Thoracoabdominal Wall Motion-Guided Biofeedback Treatment of Abdominal Distension: A Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Abdominal distention results from abdominophrenic dyssynergia (ie, diaphragmatic contraction and abdominal wall relaxation) in patients with disorders of gut-brain interaction. This study aimed to validate a simple biofeedback procedure, guided by abdominothoracic wall motion, for treating abdominal distension. METHODS: In this randomized, parallel, placebo-controlled trial, 42 consecutive patients (36 women and 6 men; ages 17-64 years) with meal-triggered visible abdominal distension were recruited. Recordings of abdominal and thoracic wall motion were obtained using inductance plethysmography via adaptable belts. The signal was shown to patients in the biofeedback group, who were taught to mobilize the diaphragm. In contrast, the signal was not shown to the patients in the placebo group, who were given a placebo capsule. Three sessions were performed over a 4-week intervention period, with instructions to perform exercises (biofeedback group) or to take placebo 3 times per day (control group) at home. Outcomes were assessed through response to an offending meal (changes in abdominothoracic electromyographic activity and girth) and clinical symptoms measured using daily scales for 7 days. RESULTS: Patients in the biofeedback group (n = 19) learned to correct abdominophrenic dyssynergia triggered by the offending meal (intercostal activity decreased by a mean ± SE of 82% ± 10%, anterior wall activity increased by a mean ± SE of 97% ± 6%, and increase in girth was a mean ± SE of 108% ± 4% smaller) and experienced improved clinical symptoms (abdominal distension scores decreased by a mean ± SE of 66% ± 5%). These effects were not observed in the placebo group (all, P < .002). CONCLUSIONS: Abdominothoracic wall movements serve as an effective biofeedback signal for correcting abdominophrenic dyssynergia and abdominal distention in patients with disorders of gut-brain interaction. ClincialTrials.gov, Number: NCT04043208.

Anatomical Laser Microdissection of the Ileum Reveals mtDNA Depletion Recovery in A Mitochondrial Neuro-Gastrointestinal Encephalomyopathy (MNGIE) Patient Receiving Liver Transplant.

mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.

Evidence of enteric angiopathy and neuromuscular hypoxia in patients with mitochondrial neurogastrointestinal encephalomyopathy.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE.NEW & NOTEWORTHY Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.

Correction of Dyssynergic Defecation, but Not Fiber Supplementation, Reduces Symptoms of Functional Dyspepsia in Patients With Constipation in a Randomized Trial.

BACKGROUND & AIMS: Patients with functional dyspepsia are believed to have increased sensitivity of the gastrointestinal tract, and some also have functional constipation. We investigated whether in patients with functional dyspepsia, correction of dyssynergic defecation can reduce postprandial fullness. METHODS: We performed a parallel trial at 2 referral centers in Spain, from June 2016 through January 2018 of 50 patients who fulfilled the Rome IV criteria for functional dyspepsia with postprandial distress syndrome and functional constipation and dyssynergic defecation. After a 2-week pretreatment phase, the patients were randomly assigned to groups that learned to correct dyssynergic defecation (2-3 sessions of biofeedback combined with instructions for daily exercise; n = 25) or received dietary fiber supplementation (3.5 g plantago ovata per day; n = 25) for 4 weeks. The primary outcome was change in postprandial abdominal fullness, measured daily on a scale of 0-10, during the last 7 days treatment phase vs the last 7 days of the pretreatment phase. Anal gas evacuations were measured (by an event marker) during the last 2 days of the pretreatment vs treatment phases. RESULTS: Biofeedback treatment corrected dyssynergic defecation in 19/25 patients; corrected dyssynergic defection reduced postprandial fullness by 22%±1% in these patients (P < .001), and reduced the number of anal evacuations by 21%±8% (P = .009). Fiber supplementation did not reduce postprandial fullness or anal evacuations (P ≤ .023 between groups for both parameters in the intent to treat analysis). CONCLUSIONS: Diagnosis and correction of dyssynergic defecation reduces dyspeptic symptoms by more than 20% in patients with functional dyspepsia and associated constipation. Dietary fiber supplementation does not reduce symptoms in these patients. ClinicalTrials.gov no: NCT02956187.

Recommendations of the Spanish Association of Neurogastroenterology and Motility (ASENEM) to restart the activity of gastrintestinal motility laboratories after the state of alarm called due to the Covid-19 pandemic. / Recomendaciones de la Asociación Española de Neurogastroenterología y Motilidad (ASENEM) para el reinicio de la actividad de los laboratorios de motilidad digestiva, tras el confinamiento por el estado de alarma decretado a raíz de la pandemia por COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was responsible for the outbreak of the 2019 coronavirus disease (COVID-19), which is now considered as a pandemic. The prevention strategies adopted have included social distancing measures and the modification, reduction or interruption of a large proportion of routine healthcare activity. This has had a significant impact on the care provided in Gastrointestinal Motility Units. Having passed the peak, in terms of mortality and infections, a gradual reduction in transmission figures has been observed in Spain and other European countries. The risk of reactivation, however, remains high, so it is necessary to have a plan in place that allows healthcare centres to safely resume, for their patients and professionals, instrumental examinations linked to the management of motor pathology. Based on the available scientific evidence and the consensus of a panel of experts, the Spanish Association of Neurogastroenterology and Motility (ASENEM) has drawn up a series of practical recommendations, which have been adapted to the risks inherent in each activity. These include individual protection proposals, as well as organisational and structural measures, which are conceived to allow for the gradual resumption of examinations while minimising the possibility of contagion.

Enteric neuron density correlates with clinical features of severe gut dysmotility.

Gastrointestinal (GI) symptoms can originate from severe dysmotility due to enteric neuropathies. Current methods used to demonstrate enteric neuropathies are based mainly on classic qualitative histopathological/immunohistochemical evaluation. This study was designed to identify an objective morphometric method for paraffin-embedded tissue samples to quantify the interganglionic distance between neighboring myenteric ganglia immunoreactive for neuron-specific enolase, as well as the number of myenteric and submucosal neuronal cell bodies/ganglion in jejunal specimens of patients with severe GI dysmotility. Jejunal full-thickness biopsies were collected from 32 patients (22 females; 16-77 yr) with well-characterized severe dysmotility and 8 controls (4 females; 47-73 yr). A symptom questionnaire was filled before surgery. Mann-Whitney U test, Kruskal-Wallis coupled with Dunn's posttest and nonparametric linear regression tests were used for analyzing morphometric data and clinical correlations, respectively. Compared with controls, patients with severe dysmotility exhibited a significant increase in myenteric interganglionic distance (P = 0.0005) along with a decrease in the number of myenteric (P < 0.00001) and submucosal (P < 0.0004) neurons. A 50% reduction in the number of submucosal and myenteric neurons correlated with an increased interganglionic distance and severity of dysmotility. Our study proposes a relatively simple tool that can be applied for quantitative evaluation of paraffin sections from patients with severe dysmotility. The finding of an increased interganglionic distance may aid diagnosis and limit the direct quantitative analysis of neurons per ganglion in patients with an interganglionic distance within the control range.NEW & NOTEWORTHY Enteric neuropathies are challenging conditions characterized by a severe impairment of gut physiology, including motility. An accurate, unambiguous assessment of enteric neurons provided by quantitative analysis of routine paraffin sections may help to define neuropathy-related gut dysmotility. We showed that patients with severe gut dysmotility exhibited an increased interganglionic distance associated with a decreased number of myenteric and submucosal neurons, which correlated with symptoms and clinical manifestations of deranged intestinal motility.

Effects of Prebiotics vs a Diet Low in FODMAPs in Patients With Functional Gut Disorders.

Prebiotics and diets low in fermentable oligo-, di-, mono-saccharides and polyols (low-FODMAP diet) might reduce symptoms in patients with functional gastrointestinal disorders, despite reports that some nonabsorbable, fermentable meal products (prebiotics) provide substrates for colonic bacteria and thereby increase gas production. We performed a randomized, parallel, double-blind study of patients with functional gastrointestinal disorders with flatulence. We compared the effects of a prebiotic supplement (2.8 g/d Bimuno containing 1.37 g beta-galactooligosaccharide) plus a placebo (Mediterranean-type diet (prebiotic group, n = 19) vs a placebo supplement (2.8 g xylose) plus a diet low in FODMAP (low-FODMAP group, n = 21) for 4 weeks; patients were then followed for 2 weeks. The primary outcome was effects on composition of the fecal microbiota, analyzed by 16S sequencing. Secondary outcomes were intestinal gas production and digestive sensations. After 4 weeks, we observed opposite effects on microbiota in each group, particularly in relation to the abundance of Bifidobacterium sequences (increase in the prebiotic group and decrease in the low-FODMAP group; P = .042), and Bilophila wadsworthia (decrease in the prebiotic group and increase in the low-FODMAP group; P = .050). After 4 weeks, both groups had statistically significant reductions in all symptom scores, except reductions in flatulence and borborygmi were not significant in the prebiotic group. Although the decrease in symptoms persisted for 2 weeks after patients discontinued prebiotic supplementation, symptoms reappeared immediately after patients discontinued the low-FODMAP diet. Intermittent prebiotic administration might therefore be an alternative to dietary restrictions for patients with functional gut symptoms. ClinicalTrials.gov no.: NCT02210572.

Correction of Abdominal Distention by Biofeedback-Guided Control of Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.

BACKGROUND & AIMS: Abdominal distention is produced by abnormal somatic postural tone. We developed an original biofeedback technique based on electromyography-guided control of abdominothoracic muscular activity. We performed a randomized, placebo-controlled study to demonstrate the superiority of biofeedback to placebo for the treatment of abdominal distention. METHODS: At a referral center in Spain, we enrolled consecutive patients with visible abdominal distention who fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1 man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2 patients assigned to biofeedback were not valid for analysis. Abdominothoracic muscle activity was recorded by electromyography. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas patients in the placebo received no instructions and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. The primary outcomes were subjective sensation of abdominal distention, measured by graphic rating scales for 10 consecutive days before and after the intervention. RESULTS: Patients in the biofeedback group effectively learned to reduce intercostal activity (by a mean 45% ± 3%), but not patients in the placebo group (reduced by a mean 5% ± 2%; P < .001). Patients in the biofeedback group learned to increase anterior wall muscle activity (by a mean 101% ± 10%), but not in the placebo group (decreased by a mean 4% ± 2%; P < .001). Biofeedback resulted in a 56% ± 1% reduction of abdominal distention (from a mean score of 4.6 ± 0.2 to 2.0 ± 0.2), whereas patients in the placebo group had a reduction of only 13% ± 8% (from a mean score of 4.7 ± 0.1 to 4.1 ± 0.4) (P < .001). CONCLUSIONS: In a randomized trial of patients with a functional intestinal disorder, we found that abdominal distention can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity, compared with placebo. ClincialTrials.gov no: NCT01205100.

Bloating and Abdominal Distension: Old Misconceptions and Current Knowledge.

Bloating, as a symptom and abdominal distension, as a sign, are both common functional-type complaints and challenging to manage effectively. Individual patients may weight differently the impact of bloating and distension on their well-being. Complaints may range from chronic highly distressing pain to simply annoying and unfashionable protrusion of the abdomen. To avoid mishaps, organic bloating, and distension should always be considered first and appropriated assessed. Functional bloating and distension often present in association with other manifestations of irritable bowel syndrome or functional dyspepsia and in that context patients tend to regard them as most troublesome. A mechanism-based management bloating and distension should be ideal but elucidating key operational mechanisms in individual patients is not always feasible. Some clues may be gathered through a detailed dietary history, by assessing bowel movement frequency and stool consistency and special imaging technique to measure abdominal shape during episodes of distension. In severe, protracted cases it may be appropriate to refer the patient to a specialized center where motility, visceral sensitivity, and abdominal muscle activity in response to intraluminal stimuli may be measured. Therapeutic resources focussed upon presumed or demonstrated pathogenetic mechanism include dietary modification, microbiome modulation, promoting gas evacuation, attenuating visceral perception, and controlling abdominal wall muscle activity via biofeedback.

High-resolution manometry in patients with idiopathic inflammatory myopathy: Elevated prevalence of esophageal involvement and differences according to autoantibody status and clinical subset.

INTRODUCTION: In this study we assessed high-resolution manometry (HRM) findings in patients with dermatomyositis and polymyositis. METHODS: From 2008 to 2015, we performed a cross-sectional study of myositis patients. A survey of esophageal symptoms and HRM data were analyzed and compared among different clinical and serologic groups. RESULTS: Twenty-four (45%) of the 53 patients included in the study had manometric involvement that was not correlated with any esophageal symptom (P = 0.8). Failed waves (34% vs. 0%, P = 0.004) and decreased upper esophageal sphincter pressure (50 vs. 70 mm Hg, P = 0.03) were more common in polymyositis than in dermatomyositis patients. Jackhammer esophagus was more common in anti-TIF1-γ patients (30% vs. 9%, P = 0.04), and lower esophageal sphincter involvement (47% vs. 25%, P = 0.03) was more prevalent in patients with the antisynthetase syndrome. CONCLUSIONS: Esophageal involvement is common in myositis patients, but it correlates poorly with esophageal symptoms. Specific clinical and serologic groups have different manometric features. Muscle Nerve 56: 386-392, 2017.

Effect of Chicory-derived Inulin on Abdominal Sensations and Bowel Motor Function.

GOAL: To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas. BACKGROUND: Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect. STUDY: Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention. RESULTS: Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo). CONCLUSIONS: A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.

Effect of prucalopride on intestinal gas tolerance in patients with functional bowel disorders and constipation.

BACKGROUND AND AIM: Patients with functional bowel disorders develop gas retention and symptoms in response to intestinal gas loads that are well tolerated by healthy subjects. Stimulation of 5HT-4 receptors in the gut has both prokinetic and antinociceptive effects. The aim of this study is to determine the effect of prucalopride, a highly selective 5HT-4 agonist, on gas transit and tolerance in women with functional bowel disorders complaining of constipation. METHODS: Twenty-four women with functional bowel disorders complaining of constipation were included in the study. Patients were studied twice on separate days in a cross-over design. On each study day, an intestinal gas challenge test was performed. During the five previous days, prucalopride (2 mg/day) or placebo was administered. Abdominal symptoms, stool frequency, and stool consistency were recorded during the treatment period on daily questionnaires. RESULTS: During the gas challenge test, prucalopride did not decrease the volume of gas retained in the subset of patients who had significant gas retention (≥ 200 mL) while on placebo. However, in those patients who had increased symptoms during the gas test (≥ 3 on a 0 to 6 scale) when on placebo, prucalopride did significantly reduce the perception of symptoms (2.3 ± 0.5 mean score vs 3.5 ± 0.3 on placebo; P = 0.045). During the treatment period with prucalopride, patients exhibited an increase in the total number of bowel movements and decreased stool consistency compared with placebo. CONCLUSION: Prucalopride reduces abdominal symptoms without modifying gas retention when patients with functional bowel disorders are challenged with the gas transit and tolerance test. European Clinical Trials Database (EudraCT2011-006354-86).

Abdominothoracic mechanisms of functional abdominal distension and correction by biofeedback.

BACKGROUND & AIMS: In patients with functional gut disorders, abdominal distension has been associated with descent of the diaphragm and protrusion of the anterior abdominal wall. We investigated mechanisms of abdominal distension in these patients. METHODS: We performed a prospective study of 45 patients (42 women, 24-71 years old) with functional intestinal disorders (27 with irritable bowel syndrome with constipation, 15 with functional bloating, and 3 with irritable bowel syndrome with alternating bowel habits) and discrete episodes of visible abdominal distension. Subjects were assessed by abdominothoracic computed tomography (n = 39) and electromyography (EMG) of the abdominothoracic wall (n = 32) during basal conditions (without abdominal distension) and during episodes of severe abdominal distension. Fifteen patients received a median of 2 sessions (range, 1-3 sessions) of EMG-guided, respiratory-targeted biofeedback treatment; 11 received 1 control session before treatment. RESULTS: Episodes of abdominal distension were associated with diaphragm contraction (19% ± 3% increase in EMG score and 12 ± 2 mm descent; P < .001 vs basal values) and intercostal contraction (14% ± 3% increase in EMG scores and 6 ± 1 mm increase in thoracic antero-posterior diameter; P < .001 vs basal values). They were also associated with increases in lung volume (501 ± 93 mL; P < .001 vs basal value) and anterior abdominal wall protrusion (32 ± 3 mm increase in girth; P < .001 vs basal). Biofeedback treatment, but not control sessions, reduced the activity of the intercostal muscles (by 19% ± 2%) and the diaphragm (by 18% ± 4%), activated the internal oblique muscles (by 52% ± 13%), and reduced girth (by 25 ± 3 mm) (P ≤ .009 vs pretreatment for all). CONCLUSIONS: In patients with functional gut disorders, abdominal distension is a behavioral response that involves activity of the abdominothoracic wall. This distension can be reduced with EMG-guided, respiratory-targeted biofeedback therapy.

Randomized, Placebo-Controlled Trial of Biofeedback for the Treatment of Rumination.

OBJECTIVES: We previously demonstrated that rumination is produced by an unperceived, somatic response to food ingestion, and we developed an original biofeedback technique based on electromyography (EMG)-guided control of abdomino-thoracic muscular activity. Our aim was to demonstrate the superiority of biofeedback vs. placebo for the treatment of rumination. METHODS: Randomized, placebo-controlled trial performed in a referral center. Consecutive patients who fulfilled the Rome III criteria for rumination (18 women, 6 men; 19-79 years age) were selected and all included in the study; 1 patient assigned to placebo withdrew because of an unrelated accident. Abdomino-thoracic muscle activity after a challenge meal was recorded by EMG. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas the patients in the placebo group were not shown the signal and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. MAIN OUTCOME: number of rumination events as measured by questionnaires for 10 consecutive days before and after intervention. RESULTS: Patients on biofeedback (n=12) but not on placebo (n=11) effectively learned to reduce intercostal activity (by 51±6% vs. 10±7% increment on placebo; P<0.001) and anterior wall muscle activity (by 52±4% vs. 9±2% increment on placebo; P<0.001). Biofeedback treatment resulted in a 74±6% reduction in rumination activity (from 29±6 before to 7±2 daily events after intervention) vs. 1±14% on placebo; P=0.001 (from 21±2 before to 21±4 daily events after intervention). CONCLUSIONS: Rumination can be effectively corrected by biofeedback-guided control of abdomino-thoracic muscular activity.

Allogeneic haematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy.

Haematopoietic stem cell transplantation has been proposed as treatment for mitochondrial neurogastrointestinal encephalomyopathy, a rare fatal autosomal recessive disease due to TYMP mutations that result in thymidine phosphorylase deficiency. We conducted a retrospective analysis of all known patients suffering from mitochondrial neurogastrointestinal encephalomyopathy who underwent allogeneic haematopoietic stem cell transplantation between 2005 and 2011. Twenty-four patients, 11 males and 13 females, median age 25 years (range 10-41 years) treated with haematopoietic stem cell transplantation from related (n = 9) or unrelated donors (n = 15) in 15 institutions worldwide were analysed for outcome and its associated factors. Overall, 9 of 24 patients (37.5%) were alive at last follow-up with a median follow-up of these surviving patients of 1430 days. Deaths were attributed to transplant in nine (including two after a second transplant due to graft failure), and to mitochondrial neurogastrointestinal encephalomyopathy in six patients. Thymidine phosphorylase activity rose from undetectable to normal levels (median 697 nmol/h/mg protein, range 262-1285) in all survivors. Seven patients (29%) who were engrafted and living more than 2 years after transplantation, showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Univariate statistical analysis demonstrated that survival was associated with two defined pre-transplant characteristics: human leukocyte antigen match (10/10 versus <10/10) and disease characteristics (liver disease, history of gastrointestinal pseudo-obstruction or both). Allogeneic haematopoietic stem cell transplantation can restore thymidine phosphorylase enzyme function in patients with mitochondrial neurogastrointestinal encephalomyopathy and improve clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy in the long term. Allogeneic haematopoietic stem cell transplantation should be considered for selected patients with an optimal donor.

[Chronic diarrhoea: Definition, classification and diagnosis]. / Diarrea crónica: definición, clasificación y diagnóstico.

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

Classification of functional bowel disorders by objective physiological criteria based on endoluminal image analysis.

We have previously developed an original method to evaluate small bowel motor function based on computer vision analysis of endoluminal images obtained by capsule endoscopy. Our aim was to demonstrate intestinal motor abnormalities in patients with functional bowel disorders by endoluminal vision analysis. Patients with functional bowel disorders (n = 205) and healthy subjects (n = 136) ingested the endoscopic capsule (Pillcam-SB2, Given-Imaging) after overnight fast and 45 min after gastric exit of the capsule a liquid meal (300 ml, 1 kcal/ml) was administered. Endoluminal image analysis was performed by computer vision and machine learning techniques to define the normal range and to identify clusters of abnormal function. After training the algorithm, we used 196 patients and 48 healthy subjects, completely naive, as test set. In the test set, 51 patients (26%) were detected outside the normal range (P < 0.001 vs. 3 healthy subjects) and clustered into hypo- and hyperdynamic subgroups compared with healthy subjects. Patients with hypodynamic behavior (n = 38) exhibited less luminal closure sequences (41 ± 2% of the recording time vs. 61 ± 2%; P < 0.001) and more static sequences (38 ± 3 vs. 20 ± 2%; P < 0.001); in contrast, patients with hyperdynamic behavior (n = 13) had an increased proportion of luminal closure sequences (73 ± 4 vs. 61 ± 2%; P = 0.029) and more high-motion sequences (3 ± 1 vs. 0.5 ± 0.1%; P < 0.001). Applying an original methodology, we have developed a novel classification of functional gut disorders based on objective, physiological criteria of small bowel function.

Biofeedback-guided control of abdominothoracic muscular activity reduces regurgitation episodes in patients with rumination.

BACKGROUND & AIMS: Rumination syndrome is characterized by effortless recurrent regurgitation of recently ingested food into the mouth, with consequent expulsion or re-chewing and swallowing. We investigated whether rumination is under volitional control and can be reversed by behavioral treatment. METHODS: We performed a prospective study of 28 patients who fulfilled the Rome criteria for rumination and had no organic disorders on the basis of a thorough evaluation. The diagnosis of rumination was confirmed by intestinal manometry (abdominal compression associated with regurgitation). Patients were trained to modulate abdominothoracic muscle activity under visual control of electromyographic recordings. Recordings were made after challenge meals, before training (baseline), and during 3 treatment sessions. Outcome was measured by questionnaires administered daily for 10 days before training, immediately after training, and at 1, 3, and 6 months after training. RESULTS: By the end of the 3 sessions, patients had effectively learned to reduce intercostal activity (by 50% ± 2%; P < .001 vs basal) and anterior wall muscle activity (by 30% ± 6%; P < .001 vs basal). Patients reported 27 ± 1 regurgitation episodes/day at baseline and 8 ± 2 episodes/day immediately after treatment. Regurgitation episodes decreased further to 4 ± 1 episodes at 6 months after training. CONCLUSIONS: Rumination is produced by an unperceived somatic response to food ingestion that disrupts abdominal accommodation and can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity.

Mechanisms of postprandial abdominal bloating and distension in functional dyspepsia.

OBJECTIVE: Patients with irritable bowel syndrome and abdominal bloating exhibit abnormal responses of the abdominal wall to colonic gas loads. We hypothesised that in patients with postprandial bloating, ingestion of a meal triggers comparable abdominal wall dyssynergia. Our aim was to characterise abdominal accommodation to a meal in patients with postprandial bloating. DESIGN: A test meal (0.8 kcal/ml nutrients plus 27 g/litre polyethylenglycol 4000) was administered at 50 ml/min as long as tolerated in 10 patients with postprandial bloating (fulfilling Rome III criteria for postprandial distress syndrome) and 12 healthy subjects, while electromyographic (EMG) responses of the anterior wall (upper and lower rectus, external and internal oblique via bipolar surface electrodes) and the diaphragm (via six ring electrodes over an oesophageal tube in the hiatus) were measured. Means +/- SD were calculated. RESULTS: Healthy subjects tolerated a meal volume of 913±308 ml; normal abdominal wall accommodation to the meal consisted of diaphragmatic relaxation (EMG activity decreased by 15±6%) and a compensatory contraction (25±9% increase) of the upper abdominal wall muscles (upper rectus and external oblique), with no changes in the lower anterior muscles (lower rectus and internal oblique). Patients tolerated lower volume loads (604±310 ml; p=0.030 vs healthy subjects) and developed a paradoxical response, that is, diaphragmatic contraction (14±3% EMG increment; p<0.01 vs healthy subjects) and upper anterior wall relaxation (9±4% inhibition; p<0.01 vs healthy subjects). CONCLUSIONS: In functional dyspepsia, postprandial abdominal distension is produced by an abnormal viscerosomatic response to meal ingestion that alters normal abdominal accommodation.