Real-Life Patient Educational Recording Before Esophageal Manometry.

High-resolution esophageal manometry (HREM) is a fundamental diagnostic tool in esophagology. Educational tools for this procedure have remained scarce. This quality improvement project aimed to develop an enhanced digital recording about HREM and assess the effect on patient knowledge, anxiety, satisfaction, and procedure abortion rates. The Institute for Healthcare Improvement Model for Improvement and the self-regulation theory guided this project. An interprofessional team was formed. A video recording of the pre-, peri-, and post-HREM care was created. Participants were recruited in the following four cycles: Baseline, Workstation, Manometry, and Home. Questionnaires were collected pre- and postvideo education. The results demonstrated a significant increase in knowledge from 60% to 96% ( p < .001), 58% to 96% ( p < .001), 79% to 96% ( p < .001), and 92% to 97% ( p = .02) and reductions in anxiety from 7.1 to 5.5 ( p = .003), 7.6 to 6.1 ( p = .003), 7.1 to 6.5 ( p < .001), and 6.4 to 6.1 ( p = .03) in all four groups. Almost all (99.5%) participants liked the recorded education and only 2.6% of cases were aborted during the 1-year project implementation period from June 2020 to May 2021. Findings from this project support the positive impact of recorded patient education. An educational recording is standardized and has the potential to be implemented in variable settings.

Safety and Tolerability of High-Resolution Esophageal Manometry in Children and Adults.

INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.

Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes.

INTRODUCTION: Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes. METHODS: IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases. RESULTS: IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D. DISCUSSION: Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.

A Smartphone Application Using Artificial Intelligence Is Superior To Subject Self-Reporting When Assessing Stool Form.

INTRODUCTION: Stool form assessment relies on subjective patient reports using the Bristol Stool Scale (BSS). In a novel smartphone application (app), trained artificial intelligence (AI) characterizes digital images of users' stool. In this study, we evaluate this AI for accuracy in assessing stool characteristics. METHODS: Subjects with diarrhea-predominant irritable bowel syndrome image-captured every stool for 2 weeks using the app, which assessed images for 5 visual characteristics (BSS, consistency, fragmentation, edge fuzziness, and volume). In the validation phase, using 2 expert gastroenterologists as a gold standard, sensitivity, specificity, accuracy, and diagnostic odds ratios of subject-reported vs AI-graded BSS scores were compared. In the implementation phase, agreements between AI-graded and subject-reported daily average BSS scores were determined, and subject BSS and AI stool characteristics scores were correlated with diarrhea-predominant irritable bowel syndrome symptom severity scores. RESULTS: In the validation phase (n = 14), there was good agreement between the 2 experts and AI characterizations for BSS (intraclass correlation coefficients [ICC] = 0.782-0.852), stool consistency (ICC = 0.873-0.890), edge fuzziness (ICC = 0.836-0.839), fragmentation (ICC = 0.837-0.863), and volume (ICC = 0.725-0.851). AI outperformed subjects' self-reports in categorizing daily average BSS scores as constipation, normal, or diarrhea. In the implementation phase (n = 25), the agreement between AI and self-reported BSS scores was moderate (ICC = 0.61). AI stool characterization also correlated better than subject reports with diarrhea severity scores. DISCUSSION: A novel smartphone application can determine BSS and other visual stool characteristics with high accuracy compared with the 2 expert gastroenterologists. Moreover, trained AI was superior to subject self-reporting of BSS. AI assessments could provide more objective outcome measures for stool characterization in gastroenterology.

Qualitative Validation of a Novel VR Program for Irritable Bowel Syndrome: A VR1 Study.

INTRODUCTION: Although gut-directed psychotherapies are effective for irritable bowel syndrome (IBS), they are rarely prescribed, given a paucity of trained clinicians. Virtual reality (VR) offers a solution by allowing patients to self-practice these techniques in a standardized manner. METHODS: A multidisciplinary team developed IBS/VR, a program that transports users into immersive VR worlds that teach patients about the brain-gut axis, cognitive behavioral therapy, and gut-directed meditation. We tested IBS/VR in Rome IV IBS patients and used inductive analysis to evaluate perceptions and identify recommendations. RESULTS: We achieved thematic saturation after 9 interviews; 3 additional interviews revealed no emergent themes. After making 23 software changes based on patient feedback, we conducted 3 additional interviews which confirmed thematic saturation (N = 15 total). DISCUSSION: This study offers initial validation of the first VR program designed for IBS.

Exhaled Methane Is Associated with a Lower Heart Rate.

BACKGROUND: In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings, we hypothesized that CH4 may be affecting resting heart rate (HR) based on the potential effect of CH4 on the vagus nerve. OBJECTIVES: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting HR in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association with breath CH4 over time. METHODS: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 versus those that had a decrease in breath CH4 over 14 weeks. Last, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. RESULTS: In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0 ± 0.83 vs. 76.0 ± 0.44 beats/min, p = 0.01). In the post hoc analysis, a decrease in CH4 over time was associated with an increase in HR (median ∆ = 6.5 ± 8.32 beats/min, p = 0.0006). Last, we demonstrated a biological gradient whereby a larger drop in CH4 was associated with a greater increase in HR (R = -0.31, p = 0.03). CONCLUSION: Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate HR. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.

Breath Test Gas Patterns in Inflammatory Bowel Disease with Concomitant Irritable Bowel Syndrome-Like Symptoms: A Controlled Large-Scale Database Linkage Analysis.

INTRODUCTION: Breath testing (BT) has gained interest for diagnosing small intestinal bacterial overgrowth (SIBO) in IBD patients with irritable bowel syndrome (IBS) overlap. We aim to characterize the rate of SIBO and BT gas patterns in IBD patients with IBS-like symptoms compared to non-IBD patients. METHODS: A database of 14,847 consecutive lactulose BTs was developed from patients with IBS-like symptoms between November 2005 and October 2013. BTs were classified as normal, H2 predominant, CH4 predominant, and flatline based on criteria established from the literature. BT data linkage with electronic health records and chart review identified IBD patients along with disease phenotype, location, severity, and antibiotic response. Poisson loglinear model evaluated differences in gas patterns between the two groups. RESULTS: After excluding patients with repeat breath tests, we identified 486 IBD and 10,505 non-IBD patients with at least one BT. Positive BT was present in 57% (n = 264) of IBD patients. Crohn's disease (odds ratio (OR) 0.21, [95% confidence interval (CI) 0.11-0.38]) and ulcerative colitis (OR 0.39, [95% CI 0.22-0.70]) patients were less likely to produce excess CH4. IBD patients were more likely to have flatline BT (OR 1.82, [95% CI 1.20-2.77]). In IBD patients with SIBO, 57% improved symptomatically with antibiotics. CONCLUSION: In a cohort of IBD patients with IBS-like symptoms, a high rate of patients had positive BT and symptomatic improvement with antibiotics. In IBD, methanogenesis is suppressed and flatline BT is more frequent, suggesting excess hydrogenotrophic bacteria. These findings suggest methanogenic and hydrogenotrophic microorganisms as potential targets for microbiome-driven biomarkers and therapies.

Electronic patient agenda forms: comparing agreement between the reason for specialty consultation reported by referring providers and patients.

OBJECTIVE: Little is known about the agreement between referring providers' reason for specialty evaluation and patients' understanding of why they are referred for consultation. Here, we compared the reason for consult (RFC) documented by referring providers during usual care vs. the perceived RFC independently reported by patients through an e-portal just prior to the specialist visit. METHODS: We performed an observational study among patients referred for gastrointestinal (GI) evaluation. Patients referred to the specialty clinic submitted their self-reported RFC using an online patient agenda form prior to their visit. Therefore, each participant had a referring provider- and patient-documented RFC. Blinded physicians reviewed the RFCs in random order using a priori coding criteria. We then compared whether the provider and patient RFC pairs were concordant (i.e., ≥1 clinical topic[s] in the RFCs matched). RESULTS: Sixty patients completed the e-portal prior to their visit, leading to 60 provider-patient RFC pairs. The RFC pairs were concordant in only 52% of cases. CONCLUSIONS: There is poor agreement between referring providers' reason for GI referral and patients' understanding of why they are visiting the clinic. Future research examining whether electronic patient agenda forms impact diagnostic and management precision, patient satisfaction, and healthcare utilization is warranted.

Hepatitis B: Working Towards a Cure.

First-line oral therapies for hepatitis B are effective at viral suppression, and treatment can lead to biochemical improvement and histologic regression. Unfortunately, recommended endpoints of treatment such as HBeAg loss and seroconversion may not be durable, with high rates of seroreversion, requiring monitoring, and unfortunately, low rates of  HBsAg loss/seroconversion. Additionally, meeting these endpoints requires years or even indefinite administration, leading to concerns regarding cost, side effects, and high rates of nonadherence. This article will review defined endpoints of therapy and their durability, the risks of long-term therapy, and the evolving new therapies aimed at a viral cure.

Radiation therapy in patients with inflammatory bowel disease and colorectal cancer: risks and benefits.

PURPOSE: The effects of radiotherapy are debated in inflammatory bowel disease (IBD). We examined IBD patients with colorectal cancer (CRC) and compared those who underwent external beam radiation therapy (EBRT) to those who did not. We then compared those same patients treated with EBRT to similarly treated non-IBD patients to ascertain differences in toxicity and perioperative outcomes. METHODS: Fifty-seven IBD patients with CRC received EBRT, of which 23 had perioperative follow-up and 15 had complete records. The 23 patients were compared to 229 IBD patients with CRC who did not receive EBRT. The 15 patients were matched, 1:2, to similarly treated non-IBD patients with CRC based on age (±5 years), treatment year (±1 year), BMI (±10 kg/m2), and clinical stage. RESULTS: There was significantly more postoperative bleeding (5.3 % vs. 0 %, p < 0.01), wound dehiscence (3.5 % vs. 0 %, p < 0.01), and perineal infection (8.8 % vs. 1.3 %, p < 0.01) in IBD patients with EBRT compared to those without EBRT. IBD patients were significantly more likely to have grade 3 or higher lower GI toxicity (40 % vs. 7 %, p = 0.02) and wound dehiscence (36 % vs. 7 %, p = 0.02) than non-IBD patients, however without significant difference in bleeding, infection, ileus, or survival. CONCLUSION: IBD patients with CRC who received EBRT were more likely than similar patients without EBRT to experience perioperative complications. These patients also experienced more lower GI toxicity than similarly treated non-IBD patients with CRC. The expected decrease in survival in IBD-associated CRC was not observed. Thus, EBRT may contribute to a survival benefit in this group.

Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi.

Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the ß-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity.

Structure and function of a "yellow" protein from saliva of the sand fly Lutzomyia longipalpis that confers protective immunity against Leishmania major infection.

LJM11, an abundant salivary protein from the sand fly Lutzomyia longipalpis, belongs to the insect "yellow" family of proteins. In this study, we immunized mice with 17 plasmids encoding L. longiplapis salivary proteins and demonstrated that LJM11 confers protective immunity against Leishmania major infection. This protection correlates with a strong induction of a delayed type hypersensitivity (DTH) response following exposure to L. longipalpis saliva. Additionally, splenocytes of exposed mice produce IFN-γ upon stimulation with LJM11, demonstrating the systemic induction of Th1 immunity by this protein. In contrast to LJM11, LJM111, another yellow protein from L. longipalpis saliva, does not produce a DTH response in these mice, suggesting that structural or functional features specific to LJM11 are important for the induction of a robust DTH response. To examine these features, we used calorimetric analysis to probe a possible ligand binding function for the salivary yellow proteins. LJM11, LJM111, and LJM17 all acted as high affinity binders of prohemostatic and proinflammatory biogenic amines, particularly serotonin, catecholamines, and histamine. We also determined the crystal structure of LJM11, revealing a six-bladed ß-propeller fold with a single ligand binding pocket located in the central part of the propeller structure on one face of the molecule. A hypothetical model of LJM11 suggests a positive electrostatic potential on the face containing entry to the ligand binding pocket, whereas LJM111 is negative to neutral over its entire surface. This may be the reason for differences in antigenicity between the two proteins.