Cancer Risk According to Alcohol Consumption Trajectories: A Population-based Cohort Study of 2.8 Million Korean Men.

BACKGROUND: Alcohol drinking behaviors change temporally and can lead to changes in related cancer risks; previous studies have been unable to identify the association between the two using a single-measurement approach. Thus, this study aimed to investigate the association of drinking trajectories with the cancer risk in Korean men. METHODS: A trajectory analysis using group-based trajectory modeling was performed on 2,839,332 men using data on alcohol drinking levels collected thrice during the Korean National Health Insurance Service's general health screening program conducted between 2002 and 2007. Cox proportional hazards regression was performed to evaluate the associations between drinking trajectories and cancer incidence, after adjustments for age, income, body mass index, smoking status, physical activity, family history of cancer, and comorbidities. RESULTS: During 10.5 years of follow-up, 189,617 cancer cases were recorded. Six trajectories were determined: non-drinking, light, moderate, decreasing-heavy, increasing-heavy, and steady-heavy. Light-to-heavy alcohol consumption increased the risk for all cancers combined in a dose-dependent manner (adjusted hazard ratio [aHR] 1.03; 95% confidence interval [CI], 1.02-1.05 for light drinking, aHR 1.06; 95% CI 1.05-1.08 for moderate drinking, aHR 1.19; 95% CI, 1.16-1.22 for decreasing-heavy drinking, aHR 1.23; 95% CI, 1.20-1.26 for increasing-heavy drinking, and aHR 1.33; 95% CI, 1.29-1.38 for steady-heavy drinking [P-trend <0.001]). Light-to-heavy alcohol consumption was linked to lip, oral cavity, pharyngeal, esophageal, colorectal, laryngeal, stomach, and gallbladder and biliary tract cancer risks, while heavy alcohol consumption was associated with hepatic, pancreatic, and lung cancer risks. An inverse association was observed for thyroid cancer. The cancer risks were lower for decreasing-heavy drinkers, compared to steady-heavy drinkers. CONCLUSION: No safe drinking limits were identified for cancer risks; reduction in heavy intake had protective effects.

Human Cytomegalovirus UL48 Deubiquitinase Primarily Targets Innermost Tegument Proteins pp150 and Itself To Regulate Their Stability and Protects Virions from Inclusion of Ubiquitin Conjugates.

Viral deubiquitinases (DUBs) regulate cellular innate immunity to benefit viral replication. In human cytomegalovirus (HCMV), the UL48-encoded DUB regulates innate immune responses, including NF-κB signaling. Although UL48 DUB is known to regulate its stability via auto-deubiquitination, its impact on other viral proteins is not well understood. In this study, we investigated the role of UL48 DUB in regulating the ubiquitination of viral proteins by comparing the levels of ubiquitinated viral peptides in cells infected with wild-type virus and DUB active-site mutants using mass spectrometry. We found that ubiquitinated peptides were increased in DUB mutant virus infection for 90% of viral proteins, with the innermost tegument proteins pp150 (encoded by UL32) and pUL48 itself being most significantly affected. The highly deubiquitinated lysine residues of pUL48 were mapped within its N-terminal DUB domain and the nuclear localization signal. Among them, the arginine substitution of lysine 2 (K2R) increased pUL48 stability and enhanced viral growth at low multiplicity of infection, indicating that K2 auto-deubiquitination has a role in regulating pUL48 stability. pUL48 also interacted with pp150 and increased pp150 expression by downregulating its ubiquitination. Furthermore, we found that, unlike the wild-type virus, mutant viruses expressing the UL48 protein with the DUB domain deleted or DUB active site mutated contain higher levels of ubiquitin conjugates, including the ubiquitinated forms of pp150, in their virions. Collectively, our results demonstrate that UL48 DUB mainly acts on the innermost tegument proteins pp150 and pUL48 itself during HCMV infection and may play a role in protecting virions from the inclusion of ubiquitin conjugates. IMPORTANCE Herpesviruses encode highly conserved tegument proteins that contain deubiquitinase (DUB) activity. Although the role of viral DUBs in the regulation of host innate immune responses has been established, their roles in the stability and function of viral proteins are not well understood. In this study, we performed a comparative analysis of the levels of ubiquitinated viral peptides between wild-type and DUB-inactive HCMV infections and demonstrated that the innermost tegument proteins pp150 and pUL48 (DUB itself) are major targets of viral DUB. We also show that ubiquitinated viral proteins are effectively incorporated into the virions of DUB mutant viruses but not the wild-type virus. Our study demonstrates that viral DUBs may play important roles in promoting the stability of viral proteins and inhibiting the inclusion of ubiquitin conjugates into virions.

Prevalence of human papillomavirus-related diseases in the Republic of Korea: a cross-sectional study.

OBJECTIVE: We aimed to evaluate trends in the prevalence of human papillomavirus (HPV)-related diseases in the era before the introduction of organised HPV vaccination programmes in the Republic of Korea. METHODS: This cross-sectional study used National Health Insurance Service data from 2002 to 2015 and included participants who were diagnosed with the following HPV-related diseases (codes from the International Classification of Diseases, 10th Revision): genital warts (A63.0); cancer in the head and neck (C00-C10), anus (C21), vulva (C51), vagina (C52), cervix uteri (C53) and penis (C60); carcinoma in situ (CIS) of the lip/oral cavity/pharynx (D00.0), anus (D01.3), cervix (D06), vulva (D07.1), vagina (D07.2) and penis (D07.4); benign neoplasms of the larynx (D14.1); and dysplasia of the cervix (N87), vagina (N89) and vulva (N90). For each diagnosis, the fraction of cases attributable to HPV in Korea was assessed based on the percentages of diseases attributable to HPV reported in some international studies. The age-standardised prevalence was estimated using the direct population-based method. RESULTS: The overall age-standardised prevalence of HPV-related diseases increased from 2002 to 2015, mainly due to increased prevalence of genital warts in men and cervical dysplasia and CIS in women. In women, genital wart prevalence increased from 2002 (24.4 per 100 000) to 2011 (57.1) and then decreased until 2015 (53.5); in men, the prevalence increased steadily from 2002 (22.9) to 2015 (109.4). The prevalence of cervical dysplasia and CIS increased (from 86.5 in 2002 to 484.5 in 2015, and from 60.3 in 2002 to 114.9 in 2015, respectively), but that of cervical cancer decreased (from 120.0 in 2002 to 106.9 in 2015). CONCLUSIONS: Non-organised HPV vaccination and organised cervical cancer screening may have contributed to the downward trend in genital wart prevalence and the upward trend in cervical abnormalities among women.

Application of high-sensitivity radon monitor on walk-in type radon calibration chamber at KRISS.

This paper introduces the KRISS-Rn4, a high-sensitivity radon monitor with four detection cells, installed within a walk-in type radon calibration chamber at KRISS. The KRISS-Rn4 exhibits enhanced energy resolution through channel-by-channel signal processing and data acquisition. Results reveal that it achieves lower statistical fluctuations and faster response times in monitoring test atmospheres compared to commercial devices.

Digital coincidence counting with 4πß(PPC)-γ for the standardization of 60Co.

A 4πß(PPC)-γ coincidence system has been made at KRISS based on a digital DAQ. 60Co sources were measured to verify the system. The maximum detection efficiency for beta particles was estimated to be 96.7 %. Massic activities for sample sources had 0.005 % of the sample variability error, which was well within the expanded standard uncertainty of 0.54 % (k = 2).

The ratio of osteoprotegerin to fetuin-a is independently associated with vascular stiffness in hemodialysis patients.

BACKGROUND: The aim of the present study was to compare levels of fetuin-A, osteoprotegerin (OPG), and heat shock protein (HSP)70 according to the stage of chronic kidney disease (CKD), as well as to evaluate the association between serum fetuin-A, OPG, and HSP70 concentrations with respect to vascular stiffness and calcification in hemodialysis (HD) patients. METHODS: We measured fetuin-A, OPG, and HSP70 in 35 healthy controls, 35 patients with stage 3 CKD, 35 patients with stage 4 CKD, and 81 HD patients. Using these data, we studied the association of fetuin-A, OPG, and HSP70 with clinical, biochemical, and vascular measures in HD patients. RESULTS: Levels of OPG and HSP70 were higher and fetuin-A was lower in HD patients than in healthy controls. The cardio-ankle vascular index (CAVI) showed a positive correlation with OPG (r = 0.248, p = 0.040) and the OPG/fetuin-A ratio (r = 0.260, p = 0.031). The ankle-brachial index (ABI) showed a negative correlation with OPG (r = -0.245, p = 0.031) and the OPG/fetuin-A ratio (r = -0.267, p = 0.018). Intima-media thickness (IMT) showed a positive correlation with OPG (r = 0.273, p = 0.014) and the OPG/fetuin-A ratio (r = 0.269, p = 0.015). On stepwise multiple linear regression analyses, only the logarithmic function of the OPG/fetuin-A ratio was independently associated with CAVI (ß = 13.325, SE = 6.247, p = 0.038). CONCLUSIONS: Our results demonstrate that OPG and the OPG/fetuin-A ratio are correlated with increased vascular stiffness and IMT in HD patients. In addition, the OPG/fetuin-A ratio was independently associated with vascular stiffness in HD patients.

Short-term effects of national smoking cessation service on smoking-related disease prevalence and healthcare costs: Experience from the National Health Insurance Service Smoking Cessation Intervention Program in Korea.

INTRODUCTION: We measured the short-term clinical and economic impacts of the National Health Insurance Service (NHIS) smoking cessation program, which subsidizes the cost of pharmacotherapy and medical consultations, by comparing the changes in prevalence and healthcare costs of smoking-related diseases among cessation service users, non-users, and never smokers. METHODS: Smokers who used the cessation service from 2015 to 2017 were included (n=779315). We used claims data from the NHIS, a mandatory, single-payer insurance covering the entire Korean population, to determine the number of patients with selected diseases, their healthcare utilization, and medical costs, and compared these amounts in the one year before and after enrollment. For further comparison, we also estimated disease prevalence and medical costs in matched controls by age, sex, income, and residential area, including never smokers and smokers who never used the cessation program. RESULTS: Across all 15 selected diseases, the number of patients, days spent in the hospital, and medical costs for 1 year were consistently higher after service enrollment than before. This pattern was observed for both men and women. Notably, decreased prevalence and medical costs for pneumonia were observed among individuals aged <50 years. Healthcare utilization for any kind of disease for 1 year was 97.7%, 91.1%, and 88.8% among cessation service users, never smokers, and smokers who did not use the cessation service, respectively. The disease-specific prevalence was also highest and increased more in the cessation service users compared with the control groups. CONCLUSIONS: Cessation service users were more likely to seek healthcare. Increased healthcare utilization in the first year after cessation service use may have resulted from smoking-related conditions that led individuals to attempt smoking cessation.

Adherence to Cancer Prevention Guidelines and Cancer Incidence and Mortality: A Population-Based Cohort Study.

PURPOSE: This study aimed to estimate the risk of cancer incidence and mortality according to adherence to lifestyle-related cancer prevention guidelines. MATERIALS AND METHODS: Men and women who participated in the general health screening program in 2002 and 2003 provided by the National Health Insurance Service were included (n=8,325,492). Self-reported smoking, alcohol consumption, and physical activity habits and directly measured body mass index were collected. The participants were followed up until the date of cancer onset or death or 31 December 2018. The Cox proportional hazard model was used to evaluate the hazard ratio (HR) for cancer incidence and mortality according to different combinations of lifestyle behaviors. RESULTS: Only 6% of men and 15% of women engaged in healthy behavior at baseline, such as not smoking, not drinking alcohol, being moderately or highly physically active, and within a normal body mass index range. Compared to the best combination of healthy lifestyle behaviors, the weak and moderate associations with increased all cancer incidence (HR < 1.7) and mortality (HR < 2.5) were observed in those with heavy alcohol consumption and in former or current smokers. HRs of cancer mortality were significantly increased among current smokers in most combinations. CONCLUSION: Compared to full adherence to cancer prevention recommendations, unhealthy behaviors increase cancer risk. As few people meet these recommendations, there is a great opportunity for cancer prevention.

Alcoholic liver disease in relation to cancer incidence and mortality: Findings from a large, matched cohort study in South Korea.

AIM: To estimate the risk of cancer incidence and mortality among patients with alcoholic liver disease in South Korea. METHODS: A matched cohort study was conducted, including 1,042,185 men (alcoholic liver disease cases: 208,437; controls: 833,748) and 100,400 women (alcoholic liver disease cases: 20,080; controls: 80,320), matched for sex, age, smoking, alcohol consumption, and body mass index at a 1:4 ratio. The risk of cancer incidence and mortality in the alcoholic liver disease group was assessed using Cox proportional hazards regression models. RESULTS: Both men and women with alcoholic liver disease had an elevated risk of all-cancer and liver cancer incidence and mortality in comparison with the control group. In men, alcoholic liver disease was associated with a significantly higher risk of development of 10 cancer types, including lip, oral cavity, and pharynx; esophagus; liver; gallbladder and biliary tract; pancreas; larynx; lung; kidney; thyroid gland; and leukemia. Subgroup analysis by hepatitis B and C infection showed increased hazard ratios of all cancer incidences and mortality in the alcoholic liver disease group, regardless of hepatitis B or C infection status. In both sexes, a higher number and more years of hospital or clinic visits for alcoholic liver disease were associated with an increased risk of incidence and mortality from all cancers and liver cancer. A more profound dose-response relationship between alcoholic liver disease and alcohol consumption was observed in women than in men. CONCLUSIONS: Our findings emphasize the need for a clinical surveillance program and the early detection of cancer in patients with alcoholic liver disease.

Gastroesophageal reflux disease and risk of cancer: Findings from the Korean National Health Screening Cohort.

AIM: Little is known about the association of cancers other than esophageal adenocarcinoma with gastroesophageal reflux disease (GERD). This study aimed to examine the association between GERD and the risk of different types of cancer. METHODS: A cohort study was conducted using data from the National Health Screening Cohort. We included 10,261 GERD patients and 30,783 non-GERD individuals who were matched in a 1:3 ratio by age and sex. All participants were followed-up until cancer diagnosis, death, or end of the study (December 31, 2015). Hazard ratios were calculated using the Cox proportional hazards model, adjusting for smoking and alcohol consumption, physical activity, body mass index, income, area, and Charlson Comorbidity Index. RESULTS: The median follow-up time was 9.9 years. GERD was associated with an increased risk of esophageal (adjusted hazard ratios [aHR] = 3.20 [1.89-5.41]), laryngeal (aHR = 5.42 [2.68-10.96]), and thyroid cancers (aHR = 1.91 [1.55-2.34]) after controlling for all covariates. The results were consistent when examining GERD with esophagitis (K210) and without esophagitis (K219) separately. For thyroid cancer, the results were insignificant after controlling for having ever-received thyroid biopsy procedures. A dose-response relationship was found between GERD and esophageal cancer as well as laryngeal cancer, with patients with a longer duration of GERD treatment showing a stronger effect. In contrast, GERD was associated with a reduced risk of colorectal (aHR = 0.73 [0.59-0.90]), liver (aHR = 0.67 [0.51-0.89]), and pancreatic cancers (aHR = 0.43 [0.24-0.76]), which might have resulted from differences in healthcare utilization between GERD and non-GERD groups. CONCLUSION: GERD was associated with an increased risk of esophageal and laryngeal cancers. Additionally, early detection and treatment of precancerous lesions among the GERD group could lead to a lower risk of colorectal, liver, and pancreatic cancers.

Trajectory of physical activity frequency and cancer risk: Findings from a population-based cohort study.

BACKGROUND: Physical activity (PA) changes throughout an individual's life, but the association between such changes and cancer risk seems to be overlooked in the literature. Thus, this study aimed to examine the association between the trajectories of PA frequency and cancer incidence among middle-aged Korean adults. METHODS: A total of 1,476,335 eligible participants (992,151 men and 484,184 women) aged ≥40 years from the National Health Insurance Service cohort (2002-2018) were included. Assessment of PA frequency was a self-reported measure, based on the question: "How many times per week do you perform exercise that makes you sweat?". PA frequency trajectories (i.e., trajectory classes of change in PA frequency) from 2002 to 2008 were identified using group-based trajectory modeling. Cox proportional hazards regression was used to assess the associations between the PA trajectories and cancer incidence. RESULTS: Five PA frequency trajectories over 7 years were identified: persistently low (men:73.5%; women:74.7%), persistently moderate (men:16.2%; women:14.6%), high-to-low (men:3.9%; women:3.7%), low-to-high (men:3.5%; women:3.8%), and persistently high (men:2.9%; women:3.3%). Compared with persistently low frequency, maintaining a high PA frequency was associated with a lower risk of all cancers (Hazard ratio (HR) = 0.92, 95%CI = 0.87-0.98) and breast cancer (HR = 0.82, 95%CI = 0.70-0.96) among women. There was a lower risk for thyroid cancer among men in the high-to-low (HR = 0.83, 95%CI = 0.71-0.98), low-to-high (HR = 0.80, 95%CI = 0.67-0.96), and high PA trajectories (HR = 0.82, 95%CI = 0.68-0.99). There was a significant association between moderate trajectory and lung cancer in men (HR = 0.88, 95%CI = 0.80-0.95), in both smoking and non-smoking men. CONCLUSION: Long-term persistent high frequency of PA as part of the daily routine should be widely promoted and encouraged to reduce the risk for all cancer development in women.

Mortality risk according to smoking trajectories after cancer diagnosis among Korean male cancer survivors: A population-based cohort study.

INTRODUCTION: Previous research on post-diagnosis smoking among cancer survivors mainly relied on smoking status, which may not fully reflect the impact of changes in smoking levels. This study aimed to evaluate mortality risk according to smoking trajectories among Korean male cancer survivors, using a trajectory approach to comprehensively capture smoking patterns. METHODS: The study included 110555 men diagnosed with cancer between 2002 and 2018 from the Korean National Health Information Database. Group-based trajectory modelling was used to identify post-diagnosis smoking trajectories among pre-diagnosis current smokers (n=45331). Cox hazards models were fitted to evaluate mortality risk according to smoking trajectories for pooled cancers, pooled smoking-related cancers, smoking-unrelated cancers, and gastric, colorectal, liver, and lung cancers. RESULTS: Smoking trajectories included light-smoking quitters, heavy-smoking quitters, consistent moderate smokers, and decreasing heavy smokers. Smoking significantly increased all-cause and cancer mortality risks in cancer patients for pooled cancers, pooled smoking-related cancers, and pooled smoking-unrelated cancers. Compared to non-smokers, all-cause mortality risk for pooled cancers significantly increased according to smoking trajectories:(AHR=1.33; 95% CI: 1.27-1.40), (AHR=1.39; 95% CI: 1.34-1.44), (AHR=1.44; 95% CI: 1.34-1.54), and (AHR=1.47; 95% CI: 1.36-1.60), respectively. Smoking increased all-cause and cancer mortality risks in gastric and colorectal cancer patients and cancer-specific mortality in lung cancer patients. The significant associations of smoking trajectories with all-cause and cancer mortality risks were primarily observed in 5-year survivors but not in short-term survivors. Among heavy smokers, smoking cessation significantly reduced all-cause mortality risk in the long-term. CONCLUSIONS: The post-diagnosis smoking trajectory independently predicts cancer prognosis among male cancer patients. Proactive cessation support should be strengthened, particularly for those who smoke heavily.

Effects of Thrombin-Based Hemostatic Agent in Total Knee Arthroplasty: Meta-Analysis.

The effectiveness of Floseal, a thrombin-based hemostatic matrix, in total knee arthroplasty (TKA) in minimizing blood loss and transfusion requirements remains a topic of debate. This meta-analysis aims to evaluate the up-to-date randomized controlled trials (RCTs) on the efficacy and safety of Floseal in TKA. A comprehensive search was conducted in electronic databases to identify relevant RCTs. The methodological quality of the included studies was assessed, and data extraction was performed. The pooled effect sizes were calculated using standardized mean difference (SMD) or odds ratios (OR) with 95% confidence intervals (CIs). Eight studies involving 904 patients were included in the meta-analysis. The use of a thrombin-based hemostatic agent significantly reduced hemoglobin decline (SMD = -0.49, 95% CI: -0.92 to -0.07) and the risk of allogenic transfusion (OR = 0.45, 95% CI: 0.25 to 0.81) but showed no significant difference in the volume of drainage or total blood loss. Funnel plots showed no evidence of publication bias. This meta-analysis provides robust evidence supporting the effectiveness of Floseal in reducing hemoglobin decline and transfusion in TKA. Further well-designed RCTs with longer follow-up periods are warranted to assess long-term efficacy and safety.

Chronic pancreatitis and cancer risk in a matched cohort study using national claims data in South Korea.

This study aimed to examine the association between chronic pancreatitis (CP) and cancer incidence and mortality among the Korean population. Based on a cancer-free cohort of 8,317,616 individuals between 2002 and 2010, a matched cohort study was conducted, including 10,899 patients with CP, matched for sex and age with 32,697 individuals without CP. The case and control groups were followed up until the date of onset of cancer or death or the end of follow-up date (December 31, 2018). Cox proportional hazards regression was performed to assess the risk of cancer incidence and mortality. Compared to the control group, patients with CP had a higher risk of all cancers with a hazard ratio (HR) of 1.2 [95% confidence interval (CI) 1.1-1.3]. CP was associated with an increased risk of esophageal cancer (HR 3.9, 95% CI 1.8-8.5) and pancreatic cancer (HR 3.9, 95% CI 2.7-5.5) and a decreased risk of colorectal cancer (HR 0.7, 95% CI 0.5-0.9). Regarding cancer mortality, patients with CP had a 1.2-fold risk of all cancer mortality (95% CI 1.1-1.4), compared with the control group. Patients with CP had a higher risk of death from esophageal cancer (HR 3.5, 95% CI 1.5-8.0) and pancreatic cancer (HR 3.3, 95% CI 2.3-4.7) but had a lower risk of death due to stomach cancer (HR 0.4, 95% CI 0.2-0.8). Patients with CP had a higher risk for both incidence and mortality of all cancer types, especially pancreatic and esophageal cancers, compared with the sex- and age-matched control group.

The Panax ginseng Berry Extract and Soluble Whey Protein Hydrolysate Mixture Ameliorates Sarcopenia-Related Muscular Deterioration in Aged Mice.

Sarcopenia is prevalent as the aging population grows. Therefore, the need for supplements for the elderly is increasing. This study aimed to investigate the efficacy and mechanism of a Panax ginseng berry extract (GBE) and soluble whey protein hydrolysate (WPH) mixture on a sarcopenia-related muscular deterioration in aged mice. Ten-month-old male C57BL/6J mice were administered three different doses of the GBE + WPH mixture for 8 weeks; 700 mg/kg, 900 mg/kg, and 1100 mg/kg. Grip strength, serum inflammatory cytokines level, and mass of muscle tissues were estimated. The deteriorating function of aging muscle was investigated via protein or gene expression. Grip strength and mass of three muscle tissues were increased significantly in a dose-dependent manner, and increased anti-inflammatory cytokine alleviated systemic inflammatory state. The mixture resolved the imbalance of muscle protein turnover through activation of the PI3K/Akt pathway and increased gene expression of the muscle regeneration-related factors, while decreasing myostatin, which interferes with muscle protein synthesis and regeneration. Furthermore, we confirmed that increased mitochondria number in muscle with the improvement of mitochondrial biogenesis. These physiological changes were similar to the effects of exercise.

Weight-change trajectory in relation to cancer risk: findings from a nationwide cohort study in South Korea.

OBJECTIVE: This study examined relationships between weight-change trajectories and all cancers and obesity-related cancer risks. METHODS: A total of 1,882,304 men and 899,912 women from the 2002 to 2017 National Health Insurance Service cohort were included. Weight-change trajectories in 2002 to 2009, according to BMI, were determined using group-based trajectory modeling. Cox proportional hazards regression assessed associations between trajectories and cancer incidence. RESULTS: Overall, >50% of individuals maintained stable weight, as did two-thirds of those in the overweight and obesity groups. A total of 64,725 men and 37,608 women developed incident cancer. Weight stability in overweight or obesity groups was associated with greater cancer risk. In both sexes, higher weight across BMI groups increased risks of all cancers, obesity-related cancers and thyroid, colorectal, stomach, liver, prostate, and postmenopausal breast cancer. Stratified by BMI, weight gain increased risks of all cancers and obesity-related cancers in men with obesity class I and women with overweight. Weight loss decreased risks of obesity-related cancers, thyroid cancer, and kidney cancer among men with overweight, premenopausal breast, endometrial, and ovarian cancer in women with overweight, and obesity-related cancers and thyroid cancer in women with class I obesity. CONCLUSIONS: Maintaining weight and avoiding weight gain are crucial for reducing cancer risk, but achieving a stable, normal BMI optimizes cancer prevention.

Association between sarcopenia defined as low lean mass by dual-energy X-ray absorptiometry and comorbidities of rheumatoid arthritis: Results of a nationwide cross-sectional health examination.

BACKGROUND: To examine the association between sarcopenia and comorbidities among patients with rheumatoid arthritis (RA). METHODS: We selected RA patients and age- and sex-matched non-RA controls at a 1:5 ratio from 2008-2011 Korea National Health and Nutrition Examination Survey database. Sarcopenia was defined by appendicular skeletal muscle mass. After investigating associations between sarcopenia and individual comorbidities among RA patients, we performed a stratified analysis comparing three subgroups (RA/sarcopenia, RA/non-sarcopenia, non-RA/sarcopenia) versus a non-RA/non-sarcopenia subgroup to evaluate interactive as well as independent effects of sarcopenia and RA on comorbidities. Health-related behaviors (exercise, smoking, drinking, and diet) were also examined. The weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, sex, and income. RESULTS: We included 400 RA patients and 2,000 non-RA controls (mean age 57.4 years, 79.6% female). Sarcopenia was observed in 20.5% of RA and 19.3% of non-RA group. Among RA patients, sarcopenia was associated with obesity (OR 2.61, 95% CI 1.42-4.83), dyslipidemia (3.09, 1.37-6.99), diabetes (2.07, 0.99-4.33), chronic obstructive pulmonary disease (18.77, 2.40-146.55), and hepatitis B ever-infection (8.69, 1.15-65.58). Among three stratified subgroups, only a RA/sarcopenia subgroup was associated with such comorbidities, cardiovascular diseases, and depression compared to a non-RA/non-sarcopenia subgroup. Health-related behaviors were comparable between patients with and without sarcopenia. CONCLUSIONS: In this nation-wide cross-sectional study, a wide spectrum of comorbidities were preferentially found among RA patients with sarcopenia than without, suggesting that sarcopenia is significantly associated with RA-related comorbidities. Particular attention should be paid to comorbidities of sarcopenic RA patients.

Cardiovascular safety associated with febuxostat versus allopurinol among patients with gout: Update with accumulated use of febuxostat.

BACKGROUND: To re-evaluate comparative cardiovascular (CV) safety of febuxostat versus allopurinol among patients with gout following recent accumulated use of febuxostat. METHODS: Using 2011-2019 Korea National Health Insurance database, we conducted a cohort study comparing gout patients initiating febuxostat versus allopurinol, 1:1 matched on a propensity-score (PS) for >60 covariates. The primary outcome was a composite endpoint of myocardial infarction, coronary revascularization, and stroke. Secondary outcomes were individual components of the primary outcome, hospitalized heart failure, and all-cause mortality. Subgroup analyses were done for those at high CV risk, long-term users (follow-up >3 years), and those without chronic kidney disease. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We included 160,930 PS-matched pairs of febuxostat and allopurinol users (mean age 59.3 years, 79.6% male). Incidence rates of the primary outcome were 2.06 and 2.27 per 100 person-years for febuxostat and allopurinol users, respectively, with a HR [95% CI] of 1.03 [0.95-1.12] comparing febuxostat versus allopurinol initiators. We also observed similar risks for secondary outcomes, except for reduced all-cause mortality among febuxostat users (HR [95% CI] of 0.84 [0.78-0.91]). Subgroup analyses also showed non-inferior CV safety of febuxostat. CONCLUSION: In this population-based cohort study including the largest number of febuxostat users to date, we found non-inferior CV safety of febuxostat versus allopurinol. There was a 16% reduction in all-cause mortality among febuxostat users.

Smoking trajectory and cancer risk: A population-based cohort study.

INTRODUCTION: Smoking behavior can change with time and lead to different health outcomes. This study explored the trajectory of smoking and its relationship with cancer incidence and mortality among Korean male adults. METHODS: We used 2002-2018 data from the National Health Insurance Service (NHIS). Smoking status was repeatedly measured in four waves of general health examinations provided by the NHIS between 2002 and 2009. Cancer incidence and mortality were tracked from 2010 to 2018. Trajectory analysis was used to identify the patterns of smoking. The hazard ratio was calculated using Cox proportional regression models. RESULTS: For the 2448548 men (≥20 years), 137788 cases of cancers and 41146 cancer deaths were found. We identified six trajectory groups: never smokers, former smokers, new current smokers, decreasing light smokers, steady moderate smokers, and steady heavy smokers. All smoking groups had an increased risk of cancer. The steady heavy smokers showed higher cancer incidence and mortality rate than the steady non-smokers (hazard ratio, HR=1.53; 95% CI: 1.49-1.58 and HR=2.64; 95% CI: 2.50-2.79, respectively). The cancer-specific analysis showed that the larynx and lung cancer incidence and mortality rate of the smoking group were higher than in never smokers. CONCLUSIONS: Smoking, even at low doses, increases the risk of most cancers in men. Quitting or reducing smoking, especially at a young age, can lower cancer incidence and mortality. This study may provide more objective results on the relationship between smoking and cancer, because smoking behavior was examined at multiple time points.