BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results.
METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis.
RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort.
CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

OBJECTIVE: Vocal process granuloma (VPG) is a chronic condition resulting from a mucoperichondrial injury of vocal process. Initial conservative treatment typically involves vocal hygiene education and antireflux medication. Treatment challenges arise with refractory cases. Outcomes of second-line treatments such as surgical excision and botulinum toxin injections remain inconsistent. Thus, we propose this study to investigate the effectiveness of intralesional steroid injections for refractory VPG.
METHODS: We conducted a retrospective review of 23 patients with VPG who showed no improvement after 3 months of proton pump inhibitors. These patients underwent one to three courses of monthly in-office intralesional steroid injections as a second-line therapy. Treatment outcomes were evaluated by measuring the size of the VPG relative to the length of the vocal folds before and after the final injection procedure.
RESULTS: Results showed a significant reduction in VPG size from baseline of 27.74 ± 15.06 to 5.48 ± 8.95 (p < .001). 15 out of 23 patients were responsive (size reduction ≥ 75%) to intralesional steroid injection. Alcohol consumption and longer symptom duration were associated with a poor response (size reduction <75%), whereas prior intubation was associated with better response.
CONCLUSIONS: For refractory VPG not responding to conservative treatment, intralesional steroid injection appears to be a promising alternative option without significant adverse effects.

Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder posing diagnostic and therapeutic challenges. Diagnosis should be objectively defined with endoscopy and pH testing, while novel metrics may augment diagnosis for inconclusive GERD cases, including the postreflux swallow-induced peristaltic wave index and esophageal mucosal impedance. Conditions that overlap with or mimic GERD should be considered such as achalasia, rumination, and eosinophilic esophagitis. Genetic testing for proton pump inhibitor metabolism is an option for precision therapy in complex persistent GERD. Proton pump inhibitor refractory GERD may require medical, surgical, or endoscopic therapies. The presence of GERD should be objectively evaluated in achalasia patients treated with peroral endoscopic myotomy, and further studies are needed to determine timing of this evaluation. Patients with scleroderma are at a high risk for GERD owing to abnormal esophageal motility and should be managed with aggressive medical therapy and lifestyle changes given the high prevalence of esophagitis and Barrett\'s esophagus in this population. Further studies are needed to understand the complex mechanisms of GERD in idiopathic pulmonary fibrosis and lung transplantation.

UNASSIGNED: Vonoprazan-based eradication therapies have a higher eradication rate than usual proton pump inhibitor (PPI)-based therapies in treating Helicobacter pylori infection. Should we use vonoprazan to treat patients who failed multiple eradication therapies? Because the drug is not available in most countries, we propose 2-dimension tailor-made therapy (2dTMT) without using vonoprazan.
UNASSIGNED: Patients who failed twice or more PPI-based triple therapies were recruited. Patients underwent CYP2C19 genotype and antibiotic susceptibility tests (ASTs). PPI doses per day were decided as per the CYP2C19 genotype: twice for poor and 4 times for extensive metabolizers (dimension 1). Two antibiotics were selected as per the results of the AST in each patient (dimension 2). Regimens of 2dTMT included 2 susceptible antibiotics and a PPI. For those who could not have enough information with the AST, tailor-made PPI dosing was indicated with empirically selected 2 antibiotics (one-dimension tailor-made therapy [1dTMT]).
UNASSIGNED: Of 51 candidates with multiple eradication failures, 37 patients underwent the genotype test and AST, and 24 succeeded to obtain sufficient information to select 2 susceptible antibiotics. Of them, 22 patients accepted to receive 14-day 2dTMT. Of the residual patients, 12 accepted to receive 14-day 1dTMT. The mean eradication rate of 2dTMT was 86.4% (95% confidence interval [CI]: 65.1%-98.8%) in intention-to-treat and 90.5% (95% CI: 69.6%-98.8%) in per-protocol analyses, whereas that of 1dTMT was 75.0% (95% CI: 42.8%-94.5%) in intention-to-treat and 90.0% (95% CI: 55.5%-99.7%) in per-protocol analyses.
UNASSIGNED: Without vonoprazan, 14-day 2dTMT could be one of the salvage therapies for patients with multiple eradication failures. In cases of insufficient information with the AST, 14-day 1dTMT could be an alternative therapy. Clinical Trials Registry number, UMIN000022154 (https://www.umin.ac.jp/icdr/index.html).

Our understanding of the use of acid-suppressant drugs (ASDs) in companion animals is largely centered around the treatment of acid-related disorders including gastroesophageal reflux and gastrointestinal ulceration. The companion article by Grady et al, JAVMA, October 2024, summarizes our current knowledge of the efficacy of and indications for ASDs for the treatment of acid-related disorders. Far less is understood about both the benefits of and potential for adverse effects of ASDs outside of the parietal cell including those directed toward inflammation and immunomodulation, tumorigenesis, fibrosis, and oxidative stress. In this Currents in One Health article, we summarize the pH-independent properties of ASDs as demonstrated in studies conducted largely in humans and rodents. The objective of this review is to highlight and increase awareness of the pH-independent effects of ASDs to elucidate the need for further veterinary research in this area.

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OBJECTIVE: Post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been shown to influence proton pump inhibitor (PPI) response in GERD patients. However, currently, little data concerning these variables in patients with reflux hypersensitivity (RH) are available. In this study, we aimed to evaluate, in RH patients, the prevalence of PPI responders and nonresponders and investigate the predictive value of impedance-pH variables, including PSPW and MNBI, on responses to PPI.
METHODS: A total of 108 RH patients who met ROME IV criteria were prospectively recruited from June 2018 to December 2022. The prevalence of PPI responders/nonresponders was calculated, and impedance-pH variables were compared between the response and nonresponse groups. Multiple logistic regression was used to investigate predictors for PPI response.
RESULTS: Among 108 patients with RH, 60 patients (55.56%) were the PPI responders, and 48 (44.44%) were the nonresponders. Compared with the nonresponders, the PPI responders had a lower PSPW index (47.05 ± 4.43 vs 51.33 ± 3.50, P = 0.004) and a decreased value of MNBI (1866.68 ± 390.62 vs 2181.14 ± 338.42, P = 0.017). Multivariate logistic regression revealed that only the pathologic PSPW index (OR: 2.064) and MNBI (OR: 1.800) significantly influenced PPI response.
CONCLUSIONS: Nearly half of RH patients were PPI nonresponders. Impedance-pH monitoring was more valuable than pH-only monitoring in associating PPI response to reflux in RH patients owing to the appraisal of the PSPW index and MNBI.

OBJECTIVE: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD.
METHODS: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events.
RESULTS: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p = .036 and .045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough.
CONCLUSIONS: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI.
BACKGROUND: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100 .

BACKGROUND: Proton pump inhibitors (PPIs) reportedly reduce upper gastrointestinal bleeding (UGIB) in patients undergoing percutaneous coronary intervention (PCI). However, whether the benefits of PPIs differ in high-risk subgroups is unknown.
RESULTS: Among 24,563 patients undergoing first PCI in the CREDO-Kyoto registry Cohort-2 and -3, we evaluated long-term effects of PPI for UGIB, defined as GUSTO moderate/severe bleeding, in several potential high-risk subgroups. In the study population, 45.6% of patients were prescribed PPIs. Over a median 5.6-year follow-up, PPIs were associated with lower adjusted risk of UGIB (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.50-0.80; P<0.001) and a non-significant but numerically lower risk of any gastrointestinal bleeding (HR 0.84; 95% CI 0.71-1.01; P=0.06). PPIs were not associated with a lower risk of GUSTO moderate/severe bleeding (HR 1.04; 95% CI 0.94-1.15; P=0.40) or a higher adjusted risk of myocardial infarction or ischemic stroke (HR 1.00; 95% CI 0.90-1.12; P=0.97), but were associated with higher adjusted mortality risk (HR 1.18; 95% CI 1.09-1.27; P<0.001). The effects of PPIs for UGIB, myocardial infarction or ischemic stroke, and all-cause death were consistent regardless of age, sex, acute coronary syndrome, high bleeding risk, oral anticoagulant use, and type of P2Y12inhibitor.
CONCLUSIONS: PPIs were associated with a lower risk of UGIB and a neutral risk of ischemic events regardless of high-risk subgroup.

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