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.

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.

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.

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.

Association of Physical Activity with the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B.

BACKGROUND AND AIMS: In the general population, previous studies reported that physical activity was associated with risk of hepatocellular carcinoma (HCC) development. However, it is unclear whether physical activity is associated with risk of HCC development in patients with chronic hepatitis B (CHB). We aimed to elucidate the association between physical activity and risk of HCC development in CHB patients. METHODS: This nationwide cohort study involved treatment-naive patients with CHB (n = 9727) who started treatment with entecavir or tenofovir and answered self-reported questionnaires between January 2012 and December 2017, using data from the Korean National Health Insurance Service database. The primary endpoint was development of HCC. Multivariable Cox regression and competing risk analyses were used. RESULTS: During a median follow-up of 3.1 years, cumulative HCC incidence rates were 8.3%. There was an inverse association between physical activity and the risk of HCC (p < 0.001). Patients with 1000-1500 metabolic equivalent task (MET)-min/week, compared to those without physical activity, showed a significantly lower risk of HCC in both patients without cirrhosis (adjusted hazard ratio [aHR] 0.66, p = 0.02) and patients with cirrhosis (aHR 0.61, p = 0.02). In patients who were younger (<60), male, without diabetes, and with high BMI, amounts of physical activity of 1000-1500 MET-min/week showed an inverse association with the risk of HCC (aHR 0.65, 0.63, 0.65, and 0.64, respectively, all p < 0.05). CONCLUSION: Physical activity was significantly associated with a low risk of HCC in CHB patients treated with entecavir or tenofovir.

Fenofibrate Use Is Associated With Lower Mortality and Fewer Cardiovascular Events in Patients With Diabetes: Results of 10,114 Patients From the Korean National Health Insurance Service Cohort.

OBJECTIVE: We investigated the long-term clinical efficacy of fenofibrate use with regard to mortality and cardiovascular outcomes in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a population-based cohort study using data of the South Korean National Health Insurance Service from 2003 to 2014. Of 63,727 participants with diabetes aged 40-79 years, 5,057 users of fenofibrate only were compared with 5,057 nonusers of fenofibrate and/or omega-3 fatty acid with 1:1 propensity matching. The primary end point was a composite of myocardial infarction, stroke, percutaneous coronary revascularization, and cardiac death for a median of 3 years. RESULTS: The primary end point was significantly lower in fenofibrate users compared with those using neither fenofibrate nor omega-3 fatty acid (13.4 vs. 15.5 per 1,000 person-years; hazard ratio [HR] 0.76; 95% CI 0.62-0.94; P = 0.010). Cardiac death (1.8 vs. 3.1 per 1,000 person-years; HR 0.59; 95% CI 0.352-0.987; P = 0.0446), all-cause death (7.6 vs. 15.3 per 1,000 person-years; HR 0.437; 95% CI 0.340-0.562; P < 0.0001), and stroke (6.5 vs. 8.6 per 1,000 person-years; HR 0.621; 95% CI 0.463-0.833; P = 0.0015) were significantly lower in the fenofibrate group. When the duration of fenofibrate use was stratified by quartile, the risk decreased in quartile 4, with an HR of 0.347 (95% CI 0.226-0.532; P < 0.0001). In subgroup analysis, the favorable effect of fenofibrate was sustained consistently across all subsets of patients, including those classified by LDL cholesterol, HDL cholesterol, and triglyceride levels. CONCLUSIONS: Use of fenofibrate was associated with a lower rate of total and cardiac mortality and cardiovascular events in patients with type 2 diabetes during a 3-year follow-up in real-world large populations.

Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity.

Lumican, a ubiquitously expressed small leucine-rich proteoglycan, has been utilized in diverse biological functions. Recent experiments demonstrated that lumican stimulates preosteoblast viability and differentiation, leading to bone formation. To further understand the role of lumican in bone metabolism, we investigated its effects on osteoclast biology. Lumican inhibited both osteoclast differentiation and in vitro bone resorption in a dose-dependent manner. Consistent with this, lumican markedly decreased the expression of osteoclastogenesis markers. Moreover, the migration and fusion of preosteoclasts and the resorptive activity per osteoclast were significantly reduced in the presence of lumican, indicating that this protein affects most stages of osteoclastogenesis. Among RANKL-dependent pathways, lumican inhibited Akt but not MAP kinases such as JNK, p38, and ERK. Importantly, co-treatment with an Akt activator almost completely reversed the effect of lumican on osteoclast differentiation. Taken together, our findings revealed that lumican inhibits osteoclastogenesis by suppressing Akt activity. Thus, lumican plays an osteoprotective role by simultaneously increasing bone formation and decreasing bone resorption, suggesting that it represents a dual-action therapeutic target for osteoporosis.

Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study.

OBJECTIVE: Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. DESIGN: A nationwide cohort study. METHODS: Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). RESULTS: During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. CONCLUSIONS: Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

Exploring MRI based radiomics analysis of intratumoral spatial heterogeneity in locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy.

BACKGROUND: We hypothesized that spatial heterogeneity exists between recurrent and non-recurrent regions within a tumor. The aim of this study was to determine if there is a difference between radiomics features derived from recurrent versus non recurrent regions within the tumor based on pre-treatment MRI. METHODS: A total of 14 T4NxM0 NPC patients with histologically proven "in field" recurrence in the post nasal space following curative intent IMRT were included in this study. Pretreatment MRI were co-registered with MRI at the time of recurrence for the delineation of gross tumor volume at diagnosis(GTV) and at recurrence(GTVr). A total of 7 histogram features and 40 texture features were computed from the recurrent(GTVr) and non-recurrent region(GTV-GTVr). Paired t-tests and Wilcoxon signed-rank tests were carried out on the 47 quantified radiomics features. RESULTS: A total of 7 features were significantly different between recurrent and non-recurrent regions. Other than the variance from intensity-based histogram, the remaining six significant features were either from the gray-level size zone matrix (GLSZM) or the neighbourhood gray-tone difference matrix (NGTDM). CONCLUSIONS: The radiomic features extracted from pre-treatment MRI can potentially reflect the difference between recurrent and non-recurrent regions within a tumor and has a potential role in pre-treatment identification of intra-tumoral radio-resistance for selective dose escalation.

SIRT2 directs the replication stress response through CDK9 deacetylation.

Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and is a murine tumor suppressor. We show that SIRT2 directs replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication arrest. SIRT2 deficiency results in replication stress sensitivity, impairment in recovery from replication arrest, spontaneous accumulation of replication protein A to foci and chromatin, and a G2/M checkpoint deficit. SIRT2 interacts with and deacetylates CDK9 at lysine 48 in response to replication stress in a manner that is partially dependent on ataxia telangiectasia and Rad3 related (ATR) but not cyclin T or K, thereby stimulating CDK9 kinase activity and promoting recovery from replication arrest. Moreover, wild-type, but not acetylated CDK9, alleviates the replication stress response impairment of SIRT2 deficiency. Collectively, our results define a function for SIRT2 in regulating checkpoint pathways that respond to replication stress through deacetylation of CDK9, providing insight into how SIRT2 maintains genome integrity and a unique mechanism by which SIRT2 may function, at least in part, as a tumor suppressor protein.