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Aims Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH. Methods A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified. Results Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease. Conclusions Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Aims Mismatches between the risk status of a patient and coronary imaging data can lead to conflicting strategies to prevent a cardiovascular event. We evaluated whether statin use was associated with cardiovascular benefit in high-risk individuals whose coronary computed tomography angiography (CCTA) results showed normal coronary arteries. Methods Among asymptomatic individuals whose CCTA showed normal or near normal coronary arteries, 3,389 persons with high- or very-high-risk status were included in this retrospective study. After 1:2 propensity score matching, 906 individuals (302 new statin users and 604 controls; mean age 61 years; male 58%) were analysed. The primary outcome variable was major adverse cardiovascular and cerebrovascular events (MACCEs) that consisted of cardiovascular death, nonfatal myocardial infarction, coronary revascularisation, and nonfatal ischemic stroke. Results At a median follow-up of 5.8 years, 20 statin users and 17 controls (7.4 and 5.6 events/1,000 person-year, respectively; hazard ratio [HR) 1.04; p=0.92) experienced MACCE. Kaplan-Meier curves showed similar MACCE rates in both groups (p=0.91). In separate analyses for persons with normal (p=0.29) or near normal coronary arteries (p=0.67), MACCE rates did not differ between the groups. Age (HR 1.04; p=0.044), male sex (HR 3.06, p=0.018), and smoking (HR 2.87, p=0.019) were independently associated with MACCEs. In subgroup analyses, no significant factors affected the relationship between statin use and MACCEs. Conclusions Statin use was not associated with cardiovascular risk reduction in high-risk persons with normal or near normal coronary arteries. More individualised lipid-lowering therapy may benefit this population.

Protein phase separation in biological systems has captured the attention of scientists in the last decade; however, the main mechanism underlying protein phase separation in cells remains unclear. Biologists, physicists, and chemists have all tried to understand this important biological phenomenon, each using their own unique techniques and language. Each subject has its advantages in explaining protein phase separation; however, in this study, we find that the chemical language of molecular structure is the key to explaining the mechanism underlying protein phase separation. Using fluroescence microscopy and molecular dynamics, this study identifies small multivalently charged biomolecules, such as nucleoside triphosphate (negatively charged) and polyamine (positively charged), as important drivers of phase separation of highly charged proteins in cells.

Although there are many genetic loci in noncoding regions associated with vascular disease, studies on long noncoding RNAs (lncRNAs) discovered from human plaques that affect atherosclerosis have been highly limited. We aimed to identify and functionally validate a lncRNA using human atherosclerotic plaques. Human aortic samples were obtained from patients who underwent aortic surgery, and tissues were classified according to atherosclerotic plaques. RNA was extracted and analyzed for differentially expressed lncRNAs in plaques. Human aortic smooth muscle cells (HASMCs) were stimulated with oxidized low-density lipoprotein (oxLDL) to evaluate the effect of the identified lncRNA on the inflammatory transition of the cells. Among 380 RNAs differentially expressed between the plaque and control tissues, lncRNA HSPA7 was selected and confirmed to show upregulated expression upon oxLDL treatment. HSPA7 knockdown inhibited the migration of HASMCs and the secretion and expression of IL-1β and IL-6; however, HSPA7 knockdown recovered the oxLDL-induced reduction in the expression of contractile markers. Although miR-223 inhibition promoted the activity of Nf-κB and the secretion of inflammatory proteins such as IL-1β and IL-6, HSPA7 knockdown diminished these effects. The effects of miR-223 inhibition and HSPA7 knockdown were also found in THP-1 cell-derived macrophages. The impact of HSPA7 on miR-223 was mediated in an AGO2-dependent manner. HSPA7 is differentially increased in human atheroma and promotes the inflammatory transition of vascular smooth muscle cells by sponging miR-223. For the first time, this study elucidated the molecular mechanism of action of HSPA7, a lncRNA of previously unknown function, in humans., Atherosclerosis: Identifying noncoding RNA effect A long non-coding RNA (lncRNA) called HSPA7 promotes the development of atherosclerosis, plaque in arteries. Many atherosclerosis-related genetic loci are in noncoding regions of genome, but there has been an incomplete understanding of them. Sang-Hak Lee at Yonsei University College of Medicine, Seoul, South Korea, and co-workers set out to identify a lncRNA involved in atherosclerosis and investigate its mode of action. Comparison of aortic tissues allowed them to identify lncRNAs more abundant in atherosclerotic tissue but less in healthy tissue. Of the 380 lncRNAs identified, only HSPA7 reliably increased when aortic cells were treated with a trigger of atherosclerosis. Inhibiting HSPA7 restored normal function in vascular cells, decreasing migration and inflammation. Further investigation showed that HSPA7 blocks the activity of miR-223, a microRNA that suppresses inflammation. These results identify a potential therapeutic target for atherosclerosis.

PURPOSE Residual cardiovascular risk reduction by fenofibrate in patients with high serum triglyceride (TG) levels despite previous statin monotherapy is not well characterized. The purpose of this study was to evaluate the efficacy and safety of a combination of choline fenofibrate and statin in patients with inadequately controlled TG levels despite previous statin monotherapy. METHODS This prospective, multicenter, randomized, double-blind study was conducted in Korea. A total of 133 patients with controlled LDL-C but elevated TG levels, already receiving statin monotherapy, were enrolled in the study, which was conducted from July 2018 to December 2019. Patients were randomly assigned to receive combination therapy with choline fenofibrate and statin or statin monotherapy in a 1:1 ratio. After 8 weeks of treatment, the lipid profiles and safety parameters of the patients in the 2 groups were compared. FINDINGS The study included 127 patients (64 in the combination group and 63 in the control group) older than 19 years. After 8 weeks of therapy, mean serum TG levels significantly decreased from 269.8 to 145.5 mg/dL (P < 0.0001) in the combination therapy group, whereas no significant changes occurred in the statin monotherapy group (from 271.1 to 280.5 mg/dL). Contrarily, the mean serum HDLC levels significantly increased from 45.0 to 50.4 mg/dL (P = 0.0004) in the combination therapy group, whereas there were no significant changes in the monotherapy group (from 44.3 to 44.7 mg/dL). There were no additional serious adverse events in the combination therapy group compared with the statin monotherapy group. IMPLICATIONS The combination therapy using choline fenofibrate and statin was found to be effective in serum TG control and likely tolerable in patients with high TG levels despite statin monotherapy. A larger study, conducted for a longer duration, is needed to evaluate the effectiveness of this combination in reducing cardiovascular risk. ClinicalTrials.gov identifier: NCT03874260.

Background: Although biomechanical and clinical studies have reported adverse effects on the patellofemoral joint after medial open-wedge high tibial osteotomy (MOWHTO), there is a paucity of literature that describes outcomes longer than midterm follow-up. Purpose: We aimed to evaluate the mid- to long-term radiologic and clinical outcomes of the patellofemoral joint after MOWHTO and to assess whether radiologic deterioration of the patellofemoral joint affected clinical outcomes or survivorship after MOWHTO. Study Design: Case series; Level of evidence, 4. Methods: We retrospectively reviewed 170 knees that underwent MOWHTO and had a minimum 5-year follow-up. In radiologic evaluation, serial postoperative changes in the patellofemoral joint compared with the preoperative status were evaluated on the Merchant view according to the Kellgren-Lawrence grade. The American Knee Society (AKS) score, Knee injury and Osteoarthritis Outcome Score (KOOS), Kujala score, incidence of anterior knee pain, and survivorship were used to assess clinical outcomes. Using radiologic assessment of the patellofemoral joint, we divided the patients into a radiologic progression group and a radiologic nonprogression group to evaluate whether radiologic progression of patellofemoral arthritis affected long-term clinical outcomes and survivorship after MOWHTO. Results: The mean follow-up period was 96.3 months (range, 60-163 months). Arthritic progression of the patellofemoral joint on the Merchant view was observed in 44.9%, 56.3%, 66.0%, and 84.0% of the cases at 5, 7, 9, and 11 years, respectively. Clinical outcomes such as AKS scores and KOOS significantly improved after MOWHTO ( P < .001) at the latest follow-up. The incidence of anterior knee pain was 5.3% (9/170 knees). One knee (0.6%) underwent conversion to TKA due to progressive medial osteoarthritis, so the survival rate was 99.4% at a mean follow-up of 96.3 months. Despite patellofemoral degeneration over time, there were no significant differences in clinical outcomes or survivorship between patients with and without radiologic progression at the latest follow-up. Conclusion: Although degeneration of the patellofemoral joint was observed with time after MOWHTO, the related symptoms were minimal and arthritic changes in the patellofemoral joint did not affect the clinical outcomes or survivorship after MOWHTO over a mid- to long-term follow-up.

Genetic and medical insights from studies on cardioprotective phenotypes aid the development of novel therapeutics. This study identified genetic variants associated with supernormal coronary arteries using genome-wide association study data and the corresponding genes based on expression quantitative trait loci (eQTL).Study participants were selected from two Korean cohorts according to inclusion criteria that included males with high cardiovascular risk (Framingham risk score ≥ 14, 10-year risk ≥ 16%) but with normal coronary arteries (supernormal group) or coronary artery disease (control group). After screening 12,309 individuals, males meeting the supernormal phenotype (n=72) and age-matched controls (n=94) were enrolled. Genetic variants associated with the supernormal phenotype were identified using Firth's logistic regression, and eQTL was used to evaluate whether the identified variants influence the expression of particular genes in human tissues.Approximately 5 million autosomal variants were tested for association with the supernormal phenotype, and 10 independent loci suggestive of supernormal coronary arteries (p＜5.0 ×10This study identified genetic variants and eQTL genes associated with supernormal coronary arteries. These results suggest candidate genes representing potential therapeutic targets for coronary artery disease.

Background The factors affecting cardioprotective collateral circulation are still incompletely understood. Recently, characteristics, such as CpG methylation of cell-free DNA (cfDNA), have been reported as markers with clinical utility. The aim of this study was to evaluate whether cfDNA methylation patterns are associated with the grade of coronary collateral circulation (CCC). Result In this case–control study, clinical and angiographic data were obtained from 143 patients (mean age, 58 years, male 71%) with chronic total coronary occlusion. Enzymatic methyl-sequencing (EM-seq) libraries were prepared using the cfDNA extracted from the plasma. Data were processed to obtain the average methylation fraction (AMF) tables of genomic regions from which blacklisted regions were removed. Unsupervised analysis of the obtained AMF values showed that some of the changes in methylation were due to CCC. Through random forest preparation process, 256 differentially methylated region (DMR) candidates showing strong association with CCC were selected. A random forest classifier was then constructed, and the area under the curve of the receiver operating characteristic curve indicated an appropriate predictive function for CCC. Finally, 20 DMRs were identified to have significantly different AMF values between the good and poor CCC groups. Particularly, the good CCC group exhibited hypomethylated DMRs. Pathway analysis revealed five pathways, including TGF-beta signaling, to be associated with good CCC. Conclusion These data have demonstrated that differential hypomethylation was identified in dozens of cfDNA regions in patients with good CCC. Our results support the clinical utility of noninvasively obtained epigenetic signatures for predicting collateral circulation in patients with vascular diseases.

Some individuals exhibit discrepancies between risk classifications assessed using clinical factors and those obtained by vascular imaging. We aimed to evaluate whether statins provide clinical outcome benefits in patients classified as having low to moderate cardiovascular risk but with carotid plaque.This was a retrospective propensity score matching study. A total of 12,158 consecutive patients undergoing carotid ultrasound between January 2012 to February 2020 were screened. Individuals with low to moderate cardiovascular risk who were not currently recommended for statin therapy but had carotid plaques were included. Among 1,611 enrolled individuals, 806 (statin group: 403, control group: 403) were analyzed. The primary outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs: cardiovascular death, myocardial infarction, coronary revascularization, and ischemic stroke or transient ischemic attack) and all-cause mortality.During the median follow-up of 6.0 years, the incidence of MACCEs did not differ between the groups (6.1 and 5.7/1,000 person-years in the control and statin groups, respectively; adjusted hazard ratio [HR], 0.95; p=0.90). The incidence of all-cause mortality did not differ (3.9 and 3.9/1,000 person-years, respectively; adjusted HR, 1.02; p=0.97). Kaplan-Meier curves revealed similar rates of MACCEs (log-rank p=0.72) and all-cause mortality (log-rank p=0.99) in the 2 groups. Age and smoking were independent predictors of MACCEs. Subgroups exhibited no differences in clinical outcomes with statin use.Benefit of statin therapy was likely to be limited in low to moderate risk patients with carotid plaques. These results could guide physicians in clinical decision-making regarding cardiovascular prevention.

Self-assembly of AgPF

The aim of the current study was to investigate whether the impact of low-density lipoprotein-cholesterol (LDL-C) levels on cardiovascular risk is different between individuals with severe hypercholesterolemia and diabetes mellitus (DM) and those without DM.This study used the database of a National Health Insurance Service cohort of Korea. Among individuals who underwent health check-up, 2,261,332 were included and categorized into 3 groups with severe hypercholesterolemia,260, 225-259, and 190-224 mg/dL groups, and a control group (160 mg/dL). Risks of composite events (myocardial infarction [MI], coronary revascularization, and ischemic stroke) and total mortality were analyzed, according to the presence of DM.Of the study population, 5.2% had DM. During median follow-up of 6.1 years, the rates of composite events (/1,000 person-year) in non-DM and DM subjects were up to 5.66 and 8.92, respectively. Adjusted hazard ratios (aHRs) of the composite events ranged up to 3.11 and 1.44 in non-DM and DM groups, respectively (Although individuals with severe hypercholesterolemia had high cardiovascular risk when DM was present, the impact of LDL-C on the risk was attenuated in this population.

Brownian motion subject to a periodic and asymmetric potential can be biased by external, nonequilibrium fluctuations, leading to directional movement of Brownian particles. Sequence-dependent flexibility variation along double-stranded DNA has been proposed as a tool to develop periodic and asymmetric potentials for DNA binding of cationic nanoparticles with sizes below tens of nanometers. Here, we propose that repetitive stretching and relaxation of a long, double-stranded DNA molecule with periodic flexibility gradient can induce nonequilibrium fluctuations that tune the amplitude of asymmetric potentials for DNA-nanoparticle binding to result in directional transport of nanometer-sized particles along DNA. Realization of the proposed Brownian ratchet was proven by Brownian dynamics simulations of coarse-grained models of a single, long DNA molecule with flexibility variation and a cationic nanoparticle.

Investigating molecules in the gas phase is the only way to discover their intrinsic molecular properties; however, it is challenging to produce the gaseous phase of large-molecule chemicals. Thermal evaporation is typically used to convert molecules into gases, but it is still challenging to study ionic molecules in solutions in the gas phase. Electrospray ionization is one of the best methods to generate molecules in the gas phase, and it is uniquely capable of studying large biomolecules, including proteins. However, the molecular temperature required to study the spectroscopic properties of the molecules is very high. In this study, we developed a new, simple evaporation method using an ultrasonic nebulizer to obtain gas-phase molecules. Using this new equipment, we observed OH

Background: Although medial open-wedge high tibial osteotomy (MOWHTO) is the treatment of choice for patients with mild to moderate osteoarthritis with varus malalignment, concerns about inferior outcomes in patients with preoperative radiological kissing lesion (RKL) remain. Purpose: To compare the mid- to long-term clinical and radiological results and survivorship after MOWHTO in patients with versus without preoperative RKL. Study Design: Cohort study; Level of evidence, 3. Methods: Included were 122 knees in patients who underwent MOWHTO with a medial locked plate and had minimum 5-year follow-up data. The mean age at surgery was 55.9 years (range, 38-65 years), and the mean follow-up was 7.5 years (range, 5-12.8 years). All patients had undergone second-look arthroscopy around 2 years after MOWHTO. The knees were divided into an RKL group (n = 17) and no-RKL group (n = 105) based on preoperative standing radiographs. The authors compared postoperative American Knee Society (AKS) knee and function scores, range of motion, and improvements in AKS scores between groups, as well as hip-knee-ankle angle, medial proximal tibial angle, and joint-line convergence angle from preoperatively to postoperatively. Also compared were the degree of cartilage regeneration between first- and second-look arthroscopy and the survival rate after index surgery. Results: Preoperative AKS scores were significantly lower in the RKL group versus the no-RKL group (AKS knee, 79.6 ± 7.5 vs 83.8 ± 3.9, P = .037; AKS function, 68.8 ± 9.3 vs 76.0 ± 5.1, P = .006). Likewise, postoperative AKS scores were significantly lower in the RKL group versus the no-RKL group (AKS knee: 91.3 ± 4.2 vs 94.4 ± 1.6, respectively, P = .008; AKS function: 90.0 ± 10.0 vs 97.6 ± 4.5, respectively, P = .007). However, all patients had excellent postoperative AKS knee and function scores (>80). Moreover, there were no between-group differences in pre- to postoperative improvement in AKS scores, postoperative radiological changes, or grade of cartilage regeneration. The survival rates in the RKL and no-RKL groups were 100% and 97.1%, respectively ( P ≥ .999). Conclusion: Although the latest clinical scores were lower in the RKL group than in the no-RKL group, comparable results in postoperative clinical improvement, cartilage regeneration, and survivorship were observed in patients with RKL at mid- to long-term follow-up.

Correction for ‘Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules’ by Minchae Kang et al., Soft Matter, 2022, 18, 3313–3317, https://doi.org/10.1039/D2SM00384H.

Mucoid degeneration (MD) of the anterior cruciate ligament (ACL) is a well-recognized pathology characterized by the degradation of collagen fibers and infiltration of a mucoid-like substance. This study is to determine the anatomical associated factors for MD-ACL using radiographic and magnetic resonance imaging (MRI).This was a retrospective study on patients who had undergone knee arthroscopy between 2011 and 2020. The patients with MD-ACL were defined and enrolled by the MRI and arthroscopy. Eventually, 52 patients in the MD-ACL group (group 1) and 52 patients in the control group (group 2) were enrolled, following sex and age matching. Radiologic evaluation included the assessment of Kellgren-Lawrence (K-L) grade, mechanical hip-knee-ankle (HKA) angle, posterior tibial slope (PTS) angle, and Insall-Salvati ratio. The notch width index and transverse notch angle were measured on MRI, and the grade of trochlear dysplasia was defined. Logistic regression analysis, receiver operating characteristic (ROC) curves, and area under curve (AUC) were performed.The ROM was significantly decreased in group 1, whereas the PTS angle was significantly larger in group 1. Combined ganglion cysts of ACL were found in 42/52 patients (80.7%) in group 1. The risk of MD-ACL was associated with a steeper PTS angle, increased Insall-Salvati ratio, male sex, higher K-L grade, and decreased transverse notch angle and notch width index. The cutoff values in ROC analysis were found to be ≤ 28.27% for the notch width index (AUC, 0.849; p 0.001), 12.2° for the PTS angle (AUC, 0.765; p 0.001), and ≤ 47.4° for the transverse notch angle (AUC, 0.711; p 0.001), but not significant for Insall-salvati ratio.A steeper PTS angle, decreased notch width index, and transverse notch angle are significantly associated with the presence of MD-ACL. These factors should be considered during diagnosis or when determining the treatment strategy for symptomatic MD-ACL patients.Level IIIb.

Valvular inflammation triggered by hyperlipidemia has been considered as an important initial process of aortic valve disease; however, cellular and molecular evidence remains unclear. Here, we assess the relationship between plasma lipids and valvular inflammation, and identify association of low-density lipoprotein with increased valvular lipid and macrophage accumulation. Single-cell RNA sequencing analysis reveals the cellular heterogeneity of leukocytes, valvular interstitial cells, and valvular endothelial cells, and their phenotypic changes during hyperlipidemia leading to recruitment of monocyte-derived MHC-IIhi macrophages. Interestingly, we find activated PPARγ pathway in Cd36+ valvular endothelial cells increased in hyperlipidemic mice, and the conservation of PPARγ activation in non-calcified human aortic valves. While the PPARγ inhibition promotes inflammation, PPARγ activation using pioglitazone reduces valvular inflammation in hyperlipidemic mice. These results show that low-density lipoprotein is the main lipoprotein accumulated in the aortic valve during hyperlipidemia, leading to early-stage aortic valve disease, and PPARγ activation protects the aortic valve against inflammation.

Aims The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs. Methods and results In human tissues, human umbilical artery ECs, and mouse models for loss of function and gain of function of PTP4A1, we conducted histological analysis, immunostaining, laser-captured microdissection assay, lentiviral infection, small interfering RNA transfection, quantitative real-time PCR and reverse transcription-PCR, as well as luciferase reporter gene and chromatin immunoprecipitation assays. Short hairpin RNA-mediated knockdown of PTP4A1 and overexpression of PTP4A1 in ECs indicated that PTP4A1 is critical for inhibiting the expression of cell adhesion molecules (CAMs). PTP4A1 increased the transcriptional activity of upstream stimulatory factor 1 (USF1) by dephosphorylating its S309 residue and subsequently inducing the transcription of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3/A20) and the inhibition of NF-κB activity. Studies on Ptp4a1 knockout or transgenic mice demonstrated that PTP4A1 potently regulates the interleukin 1β-induced expression of CAMs in vivo. In addition, we verified that PTP4A1 deficiency in apolipoprotein E knockout mice exacerbated high-fat high-cholesterol diet-induced atherogenesis with upregulated expression of CAMs. Conclusion Our data indicate that PTP4A1 is a novel negative regulator of vascular inflammation by inducing USF1/A20 axis-mediated NF-κB inactivation. Therefore, the expression and/or activation of PTP4A1 in ECs might be useful for the treatment of vascular inflammatory diseases.

Angiotensin-converting enzyme inhibitors (ACEIs) are medications generally prescribed for patients with high cardiovascular risk; however, they are suboptimally used due to frequent adverse events (AEs). The present study aimed to identify and replicate the genetic variants associated with ACEI-related AEs in the Korean population.A two-stage approach employing genome-wide association study (GWAS)-based discovery and replication through target sequencing was used. In total, 1300 individuals received ACEIs from 2001 to 2007; among these, 228 were selected for GWAS. An additional 336 patients were selected for replication after screening 1186 subjects treated from 2008 to 2018. Candidate genes for target sequencing were selected based on the present GWAS, previous GWASs, and data from the PharmGKB database. Furthermore, association analyses were performed between no AE and AE or cough groups after target sequencing.Five genes, namelySeveral variants, including novel and known variants, were successfully replicated and found to have associations with ACEI-related AEs. These results provide rare and clinically relevant information for safer use of ACEIs.

Background There is increasing Interest in bio-prosthetic MVD as recent advances in transcatheter MV interventions, but there is limited data. Objectives The aim of this study was to identify the factors determining mitral valve (MV) dysfunction (MVD) in patients who underwent MV replacement with bio-prosthetic valves. Also, we sought to investigate clinical outcomes in patients with bio-prosthetic MVD. Methods A total of 233 patients underwent surgical bio-prosthetic MV replacement between June 1996 and May 2015. Finally, 226 patients (mean age 66.9±11.5 years, 74.3% of women) were analyzed, excluding patients who followed-up for less than 5 years and patients whose baseline or follow-up echocardiography could not be analyzed. Clinical, echocardiographic, and laboratory data were collected early after the surgery and during follow-up. MVD was defined as an increase in mean gradient ≥5 mmHg with leaflet motion limitation and/or newly developed MV regurgitation during follow-up. Clinical outcome was defined as a composite of cardiovascular death, redo MV surgery or intervention, and hospitalization for heart failure. Results During a median of 102.0 months (interquartile range 72.0 to 132.0 months), 65 patients (28.8%) revealed MVD. 8 (12.3%) patients revealed predominant MV obstruction, and 57 (87.7%) showed predominant MV regurgitation. Factors associated with bio-prosthetic MVD by multivariate regression analysis were young age at operation (hazard ratio 0.97, 95% CI 0.95–0.99, p=0.001), end-stage renal disease (hazard ratio 4.29, 95% CI 1.45–12.71, p=0.007), elevated mean diastolic pressure gradient>5.5 mmHg across the bio-prosthetic MV early after operation (hazard ratio 1.86, 95% CI 0.97–3.74, p=0.063) and anemia after operation (hazard ratio 0.84, 95% CI 0.74–0.95, p=0.007). However, the presence of hypertension, dyslipidemia, or porcine bio-prosthesis was not related to the bio-prosthetic MVD. Kaplan-Meier curves revealed significant differences in event-free survivals for the occurrence of bio-prosthetic MVD according to each factor (Figure 1). Patients with bio-prosthetic MVD showed significantly poor clinical outcomes compared with those without bio-prosthetic MVD (event-free survival 43.1% vs. 91.9%, log-rank p Conclusions Young age at operation, end-stage renal disease, elevated mean pressure gradient early after the operation, and anemia after operation were associated with bio-prosthetic MVD in patients who underwent bio-prosthetic MV replacement. Funding Acknowledgement Type of funding sources: None.

The sclera is the opaque white tissue that covers the sphere of the human eye, and this causes a complex nonlinear deformation of the vessel pattern in the sclera as the eyes move. Over the last decade, although the blood vessels of the sclera have been investigated for use as a biometric modality, very little research has been undertaken on feature extraction and matching based on this anatomical structure. To address this problem, we propose a new local spherical structure (LSS) that incorporates a vessel shape feature (VSF) to represent the geometry and texture feature of the vessel pattern. The key ideas in this work are the designs of the VSF and the LSS, which are based on the fact that the vessels lie below a sphere-shaped sclera. To create the proposed VSF, a Harris corner detector is used to extract interest points, each of which is encoded into a normalized polar histogram that represents the shape of a vessel. These points are then projected onto the surface of a sphere, and we design an LSS to represent the topological relationships between each of the points, derived from the arc distance. In the matching step, we adopt a coarse-to-fine procedure that enables a fast similarity comparison between two point pairs using the VSF and the LSS. The final matching score is obtained by combining the number of matched pairs, the total number of interest points, and the similarity. Various experiments were conducted on the UBIRIS.v1 and UTIRIS databases, the latter of which was more challenging. The proposed method showed promising performance, as it yielded an error rate equal to those of other feature extraction and matching methods. Our findings suggest that the proposed approach not only outperforms the state-of-the-art methods of sclera recognition but also illustrates how to address the issue of nonlinear deformation of the vessel pattern based on the anatomical structure of the human eye.