Potassium-competitive acid blockers (P-CABs) have emerged as a potent alternative to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease and functional dyspepsia (FD). This narrative review incorporating original meta-analyses summarizes the latest evidence from randomized controlled trials and meta-analyses, emphasizing the efficacy, safety, and clinical applications of P-CABs such as vonoprazan, tegoprazan, fexuprazan, keverprazan, and zastaprazan. P-CABs demonstrate rapid onset, sustained acid suppression, and superior healing rates in erosive esophagitis (EE), particularly in severe EE (grade C/D). Maintenance therapy in healed EE with P-CABs also yields higher endoscopic remission rates compared to PPIs. In non-erosive reflux disease, P-CABs offer rapid and sustained symptom control compared with placebo. Their pharmacologic profiles, including flexible dosing and rapid action, support on-demand therapy, potentially enhancing patient satisfaction. In addition, P-CABs may help overcome unmet needs from suboptimal efficacy of PPIs in nocturnal heartburn and extraesophageal symptoms. Emerging economic evaluation suggests P-CABs may be cost-effective in Asian healthcare systems. In FD, tegoprazan offers effective symptom relief without delaying gastric emptying, distinguishing it from PPIs. Limited clinical and real-world data indicate that second-generation P-CABs do not exhibit significant hepatotoxicity, however, long-term hypergastrinemia and mucosal changes warrant further surveillance. This review highlights the evolving role of P-CABs in gastroesophageal reflux disease and FD and emphasizes the need for further research to refine their clinical positioning, optimize therapeutic strategies, and evaluate long-term safety outcomes.

Magnesium plays an indispensable role in human health and is intricately involved in many crucial physiological and metabolic pathways. True biochemical magnesium deficiency is rarely encountered in clinical practice but subclinical and functional deficiency of magnesium appears to be more common and is reported in many chronic health disorders.

Rome V represents a major conceptual and clinical evolution in the field of disorders of gut-brain interaction (DGBI). Its most important contribution is the deliberate move away from the term "functional", a label that has often implied that symptoms are less real, less biological, or merely psychological. By emphasizing DGBI, Rome V reframes these conditions as positive diagnoses arising from altered gut-brain regulation, visceral sensitivity, motility, mucosal and immune mechanisms, microbiota, autonomic function, and central processing. Beyond terminology, Rome V introduces greater diagnostic precision. In esophageal disorders, the exclusion of gastroesophageal reflux disease and major motor disorders is aligned with Lyon Consensus 2.0 and Chicago Classification v4.0, while globus and functional chest pain are refined to avoid unnecessary interventions. In gastroduodenal disorders, functional dyspepsia is better phenotyped according to meal-related symptoms, with clearer distinctions from chronic nausea and vomiting syndrome, gastroparesis, cyclic vomiting syndrome, cannabinoid hyperemesis syndrome, rumination, and inability to belch. In bowel disorders, Rome V reintroduces abdominal discomfort into IBS criteria, changes the symptom frequency threshold, renames functional constipation as chronic constipation, and redefines abdominal bloating/distension. The anorectal section is particularly relevant because it operationalizes fecal incontinence, defines dyssynergic defecation using objective testing, and formally recognizes rectal hypo- and hypersensitivity, which may guide biofeedback therapy. Rome V also raises future challenges: implementation in clinical practice, patient-centered communication, avoidance of reductionism, development of mechanism-based research, and interpretation of forthcoming epidemiological data. Overall, Rome V promotes precision, reduces stigma, and supports more rational, mechanism-based care.

Circadian rhythms exert fundamental control over gastrointestinal and metabolic physiology, governing 24-hour patterns of motility, secretion, nutrient absorption, microbial activity, immune regulation, and hepatic metabolism. Accumulating evidence indicates that the gastrointestinal tract is not an isolated system but is tightly integrated with systemic metabolic and neuroendocrine networks, forming a coordinated gastro-circadian metabolic axis (GCMA). This axis links molecular clocks in the gut, liver, adipose tissue, and skeletal muscle with rhythmic inputs from the gut microbiome, feeding-fasting cycles, autonomic signaling, and enteroendocrine mediators. Disruption of circadian alignment, through shift work, sleep deprivation, irregular meal timing, or nocturnal light exposure, leads to desynchronization between central and peripheral clocks, promoting inflammation, impaired epithelial barrier function, dysbiosis, altered bile acid signaling, insulin resistance, and disturbed energy homeostasis. These mechanisms contribute to a wide spectrum of gastrointestinal disorders, including gastroesophageal reflux disease, functional dyspepsia, irritable bowel syndrome, metabolic dysfunction-associated steatotic liver disease, inflammatory bowel disease, and potentially gastrointestinal malignancies. This review synthesizes molecular, translational, and clinical evidence to position the GCMA as a unifying framework for understanding circadian influences on digestive and metabolic disease. Importantly, it highlights emerging therapeutic opportunities in chronotherapy, including time-optimized pharmacotherapy, chrononutrition, and microbiota-targeted interventions. While current translation is limited by interindividual chronotype variability and heterogeneous clinical evidence, advances in wearable circadian monitoring, multi-omics profiling, and computational modeling offer promising avenues for precision implementation. Integrating GCMA principles into clinical practice may improve disease outcomes and establish circadian alignment as a cornerstone of preventive and therapeutic gastroenterology.

Background: Gastroesophageal reflux symptoms (GERSs) represent the most prevalent phenotype of gastroesophageal reflux disease and frequently overlap with the symptoms of functional dyspepsia, posing diagnostic and therapeutic challenges. Limitations of long-term acid suppression have prompted interest in alternative mucosa-protective approaches. This study was conducted to evaluate the effectiveness of a novel multicomponent formulation (Tamacid-Pro®) in patients with reflux-like symptoms and negative endoscopy. Methods: In this prospective observational study, consecutive adult patients undergoing upper gastrointestinal endoscopy at a tertiary centre between January 2025 and February 2026 were screened. Patients with upper gastrointestinal symptoms lasting ≥2 months, negative endoscopy, and no evidence of Helicobacter pylori infection were enrolled. Participants received Tamacid-Pro® three times daily for 3 months. Symptom frequency and intensity were assessed at baseline and after treatment using the Reflux Disease Questionnaire (RDQ). Changes over time were analyzed using paired t-tests, and multivariable linear regression was performed to identify response predictors. Results: A total of 1035 patients were included. After 3 months of treatment, all RDQ items showed a statistically significant improvement in both frequency and intensity (p < 0.0001). Significant reductions were observed in the GERD composite score, as well as in heartburn, regurgitation, and dyspepsia dimensions (all p < 0.0001). In a multivariable analysis, female sex was independently associated with greater improvement across multiple symptom domains, whereas alcohol consumption was negatively associated with improvement in the heartburn dimension. Conclusions: In this large real-world cohort of endoscopy-negative patients, treatment with Tamacid-Pro® was associated with significant improvement in both typical reflux and dyspeptic symptoms. These findings support the role of multicomponent, mucosa-protective formulations as a valuable therapeutic option in patients with GERSs and overlapping functional gastrointestinal disorders.

Potassium-competitive acid blockers (P-CABs) represent a major advancement in acid suppression by achieving rapid and sustained inhibition of gastric acid secretion. However, stronger acid suppression does not necessarily lead to better clinical outcomes. The clinical benefits of P-CABs vary according to the disease. In gastroesophageal reflux disease, P-CABs achieve healing rates for erosive esophagitis that are comparable to those of proton pump inhibitors (PPIs), with possible advantages in severe cases; however, consistent superiority in symptom control is lacking. The evidence for functional dyspepsia also remains insufficient. By contrast, in Helicobacter pylori eradication, P-CAB-based regimens have demonstrated clear advantages, particularly in the presence of antibiotic resistance. In peptic ulcer disease, the efficacy of P-CABs is comparable to that of PPIs. Long-term safety, including the effects of sustained hypergastrinemia, remains uncertain. Furthermore, symptom improvement and mucosal healing are not always concordant, thus highlighting the need to define therapeutic goals. Therefore, P-CABs should be used selectively on the basis of disease-specific requirements rather than pharmacological potency alone. An individualized approach is essential to optimize outcomes and avoid the unnecessary escalation of acid-suppressive therapy.

Background/Objectives. Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly affects patients' quality of life (QoL). However, data on disease severity and its correlation with QoL among Vietnamese patients remain limited. This study aimed to investigate the clinical characteristics, symptom severity, and the relationship between symptom burden and quality of life in patients with IBS-D in Vietnam. Methods. A cross-sectional study was conducted on patients diagnosed with IBS-D based on the Rome IV criteria at an outpatient clinic of a tertiary hospital. Disease severity and QoL were assessed using the IBS Symptom Severity Score (IBS-SSS) and the standardized Vietnamese version of the IBS Quality of Life (IBS-QoL) questionnaire, respectively. Clinical characteristics, comorbidities, and overlap syndromes were also recorded. Results. Among the 123 patients enrolled (mean age 42.6 ± 14.5 years; 55.3% female), the median IBS-SSS score was 175 (interquartile range: 140-225), and the median IBS-QoL score was 72 (interquartile range: 54-85). The prevalence of overlap syndromes was relatively high, with functional dyspepsia accounting for 46.3% and gastroesophageal reflux disease for 8.9%. A moderate inverse correlation was observed between IBS-SSS and IBS-QoL scores (r = -0.494; p < 0.001). Notably, patients with severe IBS (IBS-SSS ≥ 300) had significantly higher rates of smoking (44.4% vs. 13.2%; p = 0.012) and diabetes (22.2% vs. 5.3%; p = 0.047) compared to the non-severe group. Conclusions. IBS-D imposes a substantial symptom burden and significantly reduces the quality of life in Vietnamese patients, particularly among those with severe disease. The high prevalence of overlap syndromes, along with contributing factors like smoking and diabetes, further increase the complexity and severity of the condition.

BACKGROUND Sarcoidosis, a rare multisystem disease characterized by non-caseating granulomas, affects the gastrointestinal system in less than 1% of cases, mainly involving the gastric antrum. Most cases are asymptomatic and are discovered incidentally during endoscopy; fewer than 1% of patients present with symptoms such as gastroesophageal reflux disease (GERD), dyspepsia, or bleeding. The relationship between gastric sarcoidosis and GERD is not well understood, posing diagnostic and treatment challenges that are not fully addressed in the current literature. This report describes a case of incidentally discovered gastric sarcoidosis presenting as GERD that improved without immunosuppressive therapy. To facilitate management, we propose an algorithm for managing GERD symptoms in the context of gastric sarcoidosis. CASE REPORT A 48-year-old man with pulmonary sarcoidosis - in remission for 7 years - presented for endoscopic evaluation of GERD and nonspecific chest pain. Vital signs, physical examination, and routine laboratory results, including a cardiac workup, were unremarkable. Upper gastrointestinal endoscopy revealed grade A esophagitis and a 6-mm antral papule. Histopathologic examination of the biopsy specimen revealed non-caseating granulomas consistent with gastric sarcoidosis. The patient's symptoms improved with escalated proton pump inhibitor therapy; immunosuppression was not required. Rheumatology consultation recommended no additional treatment, given his clinically quiescent disease and improvement in GERD symptoms. CONCLUSIONS This case highlights the diagnostic uncertainty of GERD in the presence of gastric sarcoidosis and emphasizes the importance of personalized, multidisciplinary management.

Gastroesophageal reflux disease (GERD) is a chronic relapsing disorder often inadequately controlled with proton pump inhibitors (PPIs), particularly in patients with nocturnal acid breakthrough (NAB) or non-erosive reflux disease (NERD). Tegoprazan, a potassium-competitive acid blocker (PCAB), offers rapid, potent, and CYP2C19-independent acid suppression. This systematic review and meta-analysis evaluated randomized controlled trials comparing Tegoprazan with PPIs in adults with GERD and related disorders. Databases searched included PubMed, Cochrane, Wiley, and ClinicalTrials.gov (2015-2026). Eighteen studies met inclusion criteria. In erosive esophagitis, Tegoprazan 50 mg once daily achieved mucosal healing rates of 91.1%-99.1%, non-inferior to PPIs (93.5%-98.9%; pooled RR = 1.01, 95% CI 0.98-1.05). Pharmacodynamic and clinical studies demonstrated faster acid suppression and improved nocturnal pH control versus PPIs, achieving pH ≥ 4 within 30-60 min and maintaining levels throughout the 12-h period. In nocturnal symptom analyses, Tegoprazan achieved earlier relief (1.5 vs. 3 days to first heartburn-free night) and higher proportions of heartburn-free nights (57.8% vs. 43.1%), with significantly greater complete (p = 0.038) and partial (p = 0.034) nighttime symptom resolution than Esomeprazole. In NERD, symptom resolution ranged from 42.5% to 48.9% versus 24.2% with placebo. In open-label functional dyspepsia cohorts, improvements ranged from 74.6% to 86.7% in open-label cohorts. Seven trials (n = 2492) showed higher Helicobacter pylori eradication with Tegoprazan-based therapy (RR = 1.05, 95% CI 1.01-1.09; p = 0.006; I 2 = 0%). Adverse events were mild and comparable to PPIs. Tegoprazan provides rapid, sustained acid suppression, effective nocturnal symptom control, and a modest but statistically significant improvement in H. pylori eradication, representing a potential alternative to PPIs for patients with persistent or CYP2C19-related variable response.