Bowel Motility Research Articles

Effect of small dose ketamine on morphine requirement after intestinal surgery: A randomized controlled trial

ABSTRACT Background: N-methyl-D-aspartate (NMDA) receptors are thought to be for pain memory, and blocking them can help to reduce pain. We aimed to assess the preventive effects of small doses of ketamine administered prior to the skin incision in abdominal surgery, to assess analgesic efficacy and intra-operative and post-operative side effects. Methods: 60 adult patients with ASA I and II who were scheduled for abdominal surgery were randomly divided into two groups in a prospective, double-blind study. Before the skin incision, group K received 1 mg/kg ketamine intravenously, followed by a 0.12 mg/kg/h ketamine infusion till the skin was closed. Instead of ketamine, group C received normal saline. After extubation, both groups received morphine 5 mg IV. The visual analogue scale (VAS) was used to measure analgesic effectiveness at rest and after exercise, as well as the duration to the first analgesic and morphine intake in 24 h, and analyze changes in serum CRP and IL6 levels as indicators of its impact. Also, side effects of opioid or ketamine have been recorded. Results: Within 24 h, patients in the ketamine group had a significantly lower VAS score, a longer time to the first analgesic (326.3 ± 49.5 minutes), and lower morphine consumption (6.9 ± 2.91 mg). Also, postoperative interleukin 6 and CRP showed significant difference between the two groups (p ≤ 0.05). In group K, no side effects were detectable. Conclusion: Ketamine may be a promising drug in low doses that can limit and even prevent worsened inflammation. It also resulted in decreased postoperative opioid use, decreased pain rating, earlier retains of bowel motility, and decreased incidence of side effects.

Фармакология спазмолитических средств, применяемых в терапии синдрома раздраженного кишечника

Objective of the Review: To describe and compare some pharmacodynamic and pharmacokinetic parameters of antispasmodic drugs used in complex management of irritable bowel syndrome (IBS) in the Russian Federation. Key Points. IBS is a chronic recurrent disease associated with abdominal pain and bowel disorders. The key factors of IBS pathogenesis include intestinal motility disorders and visceral hypersensitivity. Both processes are controlled by endocrine and neural systems. In a target cell, voltage-operated calcium channels mediate neuronal signals for unstriped muscles to contract and for glands to start secreting. Antispasmodic drugs are a group of products that have been used for IBS management for decades. The review describes contemporary idea of molecular mechanisms to control contraction of GIT muscle cells and a comparison of antispasmodic drugs used in complex therapy of IBS in the Russian Federation. Their key pharmacodynamic and pharmacokinetic characteristics are discussed. Conclusion. The fundamental difference of mebeverine (Duspatalin) is its ability to normalise bowel motility in patients with IBS without the need in complete motility suppression. Also, its inability to block muscarinic receptors and stimulate opioid receptors is another advantage in improving the quality of life of patients. Keywords: pharmacodynamics, pharmacokinetics, antispasmodic drugs, therapy of irritable bowel syndrome, mebeverine.

Fasted and fed small bowel motility patterns at cine-MRI in chronic intestinal pseudo-obstruction.

BackgroundChronic intestinal pseudo‐obstruction (CIPO) is a severe intestinal motility disorder of which the pathophysiology is largely unknown. This study aimed at gaining insight in fasted and fed small bowel motility in CIPO patients using cine‐MRI with caloric stimulation.MethodsEight adult patients with manometrically confirmed CIPO were prospectively included. Patients underwent a cine‐MRI protocol after an overnight fast, comprising fasting‐state scans and scans after ingestion of a meal (Nutridrink, 300 kcal). Small bowel motility was quantified resulting in a motility score in arbitrary units (AU) and visually assessed by three radiologists. Findings were compared with those in 16 healthy volunteers.Key ResultsMotility scores (median, IQR) in CIPO patients were 0.21 (0.15–0.30) in the fasting state and 0.23 (0.15–0.27) directly postprandially. In healthy volunteers, corresponding motility scores were 0.15 (0.13–0.18) and 0.22 (0.19–0.25), respectively. The postprandial change in motility score was +1% (−19 to +21%) in CIPO and +39% (+23 to +50%) in healthy volunteers (p = 0.001*). Visual analysis revealed increased small bowel contractility in four, normal in two, and decreased in two CIPO patients.Conclusions & InferencesSurprisingly, we found hyperactive small bowel motility in half of the CIPO patients, suggestive of uncoordinated motility. A wide variation in motility patterns was observed, both higher, lower, and comparable contractility compared with healthy subjects. No clear postprandial activation was seen in patients. Cine‐MRI helps to gain insight in this complex disease and can potentially impact treatment decisions in the future.

MR Measures of Small Bowel Wall T2 Are Associated With Increased Permeability.

Increased small bowel permeability leads to bacterial translocation, associated with significant morbidity and mortality. Biomarkers are needed to evaluate these changes in vivo, stratify an individual's risk, and evaluate the efficacy of interventions. MRI is an established biomarker of small bowel inflammation. To characterize changes in the small bowel with quantitative MRI measures associated with increased permeability induced by indomethacin. Prospective single-center, double-blind, two-way crossover provocation study. A provocation cohort (22 healthy volunteers) and intrasubject reproducibility cohort (8 healthy volunteers). 2D balanced turbo field echo sequences to measure small bowel wall thickness, T2 , and motility acquired at 3T. Participants were randomized to receive indomethacin or placebo prior to assessment. After a minimum 2-week washout, measures were repeated with the alternative allocation. MR measures (wall thickness, T2 , motility) at each study visit were compared to the reference standard 2-hour lactulose/mannitol urinary excretion ratio (LMR) test performed by a lab technician. All analyses were performed blind. Normality was tested (Shapiro-Wilk's test). Paired testing (Student's t-test or Wilcoxon) determined the significance of paired differences with indomethacin provocation. Pearson's correlation coefficient compared significant measures with indomethacin provocation to LMR. Intrasubject (intraclass correlation) and interrater variability (Bland-Altman) were assessed. Indomethacin provocation induced a significant increase in LMR compared to placebo (P < 0.05) and a significant increase in small bowel T2 (0.12 seconds compared to placebo 0.07 seconds, P < 0.05). Small bowel wall thickness (P = 0.17) and motility (P = 0.149) showed no significant change. T2 and LMR were positively correlated (r = 0.68, P < 0.05). T2 measurements were robust to interobserver (intraclass correlation 0.89) and intrasubject variability (Bland-Altman bias of 0.005 seconds, 95% confidence interval [CI] -0.04 to +0.05 seconds, and 0.0006 seconds, 95% CI -0.05 to +0.06 seconds). MR measures of small bowel wall T2 were significantly increased following indomethacin provocation and correlated with 2-hour LMR test results. 1 TECHNICAL EFFICACY STAGE: 2.

Inhibition of Tryptophan Hydroxylases and Monoamine Oxidase-A by the Proton Pump Inhibitor, Omeprazole-In Vitro and In Vivo Investigations.

Serotonin (5-HT) is a hormone and neurotransmitter that modulates neural activity as well as a wide range of other physiological processes including cardiovascular function, bowel motility, and platelet aggregation. 5-HT synthesis is catalyzed by tryptophan hydroxylase (TPH) which exists as two distinct isoforms; TPH1 and TPH2, which are responsible for peripheral and central 5-HT, respectively. Due to the implication of 5-HT in a number of pathologies, including depression, anxiety, autism, sexual dysfunction, irritable bowel syndrome, inflammatory bowel disease, and carcinoid syndrome, there has been a growing interest in finding modulators of these enzymes in recent years. We thus performed high-throughput screening (HTS) using a fluorescence-based thermal shift assay (DSF) to search the Prestwick Chemical Library containing 1,280 compounds, mostly FDA-approved drugs, for TPH1 binders. We here report the identification of omeprazole, a proton pump inhibitor, as an inhibitor of TPH1 and TPH2 with low micromolar potency and high selectivity over the other aromatic amino acid hydroxylases. The S-enantiomer of omeprazole, esomeprazole, has recently also been described as an inhibitor of monoamine oxidase-A (MAO-A), the main enzyme responsible for 5-HT degradation, albeit with lower potency compared to the effect on TPH1 and TPH2. In order to investigate the net effect of simultaneous inhibition of TPH and MAO-A in vivo, we administered high-dose (100 mg/kg) omeprazole to CD-1 mice for 4 days, after which the animals were subjected to the tail suspension test. Finally, central (whole brain) and peripheral (serum) 5-HT content was measured using liquid chromatography-mass spectrometry (LC-MS). Omeprazole treatment significantly increased 5-HT concentrations, both in brain and in serum, and reduced the time spent immobile in the tail suspension test relative to vehicle control. Thus, the MAO-A inhibition afforded by high-dose omeprazole appears to overcome the opposing effect on 5-HT produced by inhibition of TPH1 and TPH2. Further modification of proton pump inhibitor scaffolds may yield more selective modulators of 5-HT metabolism.

OC-0568: The effect of external beam radiotherapy on bowel motility in gynaecological cancer patients

OC-0568: The effect of external beam radiotherapy on bowel motility in gynaecological cancer patients

PO-1729: Quality assurance of deformable image registration for bowel motility quantification

PO-1729: Quality assurance of deformable image registration for bowel motility quantification

PO-1730: Development of a framework to quantify bowel motility in 3D using MRI

PO-1730: Development of a framework to quantify bowel motility in 3D using MRI

Bowel scintigraphy identifies segmental dysmotility prior to stoma closure

Abstract Introduction Stoma closure surgery (SCS; restoring intestinal continuity) in children is associated with high post-surgical complication rates with no established preventive strategies. Although many of these complications can be directly or indirectly attributable to bowel obstruction, no anatomical obstructive pathology is found in the majority. Intestinal dysmotility in children with no prior surgery is a well-known entity, which can lead to clinical features similar to anatomical obstruction. It is not known if a similar pathology could be the reason for SCS complications as well. Method & Results We retrospectively reviewed five consecutive cases in our institution between 2016 and 2018, where scintigraphy was utilized to assess bowel motility prior to SCS. The radiotracer is administered via stoma or per anum, admixed with barium for anatomical assessment. Three children had failed prior attempts at SCS (underlying disease: spontaneous neonatal perforation, necrotizing enterocolitis, colonic atresia). A fourth patient, with gastroschisis, had ongoing obstruction despite multiple stricture resections. In all these patients, a dysmotile section of bowel was identified on scintigraphy in the distal small or large bowel and was resected. Three had excellent post-surgical follow up with no complications; one patient died in the immediate postoperative period likely from unrelated cause. A fifth child had a normal bowel motility study prior to SCS and had an uneventful follow up. Conclusions Areas of segmental dysmotility in the distal gut may be the primary cause of post-SCS complications. Using a novel approach of assessing bowel motility using scintigraphy, such areas can be identified pre-operatively and resected, leading to reduced post-SCS complications. We recommend further investigation and validation in a larger prospective study.

Effect of chewing gum on bowel recovery following caesarean section: a randomized controlled trial

Background: Postoperative ileus is the most frequent complication of any abdominal surgery. In case of patients who under caesarean sections it adds to the prolonged hospital stay and morbidity. Chewing gum acts similar to sham feeding has been proven to hasten return of gastrointestinal motility in non-obstetric abdominal surgery. To study the effectiveness of chewing gum on recovery of bowel function following Caesarean section.Methods: This study, a randomized controlled trial was conducted in the Department of Obstetrics and Gynecology, JIPMER over a period of 2 months. Age, parity and details of patients who underwent caesarean section (type/indication/duration) were noted. They were randomised and allocated into two groups, group a (gum chewing group) and group B (control group). Using a verbal questionnaire time of first feeling of hunger, first passage of flatus and first passage of feces were noted.Results: Mean time of first passage of flatus in group 1 (gum chewing) was 16.04±5.7 as compared to 22.05±4.8 in group 2 (standard care) and the difference was found to be statistically significant (p&lt;0.01). Mean time of first passage of feces in group 1(gum chewing) was 27.08±3.2 as compared to 32.04±4.3 in group 2 (standard care). None of the patients in our study had any side effects with use of chewing gum.Conclusions: Chewing gum significantly improves bowel motility when administered to patients following caesarean section and may help.

S1678 Ogilvie’s Syndrome in a Patient With COVID-19 Infection

INTRODUCTION: Ogilvie’s syndrome is characterized by colonic distension without signs of mechanical obstruction and it is caused by dysfunction of the autonomic nervous system. Common causes include infections, orthopedic surgery, renal failure, electrolyte disturbance and narcotic use. It is well known that viral infections can cause autonomic dysfunction. We present a case of Ogilvie’s syndrome which might have been caused by COVID-19. CASE DESCRIPTION/METHODS: 39-year-old male with history of HTN presented to the ED with dyspnea, fever, and cough for 8 days. Chest x-ray showed findings concerning for atypical pneumonia and PCR was positive for COVID-19. On day 6 of admission, he desaturated therefore he was intubated and transferred to the ICU. Due to prolonged constipation, patient underwent x-ray abdomen which showed gaseous distention of the colon. There was no improvement with lactulose, methylnaltrexone and enemas therefore a CT scan was done which showed distended small and large bowel loops without definite obstruction (Figure 1). Patient was started on Neostigmine and electrolytes were optimally replaced. Rectal and OG tubes was also placed. C. difficile toxin was negative. He had a bowel movement 3 days after neostigmine was started. Further management was done with enemas and he eventually started having regular bowel movements. Patient was extubated on day 23 of admission. He was gradually started on a diet and transferred to the general floor. Repeat x-ray abdomen showed improvement in colonic distention. Patient was saturating well on room air on day 35 therefore he was discharged home. DISCUSSION: Several management modalities are employed to treat Ogilvie’s syndrome including conservative measures (bowel rest, NG and rectal tubes placement and electrolyte replacement), medical therapies (neostigmine) with endoscopic decompression and surgery reserved for patients without any response to neostigmine. Cessation of medications that might exacerbate symptoms and treatment of underlying infection are important. In our patient, conservative management, neostigmine, and treatment of the underlying infection improved symptoms. Since COVID-19 is a new virus, many of the effects of this virus are yet to be discovered. It has effects on the nervous system including reports of cases of GBS, transverse myelitis, anosmia, encephalitis, and CVA. It is plausible that loss of parasympathetic spinal control of bowel motility may be one such manifestation of this disease.Figure 1.: a (coronal), 1b (axial) and 1c (sagittal) show different views of abdominal CT scan demonstrating dilated loops of large bowel (red arrows).

S3359 Adult Isolated Hypoganglionosis in the Anorectal Canal

INTRODUCTION: Hirschsprung's disease (HD) is a congenital bowel innervation disorder characterized by the absence of ganglion cells in myenteric and submucosal plexus in the distal. The term ‘‘Variant HD’’ has been used to describe a heterogeneous group of intestinal innervation disorders with clinical presentation that resembles HD despite the presence of ganglionic cells seen on rectal biopsy. Isolated hypoganglionosis is a rare entity that present with persistent bowel symptoms similar to those with classical HD, however has resected bowel histopathological findings of reduced number of nerve cells in the myenteric ganglia. CASE DESCRIPTION/METHODS: We present a case report of a 19-year-old male who was diagnosed with isolated hypoganglionosis following a long history of fecal impaction and constipation since childhood. Patient presented to our institution with complaints of distended abdomen at 19 years of age. CT imaging demonstrated a massively distended rectosigmoid colon filled with abundant fecal material (Figure 1). An abdominal series revealed stool scattered throughout his colon and a dilated, saccular appearing rectum. A water soluble contrast enema exhibited a short segment (approximately 8 cm) narrowing of bowel in the region of the rectum with dilated upstream sigmoid colon (Figure 2). The remainder of the visualized bowel including proximal sigmoid, descending, transverse, ascending colon and cecum were of normal caliber. This imaging pattern was compatible with Hirschsprung's disease. The patient then underwent a laparoscopic-assisted proctosigmoidectomy with a stapled end to end coloanal anastomosis and a diverting loop ileostomy. Though the surgical pathology demonstrated the presence of ganglion cells in the sigmoid colon and rectum, the anorectal canal showed presence of rare ganglion cells (Figure 3). On follow up, the patient underwent another water soluble contrast enema that confirmed an intact anastomosis and he subsequently underwent successful ileostomy closure two months later. One week after closure, the patient had recovered well, reporting daily bowel movements with good evacuation control and no fecal incontinence. DISCUSSION: To our knowledge, this is the first case of adult HD variant, isolated hypoganglionosis, with histology demonstrating hypoganglionosis in the anorectal canal and no evidence of agangliosis in the rectum and sigmoid colon. Following removal of the remnant hypoganglionic intestinal segment, our patient’s bowel motility significantly improved.Figure 1.: Routine CT abdomen and pelvis with intravenous and oral contrast was performed on admission with axial images and coronal reformations (A and B, respectively). These images demonstrated marked sigmoid colonic fecal loading and dilation (white arrows), compatible with a chronic obstructive process such as Hirschsprung's disease.Figure 2.: Water soluble enema study was performed. (A) This study showed a short segment (8 cm) narrowing of the distal rectum (solid white arrow) with upstream dilatation of the proximal rectum (dashed white arrow). (B) The AP view demonstrates massive upstream dilation of the rectum and sigmoid colon.Figure 3.: H&E stain of anorectal canal (A) and sigmoid rectal area (B). Arrows indicate ganglion cells, which were rare in the anorectal canal region. Inserts show the higher magnification of the circled area. Bar = 50 um.

EFFICACY OF POSTOPERATIVE PARENTERAL TRIMEBUTINE MALEATE IN RECOVERY OF BOWEL FUNCTION FOLLOWING CESAREAN SECTION

Background: Postoperative ileus remains a serious clinical problem. It is one of the most important contributors to increased length of hospitalization and consumption of the health care system resources. Attempts have been made to treat several causes simultaneously to quickly restore normal postoperative bowel motility. Objective: The aim of this study was to estimate the effectiveness of postoperative parentally administered Trimebutine maleate inducing intestinal motility after cesarean section. Patients and Methods: This study included 200 patients who were selected from the outpatient clinic of Obstetrics and Gynecology at Alexandria Armed Forces Hospital. They were classified into two equal groups: Group (1): Control group underwent traditional management (oral intake of clear fluids and I.V fluids), and Group (2): were infused intravenously by a total dose of 300mg of Trimebutine maleate per day divided into 100 mg every 8 hours till first passage of flatus. Each group was subdivided into two equal subgroups: A) GA group underwent cesarean section under general anesthesia, B) SA group underwent cesarean section under spinal analgesia. Results: There was a significant difference between GA and SA of the control group in which the SA group decreased in the time in comparison to the GA group in all the outcome measures. There was a significant difference between GA of the cases group and GA of the control group in which the GA of the cases group decreased in the time in comparison to the GA group of the control in all the outcome measures. There was a significant difference between SA of the cases group and SA of the control group in which the SA of the cases group decreased in the time in comparison to the SA group of the control in all the outcome measures. Regarding pain and distension. There was a significant difference between GA and SA of the control group with more cases in the GA group, there was a significant difference between SA of the control and SA of the cases with more cases with the SA of the control. Conclusion: Trimebutine maleate (GASTREG®) routinely administrated to patients after caesarean section speeds recovery of intestinal function postoperatively by stimulating gastrointestinal motility. So GASTREG is an inexpensive, tolerable and helpful measure to postoperative care after caesarean section and other abdominal surgery.

Motility index measured by magnetic resonance enterography is associated with sex and mural thickness.

BACKGROUNDRecently, a technique has been developed to use magnetic resonance enterography (MRE) for the evaluation of small bowel motility. The hypothesis was that assessment of the motility index (MI) should reflect differences in motility between clinical conditions.AIMTo aim of the present observational, cross-sectional study was to evaluate the use of the MI in daily clinical practice.METHODSAll consecutive patients aged 18-70 years who were referred for MRE at the Department of Radiology during a 2-year period were asked to participate. Healthy volunteers were included as controls. MRE was prepared and conducted in accordance with clinical routines. On the day of examination, all the participants had to complete the visual analog scale for irritable bowel syndrome (IBS) and IBS-symptom severity scale. Maps of MI were calculated from dynamic MR images. ANOVA was used to evaluate differences in MI between groups, classified as healthy, Crohn’s disease, ulcerative colitis, IBS, other assorted disorders and dysmotility. Logistic and linear regression were applied to the MI values. All medical records were scrutinized for medical history.RESULTSIn all, 224 examinations were included (inclusion prevalence 76.3%), with 22 controls and 202 patients. There was a significant difference in the MI of the jejunum (P = 0.021) and terminal ileum (P = 0.007) between the different groups. The MI was inversely associated with the mural thickness of the terminal ileum in men (P < 0.001) and women (P = 0.063) after adjustments, and tended to be lower in men than in women (P = 0.056). Subjectively observed reduction of motility on MRI was accomplished by reduced MI of terminal ileum in men (P < 0.001) and women (P = 0.030). In women, diarrhea was inversely associated with the MI of the jejunum (P = 0.029), and constipation was positively associated with the MI of the terminal ileum (P = 0.039).CONCLUSIONAlthough MIs differ across diseases, a lower MI of the terminal ileum is mainly associated with male sex and an increased mural thickness. Symptoms are weakly associated with the MI.

Quantitative assessment of terminal ileum motility on MR enterography in Crohn disease: a feasibility study in children.

Investigate the relationship between quantified terminal ileal (TI) motility and histopathological activity grading, Crohn Disease MRI Index (CDMI) and faecal calprotectin. Retrospective review of children with Crohn disease or unclassified inflammatory bowel disease, who underwent MR enterography. Dynamic imaging for 25 patients (median age 12, range 5 to 16) was analysed with a validated motility algorithm. The TI motility score was derived. The primary reference standard was TI Endoscopic biopsy Assessment of Inflammatory Activity (eAIS) within 40days of the MR enterography. Secondary reference standards: (1) the Crohn Disease MRI Index (CDMI) and (2) faecal calprotectin levels. MR enterography median motility score was 0.17a.u. (IQR 0.12 to 0.25; range 0.05 to 0.55), and median CDMI was 3 (IQR 0 to 5.5). Forty-three percent of patients had active disease (eAIS > 0) with a median eAIS score of 0 (IQR 0 to 2; range 0 to 5). The correlation between eAIS and motility was r = - 0.58 (p = 0.004, N = 23). Between CDMI and motility, r = - 0.42 (p = 0.037, N = 25). Motility score was lower in active disease (median 0.12 vs 0.21, p = 0.020) while CDMI was higher (median 5 vs 1, p = 0.04). In a subset of 12 patients with faecal calprotectin within 3months of MR enterography, correlation with motility was r = - 0.27 (p = 0.4). Quantified terminal ileum motility decreases with increasing histopathological abnormality in children with Crohn disease, reproducing findings in adults. TI motility showed a negative correlation with an MRI activity score but not with faecal calprotectin levels. • It is feasible to perform MRI quantified bowel motility assessment in children using free-breathing techniques. • Bowel motility in children with Crohn disease decreases as the extent of intestinal inflammation increases. • Quantified intestinal motility may be a candidate biomarker for treatment efficacy in children with Crohn disease.

Coffee consumption for recovery of intestinal function after laparoscopic gynecological surgery: A randomized controlled trial.

To investigate the effect of postoperative coffee consumption on bowel motility after laparoscopic gynecological surgery. In this randomized controlled trial, patients were allocated postoperatively to 3 cups of either coffee or warm water at 6, 12, or 18h after the operation. Total hysterectomy and bilateral salpingectomy were performed on all patients. In addition, a salpingo-oophorectomy and systematic pelvic with/without para-aortic lymphadenectomy were performed according to clinical indications. The primary endpoint was time to the first passage of flatus after surgery. A total of 96 patients were enrolled; 49 patients were assigned to the coffee group, and 47 were enrolled in the control group (warm water). The median time to flatus (19 [13-35] vs. 25 [15-42] h; hazard ratio [HR] 1.9, 95% confidence interval [CI], 1.2-2.9; P=0.0009), median time to defecation (30 [22-54] vs. 38 [26-65] h, HR 2.4, 95% CI, 1.5-3.8; P<0.0001), and mean time to tolerate food (2 [2-5] vs. 3 [2-8] days, HR 1.5, 95% CI, 1.02-2.3; P=0.002) were decreased significantly in patients who consumed coffee compared with the control subjects. Postoperative ileus was observed in seven patients (14.9%) in the control group and one patient (2.0%) in the coffee group (P=0.02). No adverse events were attributed to coffee consumption. Postoperative coffee intake after laparoscopic gynecological surgery hastened the recovery of gastrointestinal function by reducing the time to the first passage of flatus, time to the first defecation, and time to tolerate a solid diet. This simple, cheap, and well-tolerated treatment merits routine use alongside other existing enhanced recovery pathways in the postoperative setting.

Quantified small bowel motility in patients with ulcerative colitis and gastrointestinal symptoms: a pilot study.

Gastrointestinal (GI) symptoms are common in patients with ulcerative colitis (UC), even when the disease is in remission, possibly due to abnormalities in GI motility. Small bowel motility can be assessed globally and in specific intestinal regions during magnetic resonance enterography (MRE) using a displacement mapping technique. To investigate whether small bowel motility in MRE differs between patients with UC and controls, and if altered motility correlates with GI symptoms. In 2016-2018, patients who were admitted for MRE, regardless of clinical indication, were consecutively invited to the study. Healthy volunteers were recruited. The participants completed a questionnaire regarding GI symptoms and relevant clinical data were reviewed in the medical records. The dynamic imaging series obtained during MRE were sent for motility mapping and a motility index (MI) was calculated in jejunum, ileum and terminal ileum in all participants. In total, 224 patients and healthy volunteers were enrolled in the study. Fifteen were diagnosed with UC and 22 were considered healthy controls. In UC, the prevalence of GI symptoms was higher than in controls (P < 0.001), both in remission and in active disease. There was no correlation between GI symptoms and small bowel motility in UC. Jejunal motility was lower in UC than in controls (P = 0.049). Jejunal motility is decreased in UC compared with healthy controls, but there is no relationship between small bowel motility and GI symptoms in UC.

Serum Scoring and Quantitative Magnetic Resonance Imaging in Intestinal Failure-Associated Liver Disease: A Feasibility Study.

(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD (n = 12), patients with IFALD steatosis (n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis (p = 0.032), Aspartate transaminase-to-Platelet Ratio Index (p < 0.001), Fibrosis-4 Index (p = 0.010), Forns Index (p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index (p = 0.002) and Fibrosis Index (p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.

Glial Cell-Derived Neurotrophic Factor Induces Enteric Neurogenesis and Improves Colon Structure and Function in Mouse Models of Hirschsprung Disease

Hirschsprung disease (HSCR) is a life-threatening birth defect in which the distal colon is devoid of enteric neural ganglia. HSCR is treated by surgical removal of aganglionic bowel, but many children continue to have severe problems after surgery. We studied whether administration of glial cell derived neurotrophic factor (GDNF) induces enteric nervous system regeneration in mouse models of HSCR. We performed studies with four mouse models of HSCR: Holstein (HolTg/Tg, a model for trisomy 21-associated HSCR), TashT (TashTTg/Tg, a model for male-biased HSCR), Piebald-lethal (Ednrbs-l//s-l, a model for EDNRB mutation-associated HSCR), and Ret9/- (with aganglionosis induced by mycophenolate). Mice were given rectal enemas containing GDNF or saline (control) from postnatal days 4 through 8. We measured survival times of mice, and colon tissues were analyzed by histology, immunofluorescence, and immunoblots. Neural ganglia regeneration and structure, bowel motility, epithelial permeability, muscle thickness, and neutrophil infiltration were studied in colon tissues and in mice. Stool samples were collected, and microbiomes were analyzed by 16S rRNA gene sequencing. Time-lapse imaging and genetic cell-lineage tracing were used to identify a source of GDNF-targeted neural progenitors. Human aganglionic colon explants from children with HSCR were cultured with GDNF and evaluated for neurogenesis. GDNF significantly prolonged mean survival times of HolTg/Tg mice, Ednrbs-l//s-l mice, and male TashTTg/Tg mice, compared with control mice, but not Ret9/- mice (which had mycophenolate toxicity). Mice given GDNF developed neurons and glia in distal bowel tissues that were aganglionic in control mice, had a significant increase in colon motility, and had significant decreases in epithelial permeability, muscle thickness, and neutrophil density. We observed dysbiosis in fecal samples from HolTg/Tg mice compared with feces from wild-type mice; fecal microbiomes of mice given GDNF were similar to those of wild-type mice except for Bacteroides. Exogenous luminal GDNF penetrated aganglionic colon epithelium of HolTg/Tg mice, inducing production of endogenous GDNF, and new enteric neurons and glia appeared to arise from Schwann cells within extrinsic nerves. GDNF application to cultured explants of human aganglionic bowel induced proliferationof Schwann cells and formation of new neurons. GDNF prolonged survival, induced enteric neurogenesis, and improved colon structure and function in 3 mouse models of HSCR. Application of GDNF to cultured explants of aganglionic bowel from children with HSCR induced proliferation of Schwann cells and formation of new neurons. GDNF might be developed for treatment of HSCR.

Early-life malnutrition causes gastrointestinal dysmotility that is sexually dimorphic.

Slow gastrointestinal (GI) transit occurs in moderate-to-severe malnutrition. Mechanisms underlying malnutrition-associated dysmotility remain unknown, partially due to lack of animal models. This study sought to characterize GI dysmotility in mouse models of malnutrition. Neonatal mice were malnourished by timed maternal separation. Alternatively, low-protein, low-fat diet was administered to dams, with malnourished neonates tested at two weeks or weaned to the same chow and tested as young adults. We determined total GI transit time by carmine red gavage, colonic motility by rectal bead latency, and both gastric emptying and small bowel motility with fluorescein isothiocyanate-conjugated dextran. We assessed histology with light microscopy, ex vivo contractility and permeability with force-transduction and Ussing chamber studies, and gut microbiota composition by 16S rDNA sequencing. Both models of neonatal malnutrition and young adult malnourished males but not females exhibited moderate growth faltering, stunting, and grossly abnormal stomachs. Progression of fluorescent dye was impaired in both neonatal models of malnutrition, whereas gastric emptying was delayed only in maternally separated pups and malnourished young adult females. Malnourished young adult males but not females had atrophic GI mucosa, exaggerated intestinal contractile responses, and increased gut barrier permeability. These sex-specific abnormalities were associated with altered gut microbial communities. Multiple models of early-life malnutrition exhibit delayed upper GI transit. Malnutrition affects young adult males more profoundly than females. These models will facilitate future studies to identify mechanisms underlying malnutrition-induced pathophysiology and sex-specific regulatory effects.