Introduction

Vonoprazan (VPZ) has been used in Japan since 2015 to eradicate Helicobacter pylori. The level of acid inhibition required for H. pylori eradication is a pH > 5.0, and VPZ treatment maintains this state for an extended period. Accordingly, VPZ reportedly has a higher eradication success rate than conventional proton pump inhibitors. However, the incidence and risk factors of gastric cancer (GC) as well as long-term prognosis after VPZ eradication of H. pylori remain unclear. Neutrophil-to-lymphocyte ratio (NLR) is an indicator of asymptomatic chronic inflammation. NLR was reported to reflect the balance between the tumor-promoting environment and the anti-tumor immune status.

Aims & Methods

This single-center cohort study included 934 consecutive patients who underwent H. pylori eradication using a VPZ regimen between February 2015 and June 2017. The patients were followed up for 5 years after H. pylori eradication. The trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046308). The eradication regimen included VPZ 40 mg/day, amoxicillin 1500 mg/day, and clarithromycin 400 mg/day for 1 week for primary eradication and VPZ 40 mg/day, amoxicillin 1500 mg/day, and metronidazole 500 mg/day for 1 week for secondary eradication. We examined the NLR at the time of eradication and investigated whether it could be a predictive marker of eradication success, risk of post-eradication GC development, and long-term prognosis.

Results

The study cohort included 57.3% men and had a mean age of 57.8 (interquartile range, 49-67) years. Of them, 3.2% had a history of GC resection. Two-thirds of all patients (59.0%, n=551) had open-type atrophy. The mean (standard deviation) NLR was 1.99 (1.20). The successful eradication rates were 92.6% (intention-to-treat) and 98.7% (per-protocol). Minor side effects (e.g., rash, diarrhea) occurred in 2.0% of all patients. A multivariate analysis showed that high NLR (odds ratio [OR], 2.96; p=0.004) was significantly associated with eradication failure. During the 5-year observation period, twelve cases of stage IA GC developed. The 3-year incidence rate was 0.87% and the 5-year incidence rate was 1.67%. The average time from eradication to diagnosis was 40.5 (6.1) months. A multivariate analysis showed that a high NLR (OR, 6.0; p=0.026), history of GC (OR, 6.9; p=0.011), and history of hypertension (OR, 5.8; p=0.016) were significantly associated with GC development. In contrast, age ≥ 70 years (p=0.402) and open-type atrophy (p=0.120) were not significant factors of GC development. A receiver operating characteristic curve showed that the optimal NLR cut-off value for new GC development at the time of eradication was 1.95 (sensitivity; 0.82, specificity; 0.65). Twelve patients died during the study period, and no treatment- or GC-related deaths were observed. A high NLR was associated with a significantly higher mortality rate (Hazard ratio [6.47], p=0.002).

Conclusion

High NLR was associated with H. pylori eradication failure using the VPZ regimen. A high NLR, history of GC, and history of hypertension were risk factors for new-onset GC within 5 years post-eradication, while a high NLR was also associated with a poor long-term prognosis after H. pylori eradication.

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

The development of gastric cancer is strongly linked to Helicobacter pylori infection. Therefore, early diagnosis and eradication of H. pylori infection can significantly lower the risk, as studies consistently show reduced cancer rate with these measures. The success in achieving such a goal depends on widespread early detection and treatment, plus effective prevention of new infections. To date, there is no effective certified vaccine against H. pylori available. This study describes the development of a novel multi-epitope H. pylori vaccine consisting of B- and T-cell epitopes from six conserved virulence factors of the bacteria.

Aims & Methods

Through comprehensive bioinformatic analysis, sixteen B- and T-cell epitopes were carefully selected, considering both MHC classes I and II for the T-cell epitopes. The recombinant Multi-Epitope-Unit antigen (MEU) was combined with flagellin as adjuvant. Additionally, recombinant Modified Vaccinia virus Ankara (MVA) encoding the MEU antigen was generated. The vaccine candidates were tested in mice. To this end, two sets of animal experiments were designed. One set to evaluate the immunogenicity of the new MEU construct, while the second set to assess the protective effect of the vaccine candidates. In the vaccination protocol, both protein- and MVA-based vaccine candidates were administered intramuscularly (IM) to C57/Bl6 mice on days 0, 7 and 14. Two weeks after the last immunization, mice in the prevention groups were challenged with three doses of the mouse adapted H. pylori SS1 strain. The groups, allocated for evaluating the immunogenicity of the new vaccine, were not exposed to infection with H. pylori or any further treatments prior to the analysis. Humoral (antibody) and cellular immune responses, along with the levels of protection and infection, were evaluated at two or four weeks post-immunization or -infection respectively. Bacterial load in prevention groups was determined through culturing of the gastric samples. The reactivity of anti-MEU antibodies, raised in immunized animals, to the H. pylori clinical isolates was also assessed via ELISA employing crude antigens of a set of 30 clinical isolates.

Results

The MEU antigen, whether adjuvanted with flagellin or in MVA construct, was observed to elicit significant antibody levels in mice, capable of reacting with crude antigens from H. pylori. The most substantial antibody response was detected towards the individual epitopes from Urease and FliD (hook-associated protein 2 homologue).
Both vaccine protocols, using the flagellin-adjuvanted MEU and the recombinant MVA, demonstrated complete protection against H. pylori infection compared to non-immunized animals. This protection was achieved through either a schedule of immunization with the protein-based vaccine candidate followed by MVA boost or two administered doses of MVA.

Conclusion

The novel MEU-based vaccine demonstrated significant immunoreactivity against H. pylori antigens. Our findings indicate a complete protection against H. pylori infection in the mice immunized with the multi-epitope unit antigen, regardless of the vaccination protocols. The reactivity of these antibodies with the bacteria native crude antigens suggests the antigen’s correct processing by the mammalian immune system. Moving forward, our next step involves assessing the therapeutics effects of the vaccine candidate.

Introduction

Endoscopic Sleeve Gastroplasty (ESG) is one of the main interventions of primary minimally invasive bariatric surgery, especially for subjects suffering from I and II class obesity^1,2. However, since obesity is a chronic, relapsing, and multifactorial disease, a second intervention may be necessary. The purpose of this study is to assess the effectiveness of endoscopic revision (Re-ESG) versus primary intervention (P-ESG).

Aims & Methods

A prospective dataset enrolling all subjects undergone ESG in a tertiary center from May 2017 to December 2023 was retrospectively analyzed. All subjects undergone Re-ESG for weight regain (WR), weight plateau (WP) or weight loss failure (WF), as defined by Lopez Nava et al.³, were enrolled. Weight loss outcomes [Absolute Weight Loss (AWL), Excess Weight Loss (EWL), Total Body Weight Loss (TBWL), Body Mass Index Loss (BMIL)] at 6-,12-,18- and 24-months after P-ESG and Re-ESG were collected and compared.

Results

Out of a total of 578 patients, 53 patients (9.2%) underwent Re-ESG: 24 for WR, 18 for WP and 12 for WF, after a mean time of 25.4 ± 11.4 months from P-ESG (35 subjects underwent revision in the first 24 months, whereas other 18 between 30 and 66 months). One subject underwent a second revision, for a total of 54 revisions.
Both P-ESG and Re-ESG were associated with significant total body weight loss and excess body weight loss up to 24 months and when compared, endoscopic revision were proven to be as effective as primary intervention, at least in the short and medium term, as showed in Table 1.

Conclusion

Our study, despite the limit of a low sample, highlights how the endoscopic revision of a previous ESG is as effective as the primary intervention in the short and medium term.
These results may pave the way for an exclusively minimal-invasive multi-step treatment of chronic obesity.

References

1. Abu Dayyeh BK, Bazerbachi F, Vargas EJ, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. The Lancet. 2022;400(10350):441-451. doi:10.1016/S0140-6736(22)01280-6
2. Saumoy M, Gandhi D, Buller S, et al. Cost-effectiveness of endoscopic, surgical and pharmacological obesity therapies: a microsimulation and threshold analyses. Gut. Published online August 8, 2023:gutjnl-2023-330437. doi:10.1136/GUTJNL-2023-330437
3. Lopez-Nava G, Sharaiha RZ, Vargas EJ, et al. Endoscopic Sleeve Gastroplasty for Obesity: a Multicenter Study of 248 Patients with 24 Months Follow-Up. Obesity Surgery. 2017;27(10):2649-2655. doi:10.1007/s11695-017-2693-7

Introduction

Esophageal variceal bleeding is a serious and fatal complication of cirrhosis. Currently, efficient noninvasive monitoring strategies are lacking. By applying artificial intelligence (AI) to computed tomography (CT) imaging, we developed an innovative tool to meet clinical needs.

Aims & Methods

This is an ambispective cohort study conducted at West China hospital between April 2021 and December 2021, patients underwent endoscopy and enhanced CT were registered. Furthermore, 97 patients with radiomic and hepatic venous pressure gradient data were enrolled from a portal hypertension database. High-risk esophageal varices (HREV) were defined as either moderate-severe varicose (HREV-1) or EV requiring intervention (HREV-2). Deep learning was used to develop segmentation and EV quantification models. The EV bleeding prediction model was established using least absolute shrinkage and selection operator (LASSO) regression and logistic regression analysis. The area under the curve (AUC) was calculated for efficiency evaluation. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2300069865) and is completed.

Results

A total of 2291 patients in the retrospective (n=780) and prospective (n=1511) cohorts were included. The internal and external validation cohort AUCs were 0.976 and 0.951 for EV vs. non-EV, 0.986 and 0.951 for HREV-1, and 0.978 and 0.898 for HREV-2, respectively. We found that volume (p=0.0348) and AI-10 (p=0.0196) were closely related to portal pressure. We further analyzed the AI features and bleeding events for patients with cirrhosis in the retrospective (n=254) and prospective (n=569) cohorts and applied the EV bleeding prediction model (validation cohort AUCs of 0.669, 0.701 and 0.705 at 1, 3, and 6 months, respectively), which was not inferior to that of endoscopic signs (p > 0.05).

Conclusion

Enhanced CT assisted by AI is a promising noninvasive strategy for quantifying EV, recognizing HREV and predicting short-term bleeding risk and has the potential to replace simple gastroscopy for diagnosis or monitoring. This approach could decrease unnecessary gastroscopy to some extent.

Disclosure

The authors have declared no competing interests.

Introduction

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated oesophageal disease that is showing a skyrocketing increase of new diagnoses in last two decades. Although tons of papers have been published clarifying several aspects of this disease, most of the evidences come from high volume – referral centres that may be not representative of the whole EoE population. In fact, little is known about demographic and clinical features as well as treatment outcomes of patients managed in community hospitals.

Aims & Methods

Between January 2021 and June 2023, we prospectively enrolled all EoE patients evaluated for the first time at two different centres: 1) a high-volume tertiary-care centre, the University Hospital of Padua (PH), that represent a national referral centre; 2) a low-volume community hospital, the hospital of Feltre (FH), with a catchment area of about 25,000 people, both located in the North-East of Italy. The diagnosis of EoE was made according to the latest international guidelines. Endoscopic features were assessed according to EREFS score (0-8 points). Histological remission was considered for eosinophilic peak <15 eos/HPF.
The main goals of our study were to compare the cohorts of EoE patients from a community and a tertiary care centre in terms of demographic and clinical features as well as to assess differences in the rate of histological response to medical treatments.

Results

Overall, 210 patients were consecutively enrolled, 177 (84.3%) in the tertiary centre (PH) and 33 (15.7%) in the community one (FH). We did not find any significant difference between PH cohort and FH patients regarding age (34.80 vs 38.24 years, p=0.193), male prevalence (79.1% vs 72.7%, p=0.491), body mass index (22.55 vs 22.63, p=0.906), prevalence of non-atopic comorbidities (35.6% vs 21.2%, p=0.158), diagnostic delay (3.35 vs 2.62 years, p=0.682). A not significant trend in higher EREFS score values was found in PH (3.3 vs 2.7, p=0.062). There was a significant difference regarding the number of patients that were evaluated for a second opinion (77% vs 15%, p<0.001) and the prevalence of atopic comorbidities (68.9% vs 42.4%, p=0.008), both higher in PH court.
Regarding medical treatments 184 patients were treated with PPI (157, 88.7% at PH and 27, 81.8% at FH, p=0.219). There was a significant difference in the rate of PPI response comparing PH and FH patients (29.94% vs. 51.85%, p=0.044). No differences in terms of rate of responsiveness regarding swallowed flixotide puffer (44% vs 36%, p=0.295) and orodispersibile budesonide (50.9% vs 61.5%, p=0.564).

Conclusion

This study elucidated several significant aspects regarding EoE. Firstly, it revealed that EoE patients treated in peripheral hospitals may exhibit a milder phenotype, characterized by less severe endoscopic features and fewer atopic comorbidities. Conversely, more complex cases tend to be referred to specialised centres, often seeking for a second opinion. Accordingly, the rate of PPIs responsiveness was found to be higher in community hospitals and, indeed, they still hold a significant as effective therapeutic option for EoE patients. Given that most of the evidence come from high-volume referral centres, it is crucial to keep in mind these differences when assessing the wide spectrum of EoE patients. Although the need for new therapies is still a fact, the increasing prevalence of EoE also necessitates a thorough evaluation of the financial implications of these drugs.

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.