Planned Immediate Chemotherapy and Cryopreservation of Oocytes or Embryos for Fertility Preservation in Women with Malignancies.

Purpose: Oocyte and embryo cryopreservation before gonadotoxic treatment are established methods to increase the likelihood of live births. Although several sociodemographic factors were found to be associated with undergoing fertility preservation (FP) treatment, clinical characteristics such as planned immediate chemotherapy were not fully investigated. We aimed to investigate whether the planned immediate chemotherapy is related to the decision to undergo oocyte/embryo cryopreservation for FP with adjustment for other clinical characteristics. Methods: This institutional cohort study included 491 premenopausal women aged 19 years or older who visited the FP clinic at a tertiary medical center between 2006 and 2019. The primary outcome was whether the participants underwent oocyte/embryo cryopreservation. We evaluated the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of undergoing oocyte/embryo cryopreservation according to whether immediate chemotherapy was planned using univariable and multivariable logistic regression. Results: Women scheduled for immediate chemotherapy were much less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.46, 95% CI 0.27-0.76) in univariable logistic regression analysis. After adjustment for covariates such as marital status, type of malignancies, and calendar year period, women scheduled for immediate chemotherapy were still less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.31, 95% CI: 0.17-0.56). The association was not different according to the type of malignancies (p for interaction = 0.13). Regarding breast cancer, the OR for undergoing oocyte/embryo cryopreservation in women scheduled for immediate chemotherapy was robust compared with those not planned for immediate chemotherapy (OR = 0.25, 95% CI: 0.12-0.53). Conclusion: The present study demonstrated that planned immediate chemotherapy was negatively associated with undergoing oocyte/embryo cryopreservation. This information can be helpful for FP counseling.

Mitochondrial DNA copy number variation in asthma risk, severity, and exacerbations.

BACKGROUND: Asthma pathophysiology is associated with mitochondrial dysfunction. Mitochondrial DNA copy number (mtDNA-CN) has been used as a proxy of mitochondrial function, with lower levels indicating mitochondrial dysfunction in population studies of cardiovascular diseases and cancers. OBJECTIVES: We investigated whether lower levels of mtDNA-CN are associated with asthma diagnosis, severity, and exacerbations. METHODS: mtDNA-CN is evaluated in blood from 2 cohorts: UK Biobank (UKB) (asthma, n = 39,147; no asthma, n = 302,302) and Severe Asthma Research Program (SARP) (asthma, n = 1283; nonsevere asthma, n = 703). RESULTS: Individuals with asthma have lower mtDNA-CN compared to individuals without asthma in UKB (beta, -0.006 [95% confidence interval, -0.008 to -0.003], P = 6.23 × 10-6). Lower mtDNA-CN is associated with asthma prevalence, but not severity in UKB or SARP. mtDNA-CN declines with age but is lower in individuals with asthma than in individuals without asthma at all ages. In a 1-year longitudinal study in SARP, mtDNA-CN was associated with risk of exacerbation; those with highest mtDNA-CN had the lowest risk of exacerbation (odds ratio 0.333 [95% confidence interval, 0.173 to 0.542], P = .001). Biomarkers of inflammation and oxidative stress are higher in individuals with asthma than without asthma, but the lower mtDNA-CN in asthma is independent of general inflammation or oxidative stress. Mendelian randomization studies suggest a potential causal relationship between asthma-associated genetic variants and mtDNA-CN. CONCLUSION: mtDNA-CN is lower in asthma than in no asthma and is associated with exacerbations. Low mtDNA-CN in asthma is not mediated through inflammation but is associated with a genetic predisposition to asthma.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data.

BACKGROUND: No randomized controlled trials have been completed to see whether statin can decrease hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients. We used large-scale, population-based, observational data to emulate a target trial with two groups, statin user and statin non-user. METHODS: Among 1,379,708 nonunique individuals from the Korean National Health Insurance Service data, 2,915 CHB patients with serum cholesterol level of 200 mg/dL or higher who started statin therapy and 8,525 propensity-score matched CHB patients with serum cholesterol level of 200 mg/dL or higher who did not start statin therapy were analyzed for the development of HCC. In addition, liver cancer or liver-related mortality and all-cause mortality were assessed. RESULTS: During follow-up, 207 participants developed HCC. Incidence rate of HCC was 0.2 per 1,000 person-years in the statin user group and 0.3 per 1,000 person-years in the statin non-user group. Fully adjusted hazard ratio (HR) for incident HCC comparing statin user group to statin nonuser group was 0.56 (95% confidence interval [CI]: 0.39 to 0.80). The association between statin use and decreased HCC risk was consistent in all subgroups analyzed. Fully adjusted HR comparing statin user to statin nonuser was 0.59 (95% CI: 0.35 to 0.99) for liver cancer or liver-related mortality and 0.93 (95% CI: 0.78 to 1.11) for all-cause mortality. CONCLUSIONS: Statin might have a benefit for preventing HCC in CHB patients with elevated cholesterol levels. Statin should be actively considered for CHB patients with dyslipidemia.

Deleterious heteroplasmic mitochondrial mutations are associated with an increased risk of overall and cancer-specific mortality.

Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B.

BACKGROUND: Research exploring the influence of healthier lifestyle modification (LSM) on the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is limited. AIM: To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data. METHODS: Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1, 2009, and December 31, 2017, those aged ≥ 20 years who drank alcohol, smoked cigarettes, and were sedentary were analyzed. Exposure included at least one LSM, including alcohol abstinence, smoking cessation, and regular exercise. The primary outcome was HCC development, and the secondary outcome was liver-related mortality. We used 2:1 propensity score matching to account for covariates. RESULTS: With 48766 patients in the LSM group and 103560 in the control group, the adjusted hazard ratio (HR) for incident HCC and liver-related mortality was 0.92 [95% confidence interval (CI): 0.87-0.96] and 0.92 (95%CI: 0.86-0.99) in the LSM group, respectively, compared with the control group. Among the LSM group, the adjusted HR (95%CI) for incident HCC was 0.84 (0.76-0.94), 0.87 (0.81-0.94), and 1.08 (1.00-1.16) for alcohol abstinence, smoking cessation, and regular exercise, respectively. The adjusted HR (95%CI) for liver-related mortality was 0.92 (0.80-1.06), 0.81 (0.72-0.91), and 1.15 (1.04-1.27) for alcohol abstinence, smoking cessation, and regular exercise, respectively. CONCLUSION: LSM lowered the risk of HCC and mortality in patients with CHB. Thus, active LSM, particularly alcohol abstinence and smoking cessation, should be encouraged in patients with CHB.

Air pollution and mortality in patients with chronic obstructive pulmonary disease: a cohort study in South Korea.

Background: Evidence on whether long-term exposure to air pollution increases the mortality risk in patients with chronic obstructive pulmonary disease (COPD) is limited. Objectives: We aimed to investigate the associations of long-term exposure to particulate matter with diameter <10 µm (PM10) and nitrogen dioxide (NO2) with overall and disease-specific mortality in COPD patients. Design: We conducted a nationwide retrospective cohort study of 121,423 adults ⩾40 years diagnosed with COPD during 1 January to 31 December 2009. Methods: Exposure to PM10 and NO2 was estimated for residential location using the ordinary kriging method. We estimated the risk of overall mortality associated with 1-, 3-, and 5-years average concentrations of PM10 and NO2 using Cox proportional hazards models and disease-specific mortality using the Fine and Gray method adjusted for age, sex, income, body mass index, smoking, comorbidities, and exacerbation history. Results: The adjusted hazard ratios (HRs) for overall mortality associated with a 10 µg/m3 increase in 1-year PM10 and NO2 exposures were 1.004 [95% confidence interval (CI) = 0.985, 1.023] and 0.993 (95% CI = 0.984, 1.002), respectively. The results were similar for 3- and 5-year exposures. For a 10-µg/m3 increase in 1-year PM10 and NO2 exposures, the adjusted HRs for chronic lower airway disease mortality were 1.068 (95% CI = 1.024, 1.113) and 1.029 (95% CI = 1.009, 1.050), respectively. In stratified analyses, exposures to PM10 and NO2 were associated with overall mortality in patients who were underweight and had a history of severe exacerbation. Conclusion: In this large population-based study of patients with COPD, long-term PM10 and NO2 exposures were not associated with overall mortality but were associated with chronic lower airway disease mortality. PM10 and NO2 exposures were both associated with an increased risk of overall mortality, and with overall mortality in underweight individuals and those with a history of severe exacerbation.

Association of endometriosis with genital human papillomavirus infection in US women: a national population-based study.

The prevalence of genital human papillomavirus (HPV) in women with endometriosis has never been reported in a national representative survey. We aimed to investigate the association of endometriosis with the prevalence of HPV. We analyzed the data on 1768 women (representing 43,824,157 women) in the United States aged 20-54 years from the National Health and Nutrition Examination Survey in the prevaccination era (2003-2006). The diagnosis of endometriosis was based on a self-report. The prevalence of any HPV in women with endometriosis did not differ from that in women without endometriosis after controlling for potential confounders such as age, ethnicity, family income, marital status, and the number of deliveries (adjusted prevalence ratio (aPR) 0.84, 95% confidence interval (CI) 0.61-1.15). No significant association was found between the prevalence of high-risk HPV and the diagnosis of endometriosis (aPR 0.71, 95% CI 0.44-1.14). If the participants were not covered by health insurance, the prevalence of any HPV infection in women with endometriosis was higher than in those without endometriosis (aPR 1.44, 95% CI 0.94-2.20). In contrast, in a subgroup who had health insurance, a lower prevalence of any HPV infection was observed in women with endometriosis (aPR 0.71, 95% CI 0.50-1.03), and P for interaction was statistically significant (P = 0.01). There was no association between endometriosis and HPV infection in this study of HPV vaccine-naïve women of reproductive age. The association was not different by the type of HPV. However, access to healthcare may modify the association between endometriosis and HPV infection.

Validation of the IASLC Residual Tumor Classification in Patients With Stage III-N2 Non-Small Cell Lung Cancer Undergoing Neoadjuvant Chemoradiotherapy Followed By Surgery.

OBJECTIVE: The aim of this study was to validate the International Association for the Study of Lung Cancer (IASLC) residual tumor classification in patients with stage III-N2 non-small cell lung cancer (NSCLC) undergoing neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery. BACKGROUND: As adequate nodal assessment is crucial for determining prognosis in patients with clinical N2 NSCLC undergoing nCCRT followed by surgery, the new classification may have better prognostic implications. METHODS: Using a registry for thoracic cancer surgery at a tertiary hospital in Seoul, Korea, between 2003 and 2019, we analyzed 910 patients with stage III-N2 NSCLC who underwent nCCRT followed by surgery. We classified resections using IASLC criteria: complete (R0), uncertain (R[un]), and incomplete resection (R1/R2). Recurrence and mortality were compared using adjusted subdistribution hazard model and Cox-proportional hazards model, respectively. RESULTS: Of the 96.3% (n = 876) patients who were R0 by Union for International Cancer Control (UICC) criteria, 34.5% (n = 3O2) remained R0 by IASLC criteria and 37.6% (n = 329) and 28% (n = 245) migrated to R(un) and R1, respectively. Most of the migration from UICC-R0 to lASLC-R(un) and IASLC-R1/R2 occurred due to inadequate nodal assessment (85.5%) and extracapsular nodal extension (77.6%), respectively. Compared to R0, the adjusted hazard ratios in R(un) and R1/R2 were 1.20 (95% confidence interval, 0.94-1.52), 1.50 (1.17-1.52) ( P fortrend = .001) for recurrence and 1.18 (0.93-1.51) and 1.51 (1.17-1.96) for death ( P for trend = .002). CONCLUSIONS: The IASLC R classification has prognostic relevance in patients with stage III-N2 NSCLC undergoing nCCRT followed by surgery. The IASLC classification will improve the thoroughness of intraoperative nodal assessment and the completeness of resection.

Nonalcoholic Fatty Liver Disease Without Metabolic-associated Fatty Liver Disease and the Risk of Metabolic Syndrome.

BACKGROUND & AIMS: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) was proposed to replace nonalcoholic fatty liver disease (NAFLD). Some people fulfill diagnostic criteria of NAFLD but not MAFLD (NAFLD without MAFLD), but the clinical implications of NAFLD in these subjects is unknown. METHODS: We followed cohort of 12,197 men and women 20 years of age or older without metabolic dysfunction (defined by MAFLD criteria), heavy alcohol use, chronic viral hepatitis, liver cirrhosis, or malignancy for their risk of incident metabolic syndrome defined by Adult Treatment Panel III criteria. RESULTS: By design, none of the study participants had MAFLD at baseline. The prevalence of NAFLD among participants without metabolic dysfunction meeting MAFLD criteria and without significant alcohol intake was 7.6%. During 74,508 person-years of follow-up, 2179 participants developed metabolic syndrome. The fully adjusted hazard ratio for metabolic syndrome comparing participants with NAFLD to those without it was 1.61 (95% confidence interval, 1.42-1.83). The increased risk of incident metabolic syndrome associated with NAFLD persisted for all studied subgroups, and the association was stronger for those with increased waist circumference (P for interaction = .029) and those without elevated triglycerides levels (P for interaction = .047). CONCLUSION: In this large cohort, participants with NAFLD without MAFLD were at higher risk of developing metabolic syndrome compared to participants with no NAFLD and no MAFLD. Using MAFLD criteria may miss opportunities for early intervention in these subjects.

Isolated Hepatitis B Core Antibody Positivity and Long-Term Liver-Related Mortality in Korea: A Cohort Study.

INTRODUCTION: Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults. METHODS: A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records. RESULTS: During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively. DISCUSSION: In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.

Obstructive Sleep Apnea and Its Influence on Intracranial Aneurysm.

Obstructive sleep apnea syndrome (OSAS) is associated with cerebrovascular disease, which can lead to life-threatening outcomes. The purpose of the study was to investigate the relationship between OSAS and comorbid intracranial aneurysms. We retrospectively reviewed 564 patients who underwent a polysomnography and brain magnetic resonance angiography as part of their health checkup. We calculated the prevalence of an intracranial aneurysm and OSAS in patients and measured the size of the intracranial aneurysm if present. The mean patient age was 55.6 ± 8.5 years, and 82.3% of them were men. The prevalence of an intracranial aneurysm in patients with OSAS was 12.1%, which is significantly higher than patients with non-OSAS (5.9%, p = 0.031). Patients with OSAS had a much higher prevalence of intracranial aneurysms, after adjusting all possible confounding factors such as age, sex, smoking status, alcohol drinking, and body mass index (odds ratio: 2.32; 95% confidence interval: 1.07-5.04). Additionally, the OSAS group had noticeably larger aneurysms compared with those of the non-OSAS group (3.2 ± 2.0 mm vs. 2.0 ± 0.4 mm, p = 0.013). We found a significant association between OSAS and intracranial aneurysms. OSAS could be another risk factor for the development of intracranial aneurysms.

Prediction model of persistent ovulatory dysfunction in Korean women with polycystic ovary syndrome.

AIM: There is no validated tool to predict persistent ovulatory dysfunction after medication with oral contraceptives in women with polycystic ovary syndrome (PCOS), which is the most severe subtype of PCOS. We aimed to build a model to predict persistent ovulatory dysfunction after medication of oral contraceptives in women with PCOS. METHODS: A total of 286 patients with PCOS were treated with and without oral contraceptives at a tertiary academic medical center. Data were obtained from the electronic medical record system between January 2016 and March 2019. A risk prediction model was developed using multivariable logistic regression. Model 1 was based on age and chief complaints and Model 2 further included predictors evaluated during a clinic visit. Model 3 additionally included laboratory findings. RESULTS: Of the study population, ovulatory dysfunction was persistent in 117 patients (40.9%). Compared with the simple model (Models 1 and 2), the full prediction model (Model 3) had better Akaike's information criterion (286, 244 vs. 225) and the area under the curve (AUC) increased from 0.74 and 0.79 to 0.84. The full model included 7 covariates measured during the evaluation of PCOS, and two covariates were significant predictors of persistent ovulatory dysfunction in PCOS: age (OR 0.91; 95% CI 0.84-0.97), and anti-Müllerian hormone (OR 1.17; 95% CI 1.09-1.26). This model demonstrated good discrimination (AUC, 0.84) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.74). CONCLUSIONS: This prediction model was shown to be a useful method for predicting persistent ovulatory dysfunction after oral contraceptive medication in patients with PCOS.

Reclassifying the International Association for the Study of Lung Cancer Residual Tumor Classification According to the Extent of Nodal Dissection for NSCLC: One Size Does Not Fit All.

INTRODUCTION: The extent of nodal assessment may require risk-based adjustments in NSCLC. We reclassified the International Association for the Study of Lung Cancer Residual tumor classification according to the extent of nodal dissection and evaluated its long-term prognosis by tumor stage and histologic subtype. METHODS: We reclassified 5117 patients who underwent resection for clinical stages I to III NSCLC and had complete or uncertain resection by International Association for the Study of Lung Cancer classification into the following 3 groups according to compliance with three components (N1, N2, and subcarinal node) of systematic nodal dissection criteria: fully compliant group (FCG), partially compliant group (PCG), and noncompliant group (NCG). Recurrence-free survival (RFS) and overall survival (OS) were compared. RESULTS: Of the 5117 patients, 2806 (55%), 1959 (38%), and 359 (7%) were FCG, PCG, and NCG, respectively. PCG and NCG were more likely to be of lower clinical stage and adenocarcinoma with lepidic component than FCG. The 5-year RFS and OS were significantly better in NCG than in FCG or PCG (RFS, 86% versus 70% or 74%, p < 0.001; OS, 90% versus 80% or 83%, p < 0.001). In particular, NCG had better RFS and OS than FCG or PCG in clinical stage I and in lepidic-type adenocarcinoma. CONCLUSIONS: In early stage NSCLC with low-risk histologic subtype, a less rigorous nodal assessment was not associated with a worse prognosis. Although surgeons should continue to aim for complete resection and thorough nodal assessment, a uniform approach to the extent and invasiveness of nodal assessment may need to be reconsidered.

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study.

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11-4.51), cardiomyopathy (HR 2.65; 95% CI 1.90-3.68), endometrial cancer (HR 3.53; 95% CI 2.76-4.53), hypothyroidism (HR 1.29; 95% CI 1.19-1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12-3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20-1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Risk factors for hemorrhoidal disease among healthy young and middle-aged Korean adults.

Hemorrhoidal disease is a highly prevalent anorectal condition causing substantial discomfort, disability, and decreased quality of life. Evidence on preventable risk factors for hemorrhoidal disease is limited. We conducted a cross-sectional study of 194,620 healthy men and women who completed a health screening exam including colonoscopy in 2011-2017. We evaluated potential risk factors of hemorrhoidal disease, including lifestyle factors, medical history, birth history, gastrointestinal symptoms, and anthropometric measurements. The prevalence of hemorrhoidal disease was 16.6%, and it was higher in females than in males (17.2 vs. 16.3%; P < 0.001). Compared to men, the prevalence of hemorrhoidal disease was higher in parous women (adjusted odds ratio [OR] 1.06; 95% confidence interval [CI] 1.02-1.10), and lower in nulliparous women (adjusted OR 0.92; 95% CI 0.86-0.98). In the adjusted analyses, older age, female sex, smoking, overweight, and being hypertensive were independently associated with the presence of hemorrhoidal disease. The prevalence of hemorrhoidal disease was positively associated with body mass index and waist circumference in parous women. The prevalence of hemorrhoidal disease was higher in older age, females, ever-smokers, and hypertensive participants. The association of excess adiposity with the prevalence of hemorrhoidal disease differed by sex and parity.

Liver fibrosis scores and risk of liver-related mortality in young adults with chronic hepatitis B: A cohort study.

The predictive role of noninvasive liver fibrosis scores on liver-related mortality in patients with chronic hepatitis B below 40 years of age remains unclarified. We examined the association of liver fibrosis scores with liver-related mortality in young (<40 years) and older adults with hepatitis B virus (HBV) infection. A cohort study was performed in 21,360 HBsAg-positive Korean adults without liver cirrhosis or liver cancer at baseline who were followed up for up to 18 years. The liver fibrosis scores were determined using the fibrosis-4 score (FIB-4) and aspartate transaminase to platelet ratio index (APRI). Patients' vital status and cause of death were ascertained through the National Death Records. During a median follow-up of 10.2 years, 283 liver-related deaths were identified (liver-related mortality, 127.4/105 person-years). The liver fibrosis scores were significantly associated with increased risks of liver-related mortality; this association did not differ by age group (<40 vs. ≥40 years). The multivariable-adjusted hazard ratios with 95% confidence intervals for liver-related mortality comparing intermediate and high to low FIB-4 scores were 4.23 (1.99-9.00), and 15.16 (5.18-44.38), respectively, among individuals under 40, and 4.46 (3.03-6.56) and 22.47 (15.11-33.41), respectively, among older individuals. These associations were similar in analyses using APRI. In this cohort of HBsAg-positive individuals, the liver fibrosis scores were associated with increased risks of liver-related mortality in young and older adults. The liver fibrosis scores have a role in predicting liver mortality, even in young adults with HBV.

Risk of non-Hodgkin lymphoma in breast cancer survivors: a nationwide cohort study.

Several studies have suggested that estrogens have a protective function against lymphomagenesis. The treatment of breast cancer is driven by subtype classification, and the assessment of hormone receptor status is important for treatment selection. Thus, we evaluated the association between breast cancer and the incidence of NHL. We conducted a retrospective cohort study using a population-based nationwide registry in South Korea. We selected all women with newly diagnosed breast cancer between January 1st, 2002 and December 31st, 2016 who received curative treatment (N = 84,969) and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). Incident breast cancer (time-varying exposure) was the exposure and development of any type of NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mature T/NK-cell lymphomas, anaplastic large cell lymphoma (ALCL), and unspecified types of NHL, was the outcome. During follow-up, 1564 incident cases of NHL occurred. The fully adjusted Hazard Ratio (HR) for NHL associated with the development of breast cancer was 1.64 (95% CI = 1.34-2.00) after adjusting for body mass index, alcohol intake, physical activity, smoking, income, and comorbidity. The adjusted HR for NHL was much higher in participants who were aged <50 years and who received hormone therapy (either tamoxifen or aromatase inhibitors) than in those ≥50 years or who did not receive hormone therapy, respectively. The development of breast cancer was associated with a significantly increased risk of NHL, particularly follicular lymphoma and mature T/NK-cell lymphoma. In particular, the risk of NHL was higher in patients receiving hormone therapy and in younger patients.