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Abstract This study presents a novel analytical method for the quantitative and qualitative analysis of microplastics (MPs) in deionized (DI) water using Raman spectroscopy. Raman peak area ratios of 1295 cm−1 for polyethylene (PE) and 637 cm−1 for polyvinylchloride (PVC) to the broad H2O peak were utilized to establish a calibration model for the concentration of MPs dispersed in DI water at 0.1 wt% to 1.0 wt%. The calibration model demonstrated R2 values of 0.98537 for PE and 0.99511 for PVC, indicating high linearity between the peak area ratio and concentration. The calibration model was validated using mixed PE and PVC samples to confirm its applicability to real-world water bodies, where multiple types of MPs are present. The calculated standard error of calibration (SEC) and relative standard error of calibration (%RSEC) values further confirmed the accuracy of the predictions, providing a robust approach for detecting and quantifying MPs in aquatic environments.

Abstract Dyskalemia is a common electrolyte abnormality. Since dyskalemia can cause fatal arrhythmias and cardiac arrest in severe cases, it is crucial to monitor serum potassium (K+) levels on time. We developed deep learning models to detect hyperkalemia (K+ ≥ 5.5 mEq/L) and hypokalemia (K+

Abstract Background Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. Methods From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3–5) and gastrointestinal (GI) bleeding (BARC types 3–5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. Results Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18–8.78). The incidence of major bleeding and GI bleeding (BARC types 3–5) was comparable between PPI users and non-users in the PS-matched cohort. Conclusions In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Abstract Background The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or ‘on treatment’ BP on clinical outcomes in patients with DKD. Methods A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP]

Background and objectivesThe optimal timing for complete revascularization (CR) in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) remain uncertain.MethodsThis post-hoc analysis of the FRAME-AMI trial included AMI patients with MVD (n = 549). They were classified into immediate (n = 329) and staged CR (n = 220) groups. All percutaneous coronary interventions were performed during inex hospitalization. The primary endpoint was a composite of all-cause death, acute myocardial infarction, and repeated revascularization. Secondary endpoints included each component of the primary endpoint. Additional comparisons for the outcomes in ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were also performed.ResultsThe incidence of the primary endpoint was not significantly different in any of the AMI patients [12.7% [immediate CR] vs. 17.4% [staged CR], p = 0.905, adjusted hazard ratio [HR] of staged CR = 0.81, 95% confidence interval = 0.43–1.53, p = 0.528]. Other secondary endpoints were also not significantly different. Analyses of STEMI and Neither the primary or secondary endpoints of NSTEMI patients were significantly different.ConclusionsIn this post-hoc analysis of the FRAME-AMI trial, no significant difference in clinical outcomes was observed between the immediate and staged CR strategies for AMI with MVD and the subgroups, such as STEMI or NSTEMI. However, the results should be interpreted carefully because of the many limitations, including a limited sample size and a lack of statistical power. Trial Registration: FRAME-AMI clinicaltrials.gov, identifier (NCT02715518).

Carbon nanotubes (CNTs) are being used as high-performance conductive agents for fast electron transport and effective suppression of volume change in silicon (Si) electrode. However, utilization of CNTs has significant challenges, including poor dispersibility and weak interaction with Si particles. Herein, carboxylated CNTs (CNT-COOH) are employed as a mediator to form dual hydrogen bonds with the tannic acid-coated Si particles (Si@TA) and carboxymethyl cellulose (CMC) binder, through which all the constituents (active material, conductive agent, and binder) comprising the electrode are strongly connected. Also, CNT-COOH strongly attaches to Si@TA via π-π conjugation. Furthermore, the TA-coating layer serves as a protective layer from the electrolyte. As a result, the Si@TA/CNT-COOH composite electrode shows excellent cycling stability delivering a discharge-specific capacity of 1287 mAh g-1 after 200 cycles at 2 A g-1 and retains 1916 mAh g-1 even at high current density of 10 A g-1. The structural integrity of the Si@TA/CNT-COOH electrode is also confirmed by less deformation and thickness change after cycling.

Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P = .156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P -value .663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P -value .262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028

Abstract Background Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease and end-stage kidney disease. Its diverse range of manifestations complicates the treatment approach for patients. Although kidney biopsy is considered the gold standard for diagnosis, it lacks precision in predicting the progression of kidney dysfunction. Herein, we addressed whether the presence of glomerular crescents is linked to the outcomes in patients with biopsy-confirmed type 2 DKD. Methods We performed a retrospective evaluation, involving 327 patients diagnosed with biopsy-confirmed DKD in the context of type 2 diabetes, excluding cases with other glomerular diseases, from nine tertiary hospitals. Hazard ratios (HRs) were calculated using a Cox regression model to assess the risk of kidney disease progression, defined as either ≥ 50% decrease in estimated glomerular filtration rates or the development of end-stage kidney disease, based on the presence of glomerular crescents. Results Out of the 327 patients selected, ten patients had glomerular crescents observed in their biopsied tissues. Over the follow-up period (median of 19 months, with a maximum of 18 years), the crescent group exhibited a higher risk of kidney disease progression than the no crescent group, with an adjusted HR of 2.82 (1.32–6.06) (P = 0.008). The presence of heavy proteinuria was associated with an increased risk of developing glomerular crescents. Conclusion The presence of glomerular crescents is indeed linked to the progression of type 2 DKD. Therefore, it is important to determine whether there is an additional immune-mediated glomerulonephritis requiring immunomodulation, and it may be prudent to monitor the histology and repeat a biopsy.

Abstract This study evaluated the association of atherogenic index of plasma (AIP) with platelet reactivity and clinical outcomes according to acute myocardial infarction (AMI). The composite of 3-year adverse outcomes of all-cause death, myocardial infarction, and cerebrovascular accident was evaluated in 10,735 patients after successful percutaneous coronary intervention with drug-eluting stents. AIP was defined as the base 10 logarithm of the ratio of triglyceride to high-density lipoprotein cholesterol concentration. High platelet reactivity (HPR) was defined as ≥ 252 P2Y12 reactivity unit. An increase of AIP (per-0.1 unit) was related to the decreased risk of HPR [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.96–0.99; P = 0.001] in non-AMI patients, not in AMI patients (OR 0.98, 95% CI 0.96–1.01; P = 0.138). The HPR was associated with the increased risk of composite outcomes in both non-AMI and AMI patients (all-P

BackgroundLeft ventricular ejection fraction (LVEF) is a crucial prognostic indicator of acute myocardial infarction (AMI). However, there is a lack of studies on the clinical characteristics and prognosis of patients with mildly reduced ejection fraction (EF) after AMI.MethodsWe categorized 6,553 patients with AMI from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) between November 2011 and December 2015 into three groups based on their EF, as assessed by echocardiography during index hospitalization: reduced EF (LVEF ≤40%), mildly reduced EF (LVEF 41%–49%), and preserved EF (LVEF ≥50%). The primary outcome was all-cause death within 2 years. The secondary outcomes included myocardial infarction (MI), revascularization, and patient-oriented composite endpoint (POCE), which was defined as a composite of all-cause death, any MI, or revascularization.ResultsOf the total 6,553 patients, 884 (13.5%) were classified into the reduced EF group, 1,749 (26.7%) into the mildly reduced EF group, and 3,920 (59.8%) into the preserved EF group. Patients with mildly reduced EF exhibited intermediate mortality (reduced EF, 24.7%; mildly reduced EF, 8.3%; preserved EF, 4.6%; p

Introduction There is a lack of evidence to support the effectiveness of prolonged β-blocker therapy after stabilisation of patients with acute myocardial infarction (AMI) without heart failure (HF) or left ventricular systolic dysfunction.Methods and analysis The SMart Angioplasty Research Team: DEcision on Medical Therapy in Patients with Coronary Artery DIsease or Structural Heart Disease Undergoing InterventiON (SMART-DECISION) trial is a multicentre, prospective, open-label, randomised, non-inferiority trial designed to determine whether discontinuing β-blocker therapy after ≥1 year of maintenance in stabilised patients after AMI is non-inferior to continuing it. Patients eligible for participation are those without HF or left ventricular systolic dysfunction (ejection fraction >40%) who have been continuing β-blocker therapy for ≥1 year after AMI. A total of 2540 patients will be randomised 1:1 to continuation of β-blocker therapy or not. Randomisation will be stratified according to the type of AMI (ie, ST-segment-elevation MI or non-ST-segment-elevation MI), type of β-blocker (carvedilol, bisoprolol, nebivolol or other) and participating centre. The primary study endpoint is a composite of all-cause death, MI and hospitalisation for HF over a median follow-up period of 3.5 years (minimum, 2.5 years; maximum, 4.5 years). Adverse effects related to β-blocker therapy, the occurrence of atrial fibrillation, medical costs and Patient-reported Outcomes Measurement Information system-29 questionnaire responses will also be collected as secondary endpoints.Ethics and dissemination Ethics approval for this study was granted by the Institutional Review Board of Samsung Medical Center (no. 2020-10-176). Informed consent is obtained from every participant before randomisation. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.Trial registration number ClinicalTrials.gov, NCT04769362.

Background Carriers of CYP2C19 loss‐of‐function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. Methods and Results The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel‐based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3‐year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all‐cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3‐year clinical outcomes. Conclusions In older patients, the presence of any CYP2C19 loss‐of‐function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. Registration URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Abstract Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology’s future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Abstract Galectin-3 levels have been studied as a potential biomarker for predicting cardiovascular (CV) risk and mortality in hemodialysis (HD) patients. Recently, a close relationship between galectin-3 and vascular calcification (VC) has been reported. Here, we investigated the role of VC as a mediating factor in the association between galectin-3 and mortality. Serum galectin-3 and baseline aortic arch calcification (AoAC) score were measured in 477 incident HD patients. Mortality data were obtained at a median follow-up of 40 months. Causal mediation analysis was performed to examine the effect of vascular risk factors on galectin-3-related mortality. The prevalence of AoAC in HD patients was 57% (n = 272), and elevated galectin-3 levels were associated with a significantly increased risk of AoAC. When the galectin-3 level was divided by the median level of 37 ng/mL, a higher galectin group increased the risk of all-cause mortality by 1.71-fold (95% CI 1.02–2.92, p = 0.048), even after adjustment for multiple CV risk factors. Mediation analysis showed that both the direct effect of the galectin-3 on mortality (β = 0.0368, bootstrapped 95% CI [0.0113–0.0622]) and the indirect effects were significant. AoAC score and high-sensitivity CRP levels significantly mediated the association between galectin-3 and mortality (total indirect effects: β = 0.0188, bootstrapped 95% CI [0.0066–0.0352]). This study suggests that the association between high galectin-3 and mortality may be partially mediated by higher VC and inflammatory state in HD patients.

We developed a tailored 3D Agarose-well system integrated with reconstructed human skin equivalents to enhance skin penetration assessments. This system addresses common limitations in traditional trans-well reconstructions, such as dermal layer contraction and limited lateral diffusion, by entangling collagen fibrils within the Agarose-well. We evaluated the penetration behavior of three peptides, with and without skin-penetrating peptide (SPP) sequences, alongside adenosine, a known anti-wrinkle agent. Despite a SPP having a molecular weight approximately four times greater than that of adenosine, its kinetic constant was similar, with values of about 39 and 34, respectively. Moreover, this living skin equivalent system not only allowed for the evaluation of adenosine penetration, but also demonstrated its biological effects, with adenosine significantly enhancing procollagen synthesis by approximately 23% compared to the control. Overall, this novel strategy holds the potential for tailoring 3D Agarose-wells and advancing high-performance gel development, making it a promising approach for applications in tissue engineering, medical science, regenerative medicine, and cosmetics.

Abstract To evaluate the differential associations of high-risk plaque characteristics (HRPC) with resting or hyperemic physiologic indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve [FFR]), a total of 214 vessels from 127 patients with stable angina or acute coronary syndrome who underwent coronary computed tomography angiography (CCTA) and invasive physiologic assessment were investigated. HPRC were classified into quantitative (minimal luminal area 0.80 or iFR > 0.89, respectively. FFR was independently associated with both quantitative and qualitative HRPC, but iFR was only associated with quantitative HRPC. Both FFR and iFR were significantly associated with the presence of ≥ 3 HRPC, and FFR demonstrated higher discrimination ability than iFR (AUC 0.703 vs. 0.648, P = 0.045), which was predominantly driven by greater discriminating ability of FFR for quantitative HRPC (AUC 0.832 vs. 0.744, P = 0.005). In conclusion, both FFR and iFR were significantly associated with CCTA-derived HRPC. Compared with iFR, however, FFR was independently associated with the presence of qualitative HRPC and showed a higher predictive ability for the presence of ≥ 3 HRPC.

Background/Aims The Genoss DES™ is a novel, biodegradable, polymer-coated, sirolimus-eluting stent with a cobalt-chromium stent platform and thin strut. Although the safety and effectiveness of this stent have been previously investigated, real-world clinical outcomes data are lacking. Therefore, the aim of this prospective, multicenter trial was to evaluate the clinical safety and effectiveness of the Genoss DES™ in all-comer patients undergoing percutaneous coronary intervention. Methods The Genoss DES registry is a prospective, single-arm, observational trial for evaluation of clinical outcomes after Genoss DES™ implantation in all-comer patients undergoing percutaneous coronary intervention from 17 sites in South Korea. The primary endpoint was a device-oriented composite outcome of cardiac death, target vessel-related myocardial infarction (MI), and clinically driven target lesion revascularization (TLR) at 12 months. Results A total of 1,999 patients (66.4 ± 11.1 years of age; 72.8% male) were analyzed. At baseline, 62.8% and 36.7% of patients had hypertension and diabetes, respectively. The implanted stent number, diameter, and length per patient were 1.5 ± 0.8, 3.1 ± 0.5 mm, and 37.0 ± 25.0 mm, respectively. The primary endpoint occurred in 1.8% patients, with a cardiac death rate of 1.1%, target vessel-related MI rate of 0.2%, and clinically driven TLR rate of 0.8%. Conclusions In this real-world registry, the Genoss DES™ demonstrated excellent safety and effectiveness at 12 months among all-comer patients undergoing percutaneous coronary intervention. These findings suggest that the Genoss DES™ may be a viable treatment option for patients with coronary artery disease.

Abstract Background Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. Methods The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and ‘high platelet reactivity (HPR)’ was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. Results Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P

ABSTRACT: Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were –16.27 (0.93) mm Hg in the TEL/ALD/RSV group, –6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = –9.42 mm Hg; 95% CI, –11.99 to –6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: –50.03% (1.18%) in the TEL/ALD/RSV group, –39.60% (1.17%) in the ALD/ATV group (LSM difference = –10.43%; 95% CI, –13.70 to –7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX–XXX). ClinicalTrials.gov identifier: NCT03860220.

Background: A bloodstream infection is a life-threatening medical emergency, with a mortality rate of up to 30%. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can be used to identify pathogens directly from positive blood cultures. Two commercial preparation kits, SepsiTyper (Bruker Daltonics, Germany) and SepsiPrep (ASTA Corp., Korea), and two MALDI-TOF MS systems, MALDI Biotyper Sirius (Bruker Daltonics, Germany) and VITEK MS PRIME (bioM.rieux, France), are available in Korea. We examined these kits and MALDI-TOF MS systems to analyze their performance. Methods: We assessed the effectiveness of direct identification using 47 blood cultures and 3 bile cultures positive for microbial growth. The VIRTUO system (bioM.rieux, France) was used to incubate the samples after they were collected in Bact/ALERT aerobic and anaerobic bottles. The manufacturers’ protocols were followed for both the SepsiTyper and SepsiPrep kits. Results: The SepsiTyper yielded considerably more accurate identifications than did the SepsiPrep, when utilized in MALDI-TOF MS systems (P = 0.0044). However, the SepsiPrep was easier to use and the results more quickly obtained than with the SepsiTyper. The MALDI Biotyper Sirius produced more accurate identifications with the SepsiTyper than did the VITEK MS PRIME (P = 0.0736). The SepsiTyper enabled the accurate identification of five of six polymicrobial cases, utilizing either the MALDI-TOF MS systems. Conclusions: Among the pathogen ID kits tested in this study, the SepsiTyper with MALDI Biotyper Sirius performed the best. In clinical laboratories utilizing VITEK MS PRIME, it is recommended that the either the SepsiTyper or SepsiPrep kit be used for direct identification, while considering certain limitations in terms of performance.

Background Tolvaptan reduces height-adjusted total kidney volume (htTKV) and renal function decline in autosomal dominant polycystic kidney disease (ADPKD). This study was aimed at investigating the efficacy and safety of tolvaptan in Korean patients with ADPKD during the titration period. Methods This study is a multicenter, single-arm, open-label phase 4 study. We enrolled 108 patients with ADPKD (age, 19–50 years) with an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73 m2 and factors defined as indicative of rapid disease progression. After tolvaptan titration, we evaluated efficacy and side effects and assessed factors associated with the effects. Results After titration for 4 weeks, eGFR and htTKV decreased by 6.4 ± 7.9 mL/min/1.73 m2 and 16 ± 45 mL/m, respectively. No serious adverse drug reactions were observed during the titration period. The greatest eGFR decline was observed in the first week, with a starting tolvaptan dose of 45 mg. Multivariate linear regression for htTKV decline showed that the greater the change in urine osmolality (Uosm), the greater the decrease in htTKV (β, 0.436; p = 0.009) in the 1D group stratified by the Mayo Clinic image classification. Higher baseline eGFR was related to a higher htTKV reduction rate in the 1E group (β, –0.642; p = 0.009). Conclusion We observed short-term effects and safety during the tolvaptan titration period. The decline of htTKV can be predicted as a short-term effect of tolvaptan by observing Uosm changes from baseline to end of titration in 1D and baseline eGFR in 1E groups.

Abstract Background Following the strong recommendation for coronavirus disease 2019 (COVID‑19) vaccination, many patients with medical comorbidities are being immunized. However, the safety of vaccination in patients with autoimmune diseases has not been well established. We report a new case of biopsy-proven IgA vasculitis with nephritis presenting as a nephrotic syndrome after mRNA COVID-19 vaccination in a patient with a history of leukocytoclastic vasculitis. Case presentation A 76-year-old man with a history of cutaneous leukocytoclastic vasculitis presented with purpura in both lower limbs, followed by nephrotic syndrome after the second dose of BNT162b2 mRNA COVID-19 vaccination. Skin and renal biopsy revealed IgA vasculitis with nephritis. The patient’s past medical history of leukocytoclastic vasculitis and features of chronicity in renal pathology suggest an acute exacerbation of preexisting IgA vasculitis after COVID-19 vaccination. After the steroid and renin-angiotensin system inhibitor use, purpura and acute kidney injury recovered within a month. Subnephrotic proteinuria with microscopic hematuria remained upon follow-up. Conclusion Physicians should keep in mind the potential (re)activation of IgA vasculitis following mRNA COVID-19 vaccines. It is important to closely monitor COVID-19 vaccinated patients, particularly those with autoimmune diseases.

Acetogenic bacteria can utilize C1 compounds, such as carbon monoxide (CO), formate, and methanol, via the Wood-Ljungdahl pathway (WLP) to produce biofuels and biochemicals. Two novel acetogenic bacteria of the family Eubacteriaceae ES2 and ES3 were isolated from Eulsukdo, a delta island in South Korea. We conducted whole genome sequencing of the ES strains and comparative genome analysis on the core clusters of WLP with Acetobacterium woodii DSM1030T and Eubacterium limosum ATCC8486T. The methyl-branch cluster included a formate transporter and duplicates or triplicates copies of the fhs gene, which encodes formyl-tetrahydrofolate synthetase. The formate dehydrogenase cluster did not include the hydrogenase gene, which might be replaced by a functional complex with a separate electron bifurcating hydrogenase (HytABCDE). Additionally, duplicated copies of the acsB gene, encoding acetyl-CoA synthase, are located within or close to the carbonyl-branch cluster. The serum bottle culture showed that ES strains can utilize a diverse range of C1 compounds, including CO, formate, and methanol, as well as CO2. Notably, ES2 exhibited remarkable resistance to high concentrations of C1 substrates, such as 100% CO (200 kPa), 700 mM formate, and 500 mM methanol. Moreover, ES2 demonstrated remarkable growth rates under 50% CO (0.45 h−1) and 200 mM formate (0.34 h−1). These growth rates are comparable to or surpassing those previously reported in other acetogenic bacteria. Our study introduces novel acetogenic ES strains and describes their genetic and physiological characteristics, which can be utilized in C1-based biomanufacturing.

Summary: Background: The impact of titrated versus fixed intensity statin therapy in patients with coronary artery disease (CAD) and diabetes mellitus (DM) remains to be elucidated. Methods: This was a pre-specified analysis of patients with and without DM from the LODESTAR trial. Patients with CAD were randomly assigned to receive either a treat-to-target strategy with a target LDL-C level of 50–70 mg/dL or a high-intensity statin treatment. Primary outcome was the 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. Secondary outcomes were safety endpoints. This trial is registered with ClinicalTrials.gov, NCT02579499. Findings: Between September 9, 2016 and November 27, 2019, 4400 patients with CAD were enrolled in the LODESTAR trial. The median age was 65 years (interquartile range, 59–73 years), 3172 (72%) were male, and 1468 (33%) had DM at baseline. There was no significant difference in the occurrence of the primary outcome between the treat-to-target group and high-intensity statin group among patients with DM (10.5% versus 11.1%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.69–1.29, p = 0.70) and those without DM (6.9% versus 7.5%, HR 0.93, 95% CI 0.71–1.21, p = 0.58). Among patients without DM, there was a trend towards a lower risk of new-onset DM in the treat-to-target group (8.4% versus 10.4% in the high-intensity statin group, HR 0.79, 95% CI 0.62–1.01; p = 0.06). Interpretation: In patients with CAD, a treat-to-target LDL-C strategy of 50–70 mg/dL as the goal was comparable to high-intensity statin therapy in terms of 3-year clinical efficacy and safety outcomes regardless of the presence of DM. Funding: Sam Jin Pharmaceutical, Seoul, Korea and Chong Kun Dang Pharmaceutical, Seoul, Korea.

Background Sarcopenia is a prevalent complication in patients with chronic kidney disease and is associated with poor quality of life, morbidity, and mortality. Several candidate biomarkers have been evaluated for this condition. This study assessed the serum cystatin C to creatinine (serum cystatin C/Cr) ratio as a potential biomarker for sarcopenia in patients with non-dialysis-dependent chronic kidney disease. Methods This study enrolled 517 outpatients. Muscle mass (lean tissue index) was measured using a bioimpedance spectroscopic device, and muscle strength (handgrip strength) was also measured. Sarcopenia was defined as a combination of low muscle strength and low muscle mass. Results Sarcopenia was observed in 25.5% of patients, and the mean serum cystatin C/Cr ratio was significantly higher in patients with sarcopenia than in those without it (1.14 ± 0.26 vs. 1.01 ± 0.27, p < 0.001). The prevalence of sarcopenia and low lean tissue index increased as the cystatin C/Cr ratio increased. The negative predictive value of the cystatin C/Cr ratio for sarcopenia or low lean tissue index was ≥80%. Multivariate analyses revealed that when the serum cystatin C/Cr ratio increased by 1, the risk of sarcopenia, low lean tissue index, and low handgrip strength increased by 4.6-, 7.2-, and 2.6-fold, respectively (p = 0.003, p < 0.001, and p = 0.048). The association was maximized in patients with an estimated glomerular filtration rate of

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug‐eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG‐DES (Platelet Function and Genotype‐Related Long‐Term Prognosis in Drug‐Eluting Stent–Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all‐cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity‐adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20–2.12]; women with HPR: HR, 0.99 [95% CI, 0.69–1.42]) and all‐cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07–2.44]; women with HPR: HR, 0.92 [95% CI, 0.57–1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (Pinteraction=0.013) or all‐cause mortality (Pinteraction=0.025). Conclusions In this study, HPR was a differential risk factor for 1‐year MACCEs and all‐cause mortality in women and men. And it was an independent predictor of 1‐year MACCEs and all‐cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028

Multi-layered hydrogels consisting of bi- or tri-layers with different swelling ratios are designed to soft hydrogel actuators by self-folding. The successful use of multi-layered hydrogels in this application greatly relies on the precise design and fabrication of the curvature of self-folding. In general, however, the self-folding often results in an undesired mismatch with the expecting value. To address this issue, this study introduces an interfacial layer formed between each layered hydrogel, and this layer is evaluated to enhance the design and fabrication precision. By considering the interfacial layer, which forms through diffusion, as an additional layer in the multi-layered hydrogel, the degree of mismatch in the self-folding is significantly reduced. Experimental results show that as the thickness of the interfacial layer increases, the multi-layered hydrogel exhibits a 3.5-fold increase in its radius of curvature during the self-folding. In addition, the diffusion layer is crucial for creating robust systems by preventing the separation of layers in the muti-layered hydrogel during actuation, thereby ensuring the integrity of the system in operation. This new strategy for designing multi-layered hydrogels including an interfacial layer would greatly serve to fabricate precise and robust soft hydrogel actuators.

BackgroundA strong association between elevated neutrophil extracellular trap (NET) levels and poor clinical outcomes in patients with coronavirus infection 2019 (COVID-19) has been reported. However, while acute kidney injury (AKI) is a common complication of COVID-19, the role of NETs in COVID-19-associated AKI is unclear. We investigated the association between elevated NETs and AKI and the prognostic role of NETs in COVID-19 patients.MethodsTwo representative markers of NETs, circulating nucleosomes and myeloperoxidase-DNA, were measured in 115 hospitalized patients. Serum levels of interleukin [IL]-6, monocyte chemotactic protein-1 [MCP-1], plasma von Willebrand factor (vWF) and urinary biomarkers of renal tubular damage (β2-microglobulin [β2M] and kidney injury molecule 1 [KIM-1]) were measured.ResultsAKI was found in 43 patients (37.4%), and pre-existing chronic kidney disease (CKD) was a strong risk factor for AKI. Higher circulating NET levels were a significant predictor of increased risk of initial ICU admission, in-hospital mortality (adjusted HR 3.21, 95% CI 1.08–9.19) and AKI (OR 3.67, 95% CI 1.30-10.41), independent of age, diabetes, pre-existing CKD and IL-6 levels. There were strong correlations between circulating nucleosome levels and urinary KIM-1/creatinine (r=0.368, p=0.001) and β2M (r=0.218, p=0.049) levels. NETs were also strongly closely associated with serum vWF (r = 0.356, p

Background/Aims While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. Methods The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. Results The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. Conclusions We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

Acute kidney injury (AKI) is a common condition in critically ill patients, and may contribute to significant medical, social, and economic consequences, including death. Although there have been advances in medical technology, including continuous renal replacement therapy (CRRT), the mortality rate of AKI is high, and there is no fundamental treatment that can reverse disease progression. The decision to implement CRRT is often subjective and based primarily on the clinician’s judgment without consistent and concrete guidelines or protocols regarding when to initiate and discontinue CRRT and how to manage complications. Recently, several randomized controlled trials addressing the initiation of renal replacement therapy in critically ill patients with AKI have been completed, but clinical application of the findings is limited by the heterogeneity of the objectives and research designs. In this review, the advantages and disadvantages of CRRT initiation, clinical guideline recommendations, and the results of currently published clinical trials and meta-analyses are summarized to guide patient care and identify future research priorities.

Background Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events. Methods Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. We additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed. Results The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to prevalent HD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high- sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls. Conclusion In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications

Abstract Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Level of plasma nucleosome and myeloperoxidase-DNA, established in vivo markers of NETs, as well as intracellular adhesion molecule (ICAM)-1 were measured in hemodialysis (HD) patients and healthy volunteers (HV) and their prognostic role evaluated. For in vitro studies, HV-derived neutrophils and differentiated HL-60 cells by retinoic acid were used to determine the effect of uremic serum-induced NETs on human umbilical vein EC (HUVEC). The level of in vivo NETs was significantly higher in incident HD patients compared to HV, and these markers were strongly associated with ICAM-1. Specifically, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality, or vascular access failure. In vitro, HD-derived uremic serum significantly increased NET formation both in dHL-60 and isolated neutrophils compared to control serum, and these NETs decreased EC viability and induced their apoptosis. In addition, the level of ICAM-1, E-selectin and von Willebrand factor in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs. Dysregulated neutrophil activities in the uremic milieu may play a key role in vascular inflammatory responses. The high mortality and CVD rates in ESRD may be explained in part by excessive NET formation leading to EC damage and dysfunction.

Abstract Background Erythropoietin stimulating agent (ESA) has been standard of care in treating renal anaemia for the past 20 years. Many patients have limited access to ESA in view of long-term costs leading to suboptimal ESA dosage. Biosimilar epoetin is a potential cost-effective alternative to originator for optimal renal anaemia management. Objective To determine efficacy and safety of PDA10 in treating renal anaemia in haemodialysis patients, in comparison to the originator epoetin-α, Eprex®. Methods A phase 3, multicentre, multi-national, double-blind, randomised, active-controlled and parallel group study conducted over 40 weeks in Malaysia and Korea. End stage kidney disease patients undergoing regular haemodialysis who were on erythropoietin treatment were recruited. The study has 3 phases, which included a 12-week titration phase, followed by 28-week double-blind treatment phase and 24-week open-label extension phase. Results The PDA10 and Eprex® were shown to be therapeutically equivalent (p

Abstract Background Interosseous ligament vertical segment (IOLV) and calcaneofibular ligament (CFL) have been reported to be important in stabilizing the subtalar joint. Unlike CFL, there is not much information regarding the comparison of MRI results with surgical evaluation of IOLV and the comparison between 2D and 3D MRI on IOLV evaluation. The feasibility of MRI in IOLV evaluation has yet to be reported. The purpose of this study was to evaluate the validity and reliability of MRI in IOLV tear detection via correlation with arthroscopic results. We also compared the diagnostic performance of 2D and 3D MR images. Methods In this retrospective study, 52 patients who underwent subtalar arthroscopy after ankle MRI were enrolled. Arthroscopic results confirmed IOLV tear in 25 cases and intact IOLV in 27 cases. Two radiologists independently evaluated the IOLV tears using only conventional 2D images, followed by isotropic 3D images, and comparison with arthroscopic results. Results Only the 2D sequences interpreted by two readers showed a sensitivity of 64.0–96.0%, a specificity of 29.6–44.4%, a positive predictive value of 51.6–56.4%, and a negative predictive value of 57.1–88.9%. Addition of isotropic 3D sequences changed the sensitivity to 60.0–80.0%, specificity to 63.0–77.8%, positive predictive value to 64.3–76.9%, and negative predictive value to 66.7–80.8%. The overall diagnostic performance of isotropic 3D sequences (AUC values: 0.679–0.816) was higher than that of 2D sequences (AUC values: 0.568–0.647). Inter-observer and intra-observer agreement between the two readers was moderate-to-good for both 2D and 3D sequences. The diagnostic accuracy in 19 patients with tarsal sinus fat obliteration tended to increase from 26.3–42.1% to 57.9–73.7% with isotropic 3D sequences compared with 2D sequences. Conclusions Isotropic 3D MRI was feasible for the assessment of IOLV tear prior to subtalar arthroscopy. Additional 3D sequences showed higher diagnostic accuracy compared with conventional 2D sequences in IOLV evaluation. Isotropic 3D sequences may be more valuable in detecting IOLV tear in case of tarsal sinus fat obliteration.

Background Minimal change disease (MCD) is one of the most common causes of nephrotic syndrome worldwide. Hyperuricemia increases the end-stage renal disease (ESRD) risk in glomerulonephritis. In this study, we aimed to determine the effect of high serum uric acid levels on the progression to ESRD in MCD. Methods A total of 800 patients diagnosed with MCD by kidney biopsy were retrospectively analyzed. We determined the relationship of hyperuricemia with the progression to ESRD in MCD using the Cox proportional hazard model and Kaplan-Meier survival analysis. The primary outcome was defined as the initiation of dialysis or kidney transplantation. Results A total of 42 patients (5.3%) progressed to ESRD during the follow-up period. In the restricted cubic spline curve, serum uric acid levels exhibited a positive correlation with ESRD progression in patients with MCD. In the fully adjusted model, the risk of MCD progression increased by 29% for every 1 mg/dL increase in the baseline serum uric acid level (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.09–1.54; p = 0.004). Falling into the high uric acid group (serum uric acid level > 7 mg/dL in men and > 6 mg/dL in women) was also a risk factor for progression of MCD to ESRD (HR, 3.40; 95% CI, 1.59–7.31; p < 0.001). Conclusion Our study shows that hyperuricemia is an independent risk factor for the progression to ESRD in patients with MCD.

Abstract Most epidemiologic studies assessing the relationship between chronic kidney disease (CKD) and sarcopenia have been performed in dialysis patients. This study aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR), proteinuria, and sarcopenia in patients with non-dialysis-dependent CKD. A total of 892 outpatients who did not show any rapid changes in renal function were enrolled in this observational cohort study. We measured the muscle mass using bioimpedance analysis and handgrip strength (HGS), and sarcopenia was defined as low HGS and low muscle mass. Sarcopenia was found in 28.1% of the patients and its prevalence decreased as the body mass index (BMI) increased; however, in patients with BMI ≥ 23 kg/m2, the prevalence did not increase with BMI. As eGFR decreased, the lean tissue index and HGS significantly decreased. However, the eGFR did not affect the fat tissue index. The risk of sarcopenia increased approximately 1.6 times in patients with eGFR

The purpose of this study was to investigate the feasibility of the fluid-attenuated inversion recovery sequence with fat suppression (FLAIR-FS) for the assessment of ankle synovitis without contrast enhancement. FLAIR-FS and contrast-enhanced, T1-weighted sequences (CE-T1) of 94 ankles were retrospectively reviewed by two radiologists. Grading of synovial visibility (four-point scale) and semi-quantitative scoring of synovial thickness (three-point scale) were performed in four compartments of the ankle in both sequences. Synovial visibility and thickness in FLAIR-FS and CE-T1 images were compared, and agreement between both sequences was assessed. Synovial visibility grades and synovial thickness scores for FLAIR-FS images were lower than those for CE-T1 images (reader 1, p = 0.016, p < 0.001; reader 2, p = 0.009, p < 0.001). Dichotomized synovial visibility grades (partial vs. full visibility) were not significantly different between both sequences. The agreement in synovial thickness scores between the FLAIR-FS and CE-T1 images was moderate to substantial (κ = 0.41–0.65). The interobserver agreement between the two readers was fair for synovial visibility (κ = 0.27–0.32) and moderate to substantial for synovial thickness (κ = 0.54–0.74). In conclusion, FLAIR-FS is a feasible MRI sequence for the evaluation of ankle synovitis without contrast enhancement.

The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines are developed by the National Kidney Foundation in the United States; however, the guidelines have an impact on most international societies, including those in Korea. The KDOQI recently released the updated 2019 guidelines for vascular access based on numerous papers and controversies concerning vascular access since 2006, when the first guidelines were published. The new KDOQI guidelines have undergone significant changes compared to previous guidelines, including a change in the philosophy regarding a patient-centered approach using an end-stage kidney disease “Life-Plan.” In addition, there are newly developed or revised definitions and some key differences from previous guidelines. The process of adapting guidelines needs to be individualized to hemodialysis practice in each country, while agreeing with general principles and philosophy; therefore, we summarize changes in the updated guidelines and discuss the application and implementation of the new principles and concepts of the guidelines for vascular access care in Korea.

BackgroundThe role of high-flow arteriovenous fistula (AVF) in cardiovascular morbidity in hemodialysis (HD) patients is very likely under-recognized. We assessed the relationship between high access flow (Qa) and myocardial fibrosis in HD patients.MethodsMyocardial fibrosis was assessed by native T1 relaxation times on non-contrast cardiac magnetic resonance imaging and a potential marker of fibrosis. Serum levels of galectin-3, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and monocyte chemoattractant protein 1 (MCP-1) were measured in 101 HD patients who underwent regular monitoring of AVF Qa. A high-flow AVF was defined as a Qa >2 L/min.ResultsHemodialysis patients showed significantly higher galectin-3 value and increased T1 relaxation time compared to healthy volunteers, suggesting increased myocardial fibrosis in uremic cardiomyopathy. In HD patients, 20 (19.8%) had a Qa > 2L/min, and they had significantly higher cardiac output, cardiac index, left ventricular mass, and increased T1 times than those with a Qa ≤ 2 L/min. Also, serum galectin-3 and NT-proBNP levels were much higher in the high Qa group, indicating a close relationship between the high Qa, increased myocardial fibrosis, and the risk of heart failure (HF) in HD patients. It is interesting that a higher AVF Qa for myocardial fibrosis was independent of several traditional cardiovascular risk factors as well as serum levels of NT-proBNP and MCP-1.ConclusionsA supra-physiologically high Qa can be related to myocardial fibrosis and increased risk of HF in HD patients. Regular Qa monitoring could allow early detection of a high-flow AVF that could arise cardiac complications.

Abstract Although dual antiplatelet therapy is essential for patients who undergo percutaneous coronary interventions, the risk of bleeding remains an unsolved problem, and there is limited information on the potential relationship between genetic variants and major bleeding. We analyzed the correlations between four major single nucleotide polymorphisms (CYP2C19, ABCB1, PON1, and P2Y12 G52T polymorphisms) and clinical outcomes in 4489 patients from a prospective multicenter registry. The primary endpoint was major bleeding, defined as a Bleeding Academic Research Consortium ≥ 3 bleeding event. The allelic frequencies of ABCB1, PON1, and both individual and combined CYP2C19 variants did not differ significantly between patient groups with and without major bleeding. However, the allelic frequency of the P2Y12 variant differed significantly between the two groups. Focusing on the P2Y12 G52T variant, patients in the TT group had a significantly higher rate of major bleeding (6.4%; adjusted hazard ratio [HR] 2.51; 95% confidence interval [CI] 1.08–5.84; p = 0.033) than patients in the other groups (GG [2.9%] or GT [1.9%]). Therefore, the TT variant of the P2Y12 G52T polymorphism may be an independent predictor of major bleeding. Trial registration: NCT02707445 ( https://clinicaltrials.gov/ct2/show/NCT02707445?term=02707445&draw=2&rank=1 ).

Abstract Background Increased oxidative stress in end-stage renal disease is regarded as one of the important mechanisms in the atherosclerosis and muscle wasting. However, studies examining the clinical significance of oxidative stress by direct measurement of these markers and its association with volume status and sarcopenia are limited. Methods A follow-up cross-sectional study was performed in stable hemodialysis (HD) patients and serum protein carbonyl levels were measured as a biomarker of oxidative stress. Additionally, multi-frequency body composition analysis, handgrip strength (HGS) and nutritional assessments were performed at baseline. Results Eighty-eight patients undergoing HD were included and 30 (34.1%) patients died during a mean follow-up of 5.2 years. The mean patient age was 60.6 ± 13.5 years, and the mean HD duration was 50.8 ± 41.3 months. In total, 16 patients (18.2%) were overhydrated, 49 (55.7%) had low HGS and 36 (40.9%) had low muscle mass. Serum protein carbonyl levels were associated with serum levels of albumin, prealbumin and transferrin, hydration status and low HGS. Overhydration (odds ratio [OR] 7.01, 95% CI 1.77–27.79, p = 0.006), prealbumin (OR 0.91, 95% CI 0.83–0.99, p = 0.030), subjective global assessment (OR 3.52, 95% CI 1.08–11.46, p = 0.037) and sarcopenia (OR 3.41, 95% CI 1.02–11.32, p = 0.046) were significantly related to increased serum protein carbonyl levels. Multivariate analysis showed that the serum levels of protein carbonyl (Hazard ratio [HR] 2.37, 95% CI 1.02–5.55, p = 0.036), albumin (HR 0.17, 95% CI 0.06–0.46, p = 0.003), prealbumin (HR 0.86, 95% CI 0.80–0.92, p = 0.001), overhydration (HR 2.31, 95% CI 1.26–8.71, p = 0.015) and sarcopenia (HR 2.72, 95% CI 1.11–6.63, p = 0.028) were independent determinants of all-cause mortality. Conclusions Serum protein carbonyl was significantly associated with overhydration, nutritional status and sarcopenia, and could be a new predictor of mortality in patients undergoing HD.

A track-type underwater construction robot (URI-R) was developed by the Korea Institute of Ocean Science & Technology. Because URI-R uses tracks to move on the seabed, insufficient ground strength may hinder its movement. For smooth operation of URI-R on the seabed, it is important to determine the geotechnical properties of the seabed.To determine these properties, standard penetration test (SPT), cone penetration test (CPT), and sampling are used on land. However, these tests cannot be applied on the seabed due to a high cost owing to the vessel, crane, sampler, and analysis time. To overcome these problems, a free fall cone penetration tester (FFCPT) is being developed.The FFCPT is a device that acquires the geotechnical properties during impact/penetration/finish phases by free fall in water. Depth information is crucial during soil data acquisition. As the FFCPT cannot measure the penetration depth directly, it is estimated indirectly using acceleration. The estimated penetration depth was verified by results of real tests conducted on land.

The genome of the hyperthermophilic archaeon Thermococcus onnurineus NA1 contains three copies of the formate dehydrogenase (FDH) gene, fdh1, fdh2, and fdh3. Previously, we reported that fdh2, clustered with genes encoding the multimeric membrane-bound hydrogenase and cation/proton antiporter, was essential for formate-dependent growth with H2 production. However, the functionality of the other two FDH-coding genes has not yet been elucidated. Herein, we purified and characterized cytoplasmic Fdh3 to understand its functionality. The purified Fdh3 was identified to be composed of a tungsten-containing catalytic subunit (Fdh3A), an NAD(P)-binding protein (Fdh3B), and two Fe-S proteins (Fdh3G1 and Fdh3G2). Fdh3 oxidized formate with specific activities of 241.7 U/mg and 77.4 U/mg using methyl viologen and NADP+ as electron acceptors, respectively. While most FDHs exhibited NAD+-dependent formate oxidation activity, the Fdh3 of T. onnurineus NA1 showed a strong preference for NADP+ over NAD+ as a cofactor. The catalytic efficiency (kcat/Km) of Fdh3 for NADP+ was measured to be 5,281 mM−1 s−1, which is the highest among NADP-dependent FDHs known to date. Structural modeling suggested that Arg204 and Arg205 of Fdh3B may contribute to the stabilization of the 2′-phosphate of NADP(H). Fdh3 could also use ferredoxin as an electron acceptor to oxidize formate with a specific activity of 0.83 U/mg. Furthermore, Fdh3 showed CO2 reduction activity using reduced ferredoxin or NADPH as an electron donor with a specific activity of 0.73 U/mg and 1.0 U/mg, respectively. These results suggest a functional role of Fdh3 in disposing of reducing equivalents by mediating electron transfer between formate and NAD(P)H or ferredoxin.

BackgroundDulaglutide is associated with improved cardiovascular and kidney outcomes and can be a good therapeutic option for patients with type 2 diabetes with chronic kidney disease (CKD). In this study, the effects of dulaglutide on glucose-lowering efficacy and changes in renal function were analyzed.MethodsThis retrospective study involved 197 patients with type 2 diabetes with mild-to-severe CKD treated with dulaglutide for at least 3 months between January 2017 and December 2020 at two tertiary hospitals in Korea. Changes in the creatinine-based estimated glomerular filtration rate (eGFR) and HbA1c were compared before and after the use of dulaglutide in each patient.ResultsThe number of patients and mean eGFR (mL/min/1.73 m2) in CKD 2, 3a, 3b, and 4 were 94 (75.0 ± 8.5), 46 (54.8 ± 6.3), 31 (38.8 ± 4.4), and 26 (22.5 ± 5.4), respectively. Mean HbA1c level and body mass index (BMI) at the initiation of dulaglutide were 8.9% ± 1.4% and 29.1 ± 3.6 kg/m2, the median duration of the use of dulaglutide was 16 months. The use of dulaglutide was associated with a mean decrease in HbA1c by 0.9% ± 1.5% and the glucose-lowering efficacy was similar across all stages of CKD. Also, it was associated with a reduced decline in the eGFR; the mean eGFR change after the use of dulaglutide was -0.76 mL/min/1.73 m2 per year, whereas it was -2.41 mL/min/1.73 m2 before use (paired t-test, P = 0.003). The difference was more pronounced in patients with an eGFR < 60 mL/min/1.73 m2. Subgroup analysis showed that the renal protective effect was better in patients with proteinuria, age ≤ 65 years, and HbA1c < 9.0%, but showed no association with BMI.ConclusionsThe use of dulaglutide provided adequate glycemic control irrespective of CKD stage and was associated with a reduced decline in the eGFR in the CKD population.

Background and Objectives: Studies analyzing magnetic resonance imaging (MRI) after simultaneously performing lateral meniscal allograft transplantation (MAT) and capsulodesis are currently rare. This study aimed to compare the MRI results between the group that performed lateral MAT alone and the group that performed both lateral MAT and capsulodesis simultaneously. Materials and Methods: A total of 55 patients who underwent lateral MAT with a 1-year follow-up MRI were included. The patients were divided into two groups according to the surgical procedure: group I (isolated lateral MAT, n = 26) and group C (combined lateral MAT and capsulodesis, n = 29). Differences between groups were compared regarding subjective knee scores, graft extrusion, graft signal, articular cartilage loss, and joint space width (JSW). Results: The subjective knee scores improved significantly in both groups (all, p < 0.001), and there were no significant differences in these scores between both groups at the 1-year follow-up. Group C showed less coronal graft extrusion at the 1-year follow-up (1.1 ± 1.7 mm vs. 2.4 ± 1.8 mm, p < 0.001). Pathologic coronal graft extrusion (≥3 mm) was found in seven (26.9%) patients in group I and three (10.3%) in group C. Concerning the graft signal, group C showed less grade 3 signal intensity in the posterior root of the graft. There were no significant differences in preoperative and postoperative cartilage status between groups. Regarding JSW, there were no significant differences in postoperative JSW between both groups. However, in group C, JSW significantly increased from 3.9 ± 0.4 mm to 4.5 ± 1.4 mm (p = 0.031). Conclusions: In lateral MAT, capsulodesis (open decortication and suture anchor fixation) could reduce graft extrusion without complications. In the future, large-volume and long-term prospective comparative studies are needed to confirm the clinical effects following capsulodesis.

Purpose To compare the MRI findings of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) injuries in chronic lateral ankle instability (CLAI) between surgical treatment groups. Materials and Methods Fifty-two patients with CLAI were divided into the modified Broström procedure (MBP) (n = 31) and lateral ankle ligament reconstruction (LAR) (n = 21) groups. T2- weighted MRI findings between the groups were compared for caliber change, slope, signal intensity, and thickness measurements of the ligaments. Additionally, the talar tilt angles were measured on stress radiographs. Results The injured ATFL (p = 0.002 vs. p = 0.001) and CFL (p = 0.008 vs. p = 0.039) were more commonly scarce or thin and had decreased slopes in the LAR group. The mean thickness of ATFL (p = 0.002) and CFL (p = 0.002) was 1.1 ± 0.9 mm and 1.3 ± 0.8 mm, respectively, in the LAR group and 2.2 ± 1.3 mm and 2.1 ± 0.9 mm, respectively, in the MBP group. The mean talar tilt angle was greater in the LAR group (13.4 ± 3.9°) than in the MBP group (9.5 ± 3.8°) (p = 0.001). Conclusion A qualitative analysis of the ligaments on MRI is valuable in selecting the surgical method.

Background : Controversies exist whether arteriovenous fistula (AVF) placement is preferred over arteriovenous graft (AVG) for elderly patients. Current guidelines did not offer specific recommendations. Thus, this study was conducted to analyze the all-cause mortality and primary patency associated with various vascular access (VA) types according to age group. Methods : This retrospective observational study investigated the Korean insurance claims data of chronic kidney disease patients who began hemodialysis between January 2008 and December 2016. We investigated all-cause mortality associated with initial VA in incident hemodialysis patients and primary patency between AVF and AVG according to age group. Results : The proportion of patients with a tunneled dialysis catheter (TDC) that was first placed for VA increased from 18.4% in 2008 to 52.3% in 2016. Incident hemodialysis patients with a TDC or AVG for the initial VA had significantly higher mortality risk than patients with an AVF, except for patients over 85 years, who showed no significant difference in all-cause mortality regardless of VA type. In the patency analysis on initial AV access, AVG had significantly poorer primary patency than AVF in all age groups. Conclusion : AVF had better patency than AVG in all age groups; however, the benefit of AVF attenuated in the older age groups. The mortality rate between AVF and AVG was not significantly different in patients over 85 years. Therefore, a “patient-first” approach should be emphasized over a “fistula-first” approach in AV access creation for incident hemodialysis patients older than 85 years.