779, there was an 89.9% of possibility that the child has a perineal fistula. When SR ≤ 0.490 and SC ≤ 0, the possibilities of the child having prostatic/bladderneck fistulae were 91.6 and 89.5%, respectively. SC < 0 was also noted in 27 (27.8%), 19 (10.5%), and no (0%) patients of prostatic/bladderneck, bulbar, and perineal fistulae (p < 0.01), respectively. Sacral defect was noted in 63% of patients with SC ≤ 0, compared to none with SC > 0 (p < 0.01). Conclusions: The higher the rectal level is in an ARM, the lower are the objective measurements of the sacrum. SC ≤ 0 is associated with sacral defects and implies a high likelihood of prostatic/bladderneck fistulae.

The multidisciplinary management of recurrent tracheoesophageal fistula after esophageal atresia: Experience with 135 cases from a tertiary center.

BACKGROUND & AIMS: Recurrent tracheoesophageal fistula (rTEF) after esophageal atresia requires complex management across different specialties. This study reviews our experience and discusses a multidisciplinary (MDT) approach adopted in the past 4 years. METHODS: We reviewed the medical records of 100 patients with rTEF managed by an MDT approach (post-MDT group) from 2016 to 2019. These cases were compared to a historical group of 35 patients with rTEF from 2012 to 2015 (pre-MDT group). RESULTS: Of the 135 patients with rTEF, 124 were referred from other hospitals. Preoperative examination found tracheomalacia in 23 patients, vocal fold immobility in 19 patients, and laryngomalacia in five patients. The incidence of postoperative anastomotic leak, anastomotic stricture, and repeat recurrences was 28.1%, 23.0%, and 8.9%, respectively. The overall mortality rate was 4.4%. No statistical difference in postoperative complications was noted between the two groups. The duration of stay in the pediatric intensive care unit (P = 0.038), the duration of intubation (P = 0.049), the postoperative hospital stay (P = 0.011), and the total length of hospital stay (P = 0.001) were significantly lower in the post-MDT group. Mid-term follow-up showed 23 patients had pathological gastroesophageal reflux. Five of them underwent fundoplication and recovered. CONCLUSION: The MDT approach by fostering coordination of surgical, medical, radiological, and nutritional management is beneficial in the management of rTEF and leads to a satisfactory outcome .

Adjuvant steroid treatment following Kasai portoenterostomy and clinical outcomes of biliary atresia patients: an updated meta-analysis.

BACKGROUND: It is controversial whether adjuvant steroid treatment should be given to biliary atresia (BA) patients following a Kasai portoenterostomy (KPE). This study aimed to quantitatively and systematically evaluate the effect of adjuvant steroid therapy post-KPE in relation to major clinical outcomes of BA patients. METHODS: We systematically reviewed the literature in PubMed, Embase, the Cochrane Library, China Knowledge Resource Integrated Database, Wanfang Database, Scholarly and Academic Information Navigator and manually searched for relevant papers published before August, 2015. We extracted data on the effects of steroid treatment following KPE on clinical outcome, including jaundice free rate and native liver survival rate at 6 months, 1 or 2 years after KPE. The weighted overall relative risk (RR) and 95% confidence intervals (CIs) were calculated by using a random-effects model. RESULTS: Eight cohort studies and two randomized controlled trials (RCTs) were identified (n=998). Of them, 6 cohort studies and 2 trials investigated the effect of steroid treatment as compared to non-users or placebo (n=566), and 2 cohort studies compared the effects of high-dose to low-dose steroid treatment (n=432). Steroid usage increased the clearance rates of jaundice at 6 months (pooled RR: 1.32; 95% CI: 0.995-1.76; I 2=72.6%) and 1 year (pooled RR: 1.35; 95% CI: 1.12-1.61; I 2=0.0%), but not 2 years (pooled RR: 0.82; 95% CI: 0.55-1.22; I 2=0.0%) after KPE. There was no solid evidence supporting that steroid treatment would improve native liver survival rate at 6 months (pooled RR: 1.02; 95% CI: 0.90-1.15; I 2=0.0%), 1 year (pooled RR: 1.10; 95% CI: 0.91-1.34; I 2=35.2%) or 2 years (pooled RR: 1.00; 95% CI: 0.73-1.35; I 2=57.4%) after KPE. CONCLUSIONS: Adjuvant steroid treatment following KPE may improve short-term (≤1 year) clearance rate of jaundice, but no significant effects on long-term (≥2 years) clearance rate of jaundice and native liver survival rate. Studies on doses and duration of steroids, and long-term follow-up studies are warranted.

[The swine surgical expermental study of laser-assisted liposuction].

OBJECTIVE: To evaluate the advantage and disadvantage of laser-assisted liposuction compared with conventional liposuction. METHODS: Ten swines were devided into three groups, the laser liposuction group, conventional liposuction group and control group. We compared the two surgical groups with the following aspects: ecchymosi, edema, lipocrit study, hemoglobin studies and blood biochemical changes, etc. RESULTS: There is a benefit of laser-assisted liposuction in the following aspects such as ecchymosi, edema, lipocrit and postoperative complications. The two aspects, that is, ecchymosi and lipocrit study was statistically significant. Hemoglobin change was not statistically significant between the two groups. Laser-assisted liposuction did not lead to dysfunction of organs such as liver and kidney. CONCLUSIONS: Laser-assisted liposuction can significantly decrease the blood lose, ecchymosis and edema compared with conventional liposuction, and it did not give rise to dysfunction of organs.