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May 03, 2026, 09:45

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This prospective observational study by Semeya et al. provides significant real-world evidence regarding the systemic implications of Helicobacter pylori (H. pylori) infection in high-risk patients on long-term low-dose aspirin. The authors elegantly demonstrate the clinical value of successful eradication in reducing both peptic ulcer bleeding (PUB) and cardiovascular disease (CVD) progression. This research is timely and offers practical guidance for the multidisciplinary management of these complex patients. However, a few methodological and technical nuances warrant further attention to enhance the study's scientific rigor. Most notably, a critical discrepancy exists in Table 4, where row labels such as "Endoscopic" and "Histopathological" appear under the "Cardiovascular disease" header instead of specific clinical conditions. Additionally, the P-value for ischemic heart disease is inconsistently reported as P < 0.001 in the text but P = 0.006 in Table 4. Furthermore, the overall eradication rate of 51.9% achieved with levofloxacin-based triple therapy and the relatively brief 6-month follow-up period for observing chronic CVD progression present opportunities for deeper discussion. The broad range of aspirin dosages (81–325 mg) utilized without stratified analysis may also act as a confounding factor. We are currently drafting a formal Letter to the Editor to provide a more detailed appraisal of these methodological considerations and to explore the integration of advanced diagnostic technologies for optimizing risk stratification in this vulnerable population.

Replied on May 03, 2026, 13:10

Re: Reader Comments on Manuscript No. 117544 We sincerely thank the reader for their engagement with our manuscript and for taking the time to offer a detailed appraisal. We welcome this scholarly exchange and are pleased to provide the following clarifications. Regarding the observation about Table 4 row labels, we respectfully suggest that this reflects a misreading of the table structure rather than an error in the manuscript. The labels "Endoscopic" and "Histopathological" in Table 4 do not represent cardiovascular disease categories and were never intended as such. They refer to the diagnostic subgroups through which gastric pathology was classified in this study, and their appearance in the table reflects a cross-tabulation design that examines PUB associations across multiple diagnostic dimensions simultaneously. A careful reading of the table in conjunction with the corresponding results section makes this interpretive framework explicit. The data and their labeling are internally consistent and accurately reported. Concerning the perceived P-value discrepancy for IHD, we must respectfully but clearly correct this point. There is no inconsistency in our reporting. The P less than 0.001 cited in the text and abstract refers to the baseline comparison of IHD prevalence between H. pylori-positive and H. pylori-negative groups, a chi-squared analysis presented in Table 3. The P = 0.006 in Table 4 is an entirely separate figure, derived from multivariate logistic regression examining the adjusted association between PUB incidence and IHD status, with full covariate adjustment. These two values describe fundamentally different statistical questions and different analytical models. It would actually be scientifically problematic if they were identical. We therefore confirm that both values are correct as published, and the reader's comment appears to have conflated two distinct analyses from two separate tables. Regarding the eradication rate of 51.9%, our discussion section addresses this comprehensively. The rate is contextualized within the well-documented Egyptian antibiotic resistance landscape, where clarithromycin resistance approaches 40% and metronidazole resistance approaches 70%, supporting our selection of a levofloxacin-based regimen. Our observed rate is consistent with recently published Egyptian data reporting comparable outcomes with similar protocols. Importantly, the moderate eradication rate does not weaken our conclusions; it strengthens them. Demonstrating significant reductions in both PUB and CVD progression even at this real-world eradication rate underscores the clinical relevance and generalizability of our findings to populations where optimal eradication remains challenging. On the matter of follow-up duration, this was neither an oversight nor an unaddressed limitation. We explicitly acknowledged the six-month observation window in our limitations and discussion sections, clearly distinguishing between symptomatic disease progression captured within our study period and long-term atherosclerotic endpoints that require extended follow-up. Future randomized trials with longer observation periods are proposed accordingly. The six-month design was appropriate and sufficient for the specific research questions this study was powered to address. Finally, with respect to aspirin dose range, the 81 to 325 mg range reflects standard real-world secondary prevention practice and is consistent with current cardiovascular guidelines. COX-1 inhibition and prostaglandin suppression, the principal mechanisms of aspirin-induced mucosal injury relevant to our primary outcome, operate across this entire dose range. Dose stratification was not a pre-specified study objective, and its absence does not introduce confounding into our primary analyses, which were adjusted for the relevant clinical covariates. This remains a direction of interest for future pharmacological investigation. We remain fully confident in the scientific rigor and accuracy of this manuscript as published, and we welcome any formal Letter to the Editor, which we trust will further advance this clinically important discussion.