Across all patients, complete revascularization was superior to culprit-only revascularization for reduction in the risk of cardiovascular death (relative risk [RR], 0.68; 95% CI, 0.47-0.98; P=0.037; I2=21.8%) and reduction in the risk of myocardial infarction (RR, 0.65; 95% CI, 0.54-0.79; P less then 0.0001; I2=0.0%). Complete revascularization also significantly reduced the risk of unplanned revascularization (RR, 0.37; 95% CI, 0.28-0.51; P less then 0.0001; I2=64.7%). The difference in all-cause mortality with percutaneous coronary intervention was not statistically significant (RR, 0.85; 95% CI, 0.69-1.04; P=0.108; I2=0.0%). Conclusions For patients with STEMI and multivessel disease, complete revascularization with percutaneous coronary intervention significantly improves hard clinical outcomes including cardiovascular death and myocardial infarction. These data have implications for clinical practice guidelines regarding recommendations for complete revascularization following STEMI.Background There are conflicting data regarding the benefit of primary prevention implantable cardioverter-defibrillators (ICDs) in patients with diabetes mellitus and heart failure (HF) with reduced ejection fraction.  https://www.selleckchem.com/JAK.html  We aimed to assess the comparative effectiveness of ICD placement in patients with diabetes mellitus and HF with reduced ejection fraction. Methods and Results Data were obtained from the Get With the Guidelines-Health Failure registry, linked with claims from the Centers for Medicare & Medicaid Services. We used a Cox proportional hazards model censored at 5 years with propensity score matching. Of the 17 186 patients with HF with reduced ejection fraction from the Centers for Medicare & Medicaid Services claims database (6540 with diabetes mellitus; 38%), 1677 (646 with diabetes mellitus; 39%) received an ICD during their index HF hospitalization or were prescribed an ICD at discharge. Patients with diabetes mellitus and an ICD (n=646), as compared with those without an ICD (n=1031), were more likely to be younger (74 versus 78 years of age) and have coronary artery disease (68% versus 60%). After propensity matching, ICD use among patients with diabetes mellitus, as compared with those without an ICD, was associated with a reduced risk of all-cause mortality at 5 years after HF discharge (54% versus 59%; multivariable hazard ratio, 0.73; 95% CI, 0.64-0.82; P less then 0.0001). Ischemic heart disease did not modify the association between ICD use and all-cause mortality (P=0.95 for interaction). Similar results were seen in patients without diabetes mellitus. Conclusions Primary prevention ICD use among older patients with HF with reduced ejection fraction and diabetes mellitus was associated with a reduced risk of all-cause mortality. Our analysis supports current guideline recommendations for implantation of primary prevention ICDs among older patients with diabetes mellitus and HF with reduced ejection fraction.Background Colorectal cancer is the fourth leading cause of cancer-associated death in the world. The 5-year local recurrence rates in patients undergoing multimodality therapy are approximately 5-10%. The standard approach to treat locally recurrent rectal is re-irradiation followed by surgical resection. Recent reports have suggested that the treatment outcomes with carbon ion radiation therapy (CIRT) in recurrent rectal cancer are promising and have superior results compared to photon therapy. Hence, we performed a systematic review to evaluate the patterns of care and treatment outcomes of recurrent rectal cancer patients treated with CIRT.Methodology We performed a systematic search to identify the articles that reported on CIRT use in recurrent rectal cancer.Results Systematic search of PubMed and Cochrane Central resulted in 98 abstracts. Eight studies fulfilled the predefined inclusion criteria. Among eight studies, one study is a prospective phase I/II study done in Japan; three prospective studies are ongoing (PANDORA-01 trial, HIMAT1351trial, and a phase II study of reirradiation for prior CIRT), and five studies are institutional reports on role of CIRT. These studies were predominantly reported from Japan and Germany. All reports except one were performed in patients who have not received prior radiation. The most commonly utilized treatment prescription was 73.4 Gy (RBE) in 16 fractions over 4 weeks in patients without any prior history of radiation and 36 Gy in 12 fractions over 3 weeks at 3 Gy per fraction in patients with prior photon radiation to the pelvis. There is one ongoing trial assessing the role of carbon ion re-irradiation in patients who had prior CIRT for rectal cancer.Conclusion CIRT holds immense promise in improving outcomes in locally recurrent rectal cancer. There is a need for more multi-institutional prospective clinical trials to assess the role of CIRT.Background Aberrant activation of the NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat-containing receptor family pyrin domain-containing 3) inflammasome is thought to play a causative role in atherosclerosis. NLRP3 is kept in an inactive ubiquitinated state to avoid unwanted NLRP3 inflammasome activation. This study aimed to test the hypothesis that pharmacologic manipulating of NLRP3 ubiquitination blunts the assembly and activation of the NLRP3 inflammasome and protects against vascular inflammation and atherosclerosis. Since genetic studies yielded mixed results about the role for this inflammasome in atherosclerosis in low-density lipoprotein receptor- or apolipoprotein E-deficient mice, this study attempted to clarify the discrepancy with the pharmacologic approach using both models. Methods and Results We provided the first evidence demonstrating that tranilast facilitates NLRP3 ubiquitination. We showed that tranilast restricted NLRP3 oligomerization and inhibited NLRP3 inflammaso NLRP3 inflammasome, and ameliorates vascular inflammation and atherosclerosis in both low-density lipoprotein receptor- and apolipoprotein E-deficient mice.Purpose Amyloid beta is the main component of senile plaques deposited in the hippocampus of people with Alzheimer's disease (AD), with neurotoxicity and pro-apoptotic characteristics. Icaritin (ICA) has been found to have the properties of plerosis, regeneration, and anti-apoptosis in the neurocytes, its effects on Aβ-induced hippocampal neurocytes were studied in this research.Methods Different concentrations of Aβ25-35 were used to treat mouse hippocampal neuron HT22 cells to determine the optimal concentration for constructing AD model; different concentrations of ICA were used to pretreat HT22 cells to explore their effects on cell activity. Cell injury was evaluated by measuring the viability and apoptosis of HT22 cells using MTT assay, and Annexin V/PI and Hoechst 33342 staining, respectively. Western blot and qPCR were performed to detect the expressions of glucocorticoid receptor (GR), brain-derived neurotrophic factor (BDNF), and apoptosis-related factors. Oxidative stress was assessed by the biochemical analysis of Lactate dehydrogenase (LDH) release and superoxidase dismutase (SOD) activity.