Association between glucagon-like peptide-1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database.

AIM: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data. MATERIALS AND METHODS: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC025 regarding the association between GLP-1RA use and suicidality. RESULTS: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC025 0.01]). CONCLUSIONS: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population.

Prevalence, Awareness, Treatment, and Control of Type 2 Diabetes in South Korea (1998 to 2022): Nationwide Cross-Sectional Study.

BACKGROUND: Type 2 diabetes poses an increasing disease burden in South Korea. The development and management of type 2 diabetes are closely related to lifestyle and socioeconomic factors, which have undergone substantial changes over the past few decades, including during the COVID-19 pandemic. OBJECTIVE: This study aimed to investigate long-term trends in type 2 diabetes prevalence, awareness, treatment, and control. It also aimed to determine whether there were substantial alterations in the trends during the pandemic and whether these changes were more pronounced within specific demographic groups. METHODS: This study examined the prevalence, awareness, treatment, and control of type 2 diabetes in a representative sample of 139,786 South Koreans aged >30 years, using data from the National Health and Nutrition Examination Survey and covering the period from 1998 to 2022. Weighted linear regression and binary logistic regression were performed to calculate weighted ß coefficients or odds ratios. Stratified analyses were performed based on sex, age, region of residence, obesity status, educational background, household income, and smoking status. ß (difference) was calculated to analyze the trend difference between the prepandemic period and the COVID-19 pandemic. To identify groups more susceptible to type 2 diabetes, we estimated interaction terms for each factor and calculated weighted odds ratios. RESULTS: From 1998 to 2022, a consistent increase in the prevalence of type 2 diabetes was observed among South Koreans, with a notable rise to 15.61% (95% CI 14.83-16.38) during the pandemic. Awareness followed a U-shaped curve, bottoming out at 64.37% (95% CI 61.79-66.96) from 2013 to 2015 before increasing to 72.56% (95% CI 70.39-74.72) during the pandemic. Treatment also increased over time, peaking at 68.33% (95% CI 65.95-70.71) during the pandemic. Control among participants with diabetes showed no substantial change, maintaining a rate of 29.14% (95% CI 26.82-31.47) from 2020 to 2022, while control among treated participants improved to 30.68% (95% CI 27.88-33.48). During the pandemic, there was a steepening of the curves for awareness and treatment. However, while the slope of control among participants being treated increased, the slope of control among participants with diabetes showed no substantial change during the pandemic. Older populations and individuals with lower educational level exhibited less improvement in awareness and control trends than younger populations and more educated individuals. People with lower income experienced a deceleration in prevalence during the pandemic. CONCLUSIONS: Over the recent decade, there has been an increase in type 2 diabetes prevalence, awareness, treatment, and control. During the pandemic, a steeper increase in awareness, treatment, and control among participants being treated was observed. However, there were heterogeneous changes across different population groups, underscoring the need for targeted interventions to address disparities and improve diabetes management for susceptible populations.

Biomarkers and Related Factors for the Diagnosis, Risk of Coronary Artery Lesions, and Resistance to Intravenous Immunoglobulin in Kawasaki Disease: An Umbrella Review of Meta-Analyses.

Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 [95% CI, 13.58-27.56]), Serum ferritin (DOR, 24.90 [11.67-53.12]), N terminal proBNP (DOR, 21.03 [9.03-49.00]), and micro RNAs (DOR, 45.28 [6.30-325.52]), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 [95% CI, 2.37-25.09]), non-coding RNAs (DOR, 14.63 [3.24-66.14]), neutrophil to lymphocyte ratio (DOR, 6.62 [4.05-10.81]), platelet to lymphocyte ratio (DOR, 3.30 [2.10-5.19]), and C reactive protein (DOR, 6.58 [3.69-11.74]). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.

Global burden of vaccine-associated hepatobiliary and gastrointestinal adverse drug reactions, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

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 burden of anticancer drug-induced acute kidney injury and tubulointerstitial nephritis from 1967 to 2023.

This study aims to figure out the worldwide prevalence of anticancer therapy-associated acute kidney injury (AKI) and tubulointerstitial nephritis (TIN) and the relative risk of each cancer drug. We conducted an analysis of VigiBase, the World Health Organization pharmacovigilance database, 1967-2023 via disproportionate Bayesian reporting method. We further categorized the anticancer drugs into four groups: cytotoxic therapy, hormone therapy, immunotherapy, and targeted therapy. Reporting odds ratio (ROR) and information component (IC) compares observed and expected values to investigate the associations of each category of anticancer drugs with AKI and TIN. We identified 32,722 and 2056 reports (male, n = 17,829 and 1,293) of anticancer therapy-associated AKI and TIN, respectively, among 4,592,036 reports of all-drug caused AKI and TIN. There has been a significant increase in reports since 2010, primarily due to increased reports of targeted therapy and immunotherapy. Immunotherapy exhibited a significant association with both AKI (ROR: 8.92; IC0.25: 3.06) and TIN (21.74; 4.24), followed by cytotoxic therapy (7.14; 2.68), targeted therapy (5.83; 2.40), and hormone therapy (2.59; 1.24) for AKI, and by cytotoxic therapy (2.60; 1.21) and targeted therapy (1.54; 0.61) for TIN. AKI and TIN were more prevalent among individuals under 45 years of age, with a female preponderance for AKI and males for TIN. These events were reported in close temporal relationship after initiation of the respective drug (16.53 days for AKI and 27.97 days for TIN), and exhibited a high fatality rate, with 23.6% for AKI and 16.3% for TIN. These findings underscore that kidney-related adverse drug reactions are of prognostic significance and strategies to mitigate such side effects are required to optimize anticancer therapy.

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-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 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.