Association of SGLT2is with cardiovascular and reproductive diseases: a meta-analysis based on 14 large-scale randomized trials.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) can improve long-term cardio-renal outcomes in patients with diabetes, heart failure (HF), or renal failure. We aimed to investigate the association of SGLT2is with the risks of various cardiovascular and reproductive diseases. METHODS: Large-scale randomized trials enrolling more than 1000 participants and assessing SGLT2is were included. Outcomes of interest were the various serious adverse events related to cardiovascular or reproductive diseases. Meta-analysis was done to generate pooled risk ratio (RR) and 95% confidence interval (CI). RESULTS: We included 14 large trials and evaluated 169 types of cardiovascular and reproductive diseases. SGLT2is were significantly associated with the lower risks of 13 types of cardiovascular diseases, e.g., cardiac failure chronic (RR 0.70, 95% CI 0.57-0.87), cardiac failure congestive (RR 0.74, 95% CI 0.66-0.83), acute cardiac failure (RR 0.72, 95% CI 0.60-0.86), coronary artery disease (RR 0.75, 95% CI 0.58-0.97), ischemic cardiomyopathy (RR 0.72, 95% CI 0.52-0.99), atrial fibrillation (RR 0.88, 95% CI 0.78-0.99), bradycardia (RR 0.72, 95% CI 0.53-0.99), and hypertension (RR 0.70, 95% CI 0.54-0.91). SGLT2is were not significantly associated with 18 types of reproductive diseases, e.g., adenomyosis, endometrial hyperplasia, and metrorrhagia. Although SGLT2is were observed to have a significant association with a higher risk of uterine prolapse, the 95% CI of RR for this outcome was relatively wide. CONCLUSION: This meta-analysis confirms the benefits of SGLT2is against chronic congestive HF again; reveals the possible benefits of SGLT2is against acute HF, myocardial infarction, arrhythmias, and hypertension; and identifies that SGLT2is are safe in general for the reproductive system.

DDAH2 alleviates myocardial fibrosis in diabetic cardiomyopathy through activation of the DDAH/ADMA/NOS/NO pathway in rats.

Diabetic cardiomyopathy (DCM) is a form of idiopathic heart disease, with signs including hypertrophy of myocardial cells, hypertension­independent fibrosis and coronary artery disease. Considering the involvement of dimethylarginine dimethylaminohydrolase 2 (DDAH2) in diabetes, it was hypothesized that DDAH2 may be beneficial to cardiac function and myocardial fibrosis during the progression of DCM with involvement of the DDAH/asymmetric NG, NGdimethyl­L­arginine (ADMA)/nitric oxide synthase (NOS)/nitric oxide (NO) signaling pathway. Following establishment of diabetic rat models, diabetes­related blood biochemical indices and cardiac function were measured in diabetic rats treated with lentivirus expressing DDAH2, short hairpin RNA against DDAH2, or L­NNA (inhibitor of NOS) to identify the roles of DDAH2 in DCM. The functional roles of DDAH2 in DCM were further determined through detection of the levels of collagen I, matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2). The H9C2 myocardial cell line was selected for in vitro experiments. The effects of DDAH2 on the migration of myocardial cells under high glucose conditions were also examined. To further investigate the underlying regulatory mechanism of DDAH2 in DCM, the contents of ADMA and NO, and the activities of DDAH and NOS were observed. The DCM model rats treated with DDAH2 exhibited reduced left ventricular end­diastolic pressure, and decreased blood glucose, total cholesterol, triglyceride, fasting blood glucose, and fasting insulin levels, but exhibited increased left ventricular systolic pressure and maximum rate of left ventricular pressure rise/fall levels in myocardial tissues. Myocardial cells under high glucose conditions treated with DDAH2 showed reductions in collagen I, MMP2 and TIMP2, indicating that DDAH2 reduced cell migration. Decreased levels of ADMA and NO but increased levels of DDAH and NOS were observed following treatment with DDAH2, indicating that the DDAH/ADMA/NOS/NO pathway was activated. These results reveal that the overexpression of DDAH2 attenuates myocardial fibrosis and protects against DCM through activation of the DDAH/ADMA/NOS/NO pathway in DCM rats. These results indicate that DDAH2 is a potential therapeutic candidate for the treatment of DCM.

Prognostic value of plasma heart-type fatty acid-binding protein in patients with acute pulmonary embolism: a meta-analysis.

BACKGROUND: Several studies have described heart-type fatty acid-binding protein (H-FABP) from early blood samples as a predictor of outcome in acute pulmonary embolism (PE). This systematic review is designed to determine the prognostic value of H-FABP aimed for use in patients with acute PE. METHODS: Studies published prior to January 2013 in PubMed, Ovid, and Embase were reviewed, and the relationship between H-FABP and the risk of acute PE-related death or serious complications was evaluated. A summary estimate was calculated using the bivariate random-effects approach, and covariate analysis was used to examine sources of heterogeneity among studies. RESULTS: A systematic search revealed six studies containing a total of 618 patients. Elevated H-FABP level was significantly associated with short-term death (within 30 days of embolism) (OR, 40.78; 95% CI, 11.87-140.09) and with complicated clinical events (OR, 32.71; 95% CI, 11.98-89.26). The prevalence of serious complications and death in acute PE was 51% (95% CI, 43%-59%) and 31% (95% CI, 24% -39%), respectively. The combined sensitivity and specificity for the prediction of death and serious complications was 98% and 86%, respectively. CONCLUSIONS: H-FABP is associated with an increased risk of mortality or complicated clinical events in patients with acute PE across different studies with a high degree of clinical and methodologic diversity. The result suggests that H-FABP has significant prognostic value for acute PE.

Cost-effective 33-Gbps intensity modulation direct detection multi-band OFDM LR-PON system employing a 10-GHz-based transceiver.

We develop a dynamic multi-band OFDM subcarrier allocation scheme to fully utilize the available bandwidth under the restriction of dispersion- and chirp-related power fading. The experimental results successfully demonstrate an intensity-modulation-direct-detection 34.78-Gbps OFDM signal transmissions over 100-km long-reach (LR) passive-optical networks (PONs) based on a cost-effective 10-GHz EAM and a 10-GHz PIN. Considering 0-100-km transmission bandwidth of a 10-GHz EAM, the narrowest bandwidth is theoretically evaluated to occur at ~40 km, instead of 100 km. Consequently, the performances of 20-100-km PONs are experimentally investigated, and at least 33-Gbps capacity is achieved to support LR-PONs of all possible 20-100-km radii.

21 Gb/s after 100 km OFDM long-reach PON transmission using a cost-effective electro-absorption modulator.

We experimentally demonstrate a superior performance of 2.1-Tb/s·km OFDM signal transmission over 100-km long-reach PONs. While the bandwidth of a 100-km SMF transmission system is limited to 4.3 GHz due to positive chirp, we successfully achieve spectrally-efficient 21-Gb/s signaling by using a cost-effective and low-chirp EAM, and adopting the 128-QAM format and adaptive subcarrier pre-emphasis.