Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis.

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

Mortality among acute myocardial infarction patients admitted to hospitals on weekends as compared with weekdays in Taiwan.

Weekend effect has been considered to be associated with poorer quality of care and patient's survival. For acute myocardial infarction (AMI) patients, the question of whether patients admitted during off-hours have worse outcomes as compared with patients admitted during on-hours is still inconclusive. We conducted this study to explore the weekend effect in AMI patients, using a nationwide insurance database in Taiwan. Using Taiwan National Health Insurance (NHI) claims database, we designed a retrospective cohort study, and extracted 184,769 incident cases of AMI through the NHI claims database between January 2006 and December 2014. We divided the patients into weekend admission group and weekday admission group. Patients were stratified as ST elevation/non-ST elevation AMI and receiving/not receiving percutaneous coronary intervention (PCI). We used a logistic regression model to examine the relative risk of in-hospital mortality and 1-year mortality which were obtained from the Taiwan National Death Registry between study groups. We found no difference between weekend group and weekday group for risk of in-hospital mortality (15.8% vs 16.2%, standardized difference 0.0118) and risk of 1-year mortality (30.2% vs 30.9%, standardized difference 0.0164). There was no statistically significant difference among all the comparisons through the multivariate logistic regression analysis adjusting for all the covariates and stratifying by the subtypes of AMI and whether or not executing PCI during hospitalization. As for AMI patients in Taiwan, admission on weekends or weekdays did not have a significant impact on either in-hospital mortality or 1-year cumulative mortality.

Effects of preoperative serum vitamin D levels on early clinical function outcomes and the moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty.

OBJECTIVE: To investigate the impact of vitamin D levels on early clinical function outcomes and the potential risk factors of moderate-to-severe pain prevalence in postmenopausal women after primary total knee arthroplasty (TKA). METHODS: From April 2017 to December 2019, 226 women were retrospectively recruited. The women were divided into two groups based on their preoperative serum 25-hydroxyvitamin D levels: (1) vitamin D-sufficient group (≥30 ng/mL); (2) vitamin D-deficient group (<30 ng/mL). The visual analog scale, Western Ontario and McMaster Arthritis Index score, and Knee Society Score were used to evaluate clinical outcomes. Risk factors for developing postoperative moderate-to-severe knee pain were studied using multivariate binary logistic regression analyses. RESULTS: There was no significant difference in preoperative clinical function assessment between the two groups. The difference in postoperative Western Ontario and McMaster Arthritis Index score between the two groups was statistically significant (15.3 ±â€Š0.7 vs 15.6 ±â€Š0.7: P = 0.02). However, the differences in postoperative visual analog scale and Knee Society Score scores between the two groups were not significant (P > 0.05). The incidence of postoperative moderate-to-severe pain was 16.4% (95% CI 11.8%-21.9%). Multivariate logistic regression analysis revealed that vitamin D deficiency, smoking, and high body mass index were potential risk factors for moderate-to-severe knee pain in postmenopausal women early after TKA (P < 0.05). CONCLUSION: Preoperative vitamin D deficiency may adversely affect early functional outcomes in postmenopausal women after TKA. In addition, vitamin D deficiency, smoking, and high body mass index were independent risk factors for moderate-to-severe knee pain after surgery.

Long-Term Effect of Non-Selective Beta-Blockers in Patients With Rheumatoid Arthritis After Myocardial Infarction-A Nationwide Cohort Study.

Objectives: Rheumatoid arthritis (RA) is an independent nontraditional risk factor for incidence of myocardial infarction (MI) and post-MI outcome is impaired in the RA population. Use of beta-blockers improves the long-term survival after MI in the general population while the protective effect of beta-blockers in RA patients is not clear. We investigate the impact of beta-blockers on the long-term outcome of MI among RA patients. Methods: We identified RA subjects from the registries for catastrophic illness and myocardial infarction from 2003 to 2013. The enrolled subjects were divided into three groups according to the prescription of beta-blockers (non-user, non-selective, and ß1-selective beta-blockers). The primary endpoint was all-cause mortality. We adjusted clinical variables and utilized propensity scores to balance confounding bias. Cox proportional hazards regression models were used to estimate the incidence of mortality in different groups. Results: A total of 1,292 RA patients with myocardial infarction were enrolled, where 424 (32.8%), 281 (21.7%), and 587 (45.5%) subjects used non-user, non-selective, and ß1-selective beta-blockers, respectively. Use of beta-blockers was associated with lower risk of all-cause mortality after adjustment with comorbidities, medications (adjusted hazard ratio [HR] 0.871; 95% confidence interval [CI] 0.727-0.978), and propensity score (HR 0.882; 95% CI 0.724-0.982). Compared with ß1-selective beta-blockers, treatment with non-selective beta-blockers (HR 0.856; 95% CI 0.702-0.984) was significantly related to lower risk of mortality. The protective effect of non-selective beta-blockers remained in different subgroups including sex and different anti-inflammatory drugs. Conclusion: Use of beta-blockers improved prognosis in post-MI patients with RA. Treatment with non-selective beta-blockers was significantly associated with reduced risk of mortality in RA patients after MI rather than ß1-selective beta-blockers.

The periprocedural and 30-day outcomes of carotid stenting in patients with carotid artery near-occlusion.

The safety of endovascular revascularization in patients with carotid artery near occlusion (CANO) is unknown. We aimed to evaluate the peri-procedural risk in CANO patients receiving carotid artery stenting (CAS). A prospective data base with retrospective review was performed to identify patients who underwent CAS with CANO from July 2006 to July 2020, and had at least 1-month clinical follow-up data. The primary endpoints were stroke, hyperperfusion syndrome, and death within 30 days after CAS. A total of 198 patients with carotid artery stenosis were enrolled including 92 patients with CANO and 106 age and sex-matched patients with 70-99% conventional carotid stenosis. Full distal carotid collapse was found in 45 CANO patients (45/92, 49%). The technical success rate was 100%. The CANO patients had significantly longer lesion lengths compared with those of the non-CANO group. The incidence of hyperperfusion syndrome was comparable (CANO: 2.2%, non-CANO: 0.9%, P = 0.598). The risks of ischemic stroke and death within 30 days were 1.1% and 0% in the CANO group; and 1.9% and 0.9%, in the non-CANO group, respectively, without statistical difference. In conclusion, CAS is safe for patients with CANO, with a similar low 30-day peri-procedural event rate comparable to those of non-CANO.

Acute Femoral Occlusion After Adjunctive Angio-Seal Usage in Vascular Closure Following Transcatheter Aortic Valve Replacement.

We report 3 patients with acute femoral occlusion after adjunctive Angio-Seal use during transfemoral transcatheter aortic valve replacement. All occlusions were recanalized by applying elaborative strategies for chronic total occlusion recanalization. Our experience reminds operators to cautiously use the Angio-Seal as a bailout treatment, especially in patients with high-risk clinical features. (Level of Difficulty: Intermediate.).

Dynamic changes of matrix metalloproteinase-9 in patients with Klebsiella pneumoniae meningitis.

To quantitate cerebrospinal fluid (CSF) concentrations of matrix metalloproteinase 9 (MMP-9) in adult patients with Klebsiella pneumoniae meningitis and to correlate levels of MMP-9 with parameters of intrathecal inflammation and analyze the kinetic changes of MMP-9. In a prospective cohort study, levels of MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP-1) concentrations were measured in the CSF of six adult patients with meningitis and 11 controls. MMP-9 and TIMP-1 were detected in all of the six patients at presentation and follow up lumbar puncture. CSF levels of MMP-9 (6.71+/-7.29 ng/ml) and TIMP-1(454.3+/-242.9 ng/ml) were higher in patients than in the control group (0.07+/-0.11 ng/ml and 27.14+/-39.34 ng/ml, respectively). Levels of MMP-9 correlated with CSF concentrations of protein, cell count and lactate. Repeated lumbar punctures showed that levels of MMP-9 decrease during clinical recovery, although the levels of MMP-9 in the CSF are variable because of the small number of cases. The relative change in gelatin zymography is comparable to the changes of MMP-9 levels found in ELISA. MMP-9 levels in CSF may be a useful tool in follow-up in patients with K. pneumoniae meningitis.

A randomized, double-blind clinical study of the effects of Ankascin 568 plus on blood lipid regulation.

Hyperlipidemia and inflammation play important roles in the development and progression of atherosclerosis. Atherosclerosis is regarded as an inflammatory response of blood vessels to injury at the start of atherosclerotic plaque formation, which then leads to cardiovascular events. Edible fungi of the Monascus species have been used as traditional Chinese medicines in East Asia for several centuries. The fermented products of Monascus purpureus NTU 568 possess a number of functional secondary metabolites including the anti-inflammatory pigments monascin and ankaflavin. Compounds derived from M. purpureus have been shown to have hypolipidemic effects. We aimed to evaluate the effects of M. purpureus NTU 568 fermentation product an extract (Ankascin 568 plus) containing monascin and ankaflavin on blood lipids in volunteers with borderline high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) by conducting a 12-week randomized, double-blind, placebo-controlled, adaptive-design study. This study enrolled 40 subjects aged 18-65 years from a population of patients with TC and LDL-C levels of ≥180 mg/dL and 130-190 mg/dL, respectively. Measured endpoints included lipid profile, liver, kidney and thyroid function, electrolyte balance, creatinine phosphokinase, and fasting blood glucose. After 4 weeks of treatment (500 mg Ankascin 568 plus/day), the changes in the lipid levels showed that the active products had a more favorable effect than the placebo. Compared to the baseline, statistically significant decreases of 11.9% and 19.0% were observed in TC and LDL-C levels, respectively (p < 0.05 for all pairs). This study demonstrated that subjects administered one 500 mg capsule of Ankascin 568 plus for more than 4 weeks exhibited a significant reduction in serum TC and LDL-C levels. Therefore, Ankascin 568 plus may be a potentially useful agent for the regulation of blood lipids and the treatment of coronary artery diseases.

A randomized, double-blind clinical study to determine the effect of ANKASCIN 568 plus on blood glucose regulation.

Diabetes is the fourth major cause of death in Taiwan. High blood glucose can lead to macrovascular diseases, small vessel diseases (retinopathy, kidney disease), and neuropathy. This study aimed to investigate whether Monascus-fermented products (ANKASCIN 568 plus) can regulate blood glucose and blood lipids. This study enrolled 39 patients with a fasting blood glucose level between 100 mg/dL and 180 mg/dL, and a glycated hemoglobin (HbA1c) level of <9%. All patients were randomly divided into placebo (n=20) and experimental (n=19) groups. Each patient received two placebo capsules (maltodextrin) or ANKASCIN 568 plus capsules daily for 12 weeks. The patients were screened during follow-up 4 weeks after the administration of sample or placebo had been discontinued. Blood and urine samples were collected at the initial, 6th week, 12th week, and 16th week. The anthropometric indicators of blood pressure, fasting plasma glucose level, postprandial plasma glucose level, insulin level, insulin resistance, blood lipid changes, and liver, kidney, and thyroid function indices were measured. After 6 weeks, changes in fasting blood glucose, low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels showed that ANKASCIN 568 plus had a more favorable effect than the placebo. Compared to baseline, a statistically significant decrease of 8.5%, 10.3%, and 7.5% was observed in fasting blood glucose, LDL-C and, TC levels, respectively (p<0.05 for all pairs). Therefore, ANKASCIN 568 plus produced by Monascus purpureus NTU 568 fermentation may be a potentially useful agent for the regulation of blood glucose and blood lipids and for treatment of coronary artery diseases.