Search

Epidemiologic studies have suggested a possible association between air pollution and chronic obstructive pulmonary disease (COPD), but it is controversial and difficult to draw causal inferences. Five methods were adopted to evaluate the causal relationship between air pollution and COPD in European and East Asian populations by using MR Analysis. A statistically significant causal relationship between PM2.5 and COPD was observed in the European population (OR: 2.34; 95% CI: 1.06-5.05; p  = 0.033). Statistical significance remained after adjustment for confounding factors (adjusted OR: 2.28; 95% CI: 1.01-5.20; p  = 0.048). In East Asian populations, PM2.5 absorbance, a proxy for black carbon, was statistically associated with COPD (OR: 1.41; 95% CI: 1.09-1.81; p  = 0.007). We did not adjust for confounders in East Asian populations, as the association was independent of known confounders (e.g. smoking, respiratory tract infections, etc.). In conclusion, increased concentrations of PM2.5 and PM2.5 absorbance were associated with an increased risk of COPD.

Background: Height is associated with increased cancer risk, but most studies focus on Western populations. We aimed to evaluate this relationship in East Asians., Method: Observational analyses were performed utilizing data from China Kadoorie Biobank (CKB) prospective cohort. Adjusted hazard ratios (HRs) and corresponding 95 % confidence intervals (CIs) were estimated using Cox proportional hazards models. Two-sample Mendelian randomization (MR) analyses explored causal effects between height and cancer using data from Korean Genome and Epidemiology Study (KoGES), Biobank Japan (BBJ), and CKB., Results: Over a median 10.1-years follow-up, 22,731 incident cancers occurred. In observational analyses, after Bonferroni correction, each 10 cm increase in height was significantly associated with higher risk of overall cancer (HR 1.16, 95 % CI 1.14-1.19, P < 0.001), lung cancer (1.18, 95 % CI 1.12-1.24, P < 0.001), esophageal cancer (1.21, 95 % CI 1.12-1.30, P < 0.001), breast cancer (1.41, 95 % CI 1.31-1.53, P < 0.001), and cervix uteri cancer (1.29, 95 % CI 1.15-1.45, P < 0.001). Each 10 cm increase in height was suggestively associated with increased risk for lymphoma (1.18, 95 % CI 1.04-1.34, P = 0.010), colorectal cancer (1.09, 95 % CI 1.02-1.16, P = 0.010), and stomach cancer (1.07, 95 % CI 1.00-1.14, P = 0.044). In MR analyses, genetically predicted height (per 1 standard deviation increase, 8.07 cm) was suggestively associated with higher risk of lung cancer (odds ratio [OR] 1.17, 95 % confidence interval [CI] 1.02-1.35, P = 0.0244) and gastric cancer (OR 1.14, 95 % CI 1.02-1.29, P = 0.0233)., Conclusions: Taller height was significantly related to a higher risk for overall cancer, lung cancer, esophageal cancer, breast cancer, and cervix uteri cancer. Our findings suggest that height may be a potential causal risk factor for lung and gastric cancers among East Asians., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Backgrounds: The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities., Methods: Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis., Results: In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC < 0), while mortality and DALY rates decreased in all five countries (AAPC < 0). Age effects showed increasing trends for incidence, mortality and DALY rates, while the prevalence rates increased first and then decreased in older groups. The cohort effects showed downward trends from 1914-1918 to 2004-2008. Smoking was the greatest contributor and males had the higher burden than females., Conclusion: Bladder cancer was still a major public health problem in East Asia. Male and older population suffered from higher risk, and smoking played an important role. It is recommended that more efficient preventions and interventions should be operated among high-risk populations, thereby reduce bladder cancer burden in East Asia., (© 2024. The Author(s).)

Aim: To assess the global and regional burden of hip fractures associated with type 1 diabetes (T1D) from 1990 to 2021., Materials and Methods: The population attributable fraction was calculated by combining the published risk ratio with T1D prevalence (age ≥ 20 years) from the Global Burden of Disease study to estimate the T1D-associated hip-fracture burden. Trends were assessed using the age-standardized incidence rate (ASIR) and estimated annual percentage change (EAPC)., Results: The global incidence of T1D-related hip fractures was 290 180 in 2021 with an ASIR of 3.96 (95% confidence interval: 1.92-5.87) per 100 000 population and a male-to-female ratio of 0.54. At the super-regional level, the highest incidence (204 610) and ASIR (13.09 per 100 000 population; 6.40-25.53) were observed in high-income regions, in particular in Australasia and Western Europe. Notably, Australasia exhibited the highest EAPC, 2.90% in T1D-associated ASIR, followed by East Asia (2.73%). The incidence among those aged 45-64 years grew significantly in 14 regions over the past decade. Nationally, the ASIR increased in 166 countries from 1990 to 2021., Conclusions: High-income regions experienced the greatest burden of T1D-associated hip fracture, while Australasia and East Asia witnessed the largest increase over the last 32 years. Prioritizing the promotion of T1D treatment and hip-fracture screening for middle-aged females living with T1D is crucial in these regions., (© 2024 John Wiley & Sons Ltd.)

Background: In East Asia, Helicobacter pylori ( H. pylori ) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance in H. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance in H. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations., Methods: We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance in H. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance, H. pylori , and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies., Results: We identified 15 observational studies involving 4831 H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance in H. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40-62%) for metronidazole; 37% (95% CI: 20-53%) for clarithromycin; 19% (95% CI: 11-28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21-36%) and 10% (95% CI: 7-14%), highlighting the potential for diverse resistance patterns., Conclusions: H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem., Registration: PROSPERO, No. CRD42023402510., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear., Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations., Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway., Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants., Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kang, Wu, Li, Zhao, Wang and Yu.)

Background: Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer., Methods: Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association., Results: A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer., Conclusions: The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice., (© 2024. The Author(s).)

Objective: The purpose of this study is to summarize the health system response to COVID-19 in four East Asian countries, analyze the effectiveness of their health system response, and provide lessons for other countries to control the epidemic and optimize their health system response., Methods: This study investigated and summarized COVID-19 data and health system response in four East Asian countries, China, Japan, Mongolia, and South Korea from national governments and ministries of health, WHO country offices, and official websites of international organizations, to assess the effectiveness of health system measures., Result: As of June 30, 2022, all four countries are in a declining portion of COVID-19. China has two waves, and new cases increased slowly, with the total cases per million remaining within 4, indicating a low level. Japan has experienced six waves, with case growth at an all-time high, total cases per million of 250.994. Mongolia started the epidemic later, but also experienced four waves, with total cases per million of 632.658, the highest of the four countries. South Korea has seen an increasing number of new cases per wave, with a total case per million of 473.759., Conclusion: In containment strategies adopted by China and Mongolia, and mitigation strategies adopted by Japan and South Korea, health systems have played important roles in COVID-19 prevention and control. While promoting vaccination, countries should pay attention to non-pharmaceutical health system measures, as evidenced by: focusing on public information campaigns to lead public minds; strengthening detection capabilities for early detection and identification; using technical ways to participate in contact tracing, and promoting precise judging isolation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiao and Chen.)

Purpose: Previous observational studies have shown that green tea consumption is associated with a reduced incidence of digestive system cancers (DSCs). However, the observed association could be due to confounding factors. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the causal effect of green tea intake on the risk of five common DSCs., Methods: Independent genetic variants strongly associated with green tea consumption in European and East Asian populations were selected as instrumental variables in genome-wide association studies involving up to 64,949 European individuals and 152,653 East Asian individuals, respectively. The associations between genetic variants and DSCs were extracted from the FinnGen study and the Japan Biobank. The primary analysis was performed using random-effects inverse variance weighting (IVW). Other MR analyses, including weighted mode-based estimate, weighted-median, MR-Egger regression, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis, were used for sensitivity analyses. In addition, a multivariate MR design was performed to adjust for smoking and alcohol consumption., Results: The IVW results showed no causal relationship between tea intake and DSCs risk in European population (esophagus cancer: odds ratio (OR) = 1.044, 95% confidence interval (CI) 0.992-1.099, p = 0.096; stomach cancer: OR = 0.988, 95% CI 0.963-1.014, p = 0.368; colorectal cancer: OR = 1.003, 95% CI 0.992-1.015, p = 0.588; liver cancer: OR = 0.996, 95% CI 0.960-1.032, p = 0.808; pancreatic cancer: OR = 0.990, 95% CI 0.965-1.015, p = 0.432). The MR-Egger regression, MR-PRESSO analysis and other methods also confirmed the reliability of the conclusion. Similarly, no significant association was found between green tea consumption and the incidence of DSCs among East Asians. This relationship is not significant even after adjusting for smoking and alcohol consumption (P > 0.05)., Conclusion: Our study provides evidence that genetically predicted green tea intake is not causally associated with the development of DSCs in the European and East Asian population., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, β = -1.372, p = 0.045), and basophil counts (Baso, β = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza., (© 2024 Wiley Periodicals LLC.)

Background: The disease burden of colorectal cancer in East Asia has been at a high level. However, the epidemiological characteristics of the disease burden in this region have not been systematically studied., Method: Data were obtained from the Global Burden of Disease 2019 program. Joinpoint analysis was used to identify long-term trends in mortality of colorectal cancer. Independent effects of age, period, and cohort were detected by the age-period-cohort model. The Bayesian age-period-cohort model was performed to predict the burden of colorectal cancer across East Asia by 2030., Results: From 1990 to 2019, the average annual percentage change (AAPC) showed upward trends in mainland China (1.05 [95% confidence interval (CI)], 0.82, 1.28) as well as Taiwan Province of China (1.81 [95% CI], 1.51, 2.10) but downward in Japan (-0.60 [95% CI], -0.70, -0.49) (P < 0.05). Attributable risk factors for colorectal cancer in East Asia remained stable over 30 years, while the risk of metabolic factors is noteworthy in the future. In the next decade, the age-standardized death rate (ASDR) of colorectal cancer in China was predicted to surpass that of Japan and South Korea in expectation., Conclusion: The mortality of colorectal cancer is escalating in developing countries, while it is gradually declining in high-income countries across East Asia. Nonetheless, the disease burden of colorectal cancer in high-income countries remains substantial level., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Metabolic factors play a critical role in the development of digestive system cancers (DSCs), and East Asia has the highest incidence of malignant tumors in the digestive system. We performed a two-sample Mendelian randomization analysis to explore the associations between 19 metabolism-related lifestyle and clinical risk factors and DSCs, including esophageal, gastric, colorectal, hepatocellular, biliary tract, and pancreatic cancer. The causal association was explored for all combinations of each risk factor and each DSC. We gathered information on the instrumental variables (IVs) from various sources and retrieved outcome information from Biobank Japan (BBJ). The data were all from studies of east Asian populations. Finally, 17,572 DSCs cases and 195,745 controls were included. Our analysis found that genetically predicted alcohol drinking was a strong indicator of gastric cancer (odds ratio (OR) = 0.95; 95% confidence interval (CI): 0.93-0.98) and hepatocellular carcinoma (OR = 1.11; 95% CI: 1.05-1.18), whereas coffee consumption had a potential protective effect on hepatocellular carcinoma (OR = 0.69; 95% CI: 0.53-0.90). Triglyceride was potentially associated with a decreased risk of biliary tract cancer (OR = 0.53; 95% CI: 0.34-0.81), and uric acid was associated with pancreatic cancer risk (OR = 0.59; 95% CI: 0.37-0.96). Metabolic syndrome (MetS) was associated with esophageal and gastric cancer. Additionally, there was no evidence for a causal association between other risk factors, including body mass index, waist circumference, waist-to-hip ratio, educational levels, lipoprotein cholesterol, total cholesterol, glycine, creatinine, gout, and Graves' disease, and DSCs. The leave-one-out analysis revealed that the single nucleotide polymorphism (SNP) rs671 from the ALDH2 gene has a disproportionately high contribution to the causal association between alcohol drinking and gastric cancer and hepatocellular carcinoma, as well as the association between coffee consumption and hepatocellular carcinoma. The present study revealed multiple metabolism-related lifestyle and clinical risk factors and a valuable SNP rs671 for DSCs, highlighting the significance of metabolic factors in both the prevention and treatment of DSCs., (© 2024. The Author(s).)

Objective: This systematic review aims to comprehensively examine the relationship between intergenerational relationships and depression among older adults in Eastern Asian countries., Methods: For this research, a systematic search was conducted on several electronic databases including PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar search engine up until June 2023., Results: Out of 953 articles initially identified, 33 met the inclusion criteria. Emotional support and financial support emerged as crucial factors that can significantly reduce depressive symptoms among older individuals. However, there are diverse and sometimes contradictory results regarding the impact of intergenerational instrumental support on depression in older adults., Conclusion: Promoting positive intergenerational relationships and enhancing support systems can greatly benefit the mental health of older adults by addressing depression within this population. This review enhances our understanding of the complex relationship between intergenerational relationships and depression among older adults. The diverse findings on intergenerational instrumental support and depression in older adults suggest the need for further research to clarify this relationship and its nuances. This research may have practical implications for policies and interventions aimed at improving the mental well-being of older adults in Eastern Asian countries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Precision diagnosis is the keystone of clinical medicine. In East Asians, classical type 1 diabetes is uncommon in patients with youngonset diabetes diagnosed before age of 40, in whom a family history, obesity, and beta-cell and kidney dysfunction are key features. Young-onset diabetes affects one in five Asian adults with diabetes in clinic settings; however, it is often misclassified, resulting in delayed or non-targeted treatment. Complex aetiologies, long disease duration, aggressive clinical course, and a lack of evidence-based guidelines have contributed to variable care standards and premature death in these young patients. The high burden of comorbidities, notably mental illness, highlights the numerous knowledge gaps related to this silent killer. The majority of adult patients with youngonset diabetes are managed as part of a heterogeneous population of patients with various ages of diagnosis. A multidisciplinary care team led by physicians with special interest in young-onset diabetes will help improve the precision of diagnosis and address their physical, mental, and behavioral health. To this end, payors, planners, and providers need to align and re-design the practice environment to gather data systematically during routine practice to elucidate the multicausality of young-onset diabetes, treat to multiple targets, and improve outcomes in these vulnerable individuals.

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis., Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis., Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively., Conclusion: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC., Trial Registration: ClinicalTrials.gov Identifier: NCT03517449., Competing Interests: Kan Yonemori has received lecture fees from Eisai, Pfizer, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Boeringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, Sanofi, and AstraZeneca; is a member of the advisory board for Eisai, AstraZeneca, Sanofi, Genmab, Gilead, OncXerna, Takeda, Novartis, and MSD; research funding from MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe; and is principle investigator for MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Merk Biopharma, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Lymphoblastic lymphoma (LBL) is a rare, aggressive non-Hodgkin lymphoma (NHL) that has no established therapeutic approaches. The aim of this study was to investigate optimal treatments and prognostic risk models for patients with LBL in East Asia. We retrospectively examined the clinical data and treatment courses of adult patients diagnosed as LBL by WHO 2017 classification system. Median overall survival (OS) of the 78 patients with LBL was 38.3 months. There was no significant difference in OS between the patients who were treated with acute lymphoblastic leukemia (ALL)-like protocols and with NHL-like protocols (72.4 months vs 37.5 months, respectively, P = .546). The patients treated with ALL-like protocols had significantly shorter progression-free survival (PFS) (median 11.7 months for ALL-like protocols vs 27.0 months for NHL-like protocols, P = .030). A multivariable analysis found that central nervous system (CNS) prophylaxis, relapse of CNS lesions, leukemic transformation, and response to initial treatment were risk factors for OS of patients with LBL. Hematopoietic stem cell transplantation had no survival benefit, compared with chemotherapy-only treatment. Less intensive chemotherapy may be more optimal for patients in East Asia. Prophylaxis and management of CNS lesions should be emphasized throughout the treatment of LBL., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although Japan is a major endemic area for human T-lymphotropic virus type 1 (HTLV-1) and the virus has been well-studied in this region, there is limited research on HTLV-1 in surrounding regions. In this study, we determined the complete genome sequences of HTLV-1 strains isolated from Taiwan and Japan and investigated the geographic characteristics of molecular subgroups and substitution mutations to understand the spread of HTLV-1 and its correlation with human migration., Methodology/principal Findings: The complete genome sequences of 26 HTLV-1 isolates from Taiwan were determined using next-generation sequencing and were compared with those of 211 isolates from Japan in terms of subgroup and genetic mutations. In total, 15/26 (58%) isolates from Taiwan belonged to the transcontinental subgroup and 11/26 (42%) isolates belonged to the Japanese subgroup. The transcontinental subgroup was significantly more prevalent among Taiwanese isolates than Japanese isolates (58% vs 18%, P < 0.0001). The mutation rate for the complete HTLV-1 sequence was as low as 0.2%. On examining individual base substitutions, the G-to-A mutation was predominant. Bayesian phylogenetic tree analysis estimated the time to the most recent common ancestor for the transcontinental and Japanese subgroups to be 28447 years. The transcontinental subgroups from Taiwan and Japan appeared to form clusters according to their respective regions., Conclusions/significance: The transcontinental subgroup of HTLV-1 is predominant in Taiwan, while the Japanese subgroup is common in Japan. The difference in subgroup distribution may be attributed to the initial spread of the transcontinental subgroup in East Asia, followed by the influx of the Japanese subgroup., Competing Interests: The authors have declared that no conflict of interest exists., (Copyright: © 2024 Nozuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aims to estimate the transmission potential of mpox in East Asia, focusing on the hardest hit nations: Taiwan, China, Japan, and South Korea., Methods: We utilized six phenomenological dynamic growth models to fit the case incidence during the initial 30 epidemic days. The best-fit model was selected to calculate the reproduction number (R t ). Additionally, we used the latest case data and a Bayesian framework to compute the instantaneous effective R t by applying the Cori et al., Results: During the early phase, China demonstrated the highest estimated R t of 2.89 (95% CI: 1.44-3.33); followed by South Korea, 2.18 (95% CI: 0.96-3.57); Japan, 1.73 (95% CI: 0.66-3.94); and Taiwan, 1.36 (95% CI: 0.71-3.30). However, by June 30, 2023, estimated R t dropped below 1.00 in all countries: China at 0.05 (95% credible interval [CrI]: 0.02-0.10), Japan at 0.32 (95% CrI: 0.15-0.59), South Korea at 0.23 (95% CrI: 0.11-0.42), and Taiwan at 0.41 (95% CrI: 0.31-0.53), indicating the potential decline of the outbreak., Conclusions: Our analysis shows effective containment by each country. It is crucial to sustain effective management to ensure the ultimate eradication of the outbreak., Competing Interests: Declaration of competing interest Authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure., Methods: We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease (GBD) modeling framework was applied to estimate the population attributable fraction, incidence, and disability-adjusted life-years (DALYs) lost to alcohol-attributable cancer., Results: We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, esophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually were underestimated by 1.20 million., Conclusions: The burden of liver, esophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The outbreak of COVID-19 in early 2020 created dangerous public health conditions which pressured governments and health systems to respond in a rapid and effective manner. However, this type of rapid response required many governments to bypass standing; bureaucratic structures of health sector administration and political governance to quickly take; essential measures against a rapidly evolving public health threat. Each government's particular; configuration of governmental and health system decision-making created specific structural and functional challenges to these necessary centrally developed and coordinated strategies. Most East Asian governments (except Japan) succeeded relatively quickly in centralizing essential disease control and treatment initiatives in a timely manner. In contrast, a number of European countries, especially those with predominantly tax-based financing and politically managed health delivery systems, had greater difficulty in escaping bureaucratic governance and management constraints. Drawing on data about these governments' early stage COVID-19 control experiences, this article suggests that structural changes will be necessary if low-performing governments are to better respond to a pandemic. This paper also summarizes other relatively successful strategies. By adopting such strategies, nations can help overcome structural bureaucratic and administrative obstacles in responding to further waves of COVID-19 or similar future pandemic events.

Genetic analysis of inflammatory bowel disease has identified many disease susceptibility genes in a large number of cases, mainly in Europe and North America. However, because of the ethnic differences in genetic background, analysis in various ethnic groups is needed. Although genetic analysis in East Asia began at the same time as in the West, the total number of patients analyzed has remained limited in Asia. To address these issues, meta-analyses across East Asian countries are underway, and the genetic analysis of inflammatory bowel disease in East Asians is entering a new phase. New findings on the genetic background factors associated with inflammatory bowel disease originating from East Asia have also been made, such as the association between chromosomal mosaic alteration and this disease. Genetic analysis has been conducted mainly through studies that consider patients as a group. Some of these results, such as the identified relationship between the NUDT15 gene and thiopurine-related adverse events, are beginning to be applied to the actual treatment of individuals. Meanwhile, genetic analyses of rare diseases have focused on the development of diagnostic methods and therapies by identifying causative gene mutations. Recently, genetic analysis has been moving from research on populations and pedigrees to the stage of identifying and using personal genetic information of each patient, which is important for personalized medical care. To achieve this, close collaboration between specialists in complex genetic analysis and clinicians will be critical., (© 2023 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Globally, gastrointestinal cancers represent more than one-fourth of all cancer incidence and one-third of cancer-related mortality. Although there has been much progress in screening colorectal cancer, the prognosis of other gastrointestinal cancers tends to be poor. The highest burden of gastrointestinal cancers, including stomach, liver, oesophageal and gallbladder cancers, was observed in regions in East Asia. The increasing burden of gastrointestinal cancers in East Asian regions is related to population growth, ageing and the westernization of lifestyle habits in this region. Furthermore, the rising incidence of young-onset colorectal cancer is an emerging trend in East Asia. This Review provides a comprehensive and updated summary of the epidemiology of gastrointestinal cancers in East Asia, with emphasis on comparing their epidemiology in East Asia with that in Western regions, and highlights the major risk factors and implications for prevention. Overall, to optimally reduce the disease burden incurred by gastrointestinal cancers in East Asian regions, a concerted effort will be needed to modify unhealthy lifestyles, promote vaccination against the hepatitis virus, control Helicobacter pylori, liver fluke and hepatitis virus infections, increase the uptake rate of colorectal cancer screening, enhance detection of early cancers and their precursors, and improve cancer survivorship through an organized rehabilitation programme., (© 2023. Springer Nature Limited.)

Aim: This study aims to analyze and describe terrorism-related attacks in East Asia from 1970 through 2020., Background: East Asia consists of South Korea, North Korea, Singapore, Hong Kong, China, Japan, Taiwan, and Macao. According to the Global Terrorism Index (GTI) 2022, the impact of terrorism in East Asia is very low. However, the assassination of former Japanese Prime Minister Shinzo Abe on July 8, 2022 demonstrates that East Asia is not safe from terrorist attacks. This descriptive analysis of terrorist attacks in East Asia will help first responders, Emergency Medical Services (EMS), hospital-based medical providers, and policymakers establish a more refined hazard vulnerability assessment (HVA) framework and develop a Counter-Terrorism Medicine (CTM) mitigation, preparedness, response, and recovery plan., Methods: This is a descriptive observational study drawing data from the Global Terrorism Database (GTD) from January 1, 1970 through December 31, 2020. Epidemiology outcomes included primary weapon type, primary target type, the country where the incident occurred, and the number of total deaths and injured collected. Data from 2021 were not yet available at the time of this study. Results were exported into an Excel spreadsheet (Microsoft Corp.; Redmond, Washington USA) for analysis., Results: There were 779 terrorism-related events in East Asia from 1970 through 2020. In total, the attacks resulted in 1,123 deaths and 9,061 persons injured. The greatest number of attacks (371; 47.63%) occurred in Japan and the second most occurred in China (268; 34.4%). Explosives were the most used primary weapon type (308; 39.54%) in the region, followed by incendiary devices (260; 33.38%). Terrorist attacks drastically diminished from their peak of 92 in 1990, but there were additional peaks of 88 in 1996, 18 in 2000, 20 in 2008, and 36 attacks in 2014., Conclusions: A total of 779 terrorist attacks occurred from 1970 through 2020 in East Asia, resulting in 1,123 deaths and 9,061 injuries. Of those, 82.03% attacks occurred in Japan and China. Terrorist attacks drastically diminished since their peak in 1996, but there is an overall uptrend in attacks since 1999.

Aims/introduction: The EMPA-REG OUTCOME® trial demonstrated benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), on cardiovascular, renal outcomes and all-cause mortality in patients with type 2 diabetes and established cardiovascular disease. The EMPRISE study program evaluates how these effects translate in a broad population of patients with type 2 diabetes in routine clinical care across countries., Materials and Methods: The study included patients ≥18 years with type 2 diabetes initiating empagliflozin or any dipeptidyl peptidase-4 inhibitors (DPP-4i) from large administrative databases in Japan, South Korea, and Taiwan. Propensity score-matched (1:1) 'as-treated' analyses comparing the risk of cardiovascular outcomes and all-cause mortality between empagliflozin and DPP-4i use were performed in each country. Pooled hazard ratios (pHR) with 95% confidence intervals (CI) were computed using random effects meta-analysis models comparing both empagliflozin and SGLT2i with DPP-4i use, respectively. Intention-to-treat and subgroup analyses in patients with/without cardiovascular disease and in patients receiving 10 mg empagliflozin were performed., Results: The study included 28,712 and 70,233 matched patient pairs for empagliflozin/DPP-4i and SGLT2i/DPP-4i analyses, respectively. The risk of composite outcomes including (i) hospitalization for heart failure (HHF) and all-cause mortality was lower with empagliflozin (pHR 0.76, 95% CI 0.67-0.86) and SGLT2i (0.71, 0.65-0.77); (ii) combined myocardial infarction, stroke, and all-cause mortality was also lower with empagliflozin (0.74, 0.61-0.88) and SGLT2i (0.69, 0.60-0.78) compared to DPP-4i. The intention-to-treat and three subgroup analyses were consistent with results of the main analyses., Conclusions: The results suggest that both empagliflozin and SGLT2i compared with DPP-4i are associated with a lower risk of cardiovascular events and all-cause mortality in routine clinical care in East Asia., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia-Pacific region., Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing., Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %., Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia-Pacific region., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Our study aimed to evaluate the relationship between visceral obesity and its associated factors, especially sleep duration in East Asia. We conducted univariate and multivariate analyses using the data of 2538 participants (mean age 56.4 ± 10.8 years) who underwent medical checkups and computed tomography of the abdomen to calculate the visceral fat area from 2008 to 2020. We additionally performed logistic regression analyses using each sleep-duration group (< 5, 5-6, 6-7, 7-8, and ≥ 8 h) and their respective propensity scores as covariates. According to the criteria of visceral obesity(a visceral fat area ≥ 100 cm 2 ), 1147 of 1918 men (59.8%) and 131 of 620 women (21.1%) had visceral obesity. In multivariate analyses, visceral obesity was significantly associated with age, body mass index and triglyceride in both genders, high-density lipoproteins, uric acid levels, and daily alcohol consumption in men; and glycated hemoglobin (HbA1c) in women. In both multivariate and propensity score matching analyses, sleep duration of > 8 h and visceral obestiy showed a positive association in men but a negative association in women with statistical significance. In conclusion, our large-scale cross-sectional study in East Asia identified various gender-specific factors associated with visceral obesity including the long sleep duration., (© 2022. The Author(s).)

Objectives: Infant vaccination against the hepatitis B virus began in the World Health Organization South East Asia Region and the Western Pacific Region between 1983 and 2016. This systematic review examined the seroprevalence of hepatitis B surface antigen (HBsAg) in children and the rate of mother-to-child transmission (MTCT) in these regions between 1990 and 2020., Methods: MEDLINE and EMBASE were searched for articles published between January 1990 and September 2020, which reported seroprevalence of HBsAg in children aged 0-15 years and/or the rate of MTCT in the South East Asia Region and Western Pacific Region. A pragmatic review identified supporting information. This review was registered in the International Prospective Register of Systematic Reviews (#CRD42020211707)., Results: Of 115 included studies, 77 (24 countries) reported HBsAg prevalence, and 38 (nine countries) reported MTCT. The seroprevalence of HBsAg ranged between 0.0% and 27.4%, with a decreasing trend over time in each country. MTCT rates were 0.0-5.2% in infants of mothers who are hepatitis B e antigen-negative and 2.7-53.0% in infants of mothers who are hepatitis B e antigen-positive., Conclusion: After the introduction of infant hepatitis B virus vaccination programs, the countries in South East Asia Region and Western Pacific Region observed a reduction in HBsAg seroprevalence in children. Nevertheless, the risk of MTCT persists, emphasizing the importance of antenatal screening to identify high-risk pregnancies., Competing Interests: Declaration of competing interests KC declares no competing interests. YS received research grants from Gilead Sciences. ZM, NP, and CW received consulting fees from Sanofi. JCVZ and EV are Sanofi employees, a manufacturer, and distributor of many hepatitis B-containing combination vaccines and may hold shares and/or stock options in the company., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: To forecast the human immunodeficiency virus (HIV) incidence and mortality of post-neonatal population in East Asia including North Korea, South Korea, Mongolia, Japan and China Mainland and Taiwan province., Methods: The data on the incidence and mortality of HIV in post-neonatal population from East Asia were obtained from the Global Burden of Diseases (GBD). The morbidity and mortality of post-neonatal HIV population from GBD 2000 to GBD 2013 were applied as the training set and the morbidity and mortality from GBD 2014 to GBD 2019 were used as the testing set. The hybrid of ARIMA and LSTM model was used to construct the model for assessing the morbidity and mortality in the countries and territories of East Asia, and predicting the morbidity and mortality in the next 5 years., Results: In North Korea, the incidence and mortality of HIV showed a rapid increase during 2000-2010 and a gradual decrease during 2010-2019. The incidence of HIV was predicted to be increased and the mortality was decreased. In South Korea, the incidence was increased during 2000-2010 and decreased during 2010-2019, while the mortality showed fluctuant trend. As predicted, the incidence of HIV in South Korea might be increased and the mortality might be decreased during 2020-2025. In Mongolia, the incidence and mortality were slowly decreased during 2000-2005, increased during 2005-2015, and rapidly decreased till 2019. The predicted incidence and mortality of HIV showed a decreased trend. As for Japan, the incidence of HIV was rapidly increased till 2010 and then decreased till 2015. The predicted incidence of HIV in Japan was gradually increased. The mortality of HIV in Japan was fluctuant during 2000-2019 and was slowly decreased as predicted. The incidence and mortality of HIV in Taiwan during 2000-2019 was increased on the whole. The predicted incidence of HIV during was stationary and the mortality was decreased. In terms of China Mainland, the incidence and mortality of HIV was fluctuant during 2000-2019. The predicted incidence of HIV in China Mainland was stationary while the mortality was rapidly decreased., Conclusion: On the whole, the incidence of HIV combined with other diseases in post-neonatal population was increased before 2010 and then decreased during 2010-2019 while the mortality of those patients was decreased in East Asia., (© 2022. The Author(s).)

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021-2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020-2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 10 4.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs., Competing Interests: The funders did not have any influence on the analysis or interpretation of the results in this study. Authors declare no conflict of interest.

This study assesses governments' long-term non-pharmaceutical interventions upon the coronavirus disease 2019 (COVID-19) pandemic in East Asia. It advances the literature towards a better understanding of when and which control measures are effective. We (1) provide time-varying case fatality ratios and focus on the elderly's mortality and case fatality ratios, (2) measure the correlations between daily new cases (daily new deaths) and each index based on multiple domestic pandemic waves and (3) examine the lead-lag relationship between daily new cases (daily new deaths) and each index via the cross-correlation functions on the pre-whitened series. Our results show that the interventions reduce COVID-19 infections for some periods before the period of the Omicron variant. Moreover, there is no COVID-19 policy lag in Taiwan between daily new confirmed cases and each index. As of March 2022, the case fatality ratios of the elderly group in Japan, Hong Kong and South Korea are 4.69%, 4.72% and 1.48%, respectively, while the case fatality ratio of the elderly group in Taiwan is 25.01%. A government's COVID-19 vaccination distribution and prioritisation policies are pivotal for the elderly group to reduce the number of deaths. Immunising this specific group as best as possible should undoubtedly be a top priority.

In 2013, member states of the World Health Organization (WHO) South-East Asia Region* (SEAR) adopted the goal of measles elimination and rubella and congenital rubella syndrome control † by 2020 (1). In 2014, to provide impetus toward achieving this goal, the Regional Director declared measles elimination and rubella control one of the Regional Flagship Priorities. In 2019, SEAR member states declared a revised goal of eliminating both measles and rubella § by 2023 (2). The recommended strategies to achieve elimination include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities ¶ (SIAs); 2) developing and sustaining a sensitive and timely case-based surveillance system that meets recommended performance indicators**; 3) developing and maintaining an accredited laboratory network; 4) achieving timely identification, investigation, and response to measles outbreaks; and 5) collaborating with other public health initiatives to achieve the preceding four strategies. This report updates a previous report and describes progress toward measles elimination in SEAR during 2003-2020 (3). In 2002, coverage with the first dose of a measles-containing vaccine in routine immunization (MCV1) was 70%, and only three countries in SEAR had added a second routine dose of measles-containing vaccine in routine immunization (MCV2). During 2003-2020, all countries introduced MCV2, and estimated coverage with MCV1 increased 35%, from 65% to 88%, and coverage with MCV2 increased 1,233% from 6% to 80%. Approximately 938 million persons were vaccinated in SIAs. Annual reported measles incidence declined by 92%, from 57.0 to 4.8 cases per 1 million population, and estimated deaths decreased by 97%; an estimated 9.3 million deaths were averted by measles vaccination. By 2020, five countries were verified as having achieved measles elimination. To achieve measles elimination in the region by 2023, additional efforts are urgently needed to strengthen routine immunization services and improve measles-containing vaccine (MCV) coverage, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory capacity., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background and Aims: Asian countries are deemed to be high prevalence areas for gaming disorder (GD). This meta-analysis is the first to synthesize the overall prevalence of GD in East Asia and investigate characteristics that influence prevalence estimates., Methods: Systematic and independent searches were conducted across PubMed, Web of Science, Embase, PsycINFO, and the Cochrane Library since their inception to January 27, 2021. The Agency for Healthcare Research and Quality scale was used for quality assessment. A random effect model was used to calculate the overall GD prevalence and 95% confidence intervals (CIs)., Results: In total, 22 articles (26 studies) comprising 51,525 participants were included in this meta-analysis. The overall pooled prevalence of GD in East Asia was 12%, 95% CI (10%-15%); this figure was adjusted to 6%, 95% CI (3%-9%) for a representative sample. Higher prevalence was observed in males than in females (16% vs. 8%, respectively, P < 0.05). Subgroup and meta-regression analyses revealed that studies among gamers or those without random sampling reported significantly higher prevalence rates. There were no significant differences between countries/regions, sample size, quality score, proportion of males, and scale used., Discussion and Conclusions: The prevalence of GD in East Asia is higher than that in other world regions. Future studies should extend such epidemiological research to other regions to calculate the accurate prevalence of GD to benefit the local identification, prevention, policy formulation, and treatment efforts. Considering its negative effects, effective preventive and treatment measures for GD in East Asia need greater attention.

Kenji Shibuya and coauthors discuss the potential contribution of East Asian countries to global health in the light of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

Background: The East Asia region is facing an increasing burden of overweight, obesity and related noncommunicable diseases, resulting from an ongoing nutrition transition. This study aimed to document the growing burden of overweight and obesity, and the accompanying dietary shifts, in the East Asia region and describe the policy responses to this., Methods: We present noncommunicable disease risk factor collaboration data on trends in the burden of malnutrition, and Euromonitor International data on trends in dietary purchases, in the East Asia region. We searched the NOURISHING and GINA databases to identify food and nutrition policies implemented in these countries., Results: There is an ongoing nutrition transition in the East Asia region, notably in upper-middle and lower-middle income countries. The prevalence of overweight, obesity, and accompanying health conditions, purchases of ultra-processed foods and beverages, and purchasing from supermarkets, fast-food and takeaway outlets, and other convenience retailers, are increasing. The policy response to this nutrition transition is limited, with the majority of policies implemented in higher-income countries., Conclusions: East Asian countries are facing a growing burden of malnutrition, due in part to the dietary shifts occurring here. An ecological approach to policy intervention is needed to drive transformative food systems change., (© 2022 World Obesity Federation.)

Changes in the aerosol composition of sulfate (SO 4 2- ) and nitrate (NO 3 - ) from 2012 to 2019 have been captured as a paradigm shift in the region downwind of China. Specifically, SO 4 2- dramatically decreased and NO 3 - dramatically increased over downwind locations such as western Japan due to the faster reduction of SO 2 emissions than NO x emissions and the almost constant trend of NH 3 emissions from China. Emissions from China sharply decreased during COVID-19 lockdowns in February-March 2020, after which China's economic situation seemed to recover going into 2021. Given this substantial change in Chinese emissions, it is necessary to clarify the impact of long-range PM 2.5 transport into the leeward of East Asia. In this study, ground-based aerosol compositions observed at three sites in western Japan were analysed. The concentrations of PM 2.5 , SO 4 2- and NO 3 - decreased in 2020 (during COVID-19) compared with 2018-2019 (before COVID-19). In 2021 (after COVID-19), PM 2.5 and NO 3 - increased and SO 4 2- was unchanged. This suggests the returning long-range PM 2.5 transport in 2021. From numerical simulations, the status of Chinese emissions during COVID-19 did not explain this returning impact in 2021. This study shows that the status of Chinese emissions in 2021 recovered to that before COVID-19., (© 2022. The Author(s).)

Competing Interests: TM-MT was supported by research funding from the UK National Institute for Health Research (NIHR), NIHR Imperial Biomedical Research Centre, JP Moulton Charitable Foundation, and Leadiant Pharmaceuticals; and is a consultant for and shareholder in Zihipp, a company that develops gut hormone analogues of GLP-1, oxyntomodulin, glucose-dependent insulinotropic peptide, and peptide YY for obesity and diabetes. BK declares no competing interests.

Objective: To understand the epidemiology, current treatment, and disease burden of systemic lupus erythematosus (SLE) in the Asia Pacific (APAC) region., Methods: A targeted literature review of published evidence on SLE in the APAC region was conducted, using the Medline database (2008-2018), conference proceedings, and other supplementary sources., Results: The current review identified 70 studies conducted in China (n = 15), Japan (n = 13), Taiwan (n = 12), Korea (n = 9), Australia (n = 7), Hong Kong (n = 6), Singapore (n = 4), and multiple places within the APAC region (n = 4). Incidence rates (per 100,000 persons per year) ranged from 0.9-8.4, while prevalence rates ranged from 3.7-127 (per 100,000 persons); however, recent data were limited. Asian patients with SLE were reported to have higher disease severity, disease activity (higher SLE disease activity index scores), and organ damage accrual, along with increased morbidity, mortality, and susceptibility to renal involvement compared with other ethnicities in the APAC region. The risk of developing SLE is higher in the Asian population. Routinely used SLE therapies included belimumab, hydroxychloroquine, cyclophosphamide, tacrolimus, azathioprine, mycophenolate mofetil, and glucocorticoids; however, prescribing patterns varied across the region. Increased disease activity was associated with high economic burden and poor quality of life for SLE patients in the APAC region., Conclusion: SLE remains a disease with a significant unmet medical need for an innovative therapy that is well-tolerated and effective for patients in the APAC region. Further evidence is required to better characterize the disease and fully capture the burden and impact of SLE in the APAC region. This review has highlighted where there is a paucity of data from patients across the APAC region., (© 2020, American College of Rheumatology.)

Importance: Weight-for-height z score (WHZ) is a standard indicator of children's nutritional status even though it does not fully reflect body fat., Objective: To examine the combined association of WHZ and body fat with early development in the East Asia and Pacific region., Design, Setting, and Participants: Children from the East Asia-Pacific Early Child Development Scales validation study, with full data available regarding their nutritional status and outcomes, were included in this cross-sectional analysis. In brief, a multilevel stratified random sampling was used to select representative samples from each participating country in the study. WHZ and body fat were independently trichotomized using established references and were combined to form a 9-category exposure variable. Data collection was performed between 2012 and 2014, and the analyses were conducted in June 2021., Main Outcomes and Measures: The binary outcome variable of not being developmentally on track (hereafter referred to as poor development) was defined as a score less than the 25th percentile in the following domains: cognitive, language, socioemotional, motor development, and total development score. Poisson regression models were used to analyze the associations between the combined categories and poor development, adjusted for sociodemographic factors., Results: A total of 6815 children (mean [SD] age, 4.02 [0.8] years; 3434 girls [50.4%]) had full data available and were included in this study. Compared with children with normal weight and normal fat, those with wasting and low body fat had the highest likelihood of total poor development (prevalence ratio, 1.47; 95% CI, 1.28-1.70), followed by those with normal weight but low fat (prevalence ratio, 1.23; 95% CI, 1.11-1.36). Similar associations were found in language, cognitive, and socioemotional development, but not in motor development., Conclusions and Relevance: Poor development was more commonly found in children with low body fat independent of WHZ (wasted or normal weight). Early public health strategies may consider using a combination of WHZ and body fat as an indicator of poor development.

Background: The global epidemiological situation of gastric cancer has changed considerably over time, and it is essential to understand the epidemiological trends and future perspectives of gastric cancer., Summary: Although gastric cancer was common in the United States less than a century previously, it is no longer common in this country. Currently, over 60% of gastric cancers are found in Eastern Asia. In some Eastern Asian countries such as Japan and Korea, population-based gastric cancer screening has been conducted using upper gastrointestinal endoscopy or radiography to lower gastric cancer mortality. Due to earlier detection of gastric cancer, the survival of patients with gastric cancer is more favorable in these countries than in other Western countries. Even in Eastern Asia, a remarkable decrease in the age-standardized incidence and mortality of gastric cancer has been observed. This downward trend is mainly due to the reduced Helicobacter pylori infection, and this trend is considered to continue. Nevertheless, both the absolute number of incident cases and deaths of gastric cancer are still increasing at present due to the aging population. For the time being, the management of gastric cancer in elderly population is a critical issue in Eastern Asia. The absolute numbers of gastric cancer cases and deaths are believed to peak in the near future, following the decreasing age-standardized incidence and mortality. Key Messages: After a long period, gastric cancer may become a rare cancer even in Eastern Asia, and new efficient approaches for its prevention, screening, and treatment are warranted., (© 2021 S. Karger AG, Basel.)

Objective: Elder abuse (EA) is a critical social, health, and economic issue worldwide. To date, there is limited information on EA in certain similar culture-specific subpopulations, especially in East Asia. This study aims to summarize EA incidence in East Asia through a systematic review and meta-analysis and identify its variations and heterogeneity in the incidence estimates., Methods/design: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses protocol. Systematic review registration number PROSPERO CRD42020197131. A systematic literature search was performed to identify relevant articles published before July 5th, 2020, from six electronic databases. Two reviewers screened for relevance of the studies against eligible criteria and assessed the bias of the included studies independently. A random-effect model was adopted to estimate the incidence of EA, followed by subgroup analyses and multi meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analysis by Stata version 15.1., Results: Twelve eligible studies were included in the meta-analysis, which involved 79,395 subjects from 3 East Asian countries (China, Japan, and South Korea) ranging from 2004 to 2020. The overall incidence of EA was 78.33 per 1000 person-year (95% CI: 39.12-156.87) with high between-study variability (χ 2  = 15,568, d.f. = 11, p<0.001; I 2  = 99.9%). The sampling method, sample size, scope, instrument, data collection method, income classification, types of participants, and urbanity are all the sources of heterogeneity, which can explain nearly 100% of the variance between studies., Conclusions: The incidence of EA in this study is not as high as the global level. It may be furtherly underestimated in East Asia due to cultural norms. It is imperative to develop a culture-tailored EA assessment instrument to evaluate potential victims. Future studies should also identify more effective educational programs to raise the public's awareness and promote recognition ability., (© 2021 John Wiley & Sons Ltd.)

Hepatitis E virus (HEV) infection is an emerging zoonotic viral disease, with an increasingly international public health challenge. Despite the concerns that the global disease burden may be underestimated. Therefore, evaluation of the disease epidemiology in South - eastern Asia through a systematic review will assist in unraveling the burden of the disease in the subregion. A priori protocol was prepared for the systematic review and followed by a literature search involving five electronic databases. Identified publications were screened for high quality studies and the elimination of bias and relevant data extracted. A total of 4157 citations were captured, and only 35 were included in the review. A wide range of HEV seroprevalence was recorded from 2% (urban blood donors in Malaysia) to 77.7% (lowland communities in Lao PDR). Sporadic HEV infection and epidemics were also detected in the subregion. Indicating hyperendemicity of the disease in South - eastern Asia.

Kawasaki disease (KD) is an acute systemic vasculitis that occurs predominantly in children under 5 years of age. Despite much study, the etiology of KD remains unknown. However, epidemiological and immunological data support the hygiene hypothesis as a possible etiology. It is thought that more sterile or clean modern living environments due to increased use of sanitizing agents, antibiotics, and formula feeding result in a lack of immunological challenges, leading to defective or dysregulated B cell development, accompanied by low IgG and high IgE levels. A lack of B cell immunity may increase sensitivity to unknown environmental triggers that are nonpathogenic in healthy individuals. Genetic studies of KD show that all of the KD susceptibility genes identified by genome-wide association studies are involved in B cell development and function, particularly in early B cell development (from the pro-B to pre-B cell stage). The fact that intravenous immunoglobulin is an effective therapy for KD supports this hypothesis. In this review, I discuss clinical, epidemiological, immunological, and genetic studies showing that the etiopathogenesis of KD in infants and toddlers can be explained by the hygiene hypothesis, and particularly by defects or dysregulation during early B cell development.

This study investigated the environmental spatial heterogeneity of novel coronavirus (COVID-19) and spatial and temporal changes among the top-20 metropolitan cities of the Asia-Pacific. Remote sensing-based assessment is performed to analyze before and during the lockdown amid COVID-19 lockdown in the cities. Air pollution and mobility data of each city (Bangkok, Beijing, Busan, Dhaka, Delhi, Ho Chi Minh, Hong Kong, Karachi, Mumbai, Seoul, Shanghai, Singapore, Tokyo, Wuhan, and few others) have been collected and analyzed for 2019 and 2020. Results indicated that almost every city was impacted positively regarding environmental emissions and visible reduction were found in Aerosol Optical Depth (AOD), sulfur dioxide (SO 2 ), carbon monoxide (CO), and nitrogen dioxide (NO 2 ) concentrations before and during lockdown periods of 2020 as compared to those of 2019. The highest NO 2 emission reduction (~ 50%) was recorded in Wuhan city during the lockdown of 2020. AOD was highest in Beijing and lowest in Colombo (< 10%). Overall, 90% movement was reduced till mid-April, 2020. A 98% reduction in mobility was recorded in Delhi, Seoul, and Wuhan. This analysis suggests that smart mobility and partial shutdown policies could be developed to reduce environmental pollutions in the region. Wuhan city is one of the benchmarks and can be replicated for the rest of the Asian cities wherever applicable., (© 2021. The Author(s).)

Chronic active Epstein-Barr virus (CAEBV) disease is a rare condition characterised by persistent EBV infection in previously healthy individuals. Defective EBV genomes were found in East Asian patients with CAEBV. In the present study, we sequenced 14 blood EBV samples from three UK patients with CAEBV, comparing the results with saliva CAEBV samples and other conditions. We observed EBV deletions in blood, some of which may disrupt viral replication, but not saliva in CAEBV. Deletions were lost overtime after successful treatment. These findings are compatible with CAEBV being associated with the evolution and persistence of EBV + haematological clones that are lost on successful treatment., (© 2021 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)