There are unmet needs for pharmacologic agents beyond current medications, such as statins, to effectively lower low-density lipoprotein cholesterol levels to target goals, especially in patients with very high or extremely high risk. Pharmacological targeting of mRNA represents an emerging, innovative approach with the potential to expand upon current therapies. In RNA-targeted therapeutics, a novel approach is the use of chemically modified oligonucleotides to inhibit the production of target proteins at their sites of gene coding. There are two main classes of RNA-targeted therapeutics: single-stranded antisense oligonucleotides (ASOs) and double-stranded small inhibiting RNAs. ASOs are synthetic molecules with a length of 15–30 nucleotides that are designed specifically to bind to a target mRNA in a sequence-specific manner. Using these agents to inhibit the translation of key regulatory proteins, such as apolipoprotein CIII, apolipoprotein(a), and angiopoietinlike protein 3, has demonstrated treatment efficacy for dyslipidemia. Many cardiovascular outcome trials with ASOs are ongoing. As clinicians, we must carefully monitor the longterm safety and efficacy of this new modality through large clinical trials in the future.

Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabe- Tes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

Background: The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints. Methods: Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. Results: Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001). Conclusions A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.

Background: Continuous glucose monitoring (CGM) has been widely used in the management of diabetes. However, the usefulness and detailed data during perioperative status were not well studied. In this study, we described the immediate changes of glucose profiles after metabolic surgery using intermittently scanned CGM (isCGM) in individuals with type 2 diabetes mellitus (T2DM). Methods: This was a prospective, single-center, single-arm study including 20 participants with T2DM. The isCGM (FreeStyle Libre CGM) implantation was performed within 2 weeks before surgery. We compared CGM metrics of 3 days before surgery and 3 days after surgery, and performed the correlation analyses with clinical variables. Results: The mean glucose significantly decreased after surgery (147.0±40.4 to 95.5±17.1 mg/dL, P<0.001). Time in range (TIR; 70 to 180 mg/dL) did not significantly change after surgery in total. However, it was significantly increased in a subgroup of individuals with glycosylated hemoglobin (HbA1c) ≥8.0%. Time above range (>250 or 180 mg/dL) was significantly decreased in total. In contrast, time below range (<70 or 54 mg/dL) was significantly increased in total and especially in a subgroup of individuals with HbA1c <8.0% after surgery. The coefficient of variation significantly decreased after surgery. Higher baseline HbA1c was correlated with greater improvement in TIR (rho=0.607, P=0.005). Conclusion The isCGM identified improvement of mean glucose and glycemic variability, and increase of hypoglycemia after metabolic surgery, but TIR was not significantly changed after surgery. We detected an increase of TIR only in individuals with HbA1c ≥8.0%.

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

PURPOSE: To evaluate the role of linac based radiosurgery (RS) in the treatment of meningiomas, we retrospectively analyzed the results of clinical and follow up CT/MRI studies. METHODS AND MATERIALS: From the 1988 July to 1998 April, twenty patients of meningioma had been treated with 6 MV linear accelerator based radiosurgery. Of the 20 patients, four (20%) were male and 16 (80%) were female. Mean age was 51 years old (22~78 years old). Majority of intracranial location of tumor for RS were parasagittal and sphenoid wing area. RS was done for primary treatment in 6 (30%), postoperative residual lesions in 11 (55%) and regrowth after surgery in 3 (15%). Mean tumor volume was 5.72 cm3 (0.78~15.1 cm3) and secondary collimator size was 2.04 cm (1~3 cm). The periphery of tumor margin was prescribed with the mean dose of 19.6 Gy (9~30 Gy) which was 40~90% of the tumor center dose. The follow up duration ranged from 2.5 to 109 months (median 53 months). Annual CT/MRI scan was checked. RESULTS: By the follow up imaging studies, the tumor volume was reduced in 5 cases (25%), arrested growth in 14 cases (70%), and increased size in 1 case (15%). Among these responsive and stable 19 patients by imaging studies, there showed loss of contrast enhancement after CT/MRI in four patients. In clinical response, nine (45%) patients were considered improved condition, 10 (50%) patients were stable and one (5%) was worsened to be operated. This partly resulted in necrosis after surgery. CONCLUSION: The overall control rate of meningiomas with linac based RS was 95% by both imaging follow-up and clinical evaluation. With this results, linac based RS is considered safe and effective treatment method for meningioma.
Female ; Follow-Up Studies ; Humans ; Male ; Meningioma* ; Middle Aged ; Necrosis ; Particle Accelerators ; Radiosurgery* ; Retrospective Studies ; Tumor Burden

Background: Exercise capacity is known to be an independent predictor of cardiovascular events and mortality. However, most previous studies were based on Western populations.Further study is warranted for Asian patients according to ethnic or national standards. We aimed to compare prognostic values of Korean and Western nomograms for exercise capacity in Korean patients with cardiovascular disease (CVD). Methods: In this retrospective cohort study, we enrolled 1,178 patients (62 ± 11 years;78% male) between June 2015 and May 2020, who were referred for cardiopulmonary exercise testing in our cardiac rehabilitation program. The median follow-up period was 1.6 years. Exercise capacity was measured in metabolic equivalents by direct gas exchange method during the treadmill test. The nomogram for exercise capacity from healthy Korean individuals and a previous landmark Western study was used to determine the percentage of predicted exercise capacity. The primary endpoint was the composite of major adverse cardiovascular events (MACE; all-cause death, myocardial infarction, repeat revascularization, stroke and hospitalization for heart failure). Results: A multivariate analysis showed that the risk of primary endpoint was more than double (hazard ratio [HR], 2.20; 95% confidence interval [CI], 1.10–4.40) in the patients with lower exercise capacity (< 85% of predicted) by Korean nomogram. The lower exercise capacity was one of the strong independent predictors along with left ventricular ejection fraction, age, and level of hemoglobin. However, the lower exercise capacity by Western nomogram could not predict the primary endpoint (HR, 1.33; 95% CI, 0.85–2.10). Conclusion Korean patients with CVD with lower exercise capacity have higher risk of MACE.Considering inter-ethnic differences in cardiorespiratory fitness, the Korean nomogram provides more suitable reference values than the Western nomogram to determine lower exercise capacity and predict cardiovascular events in Korean patients with CVD.