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In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a lower rate of total worsening heart failure events and death from cardiovascular causes than placebo.

Humans have been colonized by Helicobacter pylori for at least 50,000 years and probably throughout their evolution. H. pylori has adapted to humans, colonizing children and persisting throughout life. Most strains possess factors that subtly modulate the host environment, increasing the risk of peptic ulceration, gastric adenocarcinoma, and possibly other diseases. H. pylori genes encoding these and other factors rapidly evolve through mutation and recombination, changing the bacteria-host interaction. Although immune and physiologic responses to H. pylori also contribute to pathogenesis, humans have evolved in concert with the bacterium, and its recent absence throughout the life of many individuals has led to new human physiological changes. These may have contributed to recent increases in esophageal adenocarcinoma and, more speculatively, other modern diseases.

Helicobacter pylori are bacteria that have coevolved with humans to be transmitted from person to person and to persistently colonize the stomach. Their population structure is a model for the ecology of the indigenous microbiota. A well-choreographed equilibrium between bacterial effectors and host responses permits microbial persistence and health of the host but confers risk of serious diseases, including peptic ulceration and gastric neoplasia.

The inter-relationships between minimal and maximal left atrial volume index (LAVI), left ventricular filling pressures and survival have not been well studied. This study aimed to compare LAVImin with LAVImax with respect to (1) relative prognostic value, and (2) correlation with left ventricular end-diastolic pressures (LVEDP), in patients with myocardial infarction (MI). A retrospective study involving consecutive patients with a first-ever MI (n = 419) was undertaken. LAVIs were determined using Simpson's biplane method from 2D echocardiography performed the day after admission. LAVmin ≥ 18 mls/m2 and LAVImax ≥ 34 mls/m2 were considered enlarged. The primary end point was composite major adverse cardiovascular events (MACE) (death/MI/heart failure). Correlation between LVEDP and LAVI was assessed in 120 patients who underwent echocardiography and cardiac catheterization either simultaneously (n = 30) or same-day (n = 90). At a median follow-up of 24 months, there were 61 MACE events. On Cox proportional hazards multivariate analysis incorporating significant clinical predictors and LVEF, whereas both LAVImin ≥ 18 mls/m2 (hazard ratio 3.15 [95% confidence interval 1.70 to 5.54], p <0.001) and LAVImax ≥ 34 mls/m2 (hazard ratio 1.79 [95% confidence interval 1.02 to 3.14], p = 0.041) were independent predictors of MACE, LAVImin showed a stronger association. Intermodel comparisons of the model chi-square and Harrell's C-statistic confirmed better prognostication with LAVImin. In the invasive cohort, because LAVImin and LAVImax had a similar correlation with LVEDP ≥ 15 mm Hg (r = 0.41 [p <0.001] vs r = 0.42 [p <0.001]), LAVmin ≥ 18 mls/m2 had a greater sensitivity for LVEDP ≥ 15 mm Hg than LAVImax ≥ 34 mls/m2 (sensitivity 59.4% vs 34.4%). In conclusion, utilizing thresholds of ≥18 and ≥34 mls/m2, respectively, LAVImin was a better predictor of survival than LAVImax, the pathophysiologic basis of which relates to a better sensitivity for elevated left ventricular filling pressures with LAVImin at these thresholds. There may be incremental clinical value in measuring LAVImin alongside LAVImax.

Background Helicobacter pylori-induced peptic ulceration is less likely to occur in patients with a strong gastric anti-inflammatory regulatory T cell (Treg) response. Migration of Tregs into the gastric mucosa is therefore important. Objective To identify the homing receptors involved in directing Tregs to the gastric mucosa, and investigate how H pylori stimulates the relevant chemokine responses. Design Gastric biopsy samples and peripheral blood were donated by 84 H pylori-infected and 46 uninfected patients. Luminex assays quantified gastric biopsy chemokine concentrations. Flow cytometry was used to characterise homing receptors on CD4+CD25hi Tregs. H pylori wild-type and isogenic mutants were used to investigate the signalling mechanisms behind CCL20 and IL-8 induction in gastric epithelial cell lines. Transwell assays were used to quantify Treg migration towards chemokines in vitro. Results CCL20, CXCL1-3 and IL-8 concentrations were significantly increased in gastric biopsy samples from H pylori-infected patients. CCR6 (CCL20 receptor), CXCR1 and CXCR2 (IL-8 and CXCL1-3 receptors) were expressed by a higher proportion of peripheral blood Tregs in infected patients. Most gastric Tregs expressed these receptors. H pylori induced CCL20 production by gastric epithelial cells via cag pathogenicity island (cagPAI)-dependent NF-κB signalling. Foxp3+, but not Foxp3−, CD4 cells from infected mice migrated towards recombinant CCL20 in vitro. Conclusions As well as increasing Treg numbers, H pylori infection induces a change in their characteristics. Expression of CCR6, CXCR1 and CXCR2 probably enables their migration towards CCL20 and IL-8 in the infected gastric mucosa. Such qualitative changes may also explain how H pylori protects against some extragastric inflammatory disorders.

Heart failure with preserved ejection fraction (HFpEF) looms as a major public heart challenge with increasing prevalence due to an ageing population. Diagnosis can be challenging due to non-specific symptomatology, low natriuretic peptide levels and equivocal diastology on resting echocardiography. Diastolic stress echocardiography represents a non-invasive option to refining the diagnosis in this subset of patients. Diastolic responses to exercise are most commonly measured with a non-invasive measure of left ventricular filling pressures (LVFP) estimated by the ratio of the early mitral inflow wave to early diastolic tissue velocity (E/e′ ratio). This is measured pre- and post-exercise , and is highly feasible. An elevation of exercise E/e′ >15 is classified as an abnormal response as per current guidelines. An alternative measure of exercise-related diastolic performance, the Diastolic Functional Reserve Index has also been proposed, but has not been as well studied as exercise E/e′. A number of studies have validated exercise E/e′ as a measure of LVFP against invasively measured LVFP using simultaneous echocardiography–catheterisation studies. The independent prognostic value of exercise E/e′ has also been well delineated in a number of studies. While diastolic stress echocardiography can be considered for all patients with suspected HFpEF, it is of particular value in patients with normal or equivocal diastolic indices on resting echocardiography.

Background Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression. Results We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori , as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation. Conclusion There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.

BackgroundPatients with HF are at a higher risk of rehospitalisation and, as such, significant costs to our healthcare system. A non-invasive method to collect body fluids and measure Gal-3 could improve the current management of HF. In this study, we investigated the potential prognostic utility of salivary Galectin-3 (Gal-3) in patients with heart failure (HF).MethodsWe collected saliva samples from patients with HF (n = 105) either at hospital discharge or during routine clinical visits. Gal-3 concentrations in saliva samples were measured by ELISA. The Kaplan–Meier survival curve analysis and Cox proportional regression model were used to determine the potential prognostic utility of salivary Gal-3 concentrations.ResultsThe primary end point was either cardiovascular death or hospitalisation. Salivary Gal-3 concentrations were significantly higher (p < 0.05) in patients with HF who subsequently experienced the primary endpoint compared to those who did not. HF patients with salivary Gal-3 concentrations > 172.58 ng/mL had a significantly (p < 0.05) higher cumulative risk of the primary endpoint compared to those with lower salivary Gal-3 concentrations. In patients with HF, salivary Gal-3 concentration was a predictor of the primary endpoint even after adjusting for other covariates.ConclusionsIn our pilot study, HF patients with salivary Gal-3 concentrations of > 172.58 ng/mL demonstrated a higher cumulative risk of the primary outcome compared to those with lower Gal-3 levels, even after adjusting for other variables. Confirming our findings in a larger multi-centre clinical trial in the future would enable salivary Gal-3 measurements to form part of routine management for patients with HF.

Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%-64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%-41%) with beta-blockers, and 32% (95% CI: 25%-39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%-7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%-10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified. The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed. Please see later in the article for the Editors' Summary.