BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder with multifactorial etiology, including genetic components. Despite numerous genetic association studies (GAS), the role of spec...BACKGROUND: Gastroesophageal reflux disease (GERD) is a prevalent gastrointestinal disorder with multifactorial etiology, including genetic components. Despite numerous genetic association studies (GAS), the role of specific gene polymorphisms in GERD susceptibility remains unclear due to inconsistent findings. AIMS: To systematically review GAS on GERD and conduct a meta-analysis to evaluate the association between specific gene polymorphisms and GERD risk. METHODS: A systematic review of PubMed, Cochrane, ScienceDirect, Scopus, DisGENET, GWASCatalog, and HuGE Phenopedia databases (2012-2024) was conducted to identify GAS for GERD. Meta-analytical methods were used to synthesize the results. RESULTS: 21 GAS, including 27,783 GERD patients and 83,857 controls, were analyzed, focusing on 132 polymorphisms across 105 genes. Meta-analysis of seven studies revealed a significant association between GNB3 rs5443 C > T and increased GERD-like symptom phenotypes (ORp = 2.24, 95 % CI: 1.56-3.21), suggesting a dominant genetic model. No significant associations were found for TNF, IL1B, or CYP2C19. Heterogeneity and potential bias were observed in some analyses, necessitating cautious interpretation of the findings. CONCLUSION: The findings support a robust association between GNB3 rs5443 C > T and susceptibility to GERD-like symptom phenotypes, suggesting a potential genetic predisposition. Additional large, well-characterized studies using standardized GERD definitions are needed to validate these results and elucidate the broader genetic landscape of the disease.
Canova L, Iavarone M, Alimenti E
… +11 more, Bruccoleri M, Argiento L, Perbellini R, Facchetti F, Uceda Renteria S, D'Ambrosio R, Degasperi E, Ierardi AM, Sangiovanni A, Vidali M, Lampertico P
BACKGROUND AND AIMS: The ASAP algorithm incorporating Age, Sex, Alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence/antagonist II (PIVKA-II) has been shown to predict hepatocellular carcinoma (HCC) deve...BACKGROUND AND AIMS: The ASAP algorithm incorporating Age, Sex, Alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence/antagonist II (PIVKA-II) has been shown to predict hepatocellular carcinoma (HCC) development. Our study evaluated the prognostic value of ASAP for early HCC recurrence after complete radiological response (CR) to locoregional therapy. METHODS: This single-center study enrolled patients with newly diagnosed HCC who achieved CR by ablation (MWTA) or chemoembolization (TACE) and available serum samples on the day of treatment. CR was evaluated by CT-scan 1 month after treatment. PIVKA-II and AFP levels were measured using Fujirebio assays. Patients were followed up every three months until recurrence, death, or last follow-up. RESULTS: 127 patients with HCC (median age 66 years, 79 % male, 79 % with viral etiology) who achieved CR were enrolled. At time of treatment, median AFP and PIVKA-II levels were 6.6 ng/mL and 144 mAU/mL, respectively, while median ASAP score was 0.60. During follow-up, HCC recurred in 72 (56.7 %) patients (63 within 24 months, early recurrence). ASAP score was the sole independent predictor of early recurrence [HR 2.57 (95 % CI 1.50-4.40), p=0.001] and its new cutoff of 0.797 (AUC 66 %, sensitivity 57 %, specificity 75 %) outperformed other scores and biomarkers. CONCLUSIONS: The ASAP score accurately predicted early HCC recurrence post-CR, warranting further validation.
BACKGROUND: Potential coeliac disease is an increasingly diagnosed condition, and the dilemma whether start a gluten-free diet is still unsolved. AIMS: We hypothesized that an exaggerated enterocyte turnover is responsib...BACKGROUND: Potential coeliac disease is an increasingly diagnosed condition, and the dilemma whether start a gluten-free diet is still unsolved. AIMS: We hypothesized that an exaggerated enterocyte turnover is responsible for an impairment of gut function leading to the development of symptoms and/or progression to villous atrophy. METHODS: The proliferation and apoptotic rates of duodenal enterocytes, assessed by anti-Ki-67 and -Caspase-3 antibodies at immunohistochemistry, of 36 adult patients with potential coeliac disease were compared to those found in a group of 32 active coeliac patients and a group of 31 controls. Statistics was computed by Fisher's exact test, Wilcoxon-Mann-Whitney rank-sum test, and Kruskal-Wallis test as appropriate, post-hoc analysis was performed by Dunn's test with Bonferroni correction. RESULTS: Nearly all patients with potential coeliac disease reported symptoms (31/36 = 86.1 %), and four out 36 developed active disease over time. A significant increase of enterocyte proliferation (p = 0.042), but not of apoptosis (p = 0.514), in comparison with control subjects was found. Notably, a significant correlation between Ki-67 expression and the progression to villous atrophy (p = 0.015) was evident. CONCLUSIONS: The maintenance of mucosal architecture in potential coeliac disease is due to enterocyte hyper-proliferation that causes the presence of immature cells on the villous lining and correlates with the development of villous atrophy.
BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a major concern, but it is unclear whether existing models can safely "rule out" patients from intensive imaging strategies. ME...BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) is a major concern, but it is unclear whether existing models can safely "rule out" patients from intensive imaging strategies. METHODS: We retrospectively studied 493 LT recipients transplanted for HCC (2002-2023). Competing-risk Fine-Gray regression with bootstrap stability selection was used to derive an illustrative score and compared with established models. Rule-out performance was evaluated by 5-year cumulative incidence. Decision curve analysis (DCA) and surveillance simulations quantified trade-offs between CT scans saved and recurrences missed under reduced protocols. RESULTS: Our model identified total tumor diameter, microvascular invasion, satellite nodules, and log(AFP) as stable predictors. DCA showed all models outperformed uniform surveillance only when 5-year recurrence exceeded 4%, with 7.5% as the upper acceptable threshold. Within this range, low-risk groups across models had 5-year recurrence risks of 2.5-5.7%. Reduced-intensity strategies could save 160-856 CTs per 100 patients while missing ≤1 recurrence with semiannual or annual two-year protocols. Cost-benefit analysis supported 4-7.5% as the optimal threshold. False negatives were uncommon (n = 13), with only two patients misclassified by all models. CONCLUSIONS: Widely used models can identify patients suitable for reduced surveillance, though none delineated a true "no-screening" group.
In the last decades, the world of hepatology has widely changed. Although relevant advances have be achieved (e.g. the way toward eradication of hepatitis C virus), many challenges are far to be won. Patients with liver...In the last decades, the world of hepatology has widely changed. Although relevant advances have be achieved (e.g. the way toward eradication of hepatitis C virus), many challenges are far to be won. Patients with liver disease continue to face noteworthy barriers to early diagnosis and effective disease management. In response to these tasks, the Italian Association for the Study of the Liver formed a multidisciplinary commission to address the unmet needs of people affected by liver diseases. We analyzed the state of the art of the following consolidated unmet needs: stigma (with particular attention to alcohol-related disease and obesity), specific criticisms of elderly, socioeconomic barriers that patients with liver disorders can face, gender gap in many aspects of liver disease and, finally, the complex issue of quality of life. For each unmet need, we proposed a key-message task and some concrete future perspectives. Preserving a holistic vision and using both multidisciplinary and interdisciplinary method, represent the only effective approach to take on the many unmet needs of patients with liver disorders.
BACKGROUND: Clinical practice currently lacks objective and accurate screening tools for minimal hepatic encephalopathy (MHE). Therefore, we aimed to develop an MHE prediction model based on common risk factors. METHODS:...BACKGROUND: Clinical practice currently lacks objective and accurate screening tools for minimal hepatic encephalopathy (MHE). Therefore, we aimed to develop an MHE prediction model based on common risk factors. METHODS: A total of 514 and 191 cirrhotic patients were included in the training and external validation cohorts, respectively. Best subset selection was applied to screen for predictors. Logistic regression was selected for model development because it outperformed four machine learning algorithms (Random Forest, Adaptive Boosting, Support Vector Machines, and Naive Bayes) in this study. Discrimination, calibration, and clinical decision-making utility of the model were evaluated. Furthermore, the model was compared with the Stroop test for MHE assessment. RESULTS: From 44 potential predictors, 6 variables were identified as significant and included in the prediction model: upper gastrointestinal bleeding (odds ratio, 4.17; 95% confidence interval, 2.53-6.88), ascites (2.86; 1.59-5.16), albumin (0.76; 0.70-0.82), ammonia-ULN-ratio (5.89; 3.43-10.13), model for end-stage liver disease (1.16; 1.08-1.26), and long-term oral lactulose (0.04; 0.01-0.11). The model exhibited robustness and outperformed the Stroop test for MHE identification, with areas under the receiver operating characteristic curves of 0.882 and 0.867 for the training and validation datasets, respectively. An interactive web-based nomogram is accessible at https://xc-web.shinyapps.io/dynnomapp/. CONCLUSIONS: This model enables rapid MHE screening.
BACKGROUND: Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder affecting the gastric oxyntic mucosa. Two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by H...BACKGROUND: Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder affecting the gastric oxyntic mucosa. Two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by Helicobacter pylori (Hp)-infection. In AAG, histological diagnosis of Hp may be challenging and serology can help assess exposure to Hp-infection. This study aimed to determine seroreactivity to Hp-antigens in AAG patients by using Hp-multiplex serology assay. METHODS: A single-centre case-control study on 178 adults: 75 patients with serological and histological AAG diagnosis, 25 controls with histologically Hp-positive-non-atrophic gastritis (Ctr-NAG-Hp+) and 78 subjects with a healthy stomach (Ctr-HS). Sera were analysed using Hp-multiplex serology assay allowing simultaneous detection of antibodies to 13 Hp-proteins. Overall positivity cutoff: seroreactivity to more than 3 Hp-antigens. RESULTS: The number of seroreactive Hp-antigens was higher in AAG than in Ctr-HS(mean±SEM 2.2±0.3 vs 1.4±0.22,p=0.02) and lower than in Ctr-NAG-Hp+ patients (mean±SEM 5.4±0.5,p<0.001).Overall Hp-seropositivity in AAG was two-fold higher than in Ctr-HS but not statistically significant (21.1% vs 10.3%,p=0.06) and lower than in Ctr-NAG-Hp+(80%,p<0.0001). Complete absence of seroreactivity was similar in AAG and Ctr-HS (29.3% vs 38.5%, p=0.23) and significantly higher than in Ctr-NAG-Hp+ (4%, p=0.009). Main immunogenic Hp-proteins were HP0010(GroEL),HP1098(HcpC),HP0695(HyuA),HP0875(Catalase),HP1564,HP0547(CagA) and HP0243(NapA) with seroreactivity in >50% of AAG patients. CONCLUSIONS: By Hp-multiplex serology, 30% of histologically Hp-negative AAG pts had no seroreactivity, likely belonging to the pure AAG type. Conversely, 20% of AAG pts showed Hp exposure, indicating that infection might have triggered gastric autoimmunity. The remaining AAG patients showed seroreactivity below cut-off for seropositivity and thus not definitively categorisable by this approach.
BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is a chronic type 2-mediated disease that impairs Quality of Life (QoL). Our aim was the transcultural adaptation and validation of the Adult Eosinophilic Esophagitis Quali...BACKGROUND/AIMS: Eosinophilic esophagitis (EoE) is a chronic type 2-mediated disease that impairs Quality of Life (QoL). Our aim was the transcultural adaptation and validation of the Adult Eosinophilic Esophagitis Quality of Life Questionnaire (EoE-QoL-A) for the Italian population. METHODS: Seventy participants (53 males, >18 years), completed the Italian version translated from the original EoE-QoL-A and validated scales to measure depression, anxiety and QoL. The reliability of total and sub-dimensions' scores, internal consistency, construct validity and test-retest reliability were assessed. The socio-demographic subgroups differences, mood and EoE-QoL-A correlations and the impact of sub-dimensions of EoE-QoL-A on mental and physical QoL were analyzed. RESULTS: The Italian EoE-QoL-A demonstrated excellent internal consistency (α=0.966), with all sub-dimensions had α-values>0.826 and test-retest reliability (ICC=0.982). Specifically, the Cronbach's α was 0.936 for Eating/diet impact, 0.826 for Social impact, 0.938 for Emotional impact, 0.852 for Disease anxiety, and 0.879 for Choking anxiety. Female patients reported significantly higher EoE-QoL-A than males (p < 0.05). Younger patients showed a higher score in the Social Impact dimension than older patients (p = 0.006). High scores on EoE-QoL-A were linked with high mood symptoms. The Emotional Impact domain was a significant predictor of mental health status (R=0.418). CONCLUSIONS: The Italian EoE-QoL-A is a valid, reliable and responsive tool for assessing QoL in adults with EoE. Emotional impact was the most affected dimension in the health-related QoL, highlighting the necessity for clinical strategies.
Fontaine L, Seksik P, Stefanescu C
… +40 more, Nachury M, Nancey S, Savoye G, Allez M, Altwegg R, Laharie D, Serrero M, Franchimont D, Mathieu N, Fumery M, Vuitton L, Nahon S, Gilletta C, Rouillon C, Nuzzo A, Bourreille A, Caron B, Buisson A, Amil M, Charkaoui M, Cadiot G, Caillo L, Simon M, Reenaers C, Hébuterne X, Plastaras L, Atanasiu C, Kwiatek S, Uzzan M, Pelletier AL, Benezech A, Vidon M, Goutorbe F, Geyl S, Cellier C, Montuclard C, Moussata D, Amiot A, Meyer A, GETAID-Diet-in-IBD study group
BACKGROUND: Diet and risk of developing inflammatory bowel disease (IBD) has been extensively studied. AIMS: To investigate the association between diet and IBD activity. METHODS: Consecutive outpatients in 40 French and...BACKGROUND: Diet and risk of developing inflammatory bowel disease (IBD) has been extensively studied. AIMS: To investigate the association between diet and IBD activity. METHODS: Consecutive outpatients in 40 French and Belgian centers completed diet and IBD activity questionnaire between April and May 2023 in a cross-sectional study. Associations between diet and clinical remission were adjusted for gender, age, body mass index, education, smoking, and past CD-surgery. RESULTS: Among 2514 patients included, 1715 had Crohn's disease (CD) and 799 had ulcerative colitis (UC). Overall, the mean age was 42.4 years, 52.3 % were women, and 56.4 % were in clinical remission. Among CD patients, clinical remission was associated with a higher intake of fruits (aOR 1.60 [1.20-2.14]) and coffee (aOR 1.57 [1.17-2.11]). Among UC patients, clinical remission was associated with a higher intake of fruits (aOR 1.72 [1.15-2.56]) and salad (aOR 1.73 [1.12-2.66]). A higher adherence to a Mediterranean diet was associated with CD (aOR 1.39 [1.06-1.84]) but not UC remission. A higher adherence to a healthy diet was not associated with either CD nor UC remission. CONCLUSIONS: CD remission was associated with higher intakes of fruits, coffee and a Mediterranean diet, while UC remission was associated with higher intakes of fruits and salad. As this was a cross-sectional study, the main limitation was the possibility of reverse causality.
Brigida M, Spadaccini M, Maida M
… +11 more, Almuhaidb A, Gadour E, Crinò SF, Dell'Anna G, Donatelli G, Andrisani G, Stasi E, Dell'Anna A, Hassan C, Mori Y, Facciorusso A
BACKGROUND: It is unknown if mucosal exposure device improves the adenoma detection rate (ADR) of computer-aided detection (CAD)-assisted colonoscopy. AIMS: We performed a meta-analysis of randomized-controlled trials (R...BACKGROUND: It is unknown if mucosal exposure device improves the adenoma detection rate (ADR) of computer-aided detection (CAD)-assisted colonoscopy. AIMS: We performed a meta-analysis of randomized-controlled trials (RCTs) to compare the diagnostic outcomes of these two approaches. METHODS: We identified 4 RCTs (2968 patients). ADR was the primary outcome. Advanced ADR (aADR), sessile serrated ADR (SSDR) and adenoma per colonoscopy (APC) were also compared. The results were expressed in terms of mean difference (MD) or risk ratio (RR) and 95% confidence intervals (CIs), and we used trial sequential analysis (TSA) to assess if the required information size (RIS) was reached. RESULTS: There was no difference in terms of ADR both in the overall series (RR 1.05, 0.98-1.12; p=0.16) and in screening colonoscopy (RR 1.15, 0.72-1.82; p=0.56). Although the RIS (3829 participants) was not reached, the futility boundaries were crossed suggesting a high likelihood of futility in further comparison of ADR. No difference was observed in terms of aADR (RR 1.13, 0.90-1.44; p=0.30) and SSDR (RR 1.11, 0.92-1.35; p=0.27). APC was significantly higher in the combined group (MD 0.14, 0.05 to 0.22; p=0.002). CONCLUSIONS: The addition of mucosal exposure devices does not increase ADR, aADR, and SSDR but increases APC.
Grillo F, Gambella A, Bozzano S
… +10 more, Paudice M, Piol N, Furnari M, Sciallero S, Pastorino A, Pessino AM, Parente P, Vanoli A, Fassan M, Mastracci L
BACKGROUND: Management of gastrointestinal (GI) cancers has shifted from conventional chemotherapy to biomarker-based precision oncology. Biomarker assessment requires adequate endoscopic biopsy tissue both in gastro-eso...BACKGROUND: Management of gastrointestinal (GI) cancers has shifted from conventional chemotherapy to biomarker-based precision oncology. Biomarker assessment requires adequate endoscopic biopsy tissue both in gastro-esophageal/gastric and colorectal carcinomas. AIMS: This study evaluated real-world endoscopic biopsy adequacy, focusing on tissue quality and suitability for biomarker analysis. METHODS: We retrospectively reviewed 819 endoscopic procedures (274 upper-GI and 545 lower-GI; time-window: January 2021-2024). Gastrointestinal pathologists reviewed 4,908 biopsies to assess diagnostic yield, number of invasive carcinoma-containing biopsies, and tumor cellularity. Biopsy adequacy was evaluated against European Society of Gastrointestinal Endoscopy (ESGE) recommendations and biomarker-specific cellularity thresholds. RESULTS: A histologic diagnosis of invasive carcinoma was established in 96 % of upper-GI and 84 % of lower-GI procedures (p<0.001). However, 41-43 % of procedures yielded fewer than six biopsies, which is below ESGE guidance. Importantly, only 66.7 % of upper-GI and 49.7 % of lower-GI biopsies contained invasive carcinoma, while the rest were composed of samples inadequate for biomarker testing (such as non-invasive lesions, mucin, necrosis, granulation tissue, and normal mucosa). Low neoplastic cellularity (<1000 tumor cells) was observed in 27 % of upper-GI and 5 % of lower-GI cases, while <20 % tumor cellularity was present in 41.7 % of colorectal biopsies. CONCLUSION: Optimizing sampling strategies and ensuring representative, high-cellularity specimens are essential to support precision oncology in GI cancers.
Inflammatory bowel disease is a chronic, relapsing-remitting condition with profound physical, psychological, and social consequences. Conventional therapies are essential for controlling intestinal inflammation but ofte...Inflammatory bowel disease is a chronic, relapsing-remitting condition with profound physical, psychological, and social consequences. Conventional therapies are essential for controlling intestinal inflammation but often fail to address behavioral and motivational dimensions critical for adherence, stress management, and quality of life. Health Coaching has emerged as a patient-centered intervention that fosters self-efficacy, resilience, and sustainable behavior change. This narrative review synthesizes current evidence on Health Coaching in chronic disease management and explores its potential application in Inflammatory bowel disease care. Across chronic conditions, Health Coaching has shown benefits in promoting behavioral change, improving self-management, and enhancing quality of life. Evidence in Inflammatory bowel disease, although limited, suggests Health Coaching may improve psychological well-being, treatment adherence, and coping. Early studies demonstrate feasibility, high satisfaction, and promising effects on stress, fatigue, and Inflammatory bowel disease-related disability. Health Coaching represents a promising adjunct to conventional Inflammatory bowel disease care by integrating medical, psychosocial, and behavioral competencies within a patient-centered framework. Future research should focus on standardizing protocols, clarifying the professional role of health coaches, and conducting rigorous trials to establish long-term clinical and economic impact. Integrating Health Coaching into multidisciplinary Inflammatory bowel disease management could optimize outcomes and advance holistic, value-based care.
M M, A P, S G
… +22 more, T V, Lhs L, S B, P P, M M, T Z, H U, Ejt A, D B, H D, T D, A G, T K, S L, B L, H M, R N, Y O, A R, A T, I M, World Endoscopy Organization (WEO) Emerging Stars Program
BACKGROUND: Colorectal cancer (CRC) screening reduces incidence and mortality, yet patient adherence remains suboptimal. Large language models may improve participation by addressing patient questions in native languages...BACKGROUND: Colorectal cancer (CRC) screening reduces incidence and mortality, yet patient adherence remains suboptimal. Large language models may improve participation by addressing patient questions in native languages, but their multilingual performance has not been systematically assessed. METHODS: From April to June 2025, we conducted a cross-continental study involving 28 countries and 23 languages. A standardized set of 15 CRC screening-related questions was translated into each language and submitted to ChatGPT (GPT-4o). Responses were independently evaluated by 140 gastroenterologists (five per country) for accuracy, completeness, and comprehensibility on a 5-point Likert scale. Statistical analyses included t-test, Chi-square, and two-way ANOVA. RESULTS: The study included experts and data from Europe, Asia, Africa, America, and Oceania. Mean scores (±SD) for accuracy, completeness, and comprehensibility were 4.1 ± 1.0, 4.1 ± 1.0, and 4.2 ± 0.9, respectively. Most languages achieved high ratings, with 73.9%, 86.9%, and 82.6% scoring ≥4 for accuracy, completeness, and comprehensibility. However, lower scores were observed in Chinese, Dutch, and Greek. Variability was also noted between countries sharing the same language, highlighting language- and context-dependent performance. DISCUSSION: ChatGPT showed strong ability to answer CRC screening questions across multiple languages, supporting its promise as a multilingual patient education tool. Nonetheless, regional variability requires careful validation before clinical integration.
Portal hypertension is a clinical syndrome with potentially life-threatening complications. Diagnosis and management in children are complex due to the invasiveness of hepatic venous pressure gradient measurement and the...Portal hypertension is a clinical syndrome with potentially life-threatening complications. Diagnosis and management in children are complex due to the invasiveness of hepatic venous pressure gradient measurement and the limited number of definitive treatment options, so that liver transplantation often remains the only definitive treatment. The influence of the immune system on the development of portal hypertension has recently received attention; however, the connection between portal hypertension, impaired immune response, and the development of liver changes has not yet been fully elucidated. This review provides an overview of the main current knowledge on the role of cytokines, immune cells, and other molecules involved in the inflammation and vascular changes associated with portal hypertension. A better understanding of the pathogenesis of portal hypertension could address the need to identify non-invasive markers for the diagnosis of portal hypertension and predictors of its complications in children. Furthermore, understanding the strong interaction between the immune system and the development of portal hypertension could be useful for identifying new potential therapeutic options, orienting therapeutic management towards immunomodulatory approaches.
The optimal strategy for preventing nonsteroidal anti-inflammatory drug-induced peptic ulcers in patients with prior peptic ulcers remains uncertain. We performed a systematic review and network meta-analysis of 22 rando...The optimal strategy for preventing nonsteroidal anti-inflammatory drug-induced peptic ulcers in patients with prior peptic ulcers remains uncertain. We performed a systematic review and network meta-analysis of 22 randomized controlled trials (7,768 patients) on nonsteroidal anti-inflammatory drug users with a documented ulcer history to compare the efficacy and safety of medications for the prevention of these ulcers. The eligible interventions included proton pump inhibitors, potassium-competitive acid blockers, cyclooxygenase-2 inhibitors, prostaglandin analogs, histamine-2 receptor antagonists, and gastric mucosal protective agents. The primary outcomes were ulcer recurrence and bleeding. The safety outcomes included treatment-emergent adverse events and discontinuation owing to adverse events. Random-effects network models estimated the relative and absolute risks, numbers needed to treat, and rankings. Compared with placebo, cyclooxygenase-2 inhibitor plus proton pump inhibitor, potassium-competitive acid blocker, cyclooxygenase-2 inhibitor alone, and proton pump inhibitor monotherapy markedly reduced ulcer recurrence (numbers needed to treat = 5-6). Similar patterns were observed for bleeding prevention. Prostaglandin analogs increased adverse events and discontinuations. Proton pump inhibitor monotherapy remains the most evidence-based first-line strategy for these patients. Cyclooxygenase-2 inhibitor plus proton pump inhibitors or potassium-competitive acid blockers may provide additional benefits in very high-risk patients, but safety and cost considerations warrant caution.