Young Lee

Background/Objectives: Hyperinsulinaemia reflects compensatory systemic insulin resistance and may indicate early metabolic–vascular dysregulation. We investigated associations between insulin dysregulation and the retinal neuronal structure, particularly ganglion cell layer (GCL) thickness, using Korea National Health and Nutrition Examination Survey (KNHANES) data. Methods: We analysed KNHANES’s 2019–2020 participants who underwent spectral-domain optical coherence tomography (SD-OCT) and fasting serum insulin assessment. SD-OCT-derived GCL and retinal nerve fibre layer (RNFL) thickness were compared with fasting insulin levels and insulin resistance, which was assessed using the homeostatic model assessment of insulin resistance. Multivariable linear regression models were adjusted for age, sex, body mass index, hypertension, diabetes, and intraocular pressure. To account for multiple comparisons across retinal thickness parameters, a false discovery rate (FDR) correction was applied separately to GCL and RNFL analyses for each exposure and model. Results: Among 6941 participants, hyperinsulinaemia was significantly associated with a reduced average GCL thickness after full adjustment (β = −0.106, 95% confidence interval [CI]: −0.179 to −0.032; FDR-adjusted p = 0.013). Significant inverse associations remained for seven of the eight GCL parameters after FDR correction, with the superior sector being the only exception. Insulin resistance was associated with a reduced average GCL thickness in the unadjusted model (β = −0.107, 95% CI: −0.169 to −0.045; FDR-adjusted p = 0.002), but the association was attenuated after multivariable adjustment and was no longer significant in the fully adjusted model (β = −0.062, 95% CI: −0.125 to 0.001; FDR-adjusted p = 0.096). No significant associations with RNFL thickness remained after multivariable adjustment and FDR correction. Conclusions: Hyperinsulinaemia was consistently associated with a reduced GCL thickness across most retinal regions, whereas associations between HOMA-IR-defined insulin resistance and GCL thickness were attenuated after multivariable adjustment and FDR correction. No significant associations with RNFL thickness remained after adjustment and multiple-comparison correction. These findings suggest a potential association between hyperinsulinaemia and early GCL thinning, warranting further investigation into its relationship with retinal neurodegeneration and glaucoma risk.

Background/Objectives: Basal metabolic rate (BMR) is implicated in age-related phenotypes, and presbyopia represents a hallmark of ocular ageing. However, the association between BMR and presbyopia remains underexplored. Therefore, using a two-sample Mendelian randomisation (MR) approach, the present study aimed to evaluate the potential causal relationship between BMR and presbyopia in individuals of European ancestry. Methods: Instrumental variables comprised single-nucleotide polymorphisms associated with BMR at genome-wide significance (p < 5.0 × 10⁻⁸), derived from genome-wide association study summary statistics from the UK Biobank. Summary statistics for presbyopia were obtained from the FinnGen project. Causal estimates were primarily assessed using the inverse-variance weighted method and further evaluated using the weighted median method, MR–Egger regression, and the MR–Pleiotropy Residual Sum and Outlier test. Results: Genetically predicted higher BMR, expressed per 1-standard-deviation increase on the inverse-rank-normalised scale, was associated with lower odds of presbyopia. The inverse-variance weighted analysis yielded an odds ratio (OR) of 0.79 (95% confidence interval [CI]: 0.67–0.93; p = 0.004), with a directionally consistent estimate from the weighted median analysis (OR = 0.76, 95% CI: 0.59–0.99; p = 0.045). MR–Egger and SIMEX-corrected MR–Egger analyses yielded estimates in the same inverse direction, although their 95% CIs included the null (OR = 0.73, 95% CI: 0.50–1.05; p = 0.093 and OR = 0.71, 95% CI: 0.47–1.06; p = 0.092, respectively). The MR-PRESSO global test was nominally significant (p = 0.049), although no individual outlier was identified. In additional MVMR analyses incorporating BMI or standing height, the direct effect of BMR was not statistically significant in either model. Conclusions: These findings suggest a potential inverse association between higher genetically predicted BMR and the odds of presbyopia. However, MVMR analyses did not support a direct effect of BMR independent of BMI or height, warranting caution in interpreting the observed association as specific to metabolic rate. Further studies are required to validate these results and clarify the underlying biological mechanisms.

Individuals with transtibial amputation have impaired postural control due to limited ankle function. Conventional energy-storing-and-return (ESAR) prosthetic feet mainly support sagittal-plane mechanics and provide limited frontal-plane adaptability. This pilot pre–post motion analysis study examined the effects of the Intersection Foot^® (IF), a torsion-adaptive ESAR prosthetic foot, on balance control in 10 male individuals with unilateral transtibial amputation. Three-dimensional motion analysis and force plate measurements were performed during five Berg Balance Scale-derived tasks. During sit-to-stand, IF reduced the mediolateral root mean square distance of center of pressure from 10.20 ± 3.59 to 8.29 ± 3.32 mm (p = 0.047) and the anteroposterior center of mass (CoM) range from 345.51 ± 31.72 to 326.45 ± 47.40 mm (p = 0.008). During tandem stance, IF increased mediolateral CoM range from 23.94 ± 18.77 to 55.99 ± 30.90 mm (p = 0.021), vertical CoM range from 4.14 ± 4.18 to 9.45 ± 7.72 mm (p = 0.038), and sound-side frontal-plane ankle ROM from 1.44 ± 1.20° to 2.48 ± 1.30° (p = 0.022). Overall, replacing the habitual feet with IF produced task-dependent biomechanical adaptations rather than uniform improvements in postural stability, suggesting reduced dynamic sway during sit-to-stand but increased whole-body and sound-limb compensatory motion during tandem stance.

Background/Objectives: The 2026 Barcelona Clinic Liver Cancer (BCLC) update recommends surgical resection for a single hepatocellular carcinoma larger than 2 cm with preserved liver function and states that age alone should not preclude surgery. How often eligible older patients undergo resection, and how they fare, remains unquantified. Methods: Using the Korean Primary Liver Cancer Registry (2008–2021), we identified 3374 patients meeting all registry-based eligibility criteria of the 2026 BCLC update. Survival was measured from the date of radiological diagnosis in every patient, with vital status and cause of death obtained by linkage to national death records. We compared use of resection and survival among patients younger than 75 years and those 75 years or older, and across resection, ablation, other treatment, and no treatment, using Cox regression, restricted mean survival time (RMST), and competing-risk models. Results: Resection was performed in 60.6% of patients younger than 75 years versus 28.9% of those 75 years or older (p < 0.001); among older patients not undergoing resection, 21.5% received none. Older age was independently associated with lower odds of resection (adjusted odds ratio 0.36, 95% CI 0.28–0.46; p < 0.001). In this age group, 5-year survival was 61.3%, 62.1%, 32.9%, and 6.5% across the four treatment categories; the adjusted hazard ratio for no treatment versus resection was 4.97 (95% CI 3.26–7.57; p < 0.001). In unadjusted analysis, mean survival within the first 5 years was 13.3 months longer after resection (RMST difference, 95% CI 9.7–16.9; p < 0.001). Findings were consistent in competing-risk, weighted, cirrhosis-adjusted, and multiply imputed analyses. Conclusions: Older patients meeting eligibility criteria underwent resection far less often than younger patients, and a substantial minority received none, a pattern associated with markedly shorter survival.

Background/Objectives: To investigate the causal relationships linking body mass index (BMI) and circulating insulin-like growth factor 1 (IGF-1) levels with diabetic maculopathy risk using two-sample Mendelian randomization (MR). Methods: A two-sample MR framework was applied, utilizing genetic instruments for BMI and IGF-1 derived from the UK Biobank. Summary-level diabetic maculopathy data were obtained from the FinnGen consortium. Genome-wide significant single-nucleotide polymorphisms (SNPs, p < 5.0 × 10⁻⁸) independently associated with each exposure were employed as instrumental variables. Primary causal estimates were obtained using the inverse-variance weighted (IVW) method. Sensitivity analyses, including MR-Egger regression, weighted median methods, and the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate robustness and potential pleiotropy. Results: Genetically predicted BMI was positively associated with diabetic maculopathy risk in both the IVW analysis (odds ratio [OR] = 1.16 (95% confidence interval [CI]: 1.04–1.30), p = 0.008) and MR-PRESSO (OR = 1.16 (95% CI: 1.04–1.28), p = 0.006). MR-PRESSO exhibited a significant relationship between higher IGF-1 levels and increased diabetic maculopathy risk (OR = 1.09 (95% CI: 1.01–1.18), p = 0.025), whereas the IVW method indicated only a suggestive association (OR = 1.08 (95% CI: 0.99–1.18), p = 0.087). Conclusions: The genetic evidence supports a causal role of insulin resistance-related traits in diabetic maculopathy development, with higher BMI and IGF-1 levels increasing diabetic maculopathy risk. These results underscore the potential contributory role of IGF-1 in disease pathogenesis and suggest that insulin resistance-related traits may represent preventive therapeutic targets.

Background/Objectives: The impact of stroke on upper extremity function in the older adult population underscores the need for accurate recovery prediction. Motor evoked potential (MEP) has been explored as a predictor of upper extremity function recovery in patients with stroke. However, research specifically targeting the geriatric population remains limited. Therefore, this study focused specifically on patients aged 65 years and older to investigate correlations between MEP parameters and upper extremity function. This study investigates correlations between MEP parameters (amplitude and latency) and upper extremity function-related measures, including Medical Research Council (MRC) scale, the Korean version of the Modified Barthel Index (K-MBI), and the Hand Function Test (HFT), including grip strength, pinch strength, the Box and Block Test, and the 9-Hole Peg Test, in older adults with stroke. Methods: A multiple linear regression model predicts upper extremity outcomes using initial MEP parameters, time, and function. The dataset includes 90 patients with stroke categorized by timing of the first MEP assessment: ≤3 months (n = 42) or >3 months (n = 48). Results: MEP amplitude and latency were significantly correlated with upper extremity function in both groups. No significant correlations were found between MEP amplitude or latency and outcome measures. Regression analysis showed that initial MEP amplitude had a limited association with outcomes, whereas latency was significantly associated with grip strength (β: −10.205, 95% CI: −19.374~−1.036) and the Box and Block Test (β: −10.204, 95% CI: −20.254~−0.154). Initial upper extremity parameters were significantly associated with K-MBI and HFT follow-up results (p < 0.05). Conclusions: Larger MEP amplitude and faster initial MEP latency were associated with improved upper extremity function in patients with stroke. In older patients, MEP latency, rather than amplitude, demonstrated greater predictive value for upper extremity function recovery, possibly due to age-related muscle atrophy, a factor not fully addressed in existing prognostic frameworks such as PREP2. These findings support the integration of MEP latency assessment into geriatric stroke prognostication, complementing existing frameworks such as PREP2, and may guide personalized rehabilitation planning to optimize functional recovery and independence.

Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10⁻⁸) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function.

Background/Objectives: This study was designed to investigate the potential causal relationship between uterine fibroids (UF) and breast cancer (BC) using genetic data in East Asian populations. Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis of UF and BC, selecting exposure-associated single-nucleotide polymorphisms (SNPs) from Biobank Japan and extracting outcome associations from the China Kadoorie Biobank for both directions. The primary estimator was inverse-variance-weighted (IVW), with robustness assessed using the weighted median, MR-Egger regression, and the MR-pleiotropy residual sum and outlier (MR-PRESSO). Results: The SNPs with (p < 5.0 × 10⁻⁸) were selected as instrumental variables for UF (n = 16) and BC (n = 7). There was no evidence of heterogeneity in either direction. Genetically predicted UF was positively associated with BC risk (odds ratio, 1.33; 95% confidence interval, 0.99–1.79; p = 0.063), although the association did not reach statistical significance in IVW. In addition, the causal effect of BC on UF was significant (odds ratio, 1.19; 95% confidence interval, 1.08–1.32; p < 0.001 in IVW). Conclusions: Our study suggested a borderline significant causal effect of UF on BC. Moreover, BC demonstrated a significant causal association with UF, underscoring the need for further research into the role of various mechanisms including estrogen in the relationship between the two diseases.

Background/Objectives: Individuals with metabolic syndrome (MetS) present reduced 25(OH)D levels. We performed a two-sample Mendelian randomization (MR) study to investigate whether causal relationships exist between 25(OH)D levels and MetS/MetS risk traits, including waist circumference, body mass index (BMI), hypertension (systolic/diastolic blood pressure), triglyceride, high-density lipoprotein cholesterol, and glucose levels. Methods: We employed genetic variants related to 25(OH)D levels from the SUNLIGHT Consortium and a European genome-wide association study meta-analysis, including UK Biobank (UKB) data, as well as variants for MetS and MetS risk traits from UKB and multiple European consortia. Several MR methods were used, i.e., inverse-variance weighted, weighted median, and MR–Egger regression. Heterogeneity and horizontal pleiotropy analyses were performed to ensure the stability of candidate single-nucleotide polymorphisms (SNPs) as the instrumental variable. We first conducted univariable MR to investigate the relationship between 25(OH)D levels and MetS, including its related risk traits, and subsequently performed multivariable MR to adjust for potential confounders. Results: This study did not provide evidence of a causal relationship between 25(OH)D levels and MetS/MetS risk traits. However, we found that several risk traits of MetS, such as waist circumference, BMI, and TG, had an inverse–causal relationship with 25(OH)D levels, suggesting that 25(OH)D levels could be secondary consequences of metabolic illnesses. Conclusions: We identified no causal relationship between 25(OH)D levels and MetS/MetS risk factors. However, 25(OH)D levels may result from MetS traits.