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What you need to know: More than 90% of duodenal ulcers are linked to H pylori infection; eradication therapy with antibiotics and proton pump inhibitors is the mainstay of treatment; A “test and treat” strategy for H pylori infection is appropriate in patients under 60 with suspected peptic ulcer disease who have no complications; Proton pump inhibitors are important in the prevention and treatment of peptic ulcer disease, but avoid their use without clear indications, and re-evaluate patients on long-term treatment; Gastric ulcers are followed up with endoscopy until healed to rule out malignancy; Urgently refer patients with complications such as bleeding, perforation, or penetration to an emergency unit.

BackgroundEosinophilic oesophagitis (EoE) is an increasingly common cause of dysphagia in both children and adults, as well as one of the most prevalent oesophageal diseases with a significant impact on physical health and quality of life. We have provided a single comprehensive guideline for both paediatric and adult gastroenterologists on current best practice for the evaluation and management of EoE.MethodsThe Oesophageal Section of the British Society of Gastroenterology was commissioned by the Clinical Standards Service Committee to develop these guidelines. The Guideline Development Group included adult and paediatric gastroenterologists, surgeons, dietitians, allergists, pathologists and patient representatives. The Population, Intervention, Comparator and Outcomes process was used to generate questions for a systematic review of the evidence. Published evidence was reviewed and updated to June 2021. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to assess the evidence and make recommendations. Two rounds of voting were held to assess the level of agreement and the strength of recommendations, with 80% consensus required for acceptance.ResultsFifty-seven statements on EoE presentation, diagnosis, investigation, management and complications were produced with further statements created on areas for future research.ConclusionsThese comprehensive adult and paediatric guidelines of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology, Hepatology and Nutrition are based on evidence and expert consensus from a multidisciplinary group of healthcare professionals, including patient advocates and patient support groups, to help clinicians with the management patients with EoE and its complications.

ObjectiveAcid exposure time (AET) from ambulatory pH studies and reflux oesophagitis are independent measurements used by the Lyon classification to diagnose GORD. This study aimed to validate AET reference ranges and diagnostic thresholds by analysis of 96-hour wireless pH studies from healthy, asymptomatic controls (HCs) and patients with and without oesophagitis.DesignHC and consecutive patients referred for wireless pH studies (off acid suppressants for >7 days) underwent 96-hour pH studies at two tertiary referral centres. Erosive oesophagitis was categorised by the Los Angeles (LA) classification. Linear regression and receiver operating curve (ROC) analysis were performed to define optimal diagnostic cut-offs.ResultsProlonged, 96-hour pH studies were completed in 39 HCs (age 28 (18–53) years, 72% female) and 944 patients (age 46 (16–85) years, 65% female), of whom 136 (14.5%) had reflux oesophagitis. Median AET in HC was 1.3% (upper 95th percentile 4.6%) for any study day and 2.6% (upper 95th percentile 6.9%) for the worst day (24-hour period) during the study. ROC analysis for average AET differentiated HC from patients with moderate-to-severe oesophagitis (LA BCD; sensitivity 87%, specificity 95%, positive predictive value (PPV) 59%, negative predictive value 99% for a cut-off AET of 4.3%; area under the receiver operating curve 0.95). Specificity was higher, but PPV was substantially lower for severe oesophagitis (LA CD). ‘Worst-day’ analysis provided similar results; however, day-to-day variability was high.ConclusionDiagnostic thresholds for average AET were identified that accurately discriminate between HCs and patients with erosive oesophagitis. The findings provide conditional support for diagnostic criteria for GORD proposed by the Lyon Consensus.

INTRODUCTION:Lymphocytic esophagitis (LyE) and eosinophilic esophagitis (EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared with EoE.METHODS:This was an international retrospective study on adults enrolled at 3 centers in Europe. We recorded clinical characteristics and endoscopy findings at baseline and symptoms, histology, and endoscopy outcomes after treatment of patients with LyE and EoE.RESULTS:Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 patients with LyE compared with 59 patients with EoE. Proton pump inhibitor response was generally lower in LyE.DISCUSSION:LyE is clinically different from EoE, but differences in treatment response need further investigation.

The cervical inlet patch is an island of heterotopic gastric mucosa, most commonly found in the proximal oesophagus. Its importance as a cause of throat symptoms has been recognised, particularly chronic globus sensation. This has led to a change in the Rome IV criteria for globus management, with emphasis on ruling out the condition. Proton pump inhibitors are often ineffective in resolving symptoms. Endoscopic studies on the use of ablative techniques, most recently radiofrequency ablation (RFA), have shown promise in reversing the CIP to mormal squamous mucosa, with subsequent symtpomatic resolution.The aim of this review is to update on the investigation and management of the CIP.

Photodynamic therapy (PDT) using 5-aminolaevulinic acid (ALA-PDT) is an attractive alternative to PDT with porfimer sodium for the treatment of high-grade dysplasia (HGD) in Barrett’s oesophagus (BO) because of the shorter duration of light photosensitivity and low risk of oesophageal stricture formation. Published results, however, show marked variation in its efficacy, and optimum treatment parameters have not been defined. This study investigated how the dose of ALA and the colour of the illuminating light influenced the biological effect. Twenty-seven patients were enrolled into a randomised controlled trial of red versus green (635 nm or 512 nm) laser light activation for the eradication of HGD with ALA-PDT in Barrett’s oesophagus. A further 21 patients were subsequently treated with the most effective regimen. Regular endoscopic follow-up with quadrantic biopsies every 2 cm was performed. The primary outcome measure was eradication of HGD. Patient’s receiving ALA at 30 mg/kg relapsed to HGD more than those receiving 60 mg/kg ( P  = 0.03). Additionally, for those treated with ALA 60 mg/kg, red laser light was more effective than green laser light ( P  = 0.008). Kaplan–Meier analysis of the 21 patients who were subsequently treated with this optimal regimen demonstrated an eradication rate of 89% for HGD and a cancer-free proportion of 96% at 36 months’ follow-up. Using an ALA dose of 60 mg/kg activated by 1,000J/cm red laser light, we found that ALA-PDT was a highly effective treatment for high-grade dysplasia in Barrett’s oesophagus.

In habitat modelling, environmental variables are assumed to be proxies of lower trophic levels distribution and by extension, of marine top predator distributions. More proximal variables, such as potential prey fields, could refine relationships between top predator distributions and their environment. In situ data on prey distributions are not available over large spatial scales but, a numerical model, the Spatial Ecosystem And POpulation DYnamics Model (SEAPODYM), provides simulations of the biomass and production of zooplankton and six functional groups of micronekton at the global scale. Here, we explored whether generalised additive models fitted to simulated prey distribution data better predicted deep-diver densities (here beaked whales Ziphiidae and sperm whales Physeter macrocephalus ) than models fitted to environmental variables. We assessed whether the combination of environmental and prey distribution data would further improve model fit by comparing their explanatory power. For both taxa, results were suggestive of a preference for habitats associated with topographic features and thermal fronts but also for habitats with an extended euphotic zone and with large prey of the lower mesopelagic layer. For beaked whales, no SEAPODYM variable was selected in the best model that combined the two types of variables, possibly because SEAPODYM does not accurately simulate the organisms on which beaked whales feed on. For sperm whales, the increase model performance was only marginal. SEAPODYM outputs were at best weakly correlated with sightings of deep-diving cetaceans, suggesting SEAPODYM may not accurately predict the prey fields of these taxa. This study was a first investigation and mostly highlighted the importance of the physiographic variables to understand mechanisms that influence the distribution of deep-diving cetaceans. A more systematic use of SEAPODYM could allow to better define the limits of its use and a development of the model that would simulate larger prey beyond 1,000 m would probably better characterise the prey of deep-diving cetaceans.

PurposeA causal biomarker for acute respiratory distress syndrome (ARDS) could fuel precision therapy options. Plasma angiopoietin-2 (ANG2), a vascular permeability marker, is a strong candidate on the basis of experimental and observational evidence. We used genetic causal inference methods—Mendelian randomization and mediation—to infer potential effects of plasma ANG2.MethodsWe genotyped 703 septic subjects, measured ICU admission plasma ANG2, and performed a quantitative trait loci (QTL) analysis to determine variants in the ANGPT2 gene associated with plasma ANG2 (p < 0.005). We then used linear regression and post-estimation analysis to genetically predict plasma ANG2 and tested genetically predicted ANG2 for ARDS association using logistic regression. We estimated the proportion of the genetic effect explained by plasma ANG2 using mediation analysis.ResultsPlasma ANG2 was strongly associated with ARDS (OR 1.59 (95% CI 1.35, 1.88) per log). Five ANGPT2 variants were associated with ANG2 in European ancestry subjects (n = 404). Rs2442608C, the most extreme cis QTL (coefficient 0.22, 95% CI 0.09–0.36, p = 0.001), was associated with higher ARDS risk: adjusted OR 1.38 (95% CI 1.01, 1.87), p = 0.042. No significant QTL were identified in African ancestry subjects. Genetically predicted plasma ANG2 was associated with ARDS risk: adjusted OR 2.25 (95% CI 1.06–4.78), p = 0.035. Plasma ANG2 mediated 34% of the rs2442608C-related ARDS risk.ConclusionsIn septic European ancestry subjects, the strongest ANG2-determining ANGPT2 genetic variant is associated with higher ARDS risk. Plasma ANG2 may be a causal factor in ARDS development. Strategies to reduce plasma ANG2 warrant testing to prevent or treat sepsis-associated ARDS.

Understanding the spawning strategies of large pelagic fish could provide insights into their underlying evolutionary drivers, but large-scale information on spawning remains limited. Here we leverage a near-global larval dataset of 15 large pelagic fish taxa to develop habitat suitability models and use these as a proxy for spawning grounds. Our analysis reveals considerable consistency in spawning in time and space, with 10 taxa spawning in spring/summer and 9 taxa spawning off Northwest Australia. Considering the vast ocean expanse available for spawning, these results suggest that the evolutionary benefits of co-locating spawning in terms of advantageous larval conditions outweigh the benefits of segregated spawning in terms of reduced competition and lower larval predation. Further, tropical species spawn over broad areas throughout the year, whereas more subtropical and temperate species spawn in more restricted areas and seasons. These insights into the spawning strategies of large pelagic fish could inform marine management, including through fisheries measures to protect spawners and through the placement of marine protected areas. Demystifying the spawning strategies of fish can help us understand their evolutionary drivers and better inform fisheries management. This study reveals the spawning strategies of pelagic fish, showing that the benefits of co-located spawning across time and space outweigh the potential drawbacks.