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 the 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 the gut-brain interaction. ClincialTrials.gov, Number: NCT04043208.

Distinctive gastrointestinal motor dysfunction in patients with MNGIE.

BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare mitochondrial disease caused by mutations in TYMP, encoding thymidine phosphorylase. Clinically it is characterized by severe gastrointestinal dysmotility associated with cachexia and a demyelinating sensorimotor polyneuropathy. Even though digestive manifestations are progressive and invariably lead to death, the features of gastrointestinal motor dysfunction have not been systematically evaluated. The objective of this study was to describe gastrointestinal motor dysfunction in MNGIE using state-of-the art techniques and to evaluate the relationship between motor abnormalities and symptoms. METHODS: Prospective study evaluating gastrointestinal motor function and digestive symptoms in all patients with MNGIE attended at a national referral center in Spain between January 2018 and July 2022. KEY RESULTS: In this period, five patients diagnosed of MNGIE (age range 16-46 years, four men) were evaluated. Esophageal motility by high-resolution manometry was abnormal in four patients (two hypoperistalsis, two aperistalsis). Gastric emptying by scintigraphy was mildly delayed in four and indicative of gastroparesis in one. In all patients, small bowel high-resolution manometry exhibited a common, distinctive dysmotility pattern, characterized by repetitive bursts of spasmodic contractions, without traces of normal fasting and postprandial motility patterns. Interestingly, objective motor dysfunctions were detected in the absence of severe digestive symptoms. CONCLUSIONS AND INFERENCES: MNGIE patients exhibit a characteristic motor dysfunction, particularly of the small bowel, even in patients with mild digestive symptoms and in the absence of morphological signs of intestinal failure. Since symptoms are not predictive of objective findings, early investigation is indicated.

Clinical significance of small bowel manometry patterns suggestive of intestinal obstruction.

INTRODUCTION: Minute rhythm and prolonged simultaneous contractions are patterns of postprandial small bowel contractile activity that historically have been considered as suggestive of mechanical intestinal obstruction; however, these patterns have been also encountered in patients with motility-like symptoms in the absence of bowel obstruction. The objective of this study was to determine the current diagnostic outcome of patients with these intestinal manometry patterns. METHODS: Retrospective study of patients with chronic digestive symptoms evaluated by intestinal manometry at our center between 2010 and 2018. RESULTS: The minute rhythm (MRP) or prolonged simultaneous contractions (PSC) postprandial patterns were detected in 61 of 488 patients (55 MRP and 6 PSC). Clinical work-up detected a previously non-diagnosed partial mechanical obstruction of the distal intestine in 10 (16%) and a systemic disorder causing intestinal neuropathy in 32 (53%). In the remaining 19 patients (31%, all with MRP), the origin of the contractile pattern was undetermined, but in 16, substantial fecal retention was detected within 7 days of the manometric procedure by abdominal imaging, and in 6 of them colonic cleansing completely normalized intestinal motility on a second manometry performed within 39 ± 30 days. CONCLUSION AND INFERENCE: Currently, the most frequent origin of MRP and PSC encountered on small bowel manometry is intestinal neuropathy, while a previously undetected mechanical obstruction is rare. Still, in a substantial proportion of patients, no underlying disease can be identified, and in them, colonic fecal retention might play a role, because in a subgroup of these patients, manometry normalized after colonic cleansing. Hence, colonic preparation may be considered prior to intestinal manometry.

Visible abdominal distension in functional gut disorders: Objective evaluation.

BACKGROUND: Visible abdominal distension has been attributed to: (A) distorted perception, (B) intestinal gas accumulation, or (C) abdominophrenic dyssynergia (diaphragmatic push and anterior wall relaxation). METHODS: A pool of consecutive patients with functional gut disorders and visible abdominal distension included in previous studies (n = 139) was analyzed. Patients (61 functional bloating, 74 constipation-predominant irritable bowel syndrome and 4 with alternating bowel habit) were evaluated twice, under basal conditions and during a self-reported episode of visible abdominal distension; static abdominal CT images were taken in 104 patients, and dynamic EMG recordings of the abdominal walls in 76, with diaphragmatic activity valid for analysis in 35. KEY RESULTS: (A) Objective evidence of abdominal distension was obtained by tape measure (increase in girth in 138 of 139 patients), by CT imaging (increased abdominal perimeter in 96 of 104 patients) and by abdominal EMG (reduced activity, i.e., relaxation, in 73 of 76 patients). (B) Intestinal gas volume was within ±300 ml from the basal value in 99 patients, and above in 5 patients, who nevertheless exhibited a diaphragmatic descent. (C) Diaphragmatic contraction was detected in 34 of 35 patients by EMG (increased activity) and in 82 of 103 patients by CT (diaphragmatic descent). CONCLUSIONS AND INFERENCES: In most patients complaining of episodes of visible abdominal distention: (A) the subjective claim is substantiated by objective evidence; (B) an increase in intestinal gas does not justify visible abdominal distention; (C) abdominophrenic dyssynergia is consistently evidenced by dynamic EMG recording, but static CT imaging has less sensitivity.

Evaluation of abdominal gas by plain abdominal radiographs.

BACKGROUND: Our aim was to determine the reliability of plain abdominal radiographs for the evaluation of abdominal gas content in patients with functional digestive symptoms. METHODS: Abdominal CT scan scout views, mimicking a conventional plain abdominal radiograph, were obtained from 30 patients both during episodes of abdominal distension and basal conditions. Physicians (n = 50) were instructed to rate the estimated volume of gas in the 60 images presented in random sequence using a scale graded from 0 to ≥600 ml. KEY RESULTS: The gas volumes estimated in the scout views differed from those measured by CT by a median of 90 (95% CI 70-102) ml, and the misestimation was not related to the absolute volume in the image. The accuracy of the observers, measured by their mean misestimation, was not related to their specialty or the training status (misestimation by 96 (95% CI 85-104) ml in staff vs 78 (70-106) ml in residents; p = 0.297). The accuracy was independent of the order of presentation of the images. Gas volume measured by CT in the images obtained during episodes of abdominal distension differed by a median of 39 (95% CI 29-66) ml from those during basal conditions, and this difference was misestimated by a median of 107 (95% CI 94-119) ml. The accuracy of these estimations was not related to the absolute gas volumes (R = -0.352; p < 0.001) or the magnitude of the differences. CONCLUSIONS & INFERENCES: Plain abdominal radiographs have limited value for the evaluation of abdominal gas volume in patients with functional gut disorders.

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.

Incongruent Views of Functioning between Patients and Gastroenterologists: A Mixed Methods Study.

Gastrointestinal patients, especially those diagnosed with functional digestive disorders (FGIDs), usually present a complex clinical picture that poses a challenge for their management in primary care. The main objective of the current research was to examine the relationship of the congruence of the perception of severity and quality of life between gastroenterologists and their patients with psychological distress and the helping attitude experienced by the latter attended in primary care centres. Additionally, we wanted to explore patients' and practitioners' perceptions. We performed a cross-sectional study with a total of 2261 patients (1562 analysed) that attended three primary care centres. Patients completed questionnaires that measured physical functioning, distress, and perception of helping attitude. Gastroenterologists registered the functional status of each participating patient. Patients were then invited to take part in the qualitative part of the study if they were considered to have incongruent views on their functioning with their gastroenterologist. In total, 52 patients took part in one of eight focus groups. Additionally, four individual interviews were carried out with three gastroenterologists and one consultation-liaison psychiatrist specialised in FGIDs. Both incongruence and functional diagnosis correlated with distress. However, incongruent views between patients and gastroenterologists explained more variance. Statistically significant differences in patients' helping attitude perception were detected between diagnostic but no incongruence groups. In the second stage of the study, a total of five themes were identified from the patient focus groups and the gastroenterologist interviews: illness-emotional and personal problems, disease-health system interaction, health system, intervention, and patients. The current research allowed us to confirm that incongruence in the perception of severity and quality of life between gastroenterologists and patients is related to psychological distress and that this occurs in a multifactorial context where the characteristics of the disorder interact with those of the health system.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Propagation patterns of jejunal motor activity measured by high-resolution water-perfused manometry.

BACKGROUND: The manometric diagnosis of severe intestinal dysmotility is performed at most institutions using catheters with 2-8 sensors 5-10 cm apart. The recent application of high-resolution manometry catheters with closely spaced sensors to other gut segments has been highly successful. The objective of the present study was to determine the feasibility of a jejunal high-resolution manometry method and to carry out a descriptive analysis of normal jejunal motor function. METHODS: A 36-channel high-resolution water-perfused manometry catheter (MMS-Laborie, Enschede, The Netherlands) was orally placed in the jejunum of 18 healthy subjects (10 men, eight women; 21-38 age range). Intestinal motility was recorded during 5 h, 3 during fasting, and 2 after a 450 kcal solid-liquid meal. Analysis of motility patterns was supported by computerized tools. KEY RESULTS: All healthy subjects except one showed at least one complete migrating motor complex during the 3 h fasting period. Phase III activity lasted 5 ± 1 min and migrated aborally at a velocity of 7 ± 3 cm/min. High-resolution spatial analysis showed that during phase III each individual contraction propagated rapidly (75 ± 37 cm/min) over a 32 ± 10 cm segment of the jejunum. During phase II, most contractile activity corresponded to propagated contractile events which increased in frequency from early to late phase II (0.5 ± 0.9 vs 2.5 ± 1.3 events/10 min, respectively; p < 0.001). After meal ingestion, non-propagated activity increased, whereas propagated events were less frequent than during late phase II. CONCLUSIONS & INFERENCES: Jejunal motility analysis with high-resolution manometry identifies propagated contractile patterns which are not apparent with conventional manometric catheters.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, underlying pathophysiology, diagnosis, treatment, and prognosis. METHODS: A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements. RESULTS: The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long-term prognosis and life expectancy are favorable. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.

Abdominothoracic Postural Tone Influences the Sensations Induced by Meal Ingestion.

Postprandial objective abdominal distention is frequently associated with a subjective sensation of abdominal bloating, but the relation between both complaints is unknown. While the bloating sensation has a visceral origin, abdominal distention is a behavioral somatic response, involving contraction and descent of the diaphragm with protrusion of the anterior abdominal wall. Our aim was to determine whether abdominal distention influences digestive sensations. In 16 healthy women we investigated the effect of intentional abdominal distention on experimentally induced bloating sensation (by a meal overload). Participants were first taught to produce diaphragmatic contraction and visible abdominal distention. After a meal overload, sensations of bloating (0 to 10) and digestive well-being (-5 to + 5) were measured during 30-s. maneuvers alternating diaphragmatic contraction and diaphragmatic relaxation. Compared to diaphragmatic relaxation, diaphragmatic contraction was associated with diaphragmatic descent (by 21 + 3 mm; p < 0.001), objective abdominal distension (32 + 5 mm girth increase; p = 0.001), more intense sensation of bloating (7.3 + 0.4 vs. 8.0 + 0.4 score; p = 0.010) and lower digestive well-being (-0.9 + 0.5 vs. -1.9 + 0.5 score; p = 0.028). These results indicate that somatic postural tone underlying abdominal distention worsens the perception of visceral sensations (ClinicalTrials.gov ID: NCT04691882).

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.

Different responses of the blockade of the P2Y1 receptor with BPTU in human and porcine intestinal tissues and in cell cultures.

BACKGROUND: Gastrointestinal smooth muscle relaxation is accomplished by activation of P2Y1 receptors, therefore this receptor plays an important role in regulation of gut motility. Recently, BPTU was developed as a negative allosteric modulator of the P2Y1 receptor. Accordingly, the aim of this study was to assess the effect of BPTU on purinergic neurotransmission in pig and human gastrointestinal tissues. METHODS: Ca2+ imaging in tSA201 cells that express the human P2Y1 receptor, organ bath and microelectrodes in tissues were used to evaluate the effects of BPTU on purinergic responses. KEY RESULTS: BPTU concentration dependently (0.1 and 1 µmol L-1 ) inhibited the rise in intracellular Ca2+ evoked by ADP in tSA201 cells. In the pig small intestine, 30 µmol L-1 BPTU reduced the fast inhibitory junction potential by 80%. Smooth muscle relaxations induced by electrical field stimulation were reduced both in pig ileum (EC50  = 6 µmol L-1 ) and colon (EC50  = 35 µmol L-1 ), but high concentrations of BPTU (up to 100 µmol L-1 ) had no effect on human colonic muscle. MRS2500 (1 µmol L-1 ) abolished all responses. Finally, 10 µmol L-1 ADPßS inhibited spontaneous motility and this was partially reversed by 30 µmol L-1 BPTU in pig, but not human colonic tissue and abolished by MRS2500 (1 µmol L-1 ). CONCLUSIONS & INFERENCES: BPTU blocks purinergic responses elicited via P2Y1 receptors in cell cultures and in pig gastrointestinal tissue. However, the concentrations needed are higher in pig tissue compared to cell cultures and BPTU was ineffective in human colonic tissue.

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.

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.

European Society for Neurogastroenterology and Motility recommendations for conducting gastrointestinal motility and function testing in the recovery phase of the COVID-19 pandemic.

BACKGROUND: During the peak of the COronaVIrus Disease 2019 (COVID-19) pandemic, care for patients with gastrointestinal motility and functional disorders was largely suspended. In the recovery phases of the pandemic, non-urgent medical care is resumed, but there is a lack of guidance for restarting and safely conducting motility and function testing. Breath tests and insertion of manometry and pH-monitoring probes carry a risk of SARS-CoV-2 spread through droplet formation. METHODS: A panel of experts from the European Society for Neurogastroenterology and Motility (ESNM) evaluated emerging national and single-center recommendations to provide the best current evidence and a pragmatic approach to ensure the safe conduct of motility and function testing for both healthcare professionals and patients. RESULTS: At a general level, this involves evaluation of the urgency of the procedure, evaluation of the infectious risk associated with the patient, the investigation and the healthcare professional(s) involved, provision of the test planning and test units, education and training of staff, and use of personnel protection equipment. Additional guidance is provided for specific procedures such as esophageal manometry, pH monitoring, and breath tests. CONCLUSIONS AND INFERENCES: The ESNM guidelines provide pragmatic and appropriate guidance for the safe conduct of motility and function testing in the COVID-19 pandemic and early recovery phase.

Sex Differences and Commonalities in the Impact of a Palatable Meal on Thalamic and Insular Connectivity.

The neural mechanisms underlying subjective responses to meal ingestion remain incompletely understood. We previously showed in healthy men an increase in thalamocortical, and a decrease in insular-cortical connectivity in response to a palatable meal. As sex is increasingly recognized as an important biological variable, we aimed to evaluate sex differences and commonalities in the impact of a well-liked meal on thalamic and anterior insular connectivity in healthy individuals. Participants (20 women and 20 age-matched men) underwent resting-state magnetic resonance imaging (rsMRI) before and after ingesting a palatable meal. In general, the insula showed extensive postprandial reductions in connectivity with sensorimotor and prefrontal cortices, while the thalamus showed increases in connectivity with insular, frontal, and occipital cortices, in both women and men. However, reductions in insular connectivity were more prominent in men, and were related to changes in meal-related sensations (satiety and digestive well-being) in men only. In contrast, increases in thalamic connectivity were more prominent in women, and were related to changes in satiety and digestive well-being in women only. These results suggest that brain imaging may provide objective and sex-specific biomarkers of the subjective feelings associated with meal ingestion.

Motor dysfunction of the gut in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Cystic fibrosis transmembrane conductance regulator is extensively expressed in the intestine and has an important role in the regulation of the viscosity and pH of gut secretions. Several studies have reported a delay in small bowel and colonic transit times in patients with CF which have been attributed to the secretory dysfunction. Our aim was to determine whether intestinal contractility is affected in these patients. METHODS: Consecutive patients with CF referred to our institution between 2014 and 2017 (n = 16) were prospectively investigated using automated non-invasive techniques for morpho-functional evaluation of the gut developed in our laboratory. On separate days, intraluminal images of the gut were obtained by capsule endoscopy and external images by abdominal MRI. Analysis of images (endoluminal and external) was performed with original, previously validated programs based on computer vision and machine learning techniques and compared with age- and sex-matched controls. KEY RESULTS: Patients with CF exhibited important reduction in contractile activity and increased retention of static turbid luminal content in the small bowel by endoluminal image analysis. Morpho-volumetric analysis of MRI images found increased ileo-colonic volumes in CF. Significant correlations between abnormalities detected by intraluminal and external imaging techniques were found. The presence and severity of digestive symptoms were not related to abnormal gut function. CONCLUSION AND INFERENCES: Impaired transit and pooling of gut contents in patients with CF is associated with impaired intestinal motility.

Testing the Food Experience in Healthy Human Volunteers: a Proof-of-Concept Study.

BACKGROUND AND AIMS: For a healthy food to be introduced to the consumer's diet, it has to be attractive, yet testing for food acceptance and the sensory postprandial responses is still not standardized. The main objective of this study was to demonstrate that healthier foods can be obtained without impact on the responses to ingestion. METHODS: A randomized, cross-over, double-blind, pilot study in non-obese, healthy men (n=8) comparing the responses to a standard sausage rich in animal fat (mortadella) versus a modified product based on a plant-derived fat analogue and an aroma. Palatability and postprandial sensations were measured on 10 cm scales and brain activity was evaluated by functional magnetic resonance imaging before and after each meal on separate days. RESULTS: Both meals were rated equally palatable and induced the same degree of homeostatic sensations (satiety, fullness) with a similar hedonic dimension (improved mood and digestive well-being). Both meals induced similar changes in brain connectivity: decreased activity in the frontal-parietal, basal ganglia and thalamus, visual occipital, sensory-motor, temporal superior and in the "default-mode" networks, while increased activity was detected in the network associated with white matter. CONCLUSION: A substantial improvement in the nutritional profile of food can be achieved without affecting the responses to ingestion.

A Fermented Milk Product with B. Lactis CNCM I-2494 and Lactic Acid Bacteria Improves Gastrointestinal Comfort in Response to a Challenge Diet Rich in Fermentable Residues in Healthy Subjects.

BACKGROUND: Healthy plant-based diets rich in fermentable residues may induce gas-related symptoms. Our aim was to determine the potential of a fermented milk product with probiotics in improving digestive comfort with such diets. METHODS: In an open design, a 3-day high-residue diet was administered to healthy subjects (n = 74 included, n = 63 completed) before and following 28 days consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. MAIN OUTCOMES: digestive sensations, number of daytime anal gas evacuations, and gas volume evacuated during 4 h after a probe meal. RESULTS: As compared to the habitual diet, the high-residue diet induced gas-related symptoms (flatulence score 4.9 vs. 1.2; p ≤ 0.0001), increased the daily number of anal gas evacuations (20.7 vs. 8.7; p < 0.0001), and impaired digestive well-being (1.0 vs. 3.4; p < 0.05). FMP consumption reduced flatulence sensation (by -1.7 [-1.9; -1.6]; p < 0.0001), reduced the number of daily evacuations (by -5.8 [-6.5; -5.1]; p < 0.0001), and improved digestive well-being (by +0.6 [+0.4; +0.7]; p < 0.05). FMP consumption did not affect the gas volume evacuated after a probe meal. CONCLUSION: In healthy subjects, consumption of a FMP containing B. lactis CNCM I-2494 and lactic acid bacteria improves the tolerance of a flatulogenic diet by subjective and objective criteria (sensations and number of anal gas evacuations, respectively).