Monotherapy versus combination therapy of statin and renin–angiotensin system inhibitor in ST-segment elevation myocardial infarction

Background: The beneficial effects of statin and renin–angiotensin system inhibitor (RASI) are well-known. In this retrospective cohort study,  2-year clinical outcomes were compared between monotherapy and combination therapy with statin and RASI in ST-segment elevation myocardial infarction (STEMI) patients after stent implantation. Methods: A total of 17,414 STEMI patients were enrolled and divided into the three groups (group A: 2448 patients, statin alone; group B: 2431 patients, RASI alone; and group C: 12,535 patients, both statin and RASI). The principal clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction, and any repeat revascularization. Results: After adjustment, the cumulative incidences of MACEs in group A (adjusted hazard ratio [aHR] 1.337; 95% confidence interval [CI] 1.064–1.679; p = 0.013) and in group B (aHR 1.375; 95% CI 1.149–1.646; p = 0.001) were significantly higher than in group C. The cumulative incidence of all-cause death in group A was significantly higher than that in group C (aHR 1.539; 95% CI 1.014–2.336; p = 0.043). The cumulative incidences of any repeat revascularization (aHR 1.317; 95% CI 1.031–1.681; p = 0.028), target lesion vascularization, and target vessel vascularization in group B were significantly higher than in group C. Conclusions: A Statin and RASI combination therapy significantly reduced the cumulative incidence of MACEs compared with a monotherapy of these drugs. Moreover, the combination therapy showed a reduced all-cause death rate compared with statin monotherapy, and a decreased repeat revascularization rate compared with RASI monotherapy

Lack of Effect of Dexamethasone on Growth of Orientia Tsutsugamushi Gilliam in Mouse L929 Cells

PURPOSE: Previous studies and our own clinical experience suggest that concurrent corticosteroid treatment for severe rickettsial disease with multiorgan failure may improve the clinical course or reduce mortality. However, the use of corticosteroids as adjunctive treatment for rickettsial diseases is controversial. We attempted to determine the influences of corticosteroid on the growth of Orientia tsutsugamushi in vitro to justify and evaluate the clinical applicability of corticosteroid in rickettsial disease. MATERIALS AND METHODS: L929 cells were infected with Orientia tsutsugamushi Gilliam. Dexamethasone was added to the cells at final concentrations of 10¹ and 10⁷ pg/mL. Cultures were incubated at 35°C and processed for flow cytometry on the 6th day after addition of dexamethasone. RESULTS: Observation on the 6th day after treatment with dexamethasone in infected cultures revealed that there was no difference in fluorescence intensity among the treatment wells. Treatment of the cells with dexamethasone at concentrations of 10¹ and 10⁷ pg/mL showed no influence on the growth of Orientia tsutsugamushi. CONCLUSION: Our results to show that isolated corticosteroid does not enhance the replication of Orientia tsutsugamushi in vitro. Concurrent use of anti-inflammatory or immunosuppressive doses of corticosteroids in conjunction with antibiotics may not have detrimental effects on the course of scrub typhus.ope

Effect of delayed hospitalization on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction

Background: We evaluated the effect of delayed hospitalization (symptom-to-door time [STD] ≥ 24 h) on 3-year clinical outcomes according to renal function in patients with non-ST-segment elevation myocardial infarction (NSTEMI) undergoing new-generation drug-eluting stent (DES) implantation. Methods: A total of 4513 patients with NSTEMI were classified into chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2, n = 1118) and non-CKD (eGFR ≥ 60 mL/min/1.73 m2, n = 3395) groups. They were further sub-classified into groups with (STD ≥ 24 h) and without (STD < 24 h) delayed hospitalization. The primary outcome was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction, any repeat coronary revascularization, and stroke. The secondary outcome was stent thrombosis (ST). Results: After multivariable-adjusted and propensity score analyses, the primary and secondary clinical outcomes were similar in patients with or without delayed hospitalization in both CKD and non-CKD groups. However, in both the STD < 24 h and STD ≥ 24 h groups, MACCE (p < 0.001 and p < 0.006, respectively) and mortality rates were significantly higher in the CKD group than in the non-CKD group. However, ST rates were similar between the CKD and non-CKD groups and between the STD < 24 h and STD ≥ 24 h groups. Conclusions: Chronic kidney disease appears to be a much more important determinant of MACCE and mortality rates than STD in patients with NSTEMI

Sex difference after acute myocardial infarction patients with a history of current smoking and long-term clinical outcomes: Results of KAMIR Registry

Background: The contribution of sex as an independent risk factor for cardiovascular disease still remains controversial. The present study investigated the impact of sex on long-term clinical outcomes in Korean acute myocardial infarction (AMI) patients with a history of current smoking on admission after drug-eluting stents (DESs). Methods: A total of 12,565 AMI patients (male: n = 11767 vs. female: n = 798) were enrolled. Major adverse cardiac events (MACEs) comprising all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization were the primary outcomes that were compared between the two groups. Probable or definite stent thrombosis (ST) was the secondary outcome. Results: After adjustment, the early (30 days) cumulative incidences of MACEs (adjusted hazard ratio [aHR]: 1.457; 95% confidence interval [CI]: 1.021–2.216; p = 0.035) and all-cause death (aHR: 1.699; 95% CI: 1.074–2.687; p = 0.023) were significantly higher in the female group than in the male group. At 2 years, the cumulative incidences of all-cause death (aHR: 1.561; 95% CI: 1.103–2.210; p = 0.012) and Re-MI (aHR: 1.880; 95% CI: 1.089–2.974; p = 0.022) were significantly higher in the female group than in the male group. However, the cumulative incidences of ST were similar between the two groups (aHR: 1.207; 95% CI: 0.583–2.497; p = 0.613). Conclusions: The female group showed worse short-term and long-term clinical outcomes compared with the male group comprised of Korean AMI patients with a history of current smoking after successful DES implantation. However, further studies are required to confirm these results

ST-elevation versus non-ST-elevation myocardial infarction after combined use of statin with renin–angiotensin system inhibitor: Data from the Korea Acute Myocardial Infarction Registry

Background: Limited data are available comparing the combined effects of statins and renin–angiotensin system inhibitor (RASI) between patients with ST-segment elevation myocardial infarction (STEMI) and those with non-STEMI (NSTEMI). We compared the effects of statins combined with RASI in STEMI and NSTEMI patients after stent implantation during a long-term follow-up period. Methods: A total of 21,890 acute myocardial infarction (AMI) patients who underwent successful stent implantation and who received statins with RASI were enrolled. They were separated into the STEMI group (n = 12,490) and the NSTEMI group (n = 9400). The major clinical endpoint was the occurrence of major adverse cardiac events (MACEs) defined as all-cause death, recurrent myocardial infarction (Re-MI), and any repeat revascularization. Results: Two propensity score-matched (PSM) groups (5891 pairs, n = 11782, C-statistic = 0.821) were generated. Even though the cumulative incidences of MACE, re-MI, total repeat revascularization were similar between the two groups, the cumulative incidences of all-cause death (hazard ratio [HR] 1.407; 95% confidence interval [CI] 1.106–1.790; p = 0.005) and cardiac death (HR 1.311; 95% CI 1.983–1.749; p = 0.046) were significantly higher in the NSTEMI group. Conclusions: In this study, statin with RASI combination therapy was more beneficial to the STEMI patients than to the NSTEMI patients in reducing all-cause death and cardiac death

Angiotensin converting enzyme inhibitors versus angiotensin II type 1 receptor blockers in patients with acute myocardial infarction and prediabetes after successful implantation of newer-generation drug-eluting stents

Background: Because limited data are available, the present study investigated 2-year major clinical outcomes after angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) therapy in patients with acute myocardial infarction (AMI) and prediabetes after successful implantation of newer-generation drug-eluting stents (DESs). Methods: Overall, 2932 patients with AMI and prediabetes were classified into two groups — the ACEIs group (n = 2059) and the ARBs group (n = 873). The primary endpoint was the occurrence of patient-oriented composite outcome (POCO), defined as all-cause death, recurrent myocardial infarction (Re-MI), or any repeat revascularization. The secondary endpoint was definite or probable stent thrombosis (ST). Results: The cumulative incidences of POCO (adjusted hazard ratio [aHR]: 1.020; 95% confidence interval [CI]: 0.740–1.404; p = 0.906), all-cause death (aHR: 1.394; 95% CI: 0.803–2.419; p = 0.238), Re-MI (aHR: 1.210; 95% CI: 0.626–2.340; p = 0.570), any repeat revascularization (aHR: 1.150; 95% CI: 0.713–1.855; p = 0.568), and ST (aHR: 1.736; 95% CI: 0.445–6.766; p = 0.427) were similar between the groups. These results were confirmed after propensity score-adjusted analysis. Conclusions: In this study, patients with AMI and prediabetes who received ACEIs or ARBs showed comparable clinical outcomes during the 2-year follow-up period

A Phenome-Based Functional Analysis of Transcription Factors in the Cereal Head Blight Fungus, Fusarium graminearum

Fusarium graminearum is an important plant pathogen that causes head blight of major cereal crops. The fungus produces mycotoxins that are harmful to animal and human. In this study, a systematic analysis of 17 phenotypes of the mutants in 657 Fusarium graminearum genes encoding putative transcription factors (TFs) resulted in a database of over 11,000 phenotypes (phenome). This database provides comprehensive insights into how this cereal pathogen of global significance regulates traits important for growth, development, stress response, pathogenesis, and toxin production and how transcriptional regulations of these traits are interconnected. In-depth analysis of TFs involved in sexual development revealed that mutations causing defects in perithecia development frequently affect multiple other phenotypes, and the TFs associated with sexual development tend to be highly conserved in the fungal kingdom. Besides providing many new insights into understanding the function of F. graminearum TFs, this mutant library and phenome will be a valuable resource for characterizing the gene expression network in this fungus and serve as a reference for studying how different fungi have evolved to control various cellular processes at the transcriptional level

Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated GNB2L1 and CAV1 expression were enriched in the EGFR TKI-resistant group. Moreover, GZMK upregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC