Heat-induced structural and chemical changes to a computationally designed miniprotein.

The de novo design of miniprotein inhibitors has recently emerged as a new technology to create proteins that bind with high affinity to specific therapeutic targets. Their size, ease of expression, and apparent high stability makes them excellent candidates for a new class of protein drugs. However, beyond circular dichroism melts and hydrogen/deuterium exchange experiments, little is known about their dynamics, especially at the elevated temperatures they seemingly tolerate quite well. To address that and gain insight for future designs, we have focused on identifying unintended and previously overlooked heat-induced structural and chemical changes in a particularly stable model miniprotein, EHEE_rd2_0005. Nuclear magnetic resonance (NMR) studies suggest the presence of dynamics on multiple time and temperature scales. Transiently elevating the temperature results in spontaneous chemical deamidation visible in the NMR spectra, which we validate using both capillary electrophoresis and mass spectrometry (MS) experiments. High temperatures also result in greatly accelerated intrinsic rates of hydrogen exchange and signal loss in NMR heteronuclear single quantum coherence spectra from local unfolding. These losses are in excellent agreement with both room temperature hydrogen exchange experiments and hydrogen bond disruption in replica exchange molecular dynamics simulations. Our analysis reveals important principles for future miniprotein designs and the potential for high stability to result in long-lived alternate conformational states.

Risk of cardiovascular disease with high-dose versus low-dose use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS). METHODS: Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use. RESULTS: Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups. CONCLUSION: In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure.

Incidence of atrial fibrillation in patients with renal infarction: A retrospective cohort analysis of the Korean national health insurance registry.

BACKGROUND: Regarding the pathophysiology of renal infarction (RI), cardioembolic causes could have large proportion. However, there are notable variations in prevalence of atrial fibrillation (AF) among patients with RI across different studies, ranging from 17 to 65%. The primary objective of this study is to analyze the incidence of AF in patients with RI. METHODS: This nationwide retrospective cohort study enrolled 5200 patients with RI from the Korean National Institute of Health Services database spanning the years 2013 to 2019. The study accessed the AF incidence rate within 12 months in patients without a prior history of AF. Events occurring within 3 months of RI diagnosis were excluded to mitigate cases diagnosed during the initial screening or those with AF diagnoses that were potentially overlooked in the past. RESULTS: AF occurred in 19.1% of patients with RI over the entire period (median: 2.5 years, interquartile range 1.04-4.25 years). The majority of AF cases (16.1%) occured within the first year, resulting in an overall incidence rate of 7.0 per 100 person-years. Patients with newly developed AF were, on average, older than those who did not develop AF (64.1 vs. 57.3 years, P < 0.001). The independent predictors of AF were identified as age, male sex, higher body mass index, current smoking, ischemic heart disease, and heart failure. CONCLUSIONS: Physicians should consider the implementation of active rhythm monitoring for patients with RI to identify potential occurrence of subclinical AF, even if not initially diagnosed during the initial screening after RI diagnosis.

Prognosis of amyotrophic lateral sclerosis patients after tracheostomy invasive ventilation in Korea.

Background: Tracheostomy invasive ventilation (TIV) is applied to a subset of amyotrophic lateral sclerosis (ALS) patients; however, its frequency and impact on prognosis vary across countries. Methods: We conducted a nationwide retrospective cohort study using Korean National Health Insurance claims data. All patients diagnosed with sporadic ALS from 2012 to 2017 were included, with the observation period until 2020. The survival time between the TIV and non-TIV groups was compared using propensity score matching analysis, and prognostic factors were assessed within the TIV group. Results: This study included 3484 ALS patients (mean [standard deviation] age, 62.4 [11.9] years, 60.4% male), among whom 1230 (35.3%) underwent TIV. After 1:1 propensity score matching, the survival duration between the two groups was not significantly different (28 vs. 25 months, p = 0.057). Cox regression indicated that older age (hazard ratios [HRs] for each decade compared to <40 years: 3.89, 3.83, 5.30, 6.78, and 8.40 [≥80 years]; p < 0.005 for all) and lower income (HR, 1.28; 95% confidence interval [CI], 1.09-1.52; p = 0.003) negatively impacted survival, while gastrostomy (HR, 0.57; 95% CI, 0.50-0.66; p < 0.001) and supportive care services (HR, 0.43; 95% CI, 0.32-0.59; p < 0.001) were associated with prolonged survival. Conclusions: TIV was administered to more than one-third of Korean ALS patients without significant survival prolongation. Older age, lower income, lack of gastrostomy, and insufficient supportive care were independent poor prognostic factors for survival, underscoring the importance of comprehensive management for ALS patients.

The role of ambulatory blood pressure monitoring in enhancing medication adherence among patients with newly diagnosed hypertension: an analysis of the National Health Insurance cohort database.

BACKGROUND: Improving adherence to antihypertensive medication (AHM) is a key challenge in hypertension management. This study aimed to assess the impact of ambulatory blood pressure monitoring (ABPM) on AHM adherence. METHODS: We utilized the Korean National Health Insurance Service database. Among patients newly diagnosed with hypertension who started AHM between July 2010 and December 2013, we compared clinical characteristics and adherence between 28,116 patients who underwent ABPM prior to starting AHM and 118,594 patients who did not undergo ABPM. Good adherence was defined as a proportion of days covered (PDC) of 0.8 or higher. RESULTS: The total study population was 146,710, with a mean age of 50.5 ± 6.4 years; 44.3% were female. Co-morbidities were noted in 4.2%. About a third of patients (33.1%) showed good adherence. The ABPM group had a notably higher PDC (total PDC: 0.64 ± 0.35 vs. 0.45 ± 0.39; P < 0.001), irrespective of the number of medications, dosing frequency, or prescription duration. After adjusting for significant clinical variables, ABPM was still closely linked with good adherence (odds ratio, 2.35; 95% confidence interval, 2.28-2.41; P < 0.001). CONCLUSIONS: In newly diagnosed hypertension, undergoing ABPM prior to AHM prescription appears to enhance adherence to AHM. The exact mechanisms driving this association warrant further exploration.

Risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs in ankylosing spondylitis.

OBJECTIVE: To examine the risk of cardiovascular disease associated with long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) in a large real-world ankylosing spondylitis (AS) cohort. METHODS: This nationwide population-based cohort study used data from the Korean National Health Insurance Database. Patients aged ≥18 years old who were newly diagnosed with AS without prior cardiovascular disease between January 2010 and December 2018 were included in this study. Controls without AS were randomly selected by age, sex, and index year. The primary outcome was cardiovascular disease, a composite outcome of ischemic heart disease, stroke, or congestive heart failure. Long-term use of NSAIDs was defined as use of NSAIDs for >365 cumulative defined daily doses. The association between long-term use of NSAIDs and incident cardiovascular disease was examined in both AS and non-AS populations. RESULTS: Among 19 775 patients with AS and 59 325 matched controls without AS, there were 1,663 and 4,308 incident cases of cardiovascular disease, showing an incidence of 16.9 and 13.8 per 1,000 person-years, respectively. Long-term use of NSAIDs was associated with increased risk of cardiovascular disease in non-AS controls (adjusted hazard ratio [aHR], 1.64; 95% CI, 1.48-1.82). In contrast, long-term use of NSAIDs did not increase the risk of cardiovascular disease in AS patients (aHR, 1.06; 95% CI, 0.94-1.20; adjusted for age, sex, socioeconomic status, body mass index, smoking status, hypertension, diabetes, hyperlipidemia, and tumor necrosis factor inhibitor use). CONCLUSION: Prolonged NSAID treatment in AS patients may not be as harmful as in the general population regarding cardiovascular risk.

Gout and the Prevalence of Dementia: A Nationwide Population-Based Study.

BACKGROUND: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported. OBJECTIVE: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population. METHODS: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout. RESULTS: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia. CONCLUSIONS: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

Temporal Trend of the Incidence and Characteristics of Renal Infarction: Korean Nationwide Population Study.

BACKGROUND: Large-scale studies about epidemiologic characteristics of renal infarction (RI) are few. In this study, we aimed to analyze the incidence and prevalence of RI with comorbidities in the South Korean population. METHODS: We investigated the medical history of the entire South Korean adult population between 2013 and 2019 using the National Health Insurance Service database (n = 51,849,591 in 2019). Diagnosis of RI comorbidities were confirmed with International Classification of Disease, Tenth Revision, Clinical Modification codes. Epidemiologic characteristics, distribution of comorbidities according to etiologic mechanisms, and trend of antithrombotic agents were estimated. RESULTS: During the 7-years, 10,496 patients were newly diagnosed with RI. The incidence rate increased from 2.68 to 3.06 per 100,000 person-years during the study period. The incidence rate of RI increased with age peaking in the 70s with 1.41 times male predominance. The most common comorbidity was hypertension, followed by dyslipidemia and diabetes mellitus. Regarding etiologic risk factor distribution, high embolic risk group, renovascular disease group, and hypercoagulable state group accounted for 16.6%, 29.1%, and 13.7% on average, respectively. For the antithrombotic treatment of RI, the prescription of antiplatelet agent gradually decreased from 17.0% to 13.0% while that of anticoagulation agent was maintained around 35%. The proportion of non-vitamin K antagonist oral anticoagulants remarkably increased from only 1.4% to 17.6%. CONCLUSION: Considering the progressively increasing incidence of RI and high prevalence of coexisting risk factors, constant efforts to raise awareness of the disease are necessary. The current epidemiologic investigation of RI would be the stepping-stone to establishing future studies about clinical outcomes and optimal treatment strategies.

Cemented versus Cementless Total Hip Arthroplasty for Femoral Head Osteonecrosis: A Study Based on National Claim Data in South Korea.

INTRODUCTION: The purpose of this study was to compare the rates of revision, periprosthetic joint infection (PJI), and periprosthetic fracture (PPF) between patients with osteonecrosis of the femoral head (ONFH) undergoing noncemented total hip arthroplasty (THA) and cemented THA using a national claim data in South Korea. METHODS: We identified patients who received THA for ONFH from January 2007 to December 2018 using ICD diagnosis codes and procedural codes. Patients were categorized into two groups according to the fixation method: with or without cement. The survivorship of THA was calculated using the following end points: revision of both the cup and stem, revision of the single component, any type of revision, PJI, and PPF. RESULTS: A total of 40,606 patients: 3,738 patients (9.2%) with cement and 36,868 patients (90.7%) without cement, received THA for ONFH. The mean age of the noncemented fixation group (56.2 ± 13.2 years) was significantly lower than that of the cemented fixation group (57.0 ± 15.7 years, P = 0.003). The risk of revision and PJI was notably higher in cemented THA (hazard ratio: 1.44 [1.21 to 1.72] and 1.66 [1.36 to 2.04], respectively). Noncemented THA had a higher 12-year survivorship compared with cemented THA with any revision and PJI as the end point. DISCUSSION: Noncemented fixation had better survivorship than cemented fixation in patients with ONFH.

Bisphenol A-induced autophagy ameliorates human B cell death through Nrf2-mediated regulation of Atg7 and Beclin1 expression by Syk activation.

The widely used plasticizer bisphenol A (BPA) is known as an endocrine-disrupting chemical (EDC). Many studies have shown that BPA contributes to diseases involving immune system alterations, but the underlying mechanisms have yet to be elucidated. We previously reported that BPA at concentration of 100 µM caused human B cell death in accordance with an increase in nuclear factor (erythroid-derived 2)-like 2(Nrf2) expression. Autophagy is a cellular process that degraded and recycles cytoplasmic constituents. Here, we investigated whether BPA induces autophagy through Nrf2, which is associated with regulation of B cell death using human WiL2-NS lymphoblast B cells. Then, cell viability was assessed by various assays using trypan blue, MTT or Celltiter glo luminescent substrate and DAPI. When WiL2-NS cells were treated with BPA, cell viability was decreased and LC3 autophagy cargo protein/puncta was increased. BPA-induced autophagy was confirmed by the modification of LC3 puncta formation or autophagy flux turnover with the treatment of hydroxychloroquine(HCQ), NH4Cl and PI3K inhibitors including 3-methyladenine(3-MA), LY294002 and wortmannin. BPA treatment increased the expression of autophagy-related gene(Atg)7 and Beclin1 as well as Nrf2 induced by the production of reactive oxygen species (ROS). The inhibition of autophagy with siAtg7 or siBeclin1 and Nrf2 depletion aggravated BPA-induced cell death. BPA enhanced the bound of Nrf2 to the specific region on Beclin1 and Atg7 promoter. Spleen tyrosine kinase(Syk) activity was enhanced in response to BPA treatment. Bay61-3606, Syk inhibitor, decreased LC3 and the expression of Atg7 and Beclin1, leading to the increase of BPA-induced B cell death. The results suggest that BPA-induced autophagy ameliorates human B cell death through Nrf2-mediated regulation of Atg7 and Beclin1 expression.

Prevalence of motor neuron diseases in gout patients: a nationwide population-based cohort study.

BACKGROUND: Increased uric acid may have a protective effect in motor neuron diseases (MNDs). The association between gout, characterized by hyperuricemia, and MNDs was not investigated previously. To estimate the prevalence of MNDs in gout patients using the Health Insurance and Review Assessment (HIRA) database, a nationwide database of South Korea. METHODS: The current descriptive study was conducted using the HIRA database. Subjects diagnosed with gout from 2011 to 2018 were included in this study. Among them, the annual prevalence of MNDs was analyzed, stratified by age and sex. Comorbidities including the Charlson Comorbidity Index score and type of prescribed gout-related drug were also demonstrated. RESULTS: The age-adjusted prevalence of MNDs per 105 persons ranged from 0.598 (95% confidence interval (CI): - 0.231-1.426) to 2.534 (95% CI: 1.100-3.968) between 2011 and 2018. Compared to previous reports, the prevalence of MNDs, especially amyotrophic lateral sclerosis (ALS), in gout patients was significantly lower than in the general population. None of the female gout patients were diagnosed with MNDs. Cerebrovascular accidents, vascular risk factors including hypertension, dyslipidemia, and diabetic complications, and the use of uric acid-lowering agents were more common in gout patients with MNDs than in those without MNDs. CONCLUSION: This study adds to the evidence of MND prevalence in gout patients. Gout might have a protective effect against the risk of MNDs.

Trends in Surgical Treatment of Femoral Head Osteonecrosis in South Korea: An Analysis Using Nationwide Claims Database.

Background: Osteonecrosis of the femoral head (ONFH) involves young or middle-aged adults, and its incidence is increasing along with increasing use of steroids in the management of organ transplantation and adjuvant therapy for malignant neoplasms. To date, no pharmacological agent has been proven to prevent or retard the progression of ONFH, and surgical procedures including joint preservation procedures and hip arthroplasties are main treatments for the disease. Although ONFH is the most common or second most common disease for hip arthroplasty in East Asian countries, the trend of surgical procedures in this region remains unknown. Thus, we evaluated trends in surgical treatment of the disease in South Korea. Methods: We identified patients with ONFH from the Korean Health Insurance Review and Assessment (HIRA) database, a nationwide medical claims database of South Korea, between January 2007 and December 2018 and calculated the proportions of following surgical procedures at each year: total hip arthroplasty (THA), hemiarthroplasty (HA), core decompression/multiple drilling, femoral osteotomy, and vascularized bone grafting. Results: The total number of procedures increased from 3,824 in 2007 to 6,929 in 2018. Overall, the rate of THA (86%) was far greater than other procedures. From 2007 to 2018, the percentage of THA among the procedures increased from 80% to 91%, while that of joint preservation procedures decreased from 11% to 5%. Conclusions: The total number of surgical procedures performed for ONFH increased and the percentage of THA increased, while that of joint preservation procedures decreased from 2007 to 2018 in South Korea.

Incidence and predictors of intracranial bleeding after coronary artery bypass graft surgery.

Background: There is a paucity of direct data on the incidence and predictors of intracranial bleeding (ICB) after coronary artery bypass graft surgery (CABG). Methods: The Korean National Health Insurance database was used to identify patients without prior ICB who underwent CABG. The outcomes of interest were the time-dependent incidence rates of ICB and the associated mortality. Results: Among 35,021 patients who underwent CABG between 2007 and 2018, 895 (2.6%) experienced an ICB during a median follow-up of 6.0 years. The 1-year cumulative incidence of ICB was 0.76%, with a relatively high incidence rate (9.93 cases per 1,000 person-years) within the first 1-30 days. Subsequent incidence rates showed a sharp decline until 3 years, followed by a steady decrease up to 10 years. The 1-year mortality rate after ICB was 38.1%, with most deaths occurring within 30 days (23.6%). The predictors of ICB after CABG were age ≥ 75 years, hypertension, pre-existing dementia, history of ischemic stroke or transient ischemic attack, and end-stage renal disease. Conclusions: In an unselected nationwide population undergoing CABG, the incidence of ICB was non-negligible and showed a relatively high incidence rate during the early postoperative period. Post-CABG ICB was associated with a high risk of premature death. Further research is needed to stratify high-risk patients and personalize therapeutic decisions for preventing ICB after CABG.

Influence of concomitant percutaneous transluminal angioplasty with percutaneous coronary intervention on clinical outcomes of stable lower extremity artery diseases.

Concomitant percutaneous transluminal angioplasty (PTA) at the time of percutaneous coronary intervention (PCI) is often performed because lower extremity artery disease (LEAD) commonly coincides with coronary artery disease. We investigated the impact of concomitant PTA on both cardiovascular and limb outcomes in the Korean National Health Insurance Service registry. Among 78,185 patients undergoing PCI, 6563 patients with stable LEAD without limb ischemia were included. After 1:5 propensity score matching was conducted, 279 patients in the PTA + PCI group and 1385 patients in the PCI group were compared. Multivariate Cox proportional hazard models showed that the risk of all-cause death was higher in the PTA + PCI group than in the PCI group, whereas the risks of myocardial infarction, repeat revascularization, stroke, cardiovascular death and bleeding events were not different between the 2 groups. In contrast, the risks of end-stage renal disease and unfavorable limb outcomes were higher in the PTA + PCI group. Mediation analyses revealed that amputation and PTA after discharge significantly mediated the association between concomitant PTA and all-cause death. Concomitant PTA was not associated with an increased risk of cardiovascular events but may increase the risk of all-cause death mediated by unfavorable renal and limb outcomes in patients with stable LEAD.

Increased risks of aortic regurgitation and atrial fibrillation in radiographic axial spondyloarthritis patients: a 10-year nationwide cohort study.

Background: To compare the incidences of aortic regurgitation, atrial fibrillation (AF), and atrioventricular (AV) block II-III between radiographic axial spondyloarthritis (r-axSpA) patients and the general population (GP). Methods: National Health Insurance Services data were used. R-axSpA patients (N = 8877) and the age- and sex-matched GP (N = 26,631) were followed from August 2006 to December 2019. Incidence rates and standardized incidence ratios (SIRs) of aortic regurgitation, AF, and AV block II-III were compared between these groups. Ten-year incidence rates and hazard ratios (HRs) were calculated by the Kaplan-Meier method and Cox regression analysis. Results: Incidence rates of aortic regurgitation, AV block II-III, and AF in the r-axSpA group were 0.42, 0.21, and 4.0 per 1000 person-years (PYs), respectively. In the r-axSpA group, the SIR for aortic regurgitation was highest among 40- to 49-year-old men (4.11). Incidence rates of aortic regurgitation and AF were higher in the r-axSpA group than in the GP group (0.42 versus 0.18 per 1000 PYs 4.00 versus 3.13 per 1000 PYs, both p < 0.001, respectively), whereas the difference was insignificant for AV block II-III (0.21 versus 0.14 per 1000 PYs, p = 0.222). In multivariate analysis, r-axSpA was associated with a higher hazard (risk) for the development of aortic regurgitation and AF [HR (95% confidence interval) = 2.55 (1.49-4.37) and 1.20 (1.04-1.39), respectively], but the difference was insignificant for AV block II-III [HR (95% confidence interval) = 1.17 (0.59-2.31)]. Conclusions: Compared with the GP, r-axSpA patients are at increased risk of aortic regurgitation and AF, but not AV block II-III. These patients should be carefully monitored for occurrence of aortic regurgitation and AF.

Structural and spectroscopic studies of spontaneously formed crystalline Eu(iii)-aliphatic dicarboxylates at room temperature.

Complexation of actinides and lanthanides with carboxylic organic ligands is a critical issue affecting radionuclide migration from deep geological disposal systems of spent nuclear fuel. A series of Eu(iii)-aliphatic dicarboxylate compounds, as chemical analogs of radioactive Am(iii) species, Eu2(Ox)3(H2O)6, Eu2(Mal)3(H2O)6, and Eu2(Suc)3(H2O)2, were synthesized and characterized using X-ray crystallography and time-resolved laser fluorescence spectroscopy to examine the ligand-dependent binding modes and the corresponding changes in spectroscopic properties. Powder X-ray crystallography results confirmed that all of the compounds presented a crystalline polymer structure with a trigonal prism square-face tricapped polyhedron geometry centered on Eu(iii) in a nine-coordinate environment involving nine oxygen atoms. This study captures the transition of the coordination modes of aliphatic dicarboxylate ligands from side-on to end-on binding as the carbon chain length increases. This transition is illustrated in malonate bindings involving a combination of side-on and end-on modes. Strongly enhanced luminescence, especially for the hypersensitive peak, indicates a low site symmetry in the formation of solid compounds. The number of remaining bound water molecules was estimated from the resultant increased luminescence lifetimes, which were in good agreement with crystal structures. The excitation-emission matrix spectra of these crystalline polymers suggest that Ox ligands promote the sensitized luminescence of Eu(iii), especially in the UV region. In the case of Mal and Suc ligands, charge transfer occurs in the opposite direction from Eu(iii) to the ligands under UV excitation, resulting in weaker luminescence.

Risk factors for second primary malignancies following thyroid cancer: a nationwide cohort study.

Objective: Thyroid cancer survivors have a high risk of second primary malignancies (SPMs). We aimed to evaluate the site-specific incidence, prognosis, and risk factors for metachronous SPMs following thyroid cancer. Design: A nationwide cohort study. Methods: This study included data from the Korea National Health Insurance Service (between 2002 and 2018). Exposure to diagnostic radiation was defined by the number of computed tomography (CT) and positron emission tomography-CT scans after the index date. A cumulative radioactive iodine (RAI) dose >100 mCi was considered high-dose RAI. Results: During the median 6 years of follow-up, among 291 640 patients, 13 083 (4.5%) developed SPMs. Thyroid cancer survivors had a 26% increased risk of SPMs compared with the general population (standardized incidence ratio: 1.26; 95% CI: 1.22-1.29). Furthermore, those with SPMs had a significantly poorer survival rate than those without SPMs (hazard ratio: 11.85; 95% CI: 11.21-12.54; P < 0.001). Significantly elevated risks were observed in myeloid leukemia and 13 solid cancer sites: lip, salivary gland, small intestine, larynx, lung, mediastinum and pleura, mesothelium, breast, corpus uteri, ovary, prostate, kidney, and bladder. Frequent diagnostic medical radiation exposure and high-dose RAI therapy were independent risk factors for several SPMs, including the cancer of salivary gland, lung, mediastinum and pleura, breast, kidney, and bladder, as well as myeloid leukemia. Conclusions: Frequent diagnostic radiation exposure and high-dose RAI therapy are independent risk factors for SPM following thyroid cancer. Clinicians need to consider minimizing unnecessary diagnostic radiation exposure and administering a high dose RAI only when justified in patients with thyroid cancer.

Annual Incidence of Dementia from 2003 to 2018 in Metropolitan Seoul, Korea: A Population-Based Study.

National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 to 2018. The customized research database of the Korean National Health Insurance Services was used. The annual crude and age-standardized incidence of dementia patients and their characteristics were analyzed. This study analyzed 108,596 incident dementia cases aged ≥60 years. The incidence rate increased from 2003 to 2011, including a rapid increment from 2007 to 2011. From 2011 to 2018, the crude (age-standardized) incidence per 105 person-years decreased from 641.51 (577.12) to 448.26 (361.23). The proportion of incident dementia cases was highest in the highest income group every year. However, the proportion of incident dementia cases in the lowest income group increased from 10.4% in 2003 to 25.8% in 2011. The annual incidence rate of dementia showed a sharp increase immediately after 2007, the year dementia support centers began to be introduced, and then stabilized after 2011. The characteristics of incident dementia cases have changed, including the proportion in the low-income group.

Risk of ischaemic stroke in patients with transient global amnesia: a propensity-matched cohort study.

BACKGROUND: The exact pathophysiological mechanism of transient global amnesia (TGA) is unknown. It is debatable whether TGA is a risk factor for stroke. Therefore, here we investigated the possibility of TGA as a risk factor for stroke in a real-world setting using large-scale nationwide health claims data. METHODS: We used health claims data from the Korean National Health Insurance Service (NHIS). Patients diagnosed with TGA between 2007 and 2013 were selected. We initially extracted patients without TGA who were preferentially matched for age and sex with the patients with TGA at a ratio of 10:1 from the whole dataset. Further, we performed 1:2 propensity score matching analysis to balance the baseline characteristics between the two groups. In the propensity score-matched dataset, we performed multivariable Cox regression analysis to investigate the association between TGA and stroke type, including ischaemic, haemorrhagic and all stroke types. RESULTS: Patients with TGA (n=14 673) were selected from the NHIS database. After extracting from the whole database (n=140 486) and propensity score matching their data at a 1:2 ratio, a total of 10 448 and 20 442 patients were finally assigned to the TGA and control groups, respectively. The multivariable Cox regression analysis demonstrated that the TGA group had a higher risk of ischaemic stroke and all types of stroke (adjusted HR=1.194; 95% CI: 1.043 to 1.368; and HR=1.197; 95% CI: 1.056 to 1.357, respectively). CONCLUSIONS: Analysis of the nationwide claims database showed that TGA could be an important risk factor for stroke, especially for ischaemic stroke.