Background: Linaclotide, a guanylate cyclase C agonist relieves irritable bowel syndrome with predominant constipation (IBS-C) symptoms, but how it improves pain in humans is unknown. Aims:To investigate the effects of linaclotide and placebo on the afferent and efferent gut-brain-gut signalling in IBS-C patients, in a randomised clinical trial. Methods:Patients with IBS-C (Rome III) and rectal hypersensitivity were randomised (2:1) to receive linaclotide (290 µg) or placebo for 10 weeks and undergo bi-directional gut and brain axis assessment using anorectal electrical stimulations and transcranial/transspinal-anorectal magnetic stimulations. Rectal sensations were examined by balloon distention. Assessments included abdominal pain, bowel symptoms and quality of life (QOL) scores. Primary outcomes were latencies of recto-cortical and cortico-rectal evoked potentials.Results: Thirty-nine patients participated; 26 received linaclotide and 13 received placebo. Rectal cortical evoked potentials latencies (milliseconds) were significantly prolonged with linaclotide compared to baseline (P1:Δ 19 ± 6, P < 0.005; N1:Δ 20 ± 7, P < 0.02) but not with placebo (P1:Δ 3 ± 5; N1:Δ 4.7 ± 5,P = 0.3) or between groups.The efferent cortico-anorectal and spino-anorectal latencies were unchanged. The maximum tolerable rectal volume (cc) increased significantly with linaclotide compared to baseline (P < 0.001) and placebo (Δ 29 ± 10 vs 4 ± 20, (P < 0.03). Abdominal pain decreased (P < 0.001) with linaclotide but not between groups. Complete spontaneous bowel movement frequency increased (P < 0.001), and IBS-QOL scores improved (P = 0.01) with linaclotide compared to baseline and placebo. There was no difference in overall responders between linaclotide and placebo (54% vs 23%, P = 0.13). Conclusions:Linaclotide prolongs afferent gut-brain signalling from baseline but both afferent and efferent signalling were unaffected compared to placebo. Linaclotide significantly improves rectal hypersensitivity, IBS-C symptoms and QOL compared to placebo.These mechanisms may explain the effects of linaclotide on pain relief in IBS-C patients. ClinicalTrials.Gov: Registered at Clinical trials.gov no NCT02078323.This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations.

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DWI can be applied as a useful tool for evaluating the T staging of rectal cancer. The interobserver agreement obtained by using DWI is better than that obtained by using T2WI.

Gastrointestinal (GI) dysfunction is common in the critical care setting and is highly associated with clinical outcomes. Opioids increase the risk for GI dysfunction and are frequently prescribed to reduce pain in critically ill patients. However, the role of opioids in GI function remains uncertain in the ICU. This review aims to describe the effect of opioids on GI motility, their potential risk of increasing infection and the treatment of GI dysmotility with opioid antagonists in the ICU setting.

INTRODUCTION: Treatments for fecal incontinence (FI) remain unsatisfactory because they do not remedy the underlying multifactorial dysfunction(s) including anorectal neuropathy. The aim of this study was to investigate the optimal dose frequency, clinical effects, and safety of a novel treatment, translumbosacral neuromodulation therapy (TNT), aimed at improving neuropathy. METHODS: Patients with FI were randomized to receive 6 sessions of weekly TNT treatments consisting of 600 repetitive magnetic stimulations over each of 2 lumbar and 2 sacral sites with either 1, 5, or 15 Hz frequency. Stool diaries, FI severity indices, anorectal neurophysiology and sensorimotor function, and quality of life were compared. Primary outcome measure was the change in FI episodes/week. Responders were patients with ≥50% decrease in weekly FI episodes. RESULTS: Thirty-three patients with FI participated. FI episodes decreased significantly (∆ ±95% confidence interval, 4.2 ± 2.8 (1 Hz); 2 ± 1.7 (5 Hz); 3.4 ± 2.5 (15 Hz); P < 0.02) in all 3 groups when compared with baseline. The 1 Hz group showed a significantly higher (P = 0.04) responder rate (91 ± 9.1%) when compared with the 5 Hz group (36 ± 18.2%) or 15 Hz (55 ± 18.2%); no difference was found between the 5 and 15 Hz groups (P = 0.667). Anal neuropathy, squeeze pressure, and rectal capacity improved significantly only in the 1 Hz (P < 0.05) group compared with baseline, but not in other groups. Quality of life domains improved significantly (P < 0.05) with 1 and 5 Hz groups. No device-related serious adverse events were noted. DISCUSSION: TNT significantly improves FI symptoms in the short term, and the 1 Hz frequency was overall better than 5 and 15 Hz. Both anorectal neuropathy and physiology significantly improved, demonstrating mechanistic improvement. TNT is a promising, novel, safe, efficacious, and noninvasive treatment for FI (see Visual Abstract, Supplementary Digital Content 3, http://links.lww.com/AJG/B598).

Los desórdenes anorrectales afectan al 20% de la población. Los trastornos comunes incluyen la incontinencia fecal, el dolor anorrectal funcional, la defecación disinérgica y otros trastornos de la defecación funcional. La manometría anorrectal, especialmente en la última década, ha surgido como una herramienta valiosa para la evaluación y el diagnóstico de estas afecciones. En esta revisión describimos nuestro enfoque para realizar un estudio meticuloso y de alta calidad, así como cumplir con los estándares mínimos para el procedimiento. Asimismo, describimos: instrucciones de preparación; composición del equipo, que incluye sonda, hardware y software; detalles técnicos del procedimiento, incluyendo varias maniobras; un análisis sistemático de los datos obtenidos mediante manometría anorrectal de alta resolución y, finalmente, cómo interpretar y generar un informe estándar.

Background/Aims Disaccharidase assay is used for assessing carbohydrate intolerance in children, but its usefulness in adults is not known. The aim of this study is to assess the prevalence of disaccharidase deficiency in patients with unexplained gastrointestinal symptoms. Methods A retrospective review of adults with chronic (> 1 year) abdominal symptoms and negative imaging and endoscopy/colonoscopy and who completed bowel symptom questionnaire and duodenal biopsy for lactase, maltase, sucrase, and palatinase was performed. A subset also underwent 25 g lactose breath test (LBT). Results One hundred twenty patients (females = 83) were evaluated, of whom 48 also underwent LBT. Fifty-six (46.7%) patients had enzyme deficiency; 44 (36.7%) had single (either lactase or maltase), 1 had 3 enzyme deficiencies, 11 (9.2 %) had all 4 disaccharidase enzyme (pan-disaccharidase) deficiency, and 64 (53.0%) had normal enzyme levels. Baseline prevalence and severity of 11 gastrointestinal symptoms were similar between normal and single enzyme deficiency groups. The sensitivity and specificity of LBT was 78.3% and 72.0%, respectively and overall agreement with lactase deficiency was 75.0%. Conclusions Isolated disaccharidase deficiency occurs in adults, usually lactase and rarely maltase, and pan-disaccharidase deficiency is rare. Baseline symptoms or its severity did not predict enzyme deficiency.