High-dose Proton Pump Inhibitor Research Articles

Evolution of the use, effectiveness and safety of bismuth-containing quadruple therapy for Helicobacter pylori infection between 2013 and 2021: results from the European registry on H. pylori management (Hp-EuReg)

BackgroundBismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of...

First-line Helicobacter pylori empirical treatment in the Czech Republic (2019–2024) – initial insights from the European registry on H. pylori management (Hp-EuReg)

Summary: Background and Aim: Helicobacter pylori (H. pylori) infection remains a significant public health concern worldwide, including in the Czech Republic. The study aims to provide an overview of the current first-line treatment approaches for H. pylori infection in the Czech Republic based on data from the European Registry on H. pylori Management (Hp-EuReg), and to evaluate the most effective treatment regimens. Methods: Hp--EuReg is an international multicentric registry on the management of H. pylori, from which we extracted data from the Czech Republic from 2019 to January 2024. This registry collects demographic information, diagnostic procedures, treatment prescriptions, and outcomes for H. pylori infection management by gastroenterologists. A modified intention-to-treat (mITT) analysis was performed to evaluate the effectiveness of the treatments. Results: A total of 546 patients from 14 centres in the Czech Republic who receive first-line treatment were analysed. Low-dose (i.e.; 20 mg omeprazole equivalent twice daily) proton pump inhibitors (PPIs) were administered in 89% of patients, and the most common length of treatments was 14 days (40%). The overall mITT effectiveness of first-line treatment was 85%, obtaining 86% when prescriptions were combined either with low-dose (20 mg omeprazole equivalent twice daily), and high dose (80 mg omeprazole equivalent twice daily) PPIs, and 82.5% with standard-dose (40 mg omeprazole equivalent twice daily) PPIs. The effectiveness of 7-day prescriptions was reported to be 83%, lower than that of 10- and 14-day, both of which achieved effectiveness of 86%. The most frequently used treatment scheme was triple therapy with PPI, amoxicillin and clarithromycin, which was used in 67% of patients, reaching 87% effectiveness both with 7- and 14-day prescriptions. Optimal (>90% mITT) effectiveness was obtained with both 10-day, sequential therapy and with 14-day non-bismuth quadruple concomitant therapy including both PPI, amoxicillin, clarithromycin and metronidazole, providing 96% (48/50 patients) and 97% (34/35 patients) cure rates, respectively. The remaining therapies provided all an effectiveness lower than 90%, the lowest one obtained with PPI, clarithromycin and metronidazole (66%; 35/53 patients). Conclusions: In the Czech Republic, the first-line empirical treatment overall effectiveness was suboptimal (<90%); however, 10-day non-bismuth quadruple sequential and 14-day concomitant therapies, both composed of PPI, amoxicillin, clarithromycin and metronidazole, achieved over 90% cure rates. Key-words: Helicobacter pylori – first-line treatment – proton pump inhibitors – Czech Republic

Immune-related gastritis: An orphan immune-related adverse event.

e24138 Background: Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology with a significant impact on patients' survival. However, they are not without shortcomings, with 70-90% of patients experiencing immune-related adverse events (irAEs(. Immune-related gastritis is a relatively uncommon irAE, literature publications are scarce and limited to case reports. We aimed to investigate this rare irAE to enhance understanding and improve patient care for oncologists and gastroenterologists. Methods: We performed a retrospective review of medical records of all cancer patients treated with ICI who completed upper gastrointestinal endoscopy during ICI treatment, at a single tertiary center between 2017 and 2023. Results: Of 2553 patients receiving immunotherapy at our medical center, 64 completed upper gastrointestinal endoscopy, and 18 (0.7%) had either endoscopic or microscopic gastritis or both. Overall, 17 (94%) patients with gastritis were symptomatic compared to only 31 of 46 patients (67%) without gastritis (p = 0.025). Epigastric pain was the most common symptom and was experienced by seven (39%) patients with gastritis, and eight (17%) patients without gastritis (P = 0.068). Other symptoms in patients with gastritis were gastrointestinal bleeding (28%), nausea (17%) and vomiting (11%). However, gastrointestinal bleeding (17%), nausea (9%), and vomiting (11%) were also experienced by patients without gastritis at similar rates (P > 0.05 for all comparisons). Two patients had grade 4 and two patients had grade 3 immune-related gastritis. Symptoms resolved in all patients, though most patients continued ICI (77%). Ten patients were treated with high-dose proton pump inhibitors (PPIs), and only four were treated with corticosteroids. Overall survival in patients experiencing gastritis was 40 months and did not differ from that of patients without gastritis (p = 0.929). Conclusions: Immune-related gastritis is an infrequent and non-lethal adverse event. Diagnosis is challenging due to non-specific symptoms, that are common among cancer patients undergoing antineoplastic therapies. Nonetheless, upon diagnosis, treatment with high doses PPIs with or without corticosteroids leads to prompt resolution.

#2633 Navigating complexity: a case report of chronic kidney disease with renal stone unravelling a rare metabolic disorder

Abstract Clinical Presentation A 48-year-old female of Asian heritage was referred for renal assessment after experiencing recurrent acute kidney injury (AKI) with incomplete recovery between episodes. This was initially attributed to dehydration and interstitial nephritis stemming from long-standing vomiting, a manifestation of gastroscopy-proven erosive gastritis, compounded by the use of high-dose proton pump inhibitors (PPI). Her relevant medical history is of right nephrectomy in 1996 due to recurrent urinary tract infections (UTIs), and previous left renal calculus in 2019 with no visible stones on further CT imaging. Despite living with a single kidney, her baseline eGFR had been normal prior to referral. While unaware of her mother's medical history, her father was recently diagnosed with kidney disease (no clear history) and her sister Wilson's disease. A kidney biopsy was undertaken given the incomplete eGFR recovery between episodes. The biopsy revealed adequate tissue including 24 glomeruli, no significant glomerular pathology was seen. There is 65% tubulointerstitial atrophy and fibrosis, and yellow to red-brown-tinged crystals within tubular lumina and epithelial cells, prompting a histiocytic reaction. These crystals were birefringent under polarized light and did not stain with Perl's and Von Kossa stain (Fig. 1a-d). Immunofluorescence was negative for all immunoglobulins and complement fractions. No immune complex/substructure deposits were seen in the glomeruli on electron microscopy. Blood tests assessing APRT activity indicated values within the carrier range (Table 1). The patient and her family have been referred for a comprehensive genetic testing for APRT genetic mutations. Treatment with Allopurinol 300 mg daily resulted in a sustained eGFR improvement from 19 to 33 ml/min/1.73m2 at 6 months after initiation (Fig. 1). Discussion Adenine phosphoribosyl transferase (APRT) deficiency, also known as Dihydroxyadenineuria, is a rare autosomal recessive inherited condition leading to kidney stones. If left untreated, up to 25% progress to end-stage kidney disease (ESKD). Although inherited, half of patient present in adulthood and may do so with laboratory findings of CKD rather than specifically with stones [1]. This case highlights the significance of precise diagnosis in calculi-related kidney diseases. Early intervention can alter the trajectory of specific conditions, averting progression to ESKD. This case is unusual in being a carrier of an autosomal recessive condition presenting with full manifestations of the disease. Patient Consent The patient has given verbal, documented consent for case publication. Acknowledgment We thank all renal and pathology staff members at Salford Care Organisation who contributed to the diagnosis and management of our case.

Proton pump inhibitor therapy after transcatheter angiography in refractory nonvariceal acute upper gastrointestinal bleeding patients: a cohort study.

Transcatheter angiography (TA) could help to diagnose and treat refractory nonvariceal upper gastrointestinal bleeding (NVUGIB). Proton pump inhibitors (PPIs) are the key medication for reducing the rebleeding rate and mortality and are usually continued after TA. It is unknown whether high-dose PPIs after TA are more effective than the standard regimen. We retrospectively collected data from patients who received TA because of refractory NVUGIB from 2010 to 2020 at West China Hospital. 244 patients were included and divided into two groups based on the first 3 days of PPIs treatment. All baseline characteristics were balanced using the inverse probability of treatment weighting method. The 30-day all-cause mortality, rebleeding rate and other outcomes were compared. The propensity score matching method was also used to verify the results. There were 86 patients in the high-dose group and 158 in the standard group. The average daily doses of PPI were 192.1 ± 17.9mg and 77.8 ± 32.0mg, respectively. Cox regression analysis showed no difference in the 30-day all-cause mortality (aHR 1.464, 95% CI 0.829 to 2.584) or rebleeding rate (aHR 1.020, 95% CI 0.693 to 1.501). There were no differences found in red blood cell transfusion, hospital stay length and further interventions, including endoscopy, repeating TA, surgery and ICU admission. The results were consistent in the subgroup analysis of patients with transcatheter arterial embolization. In refractory NVUGIB patients who received TA, regardless of whether embolization was performed, high-dose PPI treatment did not provide additional benefits compared with the standard regimen.

Genetic variations of penicillin-binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia.

Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy.Hypothesis/Gap Statement. The high eradication rate with amoxicillin-based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently.Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori, correlating with amoxicillin resistance in the Malaysian population.Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori-positive treatment-naïve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin-resistant strains (n=20) and amoxicillin-sensitive strains (n=23).Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP-motif (SKN402-404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context.Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin-based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.

Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial

High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aimed to compare the efficacy of vonoprazan vs PPI for preventing high-risk PU rebleeding after hemostasis. A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20 mg twice a day for 3 days, then 20 mg once a day for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/h for 3 days, then omeprazole 20 mg twice a day for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3-and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable between the 2 groups. The 30-day rebleeding rates in vonoprazan and PPI groups were 7.1% (7 of 98) and 10.4% (10 of 96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference,-3.3; 95% confidence interval,-11.2 to 4.7; P < .001). The 3-day and 7-day rebleeding rates in the vonoprazan group remained noninferior to PPI (P<.001 by Farrington and Manning test). All secondary outcomes were also comparable between the 2 groups. In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI. (ClinicalTrials.gov, Number: NCT05005910).

Helicobacter pylori eradication with high-dose proton pump inhibitor-amoxicillin dual therapy: A systematic review and meta-analysis

BackgroundResistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent. AimsThis study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study. MethodsSeveral open public databases, including Cochrane, EMBASE, PubMed, and MEDLINE, were searched. The results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapies were analysed. Notably, 14 out of the 16 included studies were conducted in Asian regions. ResultsThe eradication rate of HDDT was lower but not significantly different from those of control therapies (odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.67–1.26) in the intent-to-treat (ITT) analysis. A similar trend was observed in the per-protocol (PP) analysis (OR = 0.88, 95% CI = 0.47–1.63). Notably, the adverse effect risk in HDDT was significantly lower than in other therapies (I2 = 67.75%, OR = 0.42, 95% CI = 0.33–0.54, P = 0.00004). When the eradication rate of the control group was lower than 81%, HDDT was significantly better than control therapies (OR = 2.44, 95% CI = 1.23–4.84). ConclusionHDDT used four times a day for 14 days showed better efficacy and safety than the guideline treatments for H. pylori infection in areas with high antimicrobial resistance.

A169 A RARE MANIFESTATION OF ENTERITIS DUE TO IMMUNE CHECKPOINT INHIBITOR: CASE REPORT OF PYLORIC STRICTURE

Abstract Background Immune checkpoint inhibitors (ICI) are immunomodulatory antibodies used to enhance the immune response against tumor cells that have revolutionized the treatment of various malignancies. ICIs pose a risk of immune-related adverse events in various organs including the gastrointestinal tract, with diarrhea and colitis being most common. ICIs can rarely cause involvement of the upper gastrointestinal tract, with case reports of gastritis, duodenitis, and esophagitis. There are very rare reports of strictures caused by ICIs, more frequently in the lower gastrointestinal tract, and only a few reports in the esophagus or duodenum. Aims We report a rare case of an upper gastrointestinal stricture due to ICI at the pylorus. Methods Case report. Results A 38-year-old woman with breast cancer on ICI pembrolizumab presented with several weeks of nausea and early satiety. She had started pembrolizumab 8 months prior, underwent neoadjuvant chemotherapy and mastectomy months ago, and completed radiation 6 weeks earlier. She also described nocturnal reflux and heartburn, but no vomiting, weight loss, or other gastrointestinal symptoms. Her examination was normal and recent bloodwork only showed a mild normocytic anemia. EGD (esophagogastroduodenoscopy) showed friable circumferential ulceration of the distal antrum with surrounding erythema and luminal narrowing from the pyloric channel to duodenum. 1-centimetre gastroscope was not passable but 4.9-millimetre pediatric gastroscope passed into the duodenum where there were no abnormalities past the duodenal bulb. Pathology showed granulation tissue, fibrinopurulent exudate, and antral mucosa with chronic active inflammation negative for Helicobacter pylori and malignancy. Oncology felt that radiation was too far from the pylorus to be responsible for the findings. High-dose proton pump inhibitor (PPI) and soft diet were recommended with minimal symptomatic improvement. 2 months later, she developed weight loss and repeat EGD showed minimal endoscopic improvement (Figure 1). ICI-related enteritis was suspected and she was started on prednisone 50 mg daily. Her appetite and nausea significantly improved. Steroid taper was planned for 8 weeks. At 3 months, symptoms recurred with prednisone taper. EGD showed only mild improvement of the duodenal stricture. Prednisone dose was increased. On repeat EGD at 7 months, the pylorus was patent with only granular inflammation predominantly in the apex of the duodenal bulb. She tolerated a slower prednisone taper thereafter. Conclusions ICI-related inflammation is common in the lower gastrointestinal tract and can less commonly affect the upper gastrointestinal tract. This is a rare report of upper gastrointestinal stricture and the first report known to us of pyloric stricture caused by ICI. Treatment may be challenging, but was achieved with PPI and high-dose steroids with slow taper. Funding Agencies None

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

Helicobacter pylori Eradication Treatment in Older Patients.

Helicobacter pylori is the main etiopathogenetic factor of chronic gastritis, peptic ulcer disease and gastric cancer. The world's population is shifting towards older people, who have the highest prevalence of H. pylori. Aging-related peculiarities could have an impact on the treatment of H. pylori and there is still a lack of research data in the older population. The aim of this review was to summarize the findings of the most recent information, publications and studies on the issues relating to H. pylori infection in older patients. H. pylori eradication offers gastrointestinal and extra gastrointestinal benefits in older patients. Based on the main guidelines, H. pylori should be eradicated independent of the patient's age, only reconsidering cases with terminal illness and low life expectancy. Proton pump inhibitors are generally safe and well tolerated. Some antibiotics require dose adjustment only in advanced renal insufficiency and the risk of hepatotoxicity is very low. Special precautions should be taken in patients with polypharmacy and those taking aspirin or non-steroidal anti-inflammatory drugs. In older patients, H. pylori eradication treatment frequently causes only mild and short-term adverse events; however, treatment compliance is usually still very good. H. pylori treatment in older patients does not increase the risk of Clostridium difficile infection. Optimal eradication effectiveness (>90%) is mostly achieved with bismuth- and non-bismuth-based quadruple therapies. Susceptibility-guided treatment of H. pylori can contribute to increasing the effectiveness of eradication regimens in older adults. To achieve optimal H. pylori eradication effectiveness in older patients, the same guidelines, which are applied to adults, also apply to this population: avoiding repetitive treatment prescriptions, choosing quadruple therapies, prescribing longer treatment duration and administering high-dose proton pump inhibitors twice daily.

Eosinophilic esophagitis in children: A cross-sectional study from a tertiary care center.

The prevalence of eosinophilic esophagitis (EoE) is rising in the West. However, data from the Indian subcontinent is limited. In this prospective cross-sectional study, we estimated the prevalence of EoE among children undergoing elective upper gastrointestinal endoscopy (UGIE). We enrolled 200 consecutive children (123 boys, median age 10.25 years [interquartile range 8.25-14.5]) between March 2020 and November 2022 at our center. Clinical characteristics, endoscopic findings, and laboratory parameters were noted. A total of 12 mucosal biopsies (3 each from the middle and lower third of the esophagus, stomach, and duodenum) were obtained. EoE was diagnosed if the peak eosinophil count was ≥15/high-power field (HPF) in absence of gastric and duodenal eosinophilia. The commonest indications for UGIE were gastroesophageal reflux disease-like symptoms (29%), inflammatory bowel disease (22.5%), celiac disease (15%), and abdominal pain (13%). EoE was detected in seven children, suggesting an overall prevalence of 3.5%. Of the 20 children evaluated for dysphagia, 4 (20%) had EoE. Also, two of three (67%) children presented with food bolus impaction along with dysphagia had EoE. Of the seven children with EoE, three (43%) had bronchial asthma, two (28.5%) had peripheral eosinophilia, and one (14%) had elevated serum IgE. Trachealization and linear furrows were found in 57% and 71% cases, respectively. Four children received high-dose proton pump inhibitor (PPI) for 12 weeks, two received PPI+ stricture dilatation, and one received systemic steroids. All achieved clinical, endoscopic, and histopathological remission. Hospital-based prevalence of EoE among children undergoing elective UGIE was 3.5%. EoE patients had favorable outcomes with PPI.

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

S461 Dupilumab Efficacy in Eosinophilic Esophagitis Persists for Histologic, Symptomatic, and Endoscopic Outcomes Regardless of Concomitant High-Dose Proton Pump Inhibitor Use

S461 Dupilumab Efficacy in Eosinophilic Esophagitis Persists for Histologic, Symptomatic, and Endoscopic Outcomes Regardless of Concomitant High-Dose Proton Pump Inhibitor Use

CYP2C19 genotypes and osteoporotic fractures in long-term users of proton pump inhibitors: A hospital-based study.

Proton pump inhibitors (PPIs) are commonly prescribed medications. The existing data suggest that individuals at a high risk of fractures have been exposed to high doses of PPIs for prolonged durations. CYP2C19 plays a pivotal role in metabolism of PPIs and thereby influences their pharmacokinetic profile. Hence, we hypothesize that CYP2C19 genotypes may be associated with fragility fracture among PPIs users due to PPI exposure. This study aimed to investigate the association between CYP2C19 genotypes, bone mineral density (BMD), and osteoporotic fracture in a hospital-based population. This retrospective cohort study enrolled patients who were prescribed long-term PPIs at Taichung Veterans General Hospital using data extracted from the Taiwan Precision Medicine Initiative between January 2010 and April 2021. Associations between CYP2C19 phenotypes, comorbidities, and fractures in PPI users were analyzed. We enrolled 1518 long-term PPI users; 571 (38%), 727 (48%), and 220 (14%) CYP2C19 normal metabolizers (NMs), intermediate metabolizers (IMs), and poor metabolizers (PMs), respectively. Among them, 49 (3.2%) patients developed fractures within the 1-year follow-up period; 20 (3.5%) fractures in NMs, 24 (3.3%) in IMs, and 5 (2.3%) in PMs, respectively. No significant difference was observed among CYP2C19 genotypes and fracture. Additionally, BMD measurements during the 1-year follow-up period were made available among 75 participants. No significant difference in BMD between CYP2C19 PMs and non-PMs was found. This real-world, hospital-based study concludes that CYP2C19 PMs/IMs are not associated with an increased risk for fractures or reduced BMD in individuals on long-term PPI therapy.

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial

BackgroundSepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. MethodsThis study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. DiscussionThis trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock.Trial registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018.

Bismuth quadruple three-in-one single capsule three times a day increases effectiveness compared with the usual four times a day schedule: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)

BackgroundThe recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four...

BG12 A case of severe gastrointestinal bleeding while on vismodegib therapy

Abstract We report the case of a 50-year-old woman, with a history of Gorlin syndrome on vismodegib therapy, who presented with two episodes of upper gastrointestinal bleeding (UGIB) in the absence of other risk factors. Gorlin syndrome is a rare disorder characterized by multiple basal cell carcinomas (BCCs) secondary to a mutation in PTCH1. Mutations in PTCH1 lead to dysregulation of the hedgehog signalling pathway and subsequent abnormal proliferation. Vismodegib is a systemic hedgehog inhibitor that has been shown to be effective in treating advanced BCCs and Gorlin syndrome. Our patient acquired multiple BCCs which excision, photodynamic therapy and topical chemotherapy agents failed to control. Therefore, a decision to commence vismodegib was made. During treatment with vismodegib, she had a perforated gastrointestinal ulcer and required an emergency laparotomy. Vismodegib was stopped, but over the next few years, her BCCs progressed again to an excess of 50 BCCs, including large plaques of carcinoma measuring up to 12 cm in diameter. Vismodegib was restarted with a high-dose proton–pump inhibitor cover, as recommended by the gastroenterology team, and her BCCs were largely resolved. However, a second bleed occurred approximately 1 year after restarting treatment. Gastroscopies undertaken following these episodes were largely normal, showing mild, nonerosive duodenitis only, and Helicobacter pylori testing was negative. Given the lack of pre-existing risk factors and temporal relation to vismodegib therapy, the decision was made to suspend the drug. To our knowledge, this is the first case reported in the literature of UGIB associated with vismodegib. A separate case has reported colonic mucosal changes in a patient with chronic diarrhoea on vismodegib. The hedgehog protein and RNA expression have been found to be present in the gastrointestinal endothelium and mesenchyme. Evidence suggests the hedgehog pathway activation in gastrointestinal lining is involved in the wound-healing response, endothelial turnover and activation of mesenchymal immune responses. Therefore, inhibition of the hedgehog pathway via vismodegib could potentially impair the essential maintenance of the gastrointestinal endothelium. We postulate that this mechanism could have led to the presentation in our patient, through endothelial damage exposure of vessels leading to gastrointestinal bleeding. Treatment options for BCC in our patient are now limited. Vismodegib is one of the few therapies that has been shown to induce remission of symptoms and reduce disease burden. We present this case to raise awareness of this potential adverse event.

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video)

Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P= .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P= .023). No adverse events from TXA were recorded. The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).