To determine whether the cardiovascular effect of 1,25(OH)(2)D is dependent on calcium and/or phosphorus, mice with targeted deletion of the 25(OH)D 1alpha-hydroxylase and their wild-type littermates were fed a normal diet or a diet to rescue the ambient serum calcium and phosphorus levels. Mice on the normal diet were treated daily with vehicle or 1,25(OH)(2)D(3) while mice on the rescue diet received vehicle, captopril or losartan. After four weeks the vehicle-treated knockout mice developed hypertension, cardiac hypertrophy and impaired cardiac function along with an up-regulation of the renin-angiotensin system in both renal and cardiac tissues. Although the serum calcium and phosphorus levels were normalized in knockout mice on the rescue diet, abnormalities in blood pressure, cardiac structure-function and the renin-angiotensin system remained. In contrast, 1,25(OH)(2)D(3) not only normalized serum calcium and phosphorus levels but also normalized blood pressure, cardiac structure-function and the renin-angiotensin system. Treatment of the knockout mice with either captopril or losartan normalized blood pressure and cardiac structure and function although renin expression remained elevated. This study shows that 1,25(OH)2D plays a protective role in the cardiovascular system by repressing the renin-angiotensin system independent of extracellular calcium or phosphorus.

PET/CT detects more distant metastases than conventional staging in patients with NPC. The largest benefit in terms of cost and patient management was observed in the subgroup with N2-3 disease and EBV DNA ≥ 4,000 copies/mL.

Background-The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior. Methods and Results-A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex-and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had lowvoltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan-Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group (P=0.0003). Conclusions-A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT01716143.(Circ Arrhythm Electrophysiol. 2016;9:e003382.

Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.