Background:Ezetimibe has demonstrated favorable outcomes, including a reduction in cardiovascular complications and improvement in insulin resistance. However, its association with cancer risk remains unclear. This study evaluated the association between the use of ezetimibe-statin combination therapy and cancer risk using real-world data. Methods:Korean National Health Insurance Service database health records were analyzed using propensity score matching to compare the cancer-related outcomes between ezetimibe-statin combination therapy and statin monotherapy groups. Outcomes included cancer incidence, cancer-specific mortality, and all-cause mortality. Results:In a cohort of 669,036 statin users, ezetimibe-statin combination therapy was associated with a significantly lower risk of cancer (hazard ratio [HR], 0.89; P<0.001) and cancer-related mortality (HR, 0.85; P<0.001) compared with statin monotherapy. Combination therapy was also associated with a lower risk of specific cancers, including colorectal, liver, breast, pancreatic, and biliary tract cancers. These inverse associations were consistent across subgroups stratified according to age, sex, alcohol consumption/smoking history, and the presence of diabetes or hypertension (all P for interaction >0.05). Moreover, a longer duration of ezetimibe use was linked to a lower cancer risk, with the most pronounced inverse associations observed in individuals who had used the drug for ≥4 years. Conclusion:These findings suggest that ezetimibe combined with statins may be associated with a reduced risk of cancer.
Background:The C-reactive protein-triglyceride glucose index (CTI) has recently been introduced as a novel composite biomarker that integrates inflammation and insulin resistance. However, the association between CTI and incident cardiovascular disease (CVD) in individuals with hypertension remains unclear. Methods:We included 168,186 participants from the UK Biobank in this longitudinal analysis. The primary outcomes were incident coronary heart disease (CHD), atrial fibrillation (AF), heart failure (HF), and stroke. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between CTI and incident CVD outcomes. Results:In this study, CTI showed significant positive linear associations with CHD (HR, 1.19; 95% CI, 1.15 to 1.23) and stroke (HR, 1.14; 95% CI, 1.07 to 1.21), whereas nonlinear associations were observed for AF (HR, 1.08; 95% CI, 1.04 to 1.13) and HF (HR, 1.36; 95% CI, 1.28 to 1.44) among participants with hypertension. Furthermore, subgroup and sensitivity analyses confirmed the robustness of these associations. Conclusion:Our findings showed that elevated CTI levels were robustly associated with increased risks of CHD, AF, HF, and stroke, suggesting that CTI may serve as a promising predictive marker for CVD in individuals with hypertension.
Background:Obesity has been considered protective against osteoporosis due to its association with higher bone mineral density (BMD). However, metabolic dysfunction, particularly insulin resistance (IR), may compromise bone quality even with BMD preserved. Methods:This retrospective cross-sectional study (n=254) included 153 individuals with severe obesity undergoing bariatric metabolic surgery and 101 age- and sex-matched non-obese controls. BMD and trabecular bone score (TBS) were measured using dualenergy X-ray absorptiometry. A subgroup of participants with obesity was further analyzed to examine associations between IR, assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), and bone parameters. Results:BMD was significantly higher in the obese group, indicating preserved bone mass in obesity. But the proportions of spine-hip Z-score discordance was significant higher in the obese group (P=0.001). TBS displayed sitespecific findings: TBS at L1 was significantly higher in the obese group (P=0.002), whereas no significant differences were observed at L2-L4. Partially degraded or degraded TBS were higher in the obese group (P=0.021). Among participants with obesity, TBS decreased progressively across HOMA-IR quartiles (P=0.043), whereas BMD remained stable. In multivariable regression, higher HOMA-IR was independently associated with lower TBS (β=-0.0025; 95% confidence interval, -0.0043 to -0.0006; P=0.015), although this association was attenuated by hemoglobin A1c adjustment. Conclusion:Patients with obesity demonstrated site-specific reductions in trabecular bone quality, particularly in the lower lumbar spine compared with non-obese people. IR was independently and inversely associated with TBS, suggesting that metabolic dysfunction, not mechanical loading, influences bone fragility in obesity. TBS represents a valuable adjunct to BMD for assessing skeletal health in metabolically impaired obese populations.
Background:Sarcopenic obesity, characterized by reduced skeletal muscle mass accompanied by excessive visceral fat accumulation, has recently gained attention as a crucial determinant of metabolic dysfunction. Although pancreaticoduodenectomy (PD) is increasingly performed with improved surgical outcomes, the incidence and risk factors for new-onset diabetes after PD remain incompletely understood. This study investigated the impact of sarcopenic obesity on postoperative glucose metabolism. Methods:A total of 613 patients without preexisting diabetes who underwent PD between 2015 and 2023 were retrospectively analyzed. Diabetes status was evaluated preoperatively and at 3 months postoperatively (Cohort 1), and a subset of 143 patients was reassessed at 1 year (Cohort 2). Sarcopenic obesity was defined as a visceral fat area/skeletal muscle index >2.5 m2. Diabetes was defined according to the American Diabetes Association criteria. Results:At 3 months after surgery, 8.2% (50/613) of patients developed diabetes. Independent predictors included hypertension (odds ratio [OR], 2.45), elevated preoperative hemoglobin A1c (OR, 2.31), and receipt of adjuvant chemotherapy (OR, 3.15). At 1 year, 9.8% (14/143) developed diabetes, with sarcopenic obesity emerging as the sole independent predictor (OR, 3.65; 95% confidence interval, 1.09 to 14.43). Additionally, patients with sarcopenic obesity had significantly higher levels of hemoglobin A1c, Cpeptide, and insulin resistance 1 year after surgery than those without sarcopenic obesity. Conclusion:Sarcopenic obesity was associated with persistent postoperative insulin resistance. These findings suggest that sarcopenic obesity constitutes a key determinant of new-onset diabetes after PD and highlight the need for preoperative assessment and targeted metabolic interventions in this high-risk population.
Background:Few studies have investigated the association between cardiovascular health (CVH) and thyroid dysfunction, and the modifying role of depression or anxiety remains unclear. Methods:This longitudinal study included 360,332 UK Biobank participants without thyroid disease at baseline and with complete CVH scores. We examined the associations between CVH and the risks of hyperthyroidism and hypothyroidism using Cox proportional hazards regression models, quantified the relative contributions of CVH components using weighted quantile sum regression, and evaluated the mediating role of inflammatory markers. Furthermore, we investigated the modifying effects of depression and anxiety on these associations. A multi-state model was used to explore disease trajectories. Results:During a median follow-up of 12.53 years, 1,533 and 7,542 participants developed hyperthyroidism and hypothyroidism, respectively. After multivariable adjustment, each 5-point increase in CVH score was associated with a 7% (95% confidence interval [CI], 4% to 9%) lower risk of hyperthyroidism and an 8% (95% CI, 7% to 9%) lower risk of hypothyroidism. A high CVH score was associated with a 50% (95% CI, 37% to 60%) lower risk of hyperthyroidism and a 45% (95% CI, 38% to 50%) lower risk of hypothyroidism. Among the CVH components, obesity and tobacco exposure contributed most to disease risk. Inflammatory markers partially mediated these associations. Depression and anxiety modified the association between CVH and hypothyroidism, and CVH showed a protective effect across the disease trajectories. Conclusion:Maintaining favorable CVH was associated with a lower risk of thyroid dysfunction, particularly among individuals with good mental health.
Background:Thyroid cancer (TC) is a common endocrine malignancy with a rising global incidence. This study examined trends in TC incidence and mortality in the United States over the past two decades. Methods:TC mortality data from 1999-2023 and incidence data from 1999-2022 were obtained from Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. Age-adjusted incidence rates (AAIRs) and age-adjusted mortality rates (AAMRs) per 100,000 person-years were standardized to the 2000 United States standard population. Temporal trends were analyzed using the Joinpoint Regression Program to calculate annual percent changes (APCs) and average annual percent changes (AAPCs) with 95% confidence intervals. Analyses were stratified by sex, age, race, and census region. A sensitivity analysis restricted to 1999-2019 was also conducted. Results:Overall, 933,521 TC cases and 43,071 TC-related deaths were identified, with an AAIR of 12.12 and an AAMR of 0.49. Incidence rose markedly from 1999 to 2009 (APC=7.25%), stabilized during 2009-2014, and declined from 2014 to 2022 (APC=-2.42%), especially among females. In males, incidence increased until 2011 and then declined slightly. Mortality increased modestly overall (AAPC=0.30%), mainly among males and adults aged ≥75 years. The Northeast had the highest AAIR (15.73), whereas the West had the highest AAMR (0.55). Non-Hispanic Whites had increasing mortality, while non-Hispanic Blacks had the lowest incidence. Conclusion:In the United States, TC incidence shifted from increase to decline, coinciding with growing awareness of potential overdiagnosis. In contrast, mortality continued to show a modest upward trend, underscoring the importance of ongoing surveillance and focused attention to high-risk populations.
In patients with differentiated thyroid cancer, initial recurrence-risk stratification based on clinical, histopathological, and perioperative findings remains central to management during the first 1–2 years after initial treatment. Ongoing risk stratification (ORS) complements this initial assessment by continuously integrating longitudinal clinical data and treatment response, thereby refining long-term prognostic assessment and supporting individualized risk-adapted management. Building on the 2024 Korean Thyroid Association (KTA) guidelines, the 2026 KTA guideline incorporates new evidence from large Korean multicenter cohorts and comprehensive systematic reviews. The updated recommendations reinforce the continued application of ORS and provide more specific guidance on risk-adapted thyroid-stimulating hormone (TSH) targets, surveillance strategies for recurrence detection, and long-term follow-up tailored to individual recurrence risk and treatment response. Consistent with the evolving paradigm toward risk-adapted and individualized management, this revision updates recommendations regarding target serum TSH levels, serum thyroglobulin thresholds for response assessment and long-term surveillance, and follow-up intervals based on both initial-risk category and the ORS response category. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the majority of patients who have an excellent prognosis after initial therapy while ensuring individualized long-term management for patients who require closer surveillance or additional therapeutic intervention.
Background:The incidence of thyroid cancer in Korea increased rapidly for decades and started declining around the mid-2010s. However, the mortality rate is stable without significant changes. This study evaluated the long-term trends in the standardized incidence rate/standardized mortality rate (SIR/SMR) of thyroid cancer in Korea. Methods:Cancer-specific incidence data from 1999 to 2021 and mortality data from 1985 to 2023 were obtained from Statistics Korea. SIR and SMR were calculated using the 2000 and 2005 Korean mid-year resident registration populations, respectively, as the standard populations. Trends in incidence and mortality were further analyzed using joinpoint regression analysis. Results:The SIR was 7.41 per 100,000 in 1999, which peaked at 75.06 in 2012. It then decreased to 42.50 by 2015, but subsequently increased to 60.13 in 2021. SIR patterns tend to vary by age and sex. Stage-specific analyses revealed a renewed increase in both localized and distant stage cancers from 2015 onwards. Histologically, the incidence of papillary carcinoma decreased after 2010, whereas that of follicular carcinoma and medullary carcinoma showed recent upward trends. The SMR increased until the early 2000s but has since steadily declined, with the trend most evident among those aged ≥55 years. Conclusion:The incidence of thyroid cancer in Korea peaked in 2012, decreased until 2015, and has since modestly increased, particularly among men, younger adults, and patients with follicular, localized, or distant-stage disease. Thyroid cancer mortality has continually declined since the early 2000s. Continuous long-term monitoring is required to assess the effects of changes in clinical and diagnostic practices.
Background:Patients with thyroid cancer receive thyroid-stimulating hormone suppressive therapy and radioactive iodine therapy, which can alter metabolism and affect the association between lifestyle factors and cardiovascular disease (CVD) outcomes. However, it remains unclear how changes in lifestyle relate to CVD risk, particularly according to metastatic status. We investigated the impact of baseline and changing lifestyle behaviors on CVD risk among thyroid cancer patients by metastasis status. Methods:This study was a nationwide cohort study using data from the Korean National Health Insurance Service claims database with the Cancer Clinical Library Database from the Korea Clinical Data Utilization Network for Research Excellence project. Over a mean follow-up of 5.7 years, 99,742 thyroid cancer patients were analyzed. Results:Current smoking increased CVD risk in both no metastasis (NM) group (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.33 to 2.35) and the local metastasis (LM) group (HR, 1.30; 95% CI, 1.00 to 1.68), but not in those with distant metastasis. Regular activity reduced the risk in the NM group (HR, 0.84; 95% CI, 0.79 to 0.96). Alcohol consumption was not significantly associated with the CVD risk. Sustained smoking showed an increased CVD risk in both NM (HR, 1.95; 95% CI, 1.31 to 2.90) and LM (HR, 1.88; 95% CI, 1.28 to 2.77). Sustained regular physical activity was associated with a lower risk of CVD only in NM (HR, 0.68; 95% CI, 0.53 to 0.87). Conclusion:Sustained smoking increased CVD risk, while regular physical activity was associated with a lower risk of CVD, particularly in those without distant metastasis.
Glucocorticoids are widely prescribed for inflammatory diseases, but their adverse skeletal effects, particularly osteoporosis and fracture, remain clinically important. Glucocorticoid-induced osteoporosis (GIOP) is characterized by rapid disruption of bone remodeling, with an early increase in bone resorption followed by suppression of bone formation. These changes substantially increase the risk of vertebral fracture. Fracture risk in GIOP cannot be explained by reductions in bone mineral density alone; it is also thought to reflect glucocorticoid-related deterioration in bone quality and microarchitecture. Current international guidelines recommend fracture risk assessment when glucocorticoid therapy is initiated and support a risk-stratified therapeutic approach. Oral bisphosphonates remain first-line therapy for individuals at low to moderate fracture risk. For patients at higher risk, more potent antiresorptive agents, including zoledronic acid and denosumab, have been shown to improve bone mineral density. In individuals at very high fracture risk, anabolic therapy followed by antiresorptive treatment is increasingly recommended. Careful attention to treatment sequencing is essential, particularly after denosumab discontinuation, for preventing rebound-associated vertebral fractures. Recent guideline updates and comparative clinical studies have placed greater emphasis on anabolic therapy and structured treatment sequencing in order to improve skeletal outcomes. This review summarizes evolving risk-based management strategies for GIOP, focusing on treatment selection by fracture risk category and planned transitions between osteoporosis therapies.
The pharmacological management of type 2 diabetes mellitus has changed markedly over the past decade, largely in response to evidence generated by cardiovascular and renal outcome trials. Although contemporary guidelines are informed by a broadly shared evidence base, they differ in how they organize treatment concepts and translate evidence into clinical algorithms. This review compares major diabetes guidelines from the American Diabetes Association (ADA), the National Institute for Health and Care Excellence (NICE), the Japan Diabetes Society (JDS), and the Korean Diabetes Association (KDA), with particular attention to pharmacological algorithms, comorbidity-driven treatment strategies, and the conceptual principles underlying each framework. The ADA guideline uses a person-centered, risk-based approach that prioritizes sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with cardiorenal disease. The NICE guideline applies a more structured strategy, recommending early dual or triple therapy within a cost-effectiveness framework. The JDS guideline emphasizes pathophysiology-based treatment selection tailored to East Asian populations. The KDA guideline retains a glycemia-centered treatment structure while incorporating comorbidity-based decision-making and allowing early, flexible combination therapy. Thus, despite substantial convergence in the evidence base, these guidelines differ in how cardiovascular risk, glycemic control, and pathophysiological heterogeneity are incorporated into treatment decisions. The KDA framework can be viewed as a pragmatic hybrid model that integrates these dimensions and is further extended by recent consensus efforts addressing disease severity and pathophysiology.
Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), especially finerenone, have shown significant cardiorenal benefits in patients with chronic kidney disease (CKD). Clinical trials consistently report reductions in albuminuria and improved renal outcomes; however, the specific intrarenal hemodynamic mechanisms remain partially understood. nsMRAs lower albuminuria, a critical surrogate marker for CKD progression, with early reductions contributing significantly to renal benefits. These agents produce mild natriuretic effects by inhibiting aldosterone-mediated sodium reabsorption in the distal nephron, resulting in a slight reduction in extracellular volume. Additionally, nsMRAs may impact glomerular hemodynamics by mitigating aldosterone-induced constriction of the efferent arterioles and restoring tubuloglomerular feedback, while also modulating connecting tubule glomerular feedback. Collectively, these effects may contribute to lowering intraglomerular pressure and attenuating glomerular hyperfiltration. However, current evidence does not definitively show that nsMRAs are superior to steroidal mineralocorticoid receptor antagonists in correcting hyperfiltration. Their clinical benefits seem to arise from enhanced safety, tolerability, and sustained therapeutic use. This narrative review synthesizes existing clinical and experimental evidence on the intrarenal hemodynamic effects of nsMRAs, emphasizing their roles in sodium handling, natriuresis, and regulation of intraglomerular pressure.
Background:Frailty is a clinical syndrome that increases the vulnerability to adverse outcomes in older adults. C-X-C motif ligand 9 (CXCL9), a marker of chronic inflammation, has been implicated in musculoskeletal decline and mortality. However, its relationship with frailty in older individuals has not been well studied. Methods:This study included 237 community-dwelling women, aged 65 years or older, who underwent a comprehensive geriatric assessment. Serum CXCL9 levels were measured by enzyme-linked immunosorbent assay. Frailty was defined using the Fried phenotype and the Rockwood deficit accumulation index. Associations between serum CXCL9 levels and frailty outcomes were examined using a multivariate regression analysis. Results:Serum CXCL9 increased progressively across the frailty categories (robust: 239.3±110.1 pg/mL; frail: 347.5±119.0 pg/mL; P<0.001). Higher levels of CXCL9 were independently associated with a greater frailty index (β=0.0001, P<0.001), lower skeletal muscle index (β=-0.001, P=0.004), weaker grip strength (β=-0.010, P<0.001), and slower gait speed (β=-0.0003, P=0.039). Women in the highest CXCL9 quartile had 3.20-fold greater odds of frailty (95% confidence interval [CI], 1.70 to 14.56), 3.41-fold greater odds of sarcopenia (95% CI, 1.25 to 9.30), and 6.71-fold greater odds of low muscle strength (95% CI, 1.75 to 25.78) compared with the lowest quartile. Conclusion:Elevated CXCL9 levels were independently associated with greater frailty burden and adverse musculoskeletal phenotypes in older women. These findings support CXCL9 as a promising biomarker of chronic inflammation and frailty, and warrant further investigation through longitudinal studies.
