Copy number variation of gasdermin D gene is associated with atrial fibrillation-related thromboembolic stroke.

AIMS: Atrial fibrillation (AF) is one of the major causes of ischaemic stroke. In addition to clinical risk evaluated by the CHA2DS2-VASC score, the impact of genetic factors on the risk of AF-related thromboembolic stroke has been largely unknown. We found several copy number variations (CNVs) in novel genes that were associated with thromboembolic stroke risk in our AF patients by genome-wide approach. Among them, the gasdermin D (GSDMD) gene was related to inflammation. We aimed to test whether GSDMD deletion was associated with AF-related stroke. METHODS AND RESULTS: A total of 400 patients with documented non-familial AF were selected, of which 100 patients were diagnosed with ischaemic stroke. The baseline characteristics of age, sex, valvular heart disease, coronary artery disease, heart failure, and CHA2DS2-VASc scores were not statistically different between cases and controls. We found that individuals who carried GSDMD homozygous deletion genotype had a higher risk for ischaemic stroke (odds ratio 2.195; 95% confidence interval, 1.24-3.90; P = 0.007), even adjusted by CHA2DS2-VASc scores. We also validated the association of GSDMD with AF stroke in a large Caucasian population (UK Biobank). CONCLUSION: We found a link between the homozygous deletion of the GSDMD gene and an increased risk of stroke in patients with AF. This may implicate the use of therapy targeting GSDMD in the prevention of ischaemic stroke for AF patients.

On pump versus off pump coronary artery bypass grafting in patients with end-stage renal disease and coronary artery disease - A nation-wide, propensity score matched database analyses.

OBJECTIVE: The usage of on or off cardiopulmonary bypass in patients with coronary artery disease receiving coronary artery bypass grafting (CABG) surgery had been debated and had not yet been investigated thoroughly in patients with end-stage renal disease (ESRD). We aimed to study cardiovascular outcomes and total mortality in these patients by using our National Health Insurance (NHI) database. METHOD: By using our NHI ESRD claim database, we searched ESRD patients aged more than 18years, who received CABG and divided them into on pump and off pump groups. Baseline characteristics and underlying comorbidities were identified from the database. Propensity score (PS) method was used to match all the potential confounders between patients. Outcomes including mortality, myocardial infarction, stroke and repeat revascularization within 30days, 1year and whole follow-up period were also obtained. RESULT: A total of 134,410 ESRD patients were identified in the database. We included 341 patients and 543 patients who received off pump and on pump CABG respectively. The hazard ratios of different outcomes at 30days, 1year and a median of 745days after CABG did not show significant different between on, or off pump groups before and after PS match. CONCLUSION: ESRD patients with CAD undergoing either on pump or off pump CABG surgery showed similar outcomes in 30days, 1year and whole follow-up period.

Association of white blood cell count and peripheral arterial disease in patients with and without traditional risk factors.

Peripheral arterial disease (PAD) is an inflammatory process. The association between white blood cell (WBC) count and PAD in those with and without traditional risk factors is not clear. We examined data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2004. A total of 5260 participants were included. The result showed that the prevalence of PAD rose from 2.8% +/- 0.5% in the lowest quartile of plasma WBC count to 8.0% +/- 1.2% in the highest quartile. In subgroup analysis, the graded association between WBC count and PAD was significant in patients without hypertension, diabetes, smoking, chronic kidney disease (CKD), and in patients with or without hypercholesterolemia but not significant in patients with hypertension, smoking, diabetes, or CKD. In those without hypertension, diabetes, smoking, or CKD, the cutoff value for WBC count was 6.75 x 10(9)/L. We concluded that the positive association between WBC count and PAD can be demonstrated in this national survey.

Pheochromocytoma presenting as acute myocarditis with cardiogenic shock in two cases.

Pheochromocytoma is a rare, catecholamine-secreting tumor. The classic symptoms are headache, diaphoresis, and tachycardia with paroxysmal hypertension. Other less common cardio-vascular manifestations, such as arrhythmias, angina pectoris, acute myocardial infarction, dilated cardiomyopathy, acute heart failure, and cardiogenic shock, have occasionally been reported. Here, we report two middle-aged men with acute myocarditis and cardiogenic shock, who needed an intra-aortic balloon pump and extra-corporeal membrane oxygenation for life support. They were diagnosed with pheochromocytoma and underwent laparoscopic adrenectomy that restored cardiac function. These cases illustrate diagnostic and management considerations in pheochromocytoma complicated by acute myocarditis and cardiogenic shock.

Hypernatremic myopathy caused by a hypothalamic mixed germ cell tumor mimicking polymyositis.

Hypernatremic myopathy was rarely reported in the literature and its clinical features have never been well-described. We present a 22-year-old man who had adipsic hypernatremia manifested with progressive proximal muscle weakness and remarkably high creatine kinase level that has never been reported in the cases of hypernatremic myopathy. His initial presentations were similar to that of polymyositis without the evidence of central nervous system dysfunction and hypopituitarism. The serum level of sodium at the beginning of myopathy is the lowest known in the literature. All the clinical presentations in this patient resulted from a hypothalamic mixed germ cell tumor with sub-acute intra-tumoral hemorrhage.