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Purpose: To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD)., Methods: We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60 days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors., Results: The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection., Conclusion: Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate., (© 2024. The Author(s).)

Objectives: To describe incidence, clinical course, diagnostic and therapeutic management and long-term follow-up of paediatric intestinal pseudo-obstruction (PIPO) in the Netherlands between 2000 and 2020., Methods: Multicenter, national, retrospective, observational study including patients aged <18 years diagnosed with PIPO and treated between 2000 and 2020 in Dutch academic medical centres. Outcomes included demographics, incidence, symptoms, diagnostic- and treatment methods used during follow-up, number of hospital admissions and mortality., Results: Between 2000 and 2020, 43 children (median age 120 months, range 13-301, 54% female) were diagnosed with PIPO in the Netherlands. Mean incidence was 0.008/100,000/years (range 0/100 000-0.029/100 000). Twenty-six patients developed PIPO in the neonatal period. Initial symptoms were vomiting (n = 21/35, 60%) and abdominal distension (n = 14/35, 40%). Diagnostic strategies included imaging, manometry, histopathology, metabolic- and genetic screening, endoscopy and exploratory surgery. Treatment was divided in nutritional support, pharmacotherapy, colonic irrigation and surgical interventions, of which nutrition and surgery were the cornerstones for care. During the observed study period, the median number of hospital admissions was 22.5 (range 1-176) with a median of 157.5 days (range 3-840) during 20-year follow-up. Two patients (6%) died: one from sepsis and one due to a severe underlying neurological disease. Heterogeneity in diagnostic- en treatment methods existed between patients., Conclusions: PIPO is a rare, long-lasting complex disease requiring a high number of diagnostic and therapeutic interventions and hospital admissions. However, mortality rate is relatively low. Based on our results, we recommend centralization and standardization of care for this complex rare disease., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Hirschsprung disease (HSCR) and its associated disorders (AD-HSCR) often result in severe hypoperistalsis caused by enteric neuropathy, mesenchymopathy, and myopathy. Notably, HSCR involving the small intestine, isolated hypoganglionosis, chronic idiopathic intestinal pseudo-obstruction, and megacystis-microcolon-intestinal hypoperistalsis syndrome carry a poor prognosis. Ultimately, small-bowel transplantation (SBTx) is necessary for refractory cases, but it is highly invasive and outcomes are less than optimal, despite advances in surgical techniques and management. Thus, regenerative therapy has come to light as a potential form of treatment involving regeneration of the enteric nervous system, mesenchyme, and smooth muscle in affected areas. We review the cutting-edge regenerative therapeutic approaches for managing HSCR and AD-HSCR, including the use of enteric nervous system progenitor cells, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells as cell sources, the recipient intestine's microenvironment, and transplantation methods. Perspectives on the future of these treatments are also discussed., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Chronic intestinal failure (CIF) is a heterogeneous disease that affects pediatric and adult populations worldwide and requires complex multidisciplinary management. In recent years, many advances in intravenous supplementation support, surgical techniques, pharmacological management, and intestinal transplants have been published. Based on these advances, international societies have published multiple recommendations and guidelines for the management of these patients. The purpose of this paper is to show the differences that currently exist between the recommendations (ideal life) and the experiences published by different programs around the world., Methods: A review of the literature in PubMed from 1980 to 2024 was carried out using the following terms: intestinal failure, CIF, home parenteral nutrition, short bowel syndrome, chronic intestinal pseudo-obstruction, intestinal transplant, enterohormones, and glucagon-like peptide-2., Conclusions: There is a difference between what is recommended in the guidelines and consensus and what is applied in real life. Most of the world's countries are not able to offer all of the steps needed to treat this pathology. The development of cooperative networks between countries is necessary to ensure access to comprehensive treatment for most patients on all continents, but especially in low-income countries.

Paralytic ileus is a prevalent medical condition following surgery, exerting a significant financial impact on the healthcare system. Despite its considerable implications, there has been limited progress in advancing both diagnostic and curative approaches to address ileus. This study seeks to introduce alternative diagnostic methodologies rooted in Persian medicine (PM) for paralytic ileus. Our investigation involved a thorough review of literature, including The Canon of Medicine, and an exploration of various PM texts for relevant references. The findings were systematically compared with contemporary medical documentation. According to Persian medicine, paralytic ileus is classified as a type of 'Gholanj' disease. Persian medicine physicians extensively documented this disease, presenting detailed insights. While some aspects of PM viewpoints and the etiology of intestinal obstruction were humoral-theory-based, a majority of his definitions align with current medical concepts. Additionally, Persian medicine physicians proposed numerous therapeutic approaches for managing ileus, such as the Hoghne method, rectal suppositories, topical application of medicines, sitz baths, and the use of laxatives. Gaining a deeper understanding of the pathophysiology and exploring alternative treatment options outlined in Persian medicine can prove valuable for future studies aimed at enhancing the management of paralytic ileus.

Rare early-onset lower urinary tract disorders include defects of functional maturation of the bladder. Current treatments do not target the primary pathobiology of these diseases. Some have a monogenic basis, such as urofacial, or Ochoa, syndrome (UFS). Here, the bladder does not empty fully because of incomplete relaxation of its outflow tract, and subsequent urosepsis can cause kidney failure. UFS is associated with biallelic variants of HPSE2 , encoding heparanase-2. This protein is detected in pelvic ganglia, autonomic relay stations that innervate the bladder and control voiding. Bladder outflow tracts of Hpse2 mutant mice display impaired neurogenic relaxation. We hypothesized that HPSE2 gene transfer soon after birth would ameliorate this defect and explored an adeno-associated viral ( AAV ) vector-based approach. AAV9 /HPSE2, carrying human HPSE2 driven by CAG , was administered intravenously into neonatal mice. In the third postnatal week, transgene transduction and expression were sought, and ex vivo myography was undertaken to measure bladder function. In mice administered AAV9 /HPSE2 , the viral genome was detected in pelvic ganglia. Human HPSE2 was expressed and heparanase-2 became detectable in pelvic ganglia of treated mutant mice. On autopsy, wild-type mice had empty bladders, whereas bladders were uniformly distended in mutant mice, a defect ameliorated by AAV9 /HPSE2 treatment. Therapeutically, AAV9 /HPSE2 significantly ameliorated impaired neurogenic relaxation of Hpse2 mutant bladder outflow tracts. Impaired neurogenic contractility of mutant detrusor smooth muscle was also significantly improved. These results constitute first steps towards curing UFS, a clinically devastating genetic disease featuring a bladder autonomic neuropathy., Competing Interests: FL, CG, BJ, SA, AL, AG, WN, AW, NR No competing interests declared, SW is a co-founder of Bloomsbury Genetic Therapies and is a member of the SMAB of Forge Biologics, (© 2024, Lopes et al.)

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is an uncommon genetic disorder inherited in an autosomal recessive pattern that affects the muscles that line the bladder and intestines. The most common genes associated with MMIHS mutations are ACTG2, LMOD1, MYH11, MYL9, MYLK, and PDCL3. However, the complete genetic landscape of MMIHS still needs to be fully understood. The diagnosis of MMIHS can be challenging. However, advances in prenatal and diagnostic techniques, such as ultrasound and fetal urine analysis, have improved the ability to detect the syndrome early. Targeted next-generation sequencing (NGS) and other diagnostic tests can also diagnose MMIHS. The management of MMIHS involves addressing severe intestinal dysmotility, which often necessitates total parenteral nutrition (TPN), which can lead to complications such as hepatotoxicity and nutritional deficiencies. Multivisceral and intestinal transplantation has emerged as therapeutic options, offering the potential for improved outcomes and enteral autonomy. Understanding the genetic underpinnings of MMIHS is crucial for personalized care. While the prognosis varies, timely interventions and careful monitoring enhance patient outcomes. Genetic studies have given us valuable insights into the molecular mechanisms of MMIHS. These studies have identified mutations in genes involved in the development and function of smooth muscle cells. They have also shown that MMIHS is associated with defects in the signaling pathways that control muscle contraction. Continued research in the genetics of MMIHS holds promise for unraveling the complexities of MMIHS and improving the lives of affected individuals., (© 2024. Japanese Society of Gastroenterology.)

Background: The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients., Aims, Materials and Methods: The following review aims to show the importance of gastrointestinal dysfunction. Multimodal therapy for gastroparesis and paralytic ileus is discussed., Conclusion: Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital functional intestinal obstruction, characterised by megacystis (bladder distention in the absence of mechanical obstruction), microcolon and intestinal hypoperistalsis (dysmotility).We are reporting a case of a female child with normal antenatal course who presented with recurrent episodes of abdominal distension since the second day of life and underwent negative exploratory laparotomy on multiple occasions. She also had urinary retention with a grossly distended bladder, requiring drainage by clean intermittent catheterisation. Surgical procedures for bowel decompression, including gastrostomy and ileostomy, were carried out without success. Genetic analysis revealed a mutation in the human smooth muscle (enteric) gamma-actin gene (ACTG2 gene), clinching the diagnosis of MMIHS. The patient was managed with parenteral nutrition and prokinetic medications and tolerated jejunostomy feeds for a brief period before she succumbed to the illness.Female neonates or infants presenting with abdominal distension and dilated urinary tract should be investigated for MMIHS early on. A timely diagnosis will enable the early involvement of a multidisciplinary team to provide the best options available for management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively., (Copyright © 2024 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Chronic intestinal dysmotility is a rare and debilitating digestive disorder characterized by symptoms of mechanical obstruction without an organic lesion. It has diverse causes and involves various pathological mechanisms. Small bowel manometry is the preferred diagnostic method, particularly for patients with severe and progressive symptoms. The condition can be categorized as intestinal pseudo-obstruction and enteric dysmotility, both entities share abnormal small bowel motility, but with important differences in prognosis and management.

Chronic intestinal pseudo-obstruction is a rare and heterogeneous syndrome characterized by recurrent symptoms of intestinal obstruction with radiological features of dilated small or large intestine with air/fluid levels in the absence of any mechanical occlusive lesion. Several diseases may be associated with chronic intestinal pseudo-obstruction and in these cases, the prognosis and treatment are related to the underlying disease. Also, in its "primary or idiopathic" form, two subgroups of patients should be determined as they require a more specific therapeutic approach: patients whose chronic intestinal pseudo-obstruction is due to sporadic autoimmune/inflammatory mechanisms and patients whose neuromuscular changes are genetically determined. In a context of a widely heterogeneous adult population presenting chronic intestinal pseudo-obstruction, this review aims to summarize a practical diagnostic workup for identifying definite subgroups of patients who might benefit from more specific treatments, based on the etiology of their underlying condition., (© 2023 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Objectives: Antroduodenal manometry (ADM) measures antral and small bowel motility and is clinically used to evaluate upper gastrointestinal (UGI) symptoms. We aimed to evaluate its utility in guiding treatment, predicting response, and association with clinical findings., Methods: Retrospective review of 200 children undergoing ADM. ADM interpretation and parameters were compared to outcomes (response to first therapy after ADM and overall response), predominant symptom (group A, abdominal distention and/or vomiting and group B, abdominal pain and/or nausea), etiology (idiopathic or with known comorbidity), and ADM indication [suspected chronic intestinal pseudo-obstruction (CIPO) or unexplained UGI symptoms]., Results: We found an association between a normal intestinal phase III of the migrating motor complex (MMC) and idiopathic etiology, group B symptoms and unexplained UGI symptoms. No variable was associated with initial successful response. However, normal small bowel phase III of the MMC and idiopathic etiology were associated with overall successful response to treatment (including feeding tolerance and weaning of parenteral nutrition). No antral ADM parameter was associated with outcomes or other comparisons. The time to overall successful treatment response was significantly shorter in patients with a normal ADM and presence of a normal phase III of the MMC., Conclusions: The presence of the phase III of the MMC was the single ADM parameter predictive of overall treatment response, also associated to group B symptoms and idiopathic etiology. Our findings suggest that small bowel ADM parameters are more useful to predict outcomes and ADM should be performed primarily in patients presenting with abdominal distention and/or vomiting and those being evaluated for CIPO., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Enteric glial cells are emerging as critical players in the regulation of intestinal motility, secretion, epithelial barrier function, and gut homeostasis in health and disease. Enteric glia react to intestinal inflammation by converting to a 'reactive glial phenotype' and enteric gliosis, contributing to neuroinflammation, enteric neuropathy, bowel motor dysfunction and dysmotility, diarrhea or constipation, 'leaky gut', and visceral pain. The focus of the minireview is on the impact of inflammation on enteric glia reactivity in response to diverse insults such as intestinal surgery, ischemia, infections (C. difficile infection, HIV-Tat-induced diarrhea, endotoxemia and paralytic ileus), GI diseases (inflammatory bowel diseases, diverticular disease, necrotizing enterocolitis, colorectal cancer) and functional GI disorders (postoperative ileus, chronic intestinal pseudo-obstruction, constipation, irritable bowel syndrome). Significant progress has been made in recent years on molecular pathogenic mechanisms of glial reactivity and enteric gliosis, resulting in enteric neuropathy, disruption of motility, diarrhea, visceral hypersensitivity and abdominal pain. There is a growing number of glial molecular targets with therapeutic implications that includes receptors for interleukin-1 (IL-1R), purines (P2X2R, A2BR), PPARα, lysophosphatidic acid (LPAR1), Toll-like receptor 4 (TLR4R), estrogen-β receptor (ERβ) adrenergic α- 2 (α- 2 R) and endothelin B (ETBR), connexin-43 / Colony-stimulating factor 1 signaling (Cx43/CSF1) and the S100β/RAGE signaling pathway. These exciting new developments are the subject of the minireview. Some of the findings in pre-clinical models may be translatable to humans, raising the possibility of designing future clinical trials to test therapeutic application(s). Overall, research on enteric glia has resulted in significant advances in our understanding of GI pathophysiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Postoperative ileus and chronic intestinal pseudo-obstruction are intestinal motility disorders that can compromise bowel function resulting in a significant reduction in quality of life and prolonged hospital stays. While medication and nutritional support provides relief for some patients, a significant patient population remains untreated. Therefore, alternative treatment options are required. A novel framework that enables small intestine pacing and video mapping of the contractile response was developed. Pacing pulse parameters (pulse-period: 2.7, 10 s, pulse-width: 100, 400 ms, and pulse-amplitude: 4, 6, 8 mA) were systematically varied to investigate the effect of pacing on the small intestine contractility. The contractile response was quantified by computing the strain of the intestinal diameter at the pacing site. The framework was applied in vivo on porcine jejunal loops (n=4) where segmental contractions were induced in response to pacing pulses. Strain increased with increasing pulse-amplitude and pulse-width, while pacing at a period of 2.7 s elicited higher contractile strains compared to pacing at a period of 10 s at all settings (e.g., -0.18 ± 0.06 vs 0.12 ± 0.06 at 8 mA, 400 ms). For a pulse-width of 100 ms, the contractile strain continued to increase with increasing pulse-amplitude, while the induced strain was comparable for all pulse-amplitudes when paced with high pulse-width (400 ms). Therefore, pacing is an effective tool in modulating the intensity of segmental contractions.Clinical Relevance- Different pacing parameters can define contraction intensity and frequency in the small intestine. This is of therapeutic potential for treating motility disorders such as post-operative ileus and chronic intestinal pseudo-obstruction.

Objectives: Pediatric intestinal pseudo-obstruction (PIPO) management is based on nutritional, medical, and surgical care while available evidence is scarce. The aim of this study was to outline the current diagnostic and management strategies in intestinal failure (IF) teams of the European Reference Network for rare Inherited and Congenital Anomalies (ERNICA) and to compare these practices to the latest PIPO international guidelines., Methods: An online survey on institutional diagnostic and management strategies of PIPO was conducted among the ERNICA IF teams., Results: In total, 11 of 21 ERNICA IF centers from 8 countries participated. On average, 64% of teams had ≥6 and 36% had 1-5 PIPO patients under active follow-up. In total, 80 of 102 PIPO patients were parenteral nutrition (PN) dependent while each IF team had median 4 (range 0-19) PN dependent PIPO patients under follow-up. On average, each center received 1-2 new PIPO patients per year. Diagnostics mostly followed current guidelines while medical and surgical management strategies were diverse., Conclusions: Numbers of PIPO patients are low and management strategies are diverse among ERNICA IF teams. To improve PIPO patient care, regional reference centers with specialized multidisciplinary IF teams and continuous collaboration across centers are needed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Pediatric intestinal pseudo-obstruction (PIPO) is a heterogeneous and severe group of disorders with a high mortality rate. Patients with PIPO often develop malnutrition and need long-term nutrition support. This study aimed to determine the nutrition status, particularly micronutrients, during the long-term follow-up of patients with PIPO., Methods: Fifty-eight patients with PIPO were followed up for at least 6 months between January 2008 and December 2020 in our hospital. PIPO was diagnosed based on the European society for pediatric gastroenterology, hepatology, and nutrition consensus. Data on clinical characteristics, medical and surgical management, nutrition support, serum vitamins, and mineral concentrations were collected. The patients were divided into the early-onset PIPO (EO-PIPO; neonatal-onset) and late-onset PIPO (LO-PIPO; infant- or child-onset) groups., Results: The mean follow-up was 29.5 months (6-153 months). The overall survival rate was 63.8% (37 out of 58 participants) (EO-PIPO, 48.6% [17 out of 35 participants]; LO-PIPO, 87.0% [20 out of 23 participants]). Mortality in the EO-PIPO group was higher than in the LO-PIPO group (P = 0.002). Twenty-one patients died, of which 18 (85.7%) patients had EO-PIPO and 14 (66.7%) patients died under 1 year of age. Infection was the major cause of death. Severe malnutrition was observed at baseline and during follow-up in 25 (43.1%) and 6 (16.2%) patients, respectively. At baseline and during follow-up, the zinc deficiency rates were 29.6% and 26.3%, and those of vitamin D were 26.9% and 52.6%, respectively., Conclusions: Zinc and vitamin D deficiencies are common in patients with PIPO during follow-up. Therefore, additional supplements should be recommended., (© 2022 American Society for Parenteral and Enteral Nutrition.)

Background: Pediatric intestinal pseudo-obstruction (PIPO) encompasses a variety of rare, heterogeneous, and disabling disorders that severely affect gastrointestinal motility and are associated with high morbidity and mortality. PIPO management is complex and focuses on maintaining an optimal nutritional status, improving gut function, relieving symptoms, and treating complications. Nutritional issues prevail, and PIPO patients often experience severe undernutrition and faltering growth. Thus, nutritional management plays a pivotal role for achieving the most favorable clinical outcomes. The calorie and nutrient intake of each patient needs to be tailored to age, extent and severity of gut involvement and nutritional needs to support an optimal nutritional status. After defining the extent and severity of gut dysmotility, an experienced team should perform a careful nutritional assessment. An oral diet should always be encouraged and might include bite and dissolve solids, liquid diet or simple oral stimulation. If oral caloric intake is inadequate, liquid gastric feeds should provide the subsequent step. In the presence of severe gastric dysmotility, continuous post-pyloric feeding represents a viable option. In the most severe cases, parenteral nutrition (PN) is required to meet appropriate nutritional requirements., Purpose: Pediatric data on this topic are scarce and mainly extrapolated from adult studies. In this review, we discuss current evidence and knowledge regarding nutritional options, implications of the use of different feed types, including a blended diet, and the use of PN. Moreover, based on our experience and the evidence from the literature, we propose a flow chart to guide the nutritional management of PIPO patients., (© 2023 John Wiley & Sons Ltd.)

Background: Mitochondrial neurogastrointestinal encephalopathy is a rare multisystem autosomal recessive disease caused by mutations in the TYMP gene, that encodes for thymidine phosphorylase. Mitochondrial neurogastrointestinal encephalopathy is a progressive degenerative disease characterized by a distinctive tetrad of gastrointestinal dysmotility, peripheral neuropathy, ophthalmoplegia with ptosis, and asymptomatic leukoencephalopathy. It provides a diagnostic dilemma to physicians in regions like Pakistan because of a lack of genetic study availability and associated financial constraints of the population. However, with careful examination and a few basic investigations, mitochondrial neurogastrointestinal encephalopathy can be diagnosed by ruling out most of the close differentials., Case Presentation: We report the case of a 23-year-old Asian female whose chief complaints were epigastric pain, bilious emesis, weight loss for 3 months, and bilateral lower limb weakness for 20 days. All clinical signs and symptoms along with relevant investigations including nerve conduction studies, electromyography, and magnetic resonance imaging of the brain were highly suggestive of mitochondrial neurogastrointestinal encephalopathy syndrome. Because of financial constraints, genetic studies could not be performed. The patient was managed with a multidisciplinary approach involving gastroenterology, physiotherapy, and nutrition departments. Currently, therapeutic options for the disease include allogeneic hematopoietic stem cell transplant and carrier erythrocyte entrapped thymidine phosphorylase; however, these could not be provided to the patient owing to certain limitations., Conclusions: As misdiagnosis and delayed diagnosis are quite common in this disease, the prime objective of this case report is to increase the basic understanding of this disease, especially its signs and symptoms, and address the limitations regarding the diagnostic investigations and management of patients with mitochondrial neurogastrointestinal encephalopathy., (© 2022. The Author(s).)

Introduction: Miller Fisher syndrome (MFS), regarded by many scholars as a variant of Guillain Barre syndrome (GBS), accounts for approximately 5% to 10% of GBS cases. The typical clinical manifestations of MFS are extraocular muscle paralysis, ataxia, and tendon reflex loss or disappearance. To date, intestinal obstruction has rarely been reported as the initial symptom., Patient Concerns: A 48-year-old woman presenting with abdominal pain and distention was diagnosed with paralytic ileus. There was no significant improvement in symptoms after symptomatic treatment. After that, the patient developed visual rotation, with limited binocular abduction and adduction, and ataxia. Anti-ganglioside testing revealed positive anti-ganglioside antibodies., Diagnosis: The patient was diagnosed as MFS., Interventions: The early stage is mainly symptomatic treatment of paralytic ileus. After MFS was diagnosed, the patient was given large amounts of immunoglobulin and hormone shock therapy., Outcomes: After 1 week, the symptoms of intestinal obstruction and MFS gradually improved. The patient was later discharged automatically for financial reasons. Six months after discharge, the patient was interviewed by telephone, and she had recovered., Conclusion: To date, intestinal obstruction has rarely been reported as the initial symptom. In case of inconsistencies between the imaging examinations and clinical symptoms, neuroelectrophysiology and cerebrospinal fluid puncture should be performed, striving for timely detection and treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In the United States, ileus accounts for USD 750 million of healthcare expenditures annually and significantly contributes to morbidity and mortality. Despite its significance, the complete picture of mortality risk factors for these patients have yet to be fully elucidated; therefore, the aim of this study is to identify mortality risk factors in patients emergently admitted with paralytic ileus. Methods: Adult and elderly patients emergently admitted with paralytic ileus between 2005−2014 were investigated using the National Inpatient Sample Database. Clinical outcomes, therapeutic management, demographics and comorbidities were collected. Associations between mortality and all other variables were established via univariable and multivariable logistic regression models. Results: A total of 81,674 patients were included, of which 45.2% were adults, 54.8% elderly patients, 45.8% male and 54.2% female. The average adult and elderly ages were 48.3 and 78.8 years, respectively. Elderly patients displayed a significantly (p < 0.01) higher mortality rate (3.0%) than adults (0.7%). The final multivariable logistic regression model showed that for every one-day delay in operation, the odds of mortality for adult and elderly patients increased by 4.1% (p = 0.002) and 3.2% (p = 0.014), respectively. Every additional year of age corresponded to 3.8% and 2.6% increases in mortality for operatively managed adult (p = 0.026) and elderly (p = 0.015) patients. Similarly, non-operatively treated adult and elderly patients displayed associations between mortality and advanced age (p = 0.001). The modified frailty index exhibited associations with mortality in operatively treated adults, conservatively managed adults and conservatively managed elderly patients (p = 0.001). Every additional day of hospitalization increased the odds of mortality in non-operative adult and elderly patients by 7.6% and 5.8%, respectively. Female sex correlated to lower mortality rates in non-operatively managed adult patients (odds ratio = 0.71, p = 0.028). Undergoing invasive diagnostic procedures in non-operatively managed elderly patients related to reduced mortality (odds ratio = 0.78, p = 0.026). Conclusions: Patients emergently admitted for paralytic ileus with increased hospital length of stay, longer time to operation, advanced age or higher modified frailty index displayed higher mortality rates. Female sex and invasive diagnostic procedures were negatively correlated with death in nonoperatively managed patients with paralytic ileus.

Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a complex and resource-limited solution associated with its own morbidity and mortality. We conducted a scoping review to present a contemporary summary of the epidemiology, aetiology, pathophysiology, diagnosis, management and complications of PIPO.Conclusion: PIPO represents a rare disorder that is difficult to diagnose and challenging to treat, with significant morbitity and mortality. The only known cure is intestinal transplantation. What is Known: • Paediatric intestinal pseudo-obstruction is a rare, heterogeneous disorder that confers a high rate of morbidity and mortality • Complications of paediatric intestinal pseudo-obstruction include chronic pain, small intestine bacterial overgrowth and malrotation. Other complications can occur related to its management, such as line infections with parenteral nutrition or cardiac side effects of prokinetic medications What is New: • Progress in medical and surgical therapy in recent years has led to improved patient outcomes • Enteral autonomy has been reported in most patients at as early as 1 month post-transplantation., (© 2022. The Author(s).)

Inflammatory bowel disease (IBD) is a chronic gut inflammation with periods of acute flares and remission. Beneficial effects of a single dose of mesenchymal stem cell (MSC)-based treatment have been demonstrated in acute models of colitis. No studies investigated therapeutic effects of MSCs for the attenuation of enteric neuropathy in a chronic model of colitis. The short and long-term effects of MSC treatment in modulating inflammation and damage to the enteric nervous system (ENS) were studied in the Winnie mouse model of spontaneous chronic colitis highly representative of human IBD. Winnie mice received a single dose of either 1 × 10 6 human bone marrow-derived MSCs or 100µL PBS by intracolonic enema. C57BL/6 mice received 100µL PBS. Colon tissues were collected at 3 and 60 days post MSC administration to evaluate the short-term and long-term effects of MSCs on inflammation and enteric neuropathy by histological and immunohistochemical analyses. In a separate set of experiments, multiple treatments with 4 × 10 6 and 2 × 10 6 MSCs were performed and tissue collected at 3 days post treatment. Chronic intestinal inflammation in Winnie mice was associated with persistent diarrhea, perianal bleeding, morphological changes, and immune cell infiltration in the colon. Significant changes to the ENS, including impairment of cholinergic, noradrenergic and sensory innervation, and myenteric neuronal loss were prominent in Winnie mice. Treatment with a single dose of bone marrow-derived MSCs was ineffective in attenuating chronic inflammation and enteric neuropathy in Winnie., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is a rare, inherited, multisystemic autosomal recessive disorder caused by mutations in the nuclear TYMP gene. This syndrome is characterized by ptosis, external ophthalmoplegia, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and leukoencephalopathy. Our case illustrates a patient diagnosed with MNGIE and cachexia who has benefited from the initiation and maintenance of parenteral nutrition. We highlight the benefits of receiving long-term supplementary home parenteral nutrition under close monitoring for patients with this neurogastrointestinal disease in order to gain weight and maintain good health., (© 2021 American Society for Parenteral and Enteral Nutrition.)

Chronic intestinal pseudo-obstruction (CIPO) is a syndrome associating chronic or recurrent obstructive symptoms with intestinal dilation on imaging but without organic obstruction in the digestive tract. It is a rare disease with varying severity whose diagnosis is very complex. The diagnosis is based on clinical and paraclinical arguments in the context of repetitive occlusive syndromes when no mechanical obstruction of the digestive lumen is observed. Abdomino-pelvic computerized tomography (CT) must be performed to rule out a mechanical obstruction. An additional reference examination is trans-duodenal manometry of the small intestine, which is almost never normal in CIPO, but the test is rarely systematically performed. CIPO can be primary (acquired or congenital) or secondary to a systemic pathology (neurological, metabolic, etc.) resulting in neuromuscular damage to the intestinal tract. There are familial forms associated with genetic mutations. The majority of CIPO cases are idiopathic. Symptoms of the CIPO syndrome should be investigated with a complete assessment, guided by questioning and clinical examination that should also focus on urinary, neurological and cardiac involvement. Pathological tissue analysis is interesting for the etiological classification but is difficult to obtain. CIPO must be distinguished from non-CIPO intestinal dysmotility. Management must be carried out in an expert center with multidisciplinary care involving gastroenterologists, nutritionists, psychologists, radiologists, pathologists and digestive surgeons. It is essentially based on symptomatic management (especially with pro-kinetic agents and analgesics), nutritional support, as well as psychological support in view of its impact on quality of life. Surgical management is sometimes necessary., (Copyright © 2022. Published by Elsevier Masson SAS.)

Hirschsprung disease (HSCR) and Paediatric Intestinal Pseudo-obstruction (PIPO) comprise two of the most recognized and severe disorders of gastrointestinal (GI) motility. HSCR is a developmental disorder of the enteric nervous system invariably affecting the large intestine, whereas the majority of PIPO conditions represent congenital disorders of one or more components of the neuromusculature and more diffusely affect the GI tract. Histopathology is deemed the gold standard for the diagnosis of HSCR and, arguably, of PIPO, but, other diagnostic modalities such as manometric and genetic studies have seen recent advances that may increase their utility. Especially for PIPO, management is multidisciplinary and best performed in specialist referral centres. Surgery remains the only viable treatment for HSCR and appears essential to optimize and sustain feeding and viability of intestinal function in PIPO patients. Novel therapies such as neural stem cell transplants show promise for the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic Intestinal Pseudo-obstruction (CIPO) is a rare but debilitating and severe form of gastrointestinal dysmotility. The diagnosis is often made very late in the disease course due to its rarity and complexity. Treatment is mainly supportive, as there is no definitive cure. Pharmacologic therapy comprises prokinetics, antibiotics for bacterial overgrowth and pain management. Pain can also be alleviated with intestinal decompression in selected cases. Beside the pharmacologic therapy, nutrition and fluid replacement play a key role. Rarely, intestinal transplantation is necessary in patients with CIPO and intestinal failure. In this review, we describe an advanced CIPO case and provide an update of the clinical and diagnostic features and current management strategies. The goal of our review is to raise awareness around CIPO and to give practical guidance for the clinician., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Functional and motility gastrointestinal disorders are the most common complaints to the pediatric gastroenterologist. Disorders affecting the small intestine carry a significant morbidity and mortality due to the severe limitation of therapeutic interventions available and the complications associated with such interventions. Congenital colorectal disorders are rare but also carry significant morbidity and poor quality of life plus the social stigma associated with its complications. In this review, we summarize the clinical presentation, diagnostic evaluations, and the therapeutic interventions available for the most common and severe gastrointestinal functional and motility disorders of the small bowel, colon, and anorectum., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: Although nutritional care is a cornerstone in the management of pediatric intestinal failure (IF), little is known about feeding difficulty (FD) prevalence. The aim of this study was to determine the frequency of FD and associated factors and to characterize eating behaviours in two pediatric IF rehabilitation centres (Hôpital-Necker Enfants Malades (NEM), France and Alberta Children's Hospital (ACH), Canada)., Methods: Parents of children (aged 1-18 years) on home parenteral nutrition (PN) for >3 months followed at NEM and ACH completed two validated tools: Montreal Children's Feeding scale for severity of FD, Child Eating Behaviour Questionnaire and a pediatric IF-specific questionnaire for FD associated risk factors., Results: In the entire cohort (n = 59, median 5.2 years), 15% had mild, 19% had moderate and 25% had severe FD. No FD was seen in 53% vs 11% and severe FD was seen in 20% vs. 39% of the NEM and ACH cohorts respectively (p = 0.003). Current ETF was less common at NEM vs. ACH (3% vs. 50%, p < 0.001). The FD score was associated with current enteral tube feed (ETF) use (p = 0.04). Compared to healthy reference children, the NEM cohort did not differ for the enjoyment of food, whereas the ACH cohort's enjoyment was lower (p < 0.0001). The ACH cohort scored higher for food avoidance behaviours: food fussiness (p < 0.02), satiety responsiveness (p < 0.0001), and slowness in eating (p < 0.0001) while the NEM cohort was not different from healthy reference children. In the entire cohort, according to parental recall, 60% were reported to be NPO for >12 weeks in the first 6 months of life, and late introduction of purees (>9 months) and lumpy textures (>1 year) were found in 40% and 58%, respectively. Parent-recalled ETF differed between NEM and ACH in the first 6 months of life (45% vs 76%, p = 0.03)., Conclusions: Feeding difficulty and associated risk factors, including early ETF, prolonged NPO and delays in achieving feeding milestones were frequently reported in pediatric IF. Feeding medicalization with the use of ETF may inadvertently contribute to FD and eating disorder behavioural characteristics. This study highlights the need for FD prevention and an increased focus on establishing healthy eating. Future prospective study of FD, associated risk factors and clinical outcomes are merited., Competing Interests: Conflict of interest None to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose of Review: To provide an update on the recent evidence underpinning the approach to nutritional care in patients with severe primary chronic small bowel dysmotility., Recent Findings: Patients with severe chronic small intestinal dysmotility suffer nutritional and nonnutritional morbidity, both as a result of their underlying polysymptomatic, poorly understood condition and the interventions required. A proportion require artificial nutrition support; however, this is associated with impaired quality of life and associated complications. The approach to nutritional support must therefore engage a multidisciplinary team (MDT) to ensure that decisions to escalate beyond oral nutrition reflect individualised risk-benefit discussions while adopting a holistic approach to symptom management. Since nutritional outcomes are worse in those with the chronic intestinal pseudo-obstruction (CIPO) phenotype, differentiation into CIPO and non-CIPO subgroups, using a pragmatic diagnostic approach rather than invasive/poorly tolerated investigations, can be an important step in achieving nutritional care tailored to the individual., Summary: Malnutrition in patients with severe chronic small intestinal dysmotility is multifactorial. Early engagement of a broad team that includes dietitians, psychologists and pain management experts is crucial to achieving the most beneficial and least harmful patient-centred nutritional care outcomes., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We report the case of a 62-year-old female who suffered from a persistent postoperative paralytic ileus following an urgent open cholecystectomy. On the fifth postoperative day we performed a bilateral Quadratus Lumborum Block (QLB) type 1 which resulted in a progressive resolution of the condition. This case report highlights that QLB is not only limited to somatic pain control, but it can also be used to alleviate visceral pain, namely in the context of paralytic ileus management in the postoperative period., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

The article presents a clinical case of a 23-year-old patient with an extremely severe congenital form of chronic intestinal pseudoobstruction coupled with a neuromyopathy,colon malrotation, malabsorption, bacterial overgrowth syndrome, cholelithiasis and gastrostasis, which excluded bowel transplantation. Long-term treatment in the intensive care unit with combined, mainly parenteral nutrition for 6 months, using antibiotics, prokinetics, intestinal decompression allowed to achieve partial stabilization of the patients condition and transfer to home treatment with the continuation of adequate complex therapy.

Enteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. After in vivo transplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remain unclear. Therefore, we aimed to examine ENSC integration using an adapted ex vivo organotypic culture system. Donor ENSC were obtained from Wnt1 cre/+ ;R26R YFP/YFP mice allowing specific labelling, selection and fate-mapping of cells. YFP + neurospheres were transplanted to C57BL6/J (6-8-week-old) colonic tissue and maintained in organotypic culture for up to 21 days. We analysed and quantified donor cell integration within recipient tissues at 7, 14 and 21 days, along with assessing the structural and molecular consequences of ENSC integration. We found that organotypically cultured tissues were well preserved up to 21-days in ex vivo culture, which allowed for assessment of donor cell integration after transplantation. Donor ENSC-derived cells integrated across the colonic wall in a dynamic fashion, across a three-week period. Following transplantation, donor cells displayed two integrative patterns; longitudinal migration and medial invasion which allowed donor cells to populate colonic tissue. Moreover, significant remodelling of the intestinal ECM and musculature occurred upon transplantation, to facilitate donor cell integration within endogenous enteric ganglia. These results provide critical evidence on the timescale and mechanisms, which regulate donor ENSC integration, within recipient gut tissue, which are important considerations in the future clinical translation of stem cell therapies for enteric disease., (© 2021. The Author(s).)

Background: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive autosomal recessive disorder characterized by cachexia, gastrointestinal (GI) dysmotility, ptosis, peripheral neuropathy, and brain magnetic resonance imaging (MRI) white matter changes. Bi-allelic TYMP mutations lead to deficient thymidine phosphorylase (TP) activity, toxic accumulation of plasma nucleosides (thymidine and deoxyuridine), nucleotide pool imbalances, and mitochondrial DNA (mtDNA) instability. Death is mainly due to GI complications: intestinal perforation, peritonitis, and/or liver failure. Based on our previous observations in three patients with MNGIE that platelet infusions resulted in a transient 40% reduction of plasma nucleoside levels, in 2005 we performed the first hematopoietic stem cell transplantation (HSCT) worldwide as a life-long source of TP in a patient with MNGIE., Procedure: HSCT was performed in a total of six patients with MNGIE. The multiple factors involved in the prognosis of this cohort were analyzed and compared to the literature experience., Results: Cell source was bone marrow in five patients and peripheral stem cells in one, all from fully human leukocyte antigen (HLA)-matched related donors, including four who were TYMP mutation carriers. Four of six (66%) survived compared to the 37% survival rate in the literature. Reduced intensity conditioning regimen contributed to secondary graft failure in two patients. Fifteen years post HSCT, the first transplanted patient is seemingly cured. Severe GI symptoms before transplantation were mostly irreversible and were poor prognostic factors., Conclusions: Allogenic HSCT could constitute a curative therapeutic option for carefully selected, young, presymptomatic, or mildly affected patients. Timing, donor selection, and optimal conditioning protocol are major determinants of outcome. HSCT is inadvisable in patients with advanced MNGIE disease., (© 2021 Wiley Periodicals LLC.)

Background: Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder., Purpose: This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition., (© 2020 John Wiley & Sons Ltd.)

Purpose of Review: Pediatric intestinal failure is a complex condition requiring specialized care to prevent potential complications. In this article, we review the available evidence supporting recent advances in care for children with intestinal failure., Recent Findings: Multidisciplinary intestinal rehabilitation teams utilize medical and surgical management techniques to help patients achieve enteral autonomy (EA) while preventing and treating the complications associated with intestinal failure. Recent advances in lipid management strategies, minimization of intestinal failure associated liver disease, prevention of central line-associated blood stream infections, and loss of access, as well as development of promising new hormone analogue therapy have allowed promotion of intestinal adaptation. These advances have decreased the need for intestinal transplant. There have been recent advances in the care of children with intestinal failure decreasing morbidity, mortality, and need for intestinal transplantation. The most promising new therapies involve replacement of enteroendocrine hormones.

Objectives: Describe clinical characteristics, management, and outcome in a cohort of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) patients., Methods: We conducted a retrospective chart review of MMIHS patients followed at a large transplant and intestinal rehabilitation center over a period of 17 years., Results: We identified 25 patients with MMIHS (68% girls, 13 transplanted). One transplanted and 1 nontransplanted patient were lost to follow-up. We estimated 100, 100, and 86% for 5-, 10-, and 20-year survival, respectively, with only 1 death. Of the 22 patients alive at the time of study (11 transplanted, 11 nontransplanted), median age was 9.2 years (range 2.7-22.9 years). Longest posttransplant follow-up was 16 years. Seventeen patients had available prenatal imaging reports; all showed distended bladder. Eight had genetic testing (5, ACTG2; 2, MYH11; 1, MYL9). Almost all patients had normal growth with median weight z-score -0.77 (interquartile range -1.39 to 0.26), height z score -1.2 (-2.04 to -0.48) and body mass index z-score 0.23 (-0.37 to 0.93) with no statistical difference between transplanted and nontransplanted patients. All nontransplanted patients were on parenteral nutrition with minimal/no feeds, and all except 1 of the transplanted patients were on full enteral feeds. Recent average bilirubin, INR, albumin, and creatinine fell within the reference ranges., Conclusions: This is the largest single-center case series with the longest duration of follow-up for MMIHS patients. In the current era of improved intestinal rehabilitation and transplantation, MMIHS patients have excellent outcomes in survival, growth, and liver function. This observation contradicts previous reports and should alter counselling and management decisions in these patients at diagnosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Chronic intestinal pseudo-obstruction (CIPO) is a rare and challenging cause of pediatric intestinal failure, requiring long-term parenteral nutrition in most cases. Despite optimal management, some patients experience chronic abdominal pain and recurrent obstructive episodes with a major impact on their quality of life. Cannabinoids have been successfully used in some conditions. However, their use in CIPO has never been reported in the literature. We report a case of successful use of medicinal cannabinoids in a patient with CIPO, resulting in a significant reduction of abdominal pain, vomiting, and subocclusive episodes and increased appetite and weight, without major adverse events. Although further observations are required to consolidate these findings, this case may be helpful for other patients suffering from the same condition., (© 2020 American Society for Parenteral and Enteral Nutrition.)

MELAS syndrome with chronic intestinal pseudo-obstruction and neurological symptoms in a patient with a fatal evolution despite medical and surgical treatment.

Hollow visceral myopathy (HVM) is described as impaired intestinal function and motility in the absence of mechanical obstruction. In this case report, we describe a unique case of an 18-year-old female who presented to the hospital with complaints of persistent nausea, vomiting, inability to tolerate oral feeds, and substantial weight loss for 2 months. After appropriate investigations, a diagnosis of gastroparesis was established. The patient was started on metoclopramide, which led to significant symptomatic improvement, and she was eventually discharged home. One month after discharge, she presented to the hospital with symptoms similar to her initial presentation. After further laboratory and radiological investigation, she was diagnosed with severe gastroparesis and chronic intestinal pseudo-obstruction. Over the next month, the patient was given an extensive trial of multiple prokinetic agents such as mirtazapine, ondansetron, pyridostigmine, octreotide, and promethazine, but she failed to show clinical improvement. Due to failure of medical therapy, a nasojejunal feeding tube was placed for enteral nutrition. However, the patient reported worsening of her symptoms despite slow feeding rates; hence, a decision was made to start the patient on total parenteral nutrition and transfer her to a larger tertiary center for higher level of care. At the tertiary hospital, the patient was continued on total parenteral nutrition and underwent extensive evaluation. Ultimately, she was diagnosed with HVM after a laparoscopic full-thickness intestinal biopsy showed histopathological evidence of the disease. She underwent isolated small intestine transplant, which led to significant improvement of her symptoms and was eventually discharged home. The patient continues to be symptom-free and follows up with Gastroenterology and Transplant Surgery regularly. This case report highlights a rare clinical condition, HVM, as a potential diagnosis in patients with clinical features of intestinal obstruction without mechanical obstruction.

Chronic intestinal pseudo-obstruction a rare violation of the motor skills of the gastrointestinal complex, similar to mechanical obstruction, but without a mechanical obstacle. The development of chronic intestinal pseudo-obstruction is caused by a disturbance on the part of the smooth muscles and the nervous system of the gastrointestinal system. Common symptoms include constipation, abdominal pain, nausea, vomiting, bloating. Violation of peristalsis leads to food stagnation in the hinges of the small intestine, their dilation, the development of bacterial insemination syndrome. Eating disorders, bacterial contamination syndrome (CDDs) lead to impaired suction syndrome, cahexia. Treatment is aimed at providing adequate nutrition, the use of drugs that activate motor skills, suppress the growth of microbes in the small intestine, the implementation of intestinal decompression. Surgical treatment: resection of the affected segment of the gut. In the refractory course of the disease intestinal transplantation.

Background: Preclinical studies have shown that gene therapy is a feasible approach to treat mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the genetic murine model of the disease (Tymp/Upp1 double knockout, dKO) has a limited functional phenotype beyond the metabolic imbalances, and so the studies showing efficacy of gene therapy have relied almost exclusively on demonstrating correction of the biochemical phenotype. Chronic oral administration of thymidine (dThd) and deoxyuridine (dUrd) to dKO mice deteriorates the phenotype of the animals, providing a better model to test therapy approaches., Methods: dKO mice were treated with both dThd and dUrd in drinking water from weaning until the end of the study. At 8 - 11 weeks of age, mice were treated with several doses of adeno-associated virus (AAV) serotype 8 vector carrying the human TYMP coding sequence under the control of different liver-specific promoters (TBG, AAT, or HLP). The biochemical profile and functional phenotype were studied over the life of the animals., Findings: Nucleoside exposure resulted in 30-fold higher plasma nucleoside levels in dKO mice compared with non-exposed wild type mice. AAV-treatment provided elevated TP activity in liver and lowered systemic nucleoside levels in exposed dKO mice. Exposed dKO mice had enlarged brain ventricles (assessed by magnetic resonance imaging) and motor impairment (rotarod test); both were prevented by AAV treatment. Among all promoters tested, AAT showed the best efficacy., Interpretation: Our results show that AAV-mediated gene therapy restores the biochemical homeostasis in the murine model of MNGIE and, for the first time, demonstrate that this treatment improves the functional phenotype., Funding: This work was funded in part by the Spanish Instituto de Salud Carlos III, and the Generalitat de Catalunya. The disclosed funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Competing Interests: Declaration of Competing Interests RM, FV and MM report grants from the Instituto de Salud Carlos III during the conduct of the study; JT reports grants from Departament de Salut, Generalitat de Catalunya (PERIS program), during the conduct of the study; RM, MH, JT and YC report grants and non-financial support from Modis Therapeutics, personal fees and other from Modis Therapeutics, outside the submitted work; in addition, RM and MH have a patent “Deoxynucleoside therapy for diseases caused by unbalanced nucleotide pools including mitochondrial DNA depletion syndromes” (PCT/US16/038110) with royalties paid to Modis Therapeutics; MH reports grants and other support from Entrada Therapeutics, grants from Muscular Dystrophy Association and grants from NIH, outside the submitted work; FM is an employee of Spark Therapeutics; SL reports that the Nuclear Magnetic Resonance facility where she works charged the VHIR a fee for the MRI services; and RM, YC, JT and RC have a patent “Treatment of mitochondrial diseases” (PCT/EP2016/062636) with royalties paid to Modis Therapeutics., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic intestinal pseudo-obstruction (CIPO) and enteric dysmotility (ED) are small intestinal motility disorders defined by radiological and manometric criteria. In the absence of consensus guidelines, we surveyed opinions on the diagnosis and management of CIPO and ED among experts from different countries., Methods: A survey questionnaire was circulated electronically to members of the European society for Clinical Nutrition and Metabolism, European Society of Neurogastroenterology and Motility, and United European Gastroenterology. Only responses from participants completing all required components were included., Key Results: Of 154 participants, 93% agreed that CIPO and ED should be classified separately. Overall, 73% reported an increasing incidence of CIPO and ED, with hypermobile Ehlers-Danlos Syndrome the group with the largest increase in referrals (37%), particularly in the UK (P < .0001). The majority (95%) find diagnosing CIPO and ED difficult. Notably, antroduodenal manometry, a test mandated to diagnose ED, is infrequently used (only 21% respondents use in >50% cases) and full thickness biopsies were reported to seldom influence medical treatment, nutritional management, and prognosis. Respondents reported that very few treatments are useful for most patients, with bacterial overgrowth treatment, prucalopride, and psychological therapies felt to be the most useful. While only 23% of clinicians felt that parenteral nutrition (PN) improves gastrointestinal symptoms in >50% of cases, 68% reported PN dependency at 5 years in the majority of cases., Conclusions and Inferences: These data highlight the difficulties with diagnosing and managing CIPO and ED and underscore the urgent need for international, multidisciplinary, clinical practice guidelines., (© 2020 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The COVID-19 pandemic has recently spread worldwide, presenting primarily in the form of pneumonia or other respiratory disease. In addition, gastrointestinal manifestations have increasingly been reported as one of the extrapulmonary features of the virus. We report two cases of SARS-CoV-2 infection complicated by paralytic ileus. The first patient was a 33-year-old man who was hospitalized with severe COVID-19 pneumonia requiring ventilator support and intensive care. He developed large bowel dilatation and perforation of the mid-transverse colon, and underwent laparotomy and colonic resection. Histopathology of the resected bowel specimen showed acute inflammation, necrosis, and hemorrhage, supporting a role for COVID-19-induced micro-thrombosis leading to perforation. The second patient was a 33-year-old man who had severe COVID-19 pneumonia, renal failure, and acute pancreatitis. His hospital course was complicated with paralytic ileus, and he improved with conservative management. Both cases were observed to have elevated liver transaminases, which is consistent with other studies. Several authors have postulated that the angiotensin-converting enzyme 2 receptors, the host receptors for COVID-19, that are present on enterocytes in both the small and large bowel might mediate viral entry and resultant inflammation. This is a potential mechanism of paralytic ileus in cases of severe COVID-19 infection. Recognizing paralytic ileus as a possible complication necessitates timely diagnosis and management.

Background/aims: Pediatric intestinal pseudo-obstruction (PIPO) is the most severe form of intestinal dysmotility in children. This study aims to present the cases of PIPO to discuss its diagnosis, management, and prognosis., Materials and Methods: We retrospectively analyzed the medical records of the patients with PIPO between 2010 and 2018., Results: A total of 7 patients were included. The admission age was 3 days-10 years. The complaints were abdominal distention and constipation in all the patients. All the patients had passed meconium in the first 48 hours of their life. An upper gastrointestinal (GI) series revealed slow transit in 6 patients and malrotation in 2 patients. Full-thickness rectum biopsies revealed normal ganglion cells. Neurological examination revealed postinfectious pandysautonomy in 1 patient. Furthermore, 2 patients are under follow-up with ileostomy and TPN, 1 patient is with enteral feeding and ileostomy, and 3 patients are stable with pyridostigmine, enemas. Moreover, 1 patient died because of sepsis. The prognosis was not significantly correlated with initial presentation time, lag time, and presence of extraintestinal manifestations (p>0.05). The prognosis was significantly better when fewer number of operations were performed (p=0.029) Conclusion: PIPO is a broad-spectrum disease group that is difficult to diagnose and treat. It is mandatory to rule out the secondary causes of diagnosis. Medical and surgical treatments are used to support the nutritional status, prevent sepsis, and restore the intestinal motility. The prognosis was better when the secondary causes were identified and fewer operations were performed.

Endoscopic mucosal resection (EMR) is a technique developed for the removal of sessile or flat neoplastic lesions confined to the superficial layers (mucosa and submucosa) of the gastrointestinal tract. Bleeding and perforation are well-known complications of EMR. Here we report the first case of paralytic ileus after EMR of a caecal polyp. A 66-year-old man was scheduled for elective EMR of a 3.5-cm caecal polyp under general anaesthesia after a screening colonoscopy. The procedure was performed by an expert endoscopist, and air was insufflated during the procedure because of the unavailability of CO 2 . The polyp was successfully removed; the procedure duration was 81 min. After the procedure, the patient complained of abdominal pain and dyspnoea. He developed tachypnoea and tachycardia as well as oxygen desaturation with SpO 2 84%. He was administered oxygen therapy via a non-rebreather mask, following which his oxygenation improved. His abdominal X-ray findings were consistent with ileus. Therefore, a nasogastric tube was placed, and the patient was admitted to our hospital. He was managed conservatively and underwent serial abdominal X-rays that showed improvement of the ileus. On the fourth day of admission, he was started on an oral diet; on the sixth day of admission, he was discharged with resolving ileus. Computed tomography enterography performed 1 week after discharge showed complete resolution of the ileus. Factors that may have contributed to the occurrence of ileus in our patient include the use of air during the procedure, location of the polyp (caecal), duration of the procedure, effect of electrocautery, use of general anaesthesia and possibility of aspiration pneumonitis. This case report will make endoscopists aware of the abovementioned factors while performing EMR as this procedure can lead to the complication of paralytic ileus with significant patient morbidity. Conservative treatment should be attempted first before any other intervention., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)