Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics.

By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p < 5.0 × 10-8 and a Bonferroni-corrected p < 4.6 × 10-6, respectively. Of them, 32 loci and 15 genes showed a significantly different association between ER-positive and ER-negative breast cancer after Bonferroni correction. Significant ancestral differences in risk variant allele frequencies and their association strengths with breast cancer risk were identified. Of the significant associations identified in this study, 17 loci and 14 genes are located 1Mb away from any of the previously reported breast cancer risk variants. Pathways analyses including 221 putative risk genes identified multiple signaling pathways that may play a significant role in the development of breast cancer. Our study provides a comprehensive understanding of and new biological insights into the genetics of this common malignancy.

Trends for Syndromic Surveillance of Norovirus in Emergency Department Data Based on Chief Complaints.

BACKGROUND: This study compared trends in norovirus cases to determine whether chief complaint-based emergency department (ED) visit data could reflect trends of norovirus in Korea. METHODS: The ED visits from the National Emergency Department Information System database and the weekly reported number of noroviruses from the sentinel surveillance system were collected between August 2017 and December 2020. The correlation between weekly norovirus cases and weekly ED visits considering the chief complaint and discharge diagnosis code was estimated using a 3-week moving average. RESULTS: In total, 6 399 774 patients with chief complaints related to digestive system disease visited an ED. A higher correlation between reported norovirus cases and ED visit with chief complaint of vomiting and discharge diagnosis code of gastroenteritis and colitis of unspecified origin or other and unspecified gastroenteritis and colitis of infectious origin was observed (R = 0.88, P < .0001). The correlation was highest for the age group 0-4 years (R = 0.89, P < .0001). However, no correlation was observed between the reported norovirus cases and the number of ED visits with norovirus identified as a discharge diagnosis code. CONCLUSIONS: ED visit data considering a combination of chief complaints and discharged diagnosis code would be useful for early detection of infectious disease trends.

Ex vivo kidney machine perfusion: meta-analysis of randomized clinical trials.

BACKGROUND: Machine perfusion is an organ preservation strategy used to improve function over simple storage in a cold environment. This article presents an updated systematic review and meta-analysis of machine perfusion in deceased donor kidneys. METHODS: RCTs from November 2018 to July 2023 comparing machine perfusion versus static cold storage in kidney transplantation were evaluated for systematic review. The primary outcome in meta-analysis was delayed graft function. RESULTS: A total 19 studies were included, and 16 comparing hypothermic machine perfusion with static cold storage were analysed. The risk of delayed graft function was lower with hypothermic machine perfusion (risk ratio (RR) 0.77, 95% c.i. 0.69 to 0.86), even in kidneys after circulatory death (RR 0.78, 0.68 to 0.90) or brain death (RR 0.73, 0.63 to 0.84). Full hypothermic machine perfusion decreased the risk of delayed graft function (RR 0.69, 0.60 to 0.79), whereas partial hypothermic machine perfusion did not (RR 0.92, 0.69 to 1.22). Normothermic machine perfusion or short-term oxygenated hypothermic machine perfusion preservation after static cold storage was equivalent to static cold storage in terms of delayed graft function and 1-year graft survival. CONCLUSION: Hypothermic machine perfusion reduces delayed graft function risks and normothermic approaches show promise.

Trends in multiple myeloma incidence, prevalence, mortality, and survival rate in South Korea: a nationwide population-based study.

This is the first study presenting the overall descriptive epidemiology of multiple myeloma (MM), including incidence, mortality rate, and prevalence, in South Korea between 2010 and 2018 based on nationwide medical insurance coverage and mortality statistics data. The incidence of MM between 2010 and 2018 was obtained from nationwide medical claims data, and mortality data were obtained from the Korea National Statistical Office. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) and one- and five-year survival rates of patients with MM each year were estimated. There were 10,835 patients with MM aged ≥ 20 years in South Korea between 2010 and 2018. The ASIR was 2.42/100,000 in 2010 and increased to 2.71/100,000 in 2018, with an annual percent change (APC) of 1.86% (95% CI = 0.74-2.99%, P = 0.005). While this trend was significant in women, it was not statistically significant in men. The ASMR did not significantly change over time. Furthermore, the median survival time of patients with MM diagnosed between 2010 and 2018 was 3.36 years. Notably, the one-year survival rate of patients was increased from 65.3% in 2010 to 76.2% in 2017. Finally, the proportion of patients with MM who received novel therapeutic agents, such as proteasome inhibitors or immunomodulatory drugs, as first-line treatment increased from 37.7% in 2010 to 97.8% in 2018. The ASIR and prevalence of MM in South Korea increased between 2010 and 2018, especially in women and the survival rate of patients with MM has increased.

An Epidemiological Study on Legionnaires' Disease in Gyeonggi Province, Korea: Occurrence, Infection Routes, and Risk Factors for Mortality (2016-2022).

Background and Objectives: Legionnaires' disease (LD) is an acute respiratory disease with increasing annual numbers of reported domestic and global cases. This study aimed to establish foundational data for the prevention and control of LD by investigating the occurrence and infection routes of reported and suspected cases of LD in Gyeonggi Province, Korea, from January 2016 to December 2022, and by and analyzing the risk factors for death. Materials and Methods: A sex-and-age standardization was performed on LD patients and suspected cases reported in Gyeonggi Province. The monthly average number of confirmed cases was visualized using graphs, and a survival analysis was performed using Kaplan-Meier survival curves. The mortality risk ratio was estimated using the Cox proportional hazards model. Results: The incidence of LD in Gyeonggi Province mirrored the national trend, peaking in July with the highest number of confirmed and suspected cases. While there was no significant difference in survival rates by age, the survival rate was higher for suspected cases when analyzed separately. Comparing the death ratio by infection route, nosocomial infections showed the highest death ratio, and intensive care unit (ICU) admission and the presence of coinfections were significantly correlated with mortality. Factors such as nosocomial infection, admission within 1 to 3 days following diagnosis, and the development of complications were factors contributing to a higher risk of death. Conclusions: The general characteristics of patients with LD were similar to those suggested by previous studies. The proportion of community-acquired infections was lower than in previous studies, but the length of hospital stay was similar for survivors and the deceased, and the mortality rate within 30 days after diagnosis was higher for nosocomial infections. In conclusion, nosocomial infection, a period of up to 3 days from admission to diagnosis, and complications were significantly related to the mortality rate of LD.

Causes of death and associated factors with death after liver transplantation: a nationwide database study.

BACKGROUND/AIMS: This study investigated overall, 1-year, and 5-year mortality rate, the causes of death, and associated factors with death in liver transplantation recipients. METHODS: A total of 11,590 liver transplant recipients identified from National Health Insurance Service database between 2006 and 2017 were included. Factors associated with all-cause of death were analyzed by Cox proportional regression models. Cumulative mortality rate according to the underlying indication was estimated by Kaplan-Meier method. RESULTS: The 12-year survival rate for all liver transplant recipients was 68%. In the overall, 1-year, and 5-year mortality of liver transplant recipients, hepatic death was the highest contributing risk, accounting for >65% of the causes of death. Deaths from cirrhosis and liver failure accounted for a high proportion of deaths within 1 year after transplantation, and deaths from malignant tumors such as hepatocellular carcinoma were high among late-stage deaths. DISCUSSION: Although the most common cause of death from liver transplantation is due to primary disease, there was a difference in the pattern of major causes of death according to the period from transplantation to death. If appropriate medical intervention is performed at each period after transplantation, the survival rate can be improved.

Trends for syndromic surveillance of norovirus in emergency department data based on chief complaints.

BACKGROUND: This study compared the trends in norovirus cases to determine whether chief complaint-based emergency department (ED) visits data could reflect trends of norovirus in Korea. METHODS: The ED visits from the National Emergency Department Information System (NEDIS) database and the weekly reported number of noroviruses from the sentinel surveillance system were collected between August 2017 and December 2020. The correlation between weekly norovirus cases and weekly ED visits considering the chief complaint and discharge diagnosis code was estimated using a three-week moving average. RESULTS: In total, 6,399,774 patients with chief complaints of digestive system disease visited ED. A higher correlation between reported norovirus cases and ED visit with chief complaint of vomiting and discharge diagnosis code of gastroenteritis and colitis of unspecified origin or other and unspecified gastroenteritis and colitis of infectious origin was observed (R=0.88, p<.0001). The correlation was highest for the 0-4-years age group (R=0.89, p<.0001). However, no correlation was observed between the reported norovirus cases and the number of emergency department visits with norovirus identified as a discharge diagnosis code. CONCLUSIONS: ED visit data considering a combination of chief complaints and discharged diagnosis code would be available for early detection of infectious disease trends.

Increased risk of pancreatic, thyroid, prostate and breast cancers in men with a family history of breast cancer: A population-based study.

The association between a family history of breast cancer (FHBC) in female first-degree relatives (FDRs) and cancer risk in men has not been evaluated. This study aimed to compare the risks of overall and site-specific cancers in men with and without FHBC. A population-based study was conducted with 3 329 106 men aged ≥40 years who underwent national cancer screening between 2013 and 2014. Men with and without FHBC in their female FDRs were age-matched in a 1:4 ratio. Men without FHBC were defined as those without a family history of any cancer type in their FDRs. Data from 69 124 men with FHBC and 276 496 men without FHBC were analyzed. The mean follow-up period was 4.7 ± 0.9 years. Men with an FHBC in any FDR (mother or sister) had a higher risk of pancreatic, thyroid, prostate and breast cancers than those without an FHBC (adjusted hazard ratios [aHRs] (95% confidence interval [CI]): 1.35 (1.07-1.70), 1.33 (1.12-1.56), 1.28 (1.13-1.44) and 3.03 (1.130-8.17), respectively). Although an FHBC in any one of the FDRs was not associated with overall cancer risk, FHBC in both mother and sibling was a significant risk factor for overall cancer (aHR: 1.69, 95% CI:1.11-2.57) and increased the risk of thyroid cancer by 3.41-fold (95% CI: 1.10-10.61). FHBC in the mother or sister was a significant risk factor for pancreatic, thyroid, prostate and breast cancers in men; therefore, men with FHBC may require more careful BRCA1/2 mutation-related cancer surveillance.

Diagnostic performance of screening mammography according to menstrual cycle among Asian women.

PURPOSE: To investigate the performance metrics of screening mammography according to menstrual cycle week in premenopausal Asian women. METHODS: This retrospective study included 69,556 premenopausal Asian women who underwent their first screening mammography between 2011 and 2019. The presence or absence of a breast cancer diagnosis within 12 months after the index screening mammography served as the reference standard, determined by linking the study data to the national cancer registry data. Menstrual cycles were calculated, and participants were assigned to groups according to weeks 1-4. The performance metrics included cancer detection rate (CDR), sensitivity, specificity, and positive predictive value (PPV), with comparisons across menstrual cycles. RESULTS: Among menstrual cycles, the lowest CDR at 4.7 per 1000 women (95% confidence interval [CI], 3.8-5.8 per 1000 women) was observed in week 4 (all P < 0.05). The highest sensitivity of 72.7% (95% CI, 61.4-82.3) was observed in week 1, although the results failed to reach statistical significance. The highest specificity of 80.4% (95% CI, 79.5-81.3%) was observed in week 1 (P = 0.01). The lowest PPV of 2.2% (95% CI, 1.8-2.7) was observed in week 4 (all P < 0.05). CONCLUSION: Screening mammography tended to show a higher performance during week 1 and a lower performance during week 4 of the menstrual cycle among Asian women. These results emphasize the importance of timing recommendations that consider menstrual cycles to optimize the effectiveness of screening mammography for breast cancer detection.

Association of Longitudinal Mammographic Breast Density Changes with Subsequent Breast Cancer Risk.

Background Although Breast Imaging Reporting and Data System (BI-RADS) density classification has been used to assess future breast cancer risk, its reliability and validity are still debated in literature. Purpose To determine the association between overall longitudinal changes in mammographic breast density and breast cancer risk stratified by menopausal status. Materials and Methods In a retrospective cohort study using the Korean National Health Insurance Service database, women aged at least 40 years without a history of cancer who underwent three consecutive biennial mammographic screenings in 2009-2014 were followed up through December 2020. Participants were divided according to baseline breast density: fatty (BI-RADS categories a, b) versus dense (BI-RADS categories c, d) and then into subgroups on the basis of changes from the first to second and from second to third screenings. Women without change in breast density were used as the reference group. Main outcomes were incident breast cancer events, both invasive breast cancer and ductal carcinoma in situ. Cox proportion hazard regression was used to calculate the hazard ratio (HR) with adjustment for other covariables. Results Among 2 253 963 women (mean age, 59 years ± 9) there were 22 439 detected breast cancers. Premenopausal women with fatty breasts at the first screening had a higher risk of breast cancer as density increased in the second and third screenings (fatty-to-dense HR, 1.45 [95% CI: 1.27, 1.65]; dense-to-fatty HR, 1.53 [95% CI: 1.34, 1.74]; dense-to-dense HR, 1.93 [95% CI: 1.75, 2.13]). In premenopausal women with dense breasts at baseline, those in whom density continuously decreased had a 0.62-fold lower risk (95% CI: 0.56, 0.69). Similar results were observed in postmenopausal women, remaining significant after adjustment for baseline breast density or changes in body mass index (fatty-to-dense HR, 1.50 [95% CI: 1.39, 1.62]; dense-to-fatty HR, 1.42 [95% CI: 1.31, 1.53]; dense-to-dense HR, 1.62 [95% CI: 1.51, 1.75]). Conclusion In both premenopausal and postmenopausal women undergoing three consecutive biennial mammographic screenings, a consecutive increase in breast density augmented the future breast cancer risk whereas a continuous decrease was associated with a lower risk. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kataoka et al in this issue.