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The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing low-risk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Abstract We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran’s Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07–1.62; SRR = 1.56, 95% CI 1.25–1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32–6.23; SRR = 2.43, 95% CI 1.65–3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49–18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30–15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.

Abstract Background The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. Methods This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Results Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66–1.13] compared to 0.60 [0.49–0.73], 0.46 [0.38–0.56] and 0.62 [0.51–0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14–1.84] compared to 1.25 [0.99–1.58], 1.06 [0.85–1.32] and 0.86 [0.69–1.08]) and alcohol consumption (1.22 [1.01–1.48] compared to 1.10 [0.90–1.33], 1.15 [0.96–1.38], and 1.07 [0.91–1.26]). Conclusion We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Abstract Background Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. Methods A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow‐up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random‐effects meta‐analyses. Results Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06–1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07–1.60 vs 1.12, 1.01–1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02–1.28 vs 1.17, 0.77–1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02–1.46 vs 1.00, 0.62–1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77–5.86), and decreased with time (nonlinear p

Background The 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine-based estimated glomerular filtration rate (eGFRcr) equation contains a race component that is not based on biology and may cause a bias in results. Therefore, the 2021 eGFRcr and creatinine-cystatin C–based eGFR (eGFRcr-cysC) equations were developed with no consideration of race. This study compared the cardiovascular event (CVE) and all-cause mortality and CVE combined predictability among the three eGFR equations in Korean chronic kidney disease (CKD) patients. Methods This study included 2,207 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) index were used to compare the predictability of the study outcomes according to the 2009 eGFRcr, 2021 eGFRcr, and 2021 eGFRcr-cysC equations. Results The overall prevalence of CVE and all-cause mortality were 9% and 7%, respectively. There was no difference in area under the curve of ROC for CVE and mortality and CVE combined among all three equations. Compared to the 2009 eGFRcr, both the 2021 eGFRcr (NRI, 0.013; 95% confidence interval [CI], –0.002 to 0.028) and the eGFRcr-cysC (NRI, –0.001; 95% CI, –0.031 to 0.029) equations did not show improved CVE predictability. Similar findings were observed for mortality and CVE combined predictability with both the 2021 eGFRcr (NRI, –0.019; 95% CI, –0.039–0.000) and the eGFRcr-cysC (NRI, –0.002; 95% CI, –0.023 to 0.018). Conclusion The 2009 eGFRcr equation was not inferior to either the 2021 eGFRcr or eGFRcr-cysC equation in predicting CVE and the composite of mortality and CVE in Korean CKD patients.

Abstract Hypertension is a chronic disease that requires long‐term follow‐up in many patients, however, optimal visit intervals are not well‐established. This study aimed to evaluate the incidences of major cardiovascular events (MACEs) according to visit intervals. We analyzed data from 9894 hypertensive patients in the Korean Hypertension Cohort, which enrolled and followed up 11,043 patients for over 10 years. Participants were classified into five groups based on their median visit intervals (MVIs) during the 4‐year period and MACEs were compared among the groups. The patients were divided into clinically relevant MVIs of one (1013; 10%), two (1299; 13%), three (2732; 28%), four (2355; 24%), and six months (2515; 25%). The median follow‐up period was 5 years (range: 1745 ± 293 days). The longer visit interval groups did not have an increased cumulative incidence of MACE (12.9%, 11.8%, 6.7%, 5.9%, and 4%, respectively). In the Cox proportional hazards model, those in the longer MVI group had a smaller hazard ratio (HR) for MACEs or all‐cause death: 1.77 (95% confidence interval [CI], 1.45–2.17), 1.7 (95% CI: 1.41–2.05), 0.90 (95% CI: 0.74–1.09) and 0.64 (95% CI: 0.52–0.79), respectively (Reference MVI group of 75–104 days). In conclusion, a follow‐up visits with a longer interval of 3–6 months was not associated with an increased risk of MACE or all‐cause death in hypertensive patients. Therefore, once medication adjustment is stabilized, a longer interval of 3–6 months is reasonable, reducing medical expenses without increasing the risk of cardiovascular outcomes.

Abstract Since the etiology of diabetic chronic kidney disease (CKD) is multifactorial, studies on DNA methylation for kidney function deterioration have rarely been performed despite the need for an epigenetic approach. Therefore, this study aimed to identify epigenetic markers associated with CKD progression based on the decline in the estimated glomerular filtration rate in diabetic CKD in Korea. An epigenome-wide association study was performed using whole blood samples from 180 CKD recruited from the KNOW-CKD cohort. Pyrosequencing was also performed on 133 CKD participants as an external replication analysis. Functional analyses, including the analysis of disease-gene networks, reactome pathways, and protein–protein interaction networks, were conducted to identify the biological mechanisms of CpG sites. A phenome-wide association study was performed to determine the associations between CpG sites and other phenotypes. Two epigenetic markers, cg10297223 on AGTR1 and cg02990553 on KRT28 indicated a potential association with diabetic CKD progression. Based on the functional analyses, other phenotypes (blood pressure and cardiac arrhythmia for AGTR1) and biological pathways (keratinization and cornified envelope for KRT28) related to CKD were also identified. This study suggests a potential association between the cg10297223 and cg02990553 and the progression of diabetic CKD in Koreans. Nevertheless, further validation is needed through additional studies.

Introduction: High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). Methods: In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a ≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. Results: During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P = 0.006). In patients with proteinuria of

Abstract Introduction This study aimed to verify the association between ovarian cancer (OC) and reproductive‐ and lifestyle‐related risk factors stratified by the subtype of OC. Methods In this matched case–control study derived from the Korean epithelial ovarian cancer study (Ko‐EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model. Results As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high‐grade serous (HGS) OC (OR = 2.69, 95% CI = 1.15–6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR = 3.63, 95% CI = 1.39–9.49). Obesity (≥30 kg/m2) was associated with clear cell type (CLC) (OR = 4.57, 95% CI = 1.06–19.77). Spontaneous abortion was negatively associated with CLC (OR = 0.34, 95% CI = 0.13–0.90), in contrast to HGS (OR = 1.43, 95% CI = 0.96–2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR = 0.14, 95% CI = 0.05–0.39; OR = 0.23, 95% CI = 0.07–0.73; OR = 0.28, 95% CI = 0.08–0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR = 6.11, 95% CI = 1.53–24.42; OR = 3.23, 95% CI = 0.98–10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR = 0.11, 95% CI = 0.04–0.35; OR = 0.12, 95% CI = 0.02–0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR = 0.61, 95% CI = 0.40–0.93; OR = 0.51, 95% CI = 0.32–0.80, respectively), and similar negative associations were also observed in HGS (OR = 0.69; OR = 0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR = 3.92; OR = 0.41; OR = 0.72, respectively). Conclusion A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different.

Abstract The causes of chronic kidney disease (CKD) affects its outcomes. However, the relative risks for adverse outcomes according to specific causes of CKD is not well established. In a prospective cohort study from KNOW-CKD, a cohort was analyzed using overlap propensity score weighting methods. Patients were grouped into four categories according to the cause of CKD: glomerulonephritis (GN), diabetic nephropathy (DN), hypertensive nephropathy (HTN), or polycystic kidney disease (PKD). From a total of 2070 patients, the hazard ratio of kidney failure, the composite of cardiovascular disease (CVD) and mortality, and the slope of the estimated glomerular filtration rate (eGFR) decline according to the cause of CKD were compared between causative groups in a pairwise manner. There were 565 cases of kidney failure and 259 cases of composite CVD and death over 6.0 years of follow-up. Patients with PKD had a significantly increased risk for kidney failure compared to those with GN [Hazard ratio (HR) 1.82], HTN (HR 2.23), and DN (HR 1.73). For the composite outcome of CVD and death, the DN group had increased risks compared to the GN (HR 2.07), and HTN (HR 1.73) groups but not to the PKD group. The adjusted annual eGFR change for the DN and PKD groups were − 3.07 and − 3.37 mL/min/1.73 m2 per year, respectively, and all of these values were significantly different than those of the GN and HTN groups (− 2.16 and − 1.42 mL/min/1.73 m2 per year, respectively). In summary, the risk of kidney disease progression was relatively higher in patients with PKD compared to other causes of CKD. However, the composite of CVD and death was relatively higher in patients with DN-related CKD than in those with GN- and HTN-related CKD.

Background The true benefit of thyroid cancer screening is incompletely understood. This study investigated the impact of ultrasound screening on thyroid cancer outcomes through a comparison with symptomatic thyroid cancer using data from a nationwide cohort study in Korea. Methods Cox regression analysis was performed to assess the hazard ratios (HRs) for all-cause and thyroid cancer-specific mortality. Considering the possible bias arising from age, sex, year of thyroid cancer registration, and confounding factors for mortality (including smoking/drinking status, diabetes, and hypertension), all analyses were conducted with stabilized inverse probability of treatment weighting (IPTW) according to the route of detection. Results Of 5,796 patients with thyroid cancer, 4,145 were included and 1,651 were excluded due to insufficient data. In comparison with the screening group, the clinical suspicion group was associated with large tumors (17.2±14.6 mm vs. 10.4±7.9 mm), advanced T stage (3–4) (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.09 to 1.41), extrathyroidal extension (OR, 1.16; 95% CI, 1.02 to 1.32), and advanced stage (III–IV) (OR, 1.16; 95% CI, 1.00 to 1.35). In IPTW-adjusted Cox regression analysis, the clinical suspicion group had significantly higher risks of all-cause mortality (HR, 1.43; 95% CI, 1.14 to 1.80) and thyroid cancer-specific mortality (HR, 3.07; 95% CI, 1.77 to 5.29). Mediation analysis showed that the presence of thyroid-specific symptoms was directly associated with a higher risk of cancer-specific mortality. Thyroid-specific symptoms also indirectly affected thyroid cancer-specific mortality, mediated by tumor size and advanced clinicopathologic status. Conclusion Our findings provide important evidence for the survival benefit of early detection of thyroid cancer compared to symptomatic thyroid cancer.

Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q

Background/Aims This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. Methods The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. Results The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. Conclusions This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.

Abstract In patients with hypertension, left ventricular hypertrophy (LVH) represents a risk factor for cardiovascular disease and asymptomatic organ damage. Currently, electrocardiography (ECG) and two‐dimensional echocardiography (Echo) are the most widely used methods for LVH evaluation. This study aimed to compare the long‐term outcomes of LVH, as evaluated by ECG and Echo, in patients with hypertension. Patients diagnosed with hypertension as a primary disease between 2006 and 2011 were enrolled in the Korean Hypertension Cohort study. The study finally included 1743 patients who underwent both ECG and Echo. The primary endpoint was defined as the composite of major adverse cardiovascular events (MACEs) or death. Overall, LVH was identified in 747 patients. The patients were categorized into four groups according to the detection of LVH by ECG or Echo: No LVH (n = 996), LVH diagnosed by ECG alone (n = 181), LVH diagnosed by Echo alone (n = 415), LVH diagnosed by both ECG and Echo (n = 151). After adjusting for variables, the incidence of MACEs or death was significantly greater in patients with LVH diagnosed by ECG alone (hazards ratio [HR]: 1.69; 95% confidence interval [CI]: 1.22–2.35; P = .001), LVH diagnosed by Echo alone (HR: 1.54; 95% CI: 1.16–2.05; P = .002), and LVH diagnosed by both ECG and Echo (HR: 1.87; 95% CI: 1.18–2.94; P = .002) than in those with no LVH. Both ECG and Echo are efficient diagnostic tools for LVH and useful for long‐term risk stratification. Additional Echo evaluation for LVH is helpful for predicting long‐term outcomes only in patients without LVH diagnosis by ECG.

Objectives: This study aimed to identify the current patterns of cancer incidence and estimate the projected cancer incidence and mortality between 2020 and 2035 in Korea. Methods: Data on cancer incidence cases were extracted from the Korean Statistical Information Service from 2000 to 2017, and data on cancer-related deaths were extracted from the National Cancer Center from 2000 to 2018. Cancer cases and deaths were classified according to the International Classification of Diseases, 10th edition. For the current patterns of cancer incidence, age-standardized incidence rates (ASIRs) and age-standardized mortality rates were investigated using the 2000 mid-year estimated population aged over 20 years and older. A joinpoint regression model was used to determine the 2020 to 2035 trends in cancer. Results: Overall, cancer cases were predicted to increase from 265 299 in 2020 to 474 085 in 2035 (growth rate: 1.8%). The greatest increase in the ASIR was projected for prostate cancer among male (7.84 vs. 189.53 per 100 000 people) and breast cancer among female (34.17 vs. 238.45 per 100 000 people) from 2000 to 2035. Overall cancer deaths were projected to increase from 81 717 in 2020 to 95 845 in 2035 (average annual growth rate: 1.2%). Although most cancer mortality rates were projected to decrease, those of breast, pancreatic, and ovarian cancer among female were projected to increase until 2035. Conclusions: These up-to-date projections of cancer incidence and mortality in the Korean population may be a significant resource for implementing cancer-related regulations or developing cancer treatments.

Abstract Aims Increased blood pressure (BP) and decreased heart rate (HR) are signs of stabilization in patients admitted for acute HF. Changes in BP and HR during admission and their correlation with outcomes were assessed in hospitalized patients with heart failure (HF) with reduced ejection fraction (HFrEF). Methods A novel modified reverse shock index (mRSI), defined as the ratio between changes in systolic BP and HR during admission, was devised, and its prognostic value in the early outcomes of acute HF was assessed using the Korean Acute HF registry. Results Among 2697 patients with HFrEF (mean age 65.8 ± 14.9 years, 60.6% males), patients with mRSI ≥1.25 at discharge were significantly younger and were more likely to have de novo HF. An mRSI ≥1.25 was associated with a significantly lower incidence of 60‐day and 180‐day all‐cause mortality [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31–0.77; HR 0.62, 95% CI 0.45–0.85, respectively], compared with 1 ≤ mRSI

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.

Abstract Background The association between metabolic comorbidity and myocardial infarction (MI) among individuals with a family history of cardiovascular disease (CVD) is yet to be elucidated. We aimed to examine the combined effects of metabolic comorbidities, including diabetes mellitus, hypertension, and dyslipidemia, with a family history of CVD in first-degree on the risk of incident MI. Methods This cohort study consisted of 81,803 participants aged 40–89 years without a previous history of MI at baseline from the Korean Genome and Epidemiology Study. We performed Cox proportional hazard regression analysis to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for MI and early-onset MI risk associated with metabolic comorbidity in individuals with a family history of CVD. Results During a median follow-up of 5 years, 1,075 and 479 cases of total and early-onset MI were reported, respectively. According to the disease score, among individuals who had a positive family history of CVD, the HRs for MI were 1.92 (95% CI: 1.47–2.51) in individuals with one disease, 2.75 (95% CI: 2.09–3.61) in those with two diseases, and 3.74 (95% CI: 2.45–5.71) in those with three diseases at baseline compared to individuals without a family history of CVD and metabolic diseases. Similarly, an increase of the disease score among individuals with a positive family history of CVD was associated with an increase in early-onset MI risk. Conclusion Metabolic comorbidity was significantly associated with an increased risk of MI among individuals with a family history of CVD.

Abstract Amblyopia is a common visual disorder that causes significant vision problems globally. Most non-ocular risk factors for amblyopia are closely related to the intrauterine environment, and are strongly influenced by parent-origin effects. Parent-origin perinatal factors may have a direct causal inference on amblyopia development; therefore, we investigated the causal association between perinatal factors and amblyopia risk using a one-sample Mendelian Randomization (MR) with data from the UK Biobank Cohort Data (UKBB). Four distinct MR methods were employed to analyze the association between three perinatal factors (birth weight [BW], maternal smoking, and breastfeeding) and amblyopia risk, based on the summary statistics of genome-wide association studies in the European population. The inverse variance weighting method showed an inverse causal association between BW and amblyopia risk (odds ratio, 0.48 [95% CI, 0.29–0.80]; p = 0.004). Maternal smoking and breastfeeding were not causally associated with amblyopia risk. Our findings provided a possible evidence of a significant genetic causal association between low BW and increased amblyopia risk. This evidence may highlight the potential of BW as a predictive factor for visual maldevelopment and the need for careful management of amblyopia risk in patients with low BW.

Objectives We introduced the cohort studies included in the Korean Cohort Consortium (KCC), focusing on large-scale cohort studies established in Korea with a prolonged follow-up period. Moreover, we also provided projections of the follow-up and estimates of the sample size that would be necessary for big-data analyses based on pooling established cohort studies, including population-based genomic studies. Methods We mainly focused on the characteristics of individual cohort studies from the KCC. We developed “PROFAN”, a Shiny application for projecting the follow-up period to achieve a certain number of cases when pooling established cohort studies. As examples, we projected the follow-up periods for 5000 cases of gastric cancer, 2500 cases of prostate and breast cancer, and 500 cases of non-Hodgkin lymphoma. The sample sizes for sequencing-based analyses based on a 1:1 case-control study were also calculated. Results The KCC consisted of 8 individual cohort studies, of which 3 were community-based and 5 were health screening-based cohorts. The population-based cohort studies were mainly organized by Korean government agencies and research institutes. The projected follow-up period was at least 10 years to achieve 5000 cases based on a cohort of 0.5 million participants. The mean of the minimum to maximum sample sizes for performing sequencing analyses was 5917–72 102. Conclusions We propose an approach to establish a large-scale consortium based on the standardization and harmonization of existing cohort studies to obtain adequate statistical power with a sufficient sample size to analyze high-risk groups or rare cancer subtypes.

Background/Aims The optimal systolic blood pressure (SBP) goal for elderly patients with hypertension, especially to reduce cardiovascular disease (CVD) incidence and improve outcome, is unclear. This study aimed to evaluate the beneficial effects of intensive treatment for hypertension on the incidence of CVD in elderly Korean patients. Methods The HOW to Optimize eLDerly systolic Blood Pressure (HOWOLD-BP) trial is a multicenter, parallel-design, open-label, randomized controlled trial designed to evaluate whether intensive treatment (SBP ≤ 130 mmHg) will provide more benefits in lowering the incidence and mortality associated with CVD than standard treatment (SBP ≤ 140 mmHg) in elderly patients with hypertension aged ≥ 65 years. For this study, eleven university hospitals in Korea will enroll approximately 3,176 elderly patients with hypertension between 2019 and 2022. Patients will be requested to visit the clinic every 4 months for the first year and every 6 months thereafter for 36 months. Parameters, including clinic and home blood pressure, anthropometric and laboratory findings, and frailty assessments, will be collected according to the standardized protocol. The primary outcome is a composite of CVD (acute coronary syndrome, stroke, and heart failure) incidence and cardiovascular deaths. Results As of December 2021, 1,655 participants had been enrolled in the study, including 831 patients in the standard group and 824 patients in the intensive group. Conclusions The HOWOLD-BP trial is the first study performed in Korea to evaluate the beneficial effects of intensive blood pressure treatment on CVD in elderly patients with hypertension. The results of this study will help clarify the appropriate target SBP for this population.

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.

Objectives The aim of this study was to evaluate the subjective level of health-related quality of life of Korean healthcare workers using various quality-of-life instruments. Methods This study included 992 participants, who were doctors and nurses. A survey was conducted between November 28 and December 4, 2019. Data from 954 participants divided into 3 groups (physicians, residents, and nurses) were analyzed. Four measurement tools (29 questions) were used in the survey to evaluate subjective health status and well-being. Results In the Mayo Well-being Index, burnout during work (88.5%) and emotional difficulties caused by work (84.0%) were frequently cited by the respondents. Regarding questions on burnout and emotional difficulties, residents and nurses had the highest scores (91.0 and 89.6%, respectively). Emotional problems, such as anxiety, depression, and irritability, accounted for a high percentage (73.1%) of the total, while 82.2% of respondents reported that their work schedules interfered with their leisure and family time. There was no significant difference among the groups in subjective health status. However, 10.1% of the residents experienced very low quality of life, which was a higher proportion than that of physicians (2.7%) and nurses (5.2%). Conclusions The level of well-being that Korean medical workers experienced in relation to work was lower than the results of the United States healthcare workers surveyed using the same tool. This study was unique in that it conducted a subjective quality-of-life survey on Korean healthcare workers.

Abstract Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.

OBJECTIVES The aim of this study was to clarify the clinical trait of familial diabetes mellitus (DM) by analyzing participants’ risk of DM according to the age of DM onset in parents and siblings, and to evaluate individuals’ risk of DM-associated cardiometabolic diseases. METHODS Altogether, 211,173 participants aged ≥40 years from the Korean Genome and Epidemiology Study were included in this study. The participants were divided into groups based on the number (1 or 2 relatives) and age of onset (no DM and early, common, or late onset) of familial DM. Participants’ risk of DM was assessed using a Cox regression model with hazard ratios and 95% confidence intervals (CIs). A logistic regression model with odds ratios was used to evaluate associations among the participants’ likelihood of acquiring cardiometabolic diseases such as hypertension, chronic kidney disease (CKD), and cardiovascular disease. RESULTS The risk of developing DM was 2.02-fold (95% CI, 1.88 to 2.18) and 2.88-fold (95% CI, 2.50 to 3.33) higher, respectively, in participants with 1 and 2 family members diagnosed with familial DM. It was 2.72-fold (95% CI, 2.03 to 3.66) higher in those with early-onset familial DM. In the early-onset group, the respective risks of hypertension and CKD were 1.87-fold (95% CI, 1.37 to 2.55) and 4.31-fold (95% CI, 2.55 to 7.27) higher than in the control group. CONCLUSIONS The risk of DM and related cardiometabolic diseases was positively associated with the number of family members diagnosed with DM and an early diagnosis in family members with DM.

BackgroundsSome observational studies have suggested a possible association between vitamin D deficiency and CKD. However, in most studies, the causality between low levels of vitamin D and risk of renal events could not be explained. We investigated the relationship between vitamin D deficiency and risk of severe CKD stage and renal event in a large-scale prospective cohort study.MethodsWe used data from a prospective cohort of 2,144 patients with available information on serum 25-hydroxyvitamin D (25(OH)D) levels at baseline from KNOW-CKD, 2011-2015 were included. Vitamin D deficiency was defined as serum 25(OH)D levels < 15 ng/mL. We performed a cross-sectional analysis to elucidate the relationship between 25(OH)D and CKD stage using baseline CKD patient data. We further examined a cohort analysis to clarify the association between 25(OH)D and risk of renal event. Renal event was a composite of the first occurrence of a 50% decline in eGFR from the baseline value or the onset of CKD stage 5 (initiation of dialysis or kidney transplantation) across the follow-up period. We also investigated the associations of vitamin D deficiency with risk of renal event according to diabetes and overweight status.ResultsVitamin D deficiency were significantly associated with an increased risk of severe CKD stage – 1.30-fold (95% CI: 1.10-1.69) for 25(OH)D. Deficiency of 25(OH)D with 1.64-fold (95% CI: 1.32-2.65) was related to renal event compared with the reference. Furthermore, vitamin D deficiency patients with presence of DM and overweight status also displayed higher risk than non-deficient patients for risk of renal event.ConclusionVitamin D deficiency is associated with significantly increased risk of severe CKD stage and renal event.

Objectives This study aimed to identify the social and policy determinants of coronavirus disease 2019 (COVID-19) infection across 23 countries. Methods COVID-19 indicators (incidence, mortality, and fatality) for each country were calculated by direct and indirect standardization. Multivariable regression analyses were used to identify the social and policy determinants of COVID-19 infection. Results A higher number of doctors per population was related to lower incidence, mortality, and fatality rates of COVID-19 in 23 countries (β=−0.672, −0.445, and −0.564, respectively). The number of nurses/midwives per population was associated with lower mortality and fatality rates of COVID-19 in 23 countries (β=−0.215 and −0.372, respectively). Strengthening of policy restriction indicators, such as restrictions of public gatherings, was related to lower COVID-19 incidence (β=−0.423). A national Bacillus Calmette–Guérin vaccination policy conducted among special groups or in the past was associated with a higher incidence of COVID-19 in 23 countries (β=0.341). The proportion of the elderly population (aged over 70 years) was related to higher mortality and fatality rates (β=0.209 and 0.350, respectively), and income support was associated with mortality and fatality rates (β=−0.362 and −0.449, respectively). Conclusions These findings do not imply causality because this was a country-based correlation study. However, COVID-19 transmission can be influenced by social and policy determinants such as integrated health systems and policy responses to COVID-19. Various social and policy determinants should be considered when planning responses to COVID-19.

Abstract Background Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. Methods Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. Results PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35–5.17], moderately vs well-differentiated 2.33 [1.56–3.49]), as well as luminal B [HER−] and triple-negative subtypes (vs luminal A 2.15 [1.58–2.92] and 2.85 [2.17–3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2−] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16–2.28]). Conclusions PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

Abstract Background Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients. Methods A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups. Results DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c

Background/Aims Hypertension (HT) has a significant impact on public health and medical expenses. However, HT is a chronic disease that requires the long-term follow-up of a large number of patients. Methods The Korean Hypertension Cohort (KHC) study aimed to develop a model for calculating cardiovascular risk in HT patients by linking and utilizing the detailed clinical and longitudinal data from hospitals and the national health insurance claim database, respectively. This cohort had a planned sample size of over 11,000 HT patients and 100,000 non-HT controls. Eligible patients were hypertensive patients, who were presenting for the first time and were diagnosed with HT as a main disease from 2006 to 2011. Long-term survival data over a period of approximately 9 years were obtained from the national health insurance claim and national health examination data. Results This cohort enrolled 11,083 patients with HT. The mean age was 58.87 ± 11.5 years, 50.5% were male, and 31.4% were never-treated HT. Of the enrolled patients, 32.9% and 37.7% belonged to the high and moderate cardiovascular risk groups, respectively. Initial blood pressures were 149.4 ± 18.5/88.5 ± 12.5 mmHg. During the 2 years hospital data follow-up period, blood pressures lowered to 130.8 ± 14.1/78.0 ± 9.7 mmHg with 1.9 ± 1.0 tablet doses of antihypertensive medication. Cardiovascular events occurred in 7.5% of the overall patients; 8.5%, 8.8%, and 4.7% in the high, moderate, and low risk patients, respectively. Conclusions The KHC study has provided important information on the long-term outcomes of HT patients according to the blood pressure, comorbid diseases, medication, and adherence, as well as health behaviors and health resource use.

Economic evaluation is a type of comparative analysis between interventions in terms of both their resource use and health outcomes. Due to the good prognosis of thyroid cancer (TC), the socioeconomic burden of TC patients post-diagnosis is increasing. Therefore, economic evaluation studies focusing on TC are recommended. This study aimed to describe the concept and methods of economic evaluation and reviewed previous TC studies. Several previous studies compared the costs of interventions or evaluated recurrence, complications, or quality of life as measures of their effectiveness. Regarding costs, most studies focused on direct costs and applied hypothetical models. Cost-minimization analysis should be distinguished from simple cost analysis. Furthermore, due to the universality of the term “cost-effectiveness analysis” (CEA), several studies have not distinguished CEA from cost-utility analysis; this point needs to be considered in future research. Cost-benefit analyses have not been conducted in previous TC research. Since TC has a high survival rate and good prognosis, the need for economic evaluations has recently been pointed out. Therefore, correct concepts and methods are needed to obtain clear economic evaluation results. On this basis, it will be possible to provide appropriate guidelines for TC treatment and management in the future.

Background This study aimed to assess the effects of iodine intake, thyroid function, and their combined effect on the risk of papillary thyroid cancer (PTC) and papillary thyroid microcarcinoma (PTMC). Methods A case-control study was conducted including 500 community-based controls who had undergone a health check-up, and 446 overall PTC cases (209 PTC and 237 PTMC) from the Thyroid Cancer Longitudinal Study. Urinary iodine concentration (UIC), was used as an indicator of iodine intake, and serum for thyroid function. The risk of PTC and PTMC was estimated using unconditional logistic regression. Results Excessive iodine intake (UIC ≥220 μg/gCr) was associated with both PTC (odds ratio [OR], 18.13 95% confidence interval [CI], 8.87 to 37.04) and PTMC (OR, 8.02; 95% CI, 4.64 to 13.87), compared to adequate iodine intake (UIC, 85 to 219 μg/gCr). Free thyroxine (T4) levels ≥1.25 ng/dL were associated with PTC (OR, 1.97; 95% CI, 1.36 to 2.87) and PTMC (OR, 2.98; 95% CI, 2.01 to 4.41), compared to free T4 levels of 0.7 to 1.24 ng/dL. Individuals with excessive iodine intake and high free T4 levels had a greatly increased OR of PTC (OR, 43.48; 95% CI, 12.63 to 149.62), and PTMC (OR, 26.96; 95% CI, 10.26 to 70.89), compared to individuals with adequate iodine intake and low free T4 levels. Conclusion Excessive iodine intake using creatinine-adjusted UIC and high free T4 levels may have a synergistic effect on PTC and PTMC. Considering both iodine intake and thyroid function is important to assess PTC and PTMC risk.

Objective: Despite being a powerful tool to identify novel variants, genome-wide association studies (GWAS) are not sufficient to explain the biological function of variants. In this study, we aimed to elucidate at the gene level the biological mechanisms involved in gastric cancer (GC) development and to identify candidate drug target genes.Materials and methods: We conducted a systematic review for GWAS on GC following the PRISMA guidelines. Single nucleotide polymorphism (SNP)-level meta-analysis and gene-based analysis (GBA) were performed to identify SNPs and genes significantly associated with GC. Expression quantitative trait loci (eQTL), disease network, pathway enrichment, gene ontology, gene-drug, and chemical interaction analyses were conducted to elucidate the function of the genes identified by GBA.Results: A review of GWAS on GC identified 226 SNPs located in 91 genes. In the comprehensive GBA, 44 genes associated with GC were identified, among which 12 genes (THBS3, GBAP1, KRTCAP2, TRIM46, HCN3, MUC1, DAP3, EFNA1, MTX1, PRKAA1, PSCA, and ABO) were eQTL. Using disease network and pathway analyses, we identified that PRKAA, THBS3, and EFNA1 were significantly associated with the PI3K-Alt-mTOR-signaling pathway, which is involved in various oncogenic processes, and that MUC1 acts as a regulator in both the PI3K-Alt-mTOR and P53 signaling pathways. Furthermore, RPKAA1 had the highest number of interactions with drugs and chemicals.Conclusion: Our study suggests that PRKAA1, a gene in the PI3K-Alt-mTOR-signaling pathway, could be a potential target gene for drug development associated with GC in the future.Systematic Review Registration: website, identifier registration number.

Abstract Background The overall incidence of gastric cancer in women is half that in men for most global populations. Sex hormone pathways may be involved in carcinogenesis and estrogens have been postulated to protect women against gastric cancer. Aim To evaluate associations of gastric cancer with estrogen metabolites in postmenopausal women. Methods and results We performed an analysis of 233 gastric cancer cases and 281 age‐matched controls from three prospective cohorts and two case‐control studies of early‐stage gastric cancer, mainly conducted in high‐risk Asian populations. Fifteen estrogen‐parent (estrone and estradiol) and ‐metabolite analytes (2‐hydroxyestrone, 2‐hydroxyestradiol, 2‐hydroxyestrone‐3‐methyl ether, 4‐hydroxyestrone; 4‐methoxyestrone, 4‐methoxyestradiol, 2‐methoxyestrone, 2‐methoxyestradiol, estriol, 16α‐hydroxyestrone, 16‐ketoestradiol, 16‐epiestriol, and 17‐epiestriol) were measured in spot urines using liquid chromatography–tandem mass spectrometry. Odds ratios for association with each marker were estimated by logistic regression. Heterogeneity was assessed by Cochran's Q test. Study‐specific odds ratios were pooled by fixed‐effects meta‐analysis. Urinary levels of estrogen‐related molecules were not associated with gastric cancer (adjusted odds ratios ranged from 0.87 to 1.27; p‐values >.05), with low between‐study heterogeneity (p‐values >.1) for all but two metabolites (2‐hydroxyestrone‐3‐methyl ether and 2‐methoxyestradiol). Conclusion To date, this is the first comprehensive assessment of endogenous estrogens with gastric cancer risk in women. Estrogens do not appear to have an etiologic role in gastric cancer risk among postmenopausal women. Given the complex network of sex steroid hormones and their extreme variation over the lifespan, further evaluation of this hypothesis is warranted.

Background Few studies have examined the association between the early diastolic mitral inflow velocity/early diastolic mitral annulus velocity ratio (E/e’) and chronic kidney disease progression. Methods and Results We reviewed data from 2238 patients with nondialysis chronic kidney disease from the KNOW‐CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease); data from 163 patients were excluded because of missing content. A >50% decrease in estimated glomerular filtration rate from baseline, doubling of serum creatinine, or dialysis initiation and/or kidney transplantation were considered renal events. At baseline, median (interquartile range) ejection fraction and E/e’ were 64.0% (60.0%–68.0%) and 9.1 (7.4–11.9), respectively. Proportions of ejection fraction

Introduction: The renal hazard of polypharmacy has never been evaluated in predialysis chronic kidney disease (CKD) patients. Objective: We aimed to analyze the renal hazard of polypharmacy in predialysis CKD patients with stage 1–5. Method: The data of 2,238 patients from a large-scale multicenter prospective Korean study (2011–2016), excluding 325 patients with various missing data, were reviewed. Polypharmacy was defined as taking 6 or more medications at the time of enrollment; renal events were defined as a ≥50% decrease in kidney function from baseline values, doubling of the serum creatinine levels, or initiation of renal replacement treatment. Hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox proportional-hazard regression analysis. Results: Of the 1,913 patients, the mean estimated glomerular filtration rate was 53.6 mL/min/1.73 m2. The mean medication count was 4.1, and the prevalence of polypharmacy was 27.1%. During the average period of 3.6 years, 520 patients developed renal events (27.2%). Although increased medication counts were associated with increased renal hazard with HR (95% CI) of 1.056 (1.007–1.107, p = 0.025), even after adjusting for various confounders, adding comorbidity score and kidney function nullified the statistical significance. In mediation analysis, 55.6% (p = 0.016) of renal hazard in increased medication counts was mediated by the kidney function, and there was no direct effect of medication counts on renal event development. In subgroup analysis, the renal hazard of the medication counts was evident only in stage 1–3 of CKD patients (p for interaction = 0.014). Conclusions: We cannot identify the direct renal hazard of multiple medications, and most of the potential renal hazard was derived from intimate relationship with disease burden and kidney function.

Background Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. Methods This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 μIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 μIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. Conclusion The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Abstract Hyperadiponectemia is paradoxically associated with renal disease progression and mortality in chronic kidney disease (CKD). Its association with health-related quality of life (HR-QOL) is unknown. This study aimed to verify the association between adiponectin and HR-QOL in Korean pre-dialysis CKD cohort. This cross-sectional study analyzed 1551 pre-dialysis CKD patients from KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease). Participants were categorized into three tertiles (T1–T3) according to adiponectin levels. HR-QOL was assessed using SF-36. High physical component summary (PCS) and mental component summary (MCS) were defined as highest quartile of each score. Multivariate logistic regression was used to analyze odds ratio (OR) and 95% confidence interval (CI) for high PCS and MCS. Prevalence of high PCS were 33.3%, 27.5%, and 17.0% and that of high MCS were 31.7%, 24.8%, and 21.3% for T1, T2, and T3 (both p for trend

Abstract Genetic testing for BRCA1 and BRCA2 is crucial in diagnosing hereditary breast and ovarian cancer syndromes and has increased with the development of multigene panel tests. However, results classified as variants of uncertain significance (VUS) present challenges to clinicians in attempting to choose an appropriate management plans. We reviewed a total of 676 breast cancer patients included in the Korean Hereditary Breast Cancer (KOHBRA) study with a VUS on BRCA mutation tests between November 2007 and April 2013. These results were compared to the ClinVar database. We calculated the incidence and odds ratios for these variants using the Korean Reference Genome Database. A total of 58 and 91 distinct VUS in BRCA1 and BRCA2 were identified in the KOHBRA study (comprising 278 and 453 patients, respectively). A total of 27 variants in the KOHBRA study were not registered in the Single Nucleotide Polymorphism database. Among BRCA1 VUSs, 20 were reclassified as benign or likely benign, four were reclassified as pathogenic or likely pathogenic, and eight remained as VUSs according to the ClinVar database. Of the BRCA2 VUSs, 25 were reclassified as benign or likely benign, two were reclassified as pathogenic or likely pathogenic, and 33 remained as VUS according to the ClinVar database. There were 12 variants with conflicting interpretations of pathogenicity for BRCA1 and 18 for BRCA2. Among them, p.Leu1780Pro showed a particularly high odds ratio. Six pathogenic variants and one conflicting variant identified using ClinVar could be reclassified as pathogenic variants in this study. Using updated ClinVar information and calculating odds ratios can be helpful when reclassifying VUSs in BRCA1/2.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Abstract Few studies have investigated the incidence of cardiovascular disease (CVD) in the Asian chronic kidney disease (CKD) population. This study assessed the incidence of CVD, death, and a composite outcome of CVD and death in a prospective Korean predialysis CKD cohort. From a total of 2179 patients, incidence rates were analyzed, and competing risk analyses were conducted according to CKD stage. Additionally, incidence was compared to the general population. During a median 4.1 years of follow-up, the incidence of CVD, all-cause death, and the composite outcome was 17.2, 9.6, and 24.5 per 1000 person-years, respectively. These values were higher in diabetic vs. non-diabetic subjects (P

Objectives: The objective of this study was to estimate the risk of lung cancer in relation to angiotensin II receptor blocker (ARB) use among patients with hypertension from the Korean National Health Insurance Service-National Health Screening Cohort. Methods: We conducted a retrospective cohort study of patients with hypertension who started to take antihypertensive medications and had a treatment period of at least 6 months. We calculated the weighted hazard ratios (HRs) and their 95% confidence intervals (CIs) of lung cancer associated with ARB use compared with calcium channel blocker (CCB) use using inverse probability treatment weighting. Results: Among a total of 60 469 subjects with a median follow-up time of 7.8 years, 476 cases of lung cancer were identified. ARB use had a protective effect on lung cancer compared with CCB use (HR, 0.75; 95% CI, 0.59 to 0.96). Consistent findings were found in analyses considering patients who changed or discontinued their medication (HR, 0.50; 95% CI, 0.32 to 0.77), as well as for women (HR, 0.56; 95% CI, 0.34 to 0.93), patients without chronic obstructive pulmonary disease (HR, 0.75; 95% CI, 0.56 to 1.00), never-smokers (HR, 0.64; 95% CI, 0.42 to 0.99), and non-drinkers (HR, 0.69; 95% CI, 0.49 to 0.97). In analyses with different comparison antihypertensive medications, the overall protective effects of ARBs on lung cancer risk remained consistent. Conclusions: The results of the present study suggest that ARBs could decrease the risk of lung cancer. More evidence is needed to establish the causal effect of ARBs on the incidence of lung cancer.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

As the nation’s largest chronic kidney disease (CKD) cohort, the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was established to investigate the clinical course, risk factors for progression, and adverse outcomes of CKD. From 2011 to 2016, the KNOW-CKD recruited 2,238 adult patients with CKD from stage G1 to G5 who were not receiving renal replacement therapy from nine tertiary care hospitals throughout Korea. As of 2019, the KNOW-CKD has published more than 50 articles in the areas of socio-economics, nutrition, quality of life, health-related habits, CKD progression, cardiovascular comorbidity and outcome, anemia, mineral bone disease, biomarker discovery, and international and inter-ethnic comparisons. The KNOW-CKD will eventually offer a prediction model for long-term consequences of CKD, such as the occurrences of end-stage renal disease, cardiovascular disease, and death, thereby enabling the identification and treatment of at-risk populations that require extra medical attention.

Abstract Background Although more than one-third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear if DM has an adverse impact on clinical outcomes. This study compared the outcomes in patients hospitalized for AHF stratified by DM and left ventricular ejection fraction (LVEF). Methods The Korean Acute Heart Failure registry prospectively enrolled and followed 5625 patients from March 2011 to February 2019. The primary endpoints were in-hospital and overall all-cause mortality. We evaluated the impact of DM on these endpoints according to HF subtypes and glycemic control. Results During a median follow-up of 3.5 years, there were 235 (4.4%) in-hospital mortalities and 2500 (46.3%) overall mortalities. DM was significantly associated with increased overall mortality after adjusting for potential confounders (adjusted hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.22). In the subgroup analysis, DM was associated with higher a risk of overall mortality in heart failure with reduced ejection fraction (HFrEF) only (adjusted HR 1.14, 95% CI 1.02–1.27). Inadequate glycemic control (HbA1c ≥ 7.0% within 1 year after discharge) was significantly associated with a higher risk of overall mortality compared with adequate glycemic control (HbA1c

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Early detection and proper management of chronic kidney disease (CKD) can delay progression to end-stage kidney disease. We applied metabolomics to discover novel biomarkers to predict the risk of deterioration in patients with different causes of CKD. We enrolled non-dialytic diabetic nephropathy (DMN, n = 124), hypertensive nephropathy (HTN, n = 118), and polycystic kidney disease (PKD, n = 124) patients from the KNOW-CKD cohort. Within each disease subgroup, subjects were categorized as progressors (P) or non-progressors (NP) based on the median eGFR slope. P and NP pairs were randomly selected after matching for age, sex, and baseline eGFR. Targeted metabolomics was performed to quantify 188 metabolites in the baseline serum samples. We selected ten progression-related biomarkers for DMN and nine biomarkers each for HTN and PKD. Clinical parameters showed good ability to predict DMN (AUC 0.734); however, this tendency was not evident for HTN (AUC 0.659) or PKD (AUC 0.560). Models constructed with selected metabolites and clinical parameters had better ability to predict CKD progression than clinical parameters only. When selected metabolites were used in combination with clinical indicators, random forest prediction models for CKD progression were constructed with AUCs of 0.826, 0.872, and 0.834 for DMN, HTN, and PKD, respectively. Select novel metabolites identified in this study can help identify high-risk CKD patients who may benefit from more aggressive medical treatment.