Comparison of postprocedural new-onset atrial fibrillation between transcatheter and surgical aortic valve replacement: A systematic review and meta-analysis based on 16 randomized controlled trials.

BACKGROUND: Presently, transcatheter aortic valve replacement (TAVR) as an effective and convenient intervention has been adopted extensively for patients with severe aortic disease. However, after surgical aortic valve replacement (SAVR) and TAVR, the incidence of new-onset atrial fibrillation (NOAF) is prevalently found. This meta-analysis was designed to comprehensively compare the incidence of NOAF at different times after TAVR and SAVR for patients with severe aortic disease. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to October 1, 2020 was conducted for relevant studies that comparing TAVR and SAVR in the treatment of severe aortic disease. The primary outcomes were the incidence of NOAF with early, midterm and long term follow-up. The secondary outcomes included permanent pacemaker (PM) implantation, myocardial infarction (MI), cardiogenic shock, as well as mortality and other complications. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULTS: A total of 16 studies including 13,310 patients were identified. The pooled results indicated that, compared with SAVR, TAVR experienced a significantly lower incidence of 30-day/in-hospital, 1-year, 2-year, and 5-year NOAF, with pooled risk ratios (RRs) of 0.31 (95% confidence interval [CI] 0.23-0.41; 5725 pts), 0.30 (95% CI 0.24-0.39; 6321 pts), 0.48 (95% CI 0.38-0.61; 3441 pts), and 0.45 (95% CI 0.37-0.55; 2268 pts) respectively. In addition, TAVR showed lower incidence of MI (RR 0.62; 95% CI 0.40-0.97) and cardiogenic shock (RR 0.34; 95% CI 0.19-0.59), but higher incidence of permanent PM (RR 3.16; 95% CI 1.61-6.21) and major vascular complications (RR 2.22; 95% CI 1.14-4.32) at 30-day/in-hospital. At 1- and 2-year after procedure, compared with SAVR, TAVR experienced a significantly higher incidence of neurological events, transient ischemic attacks (TIA), permanent PM, and major vascular complications, respectively. At 5-year after procedure, compared with SAVR, TAVR experienced a significantly higher incidence of TIA and re-intervention respectively. There was no difference in 30-day, 1-year, 2-year, and 5-year all-cause or cardiovascular mortality as well as stroke between TAVR and SAVR. CONCLUSIONS: Our analysis showed that TAVR was superior to SAVR in decreasing the both short and long term postprocedural NOAF. TAVR was equal to SAVR in early, midterm and long term mortality. In addition, TAVR showed lower incidence of 30-day/in-hospital MI and cardiogenic shock after procedure. However, pooled results showed that TAVR was inferior to SAVR in reducing permanent pacemaker implantation, neurological events, TIA, major vascular complications, and re-intervention.

Tumor-treating fields (TTFields)-based cocktail therapy: a novel blueprint for glioblastoma treatment.

Glioblastoma is one of the most common malignant tumors in the central nervous system. Due to the high plasticity, heterogeneity and complexity of the tumor microenvironment, these tumors are resistant to almost all therapeutic strategies when they reach an advanced stage. Along with being a unique and effective way to kill cancer cells, tumor-treating fields (TTFields) has emerged as a breakthrough among glioblastoma therapies since the advent of temozolomide (TMZ), and the combination of these treatments has gradually been promoted and applied in the clinic. The combination of TTFields with other therapies is particularly suitable for this type of "cold" tumors and has attracted a large amount of attention from clinicians and researchers in the era of cancer cocktail therapy. Here, we introduced the current treatment regimen for glioblastoma, highlighting the unique advantages of TTFields in the treatment of glioblastoma. Then, we summarized current glioblastoma clinical trials that combine TTFields and other therapies. In addition, the main and potential mechanisms of TTFields were introduced to further understand the rationale for each combination therapy. Finally, we focused on the most advanced technologies applied in glioblastoma research and treatment and the prospect of their combination with TTFields. This review provides a unique overview of glioblastoma treatment.

Plasma hemoglobin and the risk of death in HIV/AIDS patients treated with antiretroviral therapy.

BACKGROUND: Previous studies concerning the effect of plasma hemoglobin (HB) and other factors that may modify the risk of death in people living with HIV/AIDS (PLHIV) treated with antiretroviral therapy (ART) are limited. RESULTS: Higher HB was independently linked to a lower death risk in PLHIV, with a decrease of 29% (13%, 43%) per standard deviation (SD) increment after adjusting for CD4, VL and other potential factors [hazard ratio (HR): 0.71, 95% confidence interval (CI): 0.57-0.87, P<0.001]. In addition, the addition of HB to the predictive model containing VL and CD4 significantly improved the C-index, by 0.69% (95% CI: 0.68%-0.71%), and net discrimination, by 0.5% (95% CI: 0.0%-1.6%, P=0.040), when predicting the death risk of PLHIV. CONCLUSIONS: A lower level of HB was an independent risk factor for HIV/AIDS-associated death in PLHIV. HB combined with VL and CD4 may be an appropriate predictive model of the death risk of PLHIV. MATERIALS AND METHODS: A propensity-score matching (PSM) approach was applied to select a total of 750 PLHIV (150 deceased and 600 living) from the AIDS prevention and control information system in the Wenzhou area from 2006 to 2018. Multivariable Cox proportional hazards regression models were formulated to estimate the effect of HB. The predictive performance improvement contributed by HB was evaluated using the C-index and net reclassification improvement.

Development and validation of a prognostic nomogram for HIV/AIDS patients who underwent antiretroviral therapy: Data from a China population-based cohort.

BACKGROUND: Accurate forecast of the death risk is crucial to the administration of people living with HIV/AIDS (PLHIV). We aimed to establish and validate an effective prognosis nomogram in PLHIV receiving antiretroviral therapy (ART). METHODS: All the data were obtained from 2006 to 2018 in the Wenzhou area from China AIDS prevention and control information system. Factors included in the nomogram were determined by univariate and multiple Cox proportional hazard analysis based on the training set. The receiver operating characteristic (ROC) and calibration curves were used to assess its predictive accuracy and discriminative ability. Its clinical utility was also evaluated using decision curve analysis (DCA), X-tile analysis and Kaplan-Meier curve, respectively in an independent validation set. FINDINGS: Independent prognostic factors including haemoglobin, viral load and CD4+ T-cell count were determined and contained in the nomogram. Good agreement between the prediction by nomogram and actual observation could be detected in the calibration curve for mortality, especially in the first year. In the training cohort, AUC (95% CI) and C-index (95% CI) were 0.93 (0.90, 0.96) and 0.90 (0.85, 0.96), respectively. In the validation set, the nomogram still revealed excellent discriminations [AUC (95% CI): 0.95 (0.91, 1.00)] and good calibration [C-index (95% CI): 0.92 (0.82-1.00)]. Moreover, DCA also demonstrated that the nomogram was clinical beneficial. Additionally, participants could be classified into three distinct (low, middle and high) risk groups by the nomogram. INTERPRETATION: The nomogram presents accurate and favourable prognostic prediction for PLHIV who underwent ART. FUNDING: This work was supported by Zhejiang Basic Public Welfare Research Project (LGF19H260011), Wenzhou Basic Public Welfare Research Project (Y20180201), the Initial Scientific Research Fund (KYQD170301), the Major Project of the Eye Hospital Wenzhou the Major Project of the Eye Hospital Wenzhou Medical University (YNZD201602). Part of this work was also funded by National Natural Science Foundation of China (81670777) and Science and Technology Innovation Activity Plan and New Talents Plan for College Students in Zhejiang Province (2019R413073). The funders had no roles in study design, data collection, data analysis, interpretation and writing of the report.

1α,25(OH)2D3 Suppresses the Migration of Ovarian Cancer SKOV-3 Cells through the Inhibition of Epithelial-Mesenchymal Transition.

Ovarian cancer is the most lethal gynecological malignancy due to its high metastatic ability. Epithelial-mesenchymal transition (EMT) is essential during both follicular rupture and epithelium regeneration. However, it may also accelerate the progression of ovarian carcinomas. Experimental studies have found that 1α,25-dihydroxyvitamin-D3 [1α,25(OH)2D3] can inhibit the proliferation of ovarian cancer cells. In this study, we investigated whether 1α,25(OH)2D3 could inhibit the migration of ovarian cancer cells via regulating EMT. We established a model of transient transforming growth factor-ß1(TGF-ß1)-induced EMT in human ovarian adenocarcinoma cell line SKOV-3 cells. Results showed that, compared with control, 1α,25(OH)2D3 not only inhibited the migration and the invasion of SKOV-3 cells, but also promoted the acquisition of an epithelial phenotype of SKOV-3 cells treated with TGF-ß1. We discovered that 1α,25(OH)2D3 increased the expression of epithelial marker E-cadherin and decreased the level of mesenchymal marker, Vimentin, which was associated with the elevated expression of VDR. Moreover, 1α,25(OH)2D3 reduced the expression level of transcription factors of EMT, such as slug, snail, and ß-catenin. These results indicate that 1α,25(OH)2D3 suppresses the migration and invasion of ovarian cancer cells by inhibiting EMT, implying that 1α,25(OH)2D3 might be a potential therapeutic agent for the treatment of ovarian cancer.

Vitamin D postpones the progression of epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene both in vitro and in vivo.

PURPOSE: Ovarian cancer is the most lethal malignancy of the female reproductive system, and the prevention and treatment of ovarian carcinoma are still far from optimal. Epidemiological studies reported that ovarian cancer risk was inversely associated with low level of 25-hydroxy vitamin D [25(OH)]. Therefore, this study focuses on exploring the chemoprevention of vitamin D on epithelial ovarian cancer induced by 7, 12-dimethylbenz [a] anthracene (DMBA). METHODS: The mouse ovarian surface epithelial cells were isolated from estrus mice by mild trypsinization and maintained in completed culture medium by repeated passaging. The malignant transformation of mouse ovarian surface epithelial cells was induced by DMBA in vitro. DMBA was directly injected into the bursa of mouse ovary to produce optimized in vivo ovarian cancer model. RESULTS: The results indicate that 1α,25 dihydroxyvitamin D3 may delay malignant transformation of mouse ovarian surface epithelial cells induced by DMBA and significantly decreased the colony formation rate from 18.4% to 3.2% (P<0.05). There was a negative correlation between incidence of DMBA-induced tumor and 25-hydroxy vitamin D level (R (2)=0.978, P<0.05). Vitamin D3 can delay the progression of ovarian cancer induced by DMBA, and the administration of vitamin D3 during the whole process worked more effectively than the administration only during tumor initiation or promotion. Moreover, we found the vitamin D3 increased the expression of E-cadherin and vitamin D receptor while it decreased the expression of ß-catenin. CONCLUSION: We succeeded in establishment of epithelial ovarian cancer models both in vitro and in vivo. The DMBA-implanted model in mice yields high incidence and specificity of epithelial derived tumors. We also found that vitamin D delays the progression of ovarian cancer. However, spontaneous epithelial ovarian carcinoma models are still to be explored for testing the preventive effects of vitamin D on epithelial ovarian cancer.

Association of the CYP24A1-rs2296241 polymorphism of the vitamin D catabolism enzyme with hormone-related cancer risk: a meta-analysis.

BACKGROUND: The evidence for vitamin D reducing cancer risk is inconsistent, and it is not clear whether this reduction is related to variation in cytochrome P450 (CYP)24A1, the only enzyme known to degrade active vitamin D. We focused on evaluating the association of CYP24A1-rs2296241 polymorphism with hormone-related cancer risk by conducting a meta-analysis. METHODS: A systematic literature search was conducted in April 2014 (updated in December 2014) to identify eligible studies. A random-effects model was used to pool the odds ratio (OR). RESULTS: Eleven studies including 5,145 cases and 5,136 controls were considered for the allelic model, and eight studies of 3,959 cases and 3,560 controls were utilized for the additive, recessive, and dominant models. There was no significant association between CYP24A1-rs2296241 and hormone-related cancer risk in any of the models, yet substantial heterogeneity was observed. Subgroup analyses indicated that CYP24A1-rs2296241 variation reduced the prostate cancer risk in the additive (OR 0.91, 95% confidence interval 0.85-0.97) and recessive (OR 0.80, 95% confidence interval 0.67-0.95) models, with no evidence of heterogeneity. CONCLUSION: This meta-analysis indicated that CYP24A1-rs2296241 polymorphism reduced the androgen-related prostate cancer risk in additive and recessive models. More genetic loci are needed to confirm the effect of CYP24A1 variation on the risk of prostate cancer.

Synergy of 1,25-dihydroxyvitamin D3 and carboplatin in growth suppression of SKOV-3 cells.

1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has been demonstrated to inhibit the growth of cancer cells. However, carboplatin is the most widely used chemotherapeutic agent to treat cancer. We hypothesized that vitamin D may enhance the antiproliferative effects of carboplatin, and tested this hypothesis in ovarian cancer SKOV-3 cells treated with carboplatin and 1,25(OH)2D3. Cell viability was determined by Cell Counting Kit-8, while cell cycle distribution, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were analyzed by flow cytometry. In these experiments, 1,25(OH)2D3 and carboplatin each provided dose-dependent suppression of SKOV-3 growth, and synergy was demonstrated between 10 nM 1,25(OH)2D3 and carboplatin. The proportion of cells in G0/G1 phase was markedly reduced by the drug combination, while the proportion of cells in G2/M phase was increased. Apoptosis did not increase in ovarian cancer cells treated with 10 nM 1,25(OH)2D3 alone; however, 1,25(OH)2D3 evidently enhanced carboplatin-induced apoptosis. Similarly, ROS production was evidently higher and MMP was lower in cells treated with the two drugs than in those treated with each drug alone. The results suggested that 1,25(OH)2D3 suppresses SKOV-3 growth and enhances the antiproliferative effect of carboplatin. The drugs function synergistically by inducing cell cycle arrest, increasing apoptosis and ROS production, and reducing MMP.