Impact Of Proton Pump Inhibitors Research Articles

S1035 The Impact of Proton Pump Inhibitors on the Efficacy and Safety of Dual Antiplatelet Therapy Following Intracranial and Carotid Artery Stent Placement: A Retrospective Cohort Study in an Underserved Community Hospital

S1035 The Impact of Proton Pump Inhibitors on the Efficacy and Safety of Dual Antiplatelet Therapy Following Intracranial and Carotid Artery Stent Placement: A Retrospective Cohort Study in an Underserved Community Hospital

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Impact of proton pump inhibitors on the efficacy of androgen receptor signaling inhibitors in metastatic castration-resistant prostate cancer patients.

Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

#1567 Risk factors for COVID-19 hospitalization and death in kidney transplant recipients: a retrospective nationwide study in Sweden

Abstract Background and Aims Kidney transplant recipients (KTRs) are particularly susceptible to infections due to their continuous immunosuppressive treatment, the presence of other comorbidities, and, in some cases, impaired kidney function. While previous research has identified certain risk factors for severe COVID-19 in KTRs, comprehensive data at a national level—minimizing regional or center-specific influences—remains scarce. Our study aimed to fill this gap by examining risk factors for severe COVID-19 at a national level. Thus, we conducted a retrospective analysis of COVID-19 outcomes, alongside demographic, clinical, and medication-related risk factors associated with hospitalization and mortality due to COVID-19, within a comprehensive national cohort of Swedish KTRs over the initial two years of the pandemic. Method We assessed the outcomes and identified risk factors associated with hospitalization and mortality from COVID-19 among all kidney transplant recipients in Sweden who were alive as of January 1, 2020 during the first two years of the pandemic (2020-2021). We utilized data from the Swedish Renal Registry (SRR) and other interconnected healthcare registries. The SRR is a nationwide registry, with almost complete coverage (>97%) of patients with kidney replacement therapy in Sweden, including KTRs. Through multivariable adjusted logistic regression models, we systematically analyzed this data to pinpoint risk factors contributing to severe COVID-19 cases in this specific patient population. Results There were 5,824 KTRs in Sweden on January 1, 2020 with a mean age 58 years, 64% men. An increased risk of severe COVID-19 was observed for patients aged between 49 to 68 years, with the highest point estimate for patients aged 49-58 years (OR 2.26, 95% CI 1.50-3.45) and those who underwent a prolonged duration of dialysis before their transplantation (aOR 1.04, CI 95% 1.01-1.07 [per one year increase]). Conversely, KTRs with a longer elapsed time since the transplantation and those who had received a kidney from a living donor had a lower risk of severe COVID-19. Compared to KTRs who were transplanted less than a year ago, those who had received their transplant 6-10 years ago or >10 years ago had an about 50% lower risk of being hospitalized or die from COVID-19 (aOR 0.49, CI 95% 0.35-0.68 and aOR 0.55, CI 95% 0.40-0.74, respectively). While no significant correlation was observed directly between hypertension and severe COVID-19, a significant association was identified with the increasing number of antihypertensive medications prescribed to a patient (P-value <.0001). Furthermore, treatment with mycophenolate mofetil and the use of a higher number of immunosuppressive drugs were associated with a higher risk of severe COVID-19. The use of proton pump inhibitors was also linked to an increased risk of severe COVID-19 (aOR 1.66, 95% CI 1.33-2.07). Conclusion Our study reveals several critical insights into the risk factors associated with severe COVID-19 among KTRs in Sweden. A key finding is the increased risk observed in individuals of working age, potentially due to higher exposure to the virus. Additionally, our findings suggest that the severity of comorbidities, rather than the presence of comorbidities themselves, may play a more significant role in increasing the risk of severe COVID-19. Importantly, our research sheds light on the potential impact of proton pump inhibitor (PPI) therapy, as a modifiable risk factor in the management of COVID-19. In general, our findings are instrumental in developing more targeted prevention and treatment strategies for COVID-19 in KTRs, aiming to improve care for this particularly vulnerable group.

Laparoscopic management of benign gastric outlet obstruction: a case series with review of literature

Surgery for peptic ulcer disease has since long become a thing of the past, in the era of proton pump inhibitors. Today, it is difficult to believe that these were common operations about 6-7 decades ago. Such has been the impact of proton pump inhibitors (PPI), that, surgery for peptic ulcer has been relegated to the realms of history. However, even in present day, in some rare clinical situations, surgeons may have to resort to surgery for patients suffering from peptic ulcer disease. Herein, we present our experience of laparoscopic surgical management of one of those rare clinical scenarios related to severe peptic ulcer disease. The clinical condition in discussion is gastric outlet obstruction caused by severe peptic ulcer disease in the first part of duodenum. We identified 8 patients (7 males and 1 female) who underwent laparoscopic vagotomy with gastrojejunostomy for benign gastric outlet obstruction, at our institution, operated upon by a single surgeon, between 2004 to 2023. All patients had undergone oesophago-gastro-duodenoscopy (OGD scopy), and contrast enhanced computerised tomography (CECT) of the abdomen. The patients were analysed for age, sex, symptoms, pre-operative evaluation, morbidity/mortality and functional outcomes. They were also reviewed to examine the length of stay, length of procedure, complications and recurrent symptoms on follow-up.

Abstract 3730: Impact of proton pump inhibitor on ICI with or without chemotherapy for NSCLC with high PD-L1 TPS

Abstract Background and Aim: Immune checkpoint inhibitors (ICIs) have been widely used for the initial treatment of non-small cell lung cancer (NSCLC). Although both ICI monotherapy and the combination of ICI plus chemotherapy (chemo-ICI) are promising therapeutic options for patients with a programmed cell death ligand-1 tumor proportion score of 50% or higher (high PD-L1), the patient's clinical background and biomarkers differentiating the two options are still not well-defined. In our prior research, we found that a history of proton pump inhibitor (PPI) use independently have negative impact with significantly shorter overall survival (OS) and progression-free survival (PFS) in NSCLC patients harboring high PD-L1 with pembrolizumab monotherapy, but not with chemo-ICI. However, this OS data remain immature. Therefore, in our current study, we extended the follow-up period and conduct additional analysis including OS data to confirm this trend. Method: Advanced NSCLC patients with high PD-L1 who had received pembrolizumab or chemo-ICI as the first-line treatment between March 2017 and December 2020 at 13 hospitals in Japan were analyzed. Survival outcomes were estimated using the Kaplan- Meier method and were compared using the log-rank test. Results: A total of 425 patients with NSCLC were included in the study, with 271 patients (median [range] age, 72 [43-90] years; 215 [79%] men) receiving pembrolizumab monotherapy as their first-line treatment and 154 patients (median [range] age, 69 [36-86] years; 121 [79%] men) receiving chemo-ICI as their first-line treatment. The median follow-up duration was 22.8 months. Among patients with a history of PPI use, both median PFS (19.3 months vs. 6.8 months; HR, 0.53; 95% CI, 0.35-0.78; P = .003) and the median OS(not reached vs. 20.4 months; HR, 0.53; 95% CI, 0.34-0.85; P = .04) were significantly longer in the chemo-ICI group compared to the pembrolizumab monotherapy group. For patients without a history of PPI use, both median PFS (11.4 months vs. 10.8 months; HR, 0.99; 95% CI, 0.76-1.3; P = .36) and the median overall survival (42.2 months vs. 29.9 months, HR, 0.84; 95% CI, 0.62-1.16; P = .33) showed no significant differences between the groups. Discussion and Conclusion: This retrospective study showed that a concomitant treatment with PPI is poor prognostic factor in patients harboring high PD-L1 and treated with ICI monotherapy compared with chemo-ICI in Japanese cohort and this tendency is durable in long-term follow-up. These results indicate that when deciding on an ICI treatment, with or without chemotherapy, it is essential to take into account a concomitant treatment with PPI. Citation Format: Ryo Sawada, Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Takashi Kijima, Koichi Takayama. Impact of proton pump inhibitor on ICI with or without chemotherapy for NSCLC with high PD-L1 TPS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3730.

Clinical Impact of Proton Pump Inhibitor and Potassium-Competitive Acid Blocker for Predicting the Curability of Endoscopic Resection in Ulcerative Early Gastric Cancer

Introduction: Endoscopic diagnosis is essential for predicting the curability of early gastric cancer (EGC; R0 resection) before treatment, but the relationship between ulcerative lesions and clinical outcomes remains unclear. We aimed to investigate the effect of proton pump inhibitor (PPI) or potassium-competitive acid blocker (P-CAB) on the morphological changes of ulcerative EGCs and its relevance to the clinical outcomes. Methods: Altogether, 143 patients with differentiated ulcerative EGC that were resected by endoscopic submucosal dissection were retrospectively identified and divided into the following two cohorts depending on their PPI/P-CAB administration status: PPI/P-CAB (n = 76) and non-PPI/P-CAB (n = 67) cohorts. Furthermore, in each cohort, the patients were further divided into the improved and unimproved subgroups based on the ulcerative changes. Results: In the PPI/P-CAB cohort, the deep submucosal invasion and lymphovascular invasion rates were significantly higher in the unimproved subgroup than in the improved subgroup, resulting in a significantly lower R0 resection rate. Contrarily, no significant differences were found between the two subgroups in the non-PPI/P-CAB cohort. The significance of PPI/P-CAB administration was observed only in the ulcerative EGCs with open-type atrophy (R0 resection rate; improved vs. unimproved, 90.9% vs. 48.0%, p = 0.001). When the finding of improved ulcer with PPI/P-CAB administration was used as the indication of endoscopic resection in ulcerative EGCs with open-type atrophy, high sensitivity (78.9%) and accuracy (76.3%) rates for the curability were observed, which were higher than those of conventional endoscopic diagnosis alone (p = 0.021). Conclusion: PPI or P-CAB administration might contribute to the potential selection of ulcerative EGCs, enabling endoscopic curative resection.

The Impact of Proton Pump Inhibitors on the Efficacy of Immune Checkpoint Inhibitor Combinations in Patients with HBV-Associated Advanced Hepatocellular Carcinoma.

There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs. We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients' survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated. A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient's OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024). PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.

Review of Impact of Proton Pump Inhibitors on GERD Patients

Review of Impact of Proton Pump Inhibitors on GERD Patients

Clinical impact of proton pump inhibitors and other co-medications on advanced melanoma patients treated with BRAF/MEK inhibitors

PurposeWhile several studies reported the influence of co-medications on immune checkpoint therapy and chemotherapy, it remains poorly studied with targeted therapy. Targeted therapies inhibiting BRAF and MEK had significantly improved management of advanced melanoma with BRAFV600 mutation over the last decade, we aimed to investigate the possible influence of co-mediations on the efficacy and toxicity of these targeted therapies (TT). MethodsWe conducted an observational study identifying patients with advanced melanoma treated with BRAF/MEK inhibitors between 2013 and 2020 in the Bordeaux University Hospital. Co-medications given within 1 month before until 3 months after the initiation of targeted therapy were recorded and classified by their mechanism or by their metabolism. Survival data were analyzed with univariable and multivariable cox regression and the combined effect of multiple factors was evaluated using a factor analysis of mixed data (FAMD). The impact of co-medications on toxicity related to TT was also assessed. ResultsA total of 192 patients were included. Although several co-medications were associated with significantly shorter overall survival (OS) and/or progression-free survival (PFS), PPIs was the only co-medication with a significant impact in multivariable analysis considering all co-medications and specific prognostic factors. Co-medications did not influence the risk, type, or timing of TT-related toxicity. Additional FAMD revealed the impact of each factor on the oncological outcomes. In a subgroup of patients, residual plasma TT concentration was available and did not differ between PPIs users and non-users. ConclusionCo-medications, especially PPIs, must be carefully assessed at the time of TT initiation.

Impact of Proton Pump Inhibitors on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review.

Proton pump inhibitors (PPIs) are widely prescribed medications for the management of various gastrointestinal disorders, primarily gastroesophageal reflux disease (GERD) and peptic ulcers. However, recent concerns have emerged regarding their potential adverse effects on kidney function and their role in the progression of chronic kidney disease (CKD). This systematic review aims to comprehensively analyze the existing literature to assess the impact of PPI use on kidney function and CKD progression. We took information from PubMed, PubMed Central (PMC), and Google Scholar articles from the last 10 years, from 2013 to 2023, and looked for links between PPI use and a number of kidney-related outcomes. These included acute kidney injury, a drop in the estimated glomerular filtration rate (eGFR), and new cases of CKD. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve were taken out and looked at to see if there were any links between PPI use and different kidney-related events, such as acute kidney injury, a drop in the estimated eGFR, and the development of CKD. The review also explores potential mechanisms underlying PPI-induced nephrotoxicity. The findings of this systematic review highlight the need for a thorough evaluation of the benefits and risks associated with PPI use, particularly in patients with pre-existing kidney conditions, in order to inform clinical decision-making and improve patient care. Further research is warranted to better understand the complex interplay between PPIs, kidney function, and CKD progression.

Investigation into the impact of proton pump inhibitors on sertraline transport across the blood-brain barrier

As a widely used antidepressant that works by inhibiting the reuptake of serotonin, sertraline exerts an antidepressant effect depending on its concentration in the brain, which might be limited by the blood-brain barrier (BBB). It is highly possible to combine proton pump inhibitors (PPIs) with sertraline in clinical trials. Nevertheless, the role played by PPIs in regulating the transport of sertraline across the BBB remains unclear. Here, the impact of PPIs on the distribution of sertraline in the brain and the mechanisms involved were investigated. A mouse brain distribution study showed that Omeprazole (OME), Pantoprazole (PAN), Ilaprazole (ILA), and Esomeprazole (ESO) increased the area under the brain concentration-time curves (AUC) for sertraline by 2.02-, 3.18-, 3.04-, and 4.21-fold, respectively, after the 14-day administration of PPIs. Besides, PPIs significantly increased the permeability of sertraline in brain perfusion experiments, with PAN having the highest rank order, followed by ILA, OME, and ESO. In the tail suspension test (TST), co-administration PPI groups showed significantly shorter immobility time than the control group. In vitro, four PPIs inhibited sertraline efflux in breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and showed a mixed inhibition type. In this study, PPIs were further found to inhibit the mRNA and protein expression of brain BCRP. To sum up, the findings of this study revealed that PPIs could enhance the brain distribution and antidepressant effect of sertraline, which may be attributed to the inhibition of BCRP expression at the BBB by PPIs.

Impact of proton pump inhibitor on quality of anticoagulant control and outcomes in atrial fibrillation patients treated with an oral anticoagulant in the COOL-AF registry

Abstract Introduction Proton pump inhibitor (PPI) is commonly prescribed in patients treated with antithrombotic therapy, assuming it will reduce bleeding risk irrespective of the risk of bleeding. Although PPI may reduce the risk of gastrointestinal bleeding in those treated with an oral anticoagulant, PPI may increase INR by accelerating warfarin absorption, thereby increasing the risk of bleeding. We aimed to assess the impact of PPI use on outcomes and quality of anticoagulant control in AF patients treated with OAC. Methods The COOL-AF registry was a nationwide prospective observational study enrolling AF patients from 27 hospitals in Thailand between 2014 and 2017. The registry aimed to evaluate antithrombotic patterns, quality of OAC control, and clinical outcomes. Clinical information of patients was collected every six months and until three years. Patients treated with oral anticoagulants (either warfarin or non-vitamin K antagonist OAC (NOAC)) were included in the present analysis. Patients receiving any PPI type and dosage at the registry entry were counted as PPI users. Poor anticoagulant control was defined as time to therapeutic range (TTR) less than 65%. The association between PPI use and outcomes, including GI bleeding, overall bleeding, all-cause mortality, and ischemic stroke or systemic embolization, were assessed in the Cox model adjusted for age, prior GI bleeding, chronic alcohol use, chronic kidney disease, liver disease, smoking, and baseline anemia. Subgroup analyses were performed in patients at high bleeding risk (HAS-BLED score ≥ 3), and in patients concomitantly treated with antiplatelet. Results Of 3,402 patients in the registry, 2568 (75.5%) were treated with OAC at baseline. The prevalence of females was 43.4%, with a mean age of 68.4 years. The majority of patients (91.1%) received warfarin. The incidence of major bleeding was 2.11 (1.79–2.48) per 100 person-years. PPI was used at baseline in 707 patients (20.8%). Compared with their counterpart, PPI was more frequently used in high-bleeding risk patients (27.3% vs. 18.1%, p < 0.001) and in those with concomitant antiplatelet therapy (37.5% vs. 17.1%, p < 0.001). The mean TTR was similar between PPI and non-PPI users (52.5% vs. 53.8%, p 0.37). PPI use was not associated with poor anticoagulant control (adjusted OR 1.12, 95% 0.89-1.40). The risk of GI bleeding in PPI users was similar to non-user (adjusted HR 1.01, 95%CI 0.59-1.75). The risk of all-cause mortality, ischemic stroke or systemic embolization, and overall bleeding was not different between PPI and non-PPI users. There was no significant interaction between PPI use and bleeding risk or concomitant antiplatelet therapy on adverse outcomes. Conclusion PPI use has no impact on major outcomes, including bleeding in AF patients treated with OAC. The practice of concomitant prescribing of PPI in patients treated with OAC is needed to be re-examined, given the potentially high impact of health care costs.PPI use and outcomes

1465P Clinical impact of proton pump inhibitor on the therapeutic outcome of non-small cell lung cancer patients with PD-L1 TPS ≥50% receiving pembrolizumab monotherapy versus immune checkpoint inhibitor plus chemotherapy: A retrospective multicenter cohort study

1465P Clinical impact of proton pump inhibitor on the therapeutic outcome of non-small cell lung cancer patients with PD-L1 TPS ≥50% receiving pembrolizumab monotherapy versus immune checkpoint inhibitor plus chemotherapy: A retrospective multicenter cohort study

154P The impact of proton pump inhibitors in the prognosis of patients with non-metastatic nasopharyngeal carcinoma

154P The impact of proton pump inhibitors in the prognosis of patients with non-metastatic nasopharyngeal carcinoma

2033MO The impact of proton pump inhibitor (PPI) exposure before immune checkpoint inhibitor (ICI) therapy on overall survival (OS): A population-based study

2033MO The impact of proton pump inhibitor (PPI) exposure before immune checkpoint inhibitor (ICI) therapy on overall survival (OS): A population-based study

Quasi Experimental Study to Ascertain Link of PPI to Bone Profile in Healthy Individuals

Proton pump inhibitor (PPI) is only acid blocking agent used for treating the disease known as gastroesophageal reflux (non-erosive), erosive esophagitis disease, dyspepsia disease and the peptic ulcer disease because of its efficacy and potency. However, overuse of it is examined an immediate result of absence of determination of need for steady treatment in many outdoor subjects Objective: To evaluate impact of proton pump inhibitor (PPI) on bone biochemistry in young individuals of Hyderabad. Methods: The study contained 227 young individuals of age 20-45 years, it was conducted in Liaquat University Hospital, Hyderabad City and Medicine OPD’s of Jamshoro. The research study is undertaken using Quasi experimental study. The study duration is 6 months starting from 15th March 2020 to 15th September 2020 and sampling technique is non – probability convenience. SPSS 21 software is used to analyze the data. The post stratification chi – square test is performed at the interval of 95% confidence, besides it the P-value is observed ≤ 0.05. Results: There is no effect on serum calcium and vitamin D levels with use of proton pump inhibitor PPI. P-value was observed 0.7 for the serum calcium and the p- value for Serum Vitamin D was 0.1. Conclusions: Hence, the study showed that proton pump inhibitor PPI use for less than 6 months have no effect on bone biochemistry.

Impact of proton pump inhibitors on the onset of gastrointestinal immune-related adverse events during immunotherapy.

The gut microbiota (GM) can influence the pathogenesis of immune-mediated adverse events (irAEs). Proton pump inhibitors (PPIs) can affect the integrity of GM, but their role in promoting irAEs is still poorly understood. In this retrospective single-center cohort study, the primary endpoint was the evaluation of the incidence of gastrointestinal (GI) irAEs in cancer patients on PPIs (exposed) versus cancer patients who were not on PPIs (unexposed). Three hundred and sixty three patients' records (248 M/115F, median age 69) were reviewed. Twenty-three exposed patients (92%) developed GI irAEs while only two unexposed patients (8%) developed GI irAEs (hazard ratio [HR] 13.22, 95% confidence interval [CI] 3.11-56.10, p < 0.000). This HR was confirmed after weighting for the propensity score (HR15.13 95% CI 3.22-71.03, p < 0.000). Chronic PPI use is associated with an increased risk of GI irAES.

The impact of proton pump inhibitors on the course of ulcerative colitis: a cohort study of over 10,000 newly diagnosed patients in Norway

Background and Aims Proton pump inhibitors (PPI) affect the gastrointestinal microbiota, which is thought to play a role in the pathogenesis of ulcerative colitis (UC). Previous studies suggest an association between PPI use and risk of incident UC as well as disease course. The aim of the study was to examine if PPI exposure is associated with disease course in UC patients. Methods A national cohort consisting of all newly diagnosed UC patients from 2010 to 2020 was defined combining data from Norwegian registries. PPI exposure was included as a time dependent variable with a 30 day time lag from starting the drug. Outcomes were starting advanced therapies including anti-TNF, systemic glucocorticoids, any additional systemic anti-inflammatory medication and undergoing colectomy during follow-up. Time-dependent Cox regressions included the variables PPI use, first systemic glucocorticoid prescription, first UC hospitalization, age-groups and sex. Results The study cohort consisted of 10,149 patients with median age 40 years (IQR 27–56) and 56% males. PPI use independently increased the risk of starting advanced therapies (HR 1.54, 95% CI 1.36–1.73, p < 0.005), starting systemic glucocorticoids (HR 1.20, 95% CI 1.07–1.34, p < 0.005), starting any additional anti-inflammatory treatment (HR 1.18, 95%CI 1.05–1.32, p < 0.01) and undergoing colectomy (HR 1.52, 95%CI 1.17–1.98, p < 0.005). Conclusions PPI use was associated with unfavorable outcomes including advanced therapy initiation, additional anti-inflammatory medications and undergoing colectomy. Although further studies are needed, the evidence suggests that PPIs could affect the course of UC and should be used cautiously in UC patients.

Impact of proton pump inhibitors on the risk of small bowelor colorectal bleeding: A systematic review and meta-analysis.

Several studies have suggested that the mucosal protective effects of proton pump inhibitors (PPIs) do not extend beyond the duodenum; however, PPIs may cause lower gastrointestinal (LGI) injury, although these relationships have not yet been fully elucidated. We searched all the relevant studies published until September 2022 that examined the risk of PPIs for LGI bleeding. We performed a meta-analysis of the risk of LGI bleeding (small bowel (SB) or colorectal bleeding) between PPI users and non-users. A subgroup analysis of patients consuming aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) was also performed. Twelve studies with 341,063 participants were included in this meta-analysis. The use of PPIs was associated with the risk of LGI bleeding (odds ratio [OR] [95% confidence interval [CI]]=1.42 [1.16-1.73]; hazard ratio [HR] [95% CI]=3.23 [1.56-6.71]). An association between PPI use and the risk of LGI bleeding was also identified in the subgroup of aspirin or NSAID users (OR [95% CI]=1.64 [1.49-1.80]; HR [95% CI]=6.55 [2.01-21.33]). In the bleeding site-specific analyses, the risk of SB bleeding was associated with PPI use (OR [95% CI]=1.54 [1.30-1.84]). PPI use was associated with an increased risk of LGI bleeding, particularly SB bleeding. This association was particularly pronounced among aspirin and NSAID users. Inappropriate PPI prescriptions should be avoided in patients with LGI bleeding and a low risk of upper gastrointestinal disease.