Three-year outcomes following non-ST-segment elevation myocardial infarction and new-generation drug-eluting stent implantation, stratified by patient age (under and over 75 years) and left ventricular ejection fraction: A prospective cohort study.

Due to limited published data, we investigated 3-year outcomes according to left ventricular ejection fraction (LVEF) in patients older and younger than 75 years with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent successful newer-generation drug-eluting stent (DES) implantation. This research analyzed the data of 4558 patients (1032 older adults [≥75 years] and 3526 younger adults [<75 years]) from the Korea Acute MI Registry-NIH. We further divided the older group based on LVEF: heart failure (HF) with reduced EF (HFrEF, ≤40%, n = 196; group A), HF with mildly reduced EF (HFmrEF, 41-49%, n = 228; group B), and HF with preserved EF (HFpEF, ≥50%, n = 608; group C). Similarly, the younger group was divided into HFrEF (group D, n = 353), HFmrEF (group E, n = 577), and HFpEF (group F, n = 2596). The primary outcome was a composite of major adverse cardiac events (MACE) at 3 years, including all-cause death, recurrent MI, any repeat revascularization, or hospitalization for HF. MACE rates were highest in the HFrEF groups (A and D), followed by the HFmrEF groups (B and E), and lowest in the HFpEF groups (C and F) for both age groups. All-cause death, cardiac death (CD), all-cause death or MI, and hospitalization for HF rates were higher in group A than in groups B and C, and higher in group D than in groups E and F. Across all LVEF categories, MACE, all-cause death, CD, and non-CD, and all-cause death or MI rates were higher in the older group. This multicenter cohort study demonstrates that older patients have higher mortality rates compared to younger patients. Additionally, MACE rates were highest in the HFrEF group, followed by the HFmrEF group, and lowest in the HFpEF group across both age groups. Further research is needed to confirm these findings.

Renin-angiotensin system inhibitors and non-ST-elevation myocardial infarction outcomes based on left ventricular ejection fraction.

BACKGROUND: We assessed left ventricular ejection fraction (LVEF) to compare the effects of renin-angiotensin system inhibitors (RASI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: We categorized 4558 patients with NSTEMI as either RASI users (3752 patients) or non-users (806 patients). The 3-year patient-oriented composite outcome (POCO), which included all-cause death, recurrent myocardial infarction, any repeat revascularization, or hospitalization for heart failure (HF), was the primary outcome. To compare clinical outcomes, a multivariable-adjusted hazard ratio (aHR) was calculated after performing multicollinearity tests on all significant confounding variables (P < 0.05). RESULTS: Among RASI users, the aHRs for POCO, all-cause death, and cardiac death were significantly higher in the HF with reduced EF (HFrEF) subgroup than in the HF with mildly reduced EF (HFmrEF) (1.610, 2.120, and 2.489; P < 0.001, <0.001, and <0.001; respectively) and HF with preserved EF (HFpEF) (2.234, 3.920, and 5.215; P < 0.001, <0.001, and <0.001; respectively) subgroups. The aHRs for these variables were significantly higher in the HFmrEF subgroup than the HFpEF subgroup (1.416, 1.843, and 2.172, respectively). Among RASI non-users, the aHRs for these variables were significantly higher in the HFrEF subgroup than the HFmrEF (2.573, 3.172, and 3.762, respectively) and HFpEF (2.425, 3.805, and 4.178, respectively) subgroups. In three LVEF subgroups, RASI users exhibited lower aHRs for POCO and all-cause death than RASI non-users. CONCLUSION: In the RASI users group, the aHRs for POCO and mortality were highest in the HFrEF subgroup, intermediate in the HFmrEF subgroup, and lowest in the HFpEF subgroup.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. METHODS: From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. RESULTS: The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. CONCLUSIONS: In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Structural basis for Mis18 complex assembly and its implications for centromere maintenance.

The centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as a microtubule attachment site. To preserve centromere identity, CENP-A levels must be maintained through active CENP-A loading during the cell cycle. A central player mediating this process is the Mis18 complex (Mis18α, Mis18ß and Mis18BP1), which recruits the CENP-A-specific chaperone HJURP to centromeres for CENP-A deposition. Here, using a multi-pronged approach, we characterise the structure of the Mis18 complex and show that multiple hetero- and homo-oligomeric interfaces facilitate the hetero-octameric Mis18 complex assembly composed of 4 Mis18α, 2 Mis18ß and 2 Mis18BP1. Evaluation of structure-guided/separation-of-function mutants reveals structural determinants essential for cell cycle controlled Mis18 complex assembly and centromere maintenance. Our results provide new mechanistic insights on centromere maintenance, highlighting that while Mis18α can associate with centromeres and deposit CENP-A independently of Mis18ß, the latter is indispensable for the optimal level of CENP-A loading required for preserving the centromere identity.

Cumulative Blood Pressure Load and Incident CKD.

RATIONALE & OBJECTIVE: The association of long-term cumulative blood pressure (BP) loads with the risk of incident chronic kidney disease (CKD) remains a matter of debate. This study investigated this association among healthy Korean adults with normal kidney function. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 5,221 participants without CKD in the Korean Genome and Epidemiology Study. Cumulative systolic and diastolic BP (SBP and DBP) loads were calculated as the ratios of the areas under the curve (AUC) for SBP≥120mm Hg or≥80mm Hg for DBP divided by the AUC for all SBP or DBP measurements during the exposure period. These AUCs were categorized into 4 groups: group 0 (reference), cumulative BP load of 0 and groups 1-3, tertiles of cumulative BP loads. OUTCOME: Primary end point was incident CKD defined as a composite of an estimated glomerular filtration rate (eGFR) below 60mL/min/1.73m2 or proteinuria greater than 1+on dipstick examination for at least 2 consecutive measurements≥90 days apart. ANALYTICAL APPROACH: Multivariable Cox proportional hazards regression to estimate the independent association of cumulative BP loads with incident CKD. RESULTS: Higher cumulative SBP and DBP loads were associated with an increased risk of incident CKD (HR, 1.23 [95% CI, 1.12-1.35] for SBP; and HR, 1.14 [95% CI, 1.04-1.26] for DBP loads for each 1.0-unit greater load). Compared with SBP group 0, groups 2 and 3 were associated with 1.94- and 1.89-fold greater risk of incident CKD. Compared with DBP group 0, groups 2 and 3 were associated with 1.42- and 1.54-fold greater risks. These associations of high cumulative BP loads with an increased risk of incident CKD remained consistent even in the subgroups not taking antihypertensive agents or without prior hypertension diagnosis. LIMITATIONS: The assessment of CKD outcomes relied on eGFR and spot urine tests. CONCLUSIONS: These findings highlight the association between high cumulative SBP and DBP loads and the occurrence of CKD, even in individuals with normal BP levels. PLAIN-LANGUAGE SUMMARY: Although hypertension is a major risk factor for chronic kidney disease (CKD), most studies have focused on single-point blood pressure (BP) measurements. To explore the association between long-term cumulative BP load and the development of CKD, 5,221 Korean adults with normal kidney function were included in this study. Cumulative systolic BP and diastolic BP load both exhibited a significant association with an increased risk of incident CKD. Notably, the association of cumulative BP loads with elevated risk of incident CKD was evident also in individuals who were not taking antihypertensive agents or who had no previous history of hypertension. These findings underscore the importance of managing long-term exposure to high BP, even in individuals with normal BP levels.

AI-driven automatic compression system for colorectal anastomosis.

Although circular staplers offer technical advancements over traditional hand-sewn techniques, their use remains challenging for unskilled users, necessitating substantial time and experience for mastery. In particular, it is challenging to apply a consistent pressure of an appropriate magnitude. We developed an automated circular anastomosis device using artificial intelligence (AI) to solve this problem. Automation through AI reduces experiential factors during the anastomosis process. We defined damage occurring during the anastomosis process, noting that a greater depth of damage indicated a more severe injury. For automated anastomosis, data at a tissue strain of 40% were used for the AI model, as this strain level showed optimal performance based on the accuracy and cost matrix. We compared the outcomes of automated anastomosis using a trained AI with those of unskilled users. The results were validated using the Shapiro-Wilk test and t tests. Compression damage was verified on collagen sheets. The AI-driven automatic compression system resulted in less damage compared to unskilled users. In particular, a more significant difference in damage was observed in poor-condition collagen than in good-condition collagen. Damage to the collagen under poor conditions was 54.8% when handled by unskilled users, while the AI-driven automatic compression system resulted in 38.9% damage. This study confirmed that novices' use of AI for automated anastomosis reduces the risk of damage, especially for tissues in poor condition.

Balloon-expandable cobalt chromium stent versus self-expandable nitinol stent for the Atherosclerotic Iliac Arterial Disease (SENS-ILIAC Trial) Trial: a randomized controlled trial.

Iliac artery angioplasty with stenting is an effective alternative treatment modality for aortoiliac occlusive diseases. Few randomized controlled trials have compared the efficacy and safety between self-expandable stent (SES) and balloon-expandable stent (BES) in atherosclerotic iliac artery disease. In this randomized, multicenter study, patients with common or external iliac artery occlusive disease were randomly assigned in a 1:1 ratio to either BES or SES. The primary end point was the 1-year clinical patency, defined as freedom from any surgical or percutaneous intervention due to restenosis of the target lesion after the index procedure. The secondary end point was a composite event from major adverse clinical events at 1 year. A total of 201 patients were enrolled from 17 major cardiovascular intervention centers in South Korea. The mean age of the enrolled patients was 66.8 ± 8.5 years and 86.2% of the participants were male. The frequency of critical limb ischemia was 15.4%, and the most common target lesion was in the common iliac artery (75.1%). As the primary end point, the 1-year clinical patency as primary end point was 99% in the BES group and 99% in the SES group (p > 0.99). The rate of repeat revascularization at 1 year was 7.8% in the BES group and 7.0% in the SES group (p = 0.985; confidence interval, 1.011 [0.341-2.995]). In our randomized study, the treatment of iliac artery occlusive disease with self-expandable versus balloon-expandable stent was comparable in 12-month clinical outcomes without differences in the procedural success or geographic miss rate regardless of the deployment method in the distal aortoiliac occlusive lesion (ClinicalTrials.gov, NCT01834495).

Increased ERCP-related adverse event from premature urgent ERCP following symptom onset in acute biliary pancreatitis with cholangitis.

Acute biliary pancreatitis (ABP) with cholangitis requires endoscopic retrograde cholangiopancreatography (ERCP) within 24 h to resolve ductal obstruction. However, this recommendation is based on the timing of emergency room (ER) visits. We wanted to determine the optimal timing of ERCP for ABP based on the timing of symptom onset, not the timing of the ER visit. We retrospectively reviewed 162 patients with ABP with cholangitis who underwent urgent ERCP (within 24 h of ER admission). Area under the receiver operating characteristic (ROC) curve (AUC) was analyzed to determine differences in complication rates according to time from symptom onset. A difference in ERCP-related adverse events (AEs) was identified, and Youden's J statistic was used to determine a cutoff time from symptom onset (18 h). We compared mortality and complications based on this cutoff. Based on time to symptom onset, significantly higher rates of aspiration pneumonia (odds ratio [OR] 4.00, 95% confidence interval [CI] 1.15-13.92, P = 0.021) and post-ERCP hypotension (OR 11.9, 95% CI 1.39-101.33, P = 0.005) were observed in the ≤ 18-h group than in the > 18-h group. The study found that patients who underwent ERCP within 18 h of symptom onset is associated with an increased risk of ERCP-related AEs.

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.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu.

Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for the mechanisms of their biological functions as well as their potential as therapeutic targets.

Improved Frequency Sweep Keying CDMA Using Faster R-CNN for Extended Ultrasonic Crosstalk Reduction.

Ultrasonic sensors are inexpensive and provide highly accurate measurements, even with simple hardware configurations, facilitating their use in various fields. When multiple ultrasonic sensors exist in the measurement space, crosstalk occurs due to other nodes, which leads to incorrect measurements. Crosstalk includes not only receiving homogeneous signals from other nodes, but also overlapping by other signals and interference by heterogeneous signals. This paper proposes using frequency sweep keying modulation to provide robustness against overlap and a faster region-based convolutional neural network (R-CNN) demodulator to reduce the interference caused by heterogeneous signals. The demodulator works by training Faster R-CNN with the spectrograms of various received signals and classifying the received signals using Faster R-CNN. Experiments implementing an ultrasonic crosstalk environment showed that, compared to on-off keying (OOK), phase-shift keying (PSK), and frequency-shift keying (FSK), the proposed method can implement CDMA even with shorter codes and is robust against overlap. Compared to correlation-based frequency sweep keying, the time-of-flight error was reduced by approximately 75%. While the existing demodulators did not consider heterogeneous signals, the proposed method ignored approximately 99% of the OOK and PSK signals and approximately 79% of the FSK signals. The proposed method performed better than the existing methods and is expected to be used in various applications.

Edge Bleeding Artifact Reduction for Shape from Focus in Microscopic 3D Sensing.

Shape from focus enables microscopic 3D sensing by combining it with a microscope system. However, edge bleeding artifacts of estimated depth easily occur in this environment. Therefore, this study analyzed artifacts and proposed a method to reduce edge bleeding artifacts. As a result of the analysis, the artifact factors are the depth of field of the lens, object texture, brightness difference between layers, and the slope of the object. Additionally, to reduce artifacts, a weighted focus measure value method was proposed based on the asymmetry of local brightness in artifacts. The proposed reduction method was evaluated through simulation and implementation. Edge bleeding artifact reduction rates of up to 60% were shown in various focus measure operators. The proposed method can be used with postprocessing algorithms and reduces edge bleeding artifacts.

The correlation between transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography in the evaluation of lower extremity perfusion according to angiosome.

The increased peripheral arterial disease (PAD) incidence associated with aging and increased incidence of cardiovascular conditions underscores the significance of assessing lower limb perfusion. This study aims to report on the correlation and utility of two novel non-invasive instruments: transcutaneous oxygen pressure (TcPO2 ) and forward-looking infrared (FLIR) thermography. A total of 68 patients diagnosed with diabetic foot ulcer and PAD who underwent vascular studies at a single institution between March 2022 and March 2023 were included. Cases with revascularization indications were treated by a cardiologist. Following the procedure, ambient TcPO2 and FLIR thermography were recorded on postoperative days 1, 7, 14, 21 and 28. In impaired limbs, TcPO2 was 12.3 ± 2 mmHg and FLIR thermography was 28.7 ± 0.9°C. TcPO2 (p = 0.002), FLIR thermography (p = 0.015) and ankle-brachial index (p = 0.047) values significantly reduced with greater vascular obstruction severity. Revascularization (n = 39) significantly improved TcPO2 (12.5 ± 1.7 to 19.1 ± 2.2 mmHg, p = 0.011) and FLIR (28.8 ± 1.8 to 32.6 ± 1.6°C; p = 0.018), especially in severe impaired angiosomes. TcPO2 significantly increased immediately post-procedure, then gradually, whereas the FLIR thermography values plateaued from day 1 to 28 post-procedure. In conclusion, FLIR thermography is a viable non-invasive tool for evaluating lower limb perfusion based on angiosomes, comparable with TcPO2 .

The impact of sex differences on 3-year outcomes of patients with non-ST-segment elevation myocardial infarction after successful stent implantation according to symptom-to-balloon time.

BACKGROUND: Because no data are available, we compared the 3-year outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) based on sex and symptom-to-balloon time (SBT). METHODS: This study included 4910 patients who were divided into two groups based on SBT: SBT <48 h (n = 3,293, 67.1%) and SBT ≥48 h (n = 1,617, 32.9%). The primary outcome was all-cause death during the 3-year follow-up period. The secondary outcome was major adverse cardiac events (MACE), defined as all-cause death, recurrent myocardial infarction, or repeat coronary revascularization. RESULTS: After adjustment, the in-hospital mortality rates for males and females in the SBT <48 h and SBT ≥48 h groups were similar. During a 3-year follow-up period, females in the SBT <48 h group had significantly higher rates of all-cause death (adjusted hazard ratio [aHR], 1.482; P = 0.006), cardiac death (CD, aHR, 1.617; P = 0.009), and MACE (aHR, 1.268; P = 0.024) than those males in the same groups. Females and males in the SBT ≥48 h group did not differ significantly in the primary and secondary outcomes. In males, the rates of all-cause death (P = 0.008) and CD (P = 0.024) were significantly higher in the SBT ≥48 h group than in the SBT <48 h group. CONCLUSIONS: This study has identified a higher 3-year mortality rate in female patients with NSTEMI and SBT <48 h compared to their male counterparts. As such, a more preventive approach may be required to reduce mortality in these female patients.

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.

Effect of delayed hospitalization on patients with non-ST-segment elevation myocardial infarction and complex lesions undergoing successful new-generation drug-eluting stents implantation.

In the absence of available data, we evaluated the effects of delayed hospitalization (symptom-to-door time [SDT] ≥ 24 h) on major clinical outcomes after new-generation drug-eluting stent implantation in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and complex lesions. In total, 4373 patients with NSTEMI were divided into complex (n = 2106) and non-complex (n = 2267) groups. The primary outcome was the 3-year rate of major adverse cardiac events (MACE), defined as all-cause death, recurrent MI, and any repeat revascularization. Secondary outcomes included the individual MACE components. In the complex group, all-cause death (adjusted hazard ratio [aHR], 1.752; p = 0.004) and cardiac death (aHR, 1.966; p = 0.010) rates were significantly higher for patients with SDT ≥ 24 h than for those with SDT < 24 h. In the non-complex group, all patients showed similar clinical outcomes. Patients with SDT < 24 h (aHR, 1.323; p = 0.031) and those with SDT ≥ 24 h (aHR, 1.606; p = 0.027) showed significantly higher rates of any repeat revascularization and all-cause death, respectively, in the complex group than in the non-complex group. Thus, in the complex group, delayed hospitalization was associated with higher 3-year mortalities.

Differences in Oligomerization of the SARS-CoV-2 Envelope Protein, Poliovirus VP4, and HIV Vpu.

Viroporins constitute a class of viral membrane proteins with diverse roles in the viral life cycle. They can self-assemble and form pores within the bilayer that transport substrates, such as ions and genetic material, that are critical to the viral infection cycle. However, there is little known about the oligomeric state of most viroporins. Here, we use native mass spectrometry (MS) in detergent micelles to uncover the patterns of oligomerization of the full-length SARS-CoV-2 envelope (E) protein, poliovirus VP4, and HIV Vpu. Our data suggest that the E protein is a specific dimer, VP4 is exclusively monomeric, and Vpu assembles into a polydisperse mixture of oligomers under these conditions. Overall, these results revealed the diversity in the oligomerization of viroporins, which has implications for mechanisms of their biological functions as well as their potential as therapeutic targets.

The impact of renal function on the three-year outcomes in patients with myocardial infarction with nonobstructive coronary arteries.

BACKGROUND: Due to limited data availability, we compared the 3-year outcomes of patients with acute myocardial infarction (AMI) and nonobstructive coronary arteries (MINOCA) and those with obstructive coronary arteries (MIOCA) according to renal function. METHODS: From a final cohort of 10,774 patients with AMI were classified into 2 groups: the chronic kidney disease (CKD) group (estimated glomerular filtration rate <60 mL/min/1.73 m2, 2,854 patients; MINOCA, 123; MIOCA, 2,731) and the non-CKD group (7,920 patients; MINOCA, 256; MIOCA, 7,664). The primary outcome was the 3-year all-cause death rate, and the secondary outcomes included cardiac death (CD), non-CD death (NCD), recurrent myocardial infarction (MI), and any revascularization. RESULTS: In both the CKD and non-CKD groups, the adjusted in-hospital mortality, 3-year all-cause death, CD, and recurrent MI rates were similar between the MINOCA and MIOCA groups, but the adjusted 3-year any revascularization rates were significantly higher in the MIOCA group than in the MINOCA group. Characteristically, in the CKD group, the adjusted 3-year NCD rate (P = 0.032) was higher in the MINOCA group than in the MIOCA group, and sepsis was the main cause of NCD in this group. In both the MINOCA and MIOCA groups, all-cause death and NCD were significantly higher in the CKD group than in the non-CKD group. CONCLUSIONS: Regardless of renal function, the MINOCA and MIOCA groups had comparable mortality rates. However, patients with MINOCA and CKD had higher NCD rates. Close monitoring of renal function and enhanced strategies are required to reduce mortality in patients with MINOCA.