Search

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF-dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas-intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation.

Background/Objectives: Pulmonary vein isolation (PVI) using radiofrequency catheter ablation with contact force (CF)-sensing technology has improved long-term outcomes in patients with atrial fibrillation. This prospective randomized study aimed to assess the efficacy and safety of CF-sensing technology for additional left atrial (LA) linear ablation of persistent AF (PerAF). Methods: After PVI, anteromitral (AM) line and roof line ablation were performed using a CF-sensing catheter. Patients were randomly assigned to either the CF-sensing (CFS) group or the CF-blind control (Blind) group. The primary endpoint was atrial arrhythmia recurrence. LA late gadolinium enhancement (LA-LGE) MRI was conducted at baseline and 1-year follow-up for long-term lesion evaluation. Results: A total of 62 patients with drug-refractory PerAF were enrolled (mean age: 58 ± 10 years; 77% male). The success rates of AM and roof line block were 97% and 100% in the CFS group (n = 33) and 93% and 90% in the Blind group (n = 29). The time to achieve block was reduced in the CFS group (AM: 36 ± 22 vs. 48 ± 28 min, p = 0.068; roof: 19 ± 14 vs. 27 ± 15 min, p = 0.031). The maximum CF for safety endpoints was significantly lower in the CFS group (AM: 42 vs. 69 g, p < 0.001; roof: 33 vs. 49 g, p = 0.003). Full linear LA-LGE formation on 1-year MRI did not differ significantly between the groups (AM: 17 vs. 36%; roof; 29 vs. 24%, both p = NS). Kaplan–Meier estimates of AF/AT-free survival after ablation procedures were 63.6% in the CFS group and 58.6% in the Blind group (log-rank p = 0.837). Conclusions: In patients with PerAF, additional LA linear ablation following PVI using CF-sensing technology improved procedural safety and reduced the time needed to achieve conduction block. However, it did not significantly influence clinical outcomes or the formation of permanent full linear lesions. [ABSTRACT FROM AUTHOR]

Bacterial pathogens utilize the factors of their hosts to infect them, but which factors they exploit remain poorly defined. Here, we show that a pathogenic Salmonella enterica serovar Typhimurium (STm) exploits host polyamines for the functional expression of virulence factors. An STm mutant strain lacking principal genes required for polyamine synthesis and transport exhibited impaired infectivity in mice. A polyamine uptake-impaired strain of STm was unable to inject effectors of the type 3 secretion system into host cells due to a failure of needle assembly. STm infection stimulated host polyamine production by increasing arginase expression. The decline in polyamine levels caused by difluoromethylornithine, which inhibits host polyamine production, attenuated STm colonization, whereas polyamine supplementation augmented STm pathogenesis. Our work reveals that host polyamines are a key factor promoting STm infection, and therefore a promising therapeutic target for bacterial infection. Bacterial pathogens often exploit host factors to enhance their infectivity. This study shows that Salmonella Typhimurium boosts host polyamine production, which is crucial for the expression and needle assembly of its type 3 secretion system. [ABSTRACT FROM AUTHOR]

Aims Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years. Methods and results Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99–4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups. Conclusion Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined. [ABSTRACT FROM AUTHOR]

Early rhythm control therapy mainly with antiarrhythmic drugs (AADs) for new-onset atrial fibrillation (AF) reduces major adverse cardiovascular events. However, negative dromotropic effects of AADs via ion channel blocking may cause bradyarrhythmias. This study aimed to evaluate the association between AAD use and the risk of pacemaker implantation or syncope in patients with new-onset AF receiving early rhythm control therapy with AADs. This study was based on data from the Korean National Health Insurance Service system. We screened all new-onset AF diagnoses that occurred from 2013 to 2019 and identified patients who were prescribed AADs within 1 year of AF diagnosis. The risk of pacemaker implantation or syncope was compared between AAD users and nonusers. A total of 770,977 new-onset AF cases were identified and 142,141 patients were prescribed AADs. After multivariate adjustment, use of AADs was associated with 3.5-, 2.0-, and 5.0-fold increased risk of pacemaker implantation or syncope, syncope, and pacemaker implantation, respectively. Propensity score–matched analysis revealed similar results, demonstrating a significant association between AAD use and the risk of pacemaker implantation or syncope. This association was consistent across various subgroups. Women were more susceptible to adverse effects of AADs than men. This study showed an association between AADs and risk of pacemaker implantation or syncope, a consistent finding across various subgroups. Precise evaluation of such risk should be undertaken before prescription of AADs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Underweight imposes significant burden on cardiovascular outcomes in patients with diabetes mellitus. However, less is known about the impact of serial change in body weight status measured as body mass index (BMI) on the risk of sudden cardiac arrest (SCA). This study investigated the association between SCA and temporal change in BMI among patients with diabetes mellitus. Methods: Based on Korean National Health Insurance Service database, participants with diabetes mellitus who underwent health examination between 2009 and 2012 and had prior health examination data (four years ago, 2005–2008) were retrospectively analyzed. BMI was measured at baseline (2005–2008) and 4-year follow-up health examination (2009–2012). Patients were classified in four groups according to the body weight status and its temporal change: sustained non-underweight, sustained underweight, previous underweight, and newly developed underweight. Primary outcome was defined as occurrence of SCA. Results: A total of 1,355,746 patients with diabetes mellitus were included for analysis, and SCA occurred in 12,554 cases. SCA was most common in newly developed underweight (incidence rate = 4.45 per 1,000 person-years), followed by sustained underweight (incidence rate = 3.90), previous underweight (incidence rate = 3.03), and sustained non-underweight (incidence rate = 1.34). Adjustment of covariates resulted highest risk of SCA in sustained underweight (adjusted hazard ratio = 2.60, 95% confidence interval [2.25–3.00], sustained non-underweight as a reference), followed by newly developed underweight (2.42, [2.15–2.74]), and previous underweight (2.12, [1.77–2.53]). Conclusions: In diabetes mellitus, sustained underweight as well as decrease in body weight during 4-year follow-up imposes substantial risk on SCA. Recovery from underweight over time had relatively lower, but yet increased risk of SCA. Both underweight and dynamic decrease in BMI can be associated with increased risk of SCA. [ABSTRACT FROM AUTHOR]