Seronegative villous atrophy (SNVA) presents a diagnostic challenge with a wide range of possible etiologies. This report details a 67-year-old woman who developed chronic watery diarrhea and weight loss following the initiation of pantoprazole for gastroesophageal reflux disease. Duodenal biopsies showed villous atrophy associated with intraepithelial lymphocytosis, while celiac serologies and HLA-DQ2/DQ8 gene testing were negative. Discontinuation of pantoprazole led to the resolution of symptoms, and follow-up biopsies showed normalizes duodenal villous architecture without inflammatory infiltrates. This case represents an association between pantoprazole and the development of seronegative villous atrophy, underscoring the need to consider medications as potential causes of enteropathy.

The absorption and bioavailability of most tyrosine kinase inhibitors are affected by gastrointestinal pH as they are weak basic lipophilic drugs. Hence, concomitant use of acid reducing agents (ARAs) is frequently restricted. Particularly comedication of crystalline dasatinib (Sprycel) and proton-pump inhibitors (PPIs) should be avoided. Drug-drug interaction (DDI) studies with PPIs report approximately 40%-80% bioavailability reduction of dasatinib. Limitations in the design of these studies do not allow for assessing the near maximum DDI as timing of PPI dosing was either not reported or 22 h prior to dasatinib intake. We conducted a DDI study of crystalline dasatinib and omeprazole in healthy, fasted participants, investigating the impact of PPI comedication on dasatinib plasma exposure at a time point when the near maximum DDI effect is expected. Participants were administered omeprazole (day 2-5) to reach steady state. On day 6, a single dose of crystalline dasatinib was given. Crystalline dasatinib dosing alone on day 1 served as control (single dose). The dosing interval between omeprazole administration and crystalline dasatinib was 10 h (median [range: 9-10 h]). Dasatinib Cmax and AUC0-24 were reduced by 96% and 89% by omeprazole comedication. Cmax was 224.6 ± 104.7 ng/mL (mean ± SD) and 8.0 ± 4.5 ng/mL (P < .0001) and AUC0-24 was 797.6 ± 274.5 and 90.6 ± 38.1 h·ng/mL (P < .0001) without and with omeprazole. T1/2 was 5.7 ± 1.5 h (mean ± SD) with crystalline dasatinib dosing alone and could not be reliably calculated with comedication. To ensure optimal patient outcome, it is vital to investigate bioavailability of pH-sensitive drugs at the maximal DDI effect of ARAs to understand the worst-case influence for efficient clinical management.

Dietary fat malabsorption contributes to poor nutritional status in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton-pump inhibitors (PPI) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve dietary fat absorption has been accepted in clinical practice despite limited evidence.

This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole to determine if PPI improved the efficacy of PERT as indicated by measures of dietary fat absorption.

Fat malabsorption via stool coefficient of fat absorption (CFA) and malabsorption blood test (MBT), gastrointestinal pH (wireless motility capsule [WMC]), and quality of life (QOL) were assessed after 14 days on both placebo or PPI (omeprazole).

Total 19 subjects enrolled, 13 were randomized, and 9 provided paired results on placebo and PPI. The 3 subject results for CFA were as follows: 1 increased, 1 decreased, and 1 was within the reference range in both tests for fat absorption. For 9 MBT subjects, 7 decreased and 2 increased fat absorption. For the 4 WMC studies, no change in transit times, nor in pH profiles were noted. No differences were seen in the domains of the two QOL questionnaires comparing placebo and PPI.

These limited descriptive pilot study results in participants with CF and EPI on PERT evaluated by stool, blood, and QOL tests did not suggest improvement in fat absorption attributable to PPI.

This study aimed to investigate the association between use of proton pump inhibitors (PPI) and frailty index (FI), and to assess the causality relationship using Mendelian randomization (MR).

A total of 9756 middle-aged and older adults from the National Health and Nutrition Examination Survey were included. The FI was evaluated using a previously validated 49-item deficit model to assess frailty status, which is one of the common approaches to measure overall health burden. We performed weighted multivariable-adjusted linear regression to assess the association between PPI use and FI, and conducted a two-sample MR to evaluate causality, employing various sensitivity analyses for robustness. The inverse variance weighted (IVW) method was used as the primary analysis.

Multiple linear regression analysis revealed a positive association between PPI use and FI (β = 0.048, 95% confidence interval [CI]: 0.042-0.054, P < .001). This association was observed in both short-term (≤ 1 year) and long-term (> 1 year) PPI users (P for trend < 0.001). The MR study also revealed a positive association between PPI use and FI based on the IVW method (β = 1.183, 95% CI: 0.474-1.892, P = .001).

While our findings suggest a potential link between PPI use and FI, they should be interpreted with caution due to the study's limitations. Although the MR analysis suggests a causal relationship, further research, particularly longitudinal studies, is needed to confirm these findings and better establish temporality.

Gastroesophageal reflux is common, and when medical therapy is ineffective, alternative treatments should be considered. Nissen fundoplication controls reflux but can be followed by side effects such as dysphagia and flatulence. To improve outcomes, modifications have been advocated.

Modifications to Nissen fundoplication and newer procedures for gastroesophageal reflux aim to improve overall outcome. Randomized controlled trials (RCTs) and long-term outcomes from large cohorts are prioritized to consider the optimal procedure for reflux and hiatus hernia.

Fundoplication is an effective treatment for gastroesophageal reflux, with success rates of >80% reported at 18-20-year follow-up. RCTs confirm that Nissen fundoplication delivers better reflux control than medication. However, some patients are troubled by side effects. Anterior and posterior partial fundoplication variants have been proposed as procedures that offer equally good reflux control, but fewer side effects, and RCTs have confirmed this with follow-up to 20 years. Which partial fundoplication is better is debated. Alternative laparoscopic or endoscopic approaches require expensive implants or equipment and deliver less reliable reflux control than partial fundoplication. Currently, level I evidence confirms that laparoscopic partial fundoplication delivers the optimal outcome in fit patients with reflux that is not well controlled by medication.

Heterocyclic compounds are increasingly used in medicinal chemistry because they are the main components of many biological processes and materials. Benzimidazole remains the core center of the heterocyclic chemical group, with essential traits such as six-five-member connected rings and two nitrogen atoms at the 1,3 position in a six-membered benzene and five-membered imidazole- fused ring system. Molecules with benzimidazole derivatives serve important functions as therapeutic agents and have shown excellent results in clinical and biological research. In this comprehensive review, we summarize marketed medications that include the benzimidazole moiety. Here, we discuss two topics: PPIs and H1 receptor antagonists. Benzimidazole derivatives are important in all fields because they have the same isostructural pharmacophore as that of naturally occurring active biomolecules. While PPIs and H1 receptor antagonists are generally safe in the short term, accumulating data suggest that their long-term use may pose concerns. This systematic review aimed to assess global PPI use in the general population. This will help researchers, medicinal chemists, and pharmaceutical scientists to create breakthrough benzimidazole-based drugs. This review can help identify novel lead compounds and optimize existing benzimidazole derivatives to improve medicinal efficacy. Benzimidazole has attracted significant interest because of its high bioavailability, stability, and biological efficiency. This page reveals and discusses typical synthesis processes for marketed pharmaceuticals in the benzimidazole class of scaffolds, MOA, and therapeutic uses.

Proton pump inhibitors (PPIs) are effective treatments for acid-related disorders but may pose tumor risks with long-term use. Current research on PPI-associated tumor adverse events (TAEs) is limited and inconclusive. This study aims to comprehensively analyze the relationship between PPIs and TAEs.

We analyzed PPI adverse reaction reports from the FDA Adverse Event Reporting System (FAERS) database spanning from 2004 to 2024, focusing on five commonly used PPIs: esomeprazole, pantoprazole, lansoprazole, omeprazole, and rabeprazole. We conducted a disproportionality analysis utilizing the Reporting Odds Ratio (ROR) to identify potential TAEs associated with PPIs. We conducted univariate logistic regression analysis to explore the influencing factors.

A total of 3,133 TAEs were identified, representing 2.36% of all PPI-related adverse events (AEs). The most common TAEs were gastric cancer (19.05%) and malignant neoplasm (7.23%). Disproportionality analysis revealed ten significant TAEs associated with PPIs, including gastric adenocarcinoma and renal cell carcinoma. The median age of those reporting TAEs was 59 (interquartile range [IQR]: 51-70), and 29.70% of them resulted in a fatality. TAEs associated with PPIs were less likely to occur in elderly patients (65-75: OR = 0.91 [0.87-0.95], p < 0.001; >75: OR = 0.93 [0.89-0.98], p < 0.01).

TAEs constitute a small but significant fraction of PPI-related AEs. This study highlights the need for cautious long-term use of PPIs and further research to understand the underlying mechanisms and risk factors. Clinicians should be aware of the potential tumor risks associated with prolonged PPI treatment.

Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS.

We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs. no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated.

The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users.

Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

The association between proton pump inhibitor (PPI) and dementia was controversial. The aim of the current study was to perform an updated pharmacovigilance analysis of the association between dementia event and PPI treatment after minimizing competition bias.

We gathered cases reported with PPI treatment based on the United States Food and Drug Administration Adverse Event Reporting System database from 2004 to 2023. We employed disproportionality algorithms, including reporting odds ratio (ROR) and the information component (IC), to detect the association between dementia event and PPI. We investigated the affection of event competition bias on the current disproportionality signal detection.

We finally included a total of 776,191 PPI cases, and 1813 cases in the dementia group. Analyzing primary suspect PPIs, we detected a significant association between dementia and PPI (ROR = 1.38, 95%CI 1.22 to 1.56; IC = 0.46, 95%CI 0.04 to 0.86). After excluding the PPI case with renal injury events, the strength of the dementia signal increased. Omeprazole (589 cases), pantoprazole (514 cases), and esomeprazole (386 cases) were the top three PPI reported with dementia events.

The current pharmacovigilance study identified a significant association between dementia and PPIs, except vonoprazan and tegoprazan, especially taking competition bias into account. Further high-quality prospective study still needed.

Multimorbidity and polypharmacy in older adults converts the detection and adequacy of potentially inappropriate drug prescriptions (PIDP) in a healthcare priority. The objectives of this study are to describe the clinical decisions taken after the identification of PIDP by clinical pharmacists, using STOPP/START criteria, and to evaluate the degree of accomplishment of these decisions.

Multicenter, prospective, non-comparative cohort study in patients aged 65 and older, hospitalized because of an exacerbation of their chronic conditions. Each possible PIDP was manually identified by the clinical pharmacist at admission and an initial decision was taken by a multidisciplinary clinical committee. At discharge, criteria were re-applied and final decisions recorded.

From all patients (n = 674), 493 (73.1%) presented at least one STOPP criteria at admission, significantly reduced up to 258 (38.3%) at discharge. A similar trend was observed for START criteria (36.7% vs. 15.7%). Regarding the top 10 most prevalent STOPP criteria, the clinical committee initially agreed to withdraw 257 (34.2%) prescriptions and to modify 93 (12.4%) prescriptions. However, the evaluation of final clinical decisions revealed that 503 (67.0%) of those STOPP criteria were ultimately amended. For the top 10 START criteria associated PIDP, the committee decided to initiate 149 (51.7%) prescriptions, while a total of 198 (68.8%) were finally introduced at discharge.

The clinical committee, through a pharmacotherapy review, succeeded in identifying and reducing the degree of prescription inadequacy, for both STOPP and START criteria, in older patients with high degree of multimorbidity and polypharmacy.

NCT02830425.

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.

Drug-induced QT interval prolongation has been reported to be related to life-threatening polymorphic ventricular tachycardia (torsade de pointes). Proton pump inhibitors (PPIs) are prescribed widely for hospitalized patients; the QT interval prolongation and torsade de pointes caused by PPIs were reported. We conducted a study to determine the association between PPI treatment and QT interval prolongation in critically ill patients.

This study included patients with electrocardiography (ECG) reports from the Medical Information Mart for Intensive Care III database (MIMIC-III). Patients younger than 18 years, missing baseline laboratories and with QT interval prolongation before intensive care unit (ICU) admission were excluded. The end point was the diagnosis of QT interval prolongation reported by ECG.

This study included 24,512 ICU patients. Of them, 11,327 patients were treated with PPIs, 4181 with histamine 2 receptor antagonists (H2RAs) and 6351 without acid suppression therapy (non-AST); the incidence of QT interval prolongation were 8.5%, 3.3% and 3.4% respectively. After adjustment for demographics, electrolytes, comorbidities and medications, PPIs were associated a higher risk of QT interval prolongation compared with H2RAs (OR 1.66, 95% CI 1.36 - 2.03) and non-AST (OR 1.54, 95% CI 1.31 - 1.82), while there was not significant difference between H2RAs and non-AST (OR 0.93, 95% CI 0.73 - 1.17). In the propensity score matching population, the results were consistent. Pantoprazole (OR 2.14, 95% CI 1.52 - 3.03) and lansoprazole (OR 1.80, 95% CI: 1.18 - 2.76) showed a higher QT prolongation risk than omeprazole. Several drugs caused higher QT prolongation risk when used in combination with PPIs.

In ICU patients, the association between PPI prescription and increased risk of QT interval prolongation was independent of known QT-prolonging factors; pantoprazole and lansoprazole had a higher risk compared with omeprazole. The combination of PPIs and other QT-prolonging drugs should be avoided.

An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption.

This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency.

A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency.

Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. 'Titration' of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections.

This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free.

Reflux esophagitis (RE) is a common chronic inflammatory disease of the esophageal mucosa with a high prevalence and recurrence rate, for which a satisfactory therapeutic strategy is still lacking. Chinese medicine has its characteristics and advantages in treating RE, and the clinical application of Xuanfu Daizhe Tang (XDT) in treating RE has achieved sound therapeutic effects. However, there needs to be more research on its mechanism of action.

The present work aimed to investigate the mechanism of XDT action in RE through the Signal Transducer and Activator of Transcription 1 (STAT1)/Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) pathway.

The main active components of XDT were analyzed by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The effect of XDT on RE was evaluated in a rat model of RE induced by "Cardioplasty + pyloric ligation + Roux-en-Y esophagojejunostomy". Each administration group was treated by gavage. The degree of damage to the esophageal mucosa was evaluated by visual observation, and the Potential of Hydrogen (PH) method and Hematoxylin-eosin staining (HE) staining were performed. Serum levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-α), and Inducible Nitric Oxide Synthase (iNOS) were measured by ELISA. Quantitative Real-time PCR (qPCR), Western Blot (WB), and Immunofluorescence (IF) methods were used to detect Claudin-4, Claudin-5, TREM-1, and p-STAT1 in esophageal tissues for studying the mechanism of action and signaling pathway of XDT. Immunohistochemistry (IHC) analysis was used to detect the expression of TREM-1 and CD68 in esophageal tissues. Flow Cytometry (FC) was used to detect the polarization of macrophages in the blood. After conducting preliminary experiments to verify our hypothesis, we performed molecular docking between the active component of XDT and STAT1 derived from rats and parallel experiments with STAT1 inhibitor. The selective increaser of STAT1 transcription (2-NP) group was used to validate the mechanism by which XDT acts.

XDT alleviated esophageal injury and attenuated histopathological changes in RE rats. XDT also inhibited the inflammatory response and decreased serum IL-1β, IL-6, TNF-α, and iNOS levels in RE rats. qPCR and WB results revealed that XDT inhibited the expression of Claudin-4, Claudin-5, TREM-1, and STAT1 in the esophageal mucosa of RE rats. IHC and FC results showed that XDT reduced TREM-1 levels in esophageal tissues and polarized macrophages toward M2. The molecular docking results showed that rat-derived STAT1 can strongly bind to Isochronogenic acid A in XDT. The parallel experimental results of STAT1 inhibitor showed that XDT has anti-inflammatory effects similar to STAT1 inhibitors. The 2-NP group confirmed that XDT exerts its therapeutic effect on reflux esophagitis through the STAT1/TREM-1 pathway, with STAT1 as the upstream protein.

This study suggests that XDT may treat reflux esophagitis by modulating the STAT1/TREM-1 pathway.

Justicia pectoralis Jacq. is traditionally applied in folk medicine in Brazil and in several Latin American countries. The leaves are used in tea form, especially in the treatment of respiratory disorders, acting as an expectorant. It also has activity in gastrointestinal disorders, and it is anti-inflammatory, antioxidant, sedative, and estrogenic, among others.

To investigate the gastroprotective activity of the methanol extract of the leaves of Justicia pectoralis Jacq. (MEJP) in different experimental models of gastric ulcers.

The adult leaves of Justicia pectoralis Jacq. were collected and cultivated in beds, with an approximate spacing of 40 × 40 cm, organic fertilization, irrigation with potable water and without shelter from light. The MEJP was prepared from the dried and pulverized leaves and concentrated under reduced pressure in a rotary evaporator. For the experimental model of gastric ulcer, Swiss male albino mice were used. The inputs used in the experiment were MEJP at three different concentrations (250, 500 and 1000 mg/kg p.o.), cimetidine (50 mg/kg p.o.), indomethacin (50 mg/kg s.c.) and vehicle (10 mL/kg p.o.).

MEJP (250, 500 and 1000 mg/kg p.o.) demonstrated gastroprotective activity, with levels of protection of 45.65%, 44.80% and 40.22%, respectively, compared to the control (vehicle). Compared with cimetidine (48.29%), MEJP showed similar gastroprotective activity.

This study demonstrated the gastroprotective activity of MEJP and contributes to validate the traditional use the species for gastric disorders and provides a pharmacological basis for its clinical potential.

Despite deprescribing initiatives to curb overutilization of proton pump inhibitors (PPIs), achieving meaningful reductions in PPI use is proving a challenge.

An international group of primary care doctors and gastroenterologists examined the literature surrounding PPI use and use-reduction to clarify: (i) what constitutes rational PPI prescribing; (ii) when and in whom PPI use-reduction should be attempted; and (iii) what strategies to use when attempting PPI use-reduction.

Before starting a PPI for reflux-like symptoms, patients should be educated on potential causes and alternative approaches including dietary and lifestyle modification, weight loss, and relaxation strategies. When commencing a PPI, patients should understand the reason for treatment, planned duration, and review date. PPI use at hospital discharge should not be continued without a recognized indication for long-term treatment. Long-term PPI therapy should be reviewed at least annually. PPI use-reduction should be based on the lack of a rational indication for long-term PPI use, not concern for PPI-associated adverse events. PPI use-reduction strategies involving switching to on-demand PPI or dose tapering, with rescue therapy for rebound symptoms, are more likely to succeed than abrupt cessation.

Acid-suppressive drugs (ASDs) are widely used in many gastric acid-associated diseases. Nocturnal acid breakthrough has been a common problem of many ASDs, such as proton-pump inhibitors (PPIs) and H2 -receptor antagonists (H2RAs). Potassium-competitive acid blockers (P-CABs) are expected to solve this continuing conundrum. This article examined major ASDs and compared them with placebo in terms of nocturnal acid-inhibitory effects, using a network meta-analysis of randomized controlled trials (RCTs).

To compare the effectiveness of major ASDs, a Bayesian network meta-analysis (NMA) was applied to process data extracted from RCTs. The plausible ranking for each regimen and some subgroups were assessed by surface under the cumulative ranking curves (SUCRA).

Fifty-five RCTs were conducted with 2015 participants. In terms of nocturnal acid-inhibitory effects, the overall results showed that tegoprazan (SUCRA 91.8%) and vonoprazan (SUCRA 91.0%) had the best performance, followed by new PPIs (including tenatoprazole and ilaprazole) (SUCRA 76.6%), additional H2RAs once at bedtime (AHB) (SUCRA 61.3%), isomer PPIs (including esomeprazole and dexlansoprazole) (SUCRA 38.6%), revaprazan (SUCRA 34.7%), traditional PPIs (including omeprazole, rabeprazole, pantoprazole, lansoprazole) (SUCRA 32.6%), H2RAs (SUCRA 23.1%), and placebo (SUCRA 0.3%). In some subgroups, the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan was better than most of the other regimens, even new PPIs and AHB.

This is the first study to compare the effect of ASDs on inhibiting nocturnal acid breakthrough. Overall, in terms of nocturnal acid-inhibitory effect, vonoprazan and tegoprazan had an advantage against other regimens including H2RAs, isomer PPIs, traditional PPIs, AHB, and new PPIs. Even in some subgroups, such as language classification (English), types of study design (crossover-RCT), age (≤40 years), BMI (18.5-24.9 kg/m2 ), continent (Asia and North America), disease status (health), the duration of therapy (2 weeks), and time of administration (at daytime or at night-time), the nocturnal acid-inhibitory effect of vonoprazan or tegoprazan were better than most regimens, even AHB and new PPIs.

Globally, over 25% of the population suffers from acid-related disorders such as dyspepsia or gastroesophageal reflux disease (GERD), and around 7.6% of Indians report having GERD symptoms on a frequent enough basis to warrant a diagnosis. Over the past three decades, proton-pump inhibitors (PPIs) have been the mainstay of medical therapy for acid-peptic diseases like GERD, etc. Additionally, they are frequently prescribed for prophylactic purposes and in conjunction with non-steroidal anti-inflammatory drugs. PPIs are generally prescribed for four to eight weeks. However, it may be prescribed for patients with comorbidities and multiple medications for a longer period of time. While this remains true in terms of effectiveness, concerns have been raised about the safety of long-term PPI use and the serious adverse effects that may result. Some of the observational and population-based cohort studies have shown an association between long-term use of PPIs and an increased risk of pneumonia, major cardiovascular events, dementia, vitamin B12 deficiency, bone fractures, gastric cancer, and kidney injury, among others. This review analyzes the clinical data supporting the long-term use of PPIs and takes a deep dive into whether these several emerging long-term concerns apply to the currently available PPIs in India. We have summarized a vast array of studies, including randomized trials, cohort studies, and meta-analyses, that report low or high incidences of major health risks linked with PPIs and have assessed their appropriateness over a given period.

The prognostic value of vitamin B12 blood levels remains controversial. An association between elevated vitamin B12 and mortality has been reported, particularly among elderly patients with cancers and liver or blood diseases. The present study explored the relationship between mortality and elevated vitamin B12 levels in a population of unscheduled inpatients in an internal medicine unit.

This retrospective observational analysis was conducted between August 2014 and December 2018. We compared 165 patients with elevated plasma vitamin B12 levels (>600 pmol/l) with a random sample of 165 patients with normal B12 levels who were hospitalized during the same period. Demographic, clinical, and biological characteristics were assessed during hospitalization. The primary endpoint was all-cause death at 1 year.

Patients with elevated B12 were younger, with a lower body mass index and lower plasma albumin than those with normal B12 (75 ± 16 years vs 79 ± 13 years, p = 0.047; 23 ± 5 vs 26 ± 7 kg/m2, p  <  0.001; and 33 ± 5 vs 35 ± 5 g/l, p  <  0.001, respectively). The prevalence of auto-immune disease and referral from an intensive care unit was higher among patients with elevated B12 (11% vs 5%, p = 0.043 and 36% vs 10%, p  <  0.001, respectively). After 1 year of follow-up, 64 (39%) patients with elevated B12 had died compared to 43 (26%) patients with normal B12 (p = 0.018). Multivariate analysis using the Cox proportional hazards regression model adjusted for age, gender, body mass index, intensive care unit hospitalization, albumin level, and the presence of solid cancer or autoimmune disease revealed elevated B12 to be associated with a significant risk of death in the first year of follow-up (hazard ratio: 1.71 [1.08-2.7], p = 0.022).

Elevated B12 is an early warning indicator of increased short-term mortality, such as independently of age, cancer, or comorbidities, in patients hospitalized in an internal medicine department.

Proton pump inhibitors (PPIs) are commonly used medications for various gastrointestinal disorders and are reported to be associated with bone fractures. A literature review was performed, which showed PPI to be associated with a shorter time to first fracture in adults aged 25 or older. There was an overall increased risk of fractures with PPI use in adults; however, such risk was not significantly higher in women over 80 years of age and adult patients with rheumatoid arthritis. In healthy adult males aged 18-50 years, PPI use was not associated with significant changes in calcium and bone metabolism with PPI use. The lack of increased risk among elderly women aged more than 80 and rheumatoid arthritis patients raises the possible confounding or effect modification by factors that affect the fracture risk with PPI use. We concluded that although observational studies show an increased risk of fractures with PPI use, warranting their use with caution in some patients, experimental evidence explaining the risk is still lacking.

The cornerstone treatment of hyperphenylalaninemia (HPA) and phenylketonuria (PKU) is a lifelong low-protein diet with phenylalanine (Phe) free L-amino acid supplements. However, the PKU diet has significant shortcomings, and there is a clinically unmet need for new therapeutics to improve patient outcomes. CDX-6114 is a modified phenylalanine ammonia-lyase (PAL) enzyme obtained by a mutation in the Anabaena variabilis PAL sequence. CodeEvolver® protein engineering technology has been applied to improve the degradation resistance of the enzyme. In our first phase I trial, 19 patients were given a single oral dose of CDX-6114 at 7.5 g, 2.5 g, 0.7 g, or placebo in a cross-over design. After an overnight fast, patients received a standardised breakfast of 20 g of protein, thus exceeding the dietary recommendations for a single meal in patients with PKU. Plasma levels of Phe and cinnamic acid (CA) were measured over a 5-h period following CDX-6114 dosing. During the development of CDX-6114, a stability assessment using reverse-phase high-performance liquid chromatography (HPLC) assay revealed two peaks. The second peak was identified as CA. It was not previously known that as part of the mechanism of action, the CA remained associated with the protein following the conversion of Phe. Thus, recalculating the historical PAL enzyme amounts in CDX-6114 bulk substance was necessary. An updated extinction coefficient was achieved by applying a correction factor of 0.771 to previously reported doses. Postprandial plasma levels of Phe increased in all dose cohorts over time between 10% and 30% from baseline, although the actual peak of Phe levels was not achieved within the 5-h observation. When accounting for the interquartile ranges, these concentrations were similar to the placebo. As plasma levels of Phe were no longer a reliable marker for pharmacodynamics, the consistently detectable amount of CA seen in all patients who received CDX-6114 provided proof of the enzymatic activity of CDX-6114 in metabolising gastrointestinal Phe. Peak levels of CA were seen shortly after CDX-6114 intake, with a rapid decline, and remained low compared with the plasma Phe levels. This pattern indicates a short half-life, possibly due to the liquid formulation or the inability to withstand the lower pH in the human stomach compared with animal models in earlier studies. This was the first trial in patients with PKU to establish the safety and tolerability of CDX-6114. A single dose of CDX-6114 was safe and well tolerated, with no serious adverse events or presence of anti-drug antibodies detected. Efficacy will be explored in future trials using an optimised formulation.

Vonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30-40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD.

This study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit.

This trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions.

https://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023.

February 18, 2023, Version 2.

To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia.

Randomised, double blind controlled trial, with central randomisation.

Thai traditional medicine hospital, district hospital, and university hospitals in Thailand.

Participants with a diagnosis of functional dyspepsia.

The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days.

Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events.

206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred.

Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect.

TCTR20221208003.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy and outcomes, leading to an expanding use in millions of patients worldwide. However, they can cause a spectrum of immune-related adverse events (irAEs). Essentially, any organs can be affected by irAEs, which have emerged as therapy-limiting side effects. In the kidneys, ICI-associated acute interstitial nephritis (ICI-AIN) leads to acute kidney injury (AKI) in 2%-5% of patients on ICI therapy. AKI associated with ICI therapy pathologically presents with AIN in nearly 90% of the cases, but the pathophysiology of ICI-AIN remains to be defined. The generation of autoreactive T cells in patients receiving AIN-inducible drugs, such as proton pump inhibitors (PPIs), is one of the leading theories, supported by a higher incidence of ICI-AIN in patients on these AIN-inducible drugs. In this review, we will discuss our understanding of the incidence, potential pathophysiological mechanisms, clinical presentations, risk factors, diagnosis, and management of PPI-related AIN and its interaction with ICI therapy.

Long-term use of proton-pump inhibitors can induce fundic gland polyps in the human stomach. However, this phenomenon has not been described in the veterinary literature. A 5-year-old intact female Maltese dog was referred to our hospital with chronic intermittent vomiting. The dog had been administered omeprazole (0.7-1.0 mg/kg PO q24 h) for the management of hydrocephalus for over 4 years; the omeprazole dose was increased to 10 mg/kg PO q24 h 8 months prior to presentation at referring hospital. Abdominal ultrasonography revealed marked thickening of the gastric wall with multi-lobulated, thickened folds. Subsequent endoscopy revealed marked polypoid lesions, and histological examination of the biopsy samples was consistent with the fundic gland polyps associated with proton-pump inhibitor use in humans. The lesions resolved after cessation of omeprazole, as assessed by ultrasonography. This report describes a case of fundic gland polyps following the long-term administration of omeprazole in a dog.

To evaluate through meta-analysis whether long-term use of proton pump inhibitor (PPI) increases the risk of precancerous lesions in the stomach.

Randomized controlled trials that compared the occurrence and progression of precancerous lesions in patients receiving PPI treatment versus non-PPI treatment were retrieved from CNKI, VIP, Wanfang, CBM, Pubmed, Embase, Web of Science, and Cochrane Library databases (from database inception to May 1, 2023). The Revman 5.3 and STATA 17.0 software were used for analysis, and subgroup analysis was conducted based on follow-up time (≤12 months and > 12 months) and lesion type (atrophic gastritis, intestinal metaplasia, and epithelial dysplasia).

Six randomized controlled trials with a total of 1623 cases were included, including 1015 cases in the experimental group and 608 cases in the control group. The meta-analysis results showed that the overall abnormal lesion rate combined with statistical relative risk (RR) = 1.31 (0.85-2.02), P = .23. Subgroup analysis showed that the follow-up time > 12 months combined result was RR = 2.21 (1.47-3.33), P = .0001, the intestinal metaplasia group combined result was RR = 1.96 (0.91-2.47), P = .04.

During long-term follow-up, patients using PPI exhibited a significantly higher incidence of overall abnormal lesions compared to the control group, particularly with a higher risk observed for intestinal metaplasia. However, there were no statistically significant differences between the 2 groups in terms of short-term follow-up and other types of lesions. It is important to exercise caution when interpreting these findings due to the limited number of nominated investigations included in the meta-analysis.

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.

Eosinophilic esophagitis is an increasingly common inflammatory allergic disease of the esophagus characterized by esophageal eosinophilia and symptoms of esophageal dysfunction. The therapeutic landscape has rapidly evolved for this emerging type 2 inflammatory disorder. We review traditional therapies including updates and expert opinions in addition to promising therapies on the horizon and the history of therapies that failed to meet end points and highlight knowledge gaps for future investigations.

Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells and shape the tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.

Ovotransferrin (OVT) has been confirmed to have anti-inflammatory activity. However, its effect and mechanism on gastric inflammation are unclear. In this study, the effect and mechanism of the OVT on the tumor necrosis factor-α (TNF-α) induced inflammatory response in gastric epithelial cells (GES-1) were investigated. The enzyme linked immunosorbent assay (ELISA) was used to determine the levels of inflammation cytokines, followed by RNA sequencing to explore the potential pathways of its anti-inflammatory effect, and then it was validated by Western blotting and pathways inhibitors. Results showed that the OVT at concentrations of 50-400 μg/mL displayed nontoxicity against GES-1 cells. Additionally, 100 μg/mL of OVT obviously reduced the secretion of interleukin (IL)-8, IL-6, and TNF-α by 63.02% (630.09/1703.98), 35.53% (935.81/1451.43), and 36.19% (964.60/1511.63), respectively. The results of RNA sequencing exhibited that the OVT significantly influences the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κB) pathways, which was verified by the levels of p-IKK, p-IκB, p-P65, p-ERK, p-JNK, and p-P38 protein. IL-8 contents released by GES-1 cells after incubation with inhibitors of NF-κB and MAPK pathways further confirmed that OVT hindered activation of these two pathways. Collectively, these results suggested that OVT was a natural protein with the potential to treat gastric inflammation.

Gastrointestinal tract involvement in systemic sclerosis concerns more than 90% of patients but is of heterogeneous clinical expression. It can involve the entire intestinal tract and be responsible for multifactorial malnutrition, which is frequent in this disease. It is a major source of deterioration in the quality of life and can even be life-threatening. Management is complex and multidisciplinary, ranging from simple hygienic and dietary measures, to specialized endoscopic or surgical interventional procedures, also including medical treatments, particularly proton pump inhibitors and prokinetics, with potential side effects. Ongoing research for new diagnostic and therapeutic tools promises to improve the management and prognosis of these patients.

Although proton pump inhibitors (PPIs) play a pivotal role in the prevention and treatment of gastric acid-related diseases and gastrointestinal adverse events caused by antiplatelet therapies, the safety of long-term use of PPIs has been questioned.

The aim of this study was to determine the effects of use of PPIs on muscle mass and bone mineral density in heart failure (HF) patients.

This was a single-center, ambispective (combined retrospective and prospective), observational study. HF patients (n = 747; 72 years of age; males, 54%) who received a dual-energy x-ray absorptiometry scan were enrolled. Muscle wasting was defined as appendicular skeletal muscle mass index (ASMI) < 7.0 kg/m² in males and <5.4 kg/m² in females. Propensity scores for the use of PPIs were calculated using a multivariate logistic regression model to minimize selection bias.

Before propensity score matching, ASMI was significantly lower in patients receiving PPIs than in patients not receiving PPIs, resulting in a higher prevalence of muscle wasting in the PPI group. Such a relationship between use of PPIs and muscle wasting remained after propensity score matching. In multivariate Cox regression analyses, use of PPIs was independently associated with presence of muscle wasting (hazard ratio 1.68, 95% confidence interval 1.05-2.69) after adjustment for established risk factors of sarcopenia. On the other hand, there were no differences in bone mineral density between the PPI group and the no-PPI group.

Use of PPIs is associated with a high risk of muscle wasting in HF patients. Caution is warranted when long-term PPI treatment is performed in sarcopenic HF patients and HF patients with several risk factors for muscle wasting.

Proton pump inhibitor (PPI) use has increased over the last decades and has been associated with multiple adverse events and potentially even overall survival.

We aimed to investigate the association between proton pump inhibitor maintenance use and all-cause and cause-specific mortality, addressing confounding by indication and duration of use.

This Swedish population-based cohort study included all adult (N = 935,236) PPI and histamine-2 receptor antagonist maintenance users (≥ 180 days use) during 2005-2014. Standardised mortality ratios (SMRs) and 95% confidence intervals were calculated for all-cause and cause-specific mortality comparing the risk among PPI/H2RA users to that of the Swedish background population, stratified by age, sex, calendar period, indication and duration of use. Multivariable Poisson regression models were used to compare PPI use to H2RA use, expressed as incidence rate ratios and 95% confidence intervals.

PPI and histamine-2 receptor antagonist use were associated with an increased risk of all-cause mortality (SMR = 1.35; 1.34-1.36; SMR = 1.31; 1.27-1.36, respectively). The highest SMRs were found in the youngest age groups. In direct comparison, PPI use showed a higher mortality risk than histamine-2 receptor antagonist use (incidence rate ratios = 1.42; 1.38-1.46). PPIs were related to increased cancer (SMR = 1.21; 1.20-1.22), and cardiovascular mortality (SMR = 1.36; 1.35-1.37). Increased SMRs were observed for most indications. Longer duration of use was associated with a higher mortality among PPI users but not among histamine-2 receptor antagonist users.

Maintenance PPI use was associated with an increased risk of all-cause and cause-specific mortality, and the risk increased with prolonged duration.

 Clostridium difficile (C. difficile) is a common cause of hospital-acquired diarrhea. It is associated with significantly higher mortality and morbidity in addition to the cost-effectiveness burden on the healthcare system. The primary risk factors for C. difficile infection (CDI) are past C. difficile exposure, proton pump inhibitors, and antibiotic usage. These risk factors are also associated with poor prognosis.

This study was performed in Dr. Sulaiman Al Habib Tertiary Hospital in the Eastern Region of Saudi Arabia. The aim was to evaluate the risk and prognostic factors of CDI and their association with the outcomes of hospital stay, such as complications, length of stay (LOS), and treatment duration.

This is a retrospective cohort study for all patients who tested for C. difficile in the medical department. The target population was all adult patients ≥16 years with positive stool toxins for C. difficile between April 2019 and July 2022. The main outcome measures are risk and poor prognostic factors for CDI.

C. difficle infection patients were included in the study; 12 (52.2%) were female, and 11 (47.8%) were male. The mean age of the patients was 58.3 (SD: 21.5) years; 13 (56.5%) patients were below 65 years, and 10 were above 65 years. Only four patients were without comorbidities, and 19 (82.6%) patients had various comorbidities. Importantly, hypertension was the most common comorbidity in 47.8% of the patients. Furthermore, advanced age significantly impacted the hospital LOS as the mean age among patients who stayed at the hospital less than four days and those who stayed ≥4 days was 49.08 (19.7) and 68.36 (19.5), respectively (P = .028).

 Advanced age was the most frequent poor prognostic factor among our inpatient participants with positive CDI. It was significantly associated with longer hospital LOS, more complications, and longer treatment duration.

Immune checkpoint inhibitors (ICIs) have been a major breakthrough in solid oncology over the past decade. The immune system and the gut microbiota are involved in their complex mechanisms of action. However, drug interactions have been suspected of disrupting the fine equilibrium necessary for optimal ICI efficacy. Thus, clinicians are facing a great deal of sometimes contradictory information on comedications with ICIs and must at times oppose conflicting objectives between oncological response and comorbidities or complications. We compiled in this review published data on the role of the microbiota in ICI efficacy and the impact of comedications. We found mostly concordant results on detrimental action of concurrent corticosteroids, antibiotics, and proton pump inhibitors. The timeframe seems to be an important variable each time to preserve an initial immune priming at ICIs initiation. Other molecules have been associated with improved or impaired ICIs outcomes in pre-clinical models with discordant conclusions in retrospective clinical studies. We gathered the results of the main studies concerning metformin, aspirin, and non-steroidal anti-inflammatory drugs, beta blockers, renin-angiotensin-aldosterone system inhibitors, opioids, and statins. In conclusion, one should always assess the necessity of concomitant treatment according to evidence-based recommendations and discuss the possibility of postponing ICI initiation or switching strategies to preserve the critical window.

Takayasu arteritis (TAK) is an autoimmune large vessel vasculitis that affects the aorta and its major branches, eventually leading to the development of aortic aneurysm and vascular stenosis or occlusion. This retrospective and prospective study aimed to investigate whether the gut dysbiosis exists in patients with TAK and to identify specific gut microorganisms related to aortic aneurysm formation/progression in TAK.

We analysed the faecal microbiome of 76 patients with TAK and 56 healthy controls (HCs) using 16S ribosomal RNA sequencing. We examined the relationship between the composition of the gut microbiota and clinical parameters.

The patients with TAK showed an altered gut microbiota with a higher abundance of oral-derived bacteria, such as Streptococcus and Campylobacter, regardless of the disease activity, than HCs. This increase was significantly associated with the administration of a proton pump inhibitor used for preventing gastric ulcers in patients treated with aspirin and glucocorticoids. Among patients taking a proton pump inhibitor, Campylobacter was more frequently detected in those who underwent vascular surgeries and endovascular therapy for aortic dilatation than in those who did not. Among the genus of Campylobacter, Campylobacter gracilis in the gut microbiome was significantly associated with clinical events related to aortic aneurysm formation/worsening in patients with TAK. In a prospective analysis, patients with a gut microbiome positive for Campylobacter were significantly more likely to require interventions for aortic dilatation than those who were negative for Campylobacter. Furthermore, patients with TAK who were positive for C. gracilis by polymerase chain reaction showed a tendency to have severe aortic aneurysms.

A specific increase in oral-derived Campylobacter in the gut may be a novel predictor of aortic aneurysm formation/progression in patients with TAK.

Analysis of the efficacy/pharmacology of long-term/lifetime medical treatment of acid hypersecretion in a large cohort of ZES patients in a prospective study. This study includes the results from all 303 patients with established ZES who were prospectively followed and received acid antisecretory treatment with either H2Rs or PPIs, with antisecretory doses individually titrated by the results of regular gastric acid testing. The study includes patients treated for short-term periods (<5 yrs), patients treated long-term (>5 yrs), and patients with lifetime treatment (30%) followed for up to 48 years (mean 14 yrs). Long-term/lifelong acid antisecretory treatment with H2Rs/PPIs can be successfully carried out in all patients with both uncomplicated and complicated ZES (i.e., with MEN1/ZES, previous Billroth 2, severe GERD). This is only possible if drug doses are individually set by assessing acid secretory control to establish proven criteria, with regular reassessments and readjustments. Frequent dose changes both upward and downward are needed, as well as regulation of the dosing frequency, and there is a primary reliance on the use of PPIs. Prognostic factors predicting patients with PPI dose changes are identified, which need to be studied prospectively to develop a useful predictive algorithm that could be clinically useful for tailored long-term/lifetime therapy in these patients.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.