Citations

AbstractContextSARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown.ObjectiveWe aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls.MethodsGastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed.ResultsPatients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR < 0.05) vs 13 genes in FD; 71 of these 100 genes were differentially expressed in DGE vs FD but only 3 between DGE patients with normal vs delayed GE. Upregulated genes in DGE include the SARS-CoV2 viral entry genes CTSL (|Fold change [FC]|=1.16; FDR < 0.05) and CTSB (|FC|=1.24; FDR < 0.05) and selected genes involved in viral replication (eg, EIF2 pathways) and inflammation (CCR2, CXCL2, and LCN2, but not other inflammation-related pathways eg, IL-2 and IL-6 signaling).ConclusionSeveral SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.

Benign anorectal disorders of structure and function are common in clinical practice. These guidelines summarize the preferred approach to the evaluation and management of defecation disorders, proctalgia syndromes, hemorrhoids, anal fissures, and fecal incontinence in adults and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations Assessment, Development and Evaluation process. When the evidence was not appropriate for Grading of Recommendations Assessment, Development and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

AbstractAimsGastric emptying is of limited utility for predicting the severity of symptoms in patients with diabetes mellitus and gastrointestinal symptoms. We evaluated the extent to which symptoms recorded during a 13C‐spirulina‐based gastric emptying breath test (GEBT) or scintigraphy predicting the severity of daily symptoms in diabetes mellitus.MethodsGastric emptying, symptoms during a gastric emptying study, either scintigraphy (n = 38) or GEBT (n = 111), and daily gastrointestinal symptoms were evaluated in 149 patients with diabetes mellitus and variably severe gastrointestinal symptoms.Key ResultsGastric emptying was normal, delayed, and rapid in 37%, 52%, and 9% measured with the GEBT and 55%, 34%, and 11% of patients measured with scintigraphy; differences between GEBT and scintigraphy were not significant. Daily symptoms were moderately severe or more intense in 58% and 21% of patients undergoing scintigraphy and GEBT (P < 0.0001). Symptoms during the GEBT (46%) and emptying thalf (3%) explained 50% of the variance in daily symptoms in the GEBT group. In the scintigraphy group, symptoms explained 29% of this variance; the thalf was insignificant. Patients who reported that one or more symptoms were more severe than the others during the GE study were more likely (OR 3.98, 95% CI 2.16, 7.33) to report the same symptom(s) as being the most severe in the daily diary.ConclusionsSymptoms during a GEBT and to a lesser extent during scintigraphy, but not gastric emptying predict the severity of daily symptoms and may serve as a biomarker in patients with diabetes mellitus.

AbstractBackgroundIt is suggested that patients with defecation disorders (DD) strain excessively or do a Valsalva maneuver (VM) during evacuation, resulting in rectoanal discoordination, which hinders rectal evacuation. However, definitive data are lacking.MethodsRectoanal pressures during evacuation and a VM were measured with seated high‐resolution manometry (HRM) in 64 healthy and 136 constipated women with a normal (84 women, C‐normal) or prolonged (52 women, C‐abnormal) balloon expulsion time (BET). The number of abnormal rectoanal parameters during evacuation and the joint distribution of pressures during evacuation and a VM were used to discriminate between controls and C‐abnormal BET patients.Key ResultsThe peak anal pressure (5 s) during a VM accounted for 0%, 26%, and 49% of the variance in anal pressure during evacuation in healthy women, C‐normal BET, and C‐abnormal BET. The association between anal pressure during a VM and evacuation was stronger in C‐abnormal BET than in healthy women and C‐normal BET (p for interaction <0.001). Fifty‐eight of 64 controls and 33 of 52 C‐abnormal BET patients had no or one abnormal parameter during evacuation; hence, the probability of C‐abnormal BET was 33/91 (36%). In patients with no or one abnormal parameter during evacuation, a logistic model based on anal pressures during evacuation and a VM discriminated between controls and patients with C‐abnormal BET with a sensitivity and a specificity of 67% and 75%.ConclusionsAssessment of rectoanal pressures during evacuation and a VM uncovers rectaoanal discoordination and facilitates the diagnosis of DD in selected patients.

Hindered by a limited understanding of the mechanisms responsible for diabetic gastroenteropathy (DGE), management is symptomatic. We investigated the duodenal mucosal expression of protein-coding genes and microRNAs (miRNA) in DGE and related them to clinical features. The diabetic phenotype, gastric emptying, mRNA, and miRNA expression and ultrastructure of duodenal mucosal biopsies were compared in 39 DGE patients and 21 controls. Among 3175 differentially expressed genes (FDR < 0.05), several mitochondrial DNA–encoded (mtDNA-encoded) genes (12 of 13 protein coding genes involved in oxidative phosphorylation [OXPHOS], both rRNAs and 9 of 22 transfer RNAs) were downregulated; conversely, nuclear DNA–encoded (nDNA-encoded) mitochondrial genes (OXPHOS) were upregulated in DGE. The promoters of differentially expressed genes were enriched in motifs for transcription factors (e.g., NRF1), which regulate mitochondrial biogenesis. Seventeen of 30 differentially expressed miRNAs targeted differentially expressed mitochondrial genes. Mitochondrial density was reduced and correlated with expression of 9 mtDNA OXPHOS genes. Uncovered by principal component (PC) analysis of 70 OXPHOS genes, PC1 was associated with neuropathy ( P = 0.01) and delayed gastric emptying ( P < 0.05). In DGE, mtDNA- and nDNA-encoded mitochondrial genes are reduced and increased — associated with reduced mitochondrial density, neuropathy, and delayed gastric emptying — and correlated with cognate miRNAs. These findings suggest that mitochondrial disturbances may contribute to delayed gastric emptying in DGE.

AbstractBackgroundThe equipment and methods for performing anorectal manometry and biofeedback therapy are different and not standardized. Normal values are influenced by age and sex. Our aims were to generate reference values, examine effects of gender and age, and compare anorectal pressures measured with diagnostic and biofeedback catheters and a portable manometry system.MethodsIn this multicenter study, anorectal pressures at rest, during squeeze, and evacuation were measured with diagnostic and biofeedback catheters using Mcompass™ portable device in healthy subjects. Balloon expulsion time and rectal sensation were evaluated. The effects of age and gender were assessed.ResultsThe final dataset comprised 108 (74 women) of 124 participants with normal rectal balloon expulsion time (less than 60 s). During squeeze, anal resting pressure increased by approximately twofold in women and threefold in men. During evacuation, anal pressure exceeded rectal pressure in 87 participants (diagnostic catheter). The specific rectoanal pressures (e.g., resting pressure) were significantly correlated and not different between diagnostic and biofeedback catheters. With the diagnostic catheter, the anal squeeze pressure and rectal pressure during evacuation were greater in men than women (p ≤ 0.02). Among women, women aged 50 years and older had lower anal resting pressure; rectal pressure and the rectoanal gradient during evacuation were greater in older than younger women (p ≤ 0.01).ConclusionsAnal and rectal pressures measured with diagnostic and biofeedback manometry catheters were correlated and not significantly different. Pressures were influenced by age and sex, providing reference values in men and women.

Abstract Fecal incontinence is a common symptom that can significantly impair quality of life. The treatment options range from conservative measures (e.g., Kegel exercises, pelvic floor biofeedback therapy, fiber supplementation, or medications) to noninvasive nerve stimulation (e.g., posterior tibial nerve stimulation and transcutaneous tibial nerve stimulation), implanted neurostimulation (i.e., sacral nerve stimulation), perianal injection of dextranomer, and anal sphincteroplasty. In this issue of the journal, a promising, uncontrolled study suggests that noninvasive, repetitive magnetic stimulation of the lumbosacral nerves significantly improved symptoms, increased anal squeeze pressure, and increased rectal compliance in patients with fecal continence. Sham-controlled studies are necessary to confirm these findings.

INTRODUCTION: Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls. METHODS: Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day. RESULTS: On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls ( P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups ( P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015. DISCUSSION: In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.