Diabetic retinopathy (DR) represents one of the most common microvascular complications of diabetes, and proliferative diabetic retinopathy (PDR) is the most vision-threatening form. Carbonic anhydrase IX (CA9), a hypoxia-inducible enzyme, has been implicated in several pathological processes, but its involvement in DR has not been clarified. In this study, three CA9 single nucleotide polymorphisms (rs3829078, rs2071676, and rs1048638) were genotyped in diabetic patients with and without DR. Clinical characteristics were compared between groups, and expression analyses were conducted using public databases and ARPE-19 cells under hyperglycemic and hypoxic conditions. No significant association was observed between CA9 variants and DR susceptibility in the overall cohort. However, among patients aged ≤60 years, carriers of the rs1048638 C/A and C/A + A/A genotypes exhibited a significantly increased risk of PDR. Expression quantitative trait locus (eQTL) data from the GTEx database revealed higher CA9 mRNA expression in tissues harboring the rs1048638 A allele. Moreover, both transcriptomic data and in vitro experiments demonstrated upregulation of CA9 in ARPE-19 cells exposed to high glucose and hypoxia. These findings suggest that the rs1048638 polymorphism may modulate CA9 expression and contribute to PDR development in younger diabetic patients through hypoxia- and glucose-related mechanisms. Collectively, our findings suggest that CA9 may serve as a potential risk biomarker associated with the progression of DR, particularly in younger patients.

Intestinal metaplasia (IM) is a premalignant condition associated with increased risk of gastric cancer-a deadly malignancy with varying geographic incidence. High-depth targeted sequencing of more than 1,500 IM samples from six countries identified 47 significantly mutated genes, including driver genes associated with high-risk populations and worse prognosis (ARID1A), KRAS/MAPK signaling (KRAS, BRAF, MAP2K1, MAP3K1, and MAP2K4), and altered mucosal immunity (PIGR). IM whole-genome sequencing and DNA methylation analysis revealed SBS17 as a specific mutational signature separating IMs from normal gastric tissues, associated with late DNA replication, genomic hypomethylation, and tobacco exposure. Beyond epithelial-derived somatic mutations, we observed elevated clonal hematopoiesis (CH) in patients with IM associated with age, smoking, and enhanced risk of progressing to gastric cancer. Patients with CH expansions exhibited co-occurring IM PIGR truncating mutations and greater colonization of the IM microenvironment by orally derived bacteria, suggesting that CH may promote IM progression by modulating host-microbe mucosal immunity.Significance: This international study identifies recurrent IM driver genes, IM-specific mutational signatures, and alterations in IM-associated immune landscapes and microbiomes. Our results highlight a role for nonepithelial somatic alterations (CH) in IM progression to gastric cancer, offering new translational opportunities for early cancer detection and interception.

To investigate the effect of a hyaluronic acid (HA)-containing artificial tear (AT) on the management of digital screen device-related asthenopia (DSA). A retrospective cohort study was conducted, and patients with DSA were categorized according to the treatment they received. A total of 120 and 88 patients/eyes were assigned to the non-HAUD and HAUD groups, respectively. The main outcomes included tear break-up time (TBUT), the Schirmer I test, meibomian gland dysfunction (MGD), ocular surface staining, and ocular symptoms. The chi-square test, independent t test, and a generalized linear model were used for statistical analysis. After the 3-month follow-up, the TBUT value was significantly higher in the HAUD group than in the non-HAUD group (P < 0.001), whereas the Schirmer I test result did not differ significantly between the groups (P = 0.319). In addition, the ocular surface staining rate (P = 0.028) and the MGD ratios (P = 0.958) were similar between the two groups. The incidences of soreness, fatigue, difficulty with digital screen use, and ocular irritation were significantly lower in the HAUD group (all P < 0.001). DED, prolonged digital screen use, and ocular surface staining were significantly correlated with poor treatment response in the non-HAUD group (all P < 0.008). In this retrospective cohort, use of an HA-containing lubricant formulation was associated with modestly better outcomes.

To evaluate the efficiency, predictability, and residual astigmatism between first- and second-generation keratorefractive lenticule extraction (KLEx) surgeries in a prominent astigmatism population. A retrospective cohort study was conducted, and individuals who underwent first- and second-generation KLEx surgeries were enrolled. A total of 31 and 35 eyes were categorized into first and second KLEx groups, respectively. Visual acuity, refraction, topographic parameters, and surgical indices were recorded. Independent t tests were used to compare the postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual astigmatism between the two groups. The difference in UDVA was not significant three months after KLEx surgery (P = 0.509), and the SEs three months after surgery also presented similar values between the two groups (P = 0.552). The first KLEx group demonstrated greater residual astigmatism than did the second KLEx group throughout the three-month follow-up period (all P < 0.05). The values of surgically induced astigmatism (SIA), difference vector (DV), magnitude of error (ME) and correction index (CoI) were significantly better in the second KLEx group via vector analysis (all P < 0.05). Old age, high steep keratometry (K), high topographic cylinder, large angle kappa, and a small optic zone were correlated with greater residual astigmatism in the first KLEx group (all P < 0.05), whereas only a small optic zone was significantly correlated with greater residual astigmatism in the second KLEx group (P = 0.047). The second-generation KLEx is correlated with a lower risk of residual astigmatism.

This article outlines how decision modeling can be used to optimize the cost-effectiveness of H. pylori screen-and-treat programs. Decision models enable the translation of data from pilot studies into locally tailored strategies by adapting test modalities, treatment options, and the need to retest specific to the local setting. We summarize existing evidence from modeling studies, which consistently demonstrate that H. pylori screen-and-treat is cost-effective across diverse populations. In addition, we discuss how decision modeling can support resource allocation, promote health equity, and guide implementation planning. Integrating H. pylori screen-and-treat into established preventive programs, such as colorectal cancer screening, may further increase efficiency and feasibility. The article concludes with a proposed research agenda to advance efficient H. pylori screen-and-treat programs across the globe.

To examine whether long-term opioid use after total knee arthroplasty (TKA) is associated with subsequent risks of major adverse cardiovascular events (MACE) and all-cause mortality in patients with knee osteoarthritis (OA). This retrospective, population-based cohort study used Taiwan’s Longitudinal Health Insurance Database (LHID) 2005 to identify patients with knee OA undergoing TKA (2002–2018). Opioid exposure was assessed during the 1-year post discharge window (long-term > 3 months vs. non-long-term < 3 months), and the index date was set at 360 days after discharge (landmark design). The primary outcome was first MACE after the index date. After 1:2 propensity score matching (PSM), adjusted hazard ratios (aHRs) were estimated using Cox models; Fine–Gray models were used for nonfatal components. In the matched cohort (2,351 long-term vs. 4,702 non-long-term users), long-term opioid use was associated with higher risks of MACE (aHR = 1.16; 95

BACKGROUND:Despite increasingly refined diagnostic strategies and regularly updated treatment guidelines, real-world outcomes of Helicobacter pylori management remain variable. Antimicrobial resistance alone does not fully explain these discrepancies, suggesting important challenges in the implementation of evidence-based care. AIMS:To identify recurring implementation-related challenges across the Helicobacter pylori care pathway and highlight priorities for improving real-world management. METHODS:This expert-informed review integrated relevant literature, international guideline documents, and structured international expert prioritisation. An initial list of implementation-related pitfalls was developed through literature review, clinical experience, and discussions among the coordinating authors and selected co-authors. Twenty-six experts from five continents participated in a structured consultation process and rated predefined pitfalls using a 5-point Likert scale. Median scores were used for relative prioritisation. RESULTS:Treatment selection and patient management emerged as the domains most consistently prioritised by participating experts. High-impact pitfalls included empirical triple therapy in high-resistance settings, inadequate patient counselling, and empirical retreatment without escalation. Additional challenges were identified across diagnostic, treatment, and follow-up domains, highlighting persistent implementation-related barriers throughout the care pathway. CONCLUSIONS:Recurring implementation-related challenges remain important barriers to optimal Helicobacter pylori management. Structured expert prioritisation highlights potential targets for improvement and supports further research and implementation-focused strategies to improve delivery of care.

Background:Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are 2 of the leading causes of vision loss worldwide. As population aging and diabetes prevalence increase, timely detection of these conditions has become essential. However, limited professionalism and insufficient training in ophthalmic screening among general medicine physicians may lead to delayed diagnosis and treatment. Artificial intelligence (AI)-assisted diagnostic tools may help to improve the screening of DR and AMD in routine clinical practice. Objective:This study aims to evaluate the clinical effectiveness and cost-effectiveness of AI-assisted fundus imaging for DR and AMD screening in adults with diabetes and older adults at risk of macular degeneration. Methods:This multicenter, 2-arm, parallel-group, open-label, individual-level randomized controlled trial and patient recruitment are performed at the settings of Family Medicine and Geriatric and Gerontology Care over 4 medical centers in Taiwan. Eligibility includes (1) diabetic individuals aged ≥20 years for DR screening, and (2) individuals aged ≥50 years for AMD screening. The study protocol has been approved by the ethics committees of all participating hospitals, and all participants will provide written informed consent. Results:The study was funded in September 2024, began on October 2, 2025, and is expected to be completed in December 2027. After the pilot implementation phase without randomization, participants will be randomized 1:1 into two groups: (1) AI-assisted screening, and (2) usual physician-only screening. The primary outcomes will include the detection rates (defined as participants with confirmed DR or AMD among all screened participants) and the positive predictive values (defined as participants with confirmed DR or AMD among those who tested positive). Cost-effectiveness analyses will be performed using data derived from the trial results. Conclusions:This study will provide robust evidence on the effectiveness of AI-assisted ophthalmic screening in improving patient eye health outcomes through timely screening and accurate early detection. This strategy may be cost-effective.

BACKGROUND:The aim of this study was to investigate the effectiveness of 0.01% topical atropine (ATR) on myopic prevention in a population with different low refractive errors. METHODS:A retrospective cohort study was conducted on children with low refractive error. They were classified according to the application of 0.01% ATR, and 55 and 67 eyes constituted the ATR and non-ATR groups, respectively. The primary outcomes were changes in spherical equivalent refraction (SER) and axial length (AXL) after a one-year interval. Statistical analysis was carried out using the independent T test and generalized linear model. RESULTS:The SER change and AXL elongation were significantly lower in the ATR group compared to the non-ATR group (P < 0.001 for both). For different initial SERs, SER and AXL progression in the individuals with plus initial SER were significantly lower than those with minus initial SER after ATR treatment (both P < 0.05). High outdoor activity was inversely correlated with myopic progression in the ATR group (P = 0.006). For the non-ATR population, young initial age, minus initial SER, and high near-work activity were related to myopic progression, while high solar exposure and high outdoor activity were inversely correlated with the development of myopic progression (all P < 0.05). CONCLUSIONS:Application of 0.01% ATR might relates to myopic prevention effect in a population with low refractive error, especially for plus initial SER.

Population-based screen-and-treat of Helicobacter pylori infection, a well-established cause of gastric cancer, is emerging as an effective strategy to reduce gastric cancer incidence and mortality, in line with recommendations from the working group convened by the International Agency for Research on Cancer. This report reviews the development of the population-based H. pylori screen-and-treat strategy as a healthcare policy for gastric cancer prevention in Taiwan from 2004 to 2025, tracing its evolution from localized pilot programs to regional initiatives and, ultimately, to full population-wide implementation. To support systematic implementation at the population level, Taiwan adopted a three-tiered foundation that includes: (1) a centralized planning committee; (2) screening service delivery through primary care providers, guided by clinical guidelines established by medical societies; and (3) community engagement to raise awareness of stomach health and promote participation in screen-and-treat programs through social media campaigns. Program execution strictly follows the principles of organized screening, supported by standardized quality indicators, integrated digital tracking systems, structured audit mechanisms, and both effectiveness and cost-effectiveness assessments. Strategies are tailored to local contexts: in the Matsu Islands, mass screening using the 13C urea breath test and subsequent eradication treatment led to reductions in H. pylori prevalence and gastric cancer incidence and mortality; in Changhua County, a pragmatic randomized clinical trial showed that stool sample-based screening using H. pylori stool antigen and fecal immunochemical testing improved participation and reduced gastric cancer incidence; and in indigenous communities, household-based approaches utilizing the 13C urea breath test could enhance H. pylori detection rate and reduce the intrafamilial transmission. In addition to the continuous assessment of its effectiveness in preventing both gastric cancer and peptic ulcer disease, it is also essential to evaluate the potential impacts on antibiotic resistance and gut microbial succession after mass H. pylori eradication. All these programs consistently maintain high standards of quality and equity, ensuring accessibility for diverse populations with varying socioeconomic positions. Collectively, it demonstrates how robust scientific evaluations, when combined with organized screening principles and systematic performance monitoring, can be effectively translated into sustainable, evidence-based programs for population-wide gastric cancer prevention.

Background The burden of gastric cancer remains substantial in Asia. Gastric premalignant conditions, including chronic atrophic gastritis, intestinal metaplasia and dysplasia, are important intermediate stages in the gastric carcinogenesis cascade. The sojourn time allows endoscopic surveillance to have a pivotal role in early detection and timely intervention.Objective This task force was commissioned by the Asian Pacific Association of Gastroenterology to formulate recommendations for the surveillance and management of Helicobacter pylori associated gastric premalignant conditions in the region.Design A systematic literature review was conducted across multiple databases, including PubMed, Cochrane Library and Embase, focusing on studies related to gastric premalignant conditions and their surveillance, particularly from Asia. The evidence quality and strength of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.Results These recommendations address four key aspects of gastric premalignant condition surveillance: (1) epidemiology and risk factors; (2) endoscopic and histopathological diagnosis; (3) risk stratification and endoscopic surveillance strategies; and (4) management strategies. 28 statements were made after multiple rounds of voting by experts. The statements offer a comprehensive, evidence based framework designed to assist clinicians in the Asia Pacific region on the early detection and management of gastric premalignant conditions.Conclusion These statements aim to provide a structured, evidence based surveillance framework for clinical practice in the Asia Pacific region, while also identifying priority areas for future research.

Importance:Helicobacter pylori infection is the leading cause of gastric cancer, yet the economic value of population-based screening and eradication remains uncertain. Objective:To project the lifetime health benefits and costs of invitation to 1-time H pylori stool antigen testing added to biennial fecal immunochemical test (FIT) screening compared with FIT alone. Design, Setting, and Participants:Lifetime cost-effectiveness analysis conducted using a Markov decision-analytic model to simulate a cohort informed by a pragmatic randomized clinical trial in Changhua County, Taiwan. The model adopted a 30-year time horizon and projected long-term outcomes, including gastric and colorectal cancer mortality, quality-adjusted life-years (QALYs; incorporating both life expectancy and health-related quality of life), and health care expenditures. Costs were evaluated from a societal perspective. One-way and probabilistic sensitivity analyses were performed. Future costs and QALYs were discounted at an annual rate of 3%. Exposures:Helicobacter pylori stool antigen testing plus FIT or FIT alone. Main Outcomes and Measures:Incremental cost-effectiveness ratio of invitation for H pylori stool antigen testing plus FIT vs FIT alone, measured as the additional cost required to gain 1 QALY per person. Secondary outcomes included net monetary benefit and benefit-cost ratio. Results:Compared with FIT alone, invitation to co-testing was more effective and less expensive (dominant), with a base-case cost-saving incremental cost-effectiveness ratio of $2094 per QALY gained (95% CI, $12 359 saved to $7291 additional cost). This resulted in a positive net monetary benefit, indicating that health benefits exceeded costs, and a benefit-cost ratio of 5.08, indicating an approximately 5-fold return on investment in the Taiwanese population. At a willingness-to-pay threshold of 1 × the Taiwan gross domestic product per QALY ($33 365), invitation to co-testing remained cost-saving in 65.7% of simulations. From a US cost perspective, invitation to co-testing was not cost-saving but remained cost-effective at the trial base-case H pylori prevalence. Sensitivity analyses identified H pylori prevalence as the dominant driver; co-testing exceeded a $100 000-per-QALY threshold when prevalence fell below 21.9%. Conclusions and Relevance:In a pragmatic real-world setting with incomplete adherence, invitation to combined H pylori stool antigen testing and FIT was more cost-effective than FIT alone, improving lifetime outcomes and yielding cost savings in Taiwan while remaining cost-effective in higher-cost settings under moderate H pylori prevalence. Trial Registration:ClinicalTrials.gov Identifier: NCT01741363.

Objectives: To evaluate the effectiveness of astigmatism correction between topographic- and manifest-based methods in individuals who underwent second-generation keratorefractive lenticule extraction (KLEx) surgery. Methods: This study was conducted with participants who underwent second-generation KLEx surgery. After exclusion, there were 46 and 43 participants in the manifest and topographic groups, respectively. The main outcomes were postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual astigmatism. The independent T-test and generalized estimate equation were used to investigate differences between the two groups. Results: Three months postoperatively, UDVA was 0.02 ± 0.04 in the manifest group and 0.00 ± 0.06 in the topographic group which also revealed no significant difference (p = 0.155). Also, the SE value in the two groups three months postoperatively was statistically similar (−0.57 ± 0.48D versus −0.63 ± 0.62D, p = 0.574). The final residual astigmatism was −0.26 ± 0.27 in the topographic group which was significantly lower than the −0.51 ± 0.40 in the manifest group (p < 0.001). Moreover, the amplitude of astigmatism change was significantly lower in the topographic group (p = 0.002). In the subgroup analysis, UDVA and residual astigmatism were significantly better in the topographic group than in the manifest group (both p < 0.05). Conclusions: The topographic-based method represents a better astigmatism correction than the manifest-based method in second-generation KLEx surgery, especially in the low astigmatism population.