Background In contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity. Methods and results CLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure. Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest. Conclusion In patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes. ClinicalTrials identifier ISRCTN43070564
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Objective To examine the effects of short-term cyclic stretch on apoptosis in alveolar type II cells (A549). To study in vitro the direct influence of alveolar type II cells on mechanical stretch. Methods A549 were treated with different doses of lipopolysaccharide (LPS), 0 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml, and then A549 were lengthened 5%, 15%, 30% using a FLEXCELL tension unit 4000, a vacuum-driven device that applies strain to cells, which were cultured in six-well plates coated with collagen-I, and 12 cycles/min for 4 hours. Apoptosis was measured using the flow cytometry method that measures annexin V and propidium iodide (PI) staining. The morphological changes of apoptotic cells were observed by transmission electron microscope. Results Apoptosis could be induced in alveolar type II cells (A549) by mechanical stretch. The percentage of annexin V + PI cells increased after being treated with cyclic stretch for 4 hours by 5%, 15%, 30% in all groups. The morphological features of apoptotic cells demonstrated by transmission electron microscope were as follows: shrinkage of the cell, chromatin condensation and aggregation under the nuclear membrane as a crescent or lump, membrane-encapsulated nuclear fragment or cell organ formed by invagination of the cell membrane, and apoptotic body formation followed by vacuolization. Conclusion Apoptosis induced by mechanical stretch and LPS is dose dependent. Mechanical stretch aggravates apoptosis especially in cells treated with LPS. Annexin V and PI double staining is a specific, sensitive, and quantitative method for analyzing apoptotic cells. It is also helpful to clarify the protective mechanism of low-volume ventilation in ARDS. Acknowledgement The study was funded by the 'One Hundred People' project of Shanghai Sanitary Bureau (03-77-20). Introduction Although extrapulmonary ALI/ARDS is a common clinical entity, most animal models used to study this disease are induced by direct lung injuries. Our intention was therefore to investigate whether a condition resembling ALI/ARDS develops during the course of a fecal peritonitis in pigs; in that case experimental peritonitis would also prove as a clinically relevant ARDS model. Methods In 10 anesthetized, mechanically ventilated, and instrumented pigs fecal peritonitis was induced by inoculating autologue feces pellets suspended in saline. Mechanical ventilation was set with VT = 8 ml/kg, FiO 2 to reach a SaO 2 target of >90%, PEEP = 10 cmH 2 O if PaO 2 /FiO 2 > 300 and 12 cmH 2 O if PaO 2 /FiO 2 < 300, and respiratory rate to obtain a PaCO 2 of 35-45 mmHg. Before as well as 12 and 24 hours after peritonitis induction we measured the PaO 2 /FiO 2 ratio, the total compliance of the respiratory system (C), calculated as VT/(P plateau -PEEP) and inspiratory airway resistance (R i ) calculated as (P max -P plateau ) / mean inspiratory flow. Data are mean [range]. Results For data see Table 1. During the course of the 24-hour study period, six of 10 animals developed gas exchange deteriorations consistent w...
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