Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

The effects of regular dental scaling on the complications and mortality after stroke: a retrospective cohort study based on a real-world database.

BACKGROUND: Previous observational studies have shown that people with dental scaling (DS) had decreased risk of stroke. However, limited information is available on the association between DS and poststroke outcomes. The present study aimed to evaluate the effects of regular DS on the complications and mortality after stroke. METHODS: We conducted a retrospective cohort study of 49,547 hospitalized stroke patients who received regular DS using 2010-2017 claims data of Taiwan's National Health Insurance. Using a propensity-score matching procedure, we selected 49,547 women without DS for comparison. Multiple logistic regressions were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of poststroke complications and in-hospital mortality associated with regular DS. RESULTS: Stroke patients with regular DS had significantly lower risks of poststroke pneumonia (OR 0.58, 95% CI 0.54-0.63), septicemia (OR 0.58, 95% CI 0.54-0.63), urinary tract infection (OR 0.68, 95% CI 0.66-0.71), intensive care (OR 0.81, 95% CI 0.78-0.84), and in-hospital mortality (OR 0.66, 95% CI 0.62-0.71) compared with non-DS stroke patients. Stroke patients with regular DS also had shorter hospital stays (p < 0.0001) and less medical expenditures (p < 0.0001) during stroke admission than the control group. Lower rates of poststroke adverse events in patients with regular DS were noted in both sexes, all age groups, and people with various types of stroke. CONCLUSION: Stroke patients with regular DS showed fewer complications and lower mortality compared with patients had no DS. These findings suggest the urgent need to promote regular DS for this susceptible population of stroke patients.

Structure-based virtual screening and biological evaluation of novel small-molecule BTK inhibitors.

Bruton tyrosine kinase (BTK) is linked to multiple signalling pathways that regulate cellular survival, activation, and proliferation. A covalent BTK inhibitor has shown favourable outcomes for treating B cell malignant leukaemia. However, covalent inhibitors require a high reactive warhead that may contribute to unexpected toxicity, poor selectivity, or reduced effectiveness in solid tumours. Herein, we report the identification of a novel noncovalent BTK inhibitor. The binding interactions (i.e. interactions from known BTK inhibitors) for the BTK binding site were identified and incorporated into a structure-based virtual screening (SBVS). Top-rank compounds were selected and testing revealed a BTK inhibitor with >50% inhibition at 10 µM concentration. Examining analogues revealed further BTK inhibitors. When tested across solid tumour cell lines, one inhibitor showed favourable inhibitory activity, suggesting its potential for targeting BTK malignant tumours. This inhibitor could serve as a basis for developing an effective BTK inhibitor targeting solid cancers.

Impact of dialysis modality on major adverse cardiovascular events and all-cause mortality: a national population-based study.

BACKGROUND: Only few studies with inconsistent results comparing the relative risk of cardiac mortality between peritoneal dialysis (PD) and hemodialysis (HD). Switches between renal replacement therapy (RRT) modalities render objective assessment of survival benefits a greater challenge. METHODS: Data were retrieved from Taiwan's National Health Insurance Database from 1 January 2006 to 31 December 2015. We included 13 662 and 41 047 long-term dialysis patients in a propensity score matching study design and a time-varying study design, respectively, to compare major adverse cardiovascular events (MACEs) between patients receiving PD and HD. We also included 109 256 dialysis patients to compare the all-cause mortality among different RRT modalities. RESULTS: For MACE, the hazard ratio (HR) for PD patients compared to HD patients was 0.95 [95% confidence interval (CI) 0.89-1.02] in the propensity score study design and 1.06 (95% CI 1.01-1.12) in the time-varying study design. For all-cause mortality, the HR for PD patients compared to HD patients was 1.09 (95% CI 1.05-1.13) in the propensity score study design and 1.13 (95% CI 1.09-1.17) in the time-varying study design. The HR for death was higher at a level of statistical significance for females (1.21, 95% CI 1.15-1.28), patients ≥65 years old (1.30, 95% CI 1.24-1.36) and diabetes mellitus (DM; 1.28, 95% CI 1.22-1.34). CONCLUSIONS: The HR for MACE is significantly higher among PD patients in time-varying design analysis. In addition, all-cause mortality was higher in PD patients compared to patients with HD, especially in those who were aged ≥65 years, female or DM.

Septicemia and mortality after noncardiac surgery associated with CHA2DS2-VASc score: a retrospective cohort study based on a real-world database.

BACKGROUND: Little was know about the association between the CHA2DS2-VASc score and postoperative outcomes. Our purpose is to evaluate the effects of CHA2DS2-VASc score on the perioperative outcomes in patients with atrial fibrillation (AF). METHODS: We identified 47,402 patients with AF over the age of 20 years who underwent noncardiac surgeries between 2008 and 2013 from claims data of the National Health Insurance in Taiwan. The CHA2DS2-VASc score was used to evaluate postoperative complications, mortality and the consumption of medical resources by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared with patients with a CHA2DS2-VASc score of 0, patients with scores ≥ 5 had an increased risk of postoperative septicemia (OR 2.76, 95% CI 2.00-3.80), intensive care (OR 2.55, 95% CI 2.12-3.06), and mortality (OR 2.04, 95% CI 1.14-3.64). There was a significant positive correlation between risk of postoperative complication and the CHA2DS2-VASc score (P < 0.0001). CONCLUSION: The CHA2DS2-VASc score was highly associated with postoperative septicemia, intensive care, and 30-day mortality among AF patients. Cardiologists and surgical care teams may consider using the CHA2DS2-VASc score to evaluate perioperative outcome risks in patients with AF.

Lipopolysaccharide pretreatment increases protease-activated receptor-2 expression and monocyte chemoattractant protein-1 secretion in vascular endothelial cells.

BACKGROUND: This study investigated whether lipopolysaccharide (LPS) increase protease-activated receptor-2 (PAR-2) expression and enhance the association between PAR-2 expression and chemokine production in human vascular endothelial cells (ECs). METHODS: The morphology of ECs was observed through microphotography in cultured human umbilical vein ECs (EA. hy926 cells) treated with various LPS concentrations (0, 0.25, 0.5, 1, and 2 µg/mL) for 24 h, and cell viability was assessed using the MTT assay. Intracellular calcium imaging was performed to assess agonist (trypsin)-induced PAR-2 activity. Western blotting was used to explore the LPS-mediated signal transduction pathway and the expression of PAR-2 and adhesion molecule monocyte chemoattractant protein-1 (MCP-1) in ECs. RESULTS: Trypsin stimulation increased intracellular calcium release in ECs. The calcium influx was augmented in cells pretreated with a high LPS concentration (1 µg/mL). After 24 h treatment of LPS, no changes in ECs viability or morphology were observed. Western blotting revealed that LPS increased PAR-2 expression and enhanced trypsin-induced extracellular signal-regulated kinase (ERK)/p38 phosphorylation and MCP-1 secretion. However, pretreatment with selective ERK (PD98059), p38 mitogen-activated protein kinase (MAPK) (SB203580) inhibitors, and the selective PAR-2 antagonist (FSLLRY-NH2) blocked the effects of LPS-activated PAR-2 on MCP-1 secretion. CONCLUSIONS: Our findings provide the first evidence that the bacterial endotoxin LPS potentiates calcium mobilization and ERK/p38 MAPK pathway activation and leads to the secretion of the pro-inflammatory chemokine MCP-1 by inducing PAR-2 expression and its associated activity in vascular ECs. Therefore, PAR-2 exerts vascular inflammatory effects and plays an important role in bacterial infection-induced pathological responses.

Nicorandil Inhibits Cyclic Strain-Induced Interleukin-8 Expression in Human Umbilical Vein Endothelial Cells.

BACKGROUND: Nicorandil, a mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channel opener, exerts protective effects on the cardiovascular system. This study examined the effect of nicorandil on cyclic strain-induced interleukin-8 (IL-8) expression in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were exposed to cyclic strain in the presence or absence of nicorandil (1-10 µmol/l); we then analyzed IL-8 expression. We also assessed the effects of nicorandil on heme oxygenase-1 (HO-1) expression and cyclic strain-modulated IL-8 expression after HO-1 silencing in HUVECs. SUMMARY: HUVECs exposed to cyclic strain showed increased IL-8 messenger RNA expression and protein secretion. Nicorandil (1-10 µmol/l) inhibited cyclic strain-induced IL-8 expression, whereas 5-hydroxydecanoate (100 µmol/l), a selective inhibitor of the mitoKATP channel, completely reversed the inhibitory effects of nicorandil on cyclic strain-induced IL-8 expression. We demonstrated that nicorandil increased HO-1 expression in HUVECs. In addition, cobalt protoporphyrin (10 µmol/l), an inducer of HO-1 expression, mimicked the effects of nicorandil and inhibited IL-8 expression under cyclic strain, whereas zinc protoporphyrin IX (10 µmol/l), an inhibitor of HO-1 expression, antagonized the effect of nicorandil. HO-1 silencing significantly abrogated the inhibitory effects of nicorandil on cyclic strain-induced IL-8 expression, suggesting that HO-1 plays a role in the mechanism of action of nicorandil. KEY MESSAGES: This study is the first to report that nicorandil inhibits cyclic strain-induced IL-8 expression through the induction of HO-1 expression in HUVECs. This finding provides valuable new insight into the molecular pathways contributing to the vasoprotective effects of nicorandil.

Influenza Vaccination Reduces Hospitalization for Heart Failure in Elderly Patients with Chronic Kidney Disease: A Population-Based Cohort Study.

BACKGROUND: Elderly patients with chronic kidney disease (CKD) are at a higher risk of hospitalization for cardiovascular diseases (CVD). Previous studies have reported the beneficial effects of the influenza vaccine in patients with CVD. However, the effects of influenza vaccination on the reduction of hospitalizations for heart failure (HF) in elderly patients with CKD remain unclear. METHODS: This cohort study comprised elderly patients (≥ 55 years of age) with a recorded diagnosis of CKD (n = 4406) between January 1, 1999 and December 31, 2008. Each patient was followed-up until the end of 2008. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the first HF hospitalization were analyzed. In addition, the patients were categorized into four groups based on their vaccination status (unvaccinated and total number of vaccinations: 1, 2-3, and ≥ 4). RESULTS: We found that elderly patients with CKD receiving influenza vaccination exhibited a lower risk of HF hospitalization (adjusted HR, 0.31; 95% CI, 0.26-0.39, p < 0.001). The protective effects of influenza vaccination remained consistent regardless of the age group (55-64, 65-74, ≥ 75), sex, and influenza seasonality. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for HF hospitalization were 0.60 (0.47-0.77), 0.30 (0.23-0.41), and 0.10 (0.06-0.16) for patients who received 1, 2-3, and ≥ 4 vaccinations during the follow-up period, respectively. CONCLUSIONS: The results revealed that elderly patients with CKD receiving annual influenza vaccination are at a lower risk of HF hospitalization.

Lycopene inhibits cyclic strain-induced endothelin-1 expression through the suppression of reactive oxygen species generation and induction of heme oxygenase-1 in human umbilical vein endothelial cells.

Lycopene is the most potent active antioxidant among the major carotenoids, and its use has been associated with a reduced risk for cardiovascular disease (CVD). Endothelin-1 (ET-1) is a powerful vasopressor synthesized by endothelial cells and plays a crucial role in the pathophysiology of CVD. However, the direct effects of lycopene on vascular endothelial cells have not been fully described. This study investigated the effects of lycopene on cyclic strain-induced ET-1 gene expression in human umbilical vein endothelial cells (HUVECs) and identified the signal transduction pathways that are involved in this process. Cultured HUVECs were exposed to cyclic strain (20% in length, 1 Hz) in the presence or absence of lycopene. Lycopene inhibited strain-induced ET-1 expression through the suppression of reactive oxygen species (ROS) generation through attenuation of p22(phox) mRNA expression and NAD(P)H oxidase activity. Furthermore, lycopene inhibited strain-induced ET-1 secretion by reducing ROS-mediated extrace-llular signal-regulated kinase (ERK) phosphorylation. Conversely, lycopene treatment enhanced heme oxygenase-1 (HO-1) gene expression through the activation of phosphoinositide 3-kinase (PI3K)/Akt pathway, followed by induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation; in addition, HO-1 silencing partially inhibited the repressive effects of lycopene on strain-induced ET-1 expression. In summary, our study showed, for the first time, that lycopene inhibits cyclic strain-induced ET-1 gene expression through the suppression of ROS generation and induction of HO-1 in HUVECs. Therefore, this study provides new valuable insight into the molecular pathways that may contribute to the proposed beneficial effects of lycopene on the cardiovascular system.

Impact of chronic kidney disease and end-stage renal disease on the mid-term adverse outcomes in diabetic patients with cardiovascular diseases.

The evidence for the impact of renal dysfunction in patients with diabetes mellitus (DM) and first cardiovascular diseases on mid-term adverse outcomes remain scarce. This study included the data of patients with DM having first atherosclerotic cardiovascular disease (ASCVD) or congestive heart failure (CHF) from the Taipei Medical University Clinical Research Database. A Cox proportional hazards regression model was used to assess the impact of chronic kidney disease (CKD) or end-stage renal disease (ESRD) on the 1-year mortality and recurrent ASCVD/CHF outcomes. We enrolled 21,320 patients with DM hospitalized for ASCVD or CHF; of them, 18,185, 2639, and 496 were assigned to the non-CKD, CKD, and ESRD groups, respectively. After propensity score matching, compared with the non-CKD group, the CKD and ESRD groups had higher mid-term all-cause mortality (adjusted hazard ratio 1.72 [95% confidence interval 1.48-1.99] and 2.77 [2.05-3.73], respectively), cardiovascular death (1.84 [1.44-2.35] and 1.87 [1.08-3.24], respectively), and recurrent hospitalization for ASCVD (1.44 [1.24-1.68] and 2.33 [1.69-3.23], respectively) and CHF (2.08 [1.75-2.47] and 1.50 [1.04-2.17], respectively). The advancing age was associated with mortality in CKD/ESRD groups. In CKD group, male sex was associated with all-cause mortality and recurrent ASCVD risk; the diuretics usage was associated with mortality and recurrent CHF risks. Our findings suggest that CKD and ESRD are significant risk factors for mid-term adverse outcomes in patients with DM and established cardiovascular diseases. Additionally, old age, male sex and diuretics usage requires attention. Further good quality studies are needed in the future.

Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1.

Natto contains a potent fibrinolytic enzyme called nattokinase (NK), which has thrombolytic, antihypertensive, antiatherosclerotic and lipid-lowering effects. Although NK has been recognized for its beneficial effect on humans with atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms involved in vascular inflammation-atherosclerosis development remain largely unknown. The current study aimed to explore the effects of NK on gene regulation, autophagy, necroptosis and inflammasome in vascular inflammation. The transcriptional profiles of NK in endothelial cells (ECs) by RNA sequencing (RNA-seq) revealed that NK affected THBS1, SRF and SREBF1 mRNA expression. In Q-PCR analysis, SRF and THBS1 were upregulated but SREBF1 was unaffected in ECs treated with NK. NK treatment induced autophagy and inhibited NLRP3 inflammasome and necroptosis in ECs. Furthermore, the inhibition of SRF or THBS1 by siRNA suppressed autophagy and enhanced the NLRP3 inflammasome and necroptosis. In a mouse model, NK reduced vascular inflammation by activating autophagy and inhibiting NLRP3 inflammasome and necroptosis. Our findings provide the first evidence that NK upregulates SRF and THBS1 genes, subsequently increasing autophagy and decreasing necroptosis and NLRP3 inflammasome formation to reduce vascular inflammation. Therefore, NK could serve as nutraceuticals or adjuvant therapies to reduce vascular inflammation and possible atherosclerosis progression.

How Long After Coronary Artery Bypass Surgery Can Patients Have Elective Safer Non-Cardiac Surgery?

Objective: To evaluate the complications and mortality after noncardiac surgeries in patients who underwent previous coronary artery bypass grafting (CABG). Methods: We used insurance data and identified patients aged ≥20 years undergoing noncardiac surgeries between 2010 and 2017 in Taiwan. Based on propensity-score matching, we selected an adequate number of patients with a previous history of CABG (within preoperative 24 months) and those who did not have a CABG history, and both groups had balanced baseline characteristics. The association of CABG with the risk of postoperative complications and mortality was estimated (odds ratio [OR] and 95% confidence interval [CI]) using multiple logistic regression analysis. Results: The matching procedure generated 2327 matched pairs for analyses. CABG significantly increased the risks of 30-day in-hospital mortality (OR 2.28, 95% CI 1.36-3.84), postoperative pneumonia (OR 1.49, 95% CI 1.12-1.98), sepsis (OR 1.49, 95% CI 1.17-1.89), stroke (OR 1.53, 95% CI 1.17-1.99) and admission to the intensive care unit (OR, 1.75, 95% CI 1.50-2.05). The findings were generally consistent across most of the evaluated subgroups. A noncardiac surgery performed within 1 month after CABG was associated with the highest risk for adverse events, which declined over time. Conclusion: Prior history of CABG was associated with postoperative pneumonia, sepsis, stroke, and mortality in patients undergoing noncardiac surgeries. Although we raised the possibility regarding deferral of non-critical elective noncardiac surgeries among patients had recent CABG when considering the risks, critical or emergency surgeries were not in the consideration of delay surgery, especially cancer surgery.

Drug repurposing screens to identify potential drugs for chronic kidney disease by targeting prostaglandin E2 receptor.

Renal inflammation and fibrosis are significantly correlated with the deterioration of kidney function and result in chronic kidney disease (CKD). However, current therapies only delay disease progression and have limited treatment effects. Hence, the development of innovative therapeutic approaches to mitigate the progression of CKD has become an attractive issue. To date, the incidence of CKD is still increasing, and the biomarkers of the pathophysiologic processes of CKD are not clear. Therefore, the identification of novel therapeutic targets associated with the progression of CKD is an attractive issue. It is a critical necessity to discover new therapeutics as nephroprotective strategies to stop CKD progression. In this research, we focus on targeting a prostaglandin E2 receptor (EP2) as a nephroprotective strategy for the development of additional anti-inflammatory or antifibrotic strategies for CKD. The in silico study identified that ritodrine, dofetilide, dobutamine, and citalopram are highly related to EP2 from the results of chemical database virtual screening. Furthermore, we found that the above four candidate drugs increased the activation of autophagy in human kidney cells, which also reduced the expression level of fibrosis and NLRP3 inflammasome activation. It is hoped that these findings of the four candidates with anti-NLRP3 inflammasome activation and antifibrotic effects will lead to the development of novel therapies for patients with CKD in the future.

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

PURPOSE: The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). METHODS: This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. RESULTS: Statin users had significantly higher odds of DED (adjusted OR = 1.12; 95% confidence interval (CI) = 1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR = 1.04; 95% CI = 0.99-1.10, p = 0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR = 0.99, 95% CI = 0.93-1.06, p = 0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR = 1.00, p = 0.922; adjusted OR = 0.94, p = 0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. CONCLUSIONS: Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Predicting 3-month and 1-year mortality for patients initiating dialysis: a population-based cohort study.

BACKGROUND: Despite the continual improvements in dialysis treatments, mortality in end-stage kidney disease (ESKD) remains high. Many mortality prediction models are available, but most of them are not precise enough to be used in the clinical practice. We aimed to develop and validate two prediction models for 3-month and 1-year patient mortality after dialysis initiation in our population. METHODS: Using population-based data of insurance claims in Taiwan, we included more than 210,000 patients who initiated dialysis between January 1, 2006, and June 30, 2015. We developed two prognostic models, which included 9 and 11 variables, respectively (including age, sex, myocardial infarction, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, peptic ulcer disease, malignancy, moderate to severe liver disease, and first dialysis in intensive care unit). RESULTS: The models showed adequate discrimination (C-statistics were 0.80 and 0.82 for 3-month and 1-year mortality, respectively) and good calibration. In both our models, the first dialysis in the intensive care unit and moderate-to-severe liver disease were the strongest risk factors for mortality. CONCLUSION: The prediction models developed in our population had good predictive ability for short-term mortality in patients initiating dialysis in Taiwan and could help in decision-making regarding dialysis initiation, at least in our setting, supporting a patient-centered approach to care.

Effect of Influenza Vaccination on the Reduction of the Incidence of Chronic Kidney Disease and Dialysis in Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus (T2DM) have a higher risk of chronic kidney disease (CKD) due to vascular complications and chronic inflammation. T2DM contributes to a higher risk of mortality and morbidity related to influenza. In Taiwan, influenza vaccination is recommended for patients with T2DM. A previous meta-analysis reported the efficacy of influenza vaccination in reducing hospitalization and mortality in patients with diabetes; however, the renal protective effect of the vaccine remains unclear. This study evaluated whether influenza vaccination could reduce the incidence of CKD and dialysis in patients with T2DM. The study cohort included all patients aged ≥55 years who were diagnosed as having T2DM between 1 January 2000 and 31 December 2012, by using data from Taiwan's National Health Insurance Research Database. Each patient was followed up with to assess factors associated with CKD. A time-dependent Cox proportional hazard regression model after adjustment for potential confounders was used to calculate the hazard ratio (HR) of CKD in the vaccinated and unvaccinated patients. The study population comprised 48,017 eligible patients with DM; 23,839 (49.7%) received influenza vaccination and the remaining 24,178 (50.3%) did not. The adjusted HRs (aHRs) for CKD/dialysis decreased in the vaccinated patients compared with the unvaccinated patients (influenza season, noninfluenza season, and all seasons: aHRs: 0.47/0.47, 0.48/0.49, and 0.48/0.48, respectively, all p < 0.0001). We observed similar protective effects against CKD during the influenza and noninfluenza seasons. Regardless of comorbidities or drug use, influenza vaccination was an independent protective factor. Furthermore, aHRs for CKD/dialysis were 0.71 (0.65−0.77)/0.77 (0.68−0.87), 0.57 (0.52−0.61)/0.69 (0.56−0.70), and 0.30 (0.28−0.33)/0.28 (0.24−0.31) in the patients who received 1, 2−3, and ≥4 vaccinations during the follow-up period, respectively. This population-based cohort study demonstrated that influenza vaccination exerts a dose-dependent and synergistic protective effect against CKD in the patients with T2DM with associated risk factors.

Nicorandil inhibits angiotensin-II-induced proliferation of cultured rat cardiac fibroblasts.

BACKGROUND/AIMS: Nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener, nitric oxide (NO) donor and antioxidant, was shown to exert a variety of pharmacological effects including cardioprotective properties. However, its mechanisms of action are not completely understood. The aims of this study were to examine whether nicorandil may alter angiotensin-II (Ang II)-induced cell proliferation and to identify the putative underlying signaling pathways in rat cardiac fibroblasts. METHODS: Cultured rat cardiac fibroblasts were pretreated with nicorandil, then stimulated with Ang II, and cell proliferation and endothelin-1 (ET-1) expression were examined. The effects of nicorandil on Ang-II-induced reactive oxygen species (ROS) formation and extracellular signal-regulated kinase (ERK) phosphorylation were also examined. In addition, the effects of nicorandil on NO production and endothelial nitric oxide synthase (eNOS) phosphorylation were tested to elucidate the intracellular mechanism. RESULTS: Nicorandil (0.1-10 µmol/l) caused a concentration-dependent inhibition of Ang-II-increased cell proliferation and ET-1 expression which were prevented by the K(ATP) channel blocker glibenclamide (1 µmol/l). Nicorandil also inhibited Ang-II-increased ROS and ERK phosphorylation. In addition, nicorandil was found to increase the NO and eNOS phosphorylation. N-nitro-L-arginine methyl ester, an inhibitor of NOS, and the short interfering RNA transfection for eNOS markedly attenuated the inhibitory effect of nicorandil on Ang-II-induced cell proliferation. CONCLUSION: Our results suggest that nicorandil prevents cardiac fibroblast proliferation, and the inhibitory effect might be associated with the opening K(ATP) channels, by interfering with the generation of ROS, and the activation of the eNOS-NO pathway.

Risk of acute atherosclerotic cardiovascular disease in patients with acute and chronic pancreatitis.

The association between pancreatitis and acute myocardial infarction or stroke remains incompletely understood. This study aimed to evaluate the long-term risk of acute atherosclerotic cardiovascular disease (ASCVD) in people with acute and chronic pancreatitis. Using research database of Taiwan's National Health Insurance, we identified 2678 patients aged ≥ 20 years with newly diagnosed pancreatitis in 2000-2008. A cohort of 10,825 adults without pancreatitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident acute ASCVD was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acute ASCVD associated with pancreatitis were calculated. Compared with the comparison cohort, the adjusted HR of acute ASCVD were 1.76 (95% CI 1.47-2.12) and 3.42 (95% CI 1.69-6.94) for people with acute pancreatitis and chronic pancreatitis, respectively. A history of alcohol-related illness (HR 9.49, 95% CI 3.78-23.8), liver cirrhosis (HR 7.31, 95% CI 1.81-29.5), and diabetes (HR 6.89, 95% CI 2.18-21.8) may worsen the risk of acute ASCVD in patients with chronic pancreatitis. Compared with people had no pancreatitis, patients with acute pancreatitis who had alcohol-related illness (HR 4.66, 95% CI 3.24-6.70), liver cirrhosis (HR 4.44, 95% CI 3.05-6.47), and diabetes (HR 2.61, 95% CI 2.03-3.36) were at increased risk of acute ASCVD. However, the cumulative use of metformin was associated with a reduced risk of acute ASCVD in the acute pancreatitis cohort (HR 0.30, 95% CI 0.17-0.50). Compared with the control group, patients with acute or chronic pancreatitis were more likely to have an increased risk of acute ASCVD, while the use of metformin reduced the risk of acute ASCVD. Our findings warrant a survey and education on acute ASCVD for patients with acute and chronic pancreatitis.

Adverse Outcomes after Non-Cardiac Surgeries in Patients with Heart Failure: A Propensity-Score Matched Study.

The impact of heart failure (HF) on postoperative outcomes is not completely understood. Our purpose is to investigate complications and mortality after noncardiac surgeries in people who had HF. In the analyses of research data of health insurance in, we identified 32,808 surgical patients with preoperative HF and 32,808 patients without HF undergoing noncardiac surgeries. We used a matching procedure with propensity score and considered basic characteristics, coexisting diseases, and information of index surgery between patients with and without HF. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for complications and mortality after noncardiac surgeries in patients with HF were analyzed in multivariate logistic regressions. HF increased the risks of postoperative acute myocardial infarction (OR 2.51, 95% CI 1.99-3.18), pulmonary embolism (OR 2.46, 95% CI 1.73-3.50), acute renal failure (OR 1.97, 95% CI 1.76-2.21), intensive care (OR 1.93, 95% CI 1.85-2.01), and 30-day in-hospital mortality (OR 1.80, 95% CI 1.59-2.04). Preoperative emergency care, inpatient care, and injections of diuretics and cardiac stimulants due to heart failure were also associated with mortality after surgery. Patients with HF had increased complications and mortality after noncardiac surgeries compared with those without HF. The surgical care team may consider revising the protocols for perioperative care in patients with HF.

Influenza vaccination reduces incidence of peripheral arterial occlusive disease in elderly patients with chronic kidney disease.

An influenza vaccination might reduce the risk of incident peripheral arterial occlusive disease (PAOD) in patients with chronic kidney disease (CKD), but supporting evidence is limited. This case-crossover study analyzed data from Taiwan's real-world National Health Insurance Research Database. This study included elderly (≥ 67 years old) patients with CKD having incident PAOD from January 1, 2006, to June 30, 2015. We defined 1 year before PAOD onset as the index date for the self-control group. A conditional logistic regression model was used to investigate exposure to an influenza vaccination for estimating the risk for incident PAOD following vaccination. In total, this study included 46,782 elderly patients with CKD having incident PAOD. The odds ratios for incident PAOD were 0.85 (95% confidence interval 0.77-0.94), 0.85 (0.79-0.92), 0.84 (0.79-0.90), and 0.85 (0.81-0.90) at 1, 2, 3, and 4 months after an influenza vaccination, respectively. We observed consistent results for the subgroups of patients with CKD and concomitant diabetes. However, we did not observe any beneficial effects of influenza vaccination in patients with advanced CKD or end-stage renal disease. This study demonstrated that influenza vaccination may be associated with a reduced risk of incident PAOD among patients with early-stage CKD.