Association of Soda Drinks and Fast Food with Allergic Diseases in Korean Adolescents: A Nationwide Representative Study.

INTRODUCTION: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). METHODS: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. RESULTS: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. CONCLUSION: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs.

Global and regional burden of vaccine-induced thrombotic thrombocytopenia, 1969-2023: Comprehensive findings with critical analysis of the international pharmacovigilance database.

OBJECTIVE: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. METHODS: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. RESULTS: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). CONCLUSION: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.

Global association of secondhand smoke exposure locations and smoking behaviour among adolescents in 99 countries.

AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.

Global and regional burden of vaccine-associated facial paralysis, 1967-2023: Findings from the WHO international pharmacovigilance database.

The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.

Cost-Utility Analysis for Colorectal Cancer Screening According to the Initiating Age of National Cancer Screening Program in Korea.

BACKGROUND: This study aimed to identify the most cost-effective strategy for colorectal cancer screening using the fecal immunochemical test (FIT), focusing on screening initiation age in Korea. METHODS: We designed Markov simulation models targeting individuals aged 40 years or older. Twelve strategies combining screening initiation ages (40, 45, or 50 years old), termination ages (80 or no limit), and intervals (1 or 2 years) were modeled, and the most cost-effective strategy was selected. The robustness of the results was confirmed using one-way and probabilistic sensitivity analyses. Furthermore, the cost-effectiveness of the qualitative and quantitative FIT methods was verified using scenario analysis. RESULTS: The 2-year interval strategy with a screening age range of 45-80 years was the most cost-effective (incremental cost-utility ratio = KRW 7,281,646/quality adjusted life years). The most sensitive variables in the results were transition rate from advanced adenoma to local cancer and discount rate. The uncertainty in the model was substantially low. Moreover, strategies starting at the age of 40 years were also cost-effective but considered suboptimal. The scenario analysis showed that there was no significant difference in cost-effectiveness between strategies with various relative screening ratio of quantitative and qualitative method. CONCLUSION: The screening method for advancing the initiation age, as presented in the 2015 revised national screening recommendations, was superior regarding cost-effectiveness. This study provides a new paradigm for the development of a national cancer screening system in Korea, which can be utilized as a scientific basis for economic evaluations.

Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor ß/Smad3 Signaling Pathway.

BACKGRUOUND: Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells. METHODS: To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-ß-treated renal cells in vitro. RESULTS: Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-ßstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-ß-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-ß secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines. CONCLUSION: Alantolactone improves renal fibrosis by inhibiting the TGF-ß/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.

Socioeconomic inequality in organized and opportunistic screening for gastric cancer: results from the Korean National Cancer Screening Survey 2009-2022.

Objectives: This study aimed to evaluate the socioeconomic inequality in gastric cancer (GC) screening in Korea. Socioeconomic inequality was assessed using both organized and opportunistic screening according to income and educational level. Methods: GC screening data were obtained from the 2009-2022 Korean National Cancer Screening Survey. The final analysis included 47,163 cancer-free men and women. The weighted cancer screening rate was estimated using joinpoint regression. The inequality indices were measured in terms of both the absolute slope index of inequality (SII) and the relative index of inequality (RII) using the Poisson regression model. Results: The organized screening rate for GC increased from 38.2% in 2009 to 70.8% in 2022, whereas the opportunistic screening rate decreased from 18.8 to 4.5%. Regarding educational inequality, a negative SII value was observed [-3.5, 95% confidence interval (CI), -7.63-0.83%] in organized screening, while a positive SII (9.30%; 95% CI, 6.69-11.91%) and RII (1.98%; 95% CI, 1.59-2.46) were observed in opportunistic screening. Furthermore, income inequality was not found in organized GC screening; however, overall SII and RII for opportunistic screening were 7.72% (95% CI, 5.39-10.5) and 1.61 (95% CI, 1.42-1.81), respectively. Conclusion: Organized screening rates have grown gradually over time and account for the majority of GC screenings in South Korea. While no socioeconomic inequalities were found in organized screening, significant socioeconomic inequalities were found in opportunistic screening.

Cluster of lifestyle risk factors for stomach cancer and screening behaviors among Korean adults.

This study aimed to investigate clustering patterns of lifestyle risk factors for stomach cancer and examine the association of risk factor clusters with stomach cancer screening adherence. Data from the 2019 Korean National Cancer Screening Survey, an annual cross-sectional nationwide survey, were used. The study population included 3539 adults aged 40-74 years with no history of cancer. Six stomach cancer risk factors, including smoking, drinking, physical inactivity, obesity, meat intake, and salted food intake, as well as stomach cancer screening behaviors, were assessed. The most frequent risk factor for stomach cancer was physical inactivity, followed by smoking in males and high salted food intake in females. Compared with participants subjects with no risk factors, those with three or more risk factors were less likely to adhere to screening guidelines (males: adjusted odds ratio [aOR] = 0.35, 95% confidence interval [CI] 0.23-0.53; females: aOR = 0.32, 95% CI 0.21-0.48). Our findings indicate a disparity in stomach cancer screening, such that those with more risk factors are less likely to get screened. Increasing public awareness, providing behavioral counseling, and targeting high-risk populations for screening interventions are critical for promoting cancer screening adherence and reducing the disparity in cancer screening.

Endoplasmic reticulum stress in pancreatic ß cells induces incretin desensitization and ß-cell dysfunction via ATF4-mediated PDE4D expression.

Pancreatic ß-cell dysfunction and eventual loss are key steps in the progression of type 2 diabetes (T2D). Endoplasmic reticulum (ER) stress responses, especially those mediated by the protein kinase RNA-like ER kinase and activating transcription factor 4 (PERK-ATF4) pathway, have been implicated in promoting these ß-cell pathologies. However, the exact molecular events surrounding the role of the PERK-ATF4 pathway in ß-cell dysfunction remain unknown. Here, we report our discovery that ATF4 promotes the expression of PDE4D, which disrupts ß-cell function via a downregulation of cAMP signaling. We found that ß-cell-specific transgenic expression of ATF4 led to early ß-cell dysfunction and loss, a phenotype that resembles accelerated T2D. Expression of ATF4, rather than C/EBP homologous protein (CHOP), promoted PDE4D expression, reduced cAMP signaling, and attenuated responses to incretins and elevated glucose. Furthermore, we found that ß-cells of leptin receptor-deficient diabetic (db/db) mice had elevated nuclear localization of ATF4 and PDE4D expression, accompanied by impaired ß-cell function. Accordingly, pharmacological inhibition of the ATF4 pathway attenuated PDE4D expression in the islets and promoted incretin-simulated glucose tolerance and insulin secretion in db/db mice. Finally, we found that inhibiting PDE4 activity with selective pharmacological inhibitors improved ß-cell function in both db/db mice and ß-cell-specific ATF4 transgenic mice. In summary, our results indicate that ER stress causes ß-cell failure via ATF4-mediated PDE4D production, suggesting the ATF4-PDE4D pathway could be a therapeutic target for protecting ß-cell function during the progression of T2D.NEW & NOTEWORTHY Endoplasmic reticulum stress has been implied to cause multiple ß-cell pathologies during the progression of type 2 diabetes (T2D). However, the precise molecular events underlying this remain unknown. Here, we discovered that elevated ATF4 activity, which was seen in T2D ß cells, attenuated ß-cell proliferation and impaired insulin secretion via PDE4D-mediated downregulation of cAMP signaling. Additionally, we demonstrated that pharmacological inhibition of the ATF4 pathway or PDE4D activity alleviated ß-cell dysfunction, suggesting its therapeutic usefulness against T2D.

Socioeconomic inequality in organized and opportunistic screening for colorectal cancer: results from the Korean National Cancer Screening Survey, 2009-2021.

OBJECTIVES: This study aimed to investigate socioeconomic status (SES)-based inequality in colorectal cancer (CRC) screening in Korea. We assessed whether the rates of opportunistic and organized CRC screening differed according to income and education levels. METHODS: We analyzed data from the Korean National Cancer Screening Survey of 27,654 cancer-free individuals, aged 50-74 years, from 2009 to 2021. The weighted cancer screening rates with trends were estimated with the average annual percentage change using joinpoint regression. Inequality was calculated in both relative and absolute terms, based on a Poisson regression model. RESULTS: The organized screening rate increased significantly from 22.1% in 2009 to 53.1% in 2020 and 50.6% in 2021, with an average annual change of 8.6% (95% confidence interval [CI], 4.9 to 12.5). In contrast, no significant trend was observed for opportunistic screening. The SES inequality in opportunistic screening uptake was indicated by a slope index of inequality (SII) of 9.74% (95% CI, 6.36 to 13.12), relative index of inequality (RII) of 2.18 (95% CI, 1.75 to 2.70) in terms of education level; and an SII of 7.03% (95% CI, 4.09 to 9.98), RII of 1.81 (95% CI, 1.41 to 2.31) in terms of measured income. Although there was an increasing trend in income inequality, no significant SES inequalities were observed in the overall estimates for organized screening. CONCLUSIONS: Organized CRC screening is effective in improving the participation rate, regardless of SES. However, significant inequalities were found in opportunistic screening, suggesting room for improvement in the overall equity of CRC screening.

Parental intention to vaccinate daughters with the human papillomavirus vaccine in Korea: a nationwide cross-sectional survey.

OBJECTIVES: We aimed to identify and compare the characteristics and factors associated with parental intention to vaccinate daughters under 12 years old against human papillomavirus (HPV), examining data from 2016 and 2020. METHODS: Data were obtained from the Korean National Cancer Screening Survey conducted in 2016 and 2020. The present study included 3,510 parents with daughters under 12 years old. Changes in parental intention-to-vaccinate rates were calculated. To identify factors associated with parental intention to vaccinate their daughters, the chi-square test and logistic regression analysis were used. RESULTS: The percentage of respondents intending to vaccinate their daughters increased from 33.4% in 2016 to 58.9% in 2020, constituting a 25.5 percentage point (%p) increase. Since 2016, the proportion of men expressing positive intention towards HPV vaccination increased by 31.5%p, while that of women demonstrated a 20.9%p increase. Logistic regression analysis indicated that parents with a strong intention to vaccinate their daughters tended to be younger, more educated, and aware of the free vaccination program available, as well as to have a history of HPV vaccination and to have undergone cervical cancer screening within 2 years, compared to those who did not intend to vaccinate. Being a mother with a history of HPV vaccination was the strongest predictor of positive intention to vaccinate a daughter. CONCLUSIONS: The intention among parents to vaccinate daughters remains relatively low, although it is rising. To increase the HPV vaccination rate, strong recommendations and education should be provided to parents and the younger generation.

Upregulation of the ERRγ-VDAC1 axis underlies the molecular pathogenesis of pancreatitis.

Emerging evidence suggest that transcription factors play multiple roles in the development of pancreatitis, a necroinflammatory condition lacking specific therapy. Estrogen-related receptor γ (ERRγ), a pleiotropic transcription factor, has been reported to play a vital role in pancreatic acinar cell (PAC) homeostasis. However, the role of ERRγ in PAC dysfunction remains hitherto unknown. Here, we demonstrated in both mice models and human cohorts that pancreatitis is associated with an increase in ERRγ gene expression via activation of STAT3. Acinar-specific ERRγ haploinsufficiency or pharmacological inhibition of ERRγ significantly impaired the progression of pancreatitis both in vitro and in vivo. Using systematic transcriptomic analysis, we identified that voltage-dependent anion channel 1 (VDAC1) acts as a molecular mediator of ERRγ. Mechanistically, we showed that induction of ERRγ in cultured acinar cells and mouse pancreata enhanced VDAC1 expression by directly binding to specific site of the Vdac1 gene promoter and resulted in VDAC1 oligomerization. Notably, VDAC1, whose expression and oligomerization were dependent on ERRγ, modulates mitochondrial Ca2+ and ROS levels. Inhibition of the ERRγ-VDAC1 axis could alleviate mitochondrial Ca2+ accumulation, ROS formation and inhibit progression of pancreatitis. Using two different mouse models of pancreatitis, we showed that pharmacological blockade of ERRγ-VDAC1 pathway has therapeutic benefits in mitigating progression of pancreatitis. Likewise, using PRSS1R122H-Tg mice to mimic human hereditary pancreatitis, we demonstrated that ERRγ inhibitor also alleviated pancreatitis. Our findings highlight the importance of ERRγ in pancreatitis progression and suggests its therapeutic intervention for prevention and treatment of pancreatitis.

Risk of upper gastrointestinal cancer and death in persons with negative screening results: results from the National Cancer Screening Program in South Korea.

BACKGROUND: The Korea National Cancer Screening Program (KNCSP) offers upper endoscopy or upper gastrointestinal series (UGIS) biannually for people aged ≥ 40 years. This study aimed to assess the effect of negative screening results on the incidence of and mortality from upper gastrointestinal (GI) cancer. METHODS: A population-based retrospective cohort of 15,850,288 men and women was constructed using data from 3 national databases. The participants were followed until the end of 2017 for data on cancer incidence and in 2019 for data on the vital status. Cox proportional hazard model with time-varying exposure was used to assess the association. RESULTS: By the end of the follow-up period, 230,783 upper GI cancer cases and 99,348 upper GI cancer deaths were recorded. Negative gastric cancer screening was significantly associated with a lower risk of upper GI cancer in both UGIS (adjusted hazard ratio [aHR] = 0.81, 95% CI = 0.80-0.82) and upper endoscopy (aHR = 0.67, 95% CI = 0.67-0.68) groups. The HRs for upper GI mortality were 0.55 (95% CI = 0.54-0.56) and 0.21 (95% CI = 0.21-0.22) for the UGIS and upper endoscopy groups, respectively. The most significant reductions in the risk of upper GI cancer (UGIS: aHR = 0.76, 95% CI = 0.74-0.77; upper endoscopy: aHR = 0.60, 95% CI = 0.59-0.61) and death (UGIS: aHR = 0.54, 95% CI = 0.52-0.55; upper endoscopy: aHR = 0.19, 95% CI = 0.19-0.20) were observed among individual aged 60-69 years. CONCLUSION: Negative screening cases, especially in upper endoscopy of the KNCSP, were associated with an overall reduction in the risk of and mortality from upper GI cancer.

Overview of the National Cancer Screening Program for Colorectal Cancer in Korea over 14 Years (2004-2017).

PURPOSE: This study aimed to evaluate the participation and follow-up test compliance rates and key performance indicators of the National Cancer Screening Program (NCSP) for colorectal cancer (CRC) from 2004 to 2017. Materials and Methods: The overall outcomes of the NCSP for CRC were analyzed using the NCSP data collected from 2004 to 2017 and the Korean Central Cancer Registry for CRC from 2005 to 2017. We cross-sectionally analyzed the participation and follow-up test compliance rates and performance indicators for each year. The trend of participation rates as an annual percentage change was assessed, and other statistical analyses were performed. RESULTS: The screening participation rates increased from 7.3% in 2004 to 30.5% in 2017. Additionally, the screening rates were higher among individuals aged 60-69 years and National Health Insurance Service beneficiaries of low-income status. However, the adherence to the follow-up test decreased from 63% in 2004 to 32% in 2017. The follow-up tests using the double-contrast barium enema method decreased from 42.2% in 2004 to 0.3% in 2017. However, follow-up tests by colonoscopy increased from 21.0% in 2004 to 31.8% in 2017. Furthermore, the positivity, false-positive, and interval CRC rates decreased, whereas the specificity increased from 2004 to 2016, indicating improved performance of CRC. CONCLUSION: The participation rates and performance of the NCSP for CRC have steadily improved, whereas adherence to follow-up tests has decreased. Additionally, there is a rapid growth in colonoscopy volume as a follow-up test. Continued efforts are required to improve the follow-up rates.

Effect of mammography screening on the long-term survival of breast cancer patients: results from the National Cancer Screening Program in Korea.

OBJECTIVES: This study investigated the effect of mammography screening on the long-term survival of breast cancer (BC) patients aged 40 years or older according to their screening history and duration since screening. METHODS: The study cohort was organized from 3 nationwide databases of the Korean National Cancer Screening Program, the Korean Central Cancer Registry, and death certificates. We included 24,387 women diagnosed with invasive BC or ductal carcinoma in situ in 2008 and 2009 and followed up until December 31, 2019. Cox proportional-hazards regression was used to investigate the effect of BC screening on the risk of death. RESULTS: Overall, 20,916 of 24,387 patients (85.8%) were alive at the end of the follow-up period (median: 10.5 years). The long-term survival rate was significantly lower in the never-screened group (80.3%) than in the screened group (88.9%) (p<0.001). A 35% reduction in the risk of BC death (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.60 to 0.70) from screening was observed. A subgroup analysis according to the cancer stage showed 62%, 36%, and 24% lower risks of BC death for the localized stage, regional stage, and distant stage, respectively. Women aged 40-49 years received the least benefit from BC screening (HR, 0.71; 95% CI, 0.62 to 0.81). CONCLUSIONS: Mammography screening was effective in reducing the risk of BC-specific death in Asian women across all cancer stages. However, this effect was relatively small among women in their 40s, suggesting that more detailed and specialized screening strategies are needed for that age group.

Impact of the COVID-19 Pandemic on Gastric Cancer Screening in South Korea: Results From the Korean National Cancer Screening Survey (2017-2021).

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has significantly disrupted cancer screening services worldwide. We aimed to measure the impact of COVID-19 on gastric cancer screening rates based on age, sex, household income, and residential area. MATERIALS AND METHODS: We analyzed data from the Korean National Cancer Screening Survey from 2017 to 2021 for adults aged 40-74 years. We evaluated the gastric cancer screening rate within two years in accordance with the National Cancer Screening Program protocol recommendations and that within the previous year. We compared the trends in the pre- and post-COVID-19 outbreak periods. RESULTS: Before the COVID-19 outbreak, there was little change in the gastric cancer screening rates until 2019. After the COVID-19 outbreak, the screening rate as per recommendation decreased from 70.8% in 2019 to 68.9% in 2020 and that for one year decreased from 32.7% in 2019 to 27.2% in 2020. However, as the COVID-19 pandemic continued after 2020, both gastric cancer screening rates as per recommendations and for one year rebounded. Although a similar trend was observed for the upper endoscopy screening rate, the upper gastrointestinal series screening rate decreased from 7.8% in 2020 to 3.1% in 2021. During the pandemic, the screening rate decreased among younger adults (40-49), those residing in metropolitan regions, and those with high incomes. CONCLUSIONS: Despite a decline in gastric cancer screening rate during the COVID-19 pandemic, the rate surged in 2021. Further studies are needed to estimate the impact of cancer screening delays on future cancer-related mortalities.

Effect of Pap smears on the long-term survival of cervical cancer patients: a nationwide population-based cohort study in Korea.

OBJECTIVES: This study aimed to investigate the effect of cervical cancer screening by Papanicolaou (Pap) smears on the long-term survival of cervical cancer patients. METHODS: We constructed a retrospective cohort of 14,903 women diagnosed with invasive cancer or carcinoma in situ in 2008 and 2009 and followed up until December 31, 2019, by using individual-level data from 3 national databases of the Korean National Cancer Screening Program, the Korean Central Cancer Registry, and death certificates. Cox proportional-hazards regression was used to investigate the effect of cervical cancer screening on mortality. RESULTS: In total, 12,987 out of 14,867 patients (87.4%) were alive at the end of the follow-up period (median: 10.5 years). Screened patients had a 38% lower risk of cervical cancer death than never-screened patients (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.54 to 0.70). Screening was associated with 59% and 35% lower risks of death, respectively, in screened patients with localized and regional stages. Furthermore, lower HRs among women who received screening were observed in all age groups, especially women aged 50-59 years (HR, 0.54; 95% CI, 0.42 to 0.69). The lowest HR for cervical cancer death was reported among patients screened within the past 2 years (HR, 0.54; 95% CI, 0.47 to 0.63), and the HRs increased with increasing time intervals. CONCLUSIONS: Pap smear screening significantly reduced the risk of cervical cancer-specific death in Korean women across all cancer stages.

Gemigliptin exerts protective effects against doxorubicin-induced hepatotoxicity by inhibiting apoptosis via the regulation of fibroblast growth factor 21 expression.

AIM: Doxorubicin is a highly effective anticancer agent that causes hepatotoxicity and cardiotoxicity in patients. Fibroblast growth factor 21, a well-known regulator of glucose and lipid metabolism, exerts cardioprotective effects. Gemigliptin and dipeptidyl peptidase-4 inhibitors are widely used in the treatment of patients with type 2 diabetes. The protective effects of gemigliptin on hepatotoxicity via the increase in fibroblast growth factor 21 expression has not yet been elucidated. This study was designed to investigate the protective effects of gemigliptin against doxorubicin-induced hepatotoxicity via the upregulation of fibroblast growth factor 21 expression in the cultured murine hepatocyte cell line, AML12. METHODS: Murine hepatocyte AML12 cells were treated with doxorubicin, fibroblast growth factor 21 and gemigliptin in 0.5% fetal bovine serum medium for 24 h at the indicated doses. Cells were transfected with the fibroblast growth factor 21 small interfering RNA for 24 h, followed by protein isolation. RESULTS: Fibroblast growth factor 21 expression levels were increased during doxorubicin-induced hepatotoxicity in the murine hepatocyte AML12 cells. Fibroblast growth factor 21 treatment prevented doxorubicin-induced hepatotoxicity by attenuating apoptosis. Gemigliptin prevented doxorubicin-induced hepatotoxicity by upregulating fibroblast growth factor 21 expression. However, the protective effects of gemigliptin were blocked by fibroblast growth factor 21 inhibition in doxorubicin-treated AML12 cells. CONCLUSION: These results indicate that gemigliptin exhibits protective effects against doxorubicin-induced hepatotoxicity by upregulating the fibroblast growth factor 21 expression levels in the cultured murine hepatocyte AML12 cells.

Effect of gastric cancer screening on long-term survival of gastric cancer patients: results of Korean national cancer screening program.

BACKGROUND: Gastric cancer (GC) is the most common cancer type in Korea. Korean National Cancer Screening Program (KNCSP) offer either upper gastrointestinal series (UGIS) or upper endoscopy biennially for adults aged ≥ 40. This study aimed to investigate the effect of cancer screening program on the long-term survival among GC patients. METHODS: A nationwide population-based cohort was constructed based on three national databases. Overall, 46,701 GC patients diagnosed in 2008 and 2009 were included in our final analysis, and they were followed-up until the end of 2019. Survival curves were estimated using the Kaplan-Meier analysis with the log-rank test. Cox proportional-hazards regression analysis was used to report the hazard ratios (HRs) with 95% confidence intervals. RESULTS: A total of 18,614/46,701 (39.9%) patients died during the median follow-up time of 10.5 years. The survival rate was higher among screened patients (65.8%) than never-screened patients (49.1%). Screened patients had 53% (HR, 0.47; 95% CI 0.45-0.48) lower risk of death from GC. The HRs of GC-specific mortality was lower in upper endoscopy group (HR = 0.36; 95% CI = 0.34-0.37) compared with UGIS (HR = 0.69; 95% CI = 0.67-0.73). Screened patients within 2 years prior to cancer diagnosis had a 35% reduction in risk of GC death. The figure decline to approximately 19% among patients with interval time since last screening of > 3 years. CONCLUSIONS: Our findings emphasized the positive effects of GC screening on long-term GC patient survival. Also, patients screened by upper endoscopy or within 2 years before diagnosis had the best survival outcomes.