Yeungnam University Medical Center

Sung S., Seo M., Park W., Lim Y., Park S., Lee G.W.

Early diagnosis and timely management are critical for determining disease outcomes and prognoses. To date, certain methods for developing disease-specific biomarkers have been reported; however, strategies for musculoskeletal disease-specific biomarker development have rarely been studied. Recent studies have highlighted the potential application of extracellular vesicles (EVs) as disease-specific biomarkers. EVs encapsulate proteins, lipids, messenger RNAs, and microRNAs derived from their cellular origin; these constituents remain stable within the EVs and can traverse the blood–brain barrier. Because of these distinctive characteristics, EVs have been actively investigated as diagnostic tools for various conditions, including cancer, inflammatory diseases, and musculoskeletal disorders. Although EVs have many advantages for biomarker development, they have not yet been fully researched in the context of musculoskeletal pathologies. The current review aimed to highlight the potential of EVs in the development of disease-specific biomarkers, summarize the processes of EV biomarkers, and discuss current limitations and future perspectives of EVs as biomarkers.

Son W.S., Lim E.J., Kim B., Choi W., Cho J., Oh J.

OBJECTIVES: To compare the consolidation quality between the anteromedial aspect of regenerated bone (AMRB) and the other areas of regenerated bone (TORB) following the induced membrane technique (IMT) for managing critical-sized tibial shaft bone defects, and determine the factors affecting consolidation quality in the AMRB. METHODS: Design: Retrospective comparative study. Setting: Academic Level I trauma center. Patients Selection Criteria: Included were patients who underwent IMT with only an intramedullary nail for tibial shaft segmental defects and serial computed tomography immediately, 6 months, and 1 year postoperatively. Outcome Measures and Comparisons: Comparison were made of regenerative bone volume, density, and corticalization between AMRB and TORB. RESULTS: This study enrolled 37 patients with a mean age of 47.7 years (range 20−79). Twenty-eight (75.7%) patients were men. Postoperatively, the AMRB exhibited significantly more negative volumetric change than TORB at 0–1 year (−20.01% ± 25.59% vs. −13.32% ± 22.48%, P = 0.028), less positive density change 0–6 months (+197.84 ± 107.95 vs. +290.14 ± 131.74 Hounsfield unit (HU), P < 0.001) and 0–1 year (+377.51 ± 150.71 HU vs. +455.48 ± 135.04 HU, P < 0.001), and lower corticalization rate in 1 year (49.77% ± 29.42% vs. 82.27 ± 19.73%, P < 0.001). Significant factors included fracture-related infection (FRI) (P = 0.047 and P = 0.048 at 0–6 months and 0–1 year, respectively) and longer defect length (P = 0.032 and P = 0.020) for the negative volumetric AMRB changes; older age (P = 0.004 and P = 0.016) for the AMRB negative density changes; higher percentage of mixed recombinant human bone morphogenetic protein-2 in graft material (P = 0.013 in 0–6 months) for the AMRB positive density change; FRI (P = 0.024) for the inferior corticalization rate of the AMRB; FRI (P = 0.026 in 0–1 year), longer defect length (P = 0.017 in 0–6 months), and higher mixed demineralized bone matrix percentage (P = 0.010 in 0–1 year) for the difference in density change between the AMRB and TORB; higher mixed demineralized bone matrix percentage (P = 0.023) for the difference between the AMRB and TORB in corticalization rates. CONCLUSIONS: The tibial shaft's anteromedial aspects demonstrated significantly inferior consolidation after IMT, especially in terms of volume at 6 months, density at 6 months and 1 year, and corticalization at 1 year postoperatively. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Lee Y.H., Kang S.H., Kim D.K., Kim J.S., Jeong K.H., Kim Y.G., Lee D., Ahn S.Y., Chung S., Sun I.O., Lee M., Hwang H.S.

Abstract Background Triglyceride-glucose (TyG) index has recently been established as an indicator of insulin resistance and has predictive value for cardiovascular (CV) disease. However, the clinical significance of the TyG index in patients undergoing hemodialysis remains unknown. Methods We prospectively enrolled 759 patients undergoing maintenance hemodialysis. The participants were divided into tertiles based on their baseline TyG index. Echocardiographic parameters, vascular calcification scores, and several plasma biomarkers were obtained and compared using the TyG index. Results The TyG index was positively correlated with levels of circulating vascular pathologic markers, endostatin (ρ=0.134, P=0.025) and vascular adhesion protein-1 (ρ=0.130, P=0.012), but not with vascular calcification score. The TyG index was not correlated with any echocardiographic parameters. Patients in tertile 3 showed the highest cumulative event rates of CV and cardiac events (P&lt;0.001 and P=0.001, respectively). In the multivariable Cox regression analysis, patients in the TyG index tertile 3 had a significantly increased risk of CV and cardiac events compared to those in the TyG index tertile 1 (adjusted hazard ratio [HR]: 1.89, 95% confidence interval [CI]: 1.08–3.30, and adjusted HR: 2.01, 95% CI: 1.05–3.82, respectively). A one standard deviation increase in the TyG index was also associated with significantly higher risks of CV and cardiac events. Conclusions The TyG index was associated with vascular pathology markers and an increased risk of adverse CV outcomes in patients undergoing hemodialysis. Our study suggests that the TyG index has the potential to assist clinicians in identifying a high CV risk in hemodialysis patients.

Lee Y., Kim G.B., Shin S.

Background: Gait disturbances characterized by asymmetries in lower limb strength and gait patterns are frequently observed in stroke patients, which increases gait variability and fall risk. However, the extent to which lower limb strength asymmetry influences gait asymmetry and variability in this population remains unclear. Methods: This cross-sectional study included 84 participants, comprising stroke survivors and age- and sex-matched healthy older adults. A portable dynamometer was used to assess lower limb strength, and inertial measurement units to analyze gait parameters. Asymmetry indices were used to quantify strength and gait asymmetries. Statistical analyses included Pearson correlations and stepwise regression to examine the relationships among lower limb strength asymmetry, gait asymmetry, and gait variability. Results: Stroke survivors exhibited significantly greater lower limb strength and gait asymmetries than healthy older adults (p < 0.001). Knee extension (KE) strength asymmetry was a significant predictor of increased gait variability in stroke survivors (R2 = 0.448, p < 0.001) but not in healthy controls. Moreover, longer poststroke duration was associated with greater asymmetry in KE strength (r = 0.42, p < 0.05) and double support time (r = 0.45, p < 0.05). Conclusions: Lower limb strength asymmetry, specifically in knee extensors, is a critical determinant of gait asymmetry and variability in stroke survivors. The association between poststroke duration and increased asymmetry indicates the progressive nature of these impairments. These findings emphasize the importance of targeted interventions to reduce strength asymmetry and address chronic impairments in poststroke rehabilitation to improve gait stability and reduce fall risk.

Lee H.J., Kim N.Y., Kim D., Son J., Choi K., Lee S., Kim I., Ko K., Ha K.E., Gwak S., Kim K., Seo J., Kim H., Shim C.Y., Ha J., et. al.

Abstract Aims This study compared echocardiography (echo) and cardiac computed tomography (CT) in measuring the Wilkins score and evaluated the potential added benefit of CT in predicting immediate percutaneous mitral valvuloplasty (PMV) outcomes in rheumatic mitral stenosis (MS) patients deemed eligible for PMV by echo. Methods and results From a multicentre registry of 3,140 patients with at least moderate MS, we included 96 patients (age 56.4 ± 11.5 years, 81% female) eligible for PMV based on echo Wilkins score (≤9) who underwent PMV and had measurable CT and echo images. We compared Wilkins scores from both modalities and analysed their relationship with unsuccessful procedural outcomes, defined as sub-optimal post-procedural mitral valve area (&lt;1.5 cm2) or newly developed mitral regurgitation Grade ≥III. The mean CT score was higher than the echo score (8.0 ± 2.4 vs. 7.3 ± 1.2 points, P = 0.005). Procedural success was achieved in 65 (67.7%) patients. Unsuccessful results occurred in 31 patients, primarily in intermediate echo score (7–9 points) group. Among patients with intermediate echo scores, 90% had high CT scores (≥9), which were associated with significantly higher rates of unsuccessful PMV compared with lower CT scores (61.1 vs. 18.9%, P &lt; 0.001). Conclusion CT-derived Wilkins scores were higher than echo-derived scores, with the most significant discrepancy in the intermediate echo score group. CT identified a subgroup of patients at higher risk for unsuccessful PMV among those with intermediate echo-based feasibility. Patients with intermediate echo-based PMV feasibility may benefit from CT-based reclassification, potentially improving patient selection and procedural outcomes.

Lim Y., Kim H.R., Lee S.B., Kim S.B., Kim D., So J., Kang K., Sung S., Choi J., Sung M., Lee Y., Park W., Lee G.W., Kim S., Seo M.

ABSTRACTBenign prostatic hyperplasia (BPH) is a distressing health problem that can cause serious complications in aging men. Androgens are implicated in the causation of BPH. Portulaca oleracea (PO) is a natural product with diverse pharmacological effects. The objective of this study was to investigate the effect of PO in a rat model of testosterone propionate (TP)‐induced BPH and explore the underlying mechanisms. Thirty‐five Sprague‐Dawley (SD) rats were divided into the following equal groups (n = 7): normal control (NC) group, TP (3 mg/kg) group, finasteride (10 mg/kg) group, 25 and 50 mg/kg PO groups.At the end of the experiment, the body weights (BWs) of the rats were measured before they were euthanized to the establishment obtain serum and prostate weight (PW). TP‐induced levels of androgen‐related proteins in the prostate were also investigated. In the TP group, prostate size, BW, serum DHT level, prostate epithelial cell thickness and androgen‐related protein level were higher than those in the NC group (p < 0.001). PO reversed TP‐induced BPH in a dose‐dependent manner (p < 0.01) and its effect was similar to that of finasteride. A similar effect of PO on the androgen‐related protein level was also observed. We successfully established a TP‐induced BPH rat model. This is the first study to demonstrate that inhibition of androgen‐related proteins using PO can alleviate BPH.

Shin I.S., Lee Y.N., Lee J.K., Kim J.S., Kim S.B., Keum J., Oh C.H., Lee K.W., Chung J., Kwon L.M., Kim N.H., Lee S.S., Son B.K., Choi M.

Kwak J., Choi K., Park J., Nam J., Lee C., Kim U., Park J., Son J.

Abstract Background Evaluation of regional left ventricle function using two-dimensional echocardiography (2DE) in patients with ischemic heart disease has limitations due to its low objectivity and qualitative nature. In addition, 2DE is limited because multiple acoustic windows are used to obtain the image, whereas three-dimensional echocardiography (3DE) uses a single window. This study aims to demonstrate the clinical utility of 3DE segmental volume analysis for evaluating regional wall motion abnormality (RWMA). Methods This retrospective study included 33 patients with ischemic heart disease and single-vessel territory RWMA confirmed on coronary angiography. RWMA was visually assessed using 2DE, generating 17-segment bull's-eye polar maps, and 3DE. In the 3DE study, two independent observers analyzed segmental volumes and segmental volume ejection fractions (SVEFs) using QLAB 3D quantification software. The optimal SVEF cutoff value differentiating normal from abnormal was determined using receiver operating curve analysis. The accuracy of 3DE in predicting culprit coronary arteries was compared with that of 2DE using Cohen κ coefficients, which also were used for interobserver and intraobserver variability assessments. Results Mean 3DE SVEFs were significantly lower in segments showing RWMA on 2DE. The optimal SVEF cutoff value was 44%, with sensitivity of 75.0% and specificity of 73.9% (area under the curve, 0.801; 95% CI, 0.763–0.838; P < 0.001). The reliability of 3DE-derived bull's-eye predictions of culprit coronary arteries was 81.8% (κ = 0.672; 95% CI, 0.555–0.789; P < 0.001). Interobserver and intraobserver variabilities were 97.0% (κ = 0.947; 95% CI, 0.894–1.00; P < 0.001) and 93.9% (κ = 0.897; 95% CI, 0.827–0.967; P < 0.001), respectively. Conclusions The 3DE segmental volume analysis effectively quantified regional left ventricle function and aligned well with 2DE and coronary angiography findings in predicting culprit coronary arteries. Thus, 3DE segmental volume analysis can serve as a quantitative and objective tool for RWMA assessment in patients with ischemic heart disease.

Kang J., Jeon K., Choi K., Choi H., Sung K.

Background Recent studies have suggested that increased brachial‐ankle pulse wave velocity (baPWV) is a risk factor for diabetes. Exploring its relationship with insulin resistance is of interest, necessitating further studies across different sexes and age groups. Methods and Results This cohort study involved 119 170 Korean adults with an average age of 39.8 years, none of whom had diabetes at baseline. As part of a health screening, baPWV measurements were taken. Over a median follow‐up period of 5.6 years, fasting blood glucose, glycated hemoglobin, insulin levels, and questionnaire responses were collected. The risk of developing diabetes was evaluated using a flexible parametric proportional hazards model with data stratified by sex and age group (<40 versus ≥40 years). During the follow‐up period, diabetes was diagnosed in 5966 participants (5.0%). A fully adjusted model found that the hazard ratios for diabetes onset associated with baPWV quartiles Q2 (1171.0–1270.5 cm/s), Q3 (1271.0–1376.0 cm/s), and Q4 (≥1376.5 cm/s) compared with Q1 (<1171.0 cm/s) were 1.06 (95% CI, 0.96–1.17), 1.25 (1.14–1.38), and 1.48 (1.34–1.62), respectively ( P for trend <0.001). A significant sex‐based interaction was noted in this association, with women showing a higher risk of diabetes development. Furthermore, higher baPWV quartiles were associated with an increased risk of developing insulin resistance, defined as the homeostatic model assessment of insulin resistance. Conclusions These findings highlight the importance of arterial stiffness, as measured by elevated baPWV, in the development of diabetes and insulin resistance. Notably, this study highlighted a strong association, particularly among women.

Seo J., Lee Y.M., Tamanna S., Bang M., Kim C., Kim D.Y., Yun N.R., Kim J., Jung S.I., Kim U.J., Kim S.E., Kim H.A., Kim E.S., Hur J., Kim Y.K., et. al.

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log10 RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log10 RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS.

Kim Y., Jang E., Hwang J., Lee K., Xayaheuang S., Choi S., Park H.

Kim A.Y., Cho K.H., Park J.W., Do J.Y., Kang S.H.

Background: Although the risk of serious bleeding following peritoneal dialysis catheter insertion is low, pericannular bleeding can increase the risk of catheter-related infections and reduce catheter survival. We aimed to analyze the risk factors for bleeding complications during peritoneal dialysis catheter insertion and assess whether temporary preemptive hemodialysis before catheterization can reduce bleeding and improve catheter survival. Methods: We retrospectively analyzed bleeding complications and catheter survival in patients who underwent temporary hemodialysis prior to peritoneal dialysis catheter insertion. Cox regression analysis was performed to determine the risk factors for bleeding complications and catheter survival. Results: Among 336 patients, 216 and 120 comprised the non-hemodialysis and hemodialysis groups, respectively. No significant association was found between temporary hemodialysis and bleeding (hazard ratio: 1.6, 95% confidence interval: 0.87–2.95, p < 0.134). Multivariate analysis revealed an inverse association of platelet count (hazard ratio: 0.99, 95% confidence interval: 0.99–0.99, p < 0.048) and hemoglobin level (hazard ratio: 0.78, 95% confidence interval: 0.61–0.99, p < 0.04) with bleeding. A positive association was observed between international normalized ratio (hazard ratio: 2.24, 95% confidence interval: 1.19–4.19, p < 0.012) and bleeding. Conversely, temporary hemodialysis was not associated with catheter survival (hazard ratio: 1.64, 95% confidence interval: 0.63–4.25, p < 0.308). Conclusions: Temporary hemodialysis before peritoneal dialysis catheter insertion did not significantly affect bleeding risk in patients with a high risk of uremic bleeding.

Ko K., Cho I., Kim D., Lee H.J., Ha K., Gwak S., Kim K., Kim W.D., Lee S., Seo J.W., Kim I., Choi K., Kim H., Son J., Shim C.Y., et. al.

Jeong J., Park J., Kim B., Kim H., Choi K., Nam J., Lee C., Son J., Park J., Her S., Chang K., Ahn T., Jeong M., Rha S., Kim H., et. al.

BackgroundData on the clinical impact of beta-blockers (BBs) in patients with myocardial infarction (MI) who had non-reduced left ventricular ejection fraction (LVEF) after percutaneous coronary intervention are limited.MethodsFrom 2016 to 2020, we evaluated a cohort of 12,101 myocardial infarction patients with a non-reduced LVEF (≥40%) from the Korean Acute Myocardial Infarction Registry V. Patients were divided into two groups based on their BB (carvedilol, bisoprolol, or nebivolol) treatment at discharge: with beta-blocker treatment (BB, n = 9,468) and without beta-blocker treatment (non-BB, n = 2,633). The primary endpoint after discharge was the occurrence of patient-oriented composite endpoints (POCEs), including all-cause mortality, any MI, or any revascularization at 1-year follow-up.ResultsThe median follow-up period was 353 days (interquartile range, 198–378 days). At 1-year follow-up, no significant differences were observed in the primary endpoint between the BB group and the non-BB group. Before propensity score (PS) matching, the POCE incidence was 3.1% in the BB group vs. 3.4% in the non-BB group [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.68–1.09, p = 0.225]. After PS matching, the POCE incidence remained similar between the two groups (3.7% vs. 3.4%, HR 1.01, 95% CI 0.76–1.35, p = 0.931). Individual outcomes, including all-cause mortality, myocardial infarction, and revascularization, also showed no significant differences between the two groups. Independent predictors of 1-year POCEs after discharge were age, chronic kidney disease, reduced LVEF, and multivessel disease.ConclusionBB treatment in patients with acute MI and non-reduced LVEF was not associated with a significant reduction in cardiovascular outcomes at 1-year follow-up.

Lee H., Jang J.G., Kim Y., Min K.H., Ahn J.H., Yoo K.H., Kang M.G., Kim J.S., Moon J.

Background/Objectives: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an important comorbidity of COPD. Although many studies have reported an association between COPD and NTM-PD, no clear estimate of the prevalence of COPD and its effects on survival times in patients with NTM-PD is available. This study aimed to investigate the prevalence of COPD and its impact on survival in patients with NTM-PD. Methods: All studies reporting the prevalence of COPD in patients with NTM between 1952 and 2021 were searched using PubMed in May 2023. The inclusion criteria were studies about patients with NTM and COPD. A random-effects meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: The pooled overall prevalence of COPD in patients with NTM-PD was 28% (95% confidence interval [CI], 22–35). Patients with NTM-PD were six times more likely to have COPD than those without NTM-PD (pooled odds ratio [OR], 6.26; 95% CI, 3.37–11.65). Male patients with NTM-PD had a four-fold higher risk of COPD than females (OR, 3.81; 95% CI, 1.18–12.35). The co-existence of COPD and NTM-PD was significantly associated with an increased risk of mortality compared with NTM-PD without COPD (OR, 3.65; 95% CI, 1.28–10.40). Conclusions: COPD is common in patients with NTM-PD, and patients with NTM-PD had a six-fold increase in the odds of having COPD than those without NTM-PD. The presence of COPD and NTM-PD had a significant negative effect on survival. These findings may support the need to assess the presence of COPD in patients with NTM-PD and the potential negative effects associated with the co-existence of COPD and NTM-PD.