Received Proton Pump Inhibitors Research Articles

Bee Honey as an Adjuvant Therapeutic Modality for Children with Functional Dyspepsia

Abstract Background Functional dyspepsia (FD) is a constellation of diverse gastrointestinal disturbing symptoms with multifactorial feature, that are not attributable to organic causes after proper medical assessment. Treatment options are unsatisfactory due to the lack of identifiable pathophysiology as well as the pharmacological therapy are less effective, so using an additional reliable non- pharmacological therapy would be promising. Bee honey has been used as a complementary and alternative medicine for its several benefits in different health aspects. Objective To assess the effect of bee honey as an adjuvant therapy among children with functional dyspepsia. Patients and Methods In this randomized controlled clinical trial (RCT) 30 patients aged (8-18) years old according to Rome IV criteria from Gastroenterology Clinic in Children’s Hospital, Ain Shams University, Egypt. Patients were randomly allocated into 2 groups; both groups received proton pump inhibitor (PPI) for 4 weeks and the intervention group received honey in addition. Both groups were re-assessed after this period. All patients were subjected to thorough history taking, physical examination and follow-up assessment which was done every week during the study period. Assessment of the severity of dyspepsia was done by using "Modified Glasgow Dyspepsia Severity Score" (MGDS) score. Results There were no significant differences in the baseline sociodemographic characteristics and total scores at the beginning of the study among both groups(p > 0.05). A significant beneficial effect of honey combined with PPI in improvement of FD and decrease severity of symptoms in intervention group which was evident from significant decreases in total score interpretation (P < 0.05). There was statistically significant difference between both groups as regards to the percentage of improvement, where the patients who received honey showed a higher percentage of cure rate (P < 0.05). Conclusion Honey supplementation combined with PPI could be used as a novel therapeutic modality in children with functional dyspepsia with high cure rate.

Genetic Markers of Helicobacter pylori Resistance to Clarithromycin and Levofloxacin in Moscow, Russia.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to develop test systems for personalized drug selection, this study was designed to analyze the molecular resistance of H. pylori using a newly developed Sanger sequencing test platform. The characteristics of the test system were determined on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100% and those to levofloxacin were 93% and 92%, respectively. The test system has been tested in real clinical practice on 112 H. pylori-positive patients who had not previously received proton pump inhibitors (PPIs) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples and those indicating resistance to levofloxacin were found in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G and to levofloxacin resistance-261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help to avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Impact of gender on the management and prognosis of oesophageal fistula after atrial fibrillation ablation - a subanalysis of the worldwide POTTER-AF study

Abstract Background Oesophageal fistula (OF) is a rare but devastating complication following atrial fibrillation (AF) ablation. The data regarding the impact of gender on the management and prognosis of OF are scarce. Methods The POTTER-AF study is a worldwide, multi-centre registry conducted under the auspices of the Working Group of Cardiac Electrophysiology of the German Cardiac Society (AGEP, DGK) which evaluated the incidence, management, and outcome of post-procedural OF following catheter ablation of AF. A total of 553 729 patients underwent ablation procedures for AF or atrial tachycardia (AT) in 214 electrophysiological centres from 35 countries between 1996 and 2022. Of them, 138 (0.025%) patients experienced postprocedural OF and data regarding the gender, management and prognosis were available in 117 patients. Herein we conducted a gender- based analysis of the patients exhibiting OF. Purpose To evaluate the impact of gender on the management and prognosis of OF. Results Females represented 47% of the study population, which is a notable finding considering that the female population represents only a minority of the patients receiving AF/AT ablation. They were less likely to have atrioesophageal fistula (90.9% vs. 100%; p=0.021). Oesophageal-pericardial fistula occurred solely in females (7.3% vs. 0%; p=0.046). Congestive heart failure was significantly less frequent in the female population (7.4% vs. 26.7%; p=0.012). No other difference was seen between genders regarding the baseline characteristics and comorbidities (Table1). The energy source, ablation technique and utilization of oesophageal temperature probes were similar for males and females. Significantly less women received proton pump inhibitors (PPI) postprocedural (64.8% vs. 84.7%; p=0.017). The median duration until onset of symptoms was 20 days for women and 16.5 days for men (p=0.14), while the median duration until OF diagnosis was 22.5 days and 19.5 days respectively (p=0.217). Significantly more women underwent echocardiography (36.4% vs. 15%; p=0.01) as diagnostic method. More women exhibited stroke (32.7% vs. 14.8%; p=0.040), while there was no significant difference regarding the incidence of septic shock, coma, cardiac arrest, cardiac tamponade, and gastro-intestinal bleeding. Significantly more women than men presented no complications other than OF (9.6% vs. 0%; p=0.026). The females were more likely to undergo endoscopic treatment (35.8% vs. 17.7%; p=0.034), but less likely to undergo direct surgical treatment, without stenting (28.3% vs. 51.6%; p=0.014) (Figure1). The mortality was 63.6% for women and 67.2% for men (p=0.70), with no difference in terms of major and minor sequelae. Conclusion Approximatively half of the patients exhibiting postprocedural OF are females. Women showed a higher rate of endoscopic treatment and a lower rate of direct surgical treatment. The survival, as well as the incidence of minor and major sequelae were similar between genders.

Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations.

The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1-49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy.

Pantoprazole promotes sustained intestinal carriage of multidrug-resistant Escherichia coli in amoxicillin-treated mice.

The main objective of this study was to compare extended-spectrum β-lactamase (ESBL) Escherichia coli fecal titers during 12 days between two groups: mice who received proton pump inhibitors (PPIs) and those that did not. We tested three different in vivo models: model 1, high inoculum (106 CFU ml-1); model 2, low inoculum (102 CFU ml-1); and model 3, low inoculum and 2-day amoxicillin wash-out. There was no significant difference between the two groups in fecal ESBL E. coli titers in models 1 and 2. The fecal titers of ESBL E. coli were probably too high to show differences in colonization related to PPI treatment. By introducing a 2-day wash-out period after stopping amoxicillin (model 3), the fecal ESBL E. coli titers were higher in the PPI-treated mice during 12 days (3 log versus 11 log day CFU g-1; P<0.05). This result highlighted that PPIs promote stable ESBL E. coli digestive carriage in mice. Fecal quantitative PCR showed that mice with low ESBL E. coli fecal titers had a much higher concentration of equol-producing bacteria, Muribaculum sp., and Adlercreutzia caecimuris. Pantoprazole treatment promotes sustained digestive carriage of ESBL E. coli in amoxicillin-treated mice.

264. A RETROSPECTIVE CHART REVIEW OF 85 PATIENTS UNDERGOING THE REFLUXSTOP PROCEDURE TO MANAGE GASTROESOPHAGEAL REFLUX DISEASE: SAFETY AND EFFICACY

Abstract Background RefluxStop is a novel surgical device that manages gastroesophageal reflux disease (GERD) by restoring the normal structure of the antireflux barrier. This is accomplished by reinstating the acute angle of His and anchoring the gastroesophageal sphincter adequately in the intraabdominal cavity. This study reports the safety and efficacy of 79 patients in the postoperative period. Methods A retrospective chart review was performed on 79 patients that underwent the RefluxStop procedure at a single institution between July 2021 and November 2022 to manage GERD symptoms after informed consent was obtained. Measures were evaluated to assess the feasibility, safety, and clinical outcomes during the follow-up period. Results 79 patients (age 49.8 ± 14 years), 46 of which were male, had a mean BMI of 25.8 ± 4.5. Associated conditions noted included esophagitis (45.6%), Barrett’s esophagus (17.7%), and hiatal hernia (57%). Hiatal hernias were large in 35% of cases, with an overall average size of 2.9 cm. Baseline symptoms included general GERD symptoms (35.4%), heartburn (29.1%), cough (13.9%), regurgitation (11.4%), retrosternal burning (10.1%), hoarseness (5.1%), abdominal pain or pressure (3.8%), nausea (2.5%), and others. Baseline GERD health-related quality of life (GERD-HRQL) score was 21.5 ± 5.2 and patients were receiving proton pump inhibitors (PPIs) for a mean of 4.7 ± 6.8 years. After surgery (10.7 ± 3.1 months), all subjects experienced significant improvement in GERD-related symptoms including dysphagia. Only 2.5% of patients required use of PPIs and no subjects required postoperative esophageal dilatation or reoperation. Additionally, there were no severe perioperative complications. Postoperatively, the mean GERD-HRQL score was significantly reduced to 1.6 ± 3.2 (92.6% improvement). Conclusion This study adds to a growing body of evidence that the RefluxStop procedure is safe and effective in management of GERD patients. Notably, a considerable improvement in PPI usage and health-related quality of life parameters were appreciated. Additional studies are required to further validate the role of this procedure in disease management.

Proton pump inhibitors in critically ill mechanically ventilated patients with COVID-19: protocol for a substudy of the Re-EValuating the Inhibition of Stress Erosions (REVISE) Trial

BackgroundCritically ill patients commonly receive proton pump inhibitors (PPIs) to prevent gastrointestinal (GI) bleeding from stress-induced ulceration. Despite widespread use in the intensive care unit (ICU), observational data suggest that PPIs may be associated with adverse outcomes in patients with COVID-19 infection. This preplanned study is nested within a large randomized trial evaluating pantoprazole versus placebo in invasively ventilated patients. The 3 objectives are as follows: (1) to describe the characteristics of patients with COVID-19 in terms of demographics, biomarkers, venous thromboembolism, tracheostomy incidence and timing, and other clinical outcomes; (2) to evaluate the impact of COVID-19 infection on clinically important GI bleeding, 90-day mortality, and other outcomes compared to a propensity-matched non-infected cohort; and (3) to explore whether pantoprazole has a differential treatment effect on clinically important GI bleeding, 90-day mortality, and other outcomes in patients with and without COVID-19 infection.MethodsThe ongoing trial Re-EValuating the Inhibition of Stress Erosions (REVISE) compares pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important GI bleeding and the primary safety outcome of 90-day mortality. The protocol described in this report is for a substudy focused on patients with COVID-19 infection that was not in the original pre-pandemic trial protocol. We developed a one-page case report form to characterize these patients including data related to biomarkers, venous thromboembolism, COVID-19 therapies, tracheostomy incidence and timing, duration of mechanical ventilation, and ICU and hospital stay. Our analysis will describe the trajectory of patients with COVID-19 infection, a propensity-matched analysis of infected and non-infected patients, and an extended subgroup analysis comparing the effect of PPI among patients with and without COVID-19 infection.DiscussionProphylactic acid suppression in invasively ventilated critically ill patients with COVID-19 infection has unknown consequences. The results of these investigations will inform practice, guidelines, and future research.Trial registrationREVISE Trial [NCT03374800 December 15, 2017], COVID-19 Cohort Study [NCT05715567 February 8, 2023].

Characteristic analysis of early gastric cancer after Helicobacter pylori eradication: a multicenter retrospective propensity score-matched study

Background Helicobacter pylori (H. pylori) is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after H. pylori eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after H. pylori eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis. Methods A total of 81 patients of EGC after H. pylori eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of H. pylori infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images. Results There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group (p < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group (p = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy (p = 0.047), map-like redness (p < 0.001) and mild activity (p < 0.001). The predominant histopathological types differed between the two groups (p < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group (p = 0.025). But different eradication intervals of H. pylori have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year (p = 0.005), mucosal map-like redness (p < 0.001), moderate mucosal atrophy (p = 0.017), and mild activity of gastric mucosa (p = 0.005) were independent characteristics of EGC after H. pylori eradication. Conclusion Our multicenter study revealed that EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.

Is There a Potential Link between Gastroesophageal Reflux Disease and Recurrent Respiratory Tract Infections in Children?

Background: The implications of gastroesophageal reflux disease in respiratory tract infections have been investigated over time. The aim of our study was to evaluate the relationship between these two pathologic entities and the outcome after proper antireflux treatment. Methods: A group of 53 children with recurrent respiratory tract infections admitted in the gastroenterology clinic of a children’s hospital in North-East Romania was investigated for gastroesophageal reflux disease through 24 h pH-metry. Those with a Boix-Ochoa score higher than 11.99 received proton pump inhibitor treatment and were reevaluated after 2 months. Results: A total of 41 children were found with a positive Boix-Ochoa score. After 2 months of antireflux therapy, eight patients still had a positive Boix-Ochoa score. Conclusions: Recurrent respiratory tract infections with symptoms resistant to treatment should be considered a reason to investigate for gastroesophageal reflux, because the symptoms may be due to micro- or macro-aspiration of the gastric refluxate or to an esophageal-bronchial reflex mediated through the vagal nerve.

Translocation of bacterial LPS is associated with self-reported cognitive abilities in men living with HIV receiving antiretroviral therapy

BackgroundGut damage allows translocation of bacterial lipopolysaccharide (LPS) and fungal β-D-glucan (BDG) into the blood. This microbial translocation contributes to systemic inflammation and risk of non-AIDS comorbidities in people living with HIV, including those receiving antiretroviral therapy (ART). We assessed whether markers of gut damage and microbial translocation were associated with cognition in ART-treated PLWH.MethodsEighty ART-treated men living with HIV from the Positive Brain Health Now Canadian cohort were included. Brief cognitive ability measure (B-CAM) and 20-item patient deficit questionnaire (PDQ) were administered to all participants. Three groups were selected based on their B-CAM levels. We excluded participants who received proton pump inhibitors or antiacids in the past 3 months. Cannabis users were also excluded. Plasma levels of intestinal fatty acid binding protein (I-FABP), regenerating islet-derived protein 3 α (REG3α), and lipopolysaccharides (LPS = were quantified by ELISA, while 1–3-β-D-glucan BDG) levels were assessed using the Fungitell assay. Univariable, multivariable, and splines analyses were performed.ResultsPlasma levels of I-FABP, REG3α, LPS and BDG were not different between groups of low, intermediate and high B-CAM levels. However, LPS and REG3α levels were higher in participants with PDQ higher than the median.Multivariable analyses showed that LPS association with PDQ, but not B-CAM, was independent of age and level of education. I-FABP, REG3α, and BDG levels were not associated with B-CAM nor PDQ levels in multivariable analyses.ConclusionIn this well characterized cohort of ART-treated men living with HIV, bacterial but not fungal translocation was associated with presence of cognitive difficulties. These results need replication in larger samples.

Proton-pump inhibitor use and hyponatremia

Proton-pump inhibitors (PPIs) are widely used. However, reports of their adverse effects are increasing. Older patients are prone to developing hyponatremia due to various factors. The special environment of a geriatric healthcare facility tends to subject these patients to long-term medication use. Therefore, we hypothesized that nursing home residents receiving PPIs will present hyponatremia. The residents of Shonan Silver Garden, a long-term care health facility for older adults, were divided into two groups: a control group (n=61) which did not receive proton-pump inhibitors and a PPI group (n=29), which received proton-pump inhibitors for at least 6 months. The PPI group was further divided into the lansoprazole group (LPZ group) and the other PPI group. Other PPI users were excluded due to small numbers. The blood test results were compared between the control and LPZ groups. In the LPZ group, blood samples were taken 1 month after the discontinuation of lansoprazole, and serum Na level was compared to the level before discontinuation. Blood Na levels in the PPI were lower than those in the control group, and hyponatremia (<136 mEq/L) was more frequent in the LPZ group than in the control group. There were no significant differences in other blood test parameters between the control and LPZ groups. At one month after the discontinuation of lansoprazole, serum Na levels were significantly increased; however, they remained lower than those in the control group. A higher rate of hyponatremia was induced in older residents of long-term care facilities who took lansoprazole for >6 months in comparison to those who did not take lansoprazole.

Dynamic assessment of serum chromogranin A and treatment response with abiraterone acetate in metastatic castration-resistant prostate cancer.

Elevated serum chromogranin A (CGA) is associated with intrinsic or treatment-related neuroendocrine differentiation (NED) in men with metastatic castration-resistant prostate cancer (mCRPC). Fluctuations in serum CGA during treatment of mCRPC have had conflicting results. We analyzed the impact of (i) rising serum CGA and (ii) baseline CGA/PSA ratio during treatment to identify associations with abiraterone acetate (AA) therapy. Between June 2013 and August 2015, 92 men with mCRPC were enrolled in a prospective trial with uniform serum CGA processing performed before initiating abiraterone acetate/prednisone (AA/P) and serially after 12 weeks of AA/P treatments. Serum CGA was measured using a homogenous automated immunofluorescent assay. Patients receiving proton pump inhibitors or with abnormal renal function were excluded due to possible false elevations of serum CGA (n = 21 excluded), therefore 71 patients were analyzed. All patients underwent a composite response assessment at 12-weeks. Kaplan-Meier estimates and Cox Regression models were used to calculate the association with time-to-treatment failure analyses and overall survival. An increase in chromogranin was associated with a lower risk of treatment failure (hazard ratio [HR]: 0.52, p = 0.0181). The median CGA/PSA ratio was 7.8 (2.6-16.0) and an elevated pretreatment CGA/PSA ratio above the median was associated with a lower risk of treatment failure (HR: 0.54 p value = 0.0185). An increase in CGA was not found to be associated with OS (HR: 0.71, 95% CI: 0.42-1.21, p = 0.207). An elevated baseline CGA/PSA ratio was not associated with OS (HR: 0.62, 95% CI: 0.37-1.03, p = 0.062). An increase in PSA after 12 weeks of treatment was associated with an increased risk of treatment failure (HR: 4.14, CI: 2.21-7.73, p = < 0.0001) and worse OS (HR: 2.93, CI: 1.57-4.45, p = < 0.0001). We show that an increasing chromogranin on AA/P and an elevated baseline CGA/PSA in patients with mCRPC were associated with a favorable response to AA/P with no changes in survival. There may be limited clinical utility in serum CGA testing to evaluate for lethal NED as AA/P did not induce lethal NED in this cohort. This highlights that not all patients with an increasing CGA have a worse OS.

Incidence and Risk Factors for Clostridioides difficile Infections in Non-COVID and COVID-19 Patients: Experience from a Tertiary Care Hospital

(1) Background: The aim of this study was to assess the incidence and the risk factors for healthcare-associated Clostridioides difficile infection (HA-CDI) in patients with COVID-19 and without this infection. (2) Methods: A single-center, prospective observational study was conducted at the University Clinical Hospital Center in Belgrade, Serbia, from January 2019 to December 2021. The entire hospital was a COVID-dedicated hospital for 12 months during the study period. The incidence density rates and risk factors for HA-CDI in patients with and without COVID-19 are presented. (3) Results: The incidence rates of HA-CDIs were three times higher in patients with COVID-19. The HA-CDI-COVID-patients were younger (69.9 ± 12.6 vs. 72.5 ± 11.6; p = 0.017), admitted from another hospital (20.5% vs. 2.9; p < 0.001), had antimicrobial therapy before CDI (99.1% vs. 91.3%, p < 0.001), received two or more antibiotics (p = 0.030) during a longer period (p = 0.035), received proton pump inhibitors (95.9% vs. 50.0%, p < 0.001) during a longer period (p = 0.012) and steroids (32.8% vs. 20.4%, p < 0.001). During the last month before their current hospitalization, a higher percentage of patients without COVID-19 disease were hospitalized in our hospital (p < 0.001). Independent predictors for HA-CDIs in patients with COVID-19 were admission from another hospital (p = 0.003), the length of antibiotic administration (0.020), and the use of steroids in therapy (p < 0.001). The HA-CDI predictors in the non-COVID patients were older age (p = 0.017), advanced-stage renal failure (p = 0.005), chemotherapy (p = 0.003), and a low albumin level (0.005). (4) Conclusion: Higher incidence rates of HAI-CDIs in COVID-19 patients did not occur due to reduced infection control precautions and hygiene measures but due to antibiotic therapy and therapy with other drugs used during the pandemic.

Prevalence and factors associated with carbapenem-resistant Enterobacterales (CRE) infection among hematological malignancies patients with CRE intestinal colonization

BackgroundKnowledge about the prevalence, factors and mortality associated with subsequent carbapenem-resistant Enterobacterales (CRE) infection among hematological malignancies (HM) patients colonized with CRE is limited.MethodsHM patients were screened for rectal CRE. A retrospective case–control study of subsequent CRE infection among HM patients colonized with CRE was conducted between January 1st, 2020 and January 31st, 2022. Cases were defined as CRE colonized patients with subsequent infection and controls were those without infection. Bacterial identification was performed using MALDI Biotyper and antimicrobial susceptibility testing of strains was carried out using the VITEK 2 system or standard broth microdilution method. Logistic analysis was used for analyzing associated factors and Kaplan–Meier method was used for survival estimates.ResultsA total of 953 HM patients were screened for rectal CRE and 98 (10.3%, 98/953) patients were colonized with CRE. Among the 98 colonized patients, 18 (18.4%, 18/98) patients developed subsequent infection. Most of the colonizing CRE isolates were Klebsiella pneumoniae (50.0%, 27/54), followed by Escherichia coli (27.8%, 15/54) and Enterobacter cloacae (9.3%, 5/54). As for the subsequent infecting CRE isolates, the dominated species was K. pneumoniae (55.6%, 10/18), followed by E. coli (33.3%, 6/18) and others (11.2%, 2/18). Receiving proton pump inhibitors and admission to ICU (P < 0.05) were the associated factors. Patients with subsequent CRE infection had significant higher mortality (33.3% vs 2.8%, P = 0.001) and shock was an associated factor (P = 0.008).ConclusionsKlebsiella pneumoniae was the dominate colonizing species and subsequent infecting species among HM patients with CRE colonization. Receiving proton pump inhibitors and admission to ICU increased the risk of subsequent CRE infection among CRE colonized HM patients. Implementing strict infection control measures targeting those high- risk patients may prevent subsequent CRE infection.

Beige Mucosa Reflecting Active Sites of Eosinophilic Esophagitis.

We evaluated a 30-year-old woman with a 7-year history of eosinophilic esophagitis (EoE) with an initial complaint of moderate dysphagia. She gradually recovered after receiving proton pump inhibitors and oral budesonide. Only proton pump inhibitors were continued as a maintenance therapy until she developed very mild dysphasia 2 months earlier. Although endoscopy using white light imaging revealed characteristic findings of EoE, such as furrows and rings, with unclear images (Figure A), narrow-band imaging (NBI) revealed beige mucosa regions more clearly (Figure B). Magnified endoscopy using NBI revealed dot-shaped intrapapillary capillary loops and the absence of subepithelial vessels in the beige mucosa (Figure C). Target biopsied beige mucosa specimens revealed numerous intraepithelial eosinophils with basal layer hyperplasia and dilated intercellular spaces, reflecting active sites of EoE, whereas in nonbeige mucosa, normal squamous epithelium with few eosinophils was observed (Figure D). A recent study revealed that the loss or thinning of the superficial differentiated cell layer due to EoE activity allows 415-nm light to contact the hemoglobin component, resulting in a beige color change under NBI (Ayaki M, et al. J Gastroenterol Hepatol. 2022). The presence of beige mucosa under NBI in EoE patients, especially in cases without prominent EoE characteristic findings in white light imaging, indicates a suitable biopsied site for correct EoE diagnosis along with its histological activity.

283. DOES PROTON PUMP INHIBITOR EXPOSURE INCREASE THE RISK OF DEVELOPING EOSINOPHILIC ESOPHAGITIS IN CHILDREN WITH ESOPHAGEAL ATRESIA?

Abstract Children with esophageal atresia (EA) receive proton pump inhibitors (PPIs) long-term due to gastroesophageal reflux disease susceptibility. They have also demonstrated greater susceptibility to eosinophilic esophagitis (EoE) compared to the general pediatric population. No studies have investigated EoE risk factors in EA. This study aimed to determine whether PPI exposure and early-life factors are associated with an increased risk for subsequent EoE development in children with EA. A retrospective chart review was undertaken at a paediatric hospital in Sydney, Australia. The study cohort consisted of children with EA who had their repair and/or follow-up at this hospital between 1 January 2005 and 31 December 2020. Children with EA and EoE (cases) were matched (1:2) with those with only EA (controls), for sex, prematurity and presence of long-gap, to compare PPI exposure. Other early-life factors were analysed without matching, using simple and multivariable logistic regression. Of the 184 children with EA, 46 (25%) developed EoE during this period. Thirty-eight EoE participants were matched to 76 controls. Children with EA and EoE received PPI for significantly higher durations (p = 0.018) and at significantly higher cumulative doses (p = 0.017) than children with EA but no EoE. Food allergy (adjusted odds ratio [aOR], 10.515; 95% confidence interval [CI], 2.659–41.581), family history of atopy (aOR, 5.312; 95% CI, 1.575–17.911) and infantile antibiotic exposure (aOR, 1.048; 95% CI, 1.011–1.086) were also significantly associated with an increased risk of developing EoE in the EA cohort. Longer durations of PPI exposure and exposure to higher cumulative doses of PPI were both associated with the subsequent development of EoE in children with EA. Other early life factors such as atopic family history, food allergy and infantile antibiotic exposure were also significantly associated with an increased risk of developing EoE in children with EA.

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors

The association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial.We retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models.Overall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28-3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23-2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36-1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93-1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10-8.05, P[interaction] = 0.032).PPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.

PULMONARY COMPLICATIONS OF ESOPHAGEAL DISEASE: ABOUT A CASE REPORT

TYPE: Late Breaking Case Report TOPIC: Pediatrics INTRODUCTION: The close anatomical relationship between the esophagus and the lung makes the latter vulnerable for esophageal diseases which are relatively common in children. CASE PRESENTATION: We report the observation of a 4-year-old girl with poly malformations suggestive of VACTERL syndrome. She underwent surgery on her first day of life for esophageal atresia with a tracheoesophageal fistula. At the age of 5 months, she developed a chronic cough and a recurrent pneumonia. The barium swallow study showed a massive supra carinal GERD, an anastomotic esophageal diverticulum and an early opacification of the bronchial tree evoking a GERD which floods the lungs or a tracheoesophageal fistula (figure). The pulmonary involvement on the thoracic CT scan was impressive with a tree-in-bud sign, parenchymatous condensations, atelectasis in retractile band, bronchiectasis and ground glass areas. she received proton pump inhibitor and anti inflammatory long term azithromycin treatment. The control barium swallow test objectified vanishing of the lung flooding. The outcome was marked by a recurrent wheezing requiring tretatment by inhaled corticosteroid. DISCUSSION: Aspiration pneumonitis is the main complication of esophageal diseases. The challenge is to determine its mechanism; is it GERD, tracheoesophageal fistula, esophageal stenosis or diverticulum as reported in this case. the objective of an early diagnosis is to not delay the appropriate treatment and to stabilize the respiratory function before irreversible damage occur, namely, bronchiectasis, bronchiolitis or lung fibrosis. CONCLUSIONS: Thus, clinical and radiological monitoring of the respiratory system in the context of esophageal disease is a crucial element to watch out for complications at an early stage. DISCLOSURE: Nothing to declare. KEYWORD: lung

Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors

ABSTRACT Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

MO136: Histological Findings in Checkpoint Inhibitor-Induced Nephropathy

Abstract BACKGROUND AND AIMS Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2]. METHOD We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy. RESULTS Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein: 12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission. Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable. Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy. CONCLUSION CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.