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.

Anti-cancer effects of metformin in a 3D co-culture model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) presents with condensed stroma that contributes to its high invasive capability. Although metformin adjuvant treatment has been suggested to improve the survival times of patients with PDAC, the mechanism responsible for that benefit has been investigated only in two-dimensional cell lines. We assessed the anti-cancer effect of metformin in a three-dimensional (3D) co-culture model to quantify the migration behavior of patient-derived PDAC organoids and primary pancreatic stellate cells (PSCs).

Culprit-Only Versus Immediate Multivessel Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicating Advanced Cardiogenic Shock Requiring Venoarterial-Extracorporeal Membrane Oxygenation.

Background Despite the benefit of culprit-only percutaneous coronary intervention (PCI) in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multi-vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit-only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient-pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC-ECMO (Samsung Medical Center-Extracorporeal Membrane Oxygenation) registries.

Age-Related Macular Degeneration With Visual Disability Is Associated With Cardiovascular Disease Risk in the Korean Nationwide Cohort.

Background Age-related macular degeneration (AMD) is the leading cause of visual disability. AMD shares some risk factors with the pathogenesis of cardiovascular disease (CVD). However, previous studies examining the association between AMD and the risk of CVD provide conflicting results.

Sex Differences in Midterm Prognostic Implications of High Platelet Reactivity After Percutaneous Coronary Intervention With Drug-Eluting Stents in East Asian Patients: Results From the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium.

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug-eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all-cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis).

Discriminative Role of Invasive Left Heart Catheterization in Patients Suspected of Heart Failure With Preserved Ejection Fraction.

Background Recently, diastolic stress testing and invasive hemodynamic measurements have been emphasized for diagnosis of heart failure with preserved ejection fraction (HFpEF) because when determined using noninvasive parameters it can fall into a nondiagnostic intermediate range. The current study evaluated the discriminative and prognostic roles of invasive measured left ventricular end-diastolic pressure in the population with suspected HFpEF, particularly for patients with intermediate Heart Failure Association Pre-test Assessment, Echocardiography & Natriuretic Peptide, Functional Testing, Final Etiology (HFA-PEFF) score. Methods and Results A total of 404 patients with symptoms or signs of HF and preserved left ventricular systolic function were enrolled.

A phase III, randomised, double-blind, multi-national clinical trial comparing SB12 (proposed eculizumab biosimilar) and reference eculizumab in patients with paroxysmal nocturnal haemoglobinuria.

Treatment of paroxysmal nocturnal haemoglobinuria (PNH) includes the monoclonal antibody eculizumab. This randomised, double-blind, multi-national cross-over Phase III study in PNH patients aimed to demonstrate the equivalence of the proposed eculizumab biosimilar SB12 and reference eculizumab (Soliris, ECU). PNH patients with lactate dehydrogenase (LDH) ≥1·5× upper limit of normal were randomised into treatment sequences SB12-ECU or ECU-SB12.

Clinical Features of Idiopathic Normal Pressure Hydrocephalus: Critical Review of Objective Findings.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic clinical triad of gait, cognitive, and urinary dysfunction, albeit incomplete in a relevant proportion of patients. The clinical findings and evolution of these symptoms have been variably defined in the literature.

Objectives: To evaluate how the phenomenology has been defined, assessed, and reported, we performed a critical review of the existing literature discussing the phenomenology of iNPH.

Trends in Incidences and Survival Rates in Pediatric In-Hospital Cardiopulmonary Resuscitation: A Korean Population-Based Study.

Background Although the outcome of cardiopulmonary resuscitation (CPR) is still unsatisfactory, there are few studies about temporal trends of in-hospital CPR incidence and mortality. We aimed to evaluate nationwide trends of in-hospital CPR incidence and its associated risk factors and mortality in pediatric patients using a database of the Korean National Health Insurance between 2012 and 2018. Methods and Results We excluded neonates and neonatal intensive care unit admissions.

Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function on Cardiovascular Death.

Background Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.

Outcomes and learning curve of endoscopic tympanoplasty: A retrospective analysis of 376 patients.

Objective: This study aimed to evaluate the procedural outcomes and learning curve of type I endoscopic tympanoplasty (ET) performed by a single surgeon.

Methods: This was a retrospective study of 376 patients who underwent type I ET performed by a single surgeon over 7 years. We evaluated the pre/post air-bone gap (ABG), time required for surgery, changes in pain after surgery, success, and failure rate of type I ET.

Anti-thymocyte globulin-mediated immunosenescent alterations of T cells in kidney transplant patients.

Objectives: Kidney transplant (KT) is the most effective treatment for end-stage renal disease. The immunosuppressant anti-thymocyte globulin (ATG) has been applied for induction therapy to reduce the risk of acute transplant rejection for patients at high immunological risk. Despite its putative role in replicative stress during immune reconstitution, the effects of ATG on T-cell immunosenescent changes remain to be understood.

Integrative analysis of DNA methylation and gene expression identifies genes associated with biological aging in Alzheimer's disease.

Introduction: The acceleration of biological aging is a risk factor for Alzheimer's disease (AD). Here, we performed weighted gene co-expression network analysis (WGCNA) to identify modules and dysregulated genesinvolved in biological aging in AD.

Methods: We performed WGCNA to identify modules associated with biological clocks and hub genes of the module with the highest module significance.

Transplantation of neuron-inducing grafts embedding positively charged gold nanoparticles for the treatment of spinal cord injury.

In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation.

Clinical Outcomes of Rhythm Control Strategies for Asymptomatic Atrial Fibrillation According to the Quality-of-Life Score: The CODE-AF (Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation) Registry.

Background Atrial fibrillation (AF) is associated with an increased risk of poor cardiovascular outcomes; appropriate rhythm control can reduce the incidence of these adverse events. Therefore, catheter ablation is recommended in symptomatic patients with AF. The aims of this study were to compare AF-related outcomes according to a baseline symptom scale score and to determine the best treatment strategy for asymptomatic patients with AF.

The impact of interval between primary cytoreductive surgery with bowel resection and initiation of adjuvant chemotherapy on survival of women with advanced ovarian cancer: a multicenter cohort study.

Objective: Our aim was to determine if the time interval between bowel resection and initiation of adjuvant chemotherapy impacts survival in advanced ovarian cancers.

Methods: This was a retrospective cohort study using data from two cancer centers, Princess Margaret Cancer Centre in Toronto, Ontario, Canada and Samsung Comprehensive Cancer Center in Seoul, South Korea. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer that underwent large bowel resection during primary cytoreductive surgery (PCS) were included.

Effect of inner ear malformations on intraoperative ECAP thresholds and postoperative auditory performance.

Objectives: This study sought to characterize the influence of inner ear malformations (IEMs) on intraoperative electrically evoked compound action potential (ECAP) and auditory performance to better understand the underlying pathophysiology related to variabilities in cochlear implant (CI) outcomes that individuals with malformed cochlea may present.

Methods: The medical records of 222 ears implanted with Cochlear Nucleus CI were reviewed. Of the total, 64 ears had radiologic evidence of IEMs, and 158 ears were normal.

Expression of PD-L1 as a predictive marker of sensitivity to immune checkpoint inhibitors in patients with advanced biliary tract cancer.

Background: Expression of programmed death-ligand 1 (PD-L1) has been reported to correlate with response to immune checkpoint inhibitors (ICIs) in various tumor types. However, there are few data on the role of PD-L1 expression as a predictive and prognostic biomarker of sensitivity to ICIs in patients with advanced biliary tract cancer (BTC).

Objectives: We evaluated the role of PD-L1 expression as a predictive and prognostic biomarker of response to ICIs in patients with advanced BTC.

Dual role of ERK2/NF-κB signaling in TRAIL sensitivity.

Targeting tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling is a promising approach in cancer treatment. Although ERK and/or NF-κB signaling is involved in the expression of TRAIL receptors (TRAIL-R), the exact underlying mechanisms remain unknown. In this study, we evaluated the role of ERK2 and NF-κB in the cytotoxicity of TRAIL during cisplatin treatment.

Prognostic Impact of Coronary Flow Reserve in Patients With Reduced Left Ventricular Ejection Fraction.

Background Intracoronary physiologic indexes such as coronary flow reserve (CFR) and left ventricular ejection fraction (LVEF) have been regarded as prognostic indicators in patients with coronary artery disease. The current study evaluated the association between intracoronary physiologic indexes and LVEF and their differential prognostic implications in patients with coronary artery disease. Methods and Results A total of 1889 patients with 2492 vessels with available CFR and LVEF were selected from an international multicenter prospective registry.

Left Ventricular Diastolic Dysfunction and Progression of Chronic Kidney Disease: Analysis of KNOW-CKD Data.

Background Few studies have examined the association between the early diastolic mitral inflow velocity/early diastolic mitral annulus velocity ratio (E/e') and chronic kidney disease progression. Methods and Results We reviewed data from 2238 patients with nondialysis chronic kidney disease from the KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease); data from 163 patients were excluded because of missing content. A >50% decrease in estimated glomerular filtration rate from baseline, doubling of serum creatinine, or dialysis initiation and/or kidney transplantation were considered renal events.

Arginine-mediated gut microbiome remodeling promotes host pulmonary immune defense against nontuberculous mycobacterial infection.

Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut-lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut-lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs.

Expression of SLC22A18 regulates oxaliplatin resistance by modulating the ERK pathway in colorectal cancer.

Although oxaliplatin-based chemotherapy is the current standard adjuvant therapy for colorectal cancer (CRC), the molecular mechanisms underlying oxaliplatin resistance remain unclear. Here, we examined the molecular mechanisms underlying SLC22A18-associated oxaliplatin resistance and strategies for overcoming oxaliplatin resistance. We evaluated the association between SLC22A18 and prognosis in 337 patients with CRC and its functional significance and studied the mechanisms through which SLC22A18 affects oxaliplatin resistance development in CRC cells, using CRC cell lines and patient-derived cells (PDCs).

International Retrospective Cohort Study of Conversion Therapy for Stage IV Gastric Cancer 1 (CONVO-GC-1).

Aim: Much attention has been paid to conversion therapy for stage IV gastric cancer, however, its operative comorbidities and survival benefit have not yet been clarified. CONVO-GC-1, an international retrospective cohort study, was designed to investigate the role of conversion surgery in Japan, Korea, and China.

Methods: The rate of operative complications was the primary endpoint and the overall survival (OS), according to the four-category criteria previously published (Gastric Cancer:19; 2016), was analyzed as the secondary endpoint.