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Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP), a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl), respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching), protection of the photosynthetic system (improving quantum yield of photosystem II) and regulation of ion homeostasis (improving the K+:Na+ ratio in leaves and roots). To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions.Highlight: Omeprazole enhances growth of tomato and increases tolerance to salinity stress through alterations of gene expression and ion uptake and transport.

Background:The best available evidence regarding non-steroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) bleeding comes from randomized controlled trials including patients who use NSAIDs to manage chronic rheumatic diseases; however, patients with varying background profiles commonly take NSAIDs for many other reasons, often without prescription, and such usage has not been well studied. Objectives and methods:To define the characteristics of patients hospitalized for upper GI bleeding in clinical practice, we conducted a case–control study among patients with endoscopy-proven major upper GI bleeding due to gastroduodenal peptic lesions and control subjects. We used adjusted logistic regression models to estimate bleeding risks. Data analysis was performed using SPSS 22.0. Results:Our analysis included 3785 cases and 6540 controls, including 1270 cases (33.55%) and 834 controls (12.75%) reporting recent use (<30 days) of NSAIDs including high-dose acetylsalicylic acid (ASA). NSAID use was associated with increased risk of upper GI bleeding, with an adjusted relative risk of 4.86 (95% CI, 4.32–5.46). Acute musculoskeletal pain (36.1%), chronic osteoarthritis (13.5%), and headache (13.6%) were the most common reasons for NSAID use. Among cases, only 17.31% took NSAIDs and 6.38% took high dose ASA due to chronic osteoarthritis. Demographic characteristics significantly differed between subjects with chronic vs. acute musculoskeletal pain. Proton pump inhibitor use was significantly higher in patients who used NSAIDs due to chronic osteoarthritis compared to patients with acute musculoskeletal pain. NSAID (65.15%) or high-dose ASA use (65.83%) preceding upper GI bleeding was most often short-term. In over half of cases (63.62%), the upper GI bleeding event was not preceded by dyspeptic warning symptoms. Conclusions:The majority of patients hospitalized due to NSAID-related upper GI bleeding reported short-term NSAID use for reasons other than chronic rheumatic disease. These findings suggest that current prevention strategies may not reach a wide population of short-term NSAID users. [ABSTRACT FROM PUBLISHER]

Pre-treatment of tomato plants with micromolar concentrations of omeprazole (OP), a benzimidazole proton pump inhibitor in mammalian systems, improves plant growth in terms of fresh weight of shoot and roots by 49 and 55% and dry weight by 54 and 105% under salt stress conditions (200 mM NaCl), respectively. Assessment of gas exchange, ion distribution, and gene expression profile in different organs strongly indicates that OP interferes with key components of the stress adaptation machinery, including hormonal control of root development (improving length and branching), protection of the photosynthetic system (improving quantum yield of photosystem II) and regulation of ion homeostasis (improving the K+:Na+ ratio in leaves and roots). To our knowledge OP is one of the few known molecules that at micromolar concentrations manifests a dual function as growth enhancer and salt stress protectant. Therefore, OP can be used as new inducer of stress tolerance to better understand molecular and physiological stress adaptation paths in plants and to design new products to improve crop performance under suboptimal growth conditions. [ABSTRACT FROM AUTHOR]

Abomasal (gastric) ulceration is a morbidity in sheep, and currently, there is a paucity of pharmacokinetic and pharmacodynamic data for gastroprotectant drugs reported for this species. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via increasing the gastric pH. The objective of this study was to report the pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single intravenous dosing. Four healthy adult Southdown cross ewes had blood collected over a 24  h time period after single intravenous dosing of esomeprazole at 1.0  mg/kg. Abomasal fluid was sampled over 24  h before and after esomeprazole administration. Plasma samples were analyzed for concentrations of esomeprazole and the esomeprazole metabolite, esomeprazole sulfone by high performance liquid chromatography. Pharmacokinetic and pharmacodynamic data were evaluated with specialized software. Esomeprazole was rapidly eliminated after IV administration. Elimination half-life, area under the curve, initial concentration (C0), and clearance were 0.2  h, 1,197  h*ng/mL, 4,321  ng/mL, and 0.83  mL/h/kg, respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16  h, 22.5  h*ng/mL, and 65.0  ng/mL, respectively. Abomasal pH was significantly elevated from 1 to 6  h after administration and remained above 4.0 for at least 8 h after administration. No adverse effects were noted in these sheep. Esomeprazole was rapidly eliminated in sheep, similar to goats. Abomasal pH was increased, but future studies will be necessary to develop a clinical management approach to the use of esomeprazole in sheep., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Smith, Gebert, Bennett, Ebner, Flynn, Mulon, Harvill, Escher, Kreuder, Bergman and Cox.)

The risk for impaired vitamin B12 status increases with age, as does the use of proton pump inhibitors (PPI). Long-term use of PPIs is associated with several nutritional deficiencies including B12. Currently, there are no recommendations for B12 screening among patients taking PPIs. Data were abstracted on B12 concentrations, B12-containing supplement use, medications, and select hematological values from a retrospective chart review of 658 adults, 391 with serum B12 concentrations, admitted to 6 different medical units at 2 regional hospitals in Southwestern Ontario between 2010 and 2012. We found no difference between PPI users and nonusers and serum B12 concentrations (404 ± 224 vs 369 ± 213 pmol/L; P = 0.0690). This may be due to use of B12 containing multivitamins in 41% of PPI users. Regression modelling found that aging increases the odds of having an impaired B12 status (<220 pmol/L) by 1.4 times and those using B12 supplements are almost 4 times more likely to have an impaired status. Mean corpuscular volume was not related to B12 status. In this population, older PPI users are more likely to be using multivitamins, which may delay nutritional deficiencies. However, the lower B12 concentrations of PPI users taking only B12 supplements is a concern and requires further research. Finally, physicians need to be aware that mean corpuscular volume is no longer recommended as an effective biomarker for B12 screening and updated screening protocols need to be used to reduce the possibility of adverse neurological effects from impaired B12 status. [ABSTRACT FROM AUTHOR]

Background Proton pump inhibitors (PPIs) are among the commonest drugs used nowadays. The aim of our study was to analyze prolonged utilization of proton pump inhibitors in medical therapy of patients with ischemic and valvular heart disease. Secondly, profile of utilization was scrutinized to patient characteristics and type of cardiovascular treatments. Methods The study included consecutive patients scheduled for cardiovascular rehabilitation 2–6 months after index cardiovascular treatment. Results Two hundred ninety-four patients (n = 294/604; 48.7%) have been using proton pump inhibitor in their therapy after index cardiovascular treatment. Cardiovascular treatments were powerfully connected with utilization of PPIs; surgery 5.77 (95%-confidence intervals [CI]: 4.05–8.22; p < 0.001) and PCI 0.15 (CI: 0.10–0.22; p < 0.001). The odds for having proton pump inhibitor in their chronic therapy were increased for atrial fibrillation 1.87 (CI: 1.08–3.23; p = 0.025) and decreased for obesity 0.65 (CI: 0.45–0.96; p = 0.035); surviving myocardial infarction 0.49 (CI: 0.29–0.83; p = 0.035). Multinomial logistic regression controlled for existence of chronic renal disease found no significant association of renal dysfunction and PPI therapy. The existence of anemia was significantly increased in patients taking PPIs than controls; 6.00 (CI: 3.85–9.33; p < 0.001). The use of PPI was also associated with worsening of metabolic profile, in part due to decreased utilization of ACE-inhibitors and statins. PPI consumption correlated with age of patients (Rho = 0.216; p < 0.001). Conclusions High proportion of cardiovascular, particularly surgical patients with ischemic and valvular heart disease utilized proton pump inhibitor in prolonged courses. Prolonged courses of PPIs were connected with existence and worsening of red blood count indexes, older age, lesser weight of patients and underutilization of cardioprotective drugs. [ABSTRACT FROM AUTHOR]

Objective Recent studies have presented conflicting results on the association between gastric acid suppression and spontaneous bacterial peritonitis (SBP). The long-term effects of gastric acid suppression on SBP in cirrhotic patients remain unclear. This study evaluated the risk of SBP in advanced decompensated cirrhotic patients with long-term gastric acid suppression. Methods Using the Taiwan National Health Insurance Research Database, we identified 4788 patients with decompensated cirrhosis from 1998 to 2011. The SBP incidence rate was compared among proton pump inhibitor (PPI), H2-receptor antagonist (H2RA), and control cohorts. Multivariate Cox proportional hazards regressions analysis was conducted to confirm the association between gastric acid suppression and SBP. Results Totally, 4788 patients were analyzed: 1870 in the PPI cohort, 1728 in the H2RA cohort, and 1190 in the control cohort. The overall incidences of SBP were 16.8, 11.9, and 9.80 per 1000 person-years in the PPI, H2RA, and control cohorts, respectively. The adjusted hazard ratio (aHR) of SBP during the follow-up period was 1.16- (95% confidence interval [CI], 0.72–1.86) and 1.00-fold (95% CI, 0.63–1.57) higher in the PPI and H2RA cohorts, respectively, than in the control cohort; the result was non-significant. Compared with the control cohort, patients with > 180 days of PPI therapy had significantly higher risks of SBP, with an aHR of 2.28 (95% CI, 1.37–3.78). Conclusions Long-term PPI use is associated with a high risk of SBP in advanced decompensated cirrhotic patients. Well-designed prospective studies are necessary to evaluate the safety of long-term PPI use in such patients. [ABSTRACT FROM AUTHOR]

Background: Gut-derived bacteraemia is a major complication in patients with haematological malignancy after chemotherapy. Objective: Our study aimed to investigate the role of proton pump inhibitors (PPIs) in the occurrence of gutderived bacteraemia. Methods: We compared data from 92 hospitalized haematological malignancy patients after chemotherapy with gut-derived bacteraemia, collected from January 2009 to July 2015, with those of 92 contemporaneous, hospitalized haematological malignancy patients without bacteraemia. We evaluated PPIs use and analysed the effects of covariates. Results: Patients with gut-derived bacteraemia had a significantly higher incidence of PPIs use (69.6%) than that of controls (47.8%). Of the patients with gut-derived bacteraemia, only 44.6% had a documented indication for PPIs therapy. The antibacterial prophylaxis rate was 38.0% in the bacteraemia group and 58.7% in the non-antibacterial group. Based on multivariable logistic regression analysis, only PPIs use (P = 0.00, odds ratio (OR) = 0.546) was found to be associated with the risk of bacteraemia whereas antibacterial prophylaxis (P = 0.00, OR = 0.652) was protective. There were no significant differences in demographics, malignancy status, length of neutropenia, complications, or steroid use between the gutderived bacteraemia and control group. Conclusions: This study suggests a potential association between PPIs use and development of gut-derived bacteraemia in haematological malignancy patients after chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use. Introduction: The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD. Methods: Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort ( n = 10,620), which was frequency matched with the comparison cohort ( n = 20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models. Results: The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40-1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39-1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53-1.18). Conclusion: GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI. [ABSTRACT FROM AUTHOR]

Background and Objective: Gastroesophageal reflux (GER) is a common condition in infants. Usually, it resolves spontaneously in 95% of cases within 12-14 months of age, but gastroesophageal reflux disease (GERD) may develop in some children. Most authors do not recommend pharmacological treatment of GER, while the management of GERD is debated. The aim of this narrative review is to analyze and summarize the available literature on the clinical use of gastric antisecretory drugs in pediatric patients with GERD., Methods: References were identified through MEDLINE, PubMed, and EMBASE search engines. Only articles in English were considered. The following keywords were used: "gastric antisecretory drugs", "H2RA", "PPI", "ranitidine", "GERD", "infant", "child"., Key Content and Findings: Increasing evidence of poor efficacy and potential risks of proton pump inhibitors (PPIs) is emerging in neonates and infants. Histamine-2 receptor antagonists (H2RAs), including ranitidine, have been used successfully in older children, although less effective than PPIs at relieving symptoms and healing GERD. However, in April 2020, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) requested manufacturers of ranitidine to remove all ranitidine products from the market due to the risk of carcinogenicity. Pediatric studies comparing effectiveness and safety of different acid-suppressing treatments for GERD are generally inconclusive., Conclusions: A proper differential diagnosis between GER and GERD is crucial to avoid the overuse of acid-suppressing medications in children. Further research should be directed towards the development of novel antisecretory drugs, with proven efficacy and good safety profile, for treating pediatric GERD, particularly in newborns and infants., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-22-401/coif). RA serves as an unpaid editorial board member of Translational Pediatrics from March 2022 to February 2024. The other authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Background. Incomplete control of troublesome regurgitation and extraesophageal manifestations of chronic gastroesophageal reflux disease (GERD) is a known limitation of proton pump inhibitor (PPI) therapy. This multicenter randomized study compared the efficacy of transoral incisionless fundoplication (TIF) against PPIs in controlling these symptoms in patients with small hiatal hernias. Methods. Between June and August 2012, 63 patients were randomized at 7 US community hospitals. Patients in the PPI group were placed on maximum standard dose (MSD). Patients in the TIF group underwent esophagogastric fundoplication using the EsophyX2 device. Primary outcome was elimination of daily troublesome regurgitation or extraesophageal symptoms. Secondary outcomes were normalization of esophageal acid exposure (EAE), PPI usage and healing of esophagitis. Results. Of 63 randomized patients (40 TIF and 23 PPI), 3 were lost to follow-up leaving 39 TIF and 21 PPI patients for analysis. At 6-month follow-up, troublesome regurgitation was eliminated in 97% of TIF patients versus 50% of PPI patients, relative risk (RR) = 1.9, 95% confidence interval (CI) = 1.2-3.11 (P = .006). Globally, 62% of TIF patients experienced elimination of regurgitation and extraesophageal symptoms versus 5% of PPI patients, RR = 12.9, 95% CI = 1.9-88.9 (P = .009). EAE was normalized in 54% of TIF patients (off PPIs) versus 52% of PPI patients (on MSD), RR = 1.0, 95% CI = 0.6-1.7 (P = .914). Ninety percent of TIF patients were off PPIs. Conclusion. At 6-month follow-up, TIF was more effective than MSD PPI therapy in eliminating troublesome regurgitation and extraesophageal symptoms of GERD. [ABSTRACT FROM PUBLISHER]

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause a high frequency of mucosal injuries in the small intestine. However, no reliable intervention, other than cessation of NSAIDs, has been established. Objective: To evaluate whether irsogladine maleate reduces these injuries while continuing NSAID therapy. Design: Prospective, interventional, endoscopist-blinded, randomized, controlled trial (RCT). Setting: University hospital. Patients: Patients regularly taking conventional NSAIDs for more than 4 weeks. Interventions: We initially examined small-intestinal mucosal injuries by capsule endoscopy (CE) and screened participants for the RCT. In the RCT, patients with any mucosal injury were randomly assigned to the irsogladine group (4 mg/day) or the control group. Main Outcome Measurements: The primary endpoint was the rate of mucosal injury improvement after 4 weeks of treatment monitored with a second CE. Results: Sixty-one patients were evaluated with the first CE. Small intestine mucosal injuries were found in 41 patients (67.2%) and erosive or ulcerative lesions in 21 patients (34.4%). The injury prevalence was not different with gastroprotective drug treatment. Of 41patients enrolled, 39 (19 patients in the irsogladine group and 20 in the control group) completed the study. The improvement rate was significantly higher in the irsogladine group (16/19 patients; 84.2%) than in the control group (9/20 patients; 45.0%; P = .02). Limitations: Asymptomatic lesions, single-institution data, and single-blind setting. Conclusion: Irsogladine maleate was effective for reducing NSAID-induced small-intestinal mucosal injury. (University Hospital Medical Information Network Clinical Trials Registry number UMIN000001507.) [Copyright &y& Elsevier]

Objectives: This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI). Background: Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain. Methods: A retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i.e., no percutaneous coronary intervention or coronary artery bypass grafting during the index hospitalization or within 7 days post-discharge). Over 2 years of follow-up, we measured the association between clopidogrel use and all-cause mortality, hospital stay for MI, and a composite endpoint of death or MI using propensity-matched multivariable Cox analyses. Results: We identified 16,365 patients with incident UA (35%) or NSTEMI (65%); 36% of these patients were prescribed clopidogrel within 7 days of discharge. In 8,562 propensity score–matched patients, clopidogrel users had lower rates of all-cause mortality (8.3% vs. 13.0%; p < 0.01; adjusted hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.54 to 0.72) and the composite of death or MI (13.5% vs. 17.4%; p < 0.01; HR: 0.74, CI: 0.66 to 0.84), but not MI alone (6.7% vs. 7.2%; p = 0.30; HR: 0.93, CI: 0.78 to 1.11), compared with nonusers of clopidogrel. The association between clopidogrel use and the composite of death or MI was significant only among patients presenting with NSTEMI (HR: 0.67; CI: 0.59 to 0.76; pint < 0.01), not among those presenting with UA (HR: 1.25; CI: 0.94 to 1.67). Conclusions: In a large, community-based cohort of patients who were medically managed after UA/NSTEMI, clopidogrel use was associated with a lower risk of death and MI, particularly among patients with NSTEMI. [Copyright &y& Elsevier]

Background & Aims: Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy (EGD) in children. However, little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure. We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain. Methods: We conducted a prospective study of 290 children (4–18 years old; mean age, 11.9 ± 3.5 years; 93 girls) who underwent EGD for the primary indication of chronic abdominal pain (216 with at least 1 alarm feature) at a US pediatric gastroenterology referral center. We collected data on demographic features (age, sex), clinical characteristics (alarm features, Rome III criteria), and EGD results for each patient. All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes. Results: Overall, EGD provided an accurate diagnosis for 109 children (38%). Diagnoses included esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%), and Crohn’s disease (0.4%). Short-term outcomes were available for 81% of patients with diagnostic findings, and medical therapy was effective in approximately 67% of these children. Conclusions: EGD is valuable for the diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD identified disorders for which medical therapy was effective in 67% of children during the year after diagnosis. [Copyright &y& Elsevier]

Abstract: Ischemic heart disease is the primary cause of death worldwide. The pathophysiological process of cardiovascular diseases is linked to atheromatous plaque formation, while plaque rupture releases thrombogenic elements, which lead to activation of platelets, blood clotting and formation of thrombi. Platelet inhibitors are used to prevent thrombosis. The present systematic review discusses the efficacy of prasugrel in terms of platelet inhibition potential and clinical prevention of cardiovascular outcomes. The balance between reduction of ischemic events as a measure of drug efficacy and the risk of bleeding is reviewed. Other adverse events observed in patients treated with this platelet inhibitor are discussed, including hematological complications, and cutaneous and hepatic idiosyncratic reactions. The complex relationship between prasugrel use and cancer promotion is also described. [Copyright &y& Elsevier]

Background: A new device for mechanical sphincter augmentation (MSA) of the lower esophageal sphincter was approved by the FDA on March 22, 2012. We report early experience with MSA, specifically addressing postoperative management. Study Design: Between October 1, 2011 and June 1, 2013, 150 patients were evaluated for MSA. Of these, 66 patients underwent device implantation; the first implant was April 10, 2012. All patients had objectively confirmed gastroesophageal reflux disease (GERD) with pH testing, acceptable esophageal motility, and no significant hiatal hernia (>3 cm). All patients experienced clinical improvement on antisecretory medication, but incomplete symptom control or medication intolerance. Results: All patients were successfully implanted without intra- or perioperative complications. Average length of hospital stay was 0.7 days. At an average follow-up of 5.8 months (range 1 to 18.6 months), 92% of patients are satisfied or neutral with their GERD condition, and 83% are proton pump inhibitor free. The GERD-Health-Related Quality of Life (HRQL) scores are similar to those of patients without GERD. There were no device ulcers or erosions and no devices explanted. Thirteen patients underwent additional testing for dysphagia or persistent symptoms. Calls with questions and nursing involvement in the first 6 months postoperatively were 3 times what is typical for fundoplication patients. Dysphagia and regurgitation were the most common concerns. All these symptoms were improving over time. Conclusions: Single-center early results are promising and parallel those from a multicenter trial. There is significant interest in MSA, with referrals and direct patient appointments specifically for MSA. Outcomes improve over time after implantation. The surgeon learning curve is different than with the Nissen, both in operative technique and postoperative management. This is a promising new offering for patients with GERD, and surgeons will need to learn how to integrate this into their practices. [Copyright &y& Elsevier]

Background: The published prevalence of Barrett's esophagus (BE) varies from 0.9% to 25%, in part because of differences in the endoscopic interpretation of the disease. Objective: We studied the accuracy of diagnosis in 130 patients previously labeled as having BE. Our aim was to determine the interobserver consistency of endoscopic findings and assess the percentage of patients with confirmed BE versus those with a revised diagnosis. Design/Setting/Patients: Patients previously diagnosed with BE of any length and due for surveillance endoscopy were eligible for study. Interventions: After intensive consensus anatomic and endoscopic review, study patients underwent endoscopy and biopsy by 1 of 3 endoscopists. BE was defined as any length of columnar-lined esophagus with goblet cells. Main Outcome Measurements: Patients were photographed/videotaped for review by the other 2 endoscopists, and BE was either confirmed or revised. Results: Eighty-eight patients (67.7%) had confirmed BE, and 42 (32.3%) had their diagnosis revised to no BE (95% confidence interval, 24.4%-41.1%) because there was no visible columnar-lined esophagus proximal to the gastric folds or no goblet cells were found on biopsy. BE length, site of previous endoscopy, age, sex, and hiatal hernia size were predictors of revision. All 3 endoscopists agreed on all confirmed BE cases and 38 of 42 of those revised. Limitations: Retrospective analysis, possible sampling error. Conclusions: BE is overdiagnosed in clinical practice with important implications for patient care including increased costs, reduced insurability, and psychological stress. The true BE cancer risk may also be underestimated. This study suggests the need for a better definition of the gastroesophageal junction, stricter accountability for BE diagnosis, and improved endoscopic education. [Copyright &y& Elsevier]

Individual variability in response and development of adverse effects to drugs is a major challenge in clinical practice. Pharmacogenomics refers to the aspect of personalized medicine where the patient's genetic information instructs the selection and dosage of therapy while also predicting its adverse effects profile. Sequencing of the entire human genome has given us the opportunity to study commonly used drugs as well as newer therapeutic agents in a new light, opening up opportunities for better drug efficacy and decreased adverse effects. This article highlights developments in pharmacogenomics, relates these to practice of gastroenterology, and outlines roadblocks in translation of this knowledge into clinical practice. [Copyright &y& Elsevier]

Gastroesophageal reflux disease (GERD) is a common condition requiring considerable medical resources. The mainstay of therapy is proton pump inhibitors (PPIs), which are effective at reducing acid reflux. In patients who have refractory acid reflux and esophagitis despite high-dose PPI, or are intolerant of the side effects of PPI therapy, surgical fundoplication is the primary therapy. The risk and cost gap between medical therapy and surgery has resulted in substantial interest in less-invasive endoscopic therapies. In this review, we discuss the underlying physiology of GERD along with the anatomic hurdles that must be overcome to develop an effective antireflux procedure. We also review the current published literature and assess the clinical efficacy of the devices that have been studied or currently are being investigated. Despite promising early studies, many of the devices fall short in high-quality randomized controlled trials. Furthermore, the physiologic aberration resulting in GERD oftentimes is addressed inadequately. Although there is certainly a need for less-invasive, safe, and effective therapy for reflux, therapy will need to withstand the established clinical efficacy of both PPI and surgical fundoplication. At present, we have the luxury of time to wait for such a device to become available. [Copyright &y& Elsevier]

Background & Aims: Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. Methods: We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. Results: In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39−0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09−0.92) (with high-dose use only). Statin use for 1−4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27−0.98). Conclusions: In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups. [Copyright &y& Elsevier]

Background & Aims: Subsquamous intestinal metaplasia (SSIM) has been observed after endotherapy in patients with neoplastic Barrett's esophagus (BE). However, it is not clear whether SSIM occurs in untreated patients. Incompletely eradicated SSIM could provide a source of recurrent disease. We assessed its prevalence in a large cohort of patients who had not received endoscopic therapy. Methods: Two experienced pathologists analyzed 138 samples of 506 resection specimens found to contain squamous epithelium from 110 patients with neoplastic BE treated by widespread endoscopic mucosal resection (92 men; mean age, 66 years). The maximum extent of SSIM was measured. Results: Of the 138 samples analyzed, 124 (89.9%) were found to contain SSIM from 108 of the 110 patients (98.2%). The mean length of SSIM was 3.3 mm (range, 0.2–9.6 mm; 25% ≥5 mm); SSIM length correlated with BE length (P < .05). In 83 of 138 samples (60.1%), the SSIM consisted partially or entirely of neoplasias of different grades, with a mean subsquamous extension of 3.3 mm; the extension correlated with grade of neoplasia (P = .0001). Conclusions: Most patients with BE with neoplasia (of all grades) have subsquamous extension of intestinal metaplasia, including subsquamous extension of lesions at the squamocolumnar junction. Therefore, biopsy and resection of neoplastic BE should extend at least 1 cm into the squamous epithelium. [Copyright &y& Elsevier]

Objectives: Achalasia has a variety of therapeutic options. We sought to determine the long-term outcome of laparoscopic myotomy in a large group of patients. Methods: We conducted a retrospective record review of 500 patients who underwent laparoscopic myotomy and follow-up with a standardized dysphagia questionnaire. Results: Between April 1998 and June 2011, 276 men and 224 women underwent a laparoscopic myotomy. Their median age was 51 years (range, 8-89 years). Preoperative symptoms included dysphagia in 472 patients (94.4%), regurgitation in 382 patients (76.4%), heartburn in 203 patients (40.6%), chest pain in 168 (33.6%) patients, and weight loss (median, 10 kg) in 264 patients (52.8%). Prior therapy (dilation in 239, botulinum toxin type A in 135, or myotomy in 30) had been performed in 303 patients (60.6%). Preoperative manometry was available in 413 patients (82.6%) and revealed a median lower esophageal sphincter pressure of 31 mm Hg (range, 0-50 mm Hg), absent peristalsis in 97.6%, and no lower esophageal sphincter relaxation in 75.1%. A laparoscopic myotomy with partial fundoplication (Toupet n = 268, Dor n = 209) was done in 477 patients (95.4%) and myotomy only in 23 patients (4.6%). Conversion to open was necessary in 16 patients (3.2%). There were 52 (10.4%) esophageal perforations—all repaired during the myotomy—and 26 (5.2%) other complications, including bleeding, atrial fibrillation, and pneumonia. There was no operative mortality. Median length of stay was 2 days (range, 1-20 days). Dysphagia questionnaires were returned by 48.2% of patients (241 out of 500) a median of 77.5 months after myotomy (range, 15-176 months). Eighty patients (32.2%) reported no problems with swallowing at the time of the survey. Of 160 patients who had swallowing problems, 40 patients (22.2%) classified the problem as mild or less, 98 patients classified the problem as moderate (70.0%), and 22 patients classified the problem as severe (15.7%). The question concerning frequency of swallowing problems was answered by 160 patients and occurred once a week or less in 70 patients (43.8%), several times a week in 41 patients (25.6%), and at least daily in 49 patients (30.6%). Analysis of all 241 patients who returned questionnaires revealed that 170 out of 241 (70.5%) reported heartburn, 89 out of 241 (36.9%) reported regurgitation, and 159 out of 241 (66.0%) had taken antacids or histamine 2 blockers or proton pump inhibitors within the past 30 days of the survey. The only factor affecting outcome was age; patients older than age 65 years had a better chance of having no difficulty swallowing at follow-up (P = .0174). Sex, prior therapy, Toupet versus Dor, conversion to open, or esophageal mucosal perforation did not affect long-term swallowing outcome. Conclusions: Laparoscopic myotomy with partial fundoplication is a safe operation. The long-term outcome is extremely effective and approximately one-third of patients have no evidence of persistent symptoms at follow-up. Furthermore, those who have persistent symptoms rarely have severe or very frequent complaints. Patients older than age 65 years tend to have a better outcome. [Copyright &y& Elsevier]

Background & Aims: Infection with Helicobacter pylori, particularly the cytotoxin-associated gene A (cagA)+ strain, is believed to protect against Barrett's esophagus, but it is not clear if it protects against gastroesophageal reflux disease (GERD). We aimed to determine whether H pylori infection is associated with GERD symptoms, erosive esophagitis, and Barrett's esophagus within the same cohort. Methods: We analyzed data from a case–control study of 533 men (ages, 50–79 y) who underwent colorectal cancer screening at 2 tertiary medical centers in Michigan between 2008 and 2011 and who also were recruited to undergo upper endoscopy. We assessed 80 additional men found to have Barrett's esophagus during clinically indicated upper-endoscopy examinations. Logistic regression was used to estimate the associations between serum antibodies against H pylori or cagA and GERD symptoms, esophagitis, and Barrett's esophagus, compared with randomly selected men undergoing colorectal cancer screens (n = 177). Results: H pylori infection was associated inversely with Barrett's esophagus (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.29–0.97), particularly the cagA+ strain (OR, 0.36; 95% CI, 0.14–0.90). There was a trend toward an inverse association with erosive esophagitis (H pylori OR, 0.63; 95% CI, 0.37–1.08; and cagA+ OR, 0.47; 95% CI, 0.21–1.03). However, GERD symptoms were not associated with H pylori infection (OR, 0.948; 95% CI, 0.548–1.64; and cagA+ OR, 0.967; 95% CI, 0.461–2.03). Conclusions: Based on a case–control study, infection with H pylori, particularly the cagA+ strain, is associated inversely with Barrett's esophagus. We observed a trend toward an inverse association with esophagitis, but not with GERD symptoms. [Copyright &y& Elsevier]

Abstract: Aspirin is integral to the secondary prevention of cardiovascular disease and acts to impair the development of platelet-mediated atherothromboembolic events by irreversible inhibition of platelet cyclooxygenase-1 (COX-1). Inhibition of this enzyme prevents the synthesis of the potent pro-aggregatory prostanoid thromboxane A2. A large number of patients continue to experience atherothromboembolic events despite aspirin therapy, so-called ‘aspirin treatment failure’, and this is multifactorial in aetiology. Approximately 10% however do not respond appropriately to aspirin in a phenomenon known as ‘aspirin resistance’, which is defined by various laboratory techniques. In this review we discuss the reasons for aspirin resistance in a systematic manner, starting from prescription of the drug and ending at the level of the platelet. Poor medication adherence has been shown to be a cause of apparent aspirin resistance, and may in fact be the largest contributory factor. Also important is high platelet turnover due to underlying inflammatory processes, such as atherosclerosis and its complications, leading to faster regeneration of platelets, and hence of COX-1, at a rate that diminishes the efficacy of once daily dosing. Recent developments include the identification of platelet glycoprotein IIIa as a potential biomarker (as well as possible underlying mechanism) for aspirin resistance and the discovery of an anion efflux pump that expels intracellular aspirin from platelets. The absolute as well as relative contributions of such factors to the phenomenon of aspirin resistance are the subject of continuing research. [Copyright &y& Elsevier]

Background & Aims: Transient lower esophageal sphincter relaxations (TLESRs) contribute to episodes of reflux. Few studies have assessed the frequencies or compositions of TLESRs and reflux episodes in patients with reflux disease. We used combined high-resolution manometry and impedance monitoring to analyze reflux episodes and esophageal motility in these patients, compared with those of healthy individuals. Methods: We evaluated the frequency of TLESRs and the relationship between the reflux pattern and esophageal pressures during TLESRs in 14 patients with nonerosive reflux disease (NERD) and 11 controls. Study participants underwent combined high-resolution manometry and impedance monitoring before and 60 minutes after a solid and liquid meal. The diagnosis of NERD was confirmed by a 24-hour pH impedance test. Results: The frequency of TLESRs did not differ between patients with NERD and controls. In patients with NERD, TLESRs were associated more often with reflux episodes than in controls (93% ± 6% vs 66% ± 19%; P < .05). Patients with NERD had a higher percentage of pure liquid reflux episodes (33% ± 15% vs 10% ± 2%; P < .05), whereas controls had a higher percentage of mixed reflux episodes (45% ± 16% vs 67% ± 17% in patients with NERD; P < .05). Patients with NERD also had a higher percentage of reflux (liquid and mixed) associated with common cavities (74% ± 18% vs 50% ± 20% in controls; P < .05). Conclusions: In contrast to previous studies, we found that TLESRs are associated more often with reflux in patients with NERD than control subjects; this association increases when only liquid and mixed refluxes are considered. These findings indicate that factors involved in the occurrence of reflux in patients with NERD during TLESRs are different from those in healthy subjects. [Copyright &y& Elsevier]

Background & Aims: Alginate rafts (polysaccharide polymers that precipitate into a low-density viscous gel when they contact gastric acid) have been reported to form at the acid pocket, an unbuffered pool of acid that floats on top of ingested food and causes postprandial acid reflux. We studied the location of an alginate formulation in relation to the acid pocket and the corresponding effects on reflux parameters and acid pocket positioning in patients with gastroesophageal reflux disease (GERD). Methods: We randomly assigned patients with symptomatic GERD and large hiatal hernias to groups who were given either 111In-labeled alginate-antacid (n = 8, Gaviscon Double Action Liquid) or antacid (n = 8, Antagel) after a standard meal. The relative positions of labeled alginate and acid pocket were analyzed for 2 hours by using scintigraphy; reflux episodes were detected by using high-resolution manometry and pH-impedance monitoring. Results: The alginate-antacid label localized to the acid pocket. The number of acid reflux episodes was significantly reduced in patients receiving alginate-antacid (3.5; range, 0−6.5; P = .03) compared with those receiving antacid (15; range, 5−20), whereas time to acid reflux was significantly increased in patients receiving alginate-antacid (63 minutes; range, 23−92) vs those receiving antacid (14 minutes; range, 9−23; P = .01). The acid pocket was located below the diaphragm in 71% of patients given alginate-antacid vs 21% of those given antacid (P = .08). There was an inverse correlation between a subdiaphragm position of the acid pocket and acid reflux (r = −0.76, P < .001). Conclusions: In a study of 16 patients with GERD, we observed that the alginate-antacid raft localizes to the postprandial acid pocket and displaces it below the diaphragm to reduce postprandial acid reflux. These findings indicate the importance of the acid pocket in GERD pathogenesis and establish alginate-antacid as an appropriate therapy for postprandial acid reflux. www.trialregister.nl, Number: NTR3602 [Copyright &y& Elsevier]

Von Hippel-Lindau (VHL) disease is a rare inherited familial syndrome complicated with various neoplasms, including neuroendocrine tumors (NETs). We herein report the first case of multiple gastric NETs in a 45-year-old man with VHL. He had multiple gastric polyps, and several endoscopic resected lesions were diagnosed as NETs. The serum gastrin level was elevated because he was taking a proton pump inhibitor (PPI). We suspected that gastrin had played a role in the development of NETs, and the remaining polyps were followed up with discontinuation of the PPI. The NETs gradually reduced in size until they became hard to notice on endoscopy and have remained nearly invisible for over eight years.

Background & Aims: Clostridium difficile infection (CDI) can cause life-threatening complications. Severe-complicated CDI is characterized by hypotension, shock, sepsis, ileus, megacolon, and colon perforation. We created a model to identify clinical factors associated with severe-complicated CDI. Methods: We analyzed data from 1446 inpatient cases of CDI (48.6% female; median age, 62.5 years; range, 0.1−103.7 years) at the Mayo Clinic from June 28, 2007, to June 25, 2010. Patients with severe-complicated CDI (n = 487) were identified as those who required admission to the intensive care unit or colectomy, or died, within 30 days of CDI diagnosis. Logistic regression models were used to identify variables that were independently associated with the occurrence of severe-complicated CDI in 2 cohorts. One cohort comprised all hospitalized patients; the other comprised a subset of these inpatients who were residents of Olmsted County, Minnesota to assess the association of comorbid conditions with the development of severe-complicated infection in a population-based cohort. The linear combinations of variables identified by using logistic regression models provided scores to predict the risk of developing severe-complicated CDI. Results: In a multivariable model that included all inpatients, increasing age, leukocyte count >15 × 109/L, increase in serum level of creatinine >1.5-fold from baseline, and use of proton pump inhibitors or narcotic medications were independently associated with severe-complicated CDI. In the secondary analysis, which included only patients from Olmsted County, comorbid conditions were not significantly associated with severe-complicated CDI. Conclusions: Older age, high numbers of leukocytes in blood samples, an increased serum level of creatinine, gastric acid suppression, and use of narcotic medications were independently associated with development of severe-complicated CDI in hospitalized patients. Early aggressive monitoring and intervention could improve outcomes. [Copyright &y& Elsevier]

Background & Aims: It is not clear whether length of Barrett's esophagus (BE) is a risk factor for high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) in patients with nondysplastic BE. We studied the risk of progression to HGD or EAC in patients with nondysplastic BE, based on segment length. Methods: We analyzed data from a large cohort of patients participating in the BE Study—a multicenter outcomes project comprising 5 US tertiary care referral centers. Histologic changes were graded as low-grade dysplasia, HGD, or EAC. The study included patients with BE of documented length without dysplasia and at least 1 year of follow-up evaluation (n = 1175; 88% male), and excluded patients who developed HGD or EAC within 1 year of their BE diagnosis. The mean follow-up period was 5.5 y (6463 patient-years). The annual risk of HGD and EAC was plotted in 3-cm increments (≤3 cm, 4–6 cm, 7–9 cm, 10–12 cm, and ≥13 cm). We calculated the association between time to progression and length of BE. Results: The mean BE length was 3.6 cm; 44 patients developed HGD or EAC, with an annual incidence rate of 0.67%/y. Compared with nonprogressors, patients who developed HGD or EAC had longer BE segments (6.1 vs 3.5 cm; P < .001). Logistic regression analysis showed a 28% increase in risk of HGD or EAC for every 1-cm increase in BE length (P = .01). Patients with BE segment lengths of 3 cm or shorter took longer to develop HGD or EAC than those with lengths longer than 4 cm (6 vs 4 y; P = nonsignificant). Conclusions: In patients with BE without dysplasia, length of BE was associated with progression to HGD or EAC. The results support the development of a risk stratification scheme for these patients based on length of BE segment. [Copyright &y& Elsevier]

The endoscopic finding of a gastric polyp and the histopathologic report that follows may leave clinicians with questions that have not been addressed in formal guidelines: do all polyps need to be excised, or can they just be sampled for biopsy? If so, which ones and how many should be sampled? What follow-up evaluation is needed, if any? This review relies on the existing literature and our collective experience to provide practical answers to these questions. Fundic gland polyps, now the most frequent gastric polyps in Western countries because of widespread use of proton pump inhibitors, and hyperplastic polyps, the second most common polyps notable for their association with gastritis and their low but important potential for harboring dysplastic or neoplastic foci, are discussed in greater detail. Adenomas have had their name changed to raised intraepithelial neoplasia and are decreasing in parallel with Helicobacter pylori infection; however, they do retain their importance as harbingers of gastric cancer, particularly in East Asia. Gastrointestinal stromal tumors have low incidence and no known associations, but their malignant potential is high; early diagnosis and proper management are crucial. Although rare and benign, inflammatory fibroid polyps need to recognized, particularly by pathologists, to avoid misdiagnosis. Gastric neuroendocrine tumors (carcinoids) are important because of their association with either atrophic gastritis or the multiple endocrine neoplasia syndromes; those that do not arise in these backgrounds have high malignant potential and require aggressive management. The review concludes with some practical suggestions on how to approach gastric polyps detected at endoscopy. [Copyright &y& Elsevier]

Background: Gastroesophageal reflux disease (GERD) is a very prevalent disorder. Medical therapy improves symptoms in some but not all patients. Antireflux surgery is an excellent option for patients with persistent symptoms such as regurgitation, as well as for those with complete symptomatic resolution on acid-suppressive therapy. However, proper patient selection is critical to achieve excellent outcomes. Study Design: A panel of experts was assembled to review data and personal experience with regard to appropriate preoperative evaluation for antireflux surgery and to construct an evidence and experience-based consensus that has practical application. Results: The presence of reflux symptoms alone is not sufficient to support a diagnosis of GERD before antireflux surgery. Esophageal objective testing is required to physiologically and anatomically evaluate the presence and severity of GERD in all patients being considered for surgical intervention. It is critical to document the presence of abnormal distal esophageal acid exposure, especially when antireflux surgery is considered, and reflux-related symptoms should be severe enough to outweigh the potential side effects of fundoplication. Each testing modality has a specific role in the diagnosis and workup of GERD, and no single test alone can provide the entire clinical picture. Results of testing are combined to document the presence and extent of the disease and assist in planning the operative approach. Conclusions: Currently, upper endoscopy, barium esophagram, pH testing, and manometry are required for preoperative workup for antireflux surgery. Additional studies with long-term follow-up are required to evaluate the diagnostic and therapeutic benefit of new technologies, such as oropharyngeal pH testing, multichannel intraluminal impedance, and hypopharyngeal multichannel intraluminal impedance, in the context of patient selection for antireflux surgery. [ABSTRACT FROM AUTHOR]

Background: This study was undertaken to evaluate our clinical experience during a 6-year period with an implantable device that augments the lower esophageal sphincter for gastroesophageal reflux disease (GERD). The device uses magnetic sphincter augmentation (MSA) to strengthen the antireflux barrier. Study Design: In a single-center, prospective case series, 100 consecutive patients underwent laparoscopic MSA for GERD between March 2007 and February 2012. Clinical outcomes for each patient were tracked post implantation and compared with presurgical data for esophageal pH measurements, symptom scores, and proton pump inhibitor (PPI) use. Results: Median implant duration was 3 years (range 378 days to 6 years). Median total acid exposure time was reduced from 8.0% before implant to 3.2% post implant (p < 0.001). The median GERD Health Related Quality of Life score at baseline was 16 on PPIs and 24 off PPIs and improved to a score of 2 (p < 0.001). Freedom from daily dependence on PPIs was achieved in 85% of patients. There have been no long-term complications, such as device migrations or erosions. Three patients had the device laparoscopically removed for persistent GERD, odynophagia, or dysphagia, with subsequent resolution of symptoms. Conclusions: Magnetic sphincter augmentation for GERD in clinical practice provides safe and long-term reduction of esophageal acid exposure, substantial symptom improvement, and elimination of daily PPI use. For candidates of antireflux surgery who have been carefully evaluated before surgery to confirm indication for MSA, MSA has become a standard treatment at our institution because control of reflux symptoms and pH normalization can be achieved with minimal side effects and preservation of gastric anatomy. [Copyright &y& Elsevier]

Background & Aims: Anti-neutrophil cytoplasmic antibodies (ANCA) are a non-uniform family of antibodies recognizing diverse components of neutrophil granulocytes. ANCA formation might be induced by protracted bacterial infections or probably reflect an abnormal immune response to commensal microorganisms. Bacterial infections are common complications in cirrhosis with high incidence of episodes caused by enteric organisms, therefore, we sought to study the presence and clinical importance of ANCA in cirrhosis. Methods: Sera of 385 patients with cirrhosis of different etiologies were assayed for ANCA of IgG, IgA, IgA1, IgA2, and secretory IgA subtypes by indirect immunofluorescence and ELISAs. The control group comprised 202 patients with chronic liver diseases without cirrhosis and 100 healthy subjects. In cirrhosis, a 2-year follow-up, observational study was conducted to assess a possible association between the presence of ANCA and clinically significant bacterial infections. Results: Prevalence of ANCA IgA was significantly higher in cirrhosis (52.2%) compared to chronic liver diseases (18.6%) or healthy controls (0%, p <0.001 for both). ANCA IgA subtyping assays revealed marked increase in the proportion of IgA2 subtype (46% of total ANCA IgA) and presence of the secretory component concurrently. Presence of ANCA IgA was associated with disease-specific clinical characteristics (Child-Pugh stage and presence of ascites, p <0.001). During a 2-year follow-up period, risk of infections was higher among patients with ANCA IgA compared to those without (41.8% vs. 23.4%, p <0.001). ANCA IgA positivity was associated with a shorter time to the first infectious complication (pLogRank <0.001) in Kaplan–Meier analysis and was identified as an independent predictor in multivariate Cox-regression analysis (HR:1.74, 95% CI: 1.18–2.56, p =0.006). Conclusions: Presence of IgA type ANCA is common in cirrhosis. Involvement of gut mucosal immune system is in center of their formation and probably reflects sustained exposure to bacterial constituents. [Copyright &y& Elsevier]

Background: A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. Study Design: According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. Results: The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). Conclusions: Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications. [Copyright &y& Elsevier]

Objective: To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. Study design: Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. Results: The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). Conclusions: Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings. [Copyright &y& Elsevier]