The Use of Coronary Imaging for Predicting Future Cardiovascular Events.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

Epidemiology and Outcomes of Non-Small Cell Lung Cancer in South Korea.

Importance: Valuable evidence regarding clinical characteristics, treatments, and outcomes for non-small cell lung cancer (NSCLC) is limited to individual hospital databases or national-level registries. The common data and federated analysis framework developed through the Extensible Platform for Observational Research in Lung Cancer (EXPLORE-LC) initiative allows for research across multiple high-quality data sources, which may provide a deeper understanding of the NSCLC landscape and identification of unmet needs of subpopulations. Objective: To describe clinical characteristics, initial treatment patterns, subsequent treatment, and overall survival (OS) of patients with NSCLC in South Korea. Design, Setting, and Participants: This multicenter cohort study included patients aged 18 years and older who were diagnosed with NSCLC between 2014 and 2019 and followed up until March 2020 at 3 tertiary hospitals in South Korea. Clinical data were collected using a common data model and clinical data warehouse. Patients who had an initial diagnosis of nonsquamous (NSQ) or squamous (SQ) NSCLC and who had received at least 1 treatment for NSCLC were included in the study. Data were analyzed from June through November 2022. Main Outcomes and Measures: The primary outcome was clinical OS for patients with NSCLC. Secondary outcomes were clinical characteristics and treatment patterns subsequent to the diagnosis of NSCLC. Results: Among 22 101 patients with NSCLC who received anticancer treatment analyzed in this study, 17 350 patients (78.5%) had NSQ and 4751 patients (21.5%) had SQ NSCLC. Clinical characteristics and outcomes and treatment patterns were assessed for 13 084 patients with NSQ cancer who had known EGFR and ALK status (75.4%; mean [SD] 62.2 [10.5] years; 6552 males [50.1%]) and all 4751 patients with SQ cancer (mean [SD] age, 67.1 [8.6] years; 4427 males [93.2%]). More than half of patients with NSQ cancer were never smokers (7399 patients [56.6%]). Patients with SQ cancer were mostly males and former or current smokers (4235 patients [89.1%]) and were diagnosed at a later clinical stage than patients with NSQ cancer (eg, stage I: 1165 patients [24.5%] vs 5388 patients [41.2%]). Patients with EGFR-positive and ALK-positive NSQ cancer diagnosed between 2017 and 2019 had better median OS than similar patients diagnosed between 2014 and 2016 (EGFR-positive: not reached [95% CI, 35.9 months to not reached] vs 28.4 months [95% CI, 25.8 to 30.0 months]; P < .001; ALK-positive: not reached [95% CI, not reached] vs 49.5 months [95% CI, 35.1 months to not reached]; P < .001). No significant difference was observed in OS from first-line treatment for patients with SQ cancer. Conclusions and Relevance: This study, which pooled medical data from multiple clinical data warehouses to produce a large study cohort, may provide meaningful insights into the clinical practice of NSCLC and underscores the value of a common data model approach. The analyzable dataset may hold great promise for future comprehensive identification of subpopulations and unmet needs.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation.

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

The LKB1-TSSK1B axis controls YAP phosphorylation to regulate the Hippo-YAP pathway.

The Hippo pathway's main effector, Yes-associated protein (YAP), plays a crucial role in tumorigenesis as a transcriptional coactivator. YAP's phosphorylation by core upstream components of the Hippo pathway, such as mammalian Ste20 kinase 1/2 (MST1/2), mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), and their substrate, large tumor suppressor 1/2 (LATS1/2), influences YAP's subcellular localization, stability, and transcriptional activity. However, recent research suggests the existence of alternative pathways that phosphorylate YAP, independent of these core upstream Hippo pathway components, raising questions about additional means to inactivate YAP. In this study, we present evidence demonstrating that TSSK1B, a calcium/calmodulin-dependent protein kinase (CAMK) superfamily member, is a negative regulator of YAP, suppressing cellular proliferation and oncogenic transformation. Mechanistically, TSSK1B inhibits YAP through two distinct pathways. Firstly, the LKB1-TSSK1B axis directly phosphorylates YAP at Ser94, inhibiting the YAP-TEAD complex's formation and suppressing its target genes' expression. Secondly, the TSSK1B-LATS1/2 axis inhibits YAP via phosphorylation at Ser127. Our findings reveal the involvement of TSSK1B-mediated molecular mechanisms in the Hippo-YAP pathway, emphasizing the importance of multilevel regulation in critical cellular decision-making processes.

Guiding Intervention for Complex Coronary Lesions by Optical Coherence Tomography or Intravascular Ultrasound.

BACKGROUND: Optical coherence tomography (OCT) and intravascular ultrasound (IVUS) have shown comparable outcomes in guiding percutaneous coronary intervention (PCI). However, their comparative effectiveness in complex coronary artery lesions remains unclear. OBJECTIVES: This study compared the effectiveness and safety of OCT-guided vs IVUS-guided PCI for complex coronary artery lesions. METHODS: This was a prespecified, main subgroup analysis of complex coronary artery lesions in the OCTIVUS (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention) trial, which included unprotected left main disease, bifurcation disease, an aorto-ostial lesion, a chronic total occlusion, a severely calcified lesion, an in-stent restenotic lesion, a diffuse long lesion, or multivessel PCI. The primary endpoint was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization. RESULTS: In 2,008 randomized patients, 1,475 (73.5%) underwent imaging-guided PCI for complex coronary artery lesions; 719 (48.7%) received OCT-guided and 756 (51.3%) IVUS-guided PCI. At a median follow-up of 2.0 years, primary endpoint event had occurred in 47 patients (6.5%) in the OCT-guided group and in 56 patients (7.4%) in the IVUS-guided group (HR: 0.87; 95% CI: 0.59-1.29; P = 0.50). These findings were consistent in adjusted analyses. The incidence of contrast-induced nephropathy was similar between the 2 groups (1.9% vs 1.5%; P = 0.46). The incidence of major procedural complications was lower in the OCT-guided group than in the IVUS-guided group (1.7% vs 3.4%; P = 0.03). CONCLUSIONS: Among patients with complex coronary artery lesions, OCT-guided PCI showed a similar risk of primary composite event of death from cardiac causes, target vessel-related myocardial infarction, or target vessel revascularization as compared with IVUS-guided PCI. (Optical Coherence Tomography Versus Intravascular Ultrasound Guided Percutaneous Coronary Intervention [OCTIVUS]; NCT03394079).

Optical Coherence Tomography-Guided or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention: The OCTIVUS Randomized Clinical Trial.

BACKGROUND: Intravascular imaging-guided percutaneous coronary intervention (PCI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) showed superior clinical outcomes compared with angiography-guided PCI. However, the comparative effectiveness of OCT-guided and IVUS-guided PCI regarding clinical outcomes is unknown. METHODS: In this prospective, multicenter, open-label, pragmatic trial, we randomly assigned 2008 patients with significant coronary artery lesions undergoing PCI in a 1:1 ratio to undergo either an OCT-guided or IVUS-guided PCI. The primary end point was a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year, which was powered for noninferiority of the OCT group compared with the IVUS group. Safety outcomes were also assessed. RESULTS: At 1 year, primary end point events occurred in 25 of 1005 patients (Kaplan-Meier estimate, 2.5%) in the OCT group and in 31 of 1003 patients (Kaplan-Meier estimate, 3.1%) in the IVUS group (absolute difference, -0.6 percentage points; upper boundary of one-sided 97.5% CI, 0.97 percentage points; P<0.001 for noninferiority). The incidence of contrast-induced nephropathy was similar (14 patients [1.4%] in the OCT group versus 15 patients [1.5%] in the IVUS group; P=0.85). The incidence of major procedural complications was lower in the OCT group than in the IVUS group (22 [2.2%] versus 37 [3.7%]; P=0.047), although imaging procedure-related complications were not observed. CONCLUSIONS: In patients with significant coronary artery lesions, OCT-guided PCI was noninferior to IVUS-guided PCI with respect to the incidence of a composite of death from cardiac causes, target vessel-related myocardial infarction, or ischemia-driven target-vessel revascularization at 1 year. The selected study population and lower-than-expected event rates should be considered in interpreting the trial. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique number: NCT03394079.

Effect of Cilostazol on Patients With Diabetes Who Underwent Endovascular Treatment for Peripheral Artery Disease.

Background No large-scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real-world registry. Methods and Results A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%; P=0.102) and the complication rate (6.9% versus 6.6%; P>0.999) were similar between the TAPT and DAPT groups. At 2-year follow-up, the incidence of major adverse limb events (16.6% versus 19.4%; P=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%; P=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158-0.794]; P=0.012). Conclusions In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.

Effects of metabolic parameters' variability on cardiovascular outcomes in diabetic patients.

BACKGROUND: Metabolic abnormalities such as dyslipidemia, glucose and high blood pressure are common in diabetic patients. Visit-to-visit variabilities in these measures have been reported as potential residual cardiovascular risk factors. However, the relationship between these variabilities and their effects on cardiovascular prognosis have not been studied. METHODS: A total of 22,310 diabetic patients with ≥ 3 measurements of systolic blood pressure (SBP), blood glucose, total cholesterol (TC), and triglyceride (TG) levels during a minimum of three years at three tertiary general hospitals were selected. They were divided into high/low variability groups for each variable based on the coefficient of variation (CV) values. The primary outcome was the incidence of major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. RESULTS: All high CV groups had a higher incidence of MACE than those with low CV (6.0% vs. 2.5% for SBP-CV groups, 5.5% vs. 3.0% for TC-CV groups, 4.7% vs. 3.8% for TG-CV groups, 5.8% vs. 2.7% for glucose-CV groups). In multivariable Cox regression analysis,, high SBP-CV (HR 1.79 [95% CI 1.54-2.07], p < 0.01), high TC-CV (HR 1.54 [95% CI 1.34-1.77], p < 0.01), high TG-CV (HR 1.15 [95% CI 1.01-1.31], p = 0.040) and high glucose-CV (HR 1.61 [95% CI 1.40-1.86], p < 0.01) were independent predictors of MACE. CONCLUSION: Variability of SBP, TC, TG and glucose are important residual risk factors for cardiovascular events in diabetic patients.

Two-Year clinical outcomes after coronary bifurcation stenting in older patients from Korea and Italy.

Background: Older patients who treated by percutaneous coronary intervention (PCI) are at a higher risk of adverse cardiac outcomes. We sought to investigate the clinical impact of bifurcation PCI in older patients from Korea and Italy. Methods: We selected 5,537 patients who underwent bifurcation PCI from the BIFURCAT (comBined Insights from the Unified RAIN and COBIS bifurcAtion regisTries) database. The primary outcome was a composite of target vessel myocardial infarction, clinically driven target lesion revascularization, and stent thrombosis at two years. Results: In patients aged ≥75 years, the mean age was 80.1 ± 4.0 years, 65.2% were men, and 33.7% had diabetes. Older patients more frequently presented with chronic kidney disease (CKD), severe coronary calcification, and left main coronary artery disease (LMCA). During a median follow-up of 2.1 years, older patients showed similar adverse clinical outcomes compared to younger patients (the primary outcome, 5.7% vs. 4.5%; p = 0.21). Advanced age was not an independent predictor of the primary outcome (p = 0.93) in overall patients. Both CKD and LMCA were independent predictors regardless of age group. Conclusions: Older patients (≥75 years) showed similar clinical outcomes to those of younger patients after bifurcation PCI. Advanced age alone should not deter physicians from performing complex PCIs for bifurcation disease.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Ovarian Real-World International Consortium (ORWIC): A multicentre, real-world analysis of epithelial ovarian cancer treatment and outcomes.

Introduction: Much drug development and published analysis for epithelial ovarian cancer (EOC) focuses on early-line treatment. Full sequences of treatment from diagnosis to death and the impact of later lines of therapy are rarely studied. We describe the establishment of an international network of cancer centers configured to compare real-world treatment pathways in UK, Portugal, Germany, South Korea, France and Romania (the Ovarian Real-World International Consortium; ORWIC). Methods: 3344 patients diagnosed with EOC (2012-2018) were analysed using a common data model and hub and spoke programming approach applied to existing electronic medical records. Consistent definition of line of therapy between sites and an efficient approach to analysis within the limitations of local information governance was achieved. Results: Median age of participants was 53-67 years old and 5-29% were ECOG >1. Between 62% and 84% of patients were diagnosed with late-stage disease (FIGO III-IV). Sites treating younger and fitter patients had higher rates of debulking surgery for those diagnosed at late stage than sites with older, more frail patients. At least 21% of patients treated with systemic anti-cancer therapy (SACT) had recurrent disease following second-line therapy (2L); up to 11 lines of SACT treatment were recorded for some patients. Platinum-based SACT was consistently used across sites at 1L, but choices at 2L varied, with hormone therapies commonly used in the UK and Portugal. The use (and type) of maintenance therapy following 1L also varied. Beyond 2L, there was little consensus between sites on treatment choice: trial compounds and unspecified combinations of other agents were common. Discussion: Specific treatment sequences are reported up to 4L and the establishment of this network facilitates future analysis of comparative outcomes per line of treatment with the aim of optimizing available options for patients with recurrent EOC. In particular, this real-world network can be used to assess the growing use of PARP inhibitors. The real-world optimization of advanced line treatment will be especially important for patients not usually eligible for involvement with clinical trials. The resources to enable this analysis to be implemented elsewhere are supplied and the network will seek to grow in coverage of further sites.

Early Invasive Strategy Based on the Time of Symptom Onset of Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: A limitation of the current guidelines regarding the timing of invasive coronary angiography for patients with non-ST-segment elevation acute coronary syndrome is the randomization time. To date, no study has reported the clinical outcomes of invasive strategy timing on the basis of the time of symptom onset. OBJECTIVES: The aim of this study was to investigate the effect of invasive strategy timing from the time of symptom onset on the 3-year clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: Among 13,104 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health, 5,856 patients with NSTE myocardial infarction were evaluated. The patients were categorized according to symptom-to-catheter (StC) time (<48 or ≥48 hours). The primary outcome was 3-year all-cause mortality. RESULTS: Overall, 3,919 patients (66.9%) were classified into the StC time <48 hours group. This group had lower all-cause mortality than the group with StC time ≥48 hours (7.3% vs 13.4%; P < 0.001). The lower risk for all-cause mortality in the group with StC time <48 hours group was consistent in all subgroups. Notably, emergency medical service use (HR: 0.31; 95% CI: 0.19-0.52) showed a lower risk for all-cause mortality than no emergency medical service use (HR: 0.54; 95% CI: 0.46-0.65; P value for interaction = 0.008). CONCLUSIONS: An early invasive strategy on the basis of StC time was associated with a decreased risk for all-cause mortality in patients with NSTEMI. Because the study was based on a prospective registry, the results should be considered hypothesis generating, highlighting the need for further research. (iCReaT Study No. C110016).

Prognostic factors for the treatment of meniscus horizontal tear.

Meniscus horizontal tears are usually degenerative. It could be asymptomatic and unrelated to knee symptoms. Therefore, there are controversies regarding treatment choices. The aim of this study was to evaluate factors that affect the results of non-surgical and surgical treatments for meniscus horizontal tears. We retrospectively studied 159 patients with meniscus horizontal tears with a minimum 2-year follow-up period. Patients were treated non-surgically or arthroscopically. The treatment results were dichotomized into success and failure. The factors considered were age, sex, joint line tenderness, mechanical symptoms, widest tear gap width on sagittal MRI, cartilage lesion grade, discoid meniscus, tear site, and joint alignment. Joint alignment and cartilage lesion grade were the factors that significantly influenced non-surgical treatment results. The widest tear gap width and cartilage lesion grade significantly affected arthroscopic surgery results. The mechanical symptoms did not show any significant relationship with either treatment result. In treating patients with meniscus horizontal tears, patients with varus alignment and advanced cartilage lesions should be informed of possible poor outcomes with non-surgical treatment. If the patient has a wide tear gap or minimal cartilage lesion, arthroscopic surgery would be a good treatment choice. The mechanical symptom was not an adequate factor for arthroscopic surgery.

Association between High Lipid Burden of Target Lesion and Slow TIMI Flow in Coronary Interventions.

Decreased thrombolysis in myocardial infarction (TIMI) flow is associated with poor clinical outcomes. However, its predictors are not fully known. A combination of near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) could be used to detect lesions at high risk of slow TIMI flow. This study evaluated 636 consecutive patients undergoing target-lesion NIRS-IVUS imaging prior to percutaneous coronary intervention (PCI). The maximal lipid core burden index over 4-mm segments (maxLCBI4mm) per target vessel was calculated. The primary endpoint was the association between maxLCBI4mm and post-interventional TIMI flow. A high lipid core burden index (LCBI) cut-off point was determined using receiver-operating characteristic analysis. Decreased TIMI flow (TIMI less than 3) occurred in 90 patients and normal TIMI flow in 546 patients. The decreased TIMI flow group showed significantly higher incidence of cardiovascular events (5.6% vs. 1.5%, log-rank p = 0.010) in three months of composite events including cardiac death, myocardial infarction, stent thrombosis, and target lesion revascularization. In multivariable analysis, a high LCBI (≥354) was independently associated with slow TIMI flow (OR, 2.59 (95% CI, 1.33-5.04), p = 0.005). High LCBI measured using NIRS-IVUS imaging was an independent predictor of decreased post-PCI TIMI flow. Performing PCI for high-LCBI lesions may necessitate adjunctive measures to prevent suboptimal post-PCI reperfusion.