Chemokines and Antimicrobial Peptides Have a cag-Dependent Early Response to Helicobacter pylori Infection in Primary Human Gastric Epithelial Cells

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.     

Factors associated with hospital mortality in community-acquired legionellosis in France

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.     

Heart rate recovery after exercise and long-term prognosis in patients with coronary artery disease

Background

The long-term prognostic value of heart rate recovery (HRR) has been incompletely documented in patients with coronary artery disease (CAD). We sought to confirm the prognostic value of HRR in a large cohort with stable CAD.

Methods

From the Coronary Artery Surgery Study registry, a database of 24,958 patients with CAD who underwent cardiac catheterization between 1974 and 1979, we identified 4097 patients with baseline exercise stress testing data. HRR was measured at 3 minutes post exercise during a passive recovery. Clinical outcomes were evaluated according to HRR in both threshold and continuous models.

Results

Median long-term follow-up was 14.7 years (interquartile range, 9.8-16.2). HRR < 46 beats per minute (Bpm) most appropriately differentiated nonsurvivors from survivors (area under receiver operating characteristic curve = 0.613) and was associated with an increased risk of all-cause death (adjusted hazard ratio = 1.15; P = 0.011). Increasing HRR was associated with a lower risk of all-cause (adjusted hazard ratio = 0.94 per 10 Bpm; 95% confidence interval, 0.91-0.97; P = 0.0005) and cardiovascular (CV) mortality (adjusted hazard ratio = 0.94 per 10 Bpm; 95% confidence interval, 0.90-0.98; P = 0.003).

Conclusions

HRR at 3 minutes independently predicts long-term all-cause and CV mortality in patients with stable CAD. Measurement of HRR at 3 minutes during passive recovery can be used as a complementary tool to identify patients with a higher total and CV risk.