Neurogastroenterology and Motility最新文献

Background: Internationally adopted Chicago Classification (CC) criteria based on adult normative data have been used to diagnose children with esophageal motility disorders undergoing high-resolution esophageal manometry (HREM). The aim of this study was to compare HREM parameters of children without dysphagia and children with dysphagia and normal findings according to CC.

Methods: HREM metrics of 41 children (13.2 (9-18) years; 20 female) without dysphagia and 41 children (13.7 (8-18) years; 30 female) with dysphagia and normal diagnosis according to CC were compared. Analyzed data included resting and integrated relaxation pressures (IRP) of upper (UES) and lower (LES) esophageal sphincters, esophageal peristaltic contractile integrals, transition zone (TZ) gaps, distal latency (DL), and manometric esophageal length to height ratio (MELH). 95%ile normative cutoffs were calculated from the cohort without dysphagia.

Key results: Proximal contractile integral (PCI), UES and LES mean resting and IRP were not significantly different between the cohorts (p > 0.3). On the contrary, distal contractile integral (DCI), TZ gap and MELH were notably different with p = 0.0002, p = 0.027, and p = 0.033 respectively. According to 95%ile normative cutoffs of DCI, TZ gap and MELH, in cohort with dysphagia 27%, 15%, and 22% of patients respectively were not normal.

Conclusion & inferences: First study ever to compare HREM parameters of children without dysphagia to children with dysphagia. Considerable proportion of children with dysphagia may be underdiagnosed according to the adult criteria. This emphasizes the need for universally accepted child-specific diagnostic protocols and norms.

Background: Dysphagia is one of the most common complaints that gastroenterologists encounter in the outpatient setting. To evaluate this common complaint, patients are often sent for a barium esophagram, a test that is widely available, inexpensive, and easy to perform. This simple test provides a reliable method to evaluate esophageal anatomy and structural abnormalities.

Purpose: This narrative reviews the history of the development and validation of the timed-barium esophagram (TBE), along with its strengths and limitations, and discusses its use in the pre- and posttreatment assessment of patients with achalasia, esophagogastric junction outflow obstruction (EGJOO), and esophageal strictures. Providing excellent anatomic detail of the esophagus and an accurate assessment of esophageal emptying, over time, the TBE has become part of the standard workup in our Swallowing Center for patients with dysphagia.

Background: Patients' report of bowel movement consistency is unreliable. We demonstrate the feasibility of long-term automated stool image data collection using a novel Smart Toilet and evaluate a deterministic computer-vision analytic approach to assess stool form according to the Bristol Stool Form Scale (BSFS).

Methods: Our smart toilet integrates a conventional toilet bowl with an engineered portal to image feces in a predetermined region of the plumbing post-flush. The smart toilet was installed in a workplace bathroom and used by six healthy volunteers. Images were annotated by three experts. A computer vision method based on deep learning segmentation and mathematically defined hand-crafted features was developed to quantify morphological attributes of stool from images.

Key results: 474 bowel movements images were recorded in total from six subjects over a mean period of 10 months. 3% of images were rated abnormal with stool consistency BSFS 2 and 4% were BSFS 6. Our image analysis algorithm leverages interpretable morphological features and achieves classification of abnormal stool form with 94% accuracy, 81% sensitivity and 95% specificity.

Conclusions: Our study supports the feasibility and accuracy of long-term, non-invasive automated stool form monitoring with the novel smart toilet system which can eliminate the patient burden of tracking bowel forms.

Background: Functional diarrhea (FDr) is a common disorder in toddlers and adults. In children, the Rome criteria define FDr as a disorder of children younger than 5 years old exclusively. However, in clinical practice, school-aged children and adolescents sometimes consult for symptoms that mimic the diagnosis of FDr. We conducted a study aimed at assessing the prevalence of FDr in school-aged children and adolescents.

Methods: A cross-sectional study was conducted in children aged 8-18 years from two schools in Colombia. Children completed self-report validated questionnaires to diagnose disorders of gut-brain interaction (DGBI) per Rome IV (QPGS-IV) for their age group and the questions related to FDr from the Rome IV questionnaire for infants and toddlers.

Key results: After excluding children with organic diseases and IBS-D, 981 participants were included (female 53.8%, White 24.7%, Indigenous 10.9%, mixed race 52.6%). Of the 981 participants, 325 (33.1%) had a DGBI. Of these, 17 children (5.2%) were diagnosed with FDr (3 participants 8-12 years; 14 participants 13-18 years). FDr was more prevalent among White children compared to non-White children (mixed race, Black, and Indigenous) (p = 0.01).

Conclusion & inferences: Despite the absence of FDr in the Rome IV criteria for children and adolescents, 1.7% of children aged 8-18 years likely have FDr. This study suggests that FDr does occur in children and adolescents. If confirmed in future studies, the diagnosis of FDr should be considered for inclusion in future editions of the Rome criteria for children of all ages.

Introduction: The American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary (ANMS GCSI-DD) is a patient-reported outcome (PRO) instrument for gastroparesis. This study evaluated the psychometric properties of the ANMS GCSI-DD and determined a meaningful change threshold using the data from a phase 2b trial in adults with moderate-to-severe idiopathic or diabetic gastroparesis (DG).

Methods: The psychometric properties of ANMS GCSI-DD were analyzed using other clinician- and patient-reported outcomes from 242 patients during the 12-week trial. Trial exit interviews were conducted in a cohort of 32 patients to capture their perspectives on meaningful change from the trial.

Results: ANMS GCSI-DD demonstrated good performance: unidimensionality scores exhibited good fit; internal consistency reliability was >0.70; test-retest reliability was above 0.90, and convergent validity showed strong correlations (0.70-0.90) with overall severity rating and moderate correlations (0.30-0.70) with other outcomes. ANMS GCSI-DD scores discriminated among groups with varying severity of gastroparesis symptoms in known-groups validity (p < 0.001) and were responsive to symptom improvement. Triangulation of the quantitative anchor-based estimates of 0.9-1.4 category points as a meaningful change in the ANMS GCSI-DD composite score, and the qualitative exit interview findings of 0.5-1.5 as meaningful change, supports a one-point change on a five-point scale (0-4) as the meaningful change threshold.

Conclusion: The ANMS GCSI-DD is a reliable and valid PRO instrument to employ in clinical development for patients with moderate-to-severe idiopathic or DG, and a one-point score change in the ANMS GCSI-DD composite score is recommended as a meaningful change threshold of symptom change.

Background: Functional defecation disorders (FDD) are a common etiology of refractory chronic constipation (CC). FDD diagnosis (dyssynergic defecation [DD] and inadequate defecatory propulsion [IDP]), requires diagnostic tests including anorectal manometry (ARM) and balloon expulsion test (BET). Biofeedback (BF) is the treatment of choice for DD. The aims of our study were to evaluate: the outcome of BF in a group of constipated patients with defecatory disorders of any etiology; the efficacy of two simple diagnostic tools in predicting BF outcome in the short-term.

Methods: One hundred and thirty-one refractory CC patients failing the BET underwent BF therapy. Before BF, all patients underwent the following: ARM. Straining questionnaire. The answers were: "belly muscles"; "anal muscles"; "both"; "Don't know/No answer." Digital rectal examination augmented by abdominal palpation on straining (augmented-DRE). The BF therapist was blinded to ARM, straining questionnaire, and augmented-DRE results.

Key results: Eighty-one patients responded to BF. Gender, age, and IBS-C showed no significant impact on BF response. Both DD and IDP responded equally to BF, while the rate of response in patients with isolated structural pelvic floor abnormalities was lower (p < 0.001). The answer "anal muscles" to straining questionnaire showed a strong association with BF response (p < 0.001). A lack in abdominal contraction and in anal relaxation on augmented-DRE were strongly associated with BF response (p < 0.01). Absence of manual maneuvers to facilitate defecation was associated with BF response (p < 0.001).

Conclusions & inferences: BF is the therapy of choice for refractory constipation due to FDD of any etiology, inducing both clinical and anorectal physiology improvement in the short term. Comorbid IBS-C did not affect outcome while symptomatic isolated pelvic floor abnormalities appeared refractory to behavior treatment. The straining questionnaire and augmented-DRE outcomes showed a strong correlation with BF response and can be implemented in clinical practice to improve the management of constipated patients by prompting early referral to BF.

Background: Impaired gastric accommodation is one of the most frequent symptoms of functional dyspepsia. The safety and efficacy of conventional treatments remain to be proven and alternative herbal therapies have been proposed to alleviate gastrointestinal symptoms. This preclinical study examined the role of herbal Amara extract (containing Artemisia absinthium, Centaurium erythraea, Cichorium intybus, Gentiana lutea, Juniperus communis, Achillea millefolium, Peucedanum ostruthium, Salvia officinalis, and Taraxacum extracts) on gastric (fundus) accommodation and the possible implication of muscarinic receptors in its regulation.

Methods: The effect of Amara extract on fundus motility was investigated in organ baths of smooth muscle strips isolated from the fundus of guinea pigs, and the role of the muscarinic receptor pathway was evaluated using functional and radioligand binding assays in cell lines expressing the M2 or M3 muscarinic receptor.

Key results: Amara extract inhibited carbachol-induced contraction of guinea pig smooth muscle strips in a dose-dependent manner. This relaxant effect was not affected by the M3 antagonist J-104129. Amara extract also inhibited M2, but not M3, receptor activity in CHO-K1 cells (IC₅₀ 219 μg mL^-1), and specifically bound the M2 receptor (IC₅₀ 294 μg mL^-1). Of the nine herbal components of Amara extract, Juniperus communis, P. ostruthium, and Salvia officinalis inhibited M2 receptor activity (IC₅₀ 32.0, 20.8, and 20.1 μg mL^-1, respectively), and P. ostruthium was sufficient to reverse carbachol-induced ex vivo contraction of guinea pig fundic smooth muscles.

Conclusion and inferences: Amara extract relaxes gastric smooth muscles by inhibiting the M2 muscarinic receptor. This study suggests the potential benefit of Amara extract for patients with impaired gastric accommodation.

Background: Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein-coupled receptor P2Y₁ receptors, increasing intracellular Ca²⁺ that activates small conductance calcium-activated potassium (SK_Ca) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α-adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α-adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon.

Methods: Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally.

Results: The α₁-adrenoceptor agonist phenylephrine (PE) (10^-8-10^-5 M) evoked concentration-dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid-circular colon at low PE concentrations, a contraction sensitive to 10^-5 M phentolamine (non-selective α-adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10^-6 M), and atropine (10^-6 M) was recorded. PE-induced relaxations were insensitive to TTX (10^-6 M) and the nonselective β-adrenoceptor blocker propranolol (10^-6 M). In contrast, PE-induced relaxations were blocked by phentolamine (10^-5 M), prazosin (10^-6 M) (α₁-adrenoceptor blocker), and RS17053 (10^-6 M) (α_1A-blocker), but not by yohimbine (10^-6 M) (α₂-adrenoceptor blocker). Apamin (10^-6 M), a SK_Ca channel blocker, abolished PE-induced relaxations.

Conclusions: Contractile responses in the circular muscle of the mid colon could be attributed to α-adrenoceptors located on enteric cholinergic neurons. Stimulation of α_1A-adrenoreceptors activates SK_Ca channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y₁ receptors.

Background: Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the phytochemical composition of beetroot juice (BJ) and its laxative potential in an experimental model of constipation and colonic dysmotility induced by loperamide (LOP) in Wistar rats.

Methods: Animals were concurrently pretreated with LOP (3 mg/kg, b.w., i.p.) and BJ (5 and 10 mL/kg, b.w., p.o.), or yohimbine (2 mg/kg, b.w., i.p.), during 1 week. The laxative activity was determined based on the weight, frequency, and water content of the feces matter. The gastric-emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical-colorimetric methods.

Key results: The in vivo study revealed that LOP induced a significant inhibition of gastrointestinal motility, negative consequences on defecation parameters, oxidative stress, and colonic mucosa lesions. Conversely, administration of BJ reestablished these parameters and restored colonic oxidative balance. Importantly, BJ treatment protected against LOP-induced inflammatory markers (pro-inflammatory cytokines and WBC) and the increase in intracellular mediators such as hydrogen peroxide, free iron, and calcium levels.

Conclusions & inferences: This study demonstrated that the bioactive compounds in BJ provided an anti-constipation effect by modulating intestinal motility and regulating oxidative stress and inflammation induced by LOP intoxication.