Cancer Risk in Graves Disease with Radioactive 131I Treatment: A Nationwide Cohort Study.

Radioactive 131I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service's National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD (International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4-5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2-12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370-630 MBq) in the RAI therapy group. During 2004-2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88-1.06); this remained at 0.96 (95% CI, 0.83-1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17-4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66-1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD.

Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study.

AIMS: Omega-3 fatty acids and fenofibrates have shown some beneficial cardiovascular effects; however, their efficacy has not been compared. This study aimed to compare the effectiveness of currently available omega-3 fatty acids and fenofibrate for reducing major adverse cardiovascular events (MACE). METHODS AND RESULTS: From a nationwide population-based cohort in South Korea (2008-2019), individuals with metabolic syndrome (≥30 years) who received statin with omega-3 fatty acids and those receiving statin with fenofibrate were matched by propensity score (n = 39 165 in both groups). The primary outcome was MACE, including ischaemic heart disease (IHD), ischaemic stroke (IS), and death from cardiovascular causes. The risk of MACE was lower [hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.74-0.83] in the fenofibrate group than in the omega-3 fatty acid group. Fenofibrate was associated with a lower incidence of IHD (HR, 0.72; 95% CI, 0.67-0.77) and hospitalization for heart failure (HR, 0.90; 95% CI, 0.82-0.97), but not IS (HR, 0.90; 95% CI, 0.81-1.00) nor death from cardiovascular causes (HR, 1.07; 95% CI, 0.97-1.17). The beneficial effect of fenofibrate compared to omega-3 fatty acids was prominent in patients with preexisting atherosclerotic cardiovascular disease and those receiving lower doses of omega-3 fatty acids (≤2 g per day). CONCLUSION: In a real-world setting, fenofibrate use was associated with a lower risk of MACE compared with low-dose omega-3 fatty acids when added to statins in people with metabolic syndrome.

Comparison of on-Statin Lipid and Lipoprotein Levels for the Prediction of First Cardiovascular Event in Type 2 Diabetes Mellitus.

BACKGRUOUND: A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented. METHODS: From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C. RESULTS: MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL. CONCLUSION: On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

Increased Risk of Hip Fracture in Patients with Acromegaly: A Nationwide Cohort Study in Korea.

BACKGRUOUND: Acromegaly leads to various skeletal complications, and fragility fractures are emerging as a new concern in patients with acromegaly. Therefore, this study investigated the risk of fractures in Korean patients with acromegaly. METHODS: We used the Korean nationwide claims database from 2009 to 2019. A total of 931 patients with acromegaly who had never used an osteoporosis drug before and were treated with surgery alone were selected as study participants, and a 1:29 ratio of 26,999 age- and sex-matched osteoporosis drug-naïve controls without acromegaly were randomly selected from the database. RESULTS: The mean age was 46.2 years, and 50.0% were male. During a median follow-up of 54.1 months, there was no difference in the risks of all, vertebral, and non-vertebral fractures between the acromegaly and control groups. However, hip fracture risk was significantly higher (hazard ratio [HR], 2.73; 95% confidence interval [CI], 1.32 to 5.65), and non-hip and non-vertebral fractures risk was significantly lower (HR, 0.40; 95% CI, 0.17 to 0.98) in patients with acromegaly than in controls; these results remained robust even after adjustment for socioeconomic status and baseline comorbidities. Age, type 2 diabetes mellitus, cardio-cerebrovascular disease, fracture history, recent use of acid-suppressant medication, psychotropic medication, and opioids were risk factors for all fractures in patients with acromegaly (all P<0.05). CONCLUSION: Compared with controls, patients surgically treated for acromegaly had a higher risk of hip fractures. The risk factors for fracture in patients with acromegaly were consistent with widely accepted risk factors in the general population.

Sex differences in mortality in patients with acromegaly: a nationwide cohort study in Korea.

OBJECTIVE: The results of previous studies on sex differences in mortality and comorbidities among patients with acromegaly are diverse. We assessed sex differences in mortality and the risk of complications in patients with acromegaly. METHODS: We included 1884 patients with acromegaly with 1:50 age- and sex-matched 94 200 controls using the Korean nationwide claims database from 2009 to 2019. RESULTS: During the median 5.51 years of follow-up, the acromegaly group had higher all-cause mortality than the control group (hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.38-2.19), with higher risk in women than men (HR 2.17 vs 1.36). The most common cause of death was malignancy. Women with acromegaly aged ≥50 years exhibited significantly higher mortality than men with acromegaly aged ≥50 years (HR 1.74 vs 0.96). In a treatment subgroup other than surgery alone, women had a higher risk of mortality than men (HR 2.82 vs 1.58). Sex differences in mortality among patients with acromegaly remained equal after adjustment for the Charlson Comorbidity Index (CCI), socioeconomic status (SES), body mass index (BMI), alcohol consumption, smoking, fasting plasma glucose, creatinine, and total cholesterol. Patients with acromegaly had elevated risks of developing major adverse cardiovascular events (MACE), atrial fibrillation, obstructive sleep apnea (OSA), diabetes mellitus (DM), end-stage renal disease (ESRD), Parkinson's disease (PD), depression, and malignancy than age- and sex-matched controls, with a higher risk of OSA and DM in women than men. CONCLUSIONS: The risk of mortality and complications in patients with acromegaly compared to age- and sex-matched controls was higher in women than in men.

Effect of a Wearable Device-Based Physical Activity Intervention in North Korean Refugees: Pilot Randomized Controlled Trial.

BACKGROUND: Effective health interventions for North Korean refugees vulnerable to metabolic disorders are currently unelucidated. OBJECTIVE: This study aimed to evaluate the effects of digital health interventions in North Korean refugees using a wearable activity tracker (Fitbit device). METHODS: We conducted a prospective, randomized, open-label study on North Korean refugees aged 19-59 years between June 2020 and October 2021 with a 12-week follow-up period. The participants were randomly assigned to either an intervention group or a control group in a 1:1 ratio. The intervention group received individualized health counseling based on Fitbit data every 4 weeks, whereas the control group wore the Fitbit device but did not receive individualized counseling. The primary and secondary outcomes were the change in the mean daily step count and changes in the metabolic parameters, respectively. RESULTS: The trial was completed by 52 North Korean refugees, of whom 27 and 25 were in the intervention and control groups, respectively. The mean age was 43 (SD 10) years, and 41 (78.8%) participants were women. Most participants (44/52, 95.7%) had a low socioeconomic status. After the intervention, the daily step count in the intervention group increased, whereas that in the control group decreased. However, there were no significant differences between the 2 groups (+83 and -521 steps in the intervention and control groups, respectively; P=.500). The effects of the intervention were more prominent in the participants with a lower-than-average daily step count at baseline (<11,667 steps/day). After the 12-week study period, 85.7% (12/14) and 46.7% (7/15) of the participants in the intervention and control groups, respectively, had an increased daily step count (P=.05). The intervention prevented the worsening of the metabolic parameters, including BMI, waist circumference, fasting blood glucose level, and glycated hemoglobin level, during the study period. CONCLUSIONS: The wearable device-based physical activity intervention did not significantly increase the average daily step count in the North Korean refugees in this study. However, the intervention was effective among the North Korean refugees with a lower-than-average daily step count; therefore, a large-scale, long-term study of this intervention type in an underserved population is warranted. TRIAL REGISTRATION: Clinical Research Information Service KCT0007999; https://cris.nih.go.kr/cris/search/detailSearch.do/23622.

Serum fibroblast growth factor 1 and its association with pancreatic beta cell function and insulin sensitivity in adults with glucose intolerance.

Background: Beneficial role of fibroblast growth factor 1 (FGF1) in the regulation of glucose metabolism and adipose tissue remodeling was suggested in rodents. This study aimed to investigate the association between serum FGF1 levels and metabolic parameters in adults with glucose intolerance. Methods: Serum FGF1 levels were examined using an enzyme-linked immunosorbent assay in 153 individuals with glucose intolerance. Associations between serum FGF1 levels and metabolic parameters, including body mass index (BMI), glycated hemoglobin (HbA1c), and 75 g oral glucose tolerance test-derived parameters, including insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and disposition index (DI), were examined. Results: Serum FGF1 was detected in 35 individuals (22.9%), possibly due to the autocrine/paracrine nature of the peptide. IGI and DI levels were significantly lower in individuals with higher FGF1 levels than in those with lower FGF1 levels or undetectable FGF1 (p=0.006 and 0.005 for IGI and DI, respectively, after adjustment for age, sex, and BMI). Univariable and multivariable analyses using the Tobit regression model also revealed a negative association between FGF1 levels and IGI and DI. The regression coefficients per 1-SD of log-transformed IGI and DI were -0.461 (p=0.013) and -0.467 (p=0.012), respectively, after adjustment for age, sex, and BMI. In contrast, serum FGF1 levels were not significantly associated with ISI, BMI, or HbA1c. Conclusions: The serum concentration of FGF1 was significantly elevated in individuals with low insulin secretion, suggesting a possible interaction between FGF1 and beta cell function in humans.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (EF), HF with mildly reduced EF, and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

Korean Society of Heart Failure Guidelines for the Management of Heart Failure: Definition and Diagnosis.

The Korean Society of Heart Failure guidelines aim to provide physicians with evidence-based recommendations for diagnosing and managing patients with heart failure (HF). In Korea, the prevalence of HF has been rapidly increasing in the last 10 years. HF has recently been classified into HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (EF), and HF with preserved EF (HFpEF). Moreover, the availability of newer therapeutic agents has led to an increased emphasis on the appropriate diagnosis of HFpEF. Accordingly, this part of the guidelines will mainly cover the definition, epidemiology, and diagnosis of HF.

All-cause and cause-specific mortality risks associated with calcium supplementation with or without vitamin D: A nationwide population-based study.

BACKGROUND: Current evidence regarding the mortality outcomes associated with calcium supplementation with or without low-dose vitamin D is conflicting. OBJECTIVES: To investigate the effects of calcium supplementation with or without vitamin D on all-cause and cause-specific mortalities in a large-scale cohort. METHODS: This study used data from the Korean National Health Insurance System database and National Death Registry. A total of 27,846 participants aged >55 years who had taken calcium supplements with or without vitamin D for at least 90 days (calcium supplementation only [CaO], n = 6256; calcium supplementation in combination with vitamin D [CaD], n = 21,590) were matched in a 1:1 ratio to those who did not take calcium or vitamin D supplements (control group) using propensity scores. RESULTS: No difference in all-cause mortality risk was found between the CaO and control groups: (adjusted hazard ratio [HR] = 1.00; 95% confidence interval [CI]: 0.92-1.10). However, all-cause mortality was lower in the CaD group (HR = 0.85; 95% CI: 0.80-0.89) compared with that in the control group. Mortality risk associated with cardiovascular disease (CVD) was decreased in the CaD group when the daily vitamin D dose received was less than 1000 IU (HR = 0.72; 95% CI: 0.64-0.81). Subgroup analysis showed significant effect of vitamin D with calcium in individuals who were female, aged ≥65 years or had previous history of cancer or CVD. CONCLUSION: In combination with calcium, vitamin D supplementation provides better outcomes for all-cause mortality, particularly CVD-associated mortality, in a duration-dependent manner.

Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer.

BACKGROUND: We aimed to investigate whether the risk of second primary malignancy (SPM) in patients with thyroid cancer (TC) receiving radioactive iodine (RAI) therapy rises in a cumulative, dose-dependent manner compared with those not undergoing RAI. METHODS: Using the Korean National Health Insurance Service National Health Information Database (2002-2019), we investigated hazard ratios of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis. RESULTS: Of 217 777 patients with TC (177 385 women and 40 392 men; mean [SD] age, 47.2 [11.6] years), 100 448 (46.1%) received RAI therapy. The median (IQR) follow-up duration was 7.7 (5.5-10.3) years, and the median (IQR) cumulative RAI dose was 3.7 (1.9-5.6) GBq. From 2004 to 2019, SPM incidence rates were 7.30 and 6.56 per 1000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted hazard ratio of 1.09 (95% confidence interval = 1.05 to 1.13); this rate remained at 1.08 (95% confidence interval = 1.04 to 1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly, from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers were the most significantly elevated risks in patients who underwent RAI therapy. CONCLUSIONS: This study identified that SPM risk increased linearly in a dose-dependent manner in patients with TC undergoing RAI therapy compared with those not undergoing RAI therapy.

Addition of fenofibrate to statins is associated with risk reduction of diabetic retinopathy progression in patients with type 2 diabetes and metabolic syndrome: A propensity-matched cohort study.

AIM: This study aimed to determine the association between fenofibrate added to statin therapy and diabetic retinopathy progression. METHODS: In this propensity-matched study using the Korean National Health Insurance Service cohort (2002-2019), patients with type 2 diabetes and metabolic syndrome (≥ 30 years) receiving statin therapy were matched 1:2 by propensity score into the statin plus fenofibrate group (n = 22,395) and statin-only group (n = 43,191). The primary outcome was a composite of diabetic retinopathy progression including vitreous hemorrhage, vitrectomy, laser photocoagulation, intravitreous injection therapy and retinal detachment. RESULTS: The median (quartiles) follow-up duration was 44.0 (27.6-70.6) months. For the primary outcome, the incidence rate per 1,000 person-years was 9.66 in the statin-only group and 8.68 in the statin-plus-fenofibrate group. The risk of the primary outcome was significantly lower (hazard ratio [HR]=0.88; 95% confidence interval [0.81;0.96] P = 0.005) in the statin-plus-fenofibrate group than in the statin-only group. Only patients with pre-existing retinopathy showed benefits from fenofibrate treatment (HR=0.83 [0.73;0.95] P = 0.006). In addition, the statin plus fenofibrate group exhibited significantly lower risks of vitreous hemorrhage (HR= 0.86 [0.75;0.995] P = 0.042), laser photocoagulation (HR=0.86 [0.77;0.96] P = 0.009) and intravitreous injection therapy (HR=0.73 [0.59;0.90] P = 0.003) than those in the statin-only group. There was no significant interaction between the different characteristics at baseline and the treatment effect. CONCLUSION: The addition of fenofibrate to statins was associated with significantly lower risk of diabetic retinopathy progression than statin therapy alone in patients with type 2 diabetes and metabolic syndrome.

Assessment of existing anthropometric indices for screening sarcopenic obesity in older adults.

Sarcopenic obesity is defined as the presence of high fat mass and low muscle mass combined with low physical function, and it is closely related with the onset of cardiovasular diseases (CVD). The existing anthropometric indices, which are being utilised in clinical practice as predictors of CVD, may also be used to screen sarcopenic obesity, but their feasibility remained unknown. Using cross-sectional data of 2031 participants aged 70-84 years (mean age, 75·9 ± 3·9 years; 49·2 % women) from the Korean Frailty and Aging Cohort Study, we analysed the association of anthropometric indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and weight-adjusted waist index (WWI) with sarcopenic obesity. Body composition was measured using dual-energy X-ray absorptiometry. Higher WWI, WHtR and WC quartiles were associated with higher risk of sarcopenic obesity; the odds ratio (OR) of sarcopenic obesity were highest in the fourth quartile of the WWI (OR: 10·99, 95 % CI: 4·92-24·85, Pfor trend < 0·001). WWI provided the best diagnostic power for sarcopenic obesity in men (area under the receiver operating characteristic curve: 0·781, 95 % CI: 0·751-0·837). No anthropometric indices were significantly associated with sarcopenic obesity in women. WWI was the only index that was negatively correlated with physical function in both men and women. WWI showed the strongest association with sarcopenic obesity, defined by high fat mass and low muscle mass combined with low physical function only in older men. No anthropometric indices were associated with sarcopenic obesity in older women.

Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation.

PURPOSE: BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. MATERIALS AND METHODS: Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. RESULTS: A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. CONCLUSION: We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Atrial Cardiomyopathy with Impaired Functional Reserve in Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND: Impaired atrial functional reserve during exercise may represent an early stage of atrial cardiomyopathy. To test this hypothesis, the authors evaluated left atrial (LA) and left ventricular (LV) function reserve during exercise in patients with paroxysmal atrial fibrillation (PAF). METHODS: Sixty-one patients with PAF undergoing radiofrequency catheter ablation and 38 healthy control subjects were prospectively enrolled. LV global longitudinal strain and LA reservoir strain (RS) were measured at rest and during supine bicycle exercise. To identify the early stage of atrial cardiomyopathy without LA structural remodeling, patients with PAF were divided into two groups according to LA volume index (LAVI): atrial fibrillation (AF) group 1 (LAVI ≥ 34 mL/m2) and AF group 2 (LAVI < 34 mL/m2). RESULTS: LV ejection fraction and global longitudinal strain did not differ between patients with AF and control subjects. LAVI and LA RS did not differ between AF group 2 and control subjects. During exercise, LV global longitudinal strain improved in all groups. Increases in LA RS were attenuated in both AF groups, which also exhibited lower LA functional reserve index than the control subjects. Although resting LA RS was similar between AF group 2 and control subjects, LA functional reserve index was significantly lower in AF group 2. LA functional reserve index was associated with risk for AF recurrence (hazard ratio, 0.852; 95% CI, 0.736-0.988). CONCLUSIONS: Atrial cardiomyopathy can be anticipated by impaired LA functional reserve during exercise in patients with AF, even in those with normal-sized left atria. Atrial cardiomyopathy occurs independently of changes in LV function and is associated with the recurrence of AF in patients with PAF after radiofrequency catheter ablation.

Temporal trends in heart failure over 11 years in the aging Korean population: A retrospective study using the national health insurance database.

BACKGROUND: Understanding national trends of heart failure (HF) is crucial for establishing prevention and treatment strategies. We aimed to investigate the 11-year trends of HF in the South Korean population. METHODS: Using the Korean National Health Insurance Service database, we identified 3,446,256 patients with HF between 2004 and 2014. RESULTS: The prevalence of HF was 1.42% in 2004, steadily increasing to 1.98% in 2014. However, the age-adjusted prevalence of HF remained stable (1.43% in 2014). The incidence of HF was 6.1/1000 person-years in 2004 and remained at similar levels, reaching 5.4/1000 person-years in 2014. The age-adjusted incidence of HF slowly decreased to 3.94/1000 person-years in 2014. The event rate for hospitalized patients with HF remained stable increasing from 1.40 in 2004 to 1.87/1000 person-years in 2014, and the age-adjusted event rate of hospitalized HF decreased to 1.22 in 2014. CONCLUSIONS: In South Korea, between 2004 and 2014, the prevalence of HF increased while the incidence of HF remained stable. Furthermore, the age-adjusted HF prevalence was stable, and the age-adjusted incidence decreased. This indicates that the aging population is the main cause of the increasing national burden associated with HF and that further attention is warranted in the management of HF in older adults.

Prognostic Value of Short-Term Follow-up of Multiple Biomarkers After Discharge in Hospitalized Patients With Acute Heart Failure (POSTBIO-HF): Rationale and Study Design.

Several surrogate biomarkers possess prognostic significance for heart failure (HF), and a decline in their respective values may predict clinical improvement. However, data on the prognostic value of these biomarkers during short-term follow-up after discharge in acute decompensated HF are scarce. We aim to evaluate the prognostic value of short-term follow-up of surrogate biomarkers for predicting the prognosis of hospitalized patients with acute decompensated HF. This multi-center, prospective study will enroll consecutive hospitalized patients with acute decompensated HF. All patients will undergo sampling and comparison of biomarkers, including plasma N-terminal pro-brain natriuretic peptide, growth differentiation factor 15, troponin-T, high-sensitivity C-reactive protein, and urinary albumin/creatinine ratio obtained within 1 month and 6 months after discharge from the index admission. The primary endpoint is a composite of cardiovascular mortality or HF hospitalization during 1 year of follow-up. We will investigate the prognostic value of multiple biomarkers for the primary endpoint. This trial will provide robust evidence for novel multi-biomarker strategies for acute decompensated HF in real-world settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04437628.

Identification of Healthy and Unhealthy Lifestyles by a Wearable Activity Tracker in Type 2 Diabetes: A Machine Learning-Based Analysis.

Lifestyle is a critical aspect of diabetes management. We aimed to define a healthy lifestyle using objectively measured parameters obtained from a wearable activity tracker (Fitbit) in patients with type 2 diabetes. This prospective observational study included 24 patients (mean age, 46.8 years) with type 2 diabetes. Expectation-maximization clustering analysis produced two groups: A (n=9) and B (n=15). Group A had a higher daily step count, lower resting heart rate, longer sleep duration, and lower mean time differences in going to sleep and waking up than group B. A Shapley additive explanation summary analysis indicated that sleep-related factors were key elements for clustering. The mean hemoglobin A1c level was 0.3 percentage points lower at the end of follow-up in group A than in group B. Factors related to regular sleep patterns could be possible determinants of lifestyle clustering in patients with type 2 diabetes.

Maternal Pre-Pregnancy Obesity and Gestational Diabetes Mellitus Increase the Risk of Childhood Obesity.

Previous studies have shown inconsistent results regarding the effects of maternal gestational diabetes mellitus (GDM) and pre-pregnancy obesity (PPO) on childhood obesity. This study aimed to determine the risk for early childhood obesity based on maternal GDM and PPO. This nationwide study used data obtained from the National Health Information Database in South Korea. The participants were divided into four groups based on maternal GDM and PPO, and 1:1 matching was performed. Each group had 1319 participants. A generalized estimating equation model was used to analyze the changes in body mass index percentile of children with age, and simple and multiple conditional logistic regression models were used to compare the prevalence of childhood obesity at 5 years. Children whose mothers had both PPO and GDM, only PPO, or only GDM had a 4.46 (95% CI: 3.28−6.05, p < 0.001), 3.11 (95% CI: 2.27−4.26, p < 0.001), or 1.58 (95% CI: 1.12−2.23, p = 0.010) times higher risk, respectively, of developing childhood obesity than children whose mothers had neither PPO nor GDM. Maternal PPO increases the risk for childhood obesity to a higher degree than maternal GDM, and the presence of both increases the risk even further.

Critical shear stress of red blood cells as a novel integrated biomarker for screening chronic kidney diseases in cases of type 2 diabetes.

BACKGROUND: The glomerular filtration rate (GFR) and albumin-to-creatinine ratio (ACR) have been widely used to identify and manage diabetic kidney disease (DKD). However, classifications based on these two indices do not always concur in terms of DKD diagnosis; for example, cases of high ACR with normal GFR or normal ACR with low GFR may occur. A recent study suggested that critical shear stress (CSS), a hemorheological parameter to represent aggregating force of red blood cells (RBCs), is a potential screening index for DKD. In the present study, we investigated the diagnostic potential of CSS for DKD according to the KDIGO 2012 Guideline. METHODS: A total of 378 patients with type 2 diabetes who visited Yeungnam University Hospital between 2014 and 2017 were included. CSS was measured using a transient microfluidic hemorheometer, Rheoscan-D300® (Rheomeditech, Seoul, Republic of Korea) with whole blood. Patients who were DKD negative (green zone) were compared with patients who were DKD positive (red zone) as Model 1 and patients at risk for (orange zone) and red zones as Model 2, respectively. RESULTS: After exclusion criteria such as eGFR < 30 mL/min/1.73 m2, alcoholism, and macrovascular complications were applied, the sensitivity and specificity were 100% and 77.8% for Model 1 and 75.0% and 72.0% for Model 2, respectively. The diagnostic accuracy measures of the CSS for Model 1 were found to be highly accurate or have the potential to alter clinical decisions. Similarly, the diagnostic accuracy measures of CSS for Model 2 were found to provide useful information, despite them expanding to the orange and red zones. CONCLUSION: DKD was successfully identified using a novel integrated hemorheological index of CSS that satisfied both ACR and GFR criteria. Therefore, CSS may be useful for the additive diagnosis of DKD with GFR and uACR.