The mammalian intestine is host to a microbial community that prevents pathogen expansion through unknown mechanisms, while antibiotic treatment can increase susceptibility to enteric pathogens. Here ...we show that streptomycin treatment depleted commensal, butyrate-producing Clostridia from the mouse intestinal lumen, leading to decreased butyrate levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by tributyrin treatment. Clostridia depletion and aerobic Salmonella expansion were also observed in the absence of streptomycin treatment in genetically resistant mice but proceeded with slower kinetics and required the presence of functional Salmonella type III secretion systems. The Salmonella cytochrome bd-II oxidase synergized with nitrate reductases to drive luminal expansion, and both were required for fecal-oral transmission. We conclude that Salmonella virulence factors and antibiotic treatment promote pathogen expansion through the same mechanism: depletion of butyrate-producing Clostridia to elevate epithelial oxygenation, allowing aerobic Salmonella growth.
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•Salmonella-induced colitis drives a depletion of butyrate-producing Clostridia•Antibiotic-mediated depletion of Clostridia increases colonocyte oxygenation•Increased epithelial oxygenation drives an aerobic post-antibiotic pathogen expansion•A respiration-driven Salmonella expansion in the gut is required for transmission
Paradoxically, antibiotic treatment can promote relapse of Salmonella gastroenteritis. Rivera-Chávez et al. show that antibiotic treatment lowers colonization resistance by depleting butyrate-producing Clostridia. Decreased butyrate availability increases epithelial oxygenation, thereby fueling aerobic pathogen expansion in the gut lumen. Aerobic respiration synergizes with nitrate respiration to drive fecal-oral transmission of Salmonella.
Patients with acute decompensated heart failure were randomly assigned to receive sacubitril–valsartan or enalapril. At 8 weeks, the sacubitril–valsartan group had a greater reduction in the ...N-terminal pro–B-type natriuretic peptide concentration than the enalapril group.
In a trial involving 10,003 patients with suspected coronary artery disease, clinical outcomes at 2 years were not improved with an initial strategy of CT angiography, as compared with functional ...testing (exercise ECG, nuclear stress testing, or stress echocardiography).
New-onset, stable chest pain is a common clinical problem that results in approximately 4 million stress tests annually in the United States in ambulatory patients without diagnosed heart disease.
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Despite advances in cardiac testing, there is scant information on health-related outcomes and little consensus about which noninvasive test is preferable.
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As a result, current patterns of care have been questioned, including the testing of very-low-risk populations
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and the catheterization of patients who do not have obstructive coronary artery disease (CAD).
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The development of coronary computed tomographic angiography (CTA) and its application in this context has the potential to . . .
Citrobacter rodentium uses a type III secretion system (T3SS) to induce colonie crypt hyperplasia in mice, thereby gaining an edge during its competition with the gut microbiota through an unknown ...mechanism. Here, we show that by triggering colonie crypt hyperplasia, the C. rodentium T3SS induced an excessive expansion of undifferentiated Ki67-positive epithelial cells, which increased oxygénation of the mucosal surface and drove an aerobic C. rodentium expansion in the colon. Treatment of mice with the -secretase inhibitor dibenzazepine to diminish Notch-driven colonie crypt hyperplasia curtailed the fitness advantage conferred by aerobic respiration during C. rodentium infection. We conclude that C. rodentium uses its T3SS to induce histopathological lesions that generate an intestinal microenvironment in which growth of the pathogen is fueled by aerobic respiration.
Objectives This study sought to test the hypothesis that semiautomated calculation of left ventricular global longitudinal strain (GLS) can identify high-risk subjects among patients with myocardial ...infarctions (MIs) with left ventricular ejection fractions (LVEFs) >40%. Background LVEF is a key determinant in decision making after acute MI, yet it is relatively indiscriminant within the normal range. Novel echocardiographic deformation parameters may be of particular clinical relevance in patients with relatively preserved LVEFs. Methods Patients with MIs and LVEFs >40% within 48 h of admission for coronary angiography were prospectively included. All patients underwent echocardiography with semiautomated measurement of GLS. The primary composite endpoint (all-cause mortality and hospitalization for heart failure) was analyzed using Cox regression analyses. The secondary endpoints were cardiac death and heart failure hospitalization. Results A total of 849 patients (mean age 61.9 ± 12.0 years, 73% men) were included, and 57 (6.7%) reached the primary endpoint (median follow-up 30 months). Significant prognostic value was found for GLS (hazard ratio HR: 1.20; 95% confidence interval CI: 1.10 to 1.32; p < 0.001). GLS > −14% was associated with a 3-fold increase in risk for the combined endpoint (HR: 3.21; 95% CI: 1.82 to 5.67; p < 0.001). After adjustment for other variables, GLS remained independently related to the combined endpoint (HR: 1.14; 95% CI: 1.04 to 1.26; p = 0.007). For the secondary endpoints, GLS > −14% was significantly associated with cardiovascular death (HR: 12.7; 95% CI: 3.0 to 54.6; p < 0.001) and heart failure hospitalization (HR: 5.31; 95% CI: 1.50 to 18.82; p < 0.001). Conclusions Assessment of GLS using a semiautomated algorithm provides important prognostic information in patients with LVEFs >40% above and beyond traditional indexes of high-risk MI.
The role of myocardial viability assessment in identifying patients with ischemic cardiomyopathy who will benefit from surgical revascularization is controversial. This study assessed myocardial ...viability and its relationship to long-term outcomes in 601 patients with ischemic cardiomyopathy who were assigned to surgical revascularization plus medical therapy or medical therapy alone.
Purpose of Review
The purpose of this review it to summarize the current literature on remodeling after myocardial infarction, inclusive of pathophysiological considerations, imaging modalities, ...treatment strategies, and future directions.
Recent Findings
As patients continue to live longer after myocardial infarction (MI), the prevalence of post-MI heart failure continues to rise. Changes in the left ventricle (LV) after MI involve complex interactions between cellular and extracellular components, under neurohormonal regulation. Treatments to prevent adverse LV remodeling and promote reverse remodeling in the post-MI setting include early revascularization, pharmacotherapy aimed at neurohormonal blockade, and device-based therapies that address ventricular dyssynchrony.
Summary
Despite varying definitions of adverse LV remodeling examined across multiple imaging modalities, the presence of an enlarged LV cavity and/or reduced ejection fraction is consistently associated with poor clinical outcomes. Advances in our knowledge of the neurohormonal regulation of adverse cardiac remodeling have been instrumental in generating therapies aimed at arresting adverse remodeling and promoting reserve remodeling. Further investigation into other specific mechanisms of adverse LV remodeling and pathways to disrupt these mechanisms is ongoing and may provide incremental benefit to current evidence-based therapies.
The optimal combination drug therapy for treatment of hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. This double-blind trial, in which high-risk ...patients with hypertension were randomly assigned to treatment with benazepril plus either amlodipine or hydrochlorothiazide, showed that benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular events in this population.
This double-blind trial showed that benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular events in high-risk patients with hypertension.
There is incomplete evidence that the cardiovascular benefits of specific classes of antihypertensive drugs extend beyond lowering blood pressure.
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A review of clinical trials involving patients with hypertension who were at high risk for cardiovascular events showed that treatment with multiple antihypertensive medications was often necessary to attain blood-pressure goals recommended by guidelines.
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In previous trials designed to test single agents, other drugs were often added for blood-pressure control, thus confounding the interpretation of the effects of the initial drug on the study end points.
Initial therapy for hypertension with a combination of drugs is recommended by both the . . .
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