Familial risk of seropositive rheumatoid arthritis and interaction with smoking: a population-based cohort study.

OBJECTIVES: We evaluated the familial risk of seropositive rheumatoid arthritis (RA) and examined interactions between family history and smoking. METHODS: Using the National Health Insurance and Health Screening Program databases, which include information on familial relationships and lifestyle factors, we identified 5 524 403 individuals with first-degree relatives (FDRs) from 2002-2018. We calculated familial risk using hazard ratios (HRs) with 95% CIs which compare the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using the relative excess risk due to interaction (RERI). RESULTS: Individuals with affected FDR had 4.52-fold (95% CI 3.98, 5.12) increased risk of disease compared with those with unaffected FDR. Familial risk adjusted for lifestyle factors decreased slightly (HR 4.49), suggesting that a genetic contribution is the predominant driver in the familial aggregation of RA. Smoking was associated with an increased risk of disease that was more pronounced among heavy (HR 1.92 95% CI 1.70, 2.18) compared with moderate (HR 1.15 95% CI 1.04, 1.28) smoking. In the interaction analysis, the risk associated with the combined effect of smoking and family history was higher than the sum of their individual effects, though statistically non-significant (RERI 1.30 95% CI ‒0.92, 3.51). Heavy smokers with a positive family history showed a prominent interaction (RERI 4.13 95% CI ‒0.88, 9.13) which exceeded moderate smokers (RERI 0.61 95% CI ‒1.90, 3.13), suggesting a dose-response interaction pattern. CONCLUSION: Our findings indicate the possibility of an interaction between RA-associated genes and smoking.

Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer?

OBJECTIVE: The risk of developing endometrial hyperplasia after diagnosis of endometriosis has not been determined. Moreover, the risk of endometrial cancer associated with endometriosis is unclear. This nationwide population-based study investigated the associations of endometrial hyperplasia and endometrial cancer with endometriosis, after adjusting for covariates. METHODS: This population-based observational study analyzed data from the Korean National Health Insurance (NHI) database, including 147,869 women who were diagnosed with endometriosis from 2002 to 2017, with each patient matched to 20 control women without endometriosis. Cox proportional hazard regression analyses were performed to estimate the hazard ratios (HRs) of endometrial hyperplasia, endometrial cancer, and mortality from endometrial cancer. RESULTS: Among three million women in this population, 16,377 women were diagnosed with endometrial hyperplasia, and 1795 women were diagnosed with endometrial cancer over 19,931,794 person-years of follow-up. Women with endometriosis were at significantly higher risks of endometrial hyperplasia (adjusted hazard ratio [aHR] 1.85, 95% confidence interval [CI] 1.75-1.95), and endometrial cancer (aHR 1.35, 95% CI 1.12-1.63) were compared with control women after adjustment for covariates. A diagnosis of endometriosis did not affect survival in patients with endometrial cancer. CONCLUSION: The risks of endometrial hyperplasia and endometrial cancer were found to be significantly higher in women with than without endometriosis. The presence of endometriosis did not affect overall survival in women with endometrial cancer. Additional long-term prospective studies with adequate control of confounders are needed.

Response to Toshihide Tsuda, Yumiko Miyano and Eiji Yamamoto [1].

BACKGROUND: Using a toolkit approach, Tsuda et al. critiqued work carried out by or in collaboration with the International Agency for Research on Cancer (IARC/WHO), including the IARC technical publication No. 46 on "Thyroid health monitoring after nuclear accidents" (TM-NUC), the project on nuclear emergency situations and improvement on medical and health surveillance (SHAMISEN), and the IARC-led work on global thyroid cancer incidence patterns as per IARC core mandate. MAIN BODY: We respond on the criticism of the recommendations of the IARC technical publication No. 46, and of global thyroid cancer incidence evaluation. CONCLUSION: After nuclear accidents, overdiagnosis can still happen and must be included in informed decision making when providing a system of optimal help for cases of radiation-induced thyroid cancer, to minimize harm to people by helping them avoid diagnostics and treatment they may not need.

Statin use and incidence and mortality of breast and gynecology cancer: A cohort study using the National Health Insurance claims database.

Previous studies have reported inconsistent findings concerning the impact of statin use on cancer prevention. Our study examined the association between statin use and cancer incidence and mortality related to breast and gynecologic cancers in South Korea. A population-based cohort study was conducted using the National Health Insurance claims database. Women aged 45 to 70 years old who had taken statins for at least 6 months were compared to statin non-users of the same age from January 2005 to June 2013. The primary outcomes were cancer incidence and mortality related to breast cancer, total gynecologic cancers, cervix uteri cancer and ovarian cancer. Cox proportional hazards regression was conducted to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). Out of 587 705 women, there were 3591 cases of breast cancer, 2239 cases of gynecologic cancers and 565 breast and total gynecologic cancer deaths during 7.6 person-years. The aHRs for the association between the risk of each cancer and statin use were 0.88 (95% CI 0.79-0.97) for breast cancer and 0.83 (95% CI 0.67-0.99) for cervix uteri cancer. Statin use was associated with decreased breast cancer mortality (HR = 0.65, 95% CI 0.43-0.99) and total gynecologic cancer mortality (HR = 0.70, 95% CI 0.50-0.98). A dose-response relationship was only found for all-cancer mortality. Statin use for at least 6 months was significantly associated with a lower risk of breast and cervix uteri cancer incidence, and with lower mortality of breast and gynecologic cancers. Further research on these associations will be needed.

Outcomes of living liver donors are worse than those of matched healthy controls.

BACKGROUND & AIMS: Donor death is the most serious complication of living liver donation but is reported rarely. We investigated the actual mortality of living liver donors (LLDs) compared with matched control groups based on analysis of the Korean National Health Insurance Services (NHIS) database. METHODS: This cohort study included 12,372 LLDs who donated a liver graft between 2002 and 2018, and were registered in the Korean Network for Organ Sharing. They were compared to 3 matched control groups selected from the Korean NHIS and comprising a total of 123,710 individuals: healthy population (Group I); general population without comorbidities (Group II); and general population with comorbidities (Group III). RESULTS: In this population, 78.5% of living liver donors were 20-39 years old, and 64.7% of all donors were male. Eighty-nine donors (0.7%) in the LLD group died (68 males and 21 females), a mortality rate (/1,000 person-years) of 0.91 (0.74-1.12). Mortality rate ratio and the adjusted hazard ratio of the LLD group was 2.03 (1.61-2.55) and 1.71 (1.31-2.25) compared to Control Group I, 0.75 (0.60-0.93) and 0.63 (0.49-0.82) compared to Control Group II, and 0.58 (0.46-0.71) and 0.49 (0.39-0.60) compared to Control Group III. LLD group, depression, and lower income were risk factors for adjusted mortality. The incidence of liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the LLD group was significantly higher than in Control Group I. CONCLUSIONS: Outcomes of the LLD group were worse than those of the matched healthy control group despite the small number of deaths and medical morbidities in this group. LLDs should receive careful medical attention for an extended period after donation. LAY SUMMARY: The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation.

Familial Risk of Renal Cell Cancer and Interaction with Obesity and Hyperglycemia: A Population-Based Study.

PURPOSE: We quantified the familial risk of renal cell cancer (RCC) among first-degree relatives (FDRs) on a population level, and examined interactions between family history and body mass index or blood glucose. MATERIALS AND METHODS: Using the National Health Insurance database, which covers the entire Korean population, and the National Health Screening Program, we constructed a cohort of 5,524,403 individuals with blood-related FDRs and their lifestyle factors from 2002 to 2018. We calculated familial risk using incidence risk ratios (IRRs) with 95% confidence intervals, which compares the risk of individuals with and without FDR. The combined effect and interaction of a given risk factor and family history of RCC were measured by the relative excess risk due to interaction. RESULTS: Individuals with affected FDRs showed a 2.29-fold (95% CI 1.68-3.13) increased risk of disease. Familial risk adjusted for lifestyle factors showed minimal attenuation (IRR 2.25; 95% CI: 1.65-3.08), suggesting that genetic predisposition is the main contributor in the familial aggregation of RCC. Individuals with both a positive family history and overweight/obesity (IRR 3.71, 95% CI 2.50-4.92) or hyperglycemia (IRR 4.52, 95% CI 2.59-6.45) had a significantly higher risk that exceeded the sum of their individual risks, suggesting an interaction that was statistically significant (relative excess risk due to interaction 95% CI: 0.91, -0.21-2.12; 2.21, 0.28-4.14). CONCLUSIONS: Our findings suggest an interaction between genetic and environmental factors, namely obesity and hyperglycemia. Individuals with both factors should be considered a high-risk group and advised to undergo genetic counseling.

Association Between Statins and the Risk of Kidney Cancer Incidence and Mortality Using the Korean National Health Insurance Claims Database.

BACKGROUND: Conflicting results have been reported regarding the potential preventive effects of statins on the risk of cancer. This study investigated the associations of statin use with the incidence and mortality of kidney cancer in South Korea. METHODS: In this retrospective population-based cohort study using the National Health Insurance claims database, we compared patients aged 45-70 years who had used statins for at least 6 months to non-statin users matched by age and sex from 2005 to June 2013. The main outcomes were kidney cancer incidence and mortality according to statin use. Cox proportional hazard regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs). RESULTS: In the cohort of 1 008 101 people, the aHRs for the association between statin use and the outcomes were .84 (95% CI: 0.71-.99) for kidney cancer incidence and .65 (95% CI: 0.41-.98) for kidney cancer mortality. In the matched cohort of 337 578, the risk per 1000 people of cancer incidence and mortality was 1.63, 1.07, and .24, .17 in statin users and non-users, respectively. In matched cohort, the risk of kidney cancer incidence and mortality decreased, but it is not statistically significant. Also, there was no linear relationship with increased doses. CONCLUSION: Statin use might be associated with a decreased risk of kidney cancer incidence and mortality, but it showed no statistical significance. This study was a large-scale analysis, however, further studies that are larger and multinational in scope are needed to confirm the beneficial effects of statins on survival.

Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma.

BACKGROUND AND AIM: Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones. METHODS: Patients with gallstone disease (n = 958 677) and age-matched and sex-matched controls (n = 9 586 770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones. RESULTS: Patients with gallstones showed increased risks of CCA (1.80, 1.67-1.93) and HCC (1.03, 1.00-1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76-2.14) and HCC (0.93, 0.87-0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89-6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43-4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls. CONCLUSION: The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.

Impact of Chronic Kidney Disease Severity on the Risk of Prurigo Nodularis: A Population-Based Cohort Study.

While dialysis is linked with prurigo nodularis, little is known about the impact of non-dialysis chronic kidney disease on prurigo nodularis. The influence of chronic kidney disease on development of prurigo nodularis was measured using the Korean National Health Insurance and National Health Screening Program data, identifying 17,295,576 individuals without prior prurigo nodularis. Chronic kidney disease severity was determined by the estimated glomerular filtration rate (in ml/min/1.73 m2) calculated from serum creatinine, and proteinuria detected with urine dipstick. Prurigo nodularis incidence during follow-up was determined. Over a median follow-up period of 9.72 years, 58,599 individuals developed prurigo nodularis, with an incidence rate of 3.59 per 10,000 person-years. Among different variables, estimated glomerular filtration rate was the strongest risk factor for prurigo nodularis. Compared with estimated glomerular filtration rate ≥ 90, estimat-ed glomerular filtration rate 15-29 (hazard ratio 1.31, 95% confidence interval 1.05-1.62) and end-stage renal disease (hazard ratio 1.46, 95% confidence interval 1.25-1.69) were associated with higher risks. The presence of proteinuria independently increased the risk of prurigo nodularis, increased risks associated with estimated glomerular filtration rate 15-29 and end-stage renal disease, and caused risk associated with estimated glomerular filtration rate 30-59 to become significant. With differential impact of chronic kidney disease severity on the risk of prurigo nodularis, preservation of renal function would potentially translate into lower risk of prurigo nodularis.

Guidelines for the prevention and management of children and adolescents with COVID-19.

Children are the future of the world, but their health and future are facing great uncertainty because of the coronavirus disease 2019 (COVID-19) pandemic. In order to improve the management of children with COVID-19, an international, multidisciplinary panel of experts developed a rapid advice guideline at the beginning of the outbreak of COVID-19 in 2020. After publishing the first version of the rapid advice guideline, the panel has updated the guideline by including additional stakeholders in the panel and a comprehensive search of the latest evidence. All recommendations were supported by systematic reviews and graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Expert judgment was used to develop good practice statements supplementary to the graded evidence-based recommendations. The updated guideline comprises nine recommendations and one good practice statement. It focuses on the key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin (IVIG) for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health. CONCLUSION: This updated evidence-based guideline intends to provide clinicians, pediatricians, patients and other stakeholders with evidence-based recommendations for the prevention and management of COVID-19 in children and adolescents. Larger studies with longer follow-up to determine the effectiveness and safety of systemic glucocorticoids, IVIG, noninvasive ventilation, and the vaccines for COVID-19 in children and adolescents are encouraged. WHAT IS KNOWN: • Several clinical practice guidelines for children with COVID-19 have been developed, but only few of them have been recently updated. • We developed an evidence-based guideline at the beginning of the COVID-19 outbreak and have now updated it based on the results of a comprehensive search of the latest evidence. WHAT IS NEW: • The updated guideline provides key recommendations pertinent to the following issues: identification of prognostic factors for death or pediatric intensive care unit admission; the use of remdesivir, systemic glucocorticoids and antipyretics, intravenous immunoglobulin for multisystem inflammatory syndrome in children, and high-flow oxygen by nasal cannula or non-invasive ventilation for acute hypoxemic respiratory failure; breastfeeding; vaccination; and the management of pediatric mental health.

Health and Mortality in Korean Healthcare Workers.

BACKGROUND: To evaluate the health status of healthcare workers (doctors and nurses) compared to those in the general population based on the National Health Insurance Service database and the cause of death data from Statistics Korea. METHODS: The subjects of this study were 104,484 doctors and 220,310 nurses working in healthcare facilities from 2002 to 2017, and who had undergone at least one general medical examination. Based on the subject definition, the subject data were extracted from the National Health Insurance healthcare facility database and qualification database. We collected medical use details included in the research database, general medical examination results, medical history included in the health examination database, and additional data on the cause of death from the National Statistics database to analyze the main cause of death and mortality. RESULTS: In terms of the major causes of death and mortality among healthcare workers, the mortality rate associated with intentional self-harm, injury, transportation accident, heart disease, addiction, and falling was significantly higher than that in the general population. Further, the prevalence of respiratory and gastrointestinal diseases was high. When analyzing the proportional mortality ratio (PMR) by cause of death for healthcare workers, the PMR values for death related to malignant neoplasm was the highest. In terms of diseases, both doctors and nurses had higher rates of infectious diseases such as maternal sepsis, rubella, and measles. CONCLUSION: The health status of healthcare workers differs from that of the general population. Thus, it is important to consider the occupational characteristics of healthcare personnel. This study is unique in that it was conducted based on medical use indicators rather than survey data.

Familial Risk of Inflammatory Bowel Disease: A Population-Based Cohort Study in South Korea.

BACKGROUND & AIMS: Despite the rapid increase in inflammatory bowel disease (IBD), population-level familial risk estimates of IBDs still are lacking in Asian-Pacific countries. We aimed to quantify the familial risk of incident IBD among first-degree relatives (FDRs) of individuals with IBD according to age, sex, and familial relationship. METHODS: Using the South Korea National Health Insurance database (2002-2017), which has complete population coverage and confirmed accuracy of both FDR information and IBD diagnoses, we constructed a cohort of 21,940,795 study subjects comprising 12 million distinct families. We calculated incidence risk ratios of ulcerative colitis (UC) or Crohn's disease (CD) in individuals of affected FDRs compared with individuals without affected FDRs. RESULTS: Of 45,717 individuals with UC and 17,848 individuals with CD, 3.8% and 3.1% represented familial cases, respectively. Overall, there was a 10.2-fold (95% CI, 9.39-11.1) and a 22.1-fold (95% CI, 20.5-24.5) significantly higher adjusted risk of UC and CD among FDRs of individuals with vs without IBD. Familial risk was highest among twins, followed by nontwin siblings, and then offspring of affected parents. Familial risk generally was higher within generations (sibling-sibling) vs between generations (parent-offspring). Familial risk also increased with the increasing number of affected FDRs. CONCLUSIONS: According to this population-based analysis, there is a substantially increased risk of IBD among FDRs of affected individuals, with the highest risk among siblings and for CD. These findings might help with an earlier diagnosis and appropriate therapeutic intervention in FDRs of individuals with IBD. Dedicated studies are needed to evaluate the contributions of shared early-in-life environmental exposures and genetic factors.

Familial risk of Behçet's disease among first-degree relatives: a population-based aggregation study in Korea.

OBJECTIVE: Previous studies have indicated that Behçet's disease (BD) has a genetic component, however population-level familial risk estimates are unavailable. We quantified the familial incidence and risk of BD in first-degree relatives (FDR) according to age, sex and type of family relationship. METHODS: Using the Korean National Health Insurance database, which has full population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 individuals comprising 12 million families, which were followed for a familial occurrence of BD from 2002 to 2017. Age- and sex-adjusted incidence risk ratios for BD were calculated in individuals with affected FDR compared with those without affected FDR. RESULTS: Among the total study population, 53 687 individuals had affected FDR, of whom 284 familial cases developed BD with an incidence of 3.57/104 person-years. The familial risk (incidence) for BD was increased to 13.1-fold (2.71/104 person-years) in individuals with an affected father, 13.9-fold (3.11/104 person-years) with affected mother, 15.2-fold (4.9/104 person-years) with an affected sibling and the highest risk was 165-fold (46/104 person-years) with an affected twin. Familial risks showed age dependence, being higher in younger age groups. The sex-specific familial risk was similar in males and females. CONCLUSION: This study provides quantified estimates of familial incidence and risk in FDR of BD patients in an entire population. Familial risks were higher within generation (sibling-sibling) vs between generations (parent-offspring). This implicates complex interactions between genetic factors and shared childhood environmental exposures in the pathogenesis of BD.

Incidence, mortality, and cardiovascular diseases in pituitary adenoma in Korea: a nationwide population-based study.

PURPOSE: Few nationally representative studies have evaluated the epidemiology of PA (pituitary adenoma). This South Korean study evaluated the incidence of different PA subtypes, cardiovascular disease (CVD), and related mortality. METHODS: This population-based study evaluated 31,898 patients with PA during 2005-2015. The incidence of PA, mortality, and CVD occurrence in PA cases were evaluated during a median follow-up of 5.3 years (range: 0-10 years). Cox regression analysis was used to evaluate the associations between CVD and mortality. RESULTS: The annual incidences (per 100,000 population) were 3.5 for non-functioning pituitary adenoma (NFPA), 1.6 for prolactinoma (PRL), 0.5 for growth hormone-secreting pituitary adenoma (GH), and 0.2 for adrenocorticotropic or thyroid-stimulating hormone-secreting pituitary adenoma (ACTH + TSH). The standardized mortality ratios were 1.9 for ACTH + TSH, 1.7 for NFPA with hypopituitarism, 1.4 for NFPA without hypopituitarism, 1.3 for GH, and 1.1 for PRL. During 2005-2015, the overall incidence of CVD among PA patients was 6.6% (2106 cases), and the standardized incidence ratios were 4.1 for hemorrhagic stroke, 3.0 for ischemic stroke, and 1.7 for acute myocardial infarction. The standardized incidence ratios for stroke were significantly higher in the ACTH + TSH and NFPA groups, which also had higher risks of CVD-related mortality, relative to the PRL and GH groups. CONCLUSION: South Korea had a relatively high incidence of NFPA. The incidence of stroke was highest for ACTH + TSH and NFPA, which was directly related to mortality during long-term follow-up. Patients with these types of PA should receive stroke prevention measures to reduce their risk of mortality.

Meaning and Status of Health-related Quality of Life Recognized by Medical Professionals: a Qualitative Study.

BACKGROUND: Medical professionals must maintain their health to provide quality medical care to patients safely. However, the health-related quality of life of medical professionals is a complex issue that currently lacks a standardized evaluation approach. Therefore, the purpose of this study was to identify their perceptions of the health-related quality of life of medical professionals and explore ways to measure their quality of life as accurately. METHODS: This study explored the subjective health status and well-being of Korean medical professionals by conducting three focus group discussions (FGDs) with 12 physicians and 6 nurses (November to December 2019). In the FGD, we elicited participants' opinions on existing health-related quality of life measurement tools. Also, we analyzed transcribed data through content analysis. RESULTS: Participants in this study noted the ambiguity in the current definitions of health provided by the World Health Organization. They shared various problems of their health, mainly concerning fatigue and sleep disorders due to their work pattern. Also, participants shared anxiety, burden, and fear of negative consequences due to the complexity of their work. Participants voiced the necessity of a questionnaire on health-related quality of life that reflects the working lives of medical professionals. CONCLUSION: Medical professionals in Korea were mainly criticizing about health-related quality of life problems caused by their work characteristics. The results of this study will provide valuable information for future health-related quality of life surveys targeting medical professionals in Korea, and also help to determine the method for monitoring the health-related quality of life for health professionals. In addition, the aspects and items identified by medical professionals as important for their health-related quality of life may be used as a basis for developing a new health-related quality of life measurement tools for medical professionals.

Familial Risk for Moyamoya Disease Among First-Degree Relatives, Based on a Population-Based Aggregation Study in Korea.

BACKGROUND AND PURPOSE: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. METHODS: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. RESULTS: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/104 person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/104 person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. CONCLUSIONS: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.

Nasal polyps and future risk of head and neck cancer: A nationwide population-based cohort study.

BACKGROUND: Nasal polyps are a common condition with a significant effect on quality of life. The association between nasal polyps and future risk of head and neck cancer is unknown. OBJECTIVE: We sought to investigate the relative risk of nasal cavity and paranasal sinus (NCPS) and nasopharyngeal cancers in a nationwide, population-based, longitudinal retrospective cohort of patients with nasal polyps and matched comparators. METHODS: The 2005-2017 National Health Insurance claims and National Health Screening program databases were used to construct a cohort of patients with nasal polyps and matched comparators in Korea. The relative risk of NCPS and nasopharyngeal cancer in patients with nasal polyps was examined. RESULTS: The study consisted of 453,892 patients with nasal polyps and 4,583,938 matched comparators. The mean duration of follow-up was 6.2 years (range, 2-13 years). The incidence rate ratios of patients with nasal polyps compared with the comparators was 7.00 (95% CI, 5.28-9.25) for NCPS cancer and 1.78 (95% CI, 1.28-2.42) for nasopharyngeal cancer. Increased risks of these cancers were only evident in older subjects (age ≥50 years). There were trends toward weaker associations of nasal polyps with these cancers in younger subjects with comorbid asthma or allergic rhinitis (<50 years). CONCLUSION: Although the absolute cancer incidence is very low, the relative risk of NCPS or nasopharyngeal cancers was significantly greater in older patients with nasal polyps. Given the regional and pathologic heterogeneity of nasal polyps, further studies are needed to explore the underlying mechanisms and validate the relationships.

Nationwide population-based study showed that the rotavirus vaccination had no impact on the incidence of biliary atresia in Korea.

AIM: Rotaviruses have been associated with biliary atresia. This study investigated whether the rotavirus vaccine, which was introduced to Korea in 2008, had an impact on the incidence of biliary atresia. METHODS: We identified all rotavirus infections (n = 436 826) and biliary atresia cases (n = 528) diagnosed from 2006 to 2015 from insurance and health databases. The annual and seasonal incidence of biliary atresia and rotavirus infection rates in neonates and children were calculated. The difference in the risk of biliary atresia between rotavirus-infected and non-infected neonates was analysed. RESULTS: The incidence of rotavirus infections was 20.6 versus 13.4 per 1000 cases before (2006-2008) and after (2009-2015) vaccine implementation. However, neonatal rotavirus infection rates did not decrease, with an incidence of 14.5 versus 14.8 per 1000 cases before and after vaccination. The biliary atresia incidence remained constant at 12.0 per 100 000 cases. Rotavirus infections in neonates were a risk factor for biliary atresia (odds ratio 3.14, 95% confidence interval 1.87-5.26). CONCLUSION: Rotavirus vaccination had no impact on the incidence of biliary atresia, possibly because the vaccination did not change the neonatal rotavirus infection rate through herd immunity. However, rotavirus infections in neonates were significantly associated with biliary atresia.

Association of hyperuricemia and pulmonary hypertension: A systematic review and meta-analysis.

Objectives: To investigate the association of hyperuricemia with pulmonary hypertension (PH) in term of subsequent development, severity, and prognosis of PH.Methods: The authors systematically reviewed articles from databases and conducted meta-analyses as follows: (1) association of serum uric acid (UA) levels with the presence of PH; (2) association between serum UA levels and subsequent development of PH, in terms of odds ratio of the development of PH; and (3) association of serum UA levels with severity and prognosis of PH, in terms of pulmonary arterial pressure and hazard ratio of death.Results: Twenty-six studies published between 1999 and 2017 were included. The level of serum UA was higher in subjects with PH than subjects without PH and this finding was observed regardless of status of diuretics use or renal function. The odds ratio of the development of PH was 2.32 (95% CI, 1.05-5.15) in subjects with hyperuricemia. Pulmonary arterial pressure among subjects with PH was also higher in subjects with hyperuricemia than subjects with normouricemia. There was a 19% increased hazard ratio of death (95% CI, 1.06-1.33) among patients with PH who had hyperuricemia.Conclusion: Hyperuricemia is associated with the subsequent development, worse severity and poor prognosis of PH.

Incidence and Prognosis of Subsequent Cholangiocarcinoma in Patients with Hepatic Resection for Bile Duct Stones.

BACKGROUND AND AIM: Cholangiocarcinoma (CCA) often develops after the hepatic resection for hepatolithiasis as well as indwelling it. We studied the incidence and prognosis of subsequent CCA in patients with hepatolithiasis in South Korea. METHODS: We identified individuals with diagnosed CCA at the time of or after surgery, during 2002-2016, from the Korean National Health Insurance. The incidences and survival rates of subsequent CCA were analyzed and compared with concomitant CCA. The standardized incidence ratios (SIRs) of CCA in this cohort were evaluated in the standard Korean population. All data were stratified by the presence of intrahepatic or extrahepatic CCA, age and sex. RESULTS: Of the 7852 patients with hepatectomy for BDS, 433 (5.84%) had concomitant CCA. Over the 12-year follow-up, 107 of 7419 (1.98%) patients were diagnosed with subsequent CCA. Patients with hepatic resection for BDS revealed higher SIRs for subsequent CCA (12.89, 95% CI 10.96-15.15) in cases of both intrahepatic CCA (13.40, 10.55-17.02) and extrahepatic CCA (12.42, 9.98-15.46). The median survival time for subsequent CCA was 0.87 years, while that for concomitant CCA was 2.79 years. Having subsequent CCA (HR 2.71, 95% CI 2.17-3.40) and being male (HR 1.28, 1.05-1.57) were related to a shorter survival time. The CCA site and age at CCA diagnosis were not related to prognoses. CONCLUSIONS: Subsequent CCA developed in 2% of the patients with hepatic resection for benign BDS until 10 years and was associated with poorer prognoses than concomitant CCA. Future studies focused on the long-term surveillance for CCA in such patients are needed.