Introduction

The interplay of race and gender significantly influences the manifestation of Gastroesophageal Reflux Disease (GERD) symptoms following Helicobacter pylori (H. pylori) treatment. This multifaceted relationship, deeply rooted in biological, cultural, and socioeconomic factors, presents a complex medical challenge. Understanding these disparities is crucial for tailoring effective treatment strategies, ensuring equitable healthcare outcomes, and advancing personalized medicine in managing GERD symptoms in diverse populations post-H. pylori eradication

Aims & Methods

Our research, spanning 2009 to 2023, retrospectively analyzed patients treated for H. Pylori, ensuring a minimum one-year follow-up. We collected data encompassing comorbidities, insurance status, and socioeconomic factors, particularly targeting the emergence of GERD symptoms, Esophagitis, and duodenal ulcers, identified using CPT and ICD codes. Initially, we employed a Chi-square test of independence to evaluate the association between race and GERD symptoms. We conducted a post-hoc analysis with adjusted standardized residuals to delve deeper, pinpointing specific races with notably higher or lower GERD symptom frequencies than expected. We performed pairwise race comparisons via Chi-square tests, applying a Bonferroni correction for multiple comparisons.

Results

Between 2009 and 2023, 4,205 patients received H. Pylori treatment, with 3,329 qualifying for our study after excluding those lost to follow-up. The average age was 54.5 years, with 64% female (2,134) and 48% Caucasian (1,664). The Chi-square test revealed a significant association between Race and GERD symptoms (Chi sq stat:8.69 p-value <0.01). In-depth post-hoc pairwise comparisons showed that the Hispanic race had significantly higher rates of GERD symptoms when compared to other races Other races (p <0.01), White (p <0.01), Black (p <0.01), and Asian races (<0.01). Adjusted residual analysis further confirmed that the Hispanic race (5.54, p<0.023) showed a higher-than-expected number of GERD symptom cases. Among the Hispanic races, Patients with low socioeconomic status showed increased GERD symptoms (Chi. Sq: 7.65, P<0.01). Gender does not significantly impact GERD symptoms (Chi. sq: 0.831, P = 0.512)

Conclusion

Our study, analyzing data from 2009 to 2023 on patients treated for H. Pylori, underscores the significant influence of race and gender on GERD symptoms post-treatment. Notably, the Hispanic population exhibited a higher incidence of GERD symptoms compared to other races, with socioeconomic status further intensifying this trend. These findings highlight the need for more personalized, culturally sensitive approaches in healthcare, emphasizing the importance of considering race, gender, and socioeconomic factors in the treatment and management of GERD following H. Pylori eradication.

References

Lai Y, Shi H, Wang Z, Feng Y, Bao Y, Li Y, Li J, Wu A. Incidence trends and disparities in Helicobacter pylori related malignancy among US adults, 2000-2019. Front Public Health. 2022 Nov 28;10:1056157. doi: 10.3389/fpubh.2022.1056157. PMID: 36518580; PMCID: PMC9743990.

Introduction

With the recent rise in the occurrence of esophageal adenocarcinoma (EAC) in Western nations, there is an escalating worry regarding Barrett’s esophagus (BE). In contrast, Asian countries exhibit a lower prevalence of BE compared to their Western counterparts. Given the annual increase in chronic gastroesophageal reflux disease (GERD) cases, there is an expectation of a concurrent rise in the prevalence of BE. Consequently, we are embarking on a multicenter prospective study to assess the current prevalence of BE and pinpoint its risk factors in Taiwan.

Aims & Methods

Aim: to evaluate current prevalence and risk factors of Barrett's esophagus in Taiwan.
Methods: We carried out a prospective multicenter study involving consecutive outpatients who underwent upper gastrointestinal endoscopy for various upper gastrointestinal symptoms. Biopsies were taken from endoscopically suspected esophageal metaplasia (ESEM), clearly visible at least 1 cm above the gastroesophageal junction during endoscopy. The biopsy procedure involved obtaining standardized random samples, with four pieces taken every 2 cm from the four quarters of the esophagus exhibiting the ESEM lesion. BE was defined based on the histological confirmation of specialized intestinal metaplasia in the metaplastic esophageal epithelium.

Results

A total of 8925 subjects were enrolled in this study. The prevalence of BE was 2.6%. A total of 228 subjects with BE were detected among 751 ESEM subjects. Short segment BE (78.1 % , n = 178) was more prevalent than long segment BE (22.9 % , n = 50). The prevalence of GERD symptoms, erosive esophagitis (EE), and hiatal hernia (HH) was 52.5%, 27.3% and 7.85%, respectively. Multivariate analysis disclosed that old age [odds ratio (OR) = 1.59; 95% CI, 1.20-2.11; P <0.01], male gender (OR = 2.27; 95%CI, 1.65-3.11; P < 0.01),alcohol consumption (OR = 1.70, 95%CI, 1.19-2.44; P< 0.01), GERD symptoms (OR = 1.45, 95%CI, 1.10-1.92; P< 0.01), EE (OR = 1.94, 95%CI, 1.47-2.56; P< 0.01) and presence of hiatal hernia (OR = 2.49; 95%CI, 1.78-3.47; P < 0.001) were significant risk factors predicting BE.
Risk factors for Barrett esophagus: multivariable analysis.

Conclusion

The prevalence of BE was identified as 2.6%. Notably, advanced age (>50), male gender, alcohol consumption, symptoms of gastroesophageal reflux disease (GERD), erosive esophagitis, and the presence of hiatal hernia emerged as independently significant risk factors for Barrett's esophagus.

References

1. Sharma P. Barrett Esophagus: A Review. Jama. 2022;328(7):663-71.
2. Marques de Sá I, et al. The global prevalence of Barrett's esophagus: A systematic review of the published literature. United European Gastroenterol J. 2020;8(9):1086-105.
3. Chang CY, et al. Current status of Barrett's esophagus research in Asia. J Gastroenterol Hepatol. 2011;26(2):240-6.
4. Shiota S, et al. Prevalence of Barrett's Esophagus in Asian Countries: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2015;13(11):1907-18.
5. Chang CY, et al. The application of Prague C and M criteria in the diagnosis of Barrett's esophagus in an ethnic Chinese population. Am J Gastroenterol. 2009;104(1):13-20.
6. Fock KM, et al. Asia-Pacific consensus on the management of gastro-oesophageal reflux disease: an update focusing on refractory reflux disease and Barrett's oesophagus. Gut. 2016;65(9):1402-15.
7. Eusebi LH, et al. Global prevalence of Barrett's oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis. Gut. 2021;70(3):456-63.
8. Akiyama T, et al. Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men. BMC Gastroenterol. 2008;8:58.
9. Andrici J,et al. Hiatal hernia and the risk of Barrett's esophagus. J Gastroenterol Hepatol. 2013;28(3):415-31.

Introduction

Persulfidation of proteins (PSSH) appears functionally significant, e.g. in aging, preventing cellular oxidation, but its role in GI diseases remains clinically elusive. This posttranslational proteins modification relies on endogenous hydrogen sulfide (H₂S) signaling. GERD induces oxidation in esophageal squamous cells. However, the contribution of persulfidation and H₂S bioavailability in etiology, diagnosis or treatment of Barrett’s esophagus (BE) is unknown. We hypothesized that GERD-induced pathway-specific PSSH impairments underlie BE pathogenesis. We explored whether restoration/depletion of esophageal H₂S impacts persulfidation-sensitive, BE-associated targets and BE development.

Aims & Methods

We clinically performed a wide-scale analysis of persulfidated proteins (normalized to total proteins levels) in three-sets of endoscopic biopsies representing BE or squamous segments +/- GERD (n=4-5 each), using the recent chemoproteomic method. We used the microsurgical rat model of GERD/BE (esophago-gastroduodenal anastomosis) +/- i.g. pharmacological treatments to up-/downregulate esophageal H₂S levels over 10 weeks. In parallel, we employed in vitro model of chronic GERD +/- H₂S donors using human esophageal squamous cell lines with (NES-G2T) or without (EPC2) clinical GERD and a Barrett’s cells (BAR-T). CRISPR-Cas9 was used to knockout H2S-producing enzymes.

Results

Global persulfidation level (reflecting H₂S bioavailability) was decreased in clinical BE vs GERD-exposed squamous biopsies. GERD induced statistically significant pathway-specific PSSH changes of ≈90 proteins in squamous segments compared to patients w/o GERD. These persulfidomic alterations further increased in BE where >900 targets were deregulated. IL-1b, prostaglandin (PG)E2 pathways or mTOR-associated proteins, but not exclusively, showed persulfidation shift (e.g. PSSH fall of IL-1b-receptor antagonist (IL-1RA)). H2S-decrease was noted in vitro or in vivo after long-term GERD in rats with chronic esophageal lesions and in human squamous, but not BAR-T cells. In cells and/or rats, treatment with NaSH or GYY4137 to restore H2S induced IL-1RA and inhibited IL-1b/PGE2/mTOR signaling, RNA oxidation, limiting molecular or morphological BE development. H₂S-enzymes inactivation promoted BE-related events in both models.

Conclusion

BE is preceded by GERD-induced, pathway-specific persulfidation shifts, initiated early in squamous epithelium and enhanced in metaplasia. Decreased but stable biosynthesis of H2S reflects the adaptative resistance of the metaplastic cells to GERD. Restored H2S signaling counteracts BE development by interfering in oxidative balance and BE-associated IL-1β, PGE2 and mTOR pathways activation. These findings suggest that BE is a mechanistic outcome of reduced esophageal H₂S caused by GERD. [Funding: National Science Centre (Poland): 2016/23/D/NZ4/01913, 2019/33/B/NZ4/00616, 2023/07/X/NZ4/01052]

Introduction

Arsenic, a potent environmental toxin, has been widely reported to cause significant health problems, including liver damage and disturbances in the metabolic processes. One of the lesser-understood facets of arsenic toxicity is its impact on gut microbiota, the community of microorganisms living in the intestinal tract, which plays a crucial role in host metabolism and overall health. Previous studies have indicated that arsenic exposure can alter the composition of gut microbiota, potentially affecting the host’s metabolism of arsenic and exacerbating its toxic effects. Despite ongoing research, the mechanisms underlying the interaction between arsenic exposure, gut microbiota changes, and arsenic metabolism remain inadequately defined.

Aims & Methods

The primary objective of this study was to elucidate the dynamics of gut microbiota changes under varying levels of arsenic exposure and to understand how these changes affect arsenic metabolism and subsequent liver toxicity. We used C57BL/6 mice as a model system, exposing them to 0, 5, or 10 ppm sodium arsenite (NaAsO2) in their drinking water over a period of six months. We conducted a comprehensive analysis of the gut microbiota, focusing on folic acid (FA)/vitamin B12 (VB12)- and butyrate-synthesizing communities. Additionally, molecular interactions between arsenic and methionine synthase (MTR), an enzyme crucial for FA/VB12 utilization, were assessed using 3D molecular simulations and biochemical assays. The intervention model involved supplementation of FA and VB12 to evaluate their protective effects against arsenic-induced disturbances.

Results

Exposure to NaAsO2 significantly altered gut microbiota, with a notable increase in the abundance of FA/VB12- and butyrate-synthesizing microbiota. This shift was hypothesized to compensate for the disrupted utilization of these nutrients due to arsenic exposure. In higher arsenic exposure levels, however, the microbiota changes were inconsistent, suggesting a potential threshold beyond which the compensatory mechanism may be overwhelmed. Biochemical assays confirmed that arsenic binds to MTR, disrupting its function and further impacting FA/VB12 metabolism. The interaction was substantiated by SEC-UV-DAD and fluorescence-labeled arsenic studies, which demonstrated that arsenic directly interacts with MTR in both non-cellular and cellular systems. Our intervention model using FA and VB12 supplementation showed that it was possible to mitigate the disturbances in gut microbiota, restore MTR levels, enhance arsenic metabolism, and reduce liver injury.

Conclusion

This study provides significant insights into the interaction between arsenic exposure and gut microbiota. We demonstrated that changes in gut microbiota are not merely a consequence of arsenic exposure but are intricately linked to the metabolic processes affected by arsenic, particularly through the disruption of MTR function. The supplementation of FA and VB12 proved effective in blocking these disturbances, suggesting potential therapeutic strategies to combat arsenic toxicity. The findings emphasize the importance of considering gut microbiota in the management and treatment of arseniasis and underscore the complex interplay between environmental toxins, gut microbiota, and host metabolism. Future studies should focus on further delineating the specific pathways and mechanisms by which microbiota influence arsenic metabolism and exploring the potential for microbiota-targeted therapies in arsenic-related diseases.

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, such as gastrointestinal symptoms. Emerging evidence suggests that gut permeability and inflammation play a role in PD pathophysiology via the gut-brain axis. According to Braak’s theory, the pathological degeneration associated with PD may originate from the gut and subsequently develop in the brain through the vagus nerve.

Aims & Methods

The aims were to assess the relationship between gut permeability and neuroinflammation in a cohort of patients with PD and REM behavior disorder (RBD), a condition that often precedes the onset of PD. The study prospectively included 28 PD patients and 18 RBD patients both complaining of GI symptoms. No serious organic diseases or therapies potentially affecting GI motility were reported. Relevant demographic and clinical data were collected for all patients. There was the inclusion of 14 healthy controls (HCs). A serum ELISA assay of tumor necrosis factor (TNF), caspase-1, and lipopolysaccharide-binding protein (LBP) was performed in all participants to investigate systemic inflammatory status and gut permeability, respectively. In a total of 10 PD patients, 4 RBD patients and 9 HCs, multiple colic biopsies were obtained to assay tissue expression of inflammation markers by both western blot (WB) (i.e. caspase-1 and procaspase-1) and immunofluorescence (IF) (i.e. ASC and CD68). Data were expressed as mean ± SD, and ANOVA and Dunnett's tests were used to compare the three groups.

Results

All three groups were comparable in age and sex. Serum assays showed significantly increased LBP, in patients with PD (35.0 ± 0.25; p = 0.002) and RBD (32.2 ± 1.1; p = 0.009) compared with HCs. TNF (0.1 ± 0.02; p = 0.03) and caspase-1 (16.9 ± 9.4; p = 0.04) were significantly raised only in the PD group in comparison with HCs (Table 1). WB analysis showed significant differences in the expression of procaspase-1 (157.3 ± 17.8; p = 0.02) and caspase-1 (168.3 ± 23.3; p = 0.03) only in PD patients compared with HCs. IF showed a qualitative increase in both CD68+ macrophage infiltration and ASC expression in PD and RBD groups compared with HCs.

	PD	RBD	HCs	P-value
LBP (ng/ml)	35.0 ± 0.25	32.2 ± 1.1	23.1 ± 2.1	0.009 (RBD vs HCs) 0.002 (PD vs HCs)
Caspasi-1 (ng/ml)	16.9 ± 9.4	11.4 ± 2.1	9.9 ± 2.7	0.04 (PD vs HCs)
TNF (pg/ml)	0.1 ± 0.02	0.05 ± 0.02	0.04 ± 0.02	0.03 (PD vs HCs)

Conclusion

Our results show a bowel activation of NLRP3 inflammasome in PD, as demonstrated both by the levels of procaspase-1 and caspase-1 on WB analysis and by the increase of CD68+ macrophages and ASC in the lamina propria of colonic mucosa. Only a qualitative increase in NLRP3 activation at IF could be observed in RBD patients. However, findings from colonic biopsies, if related to elevated serum levels of TNF and caspase-1 in PD patients, and LBP in PD and RBD patients, suggest that bowel inflammation, sustained by increased gut permeability, may represent an early stage in the develop of RBD and PD.

Introduction

Endoscopic ultrasound (EUS) has broadened its diagnostic and therapeutic scopes, as it is able to target lesions <3mm. High-frequency radial EUS-miniprobes exhibit procedural time reduction, improving image quality and maneuverability. EndoSound Vision System (EndoSound, Oregon, USA) is a new EUS (N-EUS) portable device that fastens onto a standard gastroscope, enabling a free working channel. It is an affordable alternative to conventional-EUS devices; and a promising opportunity to shorten the difficult EUS learning curve.

Aims & Methods

We aim to determine the feasibility and effectiveness of N-EUS in terms of anatomical structures appropriate identification in comparison with conventional-EUS. This prospective study included patients ≥18 years-old undergoing EUS evaluation in June-November 2023 by eight endoscopists from different institutions from South and North America. Patients underwent two consecutive procedures: First, a conventional EUS with a linear-array echoendoscope (Pentax EG38-J1OUT, Pentax Medical, Germany). Then, a different endoscopist performed EUS using the N-EUS coupled to a video gastroscope with therapeutic access (EG29-i10, Pentax Medical, USA). A post-procedure ad-hoc survey was completed by the second endoscopist, to assess N-EUS acceptability in terms of endoscopists’ experience using this device.

Results

Thirty-one patients underwent conventional EUS and N-EUS: 16/31 performed by first-time N-EUS users, 15/31 by endoscopists with prior N-EUS exposure, with median procedural times of 30 and 15 minutes, respectively (p=.04). Main EUS indication was chronic dyspepsia (35.5%). Identified structures during N-EUS were the liver/gallbladder/common bile duct (30/31, 96.8%), full pancreas (29/31, 93.5%), kidneys/left kidney (24/31, 77%; 13/15 endoscopists with prior exposure vs 11/16 first-time N-EUS users; p<.001), left adrenal gland (20/31, 64.5%). Gallbladder (GB) was unobserved in 8 cases, 7/8 had prior cholecystectomy. Evaluation position was 54.8% supine; 3/31 switched to left lateral. All procedures were completed with 100% clinical and technical success, requiring navigation changes in 51.6%, mainly in first-time N-EUS users (p=.001). FNB tissue sampling was achieved in 100% cases. Endoscopists’ experience was predominantly described as “meeting clinical expectations”. The ad-hoc survey showed high psychometrics, with homogeneity among surveyed endoscopists, without redundancy (Cronbach’s alpha of .91), and a good construct validity (Kaiser-Meyer-Olkin Criterion of .728 and Barlett´s test p-value =.0005). When comparing both procedures, appropriate identification of GB or lack of, full pancreas, left/both kidneys and left adrenal gland was 31/31 vs 30/31, 31/31 vs 29/31, 31/31 vs 24/31 (p=.0233), and 29/31 vs 20/31 (p=.0158), respectively. Considering conventional EUS as a gold standard, the observed agreement of N-EUS to identify these structures were 96.8%, 93.5%, 77.4% and 64.5%, correspondingly. Observed agreement for kidneys and left adrenal gland increased when sub-analyzing the cases assessed by endoscopists with prior N-EUS exposure: 81.2% and 76.9%, respectively.

Conclusion

N-EUS is a safe, effective, and feasible tool for EUS evaluation, with high acceptability by endoscopists. Prior ex-vivo training may be warranted for first-time N-EUS users.

References

1. LeBlanc JK. An overview of endoscopic ultrasound equipment. Minerva Gastroenterol Dietol. 2008 Jun;54(2):177-87. PMID: 18319690 .
2. Varas Lorenzo, M.J., Abad Belando, R. and Sánchez-Vizcaíno Mengual, E. (2018), Miniprobe Endoscopic Sonography for Gastrointestinal Tract Assessment: A Case Series of 1451 Procedures. J Ultrasound Med, 37: 293-303. https://doi.org/10.1002/jum.14330
3. Deprez PH. Choice of endosonographic equipment and normal endosonographic anatomy. Best Pract Res Clin Gastroenterol. 2009;23(5):623-37. doi: 10.1016/j.bpg.2009.07.001 . PMID: 19744628 .

Disclosure

Carlos Robles-Medranda is a key opinion leader and consultant for Pentax Medical, Boston Scientific, Steris, Medtronic, Motus, Micro-tech, G-Tech Medical Supply, CREO Medical, EndoSound, and mdconsgroup. All other authors declare no conflicts of interest.

Introduction

Bowel, bladder and sexual dysfunction symptoms are common in patients with Inflammatory Bowel Disease (IBD). Despite significantly impacting on quality of life, few patients proactively seek help for these symptoms. For this reason clinician awareness of these functional symptoms in IBD patients is vital to identifying patients who may benefit from targeted treatment.

Aims & Methods

This study aimed to describe how well clinicians identified bowel, bladder and sexual dysfunction symptoms in IBD patients in the outpatient setting. Clinic letters from consecutive patients attending specialist IBD clinics at a tertiary hospital in the United Kingdom, from 1 January 2024, were reviewed retrospectively for documentation of bowel, bladder and sexual dysfunction symptoms. Patients with unclassified IBD, microscopic colitis, stomas and J-pouches were excluded. Data on patient demographics, IBD disease phenotype and activity were also collected.

Results

One hundred and twenty patients were included, of which 60/120 (50%) were male, 76/120 (63%) had ulcerative colitis (UC), and 44/120 (37%) had Crohn’s disease (CD), with median age 45 (range 18-88). Faecal urgency (FU) was the most commonly documented bowel symptom, documented in 26/120 (22%) patients, with 14/120 (12%) documenting the presence of FU and 12/120 (10%) documenting no FU. Faecal incontinence and constipation were each documented in 5/120 (4%) patients, and anorectal pain was documented in 3/120 (2.5%) patients. Urinary symptoms were only documented in one instance: urinary urgency in 1/120 (0.8%) patients. There was no documentation of urinary frequency or voiding dysfunction. Sexual dysfunction symptoms were not documented in any of the 120 letters, nor was impact of bowel symptoms on quality of life. FU was more frequently documented in patients with UC (11/76[14%]) compared to CD (3/44[7%]), whilst all cases of anorectal pain were documented in CD patients 3/44(7%), with no documentation of anorectal pain in any patients with UC. In patients with CD, documentation of FU was similar in remission (Harvey Bradshaw-Index (HBI) <4) and active disease (HBI≥ 4) groups (2/44 vs. 1/44, p=n.s.).

Conclusion

Bowel, bladder and sexual dysfunction symptoms are infrequently documented in patients with IBD. Failure to recognise these symptoms is likely to impair access to appropriate treatment. Introduction of a standardised reporting tool and improving IBD clinician awareness may facilitate best care for this patient group.