Risk Assessment of Hepatitis B virus-related Hepatocellular Carcinoma Development Using Transient Elastography: Systematic Review and Meta-analysis.

Background and Aims: Liver stiffness measurement (LSM) using transient elastography (TE) can assess fibrotic burden in chronic liver diseases. The systematic review and meta-analysis was conducted to determine whether LSM using TE can predict the risk of development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Methods: A systematic literature search of the Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases (from January 2010 to June 2023) was conducted. Of the 1,345 individual studies identified, 10 studies that used TE were finally registered. Hazard ratios (HRs) and the 95% confidence interval (CIs) were considered summary estimates of treatment effect sizes of ≥ 11 kilopascal (kPa) standard for HCC development. Meta-analysis was performed using the restricted Maximum Likelihood random effects model. Results: Among the ten studies, data for risk ratios for HCC development could be obtained from nine studies. When analyzed for the nine studies, the HR for HCC development was high at 3.33 (95% CI, 2.45-4.54) in CHB patients with a baseline LSM of ≥ 11 kPa compared to patients who did not. In ten studies included, LSM of ≥ 11 kPa showed the sensitivity and specificity for predicting HCC development were 61% (95% CI, 50-71%) and 78% (95% CI, 66-86%), respectively, and the diagnostic accuracy was 0.74 (95% CI, 0.70-0.77). Conclusions: The risk of HCC development was elevated in CHB patients with TE-determined LSM of ≥11 kPa. This finding suggests that TE-determined LSM values may aid the risk prediction of HCC development in CHB patients.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments.

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.

Effect of air temperature on serum 25-hydroxyvitamin D concentrations: A single institutional large-scale study in Korea.

Vitamin D deficiency is a worldwide health issue especially in women. Serum vitamin D concentrations vary depending on the weather. However, the ideal vitamin D supplementation strategy related to weather remains uncertain. We aimed to investigate the relationship between climate factors and serum 25-hydroxy vitamin D [25(OH)D] concentrations. This study included 11,272 women aged 20-79 who visited a health promotion center for annual checkups between January 2013 and December 2015. We reviewed medical records and collected daily meteorological data. We analyzed the association between serum 25(OH)D concentration and climate factors using simple and multiple regression models and then predicted serum 25(OH)D concentration using multiple fractional polynomial models. The median age of the participants was 51 years (20-79 years), and the mean serum 25(OH)D level was 17.4 ± 8.6 ng/mL. The serum 25(OH)D concentration was lower in young women than in older women. The proportions of women with adequate 25(OH)D levels were 14.9% and 47.0% in the age groups 20-29 and 70-79, respectively. The maximum level of predicted log 25(OH)D was found in September, and the minimum was found in January. In multiple regression analysis, age and monthly mean temperature were associated with 25(OH)D concentrations. Serum 25(OH)D level was predicted using the following formula: log (25(OH)D) = 2.144 + 0.009 × age + 0.018 × ((temperature + 12.4)/10)2 (P < 0.001, adjusted R2 = 0.091). Serum 25(OH)D concentrations changed according to air temperature. An adequate strategy for vitamin D supplementation, based on air temperature, is necessary to maintain healthy serum 25(OH)D levels.

A nationwide real-world study for evaluation of effectiveness and safety of T-DM1 in patients with HER2-positive metastatic breast cancer in Korea (KCSG BR19-15).

Purpose: This study aimed to investigate clinical practices and factors related to the outcomes of T-DM1 use in patients with HER2-positive metastatic breast cancer (mBC). Methods: We included patients with HER2-positive mBC who received T-DM1 as a palliative therapy between August 2017 and December 2018. The safety and outcomes of T-DM1, including overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), were evaluated. A Cox proportional hazards model was used to estimate the hazard ratio and 95% confidence interval (CI) for mortality or progression to HER2-positive mBC. Results: In total, 824 patients were enrolled during the study period. The mean age of patients was 58 years, and 516 (62.6%) patients relapsed after curative treatment. Excluding a history of endocrine therapy, 341 (41.4%) patients previously received none or first-line chemotherapy, 179 (21.7%) received second-line therapy, and 303 (36.9%) received third-or later-line chemotherapy before T-DM1 therapy. During a median follow-up of 16.8 months, the ORR was 35%, the median PFS was 6.6 months, and the median OS was not reached. The clinical factors associated with the hazard of progression were age (<65 years), poor performance status (⩾2), advanced line of palliative chemotherapy (⩾2), prior pertuzumab use, and treatment duration of palliative trastuzumab (<10 months). Common grade 3-4 adverse events were thrombocytopenia (n = 107, 13.2%), neutropenia (n = 23, 2.8%), anemia (n = 21, 2.6%), and elevated liver enzyme (n = 20, 2.5%). Hypokalemia (⩽3.0 mmol/L) and any-grade bleeding events occurred in 25 (3.1%) and 94 (22.6%) patients, respectively. Conclusion: This is the first nationwide real-world study of T-DM1 use in patients with HER2-positive mBC in Korea. The effectiveness and toxicity profiles of T-DM1 in real-world practice were comparable to those in randomized trials. Moreover, patient factors and previous anti-HER2 therapy could predict the outcomes of T-DM1 therapy.

Association between age at diagnosis of type 2 diabetes and cardiovascular morbidity and mortality risks: A nationwide population-based study.

AIMS: We aimed to investigate the association between the age at diagnosis of type 2 diabetes and the risk of cardiovascular (CVD) outcomes in comparison with nondiabetic counterparts. METHODS: A total of 634,350 patients with newly diagnosed type 2 diabetes between January 1, 2012, and December 31, 2014 were included in a Korean population cohort study. Nondiabetic matched controls were selected from the general population in a 1:2 ratio. Participants were followed until the end of 2019 for CVD outcomes and mortality. RESULTS: During 5.7 years of follow-up, patients with type 2 diabetes diagnosed at ≤40 years of age had the highest excess risk for most outcomes relative to controls, with an adjusted hazard ratio (HR) (95 % CI) of 6.08 (5.51-6.70) for total mortality, 7.10 (6.66-7.58) for hospitalization for heart failure, and 5.04 (4.86-5.24) for coronary heart disease. All risks attenuated progressively with each increasing decade of diagnostic age. CONCLUSION: In this population-based cohort study, a younger age at diagnosis of type 2 diabetes was associated with a higher relative risk of mortality and CVD outcomes. Therefore, primary prevention of type 2 diabetes is desirable at all ages but is particularly important at younger ages.

Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019).

BACKGRUOUND: The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults. METHODS: This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability. RESULTS: The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69-3.10; P=0.027-0.038), especially in daughters (OR, 2.04-4.64; P=0.029-0.034). CONCLUSION: HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and the progression of cerebral microbleeds.

Background and purpose: The angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been studied as a genetic candidate for cerebral small vessel disease (CSVD). However, no previous study has evaluated the relationship between the ACE I/D polymorphism and cerebral microbleed (CMB), an important CSVD marker. We evaluated the association between ACE I/D polymorphisms and 2-year changes in CMBs. Methods: The CHALLENGE (Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes) database was analyzed. Of 256 subjects, 186 participants who underwent a 2-year follow-up brain scan and ACE genotyping were included. Our analysis was conducted by dividing the ACE genotype into two groups (DD vs. ID/II) under the assumption of the recessive effects of the D allele. A linear mixed-effect model was used to compare the 2-year changes in the number of CMBs between the DD and combined ID/II genotypes. Results: Among 186 patients included in this study, 24 (12.9%) had the DD genotype, 91 (48.9%) had the ID genotype, and 71 (38.2%) had the II genotype. Baseline clinical characteristics and cerebral small vessel disease markers were not different between the two groups (DD vs. ID/II) except for the prevalence of hypertension (DD 66.7% vs. ID/II 84.6%; p = 0.04). A multivariate linear mixed-effects model showed that the DD carriers had a greater increase in total CMB counts than the ID/II carriers after adjusting for the baseline number of CMBs, age, sex, and hypertension (estimated mean of difference [standard error (SE)] = 1.33 [0.61]; p = 0.03). When we performed an analysis of cases divided into deep and lobar CMBs, only lobar CMBs were significantly different between the two groups (estimated mean of difference [SE] = 0.94 [0.42]; p = 0.02). Conclusion: The progression of CMBs over 2 years was greater in the ACE DD carriers compared with the combined II/ID carriers. The results of our study indicate a possible association between the ACE I/D polymorphism and CMB. A study with a larger sample size is needed to confirm this association.

Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes. Methods and analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI. Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases. Ethics and dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions. Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881).

Age- and dose-dependent effect of statin use on the risk of osteoporotic fracture in older adults.

Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporosis-related measurement has shown controversial results. In this study, we found an age, dose andduration-dependent osteoprotective effect of statins in general older population. PURPOSE: Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporotic fractures has shown controversial results. METHODS: In this study with Korean National Health Insurance Service-Senior cohort database, a total of 365,656 elderly without previous history of osteoporosis and who were started on statin since January 1 2004 were included and observed until December 31 2012. Hazard rations (HR) for major osteoporotic fractures were calculated using the weighted Cox proportional hazards model with inverse-probability of treatment weighting method. RESULTS: During 6.27 years of follow-up period, 54,959 osteoporotic fractures occurred and the majority of fractures (69.5%) were vertebral fractures. Compared with non-users, statin use was associated with a decreased risk of all outcomes with adjusted HR (95% CI) of 0.77 (0.72-0.83; P < 0.001) for major osteoporotic fractures, 0.49 (0.38-0.62; P < 0.001) for hip fractures, and 0.70 (0.64-0.77; P < 0.001) for vertebral fractures. When outcomes were examined separately by sex, the results were broadly comparable in terms of patterns of risk reduction by statin use. The patients with statin initiated at age ≥ 80 years had the highest risk reduction for most outcomes relative to non-users. Higher cumulative dose of statin was negatively associated with the osteoporotic fracture risk; 0.97 (0.91-1.02) for 30-364 cumulative daily defined dose (cDDD), 0.45 (0.40-0.51) for 365-1,094 cDDD, and 0.22 (0.15-0.33) for ≥ 1,095 cDDD. CONCLUSIONS: Our results showed that statin use was associated with significant reduction in the risk of osteoporotic fractures in general older population.

TAK-981, a SUMOylation inhibitor, suppresses AML growth immune-independently.

Acute myeloid leukemia (AML) generally has an unsatisfactory prognosis despite the recent introduction of new regimens, including targeted agents and antibodies. To find a new druggable pathway, we performed integrated bioinformatic pathway screening on large OHSU and MILE AML databases, discovered the SUMOylation pathway, and validated it independently with an external data set (totaling 2959 AML and 642 normal sample data). The clinical relevance of SUMOylation in AML was supported by its core gene expression which is correlated with patient survival, European LeukemiaNet 2017 risk classification, and AML-relevant mutations. TAK-981, a first-in-class SUMOylation inhibitor currently under clinical trials for solid tumors, showed antileukemic effects with apoptosis induction, cell-cycle arrest, and induction of differentiation marker expression in leukemic cells. It exhibited potent nanomolar activity, often stronger than that of cytarabine, which is part of the standard of care. TAK-981's utility was further demonstrated in in vivo mouse and human leukemia models as well as patient-derived primary AML cells. Our results also indicate direct and cancer cell-inherent anti-AML effects by TAK-981, different from the type 1 interferon and immune-dependent mechanism in a previous solid tumor study. Overall, we provide a proof-of-concept for SUMOylation as a new targetable pathway in AML and propose TAK-981 as a promising direct anti-AML agent. Our data should prompt studies on optimal combination strategies and transitions to clinical trials in AML.

TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patients.

BACKGROUND: Transcutaneous oxygen pressure (TcPO2) is a noninvasive, nonradiological test to measure local oxygen released from capillaries through the skin. Since it reflects the metabolic state of the lower limb, it can predict wound healing in patients with critical limb threatening ischemia (CLTI). The purpose of this study was to determine the effectiveness of TcPO2 test in evaluating wound healing potential of patients with CLTI. METHODS: This was a retrospective, single-center, nonrandomized, and observational study. A prospectively registered database of patients who visited Vascular Surgery Department of St. Mary's Hospital for CLTI and underwent TcPO2 tests from October 1, 2015 to July 1, 2021 was reviewed. Patients were divided into 2 groups: (1) those who had amputation only; and (2) those who underwent revascularization procedures. Patients whose wound healing status could not be determined were excluded. The clinical characteristics of patients, patient characteristics related to lower TcPO2 value, treatment success rate, and time for the wound to be healed were analyzed. RESULTS: A total of 84 patients were included in this study. There was no difference in background patient characteristics between the 2 groups despite better survival within 12 months and shorter healing time in the revascularization group. A total of 76 patients survived 12 months after surgery, and 63 patients were healed. Higher HbA1c, higher serum creatinine, history of stroke, and history of coronary artery disease were related to lower TcPO2 value on multiple linear regression. The cutoff value of TcPO2 was determined to be 40 mm Hg for predicting wound healing. This value was similar to those of previous studies. In addition, there was a negative correlation between TcPO2 and wound healing time. Correlations among the anklebrachial index (ABI), toe-brachial index (TBI), and TcPO2 were not determined because ABI and TBI for some patients could not be obtained due to wound condition. CONCLUSIONS: The TcPO2 value can predict the wound healing process of ischemic lower extremity injury.

Association of Early Weight Change With Cognitive Decline in Patients With Parkinson Disease.

BACKGROUND AND OBJECTIVE: To examine whether early weight change is associated with subsequent deterioration in cognitive function, including overall performance and specific domains, in Parkinson disease (PD). METHODS: This observational study used data from the Parkinson Progression Markers Initiative cohort. The patients underwent annual nonmotor assessments covering neuropsychiatric, sleep-related, and autonomic symptoms for up to 8 years of follow-up. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and detailed neuropsychological testing. Linear mixed-effects models were applied to investigate the association of early weight change with longitudinal evolution of cognitive and other nonmotor symptoms. RESULTS: A total of 358 patients with early PD were classified into weight loss (decrease of >3% body weight during the first year; n = 98), weight maintenance (within ±3%; n = 201), and weight gain (increase of >3%; n = 59) groups. The weight loss group showed a significantly faster decline in MoCA scores than the weight maintenance group (ß = -0.19, 95% CI -0.28 to -0.10). With respect to specific cognitive domains, the weight loss group showed a steeper decline in sematic fluency test scores (ß = -0.37, 95% CI -0.66 to -0.08) and MoCA phonemic fluency scores (ß = -0.18, 95% CI -0.31 to -0.05) and, to a lesser extent, Letter-Number Sequencing scores (ß = -0.07, 95% CI -0.14 to 0.01) compared with the weight maintenance group. Conversely, the weight gain group showed a slower decline in the Symbol Digit Modalities Test scores (ß = 0.34, 95% CI 0.05 to 0.63), although no association was found with longitudinal changes in MoCA scores. We did not find any significant effects of weight change on the progression of other nonmotor symptoms. DISCUSSION: Early weight loss was associated with a faster progression of decline in global cognitive function and executive function in patients with PD, whereas early weight gain was associated with a slower progression of decline in processing speed and attention. The impact of early weight change on nonmotor symptoms seemed to be specific to cognition.

Prevalence and Long-term Outcomes of CT Interstitial Lung Abnormalities in a Health Screening Cohort.

Background The association between interstitial lung abnormalities (ILAs) and long-term outcomes has not been reported in Asian health screening populations. Purpose To investigate ILA prevalence in an Asian health screening cohort and determine rates and risks for ILA progression, lung cancer development, and mortality within the 10-year follow-up. Materials and Methods This observational, retrospective multicenter study included patients aged 50 years or older who underwent chest CT at three health screening centers over a 4-year period (2007-2010). ILA status was classified as none, equivocal ILA, and ILA (nonfibrotic or fibrotic). Progression was evaluated from baseline to the last follow-up CT examination, when available. The log-rank test was performed to compare mortality rates over time between ILA statuses. Multivariable Cox proportional hazards models were used to assess factors associated with hazards of ILA progression, lung cancer development, and mortality. Results Of the 2765 included patients (mean age, 59 years ± 7 [SD]; 2068 men), 94 (3%) had a finding of ILA (35 nonfibrotic and 59 fibrotic ILA) and 119 (4%) had equivocal ILA. The median time for CT follow-up and the entire observation was 8 and 12 years, respectively. ILA progression was observed in 80% (48 of 60) of patients with ILA over 8 years. Those with fibrotic and nonfibrotic ILA had a higher mortality rate than those without ILA (P < .001 and P = .01, respectively) over 12 years. Fibrotic ILA was independently associated with ILA progression (hazard ratio [HR], 10.3; 95% CI: 6.4, 16.4; P < .001), lung cancer development (HR, 4.4; 95% CI: 2.1, 9.1; P < .001), disease-specific mortality (HR, 6.7; 95% CI: 3.7, 12.2; P < .001), and all-cause mortality (HR, 2.5; 95% CI: 1.6, 3.8; P < .001) compared with no ILA. Conclusion The prevalence of interstitial lung abnormalities (ILAs) in an Asian health screening cohort was approximately 3%, and fibrotic ILA was an independent risk factor for ILA progression, lung cancer development, and mortality. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Hatabu and Hata in this issue.

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group. Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training. Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs.

Prevalence and risk of diabetic complications in young-onset versus late-onset type 2 diabetes mellitus.

AIMS: To compare the prevalence and risk of diabetic complications between people with young-onset and late-onset type 2 diabetes mellitus (T2DM). METHODS: In this observational study, 10,447 people with T2DM had at least one study of diabetic complications: retinopathy, neuropathy, chronic kidney disease (CKD), carotid artery plaque. We use odds ratios to compare complications between young-onset T2DM (YOD) and late-onset T2DM (LOD). RESULTS: We compare 1,791 people with YOD (diagnosed < 40 years) and 8,656 with LOD (diagnosed ≥ 40 years). The YOD had a higher prevalence of these complications than the LOD (p < 0.011) after adjustment for confounding factors. Further adjustment for diabetes duration greatly attenuated the odds ratios however, neuropathy remained significantly more frequent in people with YOD (adjusted odds ratio: 1.39, 95% confidence interval: 1.13-1.71, p = 002). In cluster analysis on the 2,126 study participants who were diagnosed with T2DM within the previous two years, 47% of the YOD group were in the severe insulin-deficient diabetes cluster in comparison to 23% LOD; 28% and 44% respectively were in the mild age-related diabetes. CONCLUSION: People with YOD had a higher prevalence of complications than those with LOD, but this was mostly attributed to a longer duration of diabetes. However, the prevalence of neuropathy remained significantly higher even after adjusting for factors including the duration of diabetes.

Effect of low skeletal muscle mass and sarcopenic obesity on chronic kidney disease in patients with type 2 diabetes.

OBJECTIVE: This study aimed to investigate the association between low muscle mass or sarcopenic obesity and the risk of incident chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 3123 patients with T2DM with preserved renal function were followed up for incident CKD. Skeletal muscle mass was estimated from bioelectrical impedance analysis. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 . Sarcopenic obesity was defined as the coexistence of sarcopenia and abdominal obesity. RESULTS: During 8.9 years of follow-up, 530 (17.0%) patients developed incident CKD. When patients were divided into three groups based on sex-specific tertiles, lower muscle mass was not associated with an increased risk of incident CKD after adjustment for risk factors. However, when patients were divided into four groups according to the presence of sarcopenia and obesity, sarcopenic obesity was associated with an increased risk of incident CKD (adjusted hazard ratio 1.77; 95% CI: 1.24-2.51; p = 0.001) compared with the other groups. CONCLUSIONS: Sarcopenic obesity, but not low muscle mass alone, may increase the risk of CKD in patients with T2DM.

Prediction of antidiabetic effect after gastrectomy with Roux-en-Y reconstruction in patients with gastric cancer and type 2 diabetes.

This study investigated the antidiabetic outcomes after gastrectomy with long-limb RY reconstruction (LRYR) and the prognostic factors for remission after 1 year in patients with type 2 diabetes (T2DM) and gastric cancer. In 25 Koreans with T2DM and gastric cancer, plasma glucose and insulin levels were measured during a 75 g oral glucose tolerance test, before and 1 week after gastrectomy with LRYR. Patients were examined after 1 year and we defined glycemic control as "remission" when the HbA1c level after 1 year was <6.0% without medication. One year after surgery, 12 patients achieved HbA1c < 6.0% without medication. Among the preoperative indices, the duration of diabetes was shorter in the remission group than that in the non-remission group (median 2.0 [0-6.5] years vs 7.0 [4.5-10.0] years, P = .023). At 1 week after surgery, significant improvements in fasting, 30 minutes, 60 minutes, 90 minutes stimulated glucose levels and insulin resistance (HOMA-IR and Matsuda index) were found only in the remission group. The multivariable logistic regression analysis results showed that higher 30 minutes stimulated glucose level and HOMA-IR index at 1 week after surgery were independent factors for lower odds of 1-year diabetes remission. Shorter duration of diabetes and early postoperative improvements in 30 minutes stimulated glucose level and HOMA-IR were important determinants of long-term antidiabetic outcomes after gastrectomy with LRYR in patients with T2DM and gastric cancer.

Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice.

PURPOSE: This study aimed to evaluate the efficacy and tolerability of dapagliflozin as an add-on or a switch therapy to lobeglitazone plus metformin (MFM) in Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice. MATERIALS AND METHODS: The study included 109 patients who started dapagliflozin as add-on or switch therapy to lobeglitazone plus MFM. The primary outcome was a change in glycated hemoglobin (HbA1c) level from baseline after 12 months of treatment. Secondary outcomes included changes in fasting plasma glucose (FPG), lipid profiles, body weight, visceral fat area (VFA), and blood pressure after 12 months of treatment. RESULTS: The baseline HbA1c was 8.3±1.3% (8.7±1.5% in the add-on group and 8.1±1.0% in the switch group). After 12 months, mean HbA1c decreased (-0.91%) in all patients (p<0.05) (-1.39% in the add-on group and -0.63% in the switch group). Significant reductions in FPG were also observed in both the add-on and switch groups (-54.37 mg/dL and -24.68 mg/dL, respectively). Overall, there was a significant improvement in serum triglyceride (-24.74 mg/dL), low density lipoprotein cholesterol (-7.92 mg/dL), body weight (-2.98 kg), VFA (-9.00 cm²), and systolic blood pressure (-8.67 mm Hg). Approximately 35.8% of patients achieved HbA1c <7.0% after 12 months. CONCLUSION: Dapagliflozin, as an add-on or a switch therapy to lobeglitazone plus MFM, can be a suitable alternative for Korean patients with inadequately controlled T2DM. The combination therapy resulted in significant reductions in HbA1c levels, body weight, and blood pressure.

Differences in complication patterns in subgroups of type 2 diabetes according to insulin resistance and beta-cell function.

This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the "severe beta-cell dysfunction" group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The "severe insulin resistance" group had higher odds of carotid artery plaque presence (aOR 1.238). The "severe insulin resistance and beta-cell dysfunction" group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p < 0.05). After a median of five years of follow-up, this group distinction did not lead to a difference in risk of new diabetic retinopathy or chronic kidney disease. In addition, there was no significant difference among the groups in plaque progression risk over 8-10 years in the longitudinal follow-up analysis. The patterns of complications differ when patients with T2DM are classified according to insulin resistance and beta-cell dysfunction. However, there were no differences in the risk of developing new complications.