Peristeen® Trans Anal Irrigation in paediatric patients with anorectal malformations and spinal cord lesions: a multicentre Italian study

Aim In paediatric and adults patients with neurogenic bowel (NB), TransAnal Irrigation (TAI) of the colon has gained popularity due to the introduction of a specifically designed device. The aim of this pilot study was to present the results of TAI using Peristeen® Trans Anal Irrigation (PTAI) in a group of paediatric patients with anorectal malformations (ARM) and congenital or acquired spinal cord lesions (SCL). Method Eight Italian paediatric surgery and spina bifida centres participated in the study. The inclusion criteria were age between 6-17 years, weight above 20 kg, and unsatisfactory bowel management. Patients with chronic inflammatory bowel disease, mental disability and surgery within the previous three months were excluded. At the beginning of treatment (T0) and after three months (T1), the Bristol scale, a questionnaire assessing bowel function and two questionnaires on quality of life for patients aged 6-11 years (CHQ pf50) and 12-17 years (SF36) were administered. Results Eighty-three patients were enrolled, and seventy-eight completed the study (41 ARM, 37 SCL). At T1, constipation was reduced in ARM from 69% to 25,6% and in SCL from 92,7% to 41,5%, faecal incontinence in ARM from 50% to 18.6%, and in SCL from 39% to 9.8% and flatus incontinence in ARM from 20.9% to 9,8%, and in SCL from 31.7% to 10%. At T0, the Bristol Stool Scale types were 1-2 in 45% of ARM and 77.5% of SCL patients, whereas at T1 types 1-2 were recorded in only 2,5% of SCL patients. Quality of life (QoL) improved in both groups. In the younger group, a significant improvement in QoL was recorded in ARM patients for 8 of 9 variables and in SCL patients for 7 of 9 variables. Conclusion This study showed that PTAI resulted in a significant time reduction in colonic cleansing, increased independence from the carer, and improved QoL in paediatric patients with ARM and SCL

Short versus mid-long-term outcome of transanal irrigation in children with spina bifida and anorectal malformations

PurposeWe assessed short- and mid-long-term clinical efficacy of transanal irrigation (TAI) and its effect on the quality of life of children with spina bifida (SB) and anorectal malformations (ARM).MethodsSeventy-four pediatric patients (age 6-17years) with SB and ARM with neurogenic bowel dysfunction were enrolled for a prospective and multicentric study. Patients were evaluated before the beginning of TAI (T0), after 3months (T1) and after at least 2years (range 24-32months) (T2) using a questionnaire assessing bowel function, the Bristol scale, and two validated questionnaires on quality of life: the CHQ-PF50 questionnaire for the parents of patients aged 6-11years and the SF36 questionnaires for patients aged between 12 and 18years.ResultsSeventy-two patients completed TAI program in T1, and 67 continued into T2. Bowel outcomes (constipation and fecal incontinence) improved in both the SB and the ARM groups in the short and mid-long term. In both groups at T1 and T2, parents and children reported an improvement in quality of life and there was a significant increase of stool form types 4 and 5 as described by the Bristol scale. Common adverse effects during the study were similar at T1 and T2 without serious complications.ConclusionsWe observed a sustained improvement in bowel management and quality of life in SB and ARM children during the study, more significant in the short term than in mid-long term. To maintain success rates in the mid-long term and to reduce the dropout rate, we propose patient training and careful follow-ups

Lipid-binding proteins and lipoprotein lipase activity in human skeletal muscle : influence of physical activity and gender.

Pediatric surgeons and patient organisations agree that fewer centers for anorectal malformations with larger patient numbers are essential to reach better treatment. The European Union transacts a political process which aims to realize such centers of expertise for a multitude of rare diseases. All the centers on a specific rare disease should constitute an ERN on that disease. ARM-Net members in different countries report on first experiences with the implementation of national directives, identifying opportunities and risks of this process

Bowel function and associated risk factors at preschool and early childhood age in children with anorectal malformation type rectovestibular fistula: An ARM-Net consortium study

BACKGROUND: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel function of RVF-patients at preschool/early childhood age and determine risk factors for poor functional outcome. METHODS: A multi-center cohort study was performed. Patient characteristics, associated anomalies, sacral ratio, surgical procedures, post-reconstructive complications, one-year constipation, and Bowel Function Score (BFS) at 4-7 years of follow-up were registered. Groups with below normal (BFS < 17; subgroups 'poor' ≤ 11, and 'fair' 11 < BFS < 17) and good outcome (BFS ≥ 17) were formed. Univariable analyses were performed to detect risk factors for outcome. RESULTS: The study included 111 RVF-patients. Median BFS was 16 (range 6-20). The 'below normal' group consisted of 61 patients (55.0%). Overall, we reported soiling, fecal accidents, and constipation in 64.9%, 35.1% and 70.3%, respectively. Bowel management was performed in 23.4% of patients. Risk factors for poor outcome were tethered cord and low sacral ratio, while sacral anomalies, low sacral ratio, prior enterostomy, post-reconstructive complications, and one-year constipation were for being on bowel management. CONCLUSIONS: Although median BFS at 4-7 year follow-up is nearly normal, the majority of patients suffers from some degree of soiling and constipation, and almost 25% needs bowel management. Several factors were associated with poor bowel function outcome and bowel management. LEVEL OF EVIDENCE: Level III.status: publishe

The impact of perioperative care on complications and short term outcome in ARM type rectovestibular fistula: An ARM-Net consortium study

BACKGROUND: The impact of perioperative care interventions on postreconstructive complications and short-term colorectal outcome in patients with anorectal malformation (ARM) type rectovestibular fistula is unknown. METHODS: An ARM-Net consortium multicenter retrospective cohort study was performed including 165 patients with a rectovestibular fistula. Patient characteristics, perioperative care interventions, timing of reconstruction, postreconstructive complications and the colorectal outcome at one year of follow-up were registered. RESULTS: Overall complications were seen in 26.8% of the patients, of which 41% were regarded major. Differences in presence of enterostomy, timing of reconstruction, mechanical bowel preparation, antibiotic prophylaxis and postoperative feeding regimen had no impact on the occurrence of overall complications. However, mechanical bowel preparation, antibiotic prophylaxis ≥48 h and postoperative nil by mouth showed a significant reduction in major complications. The lowest rate of major complications was found in the group having these three interventions combined (5.9%). Multivariate analyses did not show independent significant results of any of the perioperative care interventions owing to center-specific combinations. At one year follow-up, half of the patients experienced constipation and this was significantly higher among those with preoperative mechanical bowel preparation. CONCLUSIONS: Differences in perioperative care interventions do not seem to impact the incidence of overall complications in a large cohort of European rectovestibular fistula-patients. Mechanical bowel preparation, antibiotic prophylaxis ≥48 h, and postoperative nil by mouth showed the least major complications. Independency could not be established owing to center-specific combinations of interventions. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: III.status: publishe

Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3

Endocytosis supports cell communication, growth, and pathogen infection. The species B human adenovirus serotype 3 (Ad3) is associated with epidemic conjunctivitis, and fatal respiratory and systemic disease. Here we show that Ad3 uses dynamin-independent endocytosis for rapid infectious entry into epithelial and haematopoietic cells. Unlike Ad5, which uses dynamin-dependent endocytosis, Ad3 endocytosis spatially and temporally coincided with enhanced fluid-phase uptake. It was sensitive to macropinocytosis inhibitors targeting F-actin, protein kinase C, the sodium–proton exchanger, and Rac1 but not Cdc42. Infectious Ad3 macropinocytosis required viral activation of p21-activated kinase 1 (PAK1) and the C-terminal binding protein 1 of E1A (CtBP1), recruited to macropinosomes. These macropinosomes also contained the Ad3 receptors CD46 and αv integrins. CtBP1 is a phosphorylation target of PAK1, and is bifunctionally involved in membrane traffic and transcriptional repression of cell cycle, cancer, and innate immunity pathways. Phosphorylation-defective S147A-CtBP1 blocked Ad3 but not Ad5 infection, providing a direct link between PAK1 and CtBP1. The data show that viruses induce macropinocytosis for infectious entry, a pathway used in antigen presentation and cell migration

Top-down vs. bottom-up control on vegetation composition in a tidal marsh depends on scale

The relative impact of top-down control by herbivores and bottom-up control by environmental conditions on vegetation is a subject of debate in ecology. In this study, we hypothesize that top-down control by goose foraging and bottom-up control by sediment accretion on vegetation composition within an ecosystem can co-occur but operate at different spatial and temporal scales. We used a highly dynamic marsh system with a large population of the Greylag goose (Anser anser) to investigate the potential importance of spatial and temporal scales on these processes. At the local scale, Greylag geese grub for below-ground storage organs of the vegetation, thereby creating bare patches of a few square metres within the marsh vegetation. In our study, such activities by Greylag geese allowed them to exert topdown control by setting back vegetation succession. However, we found that the patches reverted back to the initial vegetation type within 12 years. At large spatial (i.e. several square kilometres) and temporal scales (i.e. decades), high rates of sediment accretion surpassing the rate of local sea-level rise were found to drive long-term vegetation succession and increased cover of several climax vegetation types. In summary, we conclude that the vegetation composition within this tidal marsh was primarily controlled by the bottom-up factor of sediment accretion, which operates at large spatial as well as temporal scales. Topdown control exerted by herbivores was found to be a secondary process and operated at much smaller spatial and temporal scales.</p