Korean Multicenter Registry of ELUVIA Stent for Femoropopliteal Artery Disease: K-ELUVIA Registry.

BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.

Recipient blood group does not affect hepatocellular carcinoma recurrence after living donor liver transplantation in Korea.

PURPOSE: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT). METHODS: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center. RESULTS: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941). CONCLUSIONS: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Seasonal variation and prognosis in patients with acute myocardial infarction complicated by cardiogenic shock.

Background: Little is known about the association between seasonal variation and prognosis in patients with CS caused by AMI. Objectives: We investigated the 12-month clinical outcomes in patients treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) according to season. Methods: A total of 695 patients undergoing PCI for AMI complicated by CS was enrolled from 12 centers in South Korea. The study patients were divided into four groups according to season in which the AMI with CS occurred (spring, n = 178 vs. summer, n = 155 vs. autumn, n = 182 vs. winter, n = 180). We compared major adverse cardiovascular events (MACEs; the composite of cardiac death, myocardial infarction, re-hospitalization due to heart failure, and any revascularization) between the four groups. Results: The risk of MACE during the 12 months after CS was similar in the four groups: spring, 68 patients, vs. summer, 69, vs. autumn, 73, vs. winter, 68 (p = 0.587). Multivariate Cox-regression analysis revealed no significant difference in 12-month MACE among groups compared to the spring group after inverse probability of treatment weighting adjustment (summer, HR 1.40, 95 % CI 0.98-1.99, p = 0.062; autumn, HR 1.26, 95 % CI 0.89-1.80, p = 0.193; winter, HR 1.18, 95 % CI 0.83-1.67, p = 0.356). The similarity of MACE between the four groups was consistent across a variety of subgroups. Conclusions: After adjusting for baseline differences, seasonal variation seems not to influence the mid-term risk of 12-month MACE in patients treated with PCI for AMI complicated by CS. Condensed abstract: Data are limited regarding the association between seasonal variation and prognosis in patients with cardiogenic shock (CS) caused by AMI. This study divided patients undergoing PCI for AMI complicated by CS into four groups based on the season of occurrence and found no significant differences in 12-month MACE between the groups after adjusting for bias and confounding factors. Multivariate analysis revealed consistent MACE similarity across subgroups. The study suggests that seasonal variation has no impact on the mid-term risk of 12-month MACE in patients with CS caused by AMI, after adjusting for baseline differences. Trial registration: ClinicalTrials.gov NCT02985008RESCUE (REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy of left ventricular assist device for Korean patients with cardiogenic shock), NCT02985008, Registered December 5, 2016 - retrospectively and prospectively. Irb information: This study was approved by the institutional review board of Samsung Medical Center (Reference number: 2016-03-130).

Clinical Outcomes After Drug-Coated Balloon Treatment in Popliteal Artery Disease: K-POP Registry 12-Month Results.

BACKGROUND AND OBJECTIVES: The popliteal artery is generally regarded as a "no-stent zone". Limited data are available on the outcomes of drug-coated balloons (DCBs) for popliteal artery disease. This study aimed to evaluate the 12-month clinical outcomes among patients who received DCB treatment for atherosclerotic popliteal artery disease. METHODS: This prospective, multicenter registry study enrolled 100 patients from 7 Korean endovascular centers who underwent endovascular therapy using IN.PACT DCB (Medtronic) for symptomatic atherosclerotic popliteal artery disease. The primary endpoint was 12-month clinical primary patency and the secondary endpoint was clinically driven target lesion revascularization (TLR)-free rate. RESULTS: The mean age of the study cohort was 65.7±10.8 years, and 77% of enrolled patients were men. The mean lesion length was 93.7±53.7 mm, and total occlusions were present in 45% of patients. Technical success was achieved in all patients. Combined atherectomy was performed in 17% and provisional stenting was required in 11%. Out of the enrolled patients, 91 patients completed the 12-month follow-up. Clinical primary patency and TLR-free survival rates at 12 months were 76.0% and 87.2%, respectively. A multivariate Cox regression analysis identified female and longer lesion length as the significant independent predictors of loss of patency. CONCLUSIONS: DCB treatment yielded favorable 12-month clinical primary patency and TLR-free survival outcomes in patients with popliteal artery disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02698345.

Clinical Significance of Residual Ischemia in Acute Myocardial Infarction Complicated by Cardiogenic Shock Undergoing VA-ECMO.

BACKGROUND: Although culprit-only revascularization during the index procedure has been recommended in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), the reduction of residual ischemia is also emphasized to improve clinical outcomes. However, few data are available about the significance of residual ischemia in patients undergoing mechanical circulatory supports. This study aimed to evaluate the effects of residual ischemia on clinical outcomes in AMI patients undergoing venoarterial-extracorporeal membrane oxygenation (VA-ECMO). METHODS: AMI patients with multivessel disease who underwent VA-ECMO due to refractory CS were pooled from the RESCUE and SMC-ECMO registries. The included patients were classified into three groups according to residual ischemia evaluated using the residual SYNTAX score (rSS): rSS = 0, 0 < rSS ≤ 8, and rSS > 8. The primary outcome was 1-year all-cause death. RESULTS: A total of 408 patients were classified into the rSS = 0 (N = 100, 24.5%), 0 < rSS ≤ 8 (N = 136, 33.3%), and rSS > 8 (N = 172, 42.2%) groups. The cumulative incidence of the primary outcome differed significantly according to rSS (33.9% vs. 55.4% vs. 66.1% for rSS = 0, 0 < rSS ≤ 8, and rSS > 8, respectively, overall P < 0.001). In a multivariable model, rSS was independently associated with the risk of 1-year all-cause death (HRadj 1.03, 95% CI 1.01-1.05, P = 0.003). Conversely, the baseline SYNTAX score was not associated with the risk of the primary outcome. Furthermore, when patients were stratified by rSS, the primary outcome did not differ significantly between the high and low delta SYNTAX score groups. CONCLUSIONS: In AMI patients with refractory CS who underwent VA-ECMO, residual ischemia was associated with an increased risk of 1-year mortality. Future studies are needed to evaluate the efficacy and safety of revascularization strategies to minimize residual ischemia in patients with CS supported with VA ECMO. CLINICAL TRIAL REGISTRATION: REtrospective and Prospective Observational Study to Investigate Clinical oUtcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock (RESCUE), NCT02985008.

Cardiogenic shock complicating acute myocardial infarction and multivessel disease: revascularization strategy according to ischemic territory.

INTRODUCTION AND OBJECTIVES: The association of revascularization strategy with clinical outcomes according to the ischemic territory of nonculprit lesion has not been documented in patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS). This study aimed to compare outcomes between culprit-only and immediate multivessel percutaneous coronary intervention (PCI) according to ischemic territory in patients with AMI-CS. METHODS: A total of 536 patients with AMI-CS and multivessel disease from the SMART-RESCUE registry were categorized according to ischemic territory (nonculprit left main/proximal left anterior descending artery [LM/pLAD] vs culprit LM/pLAD vs no LM/pLAD). The primary outcome was a patient-oriented composite endpoint (POCE) consisting of all-cause death, myocardial infarction, rehospitalization due to heart failure, or repeat revascularization at 1 year. RESULTS: Among the total population, 108 patients had nonculprit LM/pLAD, 228 patients had culprit LM/pLAD, and 200 patients had no LM/pLAD, with the risk of POCE being higher in patients with large ischemic territory lesions (53.6% vs 53.4% vs 39.6%; P = .02). Multivessel PCI was associated with a significantly lower risk of POCE compared with culprit-only PCI in patients with nonculprit LM/pLAD (40.7% vs 66.9%; HR, 0.52; 95%CI, 0.29-0.91; P=.02), but not in those with culprit LM/pLAD (P=.46) or no LM/pLAD (P=.47). A significant interaction existed between revascularization strategy and large nonculprit ischemic territory (P=.03). CONCLUSIONS: Large ischemic territory involvement was associated with worse clinical outcomes in patients with AMI-CS and multivessel disease. Immediate multivessel PCI might improve clinical outcomes in patients with a large nonculprit ischemic burden.

Pragmatic Trial of Hospitalization Rate in Chronic Kidney Disease.

BACKGROUND: Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking. METHODS: In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death. RESULTS: We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P = 0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%). CONCLUSIONS: In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.).

Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial.

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and ß-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Outcomes of 6000 living donor liver transplantation procedures: a pioneering experience at ASAN Medical Center.

Living donor liver transplantation (LDLT) has emerged as a favorable alternative to deceased donor liver transplantation, significantly reducing waitlist mortality, particularly in Asian countries with very low deceased organ donation rates. Asan Medical Center (AMC) in South Korea has pioneered innovative LDLT surgical techniques and become established as an extremely high-volume center for LDLT. This retrospective study analyzed 6000 consecutive LDLT procedures, including 510 dual-graft procedures, performed at AMC between December 1994 and January 2021. Of these, 312 LDLT procedures were performed in children aged < 18 years. In adult recipients, liver cirrhosis (LC) related to viral hepatitis was the most common indication, occurring in 69.8% of cases. Biliary atresia (46.8%) was the most common indication for pediatric LDLT. This study demonstrated outstanding long-term outcomes, with patient survival rates at 1, 5, 10, and 20 years of 92.7%, 85.9%, 82.1%, and 70.9%, respectively, in LDLT group for adults aged 50 and under at the time of LDLT, and 92.9%, 89.0%, 88.1%, and 81.9%, respectively, in the pediatric group. The in-hospital mortality rate of adult recipients was 3.8% (n = 214/5688). This study demonstrates the importance of refined surgical techniques, selection of grafts tailored to the recipient, and comprehensive multidisciplinary perioperative patient care in expanding the scope of LDLT and improving recipient outcomes.

Predictive value of plaque characteristics for identification of lesions causing ischemia.

BACKGROUND: Functional assessment using fractional flow reserve (FFR) and anatomical assessment using optical coherence tomography (OCT) are used in clinical practice for patients with intermediate coronary stenosis. Moreover, coronary computed tomography angiography (CTA) is a common noninvasive imaging technique for evaluating suspected coronary artery disease before being referred for angiography. This study aimed to investigate the association between FFR and plaque characteristics assessed using coronary CTA and OCT for intermediate coronary stenosis. METHODS: Based on a prospective multicenter registry, 159 patients having 339 coronary lesions with intermediate stenosis were included. All patients underwent coronary CTA before being referred for coronary angiography, and both FFR measurements and OCT examinations were performed during angiography. A stenotic lesion identified with FFR ≤0.80 was deemed diagnostic of an ischemia-causing lesion. The predictive value of plaque characteristics assessed using coronary CTA and OCT for identifying lesions causing ischemia was analyzed. RESULTS: Stenosis severity and plaque characteristics on coronary CTA and OCT differed between lesions that caused ischemia and those that did not. In multivariate analysis, low attenuation plaque on coronary CTA (odds ratio [OR]=2.78; P=0.038), thrombus (OR=5.13; P=0.042), plaque rupture (OR=3.25; P=0.017), and intimal vasculature on OCT (OR=2.57; P=0.012) were independent predictors of ischemic lesions. Increasing the number of these plaque characteristics offered incremental improvement in predicting the lesions causing ischemia. CONCLUSIONS: Comprehensive anatomical evaluation of coronary stenosis may provide additional supportive information for predicting the lesions causing ischemia.

Safety of right liver donation after improving steatosis through weight loss in living donors: a retrospective study.

BACKGROUND: Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. METHODS: In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively. RESULTS: We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78-184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg (p < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m2 to 23.8 ± 3.1 kg/m2 (p < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p = 0.3185). The graft and recipient survival rates were comparable between the groups (p = 1.000). CONCLUSION: Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.

No Prognostic Impact of Graft-to-Recipient Weight Ratio on Hepatocellular Carcinoma Recurrence Following Living Donor Liver Transplantation.

BACKGROUND The effects of a low graft-to-recipient weight ratio (GRWR) on the prognosis of patients with hepatocellular carcinoma (HCC) are unclear. The present study examined whether the GRWR had an impact on the rate of HCC recurrence following living donor liver transplantation (LDLT). MATERIAL AND METHODS This retrospective observational single-center study included 856 patients who underwent LDLT for HCC between January 2006 and December 2016 at Asan Medical Center and evaluated the association between GRWR and post-transplant tumor recurrence. RESULTS Of the 856 patients who underwent LDLT for HCC, 54 (6.3%), 272 (31.8%), 274 (32.0%), and 256 (29.9%) had GRWR <0.8%, 0.8-0.99%, 1.0-1.19%, and ≥1.2%, respectively. Analysis of all patients revealed that the disease-free survival (DFS; P=0.545) and overall survival (OS; P=0.313) rates were not different in these 4 groups. Subgroups analyses also showed that GRWR did not influence survival rates in patients within (DFS: P=0.398; OS: P=0.676) and beyond (DFS: P=0.602; OS: P=0.649) the Milan criteria, or in patients with alpha-fetoprotein-des-γ-carboxyprothrombin-tumor volume scores <5log (DFS: P=0.633; OS: p=0.285) and ≥5log (DFS: P=0.674; OS: P=0.906). CONCLUSIONS GRWR less than 0.8% did not demonstrate a noteworthy prognostic influence on the oncological results among patients who had undergone LDLT for HCC. High-volume multi-center studies are necessary to validate these findings.

Candida dubliniensis in Japanese Oral Microbiota: A Cross-Sectional Study of Six Geographic Regions in Japan.

INTRODUCTION: Candida dubliniensis was reclassified from the C. albicans genotype D, and reports show its frequent detection in HIV-positive individuals and easy acquisition of antifungal drug resistance. However, the oral carriage rate in healthy people and contribution to candidiasis in Japan is unclear. METHODS: We conducted a cross-sectional survey of the C. dubliniensis carriage rate, performed genotyping and tested antifungal drug susceptibility and protease productivity. Specimens from 2432 Japanese subjects in six regions (1902 healthy individuals, 423 with candidiasis individuals, 107 HIV-positive individuals) were cultured using CHROMagarTMCandida, and the species was confirmed via 25S rDNA amplification and ITS sequences analyzed for genotyping. RESULTS: The C. dubliniensis carriage rate in healthy Japanese was low in the central mainland (0-15%) but high in the most northerly and southerly areas (30-40%). The distribution of these frequencies did not differ depending on age or disease (HIV-infection, candidiasis). Genotype I, previously identified in other countries, was most frequent in Japan, but novel genotypes were also observed. Six antifungal drugs showed higher susceptibility against C. albicans, but protease productivity was low. CONCLUSIONS: Oral C. dubliniensis has low pathogenicity with distribution properties attributed to geography and not dependent on age or disease status.

Efficacy and safety of durable versus biodegradable polymer drug-eluting stents in patients with acute myocardial infarction complicated by cardiogenic shock.

The clinical impact of different polymer technologies in newer-generation drug-eluting stents (DESs) for patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains poorly understood. We investigated the efficacy and safety of durable polymer DESs (DP-DESs) compared with biodegradable polymer DESs (BP-DESs). A total of 620 patients who underwent percutaneous coronary intervention with newer-generation DESs for AMI complicated by CS was divided into two groups based on polymer technology: the DP-DES group (n = 374) and the BP-DES group (n = 246). The primary outcome was target vessel failure (TVF) during a 12-month follow-up, defined as a composite of cardiac death, myocardial infarction, or target vessel revascularization. Both the DP-DES and BP-DES groups exhibited low stent thrombosis rates (1.3% vs. 1.6%, p = 0.660). The risk of TVF did not significantly differ between the two groups (34.2% vs. 28.5%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69-1.29, p = 0.721). This finding remained consistent after adjustment with inverse probability of treatment weighting (28.1% vs. 25.1%, HR 0.98, 95% CI 0.77-1.27, p = 0.899). In AMI patients complicated by CS, the risk of a composite of cardiac death, myocardial infarction, or target vessel revascularization was not significantly different between those treated with DP-DESs and those treated with BP-DESs.Trial registration: RESCUE registry, https://clinicaltrials.gov/ct2/show/NCT02985008 , NCT02985008.

The phosphatidylserine targeting antibody bavituximab plus pembrolizumab in unresectable hepatocellular carcinoma: a phase 2 trial.

Immune checkpoint inhibitors targeting PD-1/L1 have modest efficacy in hepatocellular carcinoma as single agents. Targeting membranous phosphatidylserine may induce pro-inflammatory and -immune stimulating effects that enhance immunotherapy activity. This hypothesis was tested in a single-arm phase 2 trial evaluating frontline bavituximab, a phosphatidylserine targeting antibody, plus pembrolizumab (anti-PD-1) in patients with unresectable hepatocellular carcinoma (NCT03519997). The primary endpoint was investigator-assessed objective response rate among evaluable patients, and secondary end points included progression-free survival, incidence of adverse events, overall survival, and duration of response. Among 28 evaluable patients, the confirmed response rate was 32.1%, which met the pre-specified endpoint, and the median progression-free survival was 6.3 months (95% CI, 1.3-11.3 months). Treatment related-adverse events of any grade occurred in 45.7% of patients, with grade 3 or greater adverse events in 14.3% of patients. Adverse events of any cause were observed in 33 patients (94.3%), with grade 3 or greater adverse events in 11 patients (31.4%). Prespecified exploratory analyses of baseline tumor specimens showed that a depletion of B cells, and the presence of fibrotic tissue and expression of immune checkpoints in stroma was associated with tumor response. These results suggest that targeting phosphatidylserine may lead to synergistic effects with PD-1 blockade without increasing toxicity rates, and future studies on this therapeutic strategy may be guided by biomarkers characterizing the pre-treatment tumor microenvironment.

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study.

INTRODUCTION: The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300 units/mL (Gla-300) in insulin-naïve Korean people with type 2 diabetes mellitus (T2DM) in a real-world setting. METHODS: This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20 years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide 1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24 weeks. RESULTS: Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week 24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4 years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4 years, P = 0.0378). CONCLUSIONS: This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Despite various efforts in managing diabetes, individuals with type 2 diabetes mellitus (T2DM) encounter numerous challenges to achieve good glycemic control. The major cause is failure to initiate insulin therapy in a timely manner, primarily because of the fear of hypoglycemia. Insulin glargine 300 units/mL (Gla-300) has smooth and prolonged activity resulting in stable and sustained glycemic control, thus reducing the risk of hypoglycemia. Studies on efficacy and safety of Gla-300 in various populations have been published globally. However, there are limited real-world studies in Asian populations. This study evaluated effectiveness and safety of Gla-300 in Korean people with T2DM who were not on insulin prior to this study but were taking oral glucose-lowering medications. The participants were assigned to two groups: general glycated hemoglobin (HbA1c) target (HbA1c < 7%) and individualized HbA1c target according to the participant's characteristics. Results showed that Gla-300 helped to achieve the glycemic target more effectively using an individualized approach. In both groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia. People who achieve glycemic target had a shorter duration of T2DM than those who did not achieve their glycemic target. This suggests that earlier insulin initiation may be a better approach and may increase the success rate of insulin therapy.

Long-Term Outcomes of Endovascular Repair Within and Outside the Instructions for Use in Korean Patients With Abdominal Aortic Aneurysm.

OBJECTIVE: Endovascular aneurysm repair (EVAR) has been used worldwide to treat abdominal aortic aneurysms (AAAs). Outcomes after EVAR within and outside the instruction for use (IFU) remain controversial. We analyzed long-term outcomes of EVAR within-the-IFU compared with that outside-the-IFU and baseline clinical/anatomical characteristics that influence outcomes of EVAR. METHODS: The study included 546 patients who underwent EVAR for infrarenal AAA from 1997 to 2021 at 2 Korean medical centers. The primary endpoint was graft-related adverse events (GRAEs), including type 1 or 3 endoleak, reintervention (included open conversion), aneurysm sac enlargement, aneurysm-related mortality (ARM), rupture, stent-graft migration, and stent thrombotic occlusion. RESULTS: The patients who underwent EVAR outside the IFU were 287 (52.6%). A neck angle of >60° was most common outside the IFU criteria (n=146, 50.9%). This study revealed that patients outside the IFU had a higher rate of GRAEs compared with patients within the IFU (hazard ratio [HR]: 1.879; 95% confidence interval [CI]: 1.045-2.386). A neck angle of >60° was a significant risk factor for GRAEs (adjusted HR: 2.229; 95% CI: 1.418-3.503), type 1 or 3 endoleak (adjusted HR: 2.640; 95% CI: 1.343-5.189), and reintervention (adjusted HR: 1.891; 95% CI: 1.055-3.388). CONCLUSIONS: Our study revealed EVAR with outside the IFU was associated with increased GRAEs, mainly attributed to endoleak and ARM, compared with EVAR with within the IFU. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak, and reintervention. CLINICAL IMPACT: Our study revealed endovascular aneurysm repair (EVAR) with outside-the-instruction for use (IFU) was associated with increased graft-related adverse events (GRAEs) compared with EVAR with within-the-IFU. In the low-risk population, the incidence of GRAEs and Aneurysm related mortality were higher in the outside-the-IFU group rather than within-the-IFU group. In addition, severe neck angulation was an independent risk factor for GRAEs, type 1 or 3 endoleak and reintervention.

Rapid Start of Antiretroviral Therapy in a Large Urban Clinic in the US South: Impact on HIV Care Continuum Outcomes and Medication Adherence.

Rapid start of antiretroviral therapy (ART) has been associated with improvement in several HIV-related outcomes in clinical trials as well as demonstration projects, but how regional and contextual differences may affect the effectiveness of this intervention necessitates further study. In this study of a large, urban, Southern US clinic-based retrospective cohort, we identified 544 patients with a new diagnosis of HIV during 2016 to 2019 and compared HIV care continuum outcomes for the first 12 months of care before and after rapid start implementation. Kaplan-Meier time-to-event curves were used to summarize time to virologic suppression, and stepwise Cox, linear, and logistic regression models were used to create multivariate models to evaluate the association between rapid start and time to virologic suppression, medication adherence, and retention in care and sustained virologic suppression, respectively. We found that rapid start was significantly associated with improved medication adherence scores (+15.37 points, 95% confidence interval [CI] 9.36-21.39, P < .01) and retention in care (adjusted odds ratio = 1.51, 95% CI 1.05-2.19, P = .03). Time to virologic suppression (median 2.46 months before, 2.56 months after rapid start) and sustained virologic suppression were not associated with rapid start in our setting. Though rapid start was associated with improved medication adherence and retention in care, more support may be needed to achieve the same outcomes seen in other studies and sustained over the entire HIV care continuum, especially in settings with significant patient and systemic barriers to care such as unstable housing, lack of Medicaid expansion, and frequent coverage interruptions.