Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

BACKGROUND: A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests. METHODS: Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks. RESULTS: SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES). CONCLUSION: Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

Association between milk consumption in middle age and frailty in later life: The Aichi Workers' cohort study.

AIM: Several studies have shown that dairy consumption in old age is effective in preventing frailty. However, there is a lack of evidence regarding the association between milk consumption during middle age and the development of frailty in old age. Therefore, we carried out an investigation to explore the association between milk consumption during middle age and development of frailty examined after over 15 years of follow up in a long-term cohort study in Japan. METHODS: We studied 265 participants aged 60-79 years (212 men and 53 women) in 2018, who participated in both the baseline survey in 2002 and the frailty assessment in 2018. The amount of milk consumption (g/day) at baseline was age- and energy-adjusted, and classified into three categories (no, low and high consumption: 0 g/day, ≤135.86 g/day, >135.86 g/day in men and 0 g/day, ≤126.44 g/day, >126.44 g/day in women). Odds ratios (OR) and 95% confidence intervals (CI) for prefrailty/frailty after adjusting for lifestyles at baseline, stratified by sex, were estimated using logistic regression analysis. RESULTS: The prevalence of prefrailty/frailty in 2018 was 37.7% and 28.3% in men and women, respectively. Milk consumption categories were inversely associated with the prevalence of prefrailty/frailty in men (OR 0.34, 95% CI 0.14-0.84 in low consumption; OR 0.31, 95% CI 0.10-0.95 in high consumption; P < 0.05), but not in women (OR 0.53, 95% CI 0.11-2.65; P = 0.44). CONCLUSIONS: In this study, milk intake in middle-aged men was inversely associated with the prevalence of prefrailty/frailty later in life. Geriatr Gerontol Int 2024; 24: 700-705.

Histotripsy - hype or hope? Review of innovation and future implications.

BACKGROUND: Histotripsy is a novel, ultrasound-based ablative technique that was recently approved by the Food and Drug Administration for hepatic targets. It has several promising additional theoretical applications that need to be further investigated. Its basis as a nonthermal cavitational technology presents a unique advantage over existing thermal ablation techniques in maximizing local effects while minimizing adjacent tissue destruction. This review discusses the technical basis and current preclinical and clinical data surrounding histotripsy. METHODS: This was a comprehensive review of the literature surrounding histotripsy and the clinical landscape of existing ablative techniques using the PubMed database. A technical summary of histotripsy's physics and cellular effect was described. Moreover, data from recent clinical trials, including Hope4Liver, and future implications regarding its application in various benign and malignant conditions were discussed. RESULTS: Preclinical data demonstrated the efficacy of histotripsy ablation in various organ systems with minimal tissue destruction when examined at the histologic level. The first prospective clinical trial involving histotripsy in hepatocellular carcinoma and liver metastases, Hope4Liver, demonstrated a primary efficacy of 95.5% with minimal complications (6.8%). This efficacy was replicated in similar trials involving the treatment of benign prostatic hypertrophy. DISCUSSION: In addition to the noninvasive ability to ablate lesions in the liver, histotripsy offers additional therapeutic potential. Early data suggest a potential complementary therapeutic effect when combining histotripsy with existing immunologic therapies because of the technology's theoretical ability to sensitize tumors to adaptive immunity. As with most novel therapies, the effect of histotripsy on the oncologic therapeutic landscape remains uncertain.

International comparison of availability for orphan drugs: focused on approved orphan drugs in South Korea.

Introduction: In this study, we aimed to comparatively analyse the indicators of availability to orphan drugs in South Korea, the United States of America, Europe Union, and Japan. Methods: For 169 drugs designated as orphan drugs in South Korea between 2012 and 2021, information on the drugs designated as orphan drugs from each jurisdiction was extracted by country. Then, the availability indicators (approval time, drug lag time, and designation gap) were analysed for the drugs approved in each jurisdiction. Results: The approval rate of drugs designated as orphan drugs were 11.22% and 6.31% in the USA and EU, respectively, which was lower than that of orphan drugs in South Korea and Japan. The highest number of approved drugs was in the USA (87 drugs), EU 27 drugs, Japan 22 drugs and Korea 21 drugs. Furthermore, the approval time significantly differed between South Korea and the other countries. South Korea had a significantly different drug lag time and designation gap compared with the USA and EU. Conclusion: Our findings show that to fundamentally improve the access to treatments for rare disease, a policy of regulatory science that can comprehensively support the early stages of research and development and commercialisation is needed.

Sex-Specific Susceptibility Loci Associated With Coronary Artery Aneurysms in Patients With Kawasaki Disease.

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is an acute vasculitis that primarily affects children under age 5 years. Approximately 20-25% of untreated children with KD and 3-5% of those treated with intravenous immunoglobulin therapy develop coronary artery aneurysms (CAAs). The prevalence of CAAs is much higher in male than in female patients with KD, but the underlying factors contributing to susceptibility to CAAs in patients with KD remain unclear. This study aimed to identify sex-specific susceptibility loci associated with CAAs in KD patients. METHODS: A sex-stratified genome-wide association study (GWAS) was performed using previously obtained GWAS data from 296 KD patients and a new replication study in an independent set of 976 KD patients by comparing KD patients without CAA (controls) and KD patients with aneurysms (internal diameter ≥5 mm) (cases). RESULTS: Six male-specific susceptibility loci, PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ (odds ratios [ORs], 2.25-9.98; p=0.00204-1.96×10-6), and 2 female-specific susceptibility loci, SMAD3 (OR, 4.59; p=0.00016) and IL1RAPL1 (OR, 4.35; p=0.00026), were significantly associated with CAAs in patients with KD. In addition, the numbers of CAA risk alleles additively contributed to the development of CAAs in patients with KD. CONCLUSIONS: A sex-stratified GWAS identified 6 male-specific (PDE1C, NOS3, DLG2, CPNE8, FUNDC1, and GABRQ) and 2 female-specific (SMAD3 and IL1RAPL1) CAA susceptibility loci in patients with KD.

Environmental risk score of multiple pollutants for kidney damage among residents in vulnerable areas by occupational chemical exposure in Korea.

This study aimed to develop an environmental risk score (ERS) of multiple pollutants (MP) causing kidney damage (KD) in Korean residents near abandoned metal mines or smelters and evaluate the association between ERS and KD by a history of occupational chemical exposure (OCE). Exposure to MP, consisting of nine metals, four polycyclic aromatic hydrocarbons, and four volatile organic compounds, was measured as urinary metabolites. The study participants were recruited from the Forensic Research via Omics Markers (FROM) study (n = 256). Beta-2-microglobulin (ß2-MG), N-acetyl-ß-D-glucosaminidase (NAG), and estimated glomerular filtration rate (eGFR) were used as biomarkers of KD. Bayesian kernel machine regression (BKMR) was selected as the optimal ERS model with the best performance and stability of the predicted effect size among the elastic net, adaptive elastic net, weighted quantile sum regression, BKMR, Bayesian additive regression tree, and super learner model. Variable importance was estimated to evaluate the effects of metabolites on KD. When stratified with the history of OCE after adjusting for several confounding factors, the risks for KD were higher in the OCE group than those in the non-OCE group; the odds ratio (OR; 95% CI) for ERS in non-OCE and OCE groups were 2.97 (2.19, 4.02) and 6.43 (2.85, 14.5) for ß2-MG, 1.37 (1.01, 1.86) and 4.16 (1.85, 9.39) for NAG, and 4.57 (3.37, 6.19) and 6.44 (2.85, 14.5) for eGFR, respectively. We found that the ERS stratified history of OCE was the most suitable for evaluating the association between MP and KD, and the risks were higher in the OCE group than those in the non-OCE group.

Inpatient Palliative Care and Healthcare Utilization Among Older Patients With Alzheimer's Disease and Related Dementia (ADRD) and High Risk of Mortality in U.S. Hospitals.

Background. Despite the potential of palliative care (PC) to enhance the quality of life for patients with advanced dementia, there is limited knowledge of its inpatient utilization patterns. This study investigated inpatient PC consultation utilization patterns and evaluated its impact on hospital length of stay (LOS) and medical costs among older patients diagnosed with Alzheimer's Disease and Related Dementia who were at a high risk of mortality (ADRD-HRM). Methods. Using the 2016-2019 National Inpatient Sample database, we conducted multivariable logistic regression analyses to identify individual and hospital characteristics influencing PC consultation utilization. We subsequently performed generalized linear models to estimate LOS (using Poisson distribution) and hospital charges (via log-transformation). Results. Our sample encompassed 965,644 hospital discharges (weighted n = 4,828,219) of patients aged 65 years and above with ADRD-HRM. Among them, 14.6% received inpatient PC. There was a notable uptrend in PC consultation utilization from 13.3% in 2016 to 16.3% in 2019 (p trend<.001). Factors positively influencing and associated with PC utilization included patients that are older, non-Hispanic White, with higher income, receiving care from teaching hospitals, and facilitated with greater bed capacity (all P < .05). Although patients who received PC were more likely to have 3.0% longer LOS (P < .001), they had 19.2% lower hospital charges (P < .001). Conclusions. PC substantially reduced hospital expenditures for older patients with ADRD-HRM, but the prevalence remained low at 14.6% in the study period. Future studies should explore the unmet needs of patients with lower sociodemographic status and those in rural hospitals to further increase their PC consultation utilization.

Associations between plasma metabolites and heavy metal exposure in residents of environmentally polluted areas.

Heavy metals are commonly released into the environment through industrial processes such as mining and refining. The rapid industrialization that occurred in South Korea during the 1960s and 1970s contributed significantly to the economy of the country; however, the associated mining and refining led to considerable environmental pollution, and although mining is now in decline in South Korea, the detrimental effects on residents inhabiting the surrounding areas remain. The bioaccumulation of toxic heavy metals leads to metabolic alterations in human homeostasis, with disruptions in this balance leading to various health issues. This study used metabolomics to explore metabolomic alterations in the plasma samples of residents living in mining and refining areas. The results showed significant increases in metabolites involved in glycolysis and the surrounding metabolic pathways, such as glucose-6-phosphate, phosphoenolpyruvate, lactate, and inosine monophosphate, in those inhabiting polluted areas. An investigation of the associations between metabolites and blood clinical parameters through meet-in-the-middle analysis indicated that female residents were more affected by heavy metal exposure, resulting in more metabolomic alterations. For women, inhabiting the abandoned mine area, metabolites in the glycolysis and pentose phosphate pathways, such as ribose-5-phosphate and 3-phosphoglycerate, have shown a negative correlation with albumin and calcium. Finally, Mendelian randomization(MR) was used to determine the causal effects of these heavy metal exposure-related metabolites on heavy metal exposure-related clinical parameters. Metabolite biomarkers could provide insights into altered metabolic pathways related to exposure to toxic heavy metals and improve our understanding of the molecular mechanisms underlying the health effects of toxic heavy metal exposure.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Successful Endovascular Management of Pseudoaneurysm following Transarterial Chemoembolization: A Case Report.

Background and Objectives: Transarterial chemoembolization (TACE) is a widely accepted treatment for hepatocellular carcinoma (HCC). Regarding TACE, arterial injuries, such as hepatic artery spasm or dissection, can also occur, although pseudoaneurysms are rare. We report a case of pseudoaneurysm following TACE. Materials and Methods: A 78-year-old man had been undergoing TACE for HCC in segment 8 of the liver for the past 5 years, with the most recent TACE procedure performed approximately 1 month prior. He presented to the emergency department with melena that persisted for 5 days. Computed tomography revealed a pseudoaneurysm in the S8 hepatic artery with hemobilia. Results: the pseudoaneurysm was successfully treated by N-Butyl-cyanoacrylate glue embolization. Conclusions: In patients that have undergone TACE presenting with melena and hemobilia identified on CT, consideration of hepatic artery pseudoaneurysm is crucial. Such cases can be safely and effectively treated with endovascular managements.

N-tert-butoxycarbonyl-methylenedioxymethamphetamine, an methylenedioxymethamphetamine derivative, exhibits rewarding and reinforcing effects by increasing dopamine levels.

An N-protected methylenedioxymethamphetamine (MDMA), N-tert-butoxycarbonyl-3,4-methylenedioxymethamphetamine (t-BOC-3,4-MDMA), contains tert-butoxycarbonyl and can remain undetected in the illicit drug market. It is a new type of precursor substance that is not a chemical intermediate and can be converted into a controlled substance, MDMA, by deprotection of the N-tert-butoxycarbonyl group. Categorization of this chemical into a precursor or psychotropic substance is an issue because it is an unprecedented precursor that could have misuse potential. Although MDMA causes rewarding and reinforcing effect through dopaminergic transmission, the misuse potential of t-BOC-3,4-MDMA has not yet been characterized. Here, we aim to evaluate the misuse potential of t-BOC-3,4-MDMA. The response to the drug at a dose of 5 mg/kg was determined by a climbing test, and its rewarding and reinforcing properties were assessed through conditioned place preference and self-administration tests. In the conditioned place preference test, intraperitoneal administration of t-BOC-3,4-MDMA (5 mg/kg) significantly altered place preference in mice. In the self-administration models, t-BOC-3,4-MDMA induced drug-taking behavior at the dose of 0.5 mg/kg/infusion (intravenous) during 2 hr sessions under fixed-ratio schedules in mice. In addition, microdialysis experiments verified that t-BOC-3,4-MDMA impacted the dopamine levels of the brain (striatum) of rats. These experimental results indicate that t-BOC-3,4-MDMA has a potential for misuse. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparison of Financial Hardship and Healthcare Utilizations Associated with Cancer in the United States Medicare Programs during the COVID-19 Pandemic.

BACKGROUND: In the United States, Medicare beneficiaries diagnosed with cancer often face significant financial challenges due to the expensive nature of cancer treatments and increased cost-sharing responsibilities. However, there is limited knowledge regarding the financial hardships and healthcare utilizations faced by those enrolled in Medicare Advantage (MA) compared to those in traditional fee-for-service Medicare (TM) during the COVID-19 pandemic. Our study aims to investigate the subjective financial hardships experienced by individuals enrolled in TM and MA and to determine whether these two Medicare programs exhibit differences in healthcare utilization during the pandemic. METHODS: We utilized data from the 2020-2022 National Health Interview Survey (NHIS), focusing on nationally representative samples of cancer survivors aged 65 or older. Financial hardship was categorized into three distinct groups: material (e.g., problems with medical bills), psychological (e.g., worry about paying), and behavioral (e.g., delayed care due to cost). Healthcare utilization included wellness visits (preventive care), emergency care services, hospitalizations, and telehealth. We used survey design-adjusted analysis to compare the study outcomes between MA and TM. RESULTS: Among a weighted sample of 4.4 million Medicare beneficiaries with cancer (mean age: 74.9), 76% were enrolled in MA plans. Cancer survivors with a college degree (59.3% vs. 49.8%) and high family income (38.2% vs. 31.1%) were more likely to enroll in MA plans. There were no significant differences in any material, psychological, or behavioral financial hardship domains between beneficiaries with MA and TM plans except forgone counseling due to cost. For healthcare utilization measures, cancer survivors in MA were more likely than those in TM to have flu vaccination (77.2% vs. 70.1%) and experience lower hospitalizations (16.0% vs. 20.0%). However, there were no differences in other health service utilizations between MA and TM. CONCLUSION: While no significant differences were observed in any materialized, psychological, or behavioral financial hardships, older cancer survivors enrolled in MA plans were more likely to receive vaccinations and lower hospitalization rates during COVID-19. Although other preventive or primary care visits (i.e., wellness visits) were higher, their difference did not reach statistical significance. As MA grows in popularity, it is essential to consistently monitor and evaluate the performance and outcomes of Medicare plans for cancer survivors as we navigate the post-pandemic landscape.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Colon cancer: the 2023 Korean clinical practice guidelines for diagnosis and treatment.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents.. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients' values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

MINocyclinE to Reduce inflammation and blood-brain barrier leakage in small Vessel diseAse (MINERVA): A phase II, randomized, double-blind, placebo-controlled experimental medicine trial.

INTRODUCTION: Cerebral small vessel disease (SVD) is a common cause of stroke/vascular dementia with few effective treatments. Neuroinflammation and increased blood-brain barrier (BBB) permeability may influence pathogenesis. In rodent models, minocycline reduced inflammation/BBB permeability. We determined whether minocycline had a similar effect in patients with SVD. METHODS: MINERVA was a single-center, phase II, randomized, double-blind, placebo-controlled trial. Forty-four participants with moderate-to-severe SVD took minocycline or placebo for 3 months. Co-primary outcomes were microglial signal (determined using 11C-PK11195 positron emission tomography) and BBB permeability (using dynamic contrast-enhanced MRI). RESULTS: Forty-four participants were recruited between September 2019 and June 2022. Minocycline had no effect on 11C-PK11195 binding (relative risk [RR] 1.01, 95% confidence interval [CI] 0.98-1.04), or BBB permeability (RR 0.97, 95% CI 0.91-1.03). Serum inflammatory markers were not affected. DISCUSSION: 11C-PK11195 binding and increased BBB permeability are present in SVD; minocycline did not reduce either process. Whether these pathophysiological mechanisms are disease-causing remains unclear. INTERNATIONAL CLINICAL TRIALS REGISTRY PORTAL IDENTIFIER: ISRCTN15483452 HIGHLIGHTS: We found focal areas of increased microglial signal and increased blood-brain barrier permeability in patients with small vessel disease. Minocycline treatment was not associated with a change in these processes measured using advanced neuroimaging. Blood-brain barrier permeability was dynamic but MRI-derived measurements correlated well with CSF/serum albumin ratio. Advanced neuroimaging is a feasible outcome measure for mechanistic clinical trials.

Intravascular imaging-guided percutaneous coronary intervention in patients with acute myocardial infarction and cardiogenic shock.

INTRODUCTION AND OBJECTIVES: There are no clinical data on the efficacy of intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI in patients with acute myocardial infarction (AMI) and cardiogenic shock. The current study sought to evaluate the impact of intravascular imaging-guided PCI in patients with AMI and cardiogenic shock. METHODS: Among a total of 28 732 patients from the nationwide pooled registry of KAMIR-NIH (November, 2011 to December, 2015) and KAMIR-V (January, 2016 to June, 2020), we selected a total of 1833 patients (6.4%) with AMI and cardiogenic shock who underwent PCI of the culprit vessel. The primary endpoint was major adverse cardiovascular events (MACE) at 1 year, a composite of cardiac death, myocardial infarction, repeat revascularization, and definite or probable stent thrombosis. RESULTS: Among the study population, 375 patients (20.5%) underwent intravascular imaging-guided PCI and 1458 patients (79.5%) underwent angiography-guided PCI. Intravascular imaging-guided PCI was associated with a significantly lower risk of 1-year MACE than angiography-guided PCI (19.5% vs 28.2%; HR, 0.59; 95%CI, 0.45-0.77; P<.001), mainly driven by a lower risk of cardiac death (13.7% vs 24.0%; adjusted HR, 0.53; 95%CI, 0.39-0.72; P<.001). These results were consistent in propensity score matching (HR, 0.68; 95%CI, 0.46-0.99), inverse probability weighting (HR, 0.61; 95%CI, 0.45-0.83), and Bayesian analysis (Odds ratio, 0.66, 95% credible interval, 0.49-0.88). CONCLUSIONS: In AMI patients with cardiogenic shock, intravascular imaging-guided PCI was associated with a lower risk of MACE at 1-year than angiography-guided PCI, mainly driven by the lower risk of cardiac death.

Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.

Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.

COVID-19 booster vaccine uptake and reduced risks for long-COVID: A cross-sectional study of a U.S. adult population.

Long-COVID (having symptoms lasting 3 months or longer post-infection) is an emerging public health concern, yet research on whether COVID-19 booster vaccines can mitigate this condition is limited. This study examined associations between booster uptake and long-COVID prevalence among U.S. adults. Data were analyzed from 8757 adults aged 18 years or older with a history of COVID-19 infection from the 2022 National Health Interview Survey. Weighted prevalence and logistic regression models examined relationships between self-reported COVID-19 booster vaccination status and long-COVID, adjusting for sociodemographics and health factors. 19.5 % reported experiencing long-COVID. Individuals receiving the COVID-19 booster vaccine had significantly lower adjusted odds of long-COVID (OR 0.75, 95 % CI 0.61-0.93) compared to unvaccinated individuals. Overall, these findings suggest that COVID-19 booster vaccination is associated with a reduced prevalence of long-COVID among the U.S. adult population, underscoring the importance of optimizing booster uptake to mitigate the long-term impacts of COVID-19.