Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

Purpose: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. Methods: 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (Cytomegalovirus, Varicella zoster virus, and Herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1st, 2006 to June 30th, 2023 in a single medical center were retrospectively enrolled. Results: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, 9 eyes (24.3%) with viral retinitis and 5 eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and 6 eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the first postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence 0.21 vs 0.85 in viral and parasitic retinitis, respectively; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval 1.22-17.27, p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the first postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. Conclusions: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the first postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

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).

Factors predicting redislocation or suture-break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation following secondary scleral-fixated IOL (SFIOL) surgery. SETTING: Two tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SFIOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SFIOL surgery between June 2014 and December 2019 at two tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: We included 237 eyes of 225 patients (169 [75.1%] men). The redislocation group was more likely to have a younger mean age at the initial SFIOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P=0.008), have a prior history of a previous suture-break (23 eyes, 52.3% vs 1 eye, 0.5%; P<0.001), and have undergone the initial SFIOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P=0.002) than was the no-redislocation group. Additionally, the redislocation group had a higher occurrence of complications (P<0.001). Multivariable regression revealed that younger age, left eye involvement, aphakic status prior to the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P<0.05) associated with redislocation. CONCLUSION: Younger age, left eye involvement, postoperative complications like ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of PRDM13 causing North Carolina macular dystrophy in Korea.

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families. Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools. Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13. Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Distal Radial Access for Coronary Procedures in a Large Prospective Multicenter Registry: The KODRA Trial.

BACKGROUND: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation. OBJECTIVES: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice. METHODS: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure. RESULTS: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure. CONCLUSIONS: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700).

Liquid-metal-based three-dimensional microelectrode arrays integrated with implantable ultrathin retinal prosthesis for vision restoration.

Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 µm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium-indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm-2) to elicit neural responses in the retina. Their low Young's modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.

Pose Tracking of Supermicrosurgical Robot Towards Multi-User Teleoperation.

This paper presents pose tracking experiments using a supermicrosurgical robot designed to consider teleoperation with multiple surgeons. Currently, existing supermicrosurgical robots assist only the primary surgeon. However, both primary and assistant surgeons need a high-precision motion for critical tasks that can easily damage microtissue. To assist multiple surgeons in supermicrosurgery with a surgical robot, dynamic collision avoidance becomes a critical issue due to the operation in a narrow surgical site. As a milestone to overcome this issue, we first developed a pose tracking algorithm by analyzing the inverse kinematics based on null-space control and a weighting matrix. Moreover, we also developed a control framework based on fully open-source software to run the pose tracking algorithm. Finally, we validated the proposed pose tracking algorithm by performing line tracing and rubber ring transferring experiments.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

Vascular abnormalities in fellow eyes of patients with unilateral coats' disease.

Coats' disease is an idiopathic retinal vascular disorder, known to usually occur unilaterally; however, recent studies have highlighted vascular abnormalities in the fellow unaffected eyes. This retrospective study investigated the peripheral vascular features and macular vascular structure of unaffected fellow eyes in patients with unilateral Coats' disease using multimodal imaging tools. We analysed images of patients, including bilateral ultra-widefield imaging, fluorescein angiography (FA), ultra-widefield FA, or standard fundus photography. Available bilateral optical coherence tomography angiography (OCT-A) images were used for macular vascular structure analysis. OCT-A parameters, including foveal avascular zone (FAZ), perfusion index, and vessel density (VD) in the superficial and deep capillary plexuses (SCP, DCP), were calculated using Image J software. The mean age at diagnosis was 34.5 ± 17.9 years. The mean final best-corrected visual acuity of the affected eyes was logMAR 0.78 ± 0.79, while that of the fellow eyes was logMAR 0.04 ± 0.12. Ten fellow eyes had microaneurysms (47.6%), two had tortuous vessel abnormalities (9.5%), and 11(52.4%) had abnormal vascular findings on FA. Although there was a trend towards larger DCP FAZ (1.201 ± 0.086 vs. 1.072 ± 0.226), and lower DCP VD (8.593 ± 1.583 vs. 10.827 ± 3.392) in the affected eyes as measured by the Cirrus machine, the difference was not statistically significant between affected and fellow eyes when measured using the Zeiss Cirrus machine (P = 0.686, P = 0.343, respectively). However, when measured with the Spectralis machine, DCP FAZ was larger in affected eyes (0.828 ± 0.426 vs. 0.254 ± 0.092, P = 0.002) and DCP VD was lower in affected eyes (6.901 ± 2.634 vs. 17.451 ± 7.207, P = 0.002) compared to the fellow eyes, while other parameters showed no significant variations. These findings indicate that there may be subtle vascular abnormalities primarily located in the peripheral regions of the unaffected fellow eyes in patients with unilateral Coats' disease, while the macular microvasculature remains unaffected.

ßTrCP1 promotes SLC35F2 protein ubiquitination and inhibits cancer progression in HeLa cells.

The solute carrier family 35 F2 (SLC35F2) belongs to membrane-bound carrier proteins that are associated with multiple cancers. The main factor that determines cancer progression is the expression level of SLC35F2. Thus, identifying the E3 ligase that controls SLC35F2 protein abundance in cancer cells is critical. Here, we identified ßTrCP1 interacting with and reducing the SLC35F2 protein level. ßTrCP1 signals SLC35F2 protein ubiquitination and reduces SLC35F2 protein half-life. The mRNA expression pattern between ßTrCP1 and SLC35F2 across a panel of cancer cell lines showed a negative correlation. Additionally, the depletion of ßTrCP1 accumulated SLC35F2 protein and promoted SLC35F2-mediated cell growth, migration, invasion, and colony formation ability in HeLa cells. Overall, we demonstrate that ßTrCP1 acts as a tumor suppressor by controlling SLC35F2 protein abundance in cancer cells. The depletion of ßTrCP1 promotes SLC35F2-mediated carcinogenesis. Thus, we envision that ßTrCP1 may be a potential target for cancer therapeutics.

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin.

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). Design: We conducted a retrospective, multicenter, observational cohort study. Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea. Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP. Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8-78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6-268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes. Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO-associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.

Influence of early dose reduction of ticagrelor on clinical outcomes following percutaneous coronary intervention for complex lesions.

Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

De-escalation from ticagrelor to clopidogrel in patients with acute myocardial infarction: the TALOS-AMI HBR substudy.

BACKGROUND: The benefits of de-escalation of P2Y12 inhibition after percutaneous coronary intervention (PCI) may differ by high bleeding risk (HBR) status. AIMS: We investigated the efficacy and safety of de-escalation from ticagrelor to clopidogrel after PCI by HBR status. METHODS: This is a non-prespecified post hoc analysis of the TicAgrelor Versus CLOpidogrel in Stabilized Patients with Acute Myocardial Infarction (TALOS-AMI) trial. Net adverse clinical events (a composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium [BARC] bleeding type 2, 3, or 5) at 1 year post-PCI were compared between the de-escalation (clopidogrel plus aspirin) and the active control (ticagrelor plus aspirin) groups by HBR status, as defined by the modification of the Academic Research Consortium (ARC) criteria. RESULTS: A total of 2,625 patients in the TALOS-AMI trial were analysed. Of these, 589 (22.4%) met the modified ARC-HBR criteria. The de-escalation group had lower primary endpoint rates than the control group in both HBR (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.26-0.84) and non-HBR (HR 0.59, 95% CI: 0.41-0.84) patients. There were no differences in treatment effect for the primary endpoint regardless of HBR status (p for interaction=0.904). BARC bleeding type 3 or 5 was less common in the de-escalation than the control group among HBR patients only (HR 0.24, 95% CI: 0.07-0.84). CONCLUSIONS: In stabilised acute myocardial infarction patients, unguided de-escalation from ticagrelor to clopidogrel was associated with a lower rate of net adverse clinical outcomes irrespective of HBR status. The effect of de-escalation of P2Y12 inhibition on reducing haemorrhagic events was greater in patients with HBR.

Ginsenoside Rg2 inhibits osteoclastogenesis by downregulating the NFATc1, c-Fos, and MAPK pathways.

Ginsenosides, among the most active components of ginseng, exhibit several therapeutic effects against cancer, diabetes, and other metabolic diseases. However, the molecular mechanism underlying the anti-osteoporotic activity of ginsenoside Rg2, a major ginsenoside, has not been clearly elucidated. This study aimed to determine the effects of ginsenoside Rg2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Results indicate that ginsenoside Rg2 inhibits RANKLinduced osteoclast differentiation of bone marrow macrophages (BMMs) without cytotoxicity. Pretreatment with ginsenoside Rg2 significantly reduced the RANKL-induced gene expression of c-fos and nuclear factor of activated T-cells (Nfatc1), as well as osteoclast-specific markers tartrate-resistant acid phosphatase (TRAP, Acp5) and osteoclast-associated receptor (Oscar). Moreover, RANKL-induced phosphorylation of mitogen-activated protein kinases (MAPKs) was decreased by ginsenoside Rg2 in BMM. Therefore, we suggest that ginsenoside Rg2 suppresses RANKLinduced osteoclast differentiation through the regulation of MAPK signaling-mediated osteoclast markers and could be developed as a therapeutic drug for the prevention and treatment of osteoporosis. [BMB Reports 2023; 56(10): 551-556].

High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing Percutaneous Coronary Intervention.

Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20-2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment.

Weissella koreensis and Pediococcus pentosaceus bacterial ghosts induce inflammatory responses as immunostimulants.

In this study, bacterial ghosts (BGs) were generated from Weissella koreensis LKS42 (WKorGs) and Pediococcus pentosacues KA94 (PPGs) by chemically inducing lysis using substances such as hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), acetic acid (CH3COOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), n-butanol, and C6H8O7. HCl-induced WKorGs and PPGs exhibited complete removal of DNA and displayed transverse membrane dissolution tunnel structures under scanning electron microscopy (SEM). Cell viability assays showed high viability of RAW 264.7 cells exposed to HCl-induced WKorGs and PPGs. Additionally, treatment with HCl-induced WKorGs and PPGs elevated mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and the anti-inflammatory cytokine IL-10 in RAW 264.7 cells. These findings suggest that HCl-induced WKorGs and PPGs have the potential to be used as inactivated bacterial immunostimulants, highlighting their promising applications in immunization and immunotherapy.