Postoperative Decrease in Bone Marrow Lesion Associated With Better Clinical Outcomes Following Medial Open-Wedge High Tibial Osteotomy.

PURPOSE: To assess serial changes of preoperative bone marrow lesion (BML) following medial open-wedge high tibial osteotomy (MOWHTO) up to 2 years and evaluate whether postoperative change of BML affected patient-reported outcome measures (PROMs) at 2 years' follow-up. Factors related to the postoperative changes in BML also were evaluated. METHODS: The current study retrospectively assessed prospectively collected data of consecutive patients between December 2016 and March 2018 who underwent MOWHTO for symptomatic knee osteoarthritis with varus malalignment (≥5°) and a minimum 2-year follow-up. Serial magnetic resonance imaging scans at preoperative and postoperative 3, 6, 18, and 24 months were performed, and the extent of BML was evaluated consecutively using 2 validated methods. Clinically, preoperative and postoperative PROMs and their achievement of minimal clinically important difference values were evaluated. The associations of the extent of BMLs with PROMs at each follow-up period over time were analyzed using a linear mixed model. Furthermore, factors related to the postoperative changes of BML were assessed. RESULTS: Of 26 patients, 21 (80.8%) had preoperative BML at medial femoral and tibial condyles. The postoperative decrease in BML was noted in 17 (81.0%) and 18 (85.7%) at medial femoral and tibial condyles. The BML decreased at postoperative 3 months and, thereafter, the extent of BML gradually reduced until postoperative 24 months. The proportion of patients achieved minimal clinically important difference was 84.6% for total Western Ontario and McMaster Universities Osteoarthritis Index scores and 80.8%, 76.9%, and 84.6% for KOOS symptom, pain, and activity of daily living subscales. Postoperative decrease in BML was significantly associated with better PROMs over postoperative 24 months. Furthermore, normo-correction (2°-5° valgus) was a significant factor for decreased BML following MOWHTO. CONCLUSIONS: Preoperative BML gradually decreased with time following MOWHTO, and the postoperative decrease in BML related with better PROMs over postoperative 24 months. Moreover, postoperative valgus alignment was a significant factor relating the postoperative decrease of BML. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review.

PURPOSE: There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin. MATERIALS AND METHODS: A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies. RESULTS: Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; p=0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; p=0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; p=0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups. CONCLUSION: This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin.

Statin therapy in individuals with intermediate cardiovascular risk.

BACKGROUND: As intermediate cardiovascular risk group accounts for a large part of the total population, determining appropriate cholesterol target in this population is critical. Herein, we investigated the optimal low-density lipoprotein cholesterol (LDL-C) level in individuals with intermediate cardiovascular risk after statin therapy. METHODS: This was a nationwide observational and validation cohort study (median duration of follow-up: 7.5 and 8.7 years, respectively), using data from the Korean National Health Insurance Service and a tertiary hospital database. Among individuals who underwent regular health examinations, those with ≥2 cardiovascular risk factors except diabetes mellitus, LDL-C 100-189 mg/dL, and newly used statins were enrolled. Of the 358,694 screened people, 57,594 met the inclusion criteria, of whom 27,793 were finally analyzed. The study population was stratified according to post-treatment LDL-C levels as follows: <100, 100-119, 120-139, and ≥ 140 mg/dL. The primary outcome variable was composite cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke). From the patients screened of Severance Hospital cohort, 1859 meeting inclusion criteria were used for validation. RESULTS: The rates of composite events ranged from 7.74 to 9.10 (mean 8.38)/1000 person-years in the three lower LDL-C groups. Adjusted hazard ratios (aHRs) ranged from 0.78 to 0.95 in the three groups with lower LDL-C, and a lower event risk was more evident in the groups that achieved LDL-C levels <120 mg/dL (p = 0.001-0.009). The total mortality risk did not differ between groups. In the validation cohort, the mean rate of composite events was 10.83/1000 person-years. aHRs ranged from 0.52 to 0.78 in the groups with lower LDL-C, and a lower risk was more obvious in patients who achieved LDL-C levels <100 mg/dL (p = 0.006-0.03). CONCLUSIONS: Individuals with intermediate cardiovascular risk who achieved LDL-C levels <120 mg/dL after statin therapy had lower event risk. This result provides clinically useful evidence on target LDL-C levels in this population.

Influence of Previous Arthroscopic Meniscectomy on Midterm to Long-term Outcomes After Medial Open-Wedge High Tibial Osteotomy.

Background: Few studies have evaluated the clinical and radiological outcomes of medial open-wedge high tibial osteotomy (MOWHTO) in patients who had previously undergone arthroscopic meniscectomy. Purpose: To verify whether previous arthroscopic meniscectomy affects the clinical and radiological outcomes of MOWHTO. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 183 consecutive knees that underwent MOWHTO and had a minimum 5 years of follow-up were retrospectively reviewed. We compared the preoperative and postoperative clinical and radiological data of 32 knees with a history of meniscectomy (previous meniscectomy group) to 151 control knees without a history of meniscectomy. Cartilage status was also compared at first- and second-look arthroscopic surgery according to the International Cartilage Repair Society grading system. Failure was defined as conversion to total knee arthroplasty or revision MOWHTO. On subgroup analysis, the previous meniscectomy group was divided into 2 subgroups based on the time from meniscectomy to MOWHTO (<3 vs ≥3 years). Results: The mean age at the time of surgery was 55.9 years (range, 38-70 years), and the mean follow-up period was 86.2 months (range, 60-164 months). The mean time between meniscectomy and MOWHTO was 48.9 months (range, 5-156 months), and all meniscectomy procedures were performed on the medial side. Preoperative patient characteristics were similar between the study groups. Clinical and radiological outcomes were not significantly different between the groups at the latest follow-up, and no significant between-group differences were observed regarding postoperative cartilage status on arthroscopic examination. One knee in the control group underwent conversion to total knee arthroplasty at 7 years postoperatively for arthritic progression. Subgroup analysis of the previous meniscectomy group indicated no significant differences in clinical outcomes based on the time from meniscectomy to MOWHTO. Conclusion: Based on the results, a history of meniscectomy did not adversely affect the midterm to long-term outcomes of MOWHTO. Furthermore, the time between previous meniscectomy and MOWHTO was not associated with the clinical outcomes of MOWHTO.

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

C-reactive protein accelerates DRP1-mediated mitochondrial fission by modulating ERK1/2-YAP signaling in cardiomyocytes.

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRPinduced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage. [BMB Reports 2023; 56(12): 663-668].

Association between frailty and physical performance in older patients with heart failure.

BACKGROUND: Frailty is an issue in patients with heart failure (HF). A Korean version of the frailty scale (K-FRAIL) has been developed. HYPOTHESIS: We aimed to analyze the relationship between the K-FRAIL scale and physical performance in patients with HF. METHODS: This study included 142 patients with HF aged ≥65 years from a single center. Muscular fitness was assessed using the handgrip test and knee extensor strength measurement. Aerobic capacity was assessed using the cardiopulmonary exercise test and 6-min walk test (6MWT). Frailty was assessed using the K-FRAIL questionnaire. RESULTS: Peak VO2 and 6MWT scores significantly decreased as frailty worsened, but handgrip and knee extensor strength did not. In the multivariate analysis, peak VO2 (ß = -.31; p = .002) and 6MWT score (ß = -.38; p < .001) showed significant inverse associations with the K-FRAIL score. Based on the receiver operating characteristic curve analysis, the cut-off values of peak VO2 (hazard ratio, 5.08; p = .023) and 6MWT (hazard ratio, 3.99; p = .020) were independent predictors of frailty. CONCLUSION: In older patients with HF, physical performance correlates with the degree of frailty. The K-FRAIL scale is correlated with the peak VO2 and 6MWT.

Clinical and MRI Outcomes of Repaired Peripheral Longitudinal Tears of the Posterior Horn of the Medial Meniscus With ACL Reconstruction: Results According to Tear Size.

Background: Arthroscopic repair of longitudinal tears in the medial meniscal posterior horn (MMPH) has been reported to result in high rates of meniscal healing when performed alongside anterior cruciate ligament reconstruction (ACLR). However, studies that have focused on longitudinal tears and their impact on clinical outcomes after arthroscopic repair are insufficient. Purpose: To investigate the clinical outcome and healing status after concomitant arthroscopic ACLR and repair of MMPH peripheral longitudinal tears, with respect to the tear length. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 263 patients who underwent concurrent arthroscopic suture repair of longitudinal tears of the MMPH and ACLR were enrolled. All patients had 2-year postoperative magnetic resonance imaging (MRI) evaluations, and 61% of patients underwent a second-look arthroscopy. The exclusion criteria were partial meniscectomies and multiligament injuries. Patients were assessed pre- and postoperatively for clinical scores, amount of anterior translation, grade of pivot shift, and presence of meniscal tear extension. According to the length of longitudinal tears, patients were classified into 2 groups: (1) patients with tears that were located in the posterior compartment and (2) patients with tears that extended to the midbody of the meniscus. Binary stepwise logistic regression analysis was used to evaluate the risk factors for unhealed menisci as identified by MRI. Results: A total of 83 patients were included in this study-52 patients (group 1) had MMPH tears without tear extension and 31 patients (group 2) had MMPH tears with tear extension. There were no differences in outcomes between the groups, including the healing rate after meniscal repair (P > .05). Based on postoperative MRI scans, 67 patients (80.7%) were categorized as completely healed and 16 patients (19.3%) as unhealed. There were no significant differences between the completely healed and unhealed groups in outcomes or the rate of preoperative midbody tear extension. Higher body mass index and lower preoperative Lysholm scores were identified as risk factors for unhealed menisci. Conclusion: Overall, the rate of complete healing of MMPH tears repaired concomitantly with ACLR was 80.7% (67/83), and midbody tear extension did not affect the healing rate of the repaired meniscus. Results indicate that suture repair for unstable MMPH tears should be considered regardless of tear size.

Ramp lesion in anterior cruciate ligament injury: a review of the anatomy, biomechanics, epidemiology, and diagnosis.

Ramp lesions, commonly observed in patients with anterior cruciate ligament (ACL) injuries, have been previously defined as longitudinal tears around the meniscocapsular junction. However, the definitions and interpretations of ramp lesions have varied, emphasizing the need to confirm their presence before surgery and the importance of direct visualization using arthroscopy. Recent histological studies have reported new findings on ramp lesions, shedding light on their attachment mechanisms. The anatomical structures around the ramp lesion, such as the posterior horn of medial meniscus (PHMM), semimembranosus (SM), posteromedial (PM) capsule, and meniscotibial ligament (MTL), were assessed regarding how these structures could be attached to each other. The studies of ramp lesions have also contributed to the progression of biomechanical studies explaining the cause and effects of ramp lesions. Ramp lesion has been proven to stabilize the anteroposterior (AP) instability of ACL. In addition, various laboratory studies have demonstrated the relationship between rotational instability of the knee joint and ramp lesions. The analysis of risk factors of ramp lesion helped to understand the injury mechanism of the lesion. Many authors have evaluated the prevalence of ramp lesions in patients with ACL injuries. The development of arthroscopy techniques has influenced the outcomes of ACL reconstruction with the easy detection of ramp lesions. This review article aims to analyze the past findings and recent advancements in anatomical, biomechanical, and epidemiological studies of ramp lesions in patients who underwent ACL reconstruction, and provide various perspectives ramp lesions in patients with ACL reconstruction.

A randomized trial of genotype-guided perindopril use.

OBJECTIVE: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension. METHODS: After screening 120 patients and randomization, 68 were assigned to genotyping ( n  = 41) and control ( n  = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event. RESULTS: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P  = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P  = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P  = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P  = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups. CONCLUSION: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).

The Association Between On-treatment Ambulatory Central Blood Pressure and Left Ventricular Reverse Remodeling in Heart Failure With Reduced Ejection Fraction.

Background and Objectives: Compared to office blood pressure (OBP), central blood pressure (CBP) and ambulatory blood pressure (BP) are known to be better markers for predicting cardiovascular events. We evaluated the association between left ventricular reverse remodeling (LVRR) and ambulatory CBP in heart failure with reduced ejection fraction (HFrEF). Methods: This study retrospectively analyzed 93 patients who performed ambulatory CBP and brachial BP (BBP) monitoring from 2018 to 2020 within 1 year after diagnosis of HFrEF at a single tertiary center. We analyzed the association between on-treatment ambulatory BPs and LVRR on follow-up echocardiography. Results: The mean age of participants was 59 years; 65.6% were men; mean LVEF was 29%. Ambulatory BP and follow-up echocardiography were done at 143 days (interquartile range [IQR], 64-267) and 454 days (IQR, 281-600) after diagnosis of HF, respectively. Baseline OBP was not different between 2 groups, but ambulatory systolic CBP was significantly higher in the LVRR group than the non-LVRR group (p=0.005). Systolic OBP (odds ratio [OR], 1.029; confidence interval [CI], 1.004-1.055; p=0.026), 24-hour ambulatory systolic CBP (OR, 1.048; CI, 1.015-1.082; p=0.004), and 24-hour ambulatory systolic BBP (OR, 1.049; CI,1.017-1.082; p=0.003) were associated with LVRR. Compared to ambulatory systolic CBP of 110-119 mmHg, 90-99 mmHg showed lower OR for LVRR. Conclusions: Low on-treatment ambulatory systolic CBP was closely related to a lower likelihood of LVRR in HFrEF than the normal range. Ambulatory CBP measured during treatment of patients with HFrEF appears to be useful in predicting outcomes.

Hepatic Cdkal1 deletion regulates HDL catabolism and promotes reverse cholesterol transport.

BACKGROUND AND AIMS: Associations between CDKAL1 variants and cholesterol efflux capacity (CEC) have been reported. This study aimed to investigate the effects of Cdkal1 deficiency on high-density lipoprotein (HDL) metabolism, atherosclerosis, and related pathways. METHODS: Lipid and glucose metabolic profiles, CEC, and in vivo reverse cholesterol transport (RCT) were compared in liver-specific Alb-Cre:Cdkal1fl/fl and Cdkal1fl/fl mice. Aortic atherosclerosis was compared in Apoe-/-Alb-Cre:Cdkal1fl/fl and Apoe-/- mice fed high-fat diets. HDL subclasses and mediators of HDL metabolism from Alb-Cre:Cdkal1fl/fl mice were examined. RESULTS: HDL-cholesterol level tended to be higher in the Alb-Cre:Cdkal1fl/fl mice (p = 0.050). Glucose and other lipid profiles were similar in the two groups of mice, irrespective of diet. The mean CEC was 27% higher (p = 0.007) in the Alb-Cre:Cdkal1fl/fl mice, as were the radioactivities of bile acids (mean difference 17%; p = 0.035) and cholesterol (mean difference 42%; p = 0.036) from faeces. The radioactivity tendency was largely similar in mice fed a high-fat diet. Atherosclerotic lesion area tended to be smaller in the Apoe-/-Alb-Cre:Cdkal1fl/fl mice than in the Apoe-/- mice (p = 0.067). Cholesterol concentrations in large HDLs were higher in the Alb-Cre:Cdkal1fl/fl mice (p = 0.024), whereas in small HDLs, they were lower (p = 0.024). Endothelial lipase (mean difference 39%; p = 0.002) and hepatic lipase expression levels (mean difference 34%; p < 0.001) were reduced in the Alb-Cre:Cdkal1fl/fl mice, whereas SR-B1 expression was elevated (mean difference 35%; p = 0.007). CONCLUSIONS: The promotion of CEC and RCT in Alb-Cre:Cdkal1fl/fl mice verified the effect of CDKAL1 seen in human genetic data. These phenotypes were related to regulation of HDL catabolism. This study suggests that CDKAL1 and associated molecules could be targets for improving RCT and vascular pathology.

Risk factors for residual popliteal cyst after arthroscopic decompression and cystectomy: Associated with degenerative cartilage lesions.

BACKGROUND: In previous studies, good results have been reported after arthroscopic treatment of popliteal cysts and concomitant intra-articular pathology. However, only a few studies have reported the associated factors with residual popliteal cysts. The aim of this study was to examine the clinical and radiographic outcomes and investigate the factors associated with the recurrence of popliteal cyst after arthroscopic cyst decompression and cyst wall resection. HYPOTHESIS: The authors hypothesized that residual popliteal cyst after arthroscopic decompression and cystectomy would be associated with degenerative cartilage lesions. PATIENTS AND METHODS: From December 2010 to December 2018, 54 patients with popliteal cysts were treated with arthroscopic decompression and cyst wall resection through an additional posteromedial cystic portal. Magnetic resonance imaging (MRI) or ultrasonography was used to observe whether the popliteal cyst had disappeared or decreased. The maximum diameter of the popliteal cyst was measured after surgery. The patients were classified into the disappeared and reduced groups according to the treatment outcome. Age, sex, symptom duration, preoperative degenerative changes based on the Kellgren-Lawrence (K-L) grade, cartilage lesions according to the International Cartilage Repair Society (ICRS) grades, synovitis, functional outcomes, and associated intra-articular lesions were compared between the two groups. The functional outcome was evaluated on the basis of the Rauschning and Lindgren knee score. The study included 22 men and 32 women, with mean age of 49.6 years (range, 5-82 years). According to the ICRS grade system, 28 (51.8%) patients had grade 0 to II, 26 (48.2%) patients had grade III to IV. RESULTS: Follow-up radiographic evaluation revealed that the cyst had completely disappeared in 20 patients (37%) and reduced in size in 34 (63%). The mean cyst size was decreased significantly from 5.7cm (range, 1.7-15cm) to 1.7cm (range, 0-6.4cm), and the Rauschning and Lindgren knee score showed improved clinical features in all the patients. Between the disappeared and reduced groups, the presence of degenerative cartilage lesions (p=0.022, odds ratio 8.702, 95% confidence interval: 1.368-55.362) showed statistically significant differences. DISCUSSION: Through the posteromedial cystic portal, cysts were completely removed in approximately 40% of patients, and the size was reduced in 60% of patients. Presence of degenerative cartilage lesion represents an associated risk factor for residual popliteal cyst. These findings could be helpful in ensuring explaining poor prognostic factors. LEVEL OF EVIDENCE: IIIb; retrospective cohort study.

Correction: Aggregation or phase separation can be induced in highly charged proteins by small charged biomolecules.

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.

Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation.

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 1ß-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.

Radiologic findings associated with mucoid degeneration of the anterior cruciate ligament.

INTRODUCTION: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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 OF EVIDENCE: Level IIIb.

Genetic Variants Associated with Supernormal Coronary Arteries.

AIMS: 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). METHODS: 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. RESULTS: Approximately 5 million autosomal variants were tested for association with the supernormal phenotype, and 10 independent loci suggestive of supernormal coronary arteries (p＜5.0×10-5) were identified. The lead variants were seven intergenic single-nucleotide polymorphisms (SNPs), including one near PBX1, and three intronic SNPs, including one in PPFIA4. Of these variants or their proxies, rs9630089, rs6427989, and rs4984694 were associated with expression levels of SLIT1 and ARHGAP19, PPFIA4, and METTL26 in human tissues, respectively. These eQTL results supported their potential biological relevance. CONCLUSIONS: This 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.

Brownian ratchet for directional nanoparticle transport by repetitive stretch-relaxation of DNA.

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.