Chorioamnionitis induces enteric nervous system injury: Effects of timing and inflammation in the ovine fetus

Background Chorioamnionitis, inflammation of the chorion and amnion, which often results from intrauterine infection, is associated with premature birth and contributes to significant neonatal morbidity and mortality, including necrotizing enterocolitis (NEC). Recently, we have shown that chronic chorioamnionitis is associated with significant structural enteric nervous system (ENS) abnormalities that may predispose to later NEC development. Understanding time point specific effects of an intra-amniotic (IA) infection on the ENS is important for further understanding the pathophysiological processes and for finding a window for optimal therapeutic strategies for an individual patient. The aim of this study was therefore to gain insight in the longitudinal effects of intrauterine LPS exposure (ranging from 5 h to 15 days before premature delivery) on the intestinal mucosa, submucosa, and ENS in fetal lambs by use of a well-established translational ovine chorioamnionitis model. Methods We used an ovine chorioamnionitis model to assess outcomes of the fetal ileal mucosa, submucosa and ENS following IA exposure to one dose of 10 mg LPS for 5, 12 or 24 h or 2, 4, 8 or 15 days. Results Four days of IA LPS exposure causes a decreased PGP9.5- and S100β-positive surface area in the myenteric plexus along with submucosal and mucosal intestinal inflammation that coincided with systemic inflammation. These changes were preceded by a glial cell reaction with early systemic and local gut inflammation. ENS changes and inflammation recovered 15 days after the IA LPS exposure. Conclusions The pattern of mucosal and submucosal inflammation, and ENS alterations in the fetus changed over time following IA LPS exposure. Although ENS damage seemed to recover after prolonged IA LPS exposure, additional postnatal inflammatory exposure, which a premature is likely to encounter, may further harm the ENS and influence functional outcome. In this context, 4 to 8 days of IA LPS exposure may form a period of increased ENS vulnerability and a potential window for optimal therapeutic strategies

Choledochal Malformation in Children: Lessons Learned from a Dutch National Study

Introduction: A choledochal malformation (CM) is a rare entity, especially in the Western world. We aimed to determine the incidence of CM in the Netherlands and the outcome of surgery for CM in childhood. Methods: All pediatric patients who underwent a surgical procedure for type I–IV CM between 1989 and 2014 were entered into the Netherlands Study group on choledochal cyst/malformation. Patients with type V CM were excluded from the present analysis. Symptoms, surgical details, short-term (30 days) complications were studied retrospectively. Results: Between January 1989 and December 2014, 91 pediatric patients underwent surgery for CM at a median age of 2.1 years (0.0–17.7 years). All patients underwent resection of the extrahepatic biliary tree with restoration of the continuity via Roux-en-Y hepaticojejunostomy. Twelve patients (12%) were operated laparoscopically. Short-term complications, mainly biliary leakage and cholangitis, occurred in 20 patients (22%), without significant correlations with weight or age at surgery or surgical approach. Long-term postoperative complications were mainly cholangitis (13%) and anastomotic stricture (4%). Eight patients (9%) required radiological intervention or additional surgery. Surgery before 1 year of age (OR 9.3) and laparoscopic surgery (OR 4.4) were associated with more postoperative long-term complications. We did not observe biliary malignancies during treatment or follow-up. Conclusion: Surgery for CM carries a significant short- and long-term morbidity. Given the low incidence, we would suggest that (laparoscopic) hepatobiliary surgery for CM should be performed in specialized pediatric surgical centers with a wide experience in laparoscopy and hepatobiliary surgery

Corrigendum: Chronic Intra-Uterine Ureaplasma parvum infection induces injury of the enteric Nervous System in Ovine Fetuses

Michael L. Beeton was not included as an author in the published article. The corrected Author Contributions Statement appears below

A prospective non-randomized two-centre study of patients with passive faecal incontinence after birth trauma and patients with soiling after anal surgery, treated by elastomer implants versus rectal irrigation.

AIM: This study is a prospective evaluation of patients with passive faecal incontinence and patients with soiling treated by elastomer implants and rectal irrigation. PATIENTS AND METHODS: Patients with passive faecal incontinence after birth trauma resulting from a defect of the internal sphincter and patients with soiling after previous anal surgery were included. All patients underwent endo-anal ultrasound, magnetic resonance imaging, and anal manometry. The patients with passive faecal incontinence were initially treated by anal sphincter exercises and biofeedback therapy during half a year. The patients completed incontinence scores, a quality of life questionnaire, and a 2-week diary card. RESULTS: The elastomer group consisted of 30 males and 45 females with a mean age of 53 years (25-77). The rectal irrigation group consisted of 32 males and 43 females with a mean age of 50 years (25-74). At 6 months follow-up, 30 patients with soiling of the rectal irrigation group and only nine patients of the elastomer group were completely cured (p = 0.02). Only three patients with passive faecal incontinence were cured in the rectal irrigation group and none in the elastomer group. Three distal migrations of elastomer implants required removal at follow-up. CONCLUSIONS: After patients had performed anal sphincter exercises, no clear improvement of passive faecal incontinence was obtained by elastomer implants or rectal irrigation. However, rectal irrigation is far more effective than elastomer implants in patients with soiling

Long-term Results of Mucosal Advancement Flap Combined With Platelet-rich Plasma for High Cryptoglandular Perianal Fistulas

BACKGROUND: The long-term closure rate of high perianal fistulas after treatment remains disappointing. OBJECTIVE: The goal of this study was the long-term closure rate of high cryptoglandular perianal fistulas mucosal advancement flap with platelet-rich plasma. DESIGN: This study retrospective in design. SETTING: This study was conducted at 2 tertiary referral hospitals. PATIENTS: Patients presenting with high cryptoglandular perianal fistulas involving the middle/upper third of sphincter complex were included. INTERVENTIONS: A staged surgical performed; After seton placement, a mucosal advancement flap was platelet-rich plasma. MAIN OUTCOME MEASURES: Recurrence was the main Incontinence was the secondary outcome. RESULTS: We operated on 25 between 2006 and 2012. Thirteen (52%) patients had previous fistula median follow-up period was 27 months. One patient (4.0%) was lost to after 4 months. Freedom from recurrence at 2 years was 0.83 (95% CI, Two of the 4 patients with a recurrence (8%) had a repeated treatment One patient (4.0%) refused another treatment, but agreed to stay in One patient (4.0%) requested a colostomy, resulting in closure of the Complications occurred in 1 patient (4.0%). Incontinence numbers were median Vaizey score of 3.0 out of a maximum of 24. LIMITATIONS: The limited by its retrospective design, lack of preoperative incontinence selection bias, and phone interview follow-up. CONCLUSION: The long-term results of patients with primary and recurrent high cryptoglandular fistulas treated with a seton followed by mucosal advancement flap and platelet-rich plasma show low recurrence, complication, and incontinence Therefore, this technique seems to be a valid option as treatment. preferably randomized controlled studies are needed to further explore surgical technique

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin