Proton Pump Research Articles

Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett’s oesophagus patients

IntroductionEpithelial-mesenchymal plasticity (EMP), the process through which epithelial cells acquire mesenchymal features, is needed for wound repair but also might contribute to cancer initiation. Earlier, in vitro studies showed that...

Humidity-Mediated Dual Ionic-Electronic Conductivity Enables High Sensitivity in MOF Chemiresistors.

In the presence of water, the electrically conductive metal-organic framework (MOF) Cu3HHTT2 (H6HHTT = 2,3,7,8,12,13-hexahydroxy-4b1,5,10,15-tetraazanaphtho[1,2,3-gh]tetraphene) provides a conduit for proton transport, thereby becoming a dual ionic-electronic conductor. Owing to its dual conducting nature and its high density of imine and open metal sites, the MOF operates as a particularly sensitive chemiresistor, whose sensing mechanism changes with relative humidity. Thus, the interaction of NH3 gas with the MOF under low humidity promotes proton transport, which translates to high sensitivity for ammonia detection. Conversely, NO2 gas hinders proton conductivity, even under high relative humidity conditions, leading to large resistance variations in the humid regime. This dual ionic-electronic conduction-based gas sensor provides superior sensitivity compared to other conventional chemiresistors under similar conditions and highlights its potential as a platform for room-temperature gas sensors.

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.

Engineering bionanoreactor in bacteria for efficient hydrogen production

Hydrogen production through water splitting is a vital strategy for renewable and sustainable clean energy. In this study, we developed an approach integrating nanomaterial engineering and synthetic biology to establish a bionanoreactor system for efficient hydrogen production. The periplasmic space (20 to 30 nm) of an electroactive bacterium, Shewanella oneidensis MR-1, was engineered to serve as a bionanoreactor to enhance the interaction between electrons and protons, catalyzed by hydrogenases for hydrogen generation. To optimize electron transfer, we used the microbially reduced graphene oxide (rGO) to coat the electrode, which improved the electron transfer from the electrode to the cells. Native MtrCAB protein complex on S. oneidensis and self-assembled iron sulfide (FeS) nanoparticles acted in tandem to facilitate electron transfer from an electrode to the periplasm. To enhance proton transport, S. oneidensis MR-1 was engineered to express Gloeobacter rhodopsin (GR) and the light-harvesting antenna canthaxanthin. This led to efficient proton pumping when exposed to light, resulting in a 35.6% increase in the rate of hydrogen production. The overexpression of native [FeFe]-hydrogenase further improved the hydrogen production rate by 56.8%. The bionanoreactor engineered in S. oneidensis MR-1 achieved a hydrogen yield of 80.4 μmol/mg protein/day with a Faraday efficiency of 80% at a potential of -0.75 V. This periplasmic bionanoreactor combines the strengths of both nanomaterial and biological components, providing an efficient approach for microbial electrosynthesis.

Utilizing Esophageal Motility Tests in Diagnosing and Evaluating Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD), a prevalent clinical condition, is often attributed to aberrant esophageal motility, leading to gastric content reflux and associated symptoms or complications. The rising incidence of GERD presents an escalating healthcare challenge. Endoscopic and esophageal reflux monitoring can provide a basis for the diagnosis of patients with gastroesophageal reflux disease, but when the diagnostic basis is at an inconclusive value, some additional supportive evidence will be needed. Advanced technology is the key to improving patient diagnosis, accurate assessment, and the development of effective treatment strategies. High-resolution esophageal manometry (HREM) and endoscopic functional lumen imaging probe (EndoFLIP) represent the forefront of esophageal motility assessment. HREM, an evolution of traditional esophageal manometry, is considered the benchmark for identifying esophageal motility disorders. Its widespread application in esophageal dynamics research highlights its diagnostic significance. Concurrently, EndoFLIP’s emerging clinical relevance is evident in diagnosing and guiding the treatment of coexisting esophageal motility issues. This review integrates contemporary research to delineate the contributions of HREM, EndoFLIP, and novel technologies in GERD. It examines their efficacy in facilitating an accurate diagnosis, differentiating similar gastrointestinal disorders, quantifying the extent of reflux, assessing the severity of the disease, forecasting patient responsiveness to proton pump inhibitor therapy, and guiding decisions for surgical interventions. The overarching aim is to deepen the understanding of GERD’s underlying mechanisms and advance the formulation of holistic, efficacious treatment approaches.

Preparation and study of a capillary electrochromatographic column prepared by conjugating β-CD COFs and gold-poly glycidyl methacrylate nanoparticles.

A new enantioselective open-tubular capillary electrochromatography (OT-CEC) was developed employing β-cyclodextrin covalent organic frameworks (β-CD COFs) conjugated gold-poly glycidyl methacrylate nanoparticles (Au-PGMA NPs) as a stationary phase. The resulting coating layer on the inner wall of the fabricated capillary column was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS), and electroosmotic flow (EOF) experiments. The performance of the fabricated capillary column was evaluated by CEC using enantiomers of seven model analytes, including two proton pump inhibitors (PPIs, omeprazole and tenatoprazole), three amino acids (AAs, tyrosine, phenylalanine, and tryptophan), and two fluoroquinolones (FQs, gatifloxacin and sparfloxacin). The influences of coating time, buffer concentration, buffer pH, and applied voltage on enantioseparation were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of seven analytes were fully resolved within 10min with high resolutions of 3.03 to 5.25. The inter- to intra-day and column-to-column repeatabilities of the fabricated capillary column were lower than 4.26%RSD. Furthermore, molecular docking studies were performed based on the chiral fabricated column and as ligand isomers of analytes using Auto Dock Tools. The binding energies and interactions acquired from docking results of analytes supported the experimental data.

Characterizing PEM fuel cell catalyst layer properties from high resolution three-dimensional digital images, Part II: Oxygen effective diffusion and proton effective conductivity tensors

The oxygen effective diffusion and proton effective conductivity tensors of a cathode catalyst layer (CCL) are computed using a two-scale approach on CCL microstructure three-dimensional images obtained by focused ion beam-scanning electron microscopy (FIB-SEM) after reconstruction of the ionomer distribution. The results show that the obtained tensors are not isotropic. It is also found that some off-diagonal components are not negligible in the case of the proton effective conductivity tensor. The simulations confirm that Knudsen diffusion has a significant impact on oxygen diffusion. The results are comparable to those obtained in previous works on synthetic images as regards the oxygen effective diffusion through-plane component but differ as regards the proton conductivity through-plane component. Contrary to previous works using synthetic images which tend to underestimate the proton conductivity, they are globally in better agreement with experimental data. The results also show that the effective proton conductivity is heterogeneous at the scale of the computational domains typically considered in several previous works due to the variability in the ionomer distribution at this scale. The impact of liquid water in the primary pores on the proton transport is explored and found to have a significant impact.

Atherogenic Effect of Homocysteine, a Biomarker of Inflammation and Its Treatment

AbstractHyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. Ischemic stroke and heart disease, coronary heart disease, and cardiovascular disease are events resulting from long-lasting and silent atherosclerosis. This paper deals with the synthesis of homocysteine (Hcy), causes of HHcy, mechanism of HHcy-induced atherosclerosis, and treatment of HHcy. Synthesis and metabolism of Hcy involves demethylation, transmethylation, and transsulfuration, and these processes require vitamin B6 and vitamin B12 folic acid (vitamin B9). Causes of HHcy include deficiency of vitamins B6, B9, and B12, genetic defects, use of smokeless tobacco, cigarette smoking, alcohol consumption, diabetes, rheumatoid arthritis, low thyroid hormone, consumption of caffeine, folic acid antagonist, cholesterol-lowering drugs (niacin), folic acid antagonist (phenytoin), prolonged use of proton pump inhibitors, metformin, and hypertension. HHcy-induced atherosclerosis may be mediated through oxidative stress, decreased availability of nitric oxide (NO), increased expression of monocyte chemoattractant protein-1, smooth muscle cell proliferation, increased thrombogenicity, and induction of arterial connective tissue. HHcy increases the generation of atherogenic biomolecules such as nuclear factor-kappa B, proinflammatory cytokines (IL-1β, IL-6, and IL-8), cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selection), growth factors (IGF-1 and TGF-β), and monocyte colony-stimulating factor which lead to the development of atherosclerosis. NO which is protective against the development of atherosclerosis is reduced by HHcy. Therapy with folic acid, vitamin B6, and vitamin B12 lowers the levels of Hcy, with folic acid being the most effective. Dietary sources of folic acid, vitamin B6, vitamin B12, omega-3 fatty acid, and green coffee extract reduce Hcy. Abstaining from drinking coffee and alcohol, and smoking also reduces blood levels of Hcy. In conclusion, HHcy induces atherosclerosis by generating atherogenic biomolecules, and treatment of atherosclerosis-induced diseases may be by reducing the levels of Hcy.

Reverse Hydrogen Spillover on Metal Oxides for Water-Promoted Catalytic Oxidation Reactions.

Understanding the water-involved mechanism on metal oxide surface and the dynamic interaction of water with active sites is crucial in solving water poisoning in catalytic reactions. Herein, this work solves this problem by designing the water-promoted function of metal oxides in the ethanol oxidation reaction. In situ multimodal spectroscopies unveil that the competitive adsorption of water-dissociated *OH species with O2 at Sn active sites results in water poisoning and the sluggish proton transfer in CoO-SnO2 imparts water-resistant effect. Carbon material as electron donor and proton transport channel optimizes the Co active sites and expedites the reverse hydrogen spillover from CoO to SnO2. The water-promoted function arises from spillover protons facilitating O2 activation on the SnO2 surface, leading to crucial *OOH intermediate formation for catalyzing C-H and C-C cleavage. Consequently, the tailored CoO-C-SnO2 showcases a remarkable 60-fold enhancement in ethanol oxidation reaction compared to bare SnO2 under high-humidity conditions.

Proton Pump Inhibitor Induced Hypomagnesemia Causing Seizures: A Rare Adverse Effect of a Commonly Used Medication

Proton Pump Inhibitor Induced Hypomagnesemia Causing Seizures: A Rare Adverse Effect of a Commonly Used Medication

Autoimmune hepatitis – an increasingly common cause of hypertransaminasaemia among children. Case report and literature review

Autoimmune hepatitis is a chronic inflammatory process of unknown ethology, characterised by high levels of transaminases and IgG antibodies, the presence of tissue autoantibodies, and a typical histological picture. In the population of children, the paediatric form of autoimmune hepatitis and autoimmune sclerosing cholangitis are collectively classified as juvenile autoimmune liver disease. The condition often coexists with other autoimmune disorders. This paper aims to present the clinical profile of a paediatric patient with full-blown autoimmune hepatitis and describe the available therapies. The patient, a 13-year-old boy, was referred to a specialised hospital because of increasing hypertransaminasaemia. The patient was hospitalised for the first time at a district hospital for abdominal pain, and during his stay, elevated transaminases were found with a tendency to increase in follow-up tests. The picture suggested an inflammatory process of the liver and biliary tract. Upper gastrointestinal endoscopy revealed lesions consistent with chronic gastritis and portal gastropathy. Treatment included thiazolidinedioic acid, vitamin K, ursodeoxycholic acid, rifaximin, ciprofloxacin, and proton pump inhibitors. Therapy is aimed at maintaining immunosuppression and inhibiting the inflammatory response that leads to cirrhosis, and most commonly uses steroids alongside proton pump inhibitors for added protection or, alternatively, mycophenolate mofetil, cyclosporine A, tacrolimus, and biologic therapy. Ursodeoxycholic acid also exhibits immunomodulatory properties and makes it possible to reduce steroid doses and thus decrease the likelihood of adverse effects of therapy.

DA-9601 has protective effects comparable to those of proton pump inhibitor and rebamipide against nonsteroidal anti-inflammatory drugs-induced upper and lower gastrointestinal bleeding in patients with rheumatoid arthritis: A nationwide study using Korean Health Insurance Review and Assessment Service database.

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA.

Evidence for NMR Relaxation Enhancement in a Protic Ionic Liquid by the Movement of Protons Independent of the Translational Diffusion of Cations.

The molecular dynamics, thermal stability, and ionic conductivity were studied in the protic ionic liquid 1-methylimidazolium bis(trifluoromethylsulfonyl)imide ([MIm][TFSI]). The relaxation of the 1H spin-lattice of cations in the measured frequency range (10 kHz to 20 MHz) and temperature (298 to 343 K) is sensitive mainly to slow processes occurring in the molecular dynamics of protic ionic liquid and dominated by the contribution of intermolecular translational diffusion. Molecular rotations give only a constant contribution and become significant in the higher frequency range. An interesting feature is the observed enhancement of the 1H spin-lattice relaxation below 0.03 MHz attributed to the exchange of protons (order of 10-5 s) between imidazolium cations. The measurements of the self-diffusion coefficient of hydrogen atoms of cation from 298 to 343 K additionally confirm the observed phenomenon. The coefficient for exchangeable protons -NH is higher than for the cation. The nuclear magnetic resonance (NMR) experiments provide unambiguous evidence for proton transport decoupled from molecular diffusion of ions and support the conclusion that the charge transport mechanism in the studied PIL includes contributions from both the vehicular and Grotthus mechanisms. The protic ionic liquid is thermally stable to about 573 K as shown by thermogravimetric analysis and its electrical conductivity is 5 × 10-2 S/cm at 423 K.

The Effect of Liquid Saturation Transients on PEM Fuel Cell Impedance: Inductive Loop and Instability of Catalyst Layer Operation

Abstract We report a physics--based model for the electrochemical impedance of a PEM fuel cell cathode. The model takes into account the transient behavior of oxygen and proton transport in the cathode catalyst layer caused by variation of the liquid saturation with cell current. Transients of the catalyst layer oxygen diffusivity result in a second capacitive arc in the Nyquist spectrum, while proton conductivity transients lead to formation of an inductive loop. In the range of capillary pressures $p_c$ in which the liquid saturation in the catalyst layer is independent of $p_c$, the loop does not form. Stability analysis of a reduced system of equations reveals that the static solution with inductive loop is unstable with respect to spatial perturbations, implying that the post--oscillatory steady state is impossible to reach.
Possible scenarios of instability development are discussed.

Omeprazole-Loaded Copper Nanoparticles for Mitochondrial Damage Mediated Synergistic Anticancer Activity against Melanoma Cells.

Metallic nanoparticles are promising candidates for anticancer therapies. Among the different metallic systems studied, copper is an affordable and biologically available metal with a high redox potential. Copper-based nanoparticles are widely used in anticancer studies owing to their ability to react with intracellular glutathione (GSH) to induce a Fenton-like reaction. However, considering the high metastatic potential and versatility of the tumor microenvironment, modalities with a single therapeutic agent may not be effective. Hence, to enhance the efficiency of chemotherapeutic drugs, repurposing them or conjugating them with other modalities is essential. Omeprazole is an FDA-approved proton pump inhibitor used in clinics for the treatment of ulcers. Omeprazole has also been studied for its ability to sensitize cancer cells to chemotherapy and induce apoptosis. Herein, we report a nanosystem comprising of copper nanoparticles encapsulating omeprazole (CuOzL) against B16 melanoma cells. The developed nanoformulation exerted significant synergistic anticancer activity when compared with either copper nanoparticles or omeprazole alone by inducing cell death through excessive ROS generation and subsequent mitochondrial damage.

O-200 Association between proton pump inhibitors use and the risk of maternal infections during pregnancy and postpartum: a Swedish population-based cohort study

Abstract Study question Is there an association between use of proton pump inhibitors (PPIs) and maternal infection during or after pregnancy and subsequent pregnancy complications? Summary answer Use of PPIs in the 3 months before pregnancy or during the first trimester was associated with an elevated risk of maternal infection. What is known already PPIs alter gastric acidity and the gut microbiome, which may increase infection risks in the general population, but their impact on pregnant women is unknown. Study design, size, duration We conducted a Nationwide population-based cohort study using data from Swedish healthcare registers. PPIs use was defined as ≥ 1 prescription fill of a PPI in the 90 days before the first day of the last menstrual period (LMP) to the end of the 1st trimester (LMP+97 days). Maternal infections were identified from the start of the 2nd trimester to 90 days postpartum and classified as mild, moderate/ severe infections, and infection-related pregnancy complications. Participants/materials, setting, methods All pregnancies resulting in live or stillbirths between 2006 to 2019 in Sweden, identified using the Medical Birth Register. Log-binomial regression was used to estimate associations (relative risk (RR) and 95% confidence intervals (CI)) between PPIs and maternal infection, adjusting for potential confounders including birth year, maternal age at delivery, early pregnancy BMI, comorbidities, smoking in early pregnancy, maternal country of birth, maternal education, and parity. Main results and the role of chance Among 1,510,560 pregnant women, 42,599 (2.8%) used PPIs, and use increased over the study period time from 1.5% in 2006 to 3.44% in 2019. Compared to pregnant women without PPI use, those with PPI use had higher rates and risks of any infection (49.7% vs 36.8%; adjusted RR 1.30, 95%CI 1.29-1.32), mild infection (20.9% vs 16.1%; adjusted RR 1.30, 95%CI 1.28-1.33), moderate to severe infection (23.4% vs 15%; adjusted RR 1.47, 95%CI 1.45-1.50), and infection-related pregnancy complications (11.2% vs 9.2; adjusted RR 1.12, 95%CI 1.09-1.15). Conclusion Our results show an association between PPI use and an elevated risk of infection in pregnant women. Next steps include the further investigation into the infection types. PPI therapy has benefits and drawbacks that should be carefully weighed, especially in patients who are prone to infections. While our study highlights potential concerns, it does not imply that all pregnant women are at increased risk. More research is needed to understand the underlying mechanisms and assess potential preventive measures. Prescribing PPIs during pregnancy should be determined on a case-by-case basis, considering the patient’s individual health state. We acknowledge the necessity for caution, particularly in vulnerable populations, and more research is needed to demonstrate clinical correlations. Limitations, reasons for caution Potential confounding by indication due to underlying morbidities cannot be fully accounted for. Further research is required to establish clinical connections. Wider implications of the findings Clinicians should carefully weigh the benefits of PPI therapy during pregnancy, particularly in patients prone to infections. Trial registration number not applicable

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.

Upper gastrointestinal bleeding on veno-arterial extracorporeal membrane oxygenation support

IntroductionPatients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support are at a high risk of hemorrhagic complications, including upper gastrointestinal bleeding (UGIB). The objective of this study was to evaluate the incidence and impact of this complication in V-A ECMO patients.Materials and methodsA retrospective single-center study (2013–2017) was conducted on V-A ECMO patients, excluding those who died within 24 h. All patients with suspected UGIB underwent esophagogastroduodenoscopy (EGD) and were analyzed and compared to the remainder of the cohort, from the initiation of ECMO until 5 days after explantation.ResultsA total of 150 V-A ECMO cases (65 after cardiac surgery and 85 due to medical etiology) were included. 90% of the patients received prophylactic proton pump inhibitor therapy and enteral nutrition. Thirty-one patients underwent EGD for suspected UGIB, with 16 confirmed cases of UGIB. The incidence was 10.7%, with a median occurrence at 10 [7–17] days. There were no significant differences in clinical or biological characteristics on the day of EGD. However, patients with UGIB had significant increases in packed red blood cells and fresh frozen plasma needs, mechanical ventilation duration and V-A ECMO duration, as well as in length of intensive care unit and hospital stays. There was no significant difference in mortality. The only independent risk factor of UGIB was a history of peptic ulcer (OR = 7.32; 95% CI [1.07–50.01], p = 0.042).ConclusionUGIB occurred in at least 1 out of 10 cases of V-A ECMO patients, with significant consequences on healthcare resources. Enteral nutrition and proton pump inhibitor prophylaxis did not appear to protect V-A ECMO patients. Further studies should assess their real benefits in these patients with high risk of hemorrhage.

Causes Responsible For Failure of Fundoplication: A Meta-Analysis

Abstract Background GERD is a very common disease nowadays. When medications like Proton Pump Inhibitors fail, Surgery becomes the treatment of choice. Objective To review and study the most common causes responsible for failure of Fundoplication and development of the most common postoperative complications (recurrence of reflux, dysphagia and gas-bloat syndrome). Patients and Methods Types of studies Published studies about the complications of Laparoscopic Fundoplication (carried out in the period between 2000 – 2021). Types of participants Patients with clinically proven complications like GERD, belching, dysphagia or unintentional slipping after Fundoplication. Results A copy of each paper identified was obtained, and relevant data was Abstracted for a quantitative overview. In case of discrepancies or when the information presented in a study is unclear, Abstraction by a second reviewer was sought to resolve the discrepancy. All included articles was assessed for quality regarding methodological strength as per the 2009 Cochrane collaboration updated guidelines for systematic reviews. Conclusion According to our results, paraesophageal hernia in addition to, disruption and tight wrap are significant causes of failure of Nissen fundoplication.

Microbiota and Resveratrol: How Are They Linked to Osteoporosis?

Osteoporosis (OP), which is characterized by a decrease in bone density and increased susceptibility to fractures, is closely linked to the gut microbiota (GM). It is increasingly realized that the GM plays a key role in the maintenance of the functioning of multiple organs, including bone, by producing bioactive metabolites such as short-chain fatty acids (SCFA). Consequently, imbalances in the GM, referred to as dysbiosis, have been identified with a significant reduction in beneficial metabolites, such as decreased SCFA associated with increased chronic inflammatory processes, including the activation of NF-κB at the epigenetic level, which is recognized as the main cause of many chronic diseases, including OP. Furthermore, regular or long-term medications such as antibiotics and many non-antibiotics such as proton pump inhibitors, chemotherapy, and NSAIDs, have been found to contribute to the development of dysbiosis, highlighting an urgent need for new treatment approaches. A promising preventive and adjuvant approach is to combat dysbiosis with natural polyphenols such as resveratrol, which have prebiotic functions and ensure an optimal microenvironment for beneficial GM. Resveratrol offers a range of benefits, including anti-inflammatory, anti-oxidant, analgesic, and prebiotic effects. In particular, the GM has been shown to convert resveratrol, into highly metabolically active molecules with even more potent beneficial properties, supporting a synergistic polyphenol–GM axis. This review addresses the question of how the GM can enhance the effects of resveratrol and how resveratrol, as an epigenetic modulator, can promote the growth and diversity of beneficial GM, thus providing important insights for the prevention and co-treatment of OP.