Life-threatening bowel complications in adults with Duchenne muscular dystrophy: a case series.

Duchenne muscular dystrophy is a progressive muscle wasting disease caused by pathogenic variants in DMD. Gastrointestinal involvement is increasingly recognised in older patients and can manifest as life-threatening bowel dysmotility. We describe a series of adults with Duchenne muscular dystrophy who developed either severe colonic pseudo-obstruction or sigmoid volvulus requiring urgent assessment and intervention. The presentations varied in their clinical picture and outcomes, but together highlight the complexity of managing gastrointestinal complications in this cohort of patients. Key considerations include pre-existing cardiorespiratory compromise and the increased risk associated with surgery and general anaesthesia. We also outline a role for home parenteral nutrition in the long-term management of associated bowel dysmotility.

Pelvic floor imaging in asymptomatic subjects.

AIM: The aim of this work was to determine the range of normal imaging features during total pelvic floor ultrasound (TPFUS) (transperineal, transvaginal, endovaginal and endoanal) and defaecation MRI (dMRI). METHOD: Twenty asymptomatic female volunteers (mean age 36.5 years) were prospectively investigated with dMRI and TPFUS. Subjects were screened with symptom questionnaires (ICIQ-B, St Mark's faecal incontinence score, obstructed defaecation syndrome score, ICIQ-V, BSAQ). dMRI and TPFUS were performed and interpreted by blinded clinicians according to previously published methods. RESULTS: The subjects comprised six parous and 14 nulliparous women, of whom three were postmenopausal. There were three with a rectocoele on both modalities and one with a rectocoele on dMRI only. There was one with intussusception on TPFUS. Two had an enterocoele on both modalities and one on TPFUS only. There were six with a cystocoele on both modalities, one on dMRI only and one on TPFUS only. On dMRI, there were 12 with functional features. Four also displayed functional features on TPFUS. Two displayed functional features on TPFUS only. CONCLUSION: This study demonstrates the presence of abnormal findings on dMRI and TPFUS without symptoms. There was a high rate of functional features on dMRI. This series is not large enough to redefine normal parameters but is helpful for appreciating the wide range of findings seen in health.

An investigation into the effect of nasogastric intubation on markers of autonomic nervous function.

BACKGROUND: Nasogastric (NG) intubation for esophageal manometry can be traumatic and may be associated with a temporary reduction/absence in esophageal peristalsis. This study explored the prevalence and effect on esophageal motor function. We also hypothesized that baseline anxiety as well as markers of autonomic nerve function were correlated to attenuated esophageal peristalsis. METHODS: Twenty-seven patients with esophageal symptoms referred for esophageal manometry investigation (mean age 56.8 ± 16.7 years, range 23-85 years) reported baseline anxiety score (Likert scale) preintubation. Patients had continuous heart rate and blood pressure measured prior to intubation and until 10 min after catheter withdrawal. Quality of motility was assessed for each 5 ml water swallow using standard Chicago Classification metrics. KEY RESULTS: Nasogastric-intubation elicited a significant increase in heart rate (p < 0.001), systolic (p < 0.001) and diastolic (p < 0.001) blood pressure, which was in part anticipatory. The median time taken for patients' first hypotensive peristalsis (Distal Contractile Integral; DCI ≥100 mmHg s cm) was 130 s (Interquartile range; 47-242 s) and for their first normal peristalsis (DCI ≥450 mm Hg s cm) was 150 s (IQR 61-320 s), with improvement and consistent stabilization in DCI there onward. This corresponded closely to the time for initial recovery of heart rate and systolic and diastolic blood pressure postintubation. CONCLUSIONS AND INFERENCES: Nasogastric intubation resulted in heightened sympathetic responses and/or dampened parasympathetic responses, and an associated temporary reduction or absence in esophageal peristalsis.

MASCC recommendations on the management of constipation in patients with advanced cancer.

PURPOSE: The Palliative Care Study Group of the Multinational Association for Supportive Care in Cancer formed a subgroup to develop evidence-based recommendations on the management of constipation in patients with advanced cancer. METHODS: These recommendations were developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials respectively. The recommendations were categorised by the level of evidence and a "category of guideline" based on the level of evidence (i.e. "recommendation", "suggestion", or "no guideline possible"). RESULTS: The group produced 15 recommendations, with varying levels of evidence and so varying categories of guideline. The recommendations relate to the assessment, the treatment, and the re-assessment of constipation. CONCLUSIONS: These recommendations provide a framework for the management of constipation in advanced cancer, although every patient needs individualised management.

Neurogenic bowel dysfunction in patients with multiple sclerosis: prevalence, impact, and management strategies.

Bowel dysfunction in patients with multiple sclerosis (MS) is highly prevalent. Constipation and fecal incontinence can coexist and alternate, impacting on the patient's quality of life and social interactions, as well as burdening the caregivers. The cost for the health care providers is also significant, with increased number of hospital admissions, treatment-related costs, and hospital appointments. The origin is multifactorial, and includes alteration of neurological pathways, polypharmacy, behavioral elements, and ability to access the toilet. Every patient with MS should be sensitively questioned about bowel function, and red flag symptoms should prompt adequate investigations. Manipulation of life style factors and establishment of a bowel regime should be attempted in the first place, and if this fails, other measures such as biofeedback and transanal irrigation should be included. A stoma can improve quality of life, and is not necessarily a last-ditch option. Antegrade colonic enemas can also be an effective option, whilst neuromodulation has not proved its role yet. Effective treatment of bowel dysfunction improves quality of life, reduces incidence of urinary tract infection, and reduces health care costs.

Long-Term Cost-Effectiveness of Transanal Irrigation in Patients with Neurogenic Bowel Dysfunction.

BACKGROUND: People suffering from neurogenic bowel dysfunction (NBD) and an ineffective bowel regimen often suffer from fecal incontinence (FI) and related symptoms, which have a huge impact on their quality of life. In these situations, transanal irrigation (TAI) has been shown to reduce these symptoms and improve quality of life. AIM: To investigate the long-term cost-effectiveness of initiating TAI in patients with NBD who have failed standard bowel care (SBC). METHODS: A deterministic Markov decision model was developed to project the lifetime health economic outcomes, including quality-adjusted life years (QALYs), episodes of FI, urinary tract infections (UTIs), and stoma surgery when initiating TAI relative to continuing SBC. A data set consisting of 227 patients with NBD due to spinal cord injury (SCI), multiple sclerosis, spina bifida and cauda equina syndrome was used in the analysis. In the model a 30-year old individual with SCI was used as a base-case. A probabilistic sensitivity analysis was applied to evaluate the robustness of the model. RESULTS: The model predicts that a 30-year old SCI patient with a life expectancy of 37 years initiating TAI will experience a 36% reduction in FI episodes, a 29% reduction in UTIs, a 35% reduction in likelihood of stoma surgery and a 0.4 improvement in QALYs, compared with patients continuing SBC. A lifetime cost-saving of £21,768 per patient was estimated for TAI versus continuing SBC alone. CONCLUSION: TAI is a cost-saving treatment strategy reducing risk of stoma surgery, UTIs, episodes of FI and improving QALYs for NBD patients who have failed SBC.

Women's views on autologous cell-based therapy for post-obstetric incontinence.

AIM: Fecal and urinary incontinence are devastating consequences of obstetric-related perineal injury. The aim of the present study is to determine acceptability to parous women of autologous cell-based therapy for fecal and urinary incontinence that arises due to pelvic diaphragm tearing during vaginal childbirth. MATERIALS & METHODS: A multiple choice questionnaire survey was offered to 76 parous women at the Maternity Unit, University College Hospital, London, UK. Seventy completed questionnaires - response rate: 92%. RESULTS: In total, 84% of women indicated a willingness to accept autologous cell-based therapy for obstetric injury-induced incontinence rather than surgery. CONCLUSION: These observational data provide an indication of likely acceptance of autologous cell-based therapies for birth injury incontinence and will help with designing new therapeutic approaches.

Aberrant Motility in Unaffected Small Bowel is Linked to Inflammatory Burden and Patient Symptoms in Crohn's Disease.

BACKGROUND: Inflammation-related enteric dysmotility has been postulated as a cause for abdominal symptoms in Crohn's disease (CD). We investigated the relationship between magnetic resonance imaging-quantified small bowel (SB) motility, inflammatory activity, and patient symptom burden. METHODS: The Harvey-Bradshaw index (HBI) and fecal calprotectin were prospectively measured in 53 patients with CD (median age, 35; range, 18-78 years) the day before magnetic resonance enterography, which included a dynamic (cine), breath-hold motility sequence, repeated to encompass the whole SB volume. A validated registration-based motility quantitation technique produced motility maps, and regions of interest were drawn to include all morphologically normal SB (i.e., excluding diseased bowel). Global SB motility was correlated with calprotectin, HBI, and symptom components (well-being, pain, and diarrhea). Adjustment for age, sex, smoking, and surgical history was made using multivariate linear regression. RESULTS: Median calprotectin was 336 (range, 0-1280). Median HBI, motility mean, and motility variance were 3 (range, 0-16), 0.33 (0.18-0.51), and 0.01 (0.0014-0.034), respectively. Motility variance was significantly negatively correlated with calprotectin (rho = -0.33, P = 0.015), total HBI (rho = -0.45, P < 0.001), well-being (rho = -0.4, P = 0.003), pain (rho = -0.27, P = 0.05), and diarrhea (rho = -0.4, P = 0.0025). The associations remained highly significant after adjusting for covariates. There was no association between mean motility and calprotectin or HBI (P > 0.05). CONCLUSIONS: Reduced motility variance in morphologically normal SB is associated with patient symptoms and fecal calprotectin levels, supporting the hypothesis that inflammation-related enteric dysmotility may explain refractory abdominal symptoms in CD.

Anal canal vector volume manometry.

BACKGROUND: Anal manometry is routinely used in the assessment of the anal sphincters in patients with fecal incontinence or suspected sphincter injury. Such physiological information is complementary to the anatomical assessment provided by anal endosonography. The evolution of 3-dimensional anal endosonography provides more diagnostically useful information in complex cases. Vector volume manometry has been developed to give a 3-dimensional view of the anal sphincters. OBJECTIVE: We reviewed the published literature on this technique, with the intention of deriving a system of standardization based on the published literature and to summarize the derivation and physiological meaning of the parameters measurable by vector volume studies, as well. DATA SOURCES: We undertook a MEDLINE search using the terms "vector volume" or "vector manometry" and "anal canal." We also reviewed further publications found from references cited in the original articles identified from the above search. STUDY SELECTION: Only English language articles of studies performed on humans were reviewed. INTERVENTION: Anal canal vector volume manometry was the intervention. RESULTS: With the development of automated puller systems and associated software, parameters such as total vector volume, maximum pressure, mean pressure, anal canal symmetry, anal canal length, and the length of the high-pressure zone can be readily calculated. LIMITATIONS: There are conflicting studies related to the clinical value of both anal manometry and vector volume manometry, in part, because of the lack of standardization of equipment and technique. CONCLUSIONS: The vector volume parameters have been shown to correlate with both imaging results and incontinence scores with automated puller systems. The clinical utility of vector volume manometry would be improved further by the standardization of equipment and technique. The main clinical utility may lie in the treatment selection and preoperative assessment of patients awaiting surgery for anal pathology that has yet to be evaluated.

The effect of different macronutrient infusions on appetite, ghrelin and peptide YY in parenterally fed patients.

BACKGROUND & AIMS: Patients receiving parenteral nutrition (PN) still feel hungry despite adequate provision of calories intravenously. It is not known whether PN or its constituent macronutrients acutely affect appetite and to what degree this may be mediated by ghrelin and peptide YY (PYY). METHODS: Six medically stable patients (four men) with intestinal failure receiving PN received an isocaloric 200 kcal infusion on three separate occasions following a 12 h fast. The infusions consisted of either carbohydrate (10% dextrose), fat (10% intralipid) or mixed protein/carbohydrate (PN). Changes in ghrelin and peptide YY levels and changes in subjective symptoms of hunger, satiety and nausea during each macronutrient infusion were assessed. RESULTS: None of the three infusions acutely affected subjective symptoms of hunger, satiety and nausea (P>0.05 ANOVA). Ghrelin levels decreased significantly during dextrose [-19.1 (-35.9, -12.4), regression coefficient (95% CI), P<0.001] and parenteral nutrition infusions [-18.2 (-26.8, -9.6), P<0.001]. Lipid infusion had no effect on ghrelin levels but led to a significant decrease in PYY [-0.076 (-0.0123, -0.028), P=0.004]. Dextrose and PN infusion had no significant effect on PYY levels. CONCLUSIONS: Dextrose and PN infusions decrease ghrelin levels. Lipid infusion does not affect ghrelin levels but in contrast to oral nutrients leads to a significant decrease in PYY. Despite these changes, in patients receiving PN, macronutrient infusions do no acutely affect appetite.

Characteristics of intestinal dendritic cells in inflammatory bowel diseases.

BACKGROUND & AIMS: Dendritic cells (DCs) recognize and respond to microbial structures using pattern recognition receptors, including Toll-like receptors (TLRs). In the intestine, DCs are pivotal in tolerance induction and direct the differentiation of T cells. We aimed to identify changes in intestinal DCs that may underlie the dysregulated immune response to enteric bacteria that occurs in patients with inflammatory bowel disease (IBD). METHODS: DCs were identified in freshly isolated lamina propria mononuclear cells by multicolor flow cytometry in patients with IBD and controls. Expression of TLR2, TLR4, and the activation/maturation marker CD40 was assessed by cell surface labeling. Production of cytokines (interleukin [IL]-12, IL-6, and IL-10) was assessed in the absence of exogenous stimulation by intracellular staining of permeabilized cells. RESULTS: In healthy controls, few intestinal DCs expressed TLR2 or TLR4, in contrast to blood DCs. DC expression of both TLRs was significantly enhanced in Crohn's disease and ulcerative colitis. DCs from inflamed tissue of patients with Crohn's disease expressed significantly higher levels of the maturation/activation marker CD40. Elevated levels of CD40 on DCs were decreased after treating patients with anti-tumor necrosis factor alpha. In Crohn's disease, but not ulcerative colitis, more colonic DCs produced IL-12 and IL-6. The number of IL-10-producing DCs did not differ significantly between patients with IBD and controls. CONCLUSIONS: In IBD, DCs are activated, their expression of microbial recognition receptors is up-regulated, and more DCs produce pathologically relevant cytokines. Intestinal DCs are likely to be key initiators or perpetuators of the inflammatory response that characterizes IBD.

Ghrelin for the gastroenterologist: history and potential.

Ghrelin, a novel 28-amino acid orexigenic peptide discovered in 1999, has given us further insights into the control of energy homeostasis and growth hormone secretion. As a natural endogenous ligand of the growth hormone secretagogue receptor, it potently stimulates growth hormone release but is also implicated in many other homeostatic mechanisms. Released from the stomach, it stimulates lactotroph and corticotroph secretion, increases appetite and adiposity, has beneficial hemodynamic effects, has prokinetic and gastric acid secretory functions in the stomach, and may even be implicated in sleep. As advances in the understanding of appetite and obesity are made, it is timely to review the possibly central role of ghrelin in these physiological and pathophysiological states. This review will discuss the recent literature concerning this exciting novel neuropeptide and discuss the possible therapeutic possibilities it may open up to us.