20260 research outputs found
Sort by
Long-term outcomes of laparoscopic distal gastrectomy for locally advanced gastric cancer: An individual patient data meta-analysis of KLASS-02 and CLASS-01 randomized controlled trials
No full textOBJECTIVE: Laparoscopic distal gastrectomy (LDG) has potential as a surgical treatment option for locally advanced gastric cancer (LAGC). However, there is uncertainty regarding the generalizability of LDG efficacy across diverse patient populations and treatment settings. This study aimed to assess the outcomes of LDG vs. open distal gastrectomy (ODG) in patients with LAGC despite differences in clinical trial populations and treatment environments. METHODS: The KLASS-02 and CLASS-01 trials are multicenter, non-inferiority, open-label, randomized controlled trials for patients with LAGC eligible for distal subtotal gastrectomy in Korea and China, respectively. Some 1,050 patients were enrolled in KLASS-02, and 1,056 patients were enrolled in CLASS-01. Individual patient data (IPD) from KLASS-02 and CLASS-01 were pooled and analyzed. RESULTS: There were 900 patients in the LDG group and 920 in the ODG group. Baseline characteristics were well balanced between groups. The LDG group had better short-term and recovery outcomes than the ODG group, although anastomotic leakage was more frequent. For patients who underwent LDG vs. ODG, 5-year overall survival (OS) was 82.7% [95% confidence interval (95% CI), 80.2%-85.2%] vs. 83.3% (95% CI, 80.9%-85.8%) (P=0.706) and 5-year recurrence-free survival (RFS) was 76.9% (95% CI, 74.1%-79.7%) vs. 77.9% (95% CI, 75.2%-80.6%) (P=0.666), respectively, with a median follow-up of 70 months. In the multivariable prognostic IPD meta-analysis, the operative approach was not independently associated with OS [hazard ratio (HR)=1.045, 95% CI, 0.833-1.311; P=0.706] or RFS (HR=1.044, 95% CI, 0.859-1.269; P=0.667) for LDG vs. ODG. In the subgroup analysis, LDG demonstrated a significant association with poorer RFS in the pT4 subgroup (HR=1.377, 95% CI, 1.022-1.760; P=0.034). CONCLUSIONS: Despite differences in patient populations, surgical practices, and postoperative treatments between trials, LDG is oncologically safe with the benefit of being minimally invasive for patients with LAGC, except for the pT4 patients. Therefore, LDG could be a good treatment alternative for patients with LAGC; however, caution should be warranted in its application for patients classified as T4
Asia–Pacific consensus for the management of osteoporosis in men
No full textOsteoporosis in men is an underdiagnosed and undertreated condition that leads to significant morbidity and mortality, particularly in the aging population. This consensus report provides tailored guidelines for diagnosing, preventing, and treating male osteoporosis in the Asia-Pacific region by integrating global best practices with regional adaptations. PURPOSE: To establish evidence-based, region-specific guidelines for the management of male osteoporosis in the Asia-Pacific region, addressing demographic and lifestyle factors. METHODS: Expert feedback was gathered through premeeting reviews, consensus conferences, and collaborative discussions. A life-course approach was employed to align international best practices with Asia-Pacific-specific needs, emphasizing continuous monitoring and intervention from middle age onward. RESULTS: The 12 consensus strategies systematically approach male osteoporosis management, addressing screening, diagnosis, treatment, and long-term follow-up. Recommendations include the assessment of fracture risk for men aged 50 years and above, use of dual-energy X-ray absorptiometry (DXA) testing for men aged 70 years and above, lifestyle modifications, and pharmacological interventions such as bisphosphonates, denosumab, and anabolic agents for high-risk patients. Secondary causes of osteoporosis were highlighted, along with the establishment of fracture liaison services (FLSs) to improve long-term care. A life-course approach was proposed to optimize bone health throughout men's lives. CONCLUSION: This consensus provides a comprehensive framework tailored to the Asia-Pacific region for diagnosing, preventing, and managing osteoporosis in men. By addressing region-specific challenges and promoting evidence-based interventions, the latest guidelines incorporating the consensus may depict the conceptual direction in reducing fracture risk and improving long-term bone health outcomes for osteoporosis in men
GULP1 as a novel diagnostic and predictive biomarker in hepatocellular carcinoma
No full textBACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is characterized by high recurrence and mortality, necessitating the identification of reliable biomarkers. In this study, we aimed to identify the predictive gene signatures for HCC recurrence and evaluate the efficiency of GULP PTB domain-containing engulfment adaptor 1 (GULP1) as a predictive and diagnostic marker and therapeutic target for HCC. METHODS: We analyzed genomic datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases via least absolute shrinkage and selection operator Cox regression and 10-fold cross-validation, leading to the development of a 15-gene risk score model, which was validated using three independent datasets. Serum GULP1 and alpha-fetoprotein levels were assessed to determine the diagnostic accuracy of the model. Using clinical cohorts and patient sera, GULP1 roles were examined, and functional assays in vitro and in vivo were used to evaluate its effects on cell growth, epithelial-mesenchymal transition (EMT), ADP-ribosylation factor 6 (ARF6) activation, and beta-catenin signaling. RESULTS: Our newly developed risk-score model accurately predicted recurrent HCC in all datasets. Among the 15 genes in the risk score model, GULP1 was overexpressed in patients with HCC and independently predicted HCC recurrence. Its expression modulation influenced cell growth and EMT, with observed effects on ARF6 activation and beta-catenin signaling pathways. CONCLUSION: GULP1 is a crucial biomarker for HCC, serving as a non-invasive diagnostic and predictive tool. It also plays key roles in HCC progression. Our findings highlight the potential use of GULP1 in treatment strategies targeting EMT and HCC recurrence to improve the personalized care and patient outcomes
Global, regional, and national burden of household air pollution, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBACKGROUND: Despite a substantial reduction in the use of solid fuels for cooking worldwide, exposure to household air pollution (HAP) remains a leading global risk factor, contributing considerably to the burden of disease. We present a comprehensive analysis of spatial patterns and temporal trends in exposure and attributable disease from 1990 to 2021, featuring substantial methodological updates compared with previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study, including improved exposure estimations accounting for specific fuel types. METHODS: We estimated HAP exposure and trends and attributable burden for cataract, chronic obstructive pulmonary disease, ischaemic heart disease, lower respiratory infections, tracheal cancer, bronchus cancer, lung cancer, stroke, type 2 diabetes, and causes mediated via adverse reproductive outcomes for 204 countries and territories from 1990 to 2021. We first estimated the mean fuel type-specific concentrations (in mug/m(3)) of fine particulate matter (PM(2.5)) pollution to which individuals using solid fuels for cooking were exposed, categorised by fuel type, location, year, age, and sex. Using a systematic review of the epidemiological literature and a newly developed meta-regression tool (meta-regression: Bayesian, regularised, trimmed), we derived disease-specific, non-parametric exposure-response curves to estimate relative risk as a function of PM(2.5) concentration. We combined our exposure estimates and relative risks to estimate population attributable fractions and attributable burden for each cause by sex, age, location, and year. FINDINGS: In 2021, 2.67 billion (95% uncertainty interval [UI] 2.63-2.71) people, 33.8% (95% UI 33.2-34.3) of the global population, were exposed to HAP from all sources at a mean concentration of 84.2 mug/m(3). Although these figures show a notable reduction in the percentage of the global population exposed in 1990 (56.7%, 56.4-57.1), in absolute terms, there has been only a decline of 0.35 billion (10%) from the 3.02 billion people exposed to HAP in 1990. In 2021, 111 million (95% UI 75.1-164) global disability-adjusted life-years (DALYs) were attributable to HAP, accounting for 3.9% (95% UI 2.6-5.7) of all DALYs. The rate of global, HAP-attributable DALYs in 2021 was 1500.3 (95% UI 1028.4-2195.6) age-standardised DALYs per 100 000 population, a decline of 63.8% since 1990, when HAP-attributable DALYs comprised 4147.7 (3101.4-5104.6) age-standardised DALYs per 100 000 population. HAP-attributable burden remained highest in sub-Saharan Africa and south Asia, with 4044.1 (3103.4-5219.7) and 3213.5 (2165.4-4409.4) age-standardised DALYs per 100 000 population, respectively. The rate of HAP-attributable DALYs was higher for males (1530.5, 1023.4-2263.6) than for females (1318.5, 866.1-1977.2). Approximately one-third of the HAP-attributable burden (518.1, 410.1-641.7) was mediated via short gestation and low birthweight. Decomposition of trends and drivers behind changes in the HAP-attributable burden highlighted that declines in exposures were counteracted by population growth in most regions of the world, especially sub-Saharan Africa. INTERPRETATION: Although the burden attributable to HAP has decreased considerably, HAP remains a substantial risk factor, especially in sub-Saharan Africa and south Asia. Our comprehensive estimates of HAP exposure and attributable burden offer a robust and reliable resource for health policy makers and practitioners to precisely target and tailor health interventions. Given the persistent and substantial impact of HAP in many regions and countries, it is imperative to accelerate efforts to transition under-resourced communities to cleaner household energy sources. Such initiatives are crucial for mitigating health risks and promoting sustainable development, ultimately improving the quality of life and health outcomes for millions of people. FUNDING: Bill & Melinda Gates Foundation
Synthetic Data-Enhanced Classification of Prevalent Osteoporotic Fractures Using Dual-Energy X-Ray Absorptiometry-Based Geometric and Material Parameters
No full textBACKGRUOUND: Bone fracture risk assessment for osteoporotic patients is essential for implementing early countermeasures and preventing discomfort and hospitalization. Current methodologies, such as Fracture Risk Assessment Tool (FRAX), provide a risk assessment over a 5- to 10-year period rather than evaluating the bone's current health status. METHODS: The database was collected by Ajou University Medical Center from 2017 to 2021. It included 9,260 patients, aged 55 to 99, comprising 242 femur fracture (FX) cases and 9,018 non-fracture (NFX) cases. To model the association of the bone's current health status with prevalent FXs, three prediction algorithms-extreme gradient boosting (XGB), support vector machine, and multilayer perceptron-were trained using two-dimensional dual-energy X-ray absorptiometry (2D-DXA) analysis results and subsequently benchmarked. The XGB classifier, which proved most effective, was then further refined using synthetic data generated by the adaptive synthetic oversampler to balance the FX and NFX classes and enhance boundary sharpness for better classification accuracy. RESULTS: The XGB model trained on raw data demonstrated good prediction capabilities, with an area under the curve (AUC) of 0.78 and an F1 score of 0.71 on test cases. The inclusion of synthetic data improved classification accuracy in terms of both specificity and sensitivity, resulting in an AUC of 0.99 and an F1 score of 0.98. CONCLUSION: The proposed methodology demonstrates that current bone health can be assessed through post-processed results from 2D-DXA analysis. Moreover, it was also shown that synthetic data can help stabilize uneven databases by balancing majority and minority classes, thereby significantly improving classification performance
Atypical Mid-Late Phase ICGA Hyperfluorescence in a Secondary MEWDS Case: A Distinct Disease or a Shift in Our Understanding of MEWDS?
No full textPURPOSE: To report a secondary multiple evanescent white dot syndrome (MEWDS) case with peculiar indocyanine green angiography (ICGA) findings. METHOD: Report of a patient with sickle cell disease (SCD) and a longstanding macular hole who developed an atypical form of secondary MEWDS. Analysis of multimodal imaging findings was performed. RESULTS: A 33-year-old female with SCD presented with a longstanding full-thickness macular hole in the left eye, but then was lost to follow-up. Upon her return nine months later, fundus examination revealed new, asymptomatic, yellowish lesions at the level of the outer retina or retinal pigment epithelium (RPE). ICGA showed a peculiar hyperfluorescence in mid-to-late phases, while fundus autofluorescence (FAF) highlighted distinct temporal patterns of hyper-autofluorescence. Some of the ICGA hyperfluorescent lesions displayed a central hypofluorescent core. The multimodal imaging findings suggest a distinct disease or a sequential mechanism in MEWDS pathophysiology. The process may begin with an initial photoreceptoritis, marked by primary self-resolving hyper-autofluorescence on FAF, followed by an early RPE dysfunction with choroidal hyperpermeability evidenced by mid-late phase ICGA hyperfluorescence, then more marked RPE dysfunction shown by late-phase ICGA hypofluorescence and FAF hyper-autofluorescence. CONCLUSION: This case describes an unusual secondary MEWDS presentation with unique imaging findings. The peculiar ICGA behavior and evolving FAF patterns may suggest either a distinct disease or a shift in our understanding of MEWDS involving photoreceptoritis, early RPE dysfunction, followed by more advanced RPE damage. The findings underscore the need for a nuanced approach to interpreting white-dot syndromes
Efficacy and safety of low-dose atorvastatin plus ezetimibe for primary hypercholesterolemia: A randomized, double-blind, multicenter phase 3 trial
No full textStudies have suggested that low-dose statin monotherapy may be insufficient for target LDL-C levels. In this randomized, double-blind, multicenter phase 3 trial, we evaluated the efficacy of combined ezetimibe and low-dose atorvastatin in 222 Korean patients with primary hypercholesterolemia. Participants received either 10-mg ezetimibe/5-mg atorvastatin (EZE10/ATV5), 10-mg ezetimibe (EZE10), 5-mg atorvastatin (ATV5), or 10-mg atorvastatin (ATV10). At 8 weeks, EZE10/ATV5 achieved the greatest LDL-C reduction (-44.8%) compared with EZE10 (-12.7%, p < 0.0001), ATV5 (-27.3%, p < 0.0001), and ATV10 (-32.0%, p = 0.0012). The combination therapy showed the highest LDL-C goal achievement rate (41.1% vs. EZE10 8.9%, p < 0.0001; ATV5 10.9%, p < 0.0001; ATV10 27.3%, p = 0.0342), particularly in moderate to high-risk patients. Additionally, EZE10/ATV5 had the lowest adverse events among all groups (6.9% vs. 15.0%, 12.3%, and 27.6%, p = 0.017), with most events being mild. These findings suggest that the combination of ezetimibe and low-dose atorvastatin provides superior lipid-lowering efficacy with an improved safety profile, offering an effective treatment for primary hypercholesterolemia in Korean patients
The Preventive Effect of Physical Activity on Gestational Diabetes Mellitus: A Korean Longitudinal Prospective Cohort Study
No full textBACKGRUOUND: To assess longitudinally physical activity patterns and intensity from pre-pregnancy to postpartum and evaluate the association between timing and type of physical activity and the development of gestational diabetes mellitus (GDM). METHODS: The Korean Pregnancy Outcome Study (KPOS) is a prospective cohort study conducted from 2013 to 2017. Our study included 3,457 participants with singleton pregnancies in KPOS, classified according to the pregnancy outcome: GDM (n=231) and normal (n=3,226). Physical activity data were collected at five time points using the short form of the International Physical Activity Questionnaire: before pregnancy, at 12, 24, and 36 gestational weeks (GW), and 6-8 weeks postpartum. Pre-pregnancy physical activity was collected through recall at 12 GW. RESULTS: Maternal age, pre-pregnancy body mass index, educational status, smoking, mini dietary assessment index, first-degree family history of diabetes, hypertension, parity, pre-existing GDM, and previous macrosomia showed significant differences between the GDM group and the normal group (P<0.05 for all). Pre-pregnancy muscle-strengthening activity was significantly associated with a lower risk of GDM (adjusted odds ratio, 0.46; 95% confidence interval, 0.25 to 0.85). CONCLUSION: These findings suggest that physical activity, such as muscle-strengthening activities before pregnancy, could be a preventive strategy to reduce GDM risk. Although the study does not provide evidence that physical activity during pregnancy and postpartum reduces GDM risk, it offers significant insights into the importance of maintaining a healthy level of physical activity from pre-pregnancy to prevent GDM
Longitudinal insights into the natural history of Type 2 diabetes among Koreans: A 20-year community-based prospective cohort study
No full textOBJECTIVE: To investigate the natural history of diabetes mellitus (DM) based on metabolic phenotypes of prediabetes in a community-based prospective study. METHODS: Individuals aged 40-69 years without DM were followed for 20 years. Glycemic parameters, including the 75 g oral glucose tolerance test, were assessed at baseline and biennially thereafter. Markov models were used to estimate each glycemic state's annual transition probabilities and average total length of residence. RESULTS: Among the 7,676 participants without DM, 205 had isolated impaired fasting glucose (iIFG), and 1,753 had impaired glucose tolerance (IGT) at baseline. During the 17.5 years of follow-up, 2,313 (30.1%) cases of DM occurred. The annual transition to DM for those with iIFG was 7.7% (95% confidence interval [CI] 6.9, 8.5) and 6.9% (95% CI 6.6, 7.3) for those with IGT. In the normoglycemia <--> iIFG --> DM model, the total length in normoglycemia was 49.4 years (95% CI 47.0, 52.1), and the length in iIFG was 6.3 years (95% CI 5.9, 6.8). In the normoglycemia <--> IGT --> DM model, the total length in normoglycemia was 34.0 years (95% CI 32.4, 35.4), and the length in IGT was 11.9 years (95% CI 11.1, 12.5). CONCLUSIONS: Individuals remained normoglycemic for long periods. However, the progression to DM occurs rapidly once prediabetes develops, regardless of the metabolic phenotype
Comparative study of 18F-labeled PET radiopharmaceuticals in an Alzheimer’s disease mouse model
No full textBACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia, characterized by memory loss, cognitive decline, and significant social and economic burdens. Despite extensive research into amyloid positron emission tomography (PET) radiopharmaceuticals, the effectiveness of various (18)F-labeled tracers for imaging amyloid plaques in AD mouse models remains uncertain. This study aimed to evaluate the performance of three radiopharmaceuticals-(18)F-florbetaben (FBB), (18)F-flutemetamol (FMM), and (18)F-florapronol (FPN)-in differentiating amyloid deposition in AD and control mice. RESULTS: (18)F-FMM and (18)F-FBB demonstrated significantly higher standardized uptake value ratios (SUVRs) in AD mice than in controls. For (18)F-FBB, the mean SUVR in AD mice was 1.06, significantly higher than the 0.81 in controls (p < 0.001). Similarly, (18)F-FMM showed a mean SUVR of 0.97 in AD mice compared to 0.94 in controls (p = 0.024). In contrast, (18)F-FPN did not show significant SUVR differences between AD and control groups (p = 0.071). Comparative analysis revealed that (18)F-FBB exhibited a significantly greater SUVR difference between AD and control groups compared to (18)F-FMM (p < 0.001). CONCLUSIONS: (18)F-FBB emerged as the most effective radiopharmaceutical for imaging amyloid deposition in AD mouse models, providing superior differentiation between AD and control groups. These findings support the optimization of amyloid PET tracers for preclinical studies, facilitating advancements in Alzheimer's research. CLINICAL TRIAL NUMBER: Not applicable