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Background: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan., Methods: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival., Results: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89)., Conclusions: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival., (© 2024. The Author(s).)

Background/aim: Hallux valgus (HV) is the most prevalent deformity affecting the forefoot; however, its genetic etiology remains unclear. In the literature, vitamin D receptor (VDR) genotypes have been reported to be associated with the risk of skeletal malformations accompanied by inflammation. This study aimed to examine the hypothesis that VDR genotypes are associated with the risk of HV., Materials and Methods: The VDR rs731236, rs1544410, rs2228570 and rs7975232 genotypes of 150 HV patients and 600 non-HV subjects were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology and examined regarding their associations with HV risk., Results: The results showed that none of the genetic frequency distributions of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significant between the HV cases and non-HV controls (p for trend=0.4055, 0.2170, 0.7220, 0.5509, respectively). Additionally, allelic frequency analysis showed that none of the allelic frequencies of VDR rs731236, rs1544410, rs2228570, or rs7975232 were significantly distributed (p=0.2285, 0.1572, 0.9278, and 0.5547, respectively). Furthermore, stratified analysis showed that no correlation was observed between VDR rs731236 and different age groups (either younger or older than 51) or sex (p=0.3953 and p=0.9576). Moreover, no correlation was found between VDR rs731236 genotype and the risk of HV in individuals within subgroups of height, weight, or body mass index (BMI) (p=0.8317, 0.5346, and p=0.8783, respectively)., Conclusion: VDR rs731236, rs1544410, rs2228570, and rs7975232 may not serve as indicators for a higher risk of HV., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: The updated World Health Organization 2020 guidelines strongly recommend an optimal physical activity level of 150-300 min/week for older adults. However, few studies have examined the relationship between different levels of physical activity and sarcopenia. Therefore, the purpose of this study was to investigate the cross-sectional associations between overall physical activity levels, gender, intensity, and the risk of sarcopenia among older Taiwanese adults., Methods: A nationwide cross-sectional telephone survey of older adults (≥ 65 years) was conducted in Taiwan from October 2019 to January 2020. Participants were interviewed to collect self-reported data on their level of physical activity (measured by the Taiwanese version of the IPAQ-SF), sarcopenia risk (measured by the SARC-F questionnaire), and sociodemographics., Results: A total of 1068 older adults were surveyed. Compared with the optimal physical activity level recommendations in the WHO guidelines and after adjusting for potential confounders and proposing an association independent of sedentary behavior, older adults with insufficient physical activity levels (< 150 min/week) were more likely to have a higher risk of sarcopenia (OR: 3.24; CI: 1.67-6.27), whereas older adults who exceeded physical activity guidelines (> 300 min/week) were more likely to have a lower risk of sarcopenia (OR: 0.39; CI: 0.20-0.78). Maintaining moderate-intensity physical activity is essential for older adults, as physical activity that exceeds the guidelines can significantly lower the risk of sarcopenia; meanwhile, insufficient physical activity can greatly increase it. Also, there seems to be a similar association between sarcopenia risk across different physical activity levels in vigorous-intensity physical activities in older adults. However, due to the small number of sarcopenia-risk participants who met or exceeded vigorous-intensity physical activity levels, further comparisons between different vigorous-intensity physical activity levels did not show significant differences in sarcopenia risk. Additionally, insufficient physical activity was found to be an important risk factor for sarcopenia in both genders, while physical activity that exceeded the guidelines prevented sarcopenia in females., Conclusions: The findings of this study highlight the potential dose-response relationship related to physical activity. The 2020 WHO guidelines provide the public with minimum recommendations for physical activity. However, exceeding these recommended levels appears to be more effective in preventing sarcopenia in older adults and may offer even greater health benefits. Future research should further explore whether exceeding these guidelines could result in additional health benefits., (© 2024. The Author(s).)

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10 - 5 . A total of 132 SNPs reached a threshold of P < 5 × 10 - 8 using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Over the past two decades, the Taiwan government promulgated some regulatory measures and promotional actions on energy efficiency promotion and renewable energy development. In March 2022, the "Taiwan's Pathway to Net-Zero Emissions in 2050" was announced to respond to the Paris Agreement. In order to achieve the goal, the Climate Change Response Act (CCRA) was passed on February 15, 2023, requiring the de-carbonization measures and adaptation strategies. The main aim of this paper was to analyze the changes in GHG emissions and renewable energy supply by using the updated data from the official statistics in connection with the trends of environmental and energy sustainability since 2000. The findings showed that total installed capacity of renewable power (especially in solar power and wind power) showed an amazing increase over the past decade, leading to the inclined GHG emissions and thus supporting the environmental and energy sustainability toward a low-carbon society. Furthermore, this paper summarized the development history and main differences concerning the carbon neutrality policy and legislation in Japan and South Korea. For achieving the staged targets of GHG emissions by 2030 and 2050, this paper finally addressed the technological approaches for achieving carbon neutrality by 2050 in Taiwan, focusing on the transformation of energy and industry, and the policy implications by all levels of government., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The European Leukemia Net recommendations provide valuable guidance in treatment decisions of patients with acute myeloid leukemia (AML). However, the genetic complexity and heterogeneity of AML are not fully covered, notwithstanding that gene expression analysis is crucial in the risk stratification of AML. The Stellae-123 score, an AI-based model that captures gene expression patterns, has demonstrated robust survival predictions in AML patients across four western-population cohorts. This study aims to evaluate the applicability of Stellae-123 in a Taiwanese cohort. The Stellae-123 model was applied to 304 de novo AML patients diagnosed and treated at the National Taiwan University Hospital. We find that the pretrained (BeatAML-based) model achieved c-indexes of 0.631 and 0.632 for the prediction of overall survival (OS) and relapse-free survival (RFS), respectively. Model retraining within our cohort further improve the cross-validated c-indexes to 0.667 and 0.667 for OS and RFS prediction, respectively. Multivariable analysis identify both pretrained and retrained models as independent prognostic biomarkers. We further show that incorporating age, Stellae-123, and ELN classification remarkably improves risk stratification, revealing c-indices of 0.73 and 0.728 for OS and RFS, respectively. In summary, the Stellae-123 gene expression signature is a valuable prognostic tool for AML patients and model retraining can improve the accuracy and applicability of the model in different populations., (© 2024. The Author(s).)

Most studies investigating the association between physical activity and osteoporosis prevention only focused on specific types of physical activity. This study's evidence regarding the combined effects or interaction of sleep duration and physical activity. The findings emphasize the role of sleep duration and physical activity in association with osteoporosis., Purpose: The associations between physical activity, sleep duration, and prevalent osteoporosis in Taiwanese adults were studied in this cross-sectional study., Methods: The Taiwan Biobank enrolled a community-based cohort of ~ 120,000 volunteers (as of April 30, 2020) between 30 and 76 years of age with no history of cancer. Amongst, bone mineral density (BMD) measures by dual-energy X-ray absorptiometry (DXA) were available in 22,402 participants. After excluding individuals who had no complete data of BMI (n = 23), MET score (n = 207), T-score (n = 8,826), and sleep duration (n = 16), 13,330 subjects were included as the primary cohort. Univariate and multivariable regression analyses were performed to determine the associations between the presence of osteoporosis, physical activity level, sleep duration, and other variables., Results: The results showed that after adjustment, subjects with physical activity < 20 METs/week and ≥ 20 METs/week (aOR = 1.017 and 0.767, respectively) were associated with risk of osteoporosis than those with zero MET. The odds of osteoporosis were not significantly lower in subjects who slept for ≥ 8 h/day (aOR = 0.934,p=0.266). In addition, compared to short sleepers with no physical activity, adults with increased physical activity ≥ 20 METs/week and sleep ≥ 8 h/day had a significantly lowest likelihood of osteoporosis (aOR = 0.702). Those with medium physical activity (< 20 METs/week) plus average sleep duration (6.5-8 h/day) did not have significant higher odds of osteoporosis (aOR = 1.129,p=0.151)., Conclusion: The findings emphasize the joint role of sleep duration and physical activity in association with osteoporosis. Adults with high physical activity plus high sleep hours have the highest BMD and lowest risk of osteoporosis., (© 2023. The Author(s).)

Background: Enterobacterales carrying bla NDM represent an emerging challenge in treating infectious diseases. In this study, we aimed to investigate the characteristics of bla NDM -producing Enterobacterales from three hospitals in southern Taiwan., Methods: Enterobacterales strains that were nonsusceptible to more than one carbapenem (ertapenem, meropenem, imipenem, or doripenem) were collected from hospitalized patients. Molecular typing for New Delhi metallo-β-lactamase (NDM) and antibiotic susceptibility tests were performed, followed by multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and plasmid analysis by PCR-based replicon typing., Results: A total of 1311 carbapenem-nonsusceptible Enterobacterales were isolated from 2017 to 2021. bla NDM -encoding genes were detected in 108 isolates, with 53 (49.1%) harboring bla NDM-1 and 55 (50.9%) harboring bla NDM-5 . The rate of bla NDM-1 detection among isolates decreased to 2% in 2021. However, the rate of E. coli harboring bla NDM-5 increased from 1% to 12% of total isolates during the study period. Of 47 NDM-5-positive E. coli isolates, 44 (93.6%) were ST8346 with high genetic relatedness. E. coli ST8346 isolates showed high-level resistance to both carbapenems and aminoglycosides. Most (38 out of 47, 80.9%) bla NDM-5 -harboring E. coli isolates co-harbored bla OXA-181 . We analyzed the regions harboring bla NDM-5 in E. coli ST8346 via PCR amplification. bla NDM-5 and bla OXA-181 were located on two separate plasmids, IncF and IncX3, respectively., Conclusion: The dissemination of E. coli ST8346 caused an increase in bla NDM-5 and bla OXA-181 co-harboring Enterobacterales in southern Taiwan, which show high-level resistance to both carbapenems and aminoglycosides. We identified a distinct IncF plasmid encoding bla NDM-5 that has the potential for rapid spread and needs further surveillance., 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Traditional Chinese medicine (TCM) is widely used by ethnic Chinese communities. TCM is covered by Taiwan's National Health Insurance (NHI) program. We evaluated the efficacy and outcomes of complementary Chinese herbal medicine (CHM) therapy in patients with cancer., Methods: This population-based cohort study was conducted using the data of patients who received a cancer diagnosis between 2005 and 2015 in Taiwan. Eligible patients were divided into standard and complementary CHM therapy groups. The complementary CHM therapy group was further divided into low cumulative dosage (LCD), medium cumulative dosage (MCD), and high cumulative dosage (HCD) subgroups. Overall survival (OS), mortality risk, cancer recurrence, and metastasis were analyzed for all cancers and five major cancers (lung, liver, breast, colorectal, and oral cancers)., Results: We included 5707 patients with cancer (standard therapy, 4797 [84.1%]; complementary CHM therapy, 910 [15.9%]; LCD, 449 [7.9%]; MCD, 374 [6.6%], and HCD, 87 [1.5%]). For the LCD, MCD, and HCD subgroups, the mortality risk was 0.83, 0.64, and 0.45, and the 11-year OS, 5-year cumulative cancer recurrence, and 5-year cumulative cancer metastasis rates were 6.1 ± 0.2, 6.9 ± 0.2, and 8.2 ± 0.4 years; 39.2%, 31.5%, and 18.8%; and 39.5%, 32.8%, and 16.6%, respectively. The cumulative cancer recurrence and metastasis rates of the standard therapy group were 40.9% and 32.8%, respectively. The cumulative recurrence and metastasis rates of all cancers, lung cancer, and liver cancer and all cancers, colorectal cancer, and breast cancer, respectively, were significantly lower in the HCD subgroup than in the other subgroups and standard therapy group ( p < 0.05)., Conclusion: Patients receiving complementary CHM therapy may have prolonged OS and reduced risks of mortality, recurrence, and metastasis. A dose-response relationship was noted between CHM therapy and mortality risk: increased dosage was associated with improved OS and reduced mortality risk., Competing Interests: Conflicts of interest: Dr, Shinn-Jang Hwang, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Proper taxonomic identification is critical to our understanding of biodiversity and the underlying evolutionary history. Here we re-examine the cast of the holotype of Chinemys pani, a geoemydid turtle from the Pleistocene of Taiwan; the actual specimen was not curated appropriately after the original publication and was most likely lost. Our results provide substantial evidence to show that Chinemys pani should be identified as Mauremys reevesii. The replica, though not ideal, preserves various morphological features that allow reliable taxonomic identification of Mauremys reevesii, including the presence of three longitudinal keels on the carapace, the second to sixth neural bones anteriorly short-sided, and the lack of a movable plastral hinge. In addition, we also confirm that the original diagnostic features that established the new taxon: Chinemys pani - are polymorphic characters of Mauremys reevesii. Our taxonomic revision of a Pleistocene geoemydid turtle from Taiwan confirms the existence of the Pleistocene Mauremys reevesii. More importantly, this study offers new insights into the origin of modern biodiversity in Taiwan and gives a straightforward example of how fossils can be applied to conservation policies., (© 2022 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Pelvic-acetabular fractures lead to high mortality in elders and their association between different groups is not known. Our results indicate that older age with pelvic-acetabular fracture was significantly associated with mortality. This finding may help planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures., Purpose: Pelvic or acetabular fractures are among main outcomes of low-energy trauma such as falls, especially in older adults. They represent approximately 3-8% of all fractures and are associated with a high mortality rate ranging from 4 to 28%. This study is aimed at comparing the incidence and trends of hip fractures and pelvic-acetabular fractures in the Taiwanese general population, gender differences in adults aged over 65 years, and mortality risk between pelvic or acetabular fractures and hip fractures and surgery trends in patients with these fractures., Methods: A retrospective study was conducted extracting data from the National Health Insurance Research Database of patients diagnosed with hip fracture and pelvic acetabular fracture between 2000 and 2018., Results: Older age with pelvic-acetabular fracture was significantly associated with increased mortality. No significant differences were found in comorbidities between the two fracture groups. Results provide clear epidemiological evidence for trends in pelvic-acetabular fractures in Taiwan and demonstrate the need for better strategies to manage these fractures and comorbidities, particularly in older adults., Conclusion: Findings of this study may aid in planning and allocating healthcare resources, risk stratification, and optimizing the treatment of pelvic fractures among older adults in Taiwan., (© 2023. The Author(s).)

Background and Objectives : In 2004, the Health Administration of Taiwan began to promote a hospital-based cancer screening quality improvement program, under the principle that "prevention is better than therapy". The aim of this study was to evaluate the effectiveness of colorectal cancer (CRC) screening in patients who received a fecal immunochemical test (FIT) at a hospital in central Taiwan. Materials and Methods : This was a retrospective study. Results : Fecal occult blood immunoassays for CRC screening were conducted in 58,891 participants, of whom 6533 were positive (positive detection rate 11.10%). The positive patients then underwent colonoscopy, and the detection rates of polyps and CRC accounted for 53.6% and 2.4% of all colonoscopy-confirmed diagnoses (3607), respectively. We further enrolled data from patients diagnosed with CRC at our hospital from 2010 to 2018. The patients with CRC were divided into two groups according to whether or not they had received fecal occult blood screening. Among the 88 patients with CRC by screening, 54 had detailed medical records including cancer stage. Of these 54 patients, 1 (1.8%) had pre-stage, 11 (20.4%) had stage I, 24 (44.4%) had stage II, 10 (18.5%) had stage III, and 8 (14.8%) had stage IV CRC. The early cancer detection rates of the screening and non-screening groups were 66.7% and 52.7%, respectively, and the difference was significant ( p = 0.00130). Conclusions : In this study, screening with FIT significantly increased the early detection of CRC. The main advantage of FIT is the non-invasiveness and low cost. It is hoped that the further adoption of early screening can increase the detection rates of colorectal polyps or early cancer to improve survival, reduce the high cost of subsequent cancer treatment, and reduce the burden on the patient and healthcare system.

Background: Aedes aegypti is the major vector of dengue that threatens public health in tropical and subtropical regions. Pyrethroid-based control strategies effectively control this vector, but the repeated usage of the same insecticides leads to resistance and hampers control efforts. Therefore, efficient and prompt monitoring of insecticide resistance in local mosquito populations is critical for dengue control., Methodology/principal Finding: We collected Ae. aegypti in southern Taiwan in March and October 2016. We analyzed the voltage-gated sodium channel (vgsc) genotypes of parentals (G0) and G1 adults after cypermethrin insecticide bioassay. Our results showed that four VGSC mutations (S989P, V1016G, F1534C, and D1763Y) associated with resistance were commonly detected in field-collected Ae. aegypti. The frequencies of these four mutations in the local mosquito population were significantly higher in October (0.29, 0.4, 0.27 and 0.11) than in March (0.09, 0.16, 0.18 and 0.03). Specific vgsc combined genotypes composed of the one to four such mutations (SGFY/SGFY, SVCD/SVCD, SGFY/PGFD, SVCD/SGFY, PGFD/PGFD, and SVCD/PGFD) shifted towards higher frequencies in October, implying their resistance role. In addition, the cypermethrin exposure bioassay data supported the field observations. Moreover, our study observed an association between the resistance level and the proportion of resistance genotypes in the population., Conclusions/significance: This is the first study to demonstrate the role of four-locus vgsc genotypes in resistance evaluation in a local Ae. aegypti population in Taiwan. This alternative method using resistance-associated genotypes as an indicator of practically insecticide resistance monitoring is a useful tool for providing precise and real-time information for decision makers., Competing Interests: The authors have declared that no competing interests exist.

Background: Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci associated with height, mainly in individuals of European ancestry., Methods: We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p-value threshold method. We also examined the association between genetically determined height (PRS 251 ) and measured height (phenotype). We performed observational (phenotype) and genetic PRS 251 association analyses of height and health-related outcomes., Results: GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci (EFEMP1, DIS3L2, ZBTB38, LCORL, HMGA1, CS, and GDF5) previously reported to play a role in height. There was a positive association between PRS 251 and measured height (p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits (p < 0.05/[14 + 49]). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol (p < 0.05/[14 + 49])., Conclusions: This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan., (© 2022. The Author(s).)

Background: Allogeneic stem cell transplantation (allo-HSCT) is the ultimate cure for acute lymphoblastic leukemia (ALL)., Aim: This study was performed to compare the outcomes of ALL patients receiving busulfan (Bu) with cyclophosphamide (Cy)-based or total body irradiation (TBI)-based regimen in a Chinese population., Methods: We enrolled 224 adult patients with ALL who received allo-HSCT at National Taiwan University Hospital between 1997 and 2016., Results: The median age at transplantation was 33 years. Before allo-HSCT, 75.9% of patients attained first or late complete remission. A total of 141 patients (62.9%) received Bu/Cy-based conditioning, either myeloablative (MA) or reduced-intensity stem cell transplantation (RIST), and 83 patients received a TBI-based regimen (MA-TBI). Patients receiving the MA-Bu regimen had longer relapse-free survival (RFS) than those receiving the MA-TBI regimen (median, 24.1 vs. 6.7 months, p = .044). There was no difference in overall survival (OS, MA-Bu vs. MA-TBI vs. RIST-Bu: 39.4 vs. 28.2 vs. 13.1 months, p = .276), treatment-related mortality (TRM), or incidences of grade 3-4 acute graft-versus-host disease (GvHD). Among patients receiving identical GvHD prophylactic regimens, there was no difference between MA-Bu and MA-TBI groups regarding the incidence of grade 3-4 acute GvHD, grade 2-4, and all-grade chronic GvHD. In subgroup analysis, patients receiving oral busulfan had comparable RFS and OS to the intravenous busulfan group (p = .436 and p = .236, respectively), but a higher TRM (25% vs. 9.8%, p = .016). In the multivariable analysis, disease status before allo-HSCT was the only risk factor impacting RFS and OS., Conclusion: In summary, patients receiving Bu/Cy-based or TBI-based regimens as conditioning had similar results in terms of OS, TRM, and acute GvHD, whereas the use of myeloablative Bu/Cy resulted in a better RFS. A Bu-based regimen could be an alternative conditioning choice for patients who are ineligible to receive TBI. Prospective and randomized controlled trials are warranted to validate the long-term outcomes., (© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

This study aimed to explore the lived experiences of Taiwanese older adults with disabilities newly admitted to long-term care facilities (LTCFs). A descriptive phenomenological method was used. Colaizzi's method analysis of 15 participant interviews revealed six themes: "living here is a last resort", "I don't like it but still have to live here", "my needs are not understood", "looking forward to emotional support", "practicing the way of survival", and "trying to make myself better". The older adults were admitted to the LTCF as they or their family members could not take care of themselves due to their disability. Participants explained their new life in the LTCF was like a prison, it was not easy for their needs to be understood. They used self-adjustment and established relationships with staff in the LTCF in order to live a stable life. They lived their lives with silence and alertness to practice the way of survival. They strived to make themselves better through rehabilitation, taking good care of their bodies, and finding their focus and value of life. It is important to pay attention to the care needs as well as life adjustment problems for newly older adults with disabilities in order to assist them in opening up new life experiences in LTCFs.

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels., 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 © 2021. Published by Elsevier B.V.)

Background/purpose: FAST and Stroke-112 are two campaigns to reduce the emergency room arrival time of stroke patients. No study has compared the effectiveness of these campaigns. This study aimed to compare recalling capacity of people in these two campaigns., Methods: A prospective, open-label randomized study was conducted in 2019. Recall ability for the items of the two campaigns on the 5th and 30th days post-education was compared using non-parametric methods. Subject characteristics including age, education level, presence of stroke in co-residents, and habitual language were evaluated using multiple ordered logistic regression., Results: There were 202 participants in FAST group and 193 participants in Stroke-112 group who completed the study. No differences were observed between the two groups in recall ability, either on day 5 or day 30 after receiving education. For both campaigns, recall ability was better for signs in the face (FAST: 87.1%, Stroke-112: 86.5%) and the arm (FAST: 87.1%, Stroke-112: 88.1%) than for abnormality in speech (FAST: 78.7%, Stroke-112: 76.7%) on day 5. Recall ability on day 30 remained the same only for the arm item (FAST: 86.1%, Stroke-112: 88.6%). The recall ability was correlated to education level equal or more than 7 years in FAST group, and was inversely correlated to age and being a stroke patient in Stroke-112 group., Conclusion: We found no difference in recall ability between the 2 campaigns. Education level was associated with recallability of FAST, and age and stroke history were associated with recallability of Stroke-112., Competing Interests: Conflict of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Carpal tunnel syndrome (CTS), 1 of the most common peripheral neuropathies of the upper extremity, has been studied for decades regarding its epidemiology and associated medical conditions. We conducted a large-scale, age- and gender-matched study from an Asian population database to investigate the relationship between the incidence and the demographic characteristics., Methods: A retrospective cohort study using data of National Health Insurance Research Database was conducted. One million enrollees in Taiwan was used to identify 9442 patients with CTS and 37,768 randomly selected controls, in a control-case ratio of 4:1. Diagnoses of CTS were ascertained from January 1, 2003, to December 31, 2012. Sociodemographic and medical characteristics were evaluated to assess the correlation with CTS., Results: Annual incidence of CTS was approximately 0.4% during the 10-year-period in Taiwan, with higher incidence rate in female sex and middle age of group (50-59 years). Among the medical conditions, previous wrist injuries, obesity, gout, and rheumatoid arthritis were associated with CTS most significantly., Conclusions: Carpal tunnel syndrome has presented a relatively constant incidence in Taiwan. Female gender with middle age seemed to have the highest incident rate during a 10-year period from 2003 to 2012. Among the risk factors of CTS, previous wrist injuries, obesity, gout, and rheumatoid arthritis were demonstrated to be the most significantly correlated comorbidities., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Health literacy (HL), which is a determinant of individuals' health as well as a personal and public asset, can be improved by community healthcare providers (CHPs) with the capability of providing HL services. The purpose of this study was to explore CHPs' familiarity with and attitudes toward HL and their confidence in implementing HL practices. A cross-sectional online survey was conducted involving a total of 104 CHPs from 20 public health centers in Taiwan. It was based on a structured questionnaire involving self-evaluation by participants. The scores for familiarity, attitudes, and confidence in implementing HL practices were mean = 4.36, SD = 1.99; mean = 7.45, SD = 1.93; and mean = 6.10, SD = 1.77 (out of 10 points), respectively. The results of the multiple regression analysis showed that the two independent variables of familiarity and attitude could predict confidence in implementing HL practices (R 2 = 0.57, F(2101) = 58.96, p < 0.001). The CHPs surveyed were not especially familiar with HL; thus, they recognized its importance, but they lacked confidence in implementing HL practices. Increasing practitioners' familiarity with HL may therefore boost their confidence in implementation. The research results can serve as a reference when planning HL education and training.

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan's herbal medicines adverse reaction database and facilitate epidemiological analysis., (© 2021. The Author(s).)

Circadian pattern influence on the incidence of out-of-hospital cardiac arrest (OHCA) has been demonstrated. However, the effect of temporal difference on the clinical outcomes of OHCA remains inconclusive. Therefore, we conducted a retrospective study in an urban city of Taiwan between January 2018 and December 2020 in order to investigate the relationship between temporal differences and the return of spontaneous circulation (ROSC), sustained (≥24 h) ROSC, and survival to discharge in patients with OHCA. Of the 842 patients with OHCA, 371 occurred in the daytime, 250 in the evening, and 221 at night. During nighttime, there was a decreased incidence of OHCA, but the outcomes of OHCA were significant poor compared to the incidents during the daytime and evening. After multivariate adjustment for influencing factors, OHCAs occurring at night were independently associated with lower probabilities of achieving sustained ROSC (aOR = 0.489, 95% CI: 0.285-0.840, p = 0.009) and survival to discharge (aOR = 0.147, 95% CI: 0.03-0.714, p = 0.017). Subgroup analyses revealed significant temporal differences in male patients, older adult patients, those with longer response times (≥5 min), and witnessed OHCA. The effects of temporal difference on the outcome of OHCA may be a result of physiological factors, underlying etiology of arrest, resuscitative efforts in prehospital and in-hospital stages, or a combination of factors.

Background: Respiratory viruses (RVs) are among the most common pathogens for both upper and lower respiratory tract infections (RTIs). However, the viral epidemiology of RV-associated RTIs in adults has long been under-recognized. Through a sensitive molecular assay, it would be possible to have a better understanding of the epidemiology of RV-associated RTIs., Material and Methods: Respiratory tract (RT) specimens from adults hospitalized due to RTIs were tested for RVs, using the multiplex PCR-based Luminex xTAG® Respiratory Viral Panel assay. A total of nineteen RVs, including influenza viruses and non-influenza respiratory viruses (NIRVs) were detected. Positive rates were compared using a chi-square test., Results: A total of 2292 samples from adult patients hospitalized with RTIs were screened for RVs. The overall positive rate was 22%, with 17.8% samples positive for at least one NIRV. NIRVs had a higher positive rate in non-winter seasons. As many as 12.7% (46/363) of the samples collected through broncho-alveolar lavage and 20.5% (176/859) of the samples collected in ICUs were positive for RVs. Distribution of corona virus (CoV), human metapneumovirus (hMPV) and parainfluenza virus (PIV) demonstrated seasonal variation. Also, temperature was associated with the positive rates of specific viruses, including CoV, respiratory syncytial virus (RSV), hMPV and PIV., Conclusion: Respiratory viruses, notably NIRVs, were frequently detected in adults hospitalized with RTIs. Several RVs were detected with distinctive seasonal variations. A substantial number of RVs were identified in lower RT specimens or from patients admitted to ICU, highlighting their important role in causing severe respiratory infection., (Copyright © 2020. Published by Elsevier B.V.)

Objective,: To investigate the genetic characteristics of idiopathic central precocious puberty (ICPP) and validate its polygenic risk for early puberty., Design and Methods: A bootstrap subsampling and genome-wide association study were performed on Taiwanese Han Chinese girls comprising 321 ICPP patients and 148 controls. Using previous GWAS data on pubertal timing, a replication study was performed. A validation group was also investigated for the weighted polygenic risk score (wPRS) of the risk of early puberty., Results: A total of 105 SNPs for the risk of ICPP were identified, of which 22 yielded an area under the receiver operating characteristic curve of 0.713 for the risk of early puberty in the validation group. A replication study showed that 33 SNPs from previous GWAS data of pubertal timing were associated with the risk of ICPP (training group: P-value < 0.05). In the validation group, a cumulative effect was observed between the wPRS and the risk of early puberty in a dose-dependent manner (validation group: Cochran-Armitage trend test: P-value < 1.00E-04; wPRS quartile 2 (Q2) (odds ratio (OR) = 5.00, 95% CI: 1.55-16.16), and wPRS Q3 (OR = 11.67, 95% CI: 2.44-55.83))., Conclusions: This study reveals the ICPP genetic characteristics with 22 independent and 33 reported SNPs in the Han Chinese population from Taiwan. This study may contribute to understand the genetic features and underlying biological pathways that control pubertal timing and pathogenesis of ICPP and also to the identification of individuals with a potential genetic risk of early puberty.

Objective: The recruitment of obstetrics and gynecology residents has been challenging in Taiwan since 2000. There are a lots factors influencing applying, including career interest and prospects, lifestyle, salary, litigation, stress level, time demands of specialty work and gender consideration. The purpose of this study was to evaluate the factors influencing the career choice of current OB/GYN residents and identify the important factors influencing recruitment., Materials and Methods: A cross-sectional questionnaire of career-decision factors was sent to all 280 residents during December, 2019. Total 16 factors were rated on a 5-point Likert and were ranking by their average score on the scale. Gender of residents was analyzed for their association with the scores by a two-sample test and two-tailed t test., Results: 91 (32.5%) residents responded and 61 were female and 30 were male. The top influencing factor was being interested in clinical expertise with an average score of 4.32. The second factor was having a great sense of accomplishment in saving people with an average score of 3.82, followed by it being easier to become a medical practitioner at 3.77. The lowest scoring factor was fewer hours of work, with an average score of 1.77 and a safer working environment with a score of 2.33 was the second lowest factor. Female residents agreed that it was easier to get specialist certification with a score of 3.0. This score was significantly higher than male doctors at 2.63 with p value of 0.017., Conclusion: Career interest and prospects were key influencing factors for applying OB/GYN residents. Minimizing the influence of detracting factors like heavy workload and medical litigation was also effective. Enrolling new residents is key to maintaining adequate staffing in specialties in healthcare. Establishing a safer work environment and determining the optimal workload will be the next reforms in the future., (Copyright © 2021. Published by Elsevier B.V.)

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195-2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427-3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.

Background: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan., Methods: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment., Results: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P < 0.001), and 6-min walk distance improved from 344 ± 147 to 450 ± 120 m (P = 0.014). Additionally, the plasma level of N-terminal pro-brain natriuretic peptide significantly decreased (P = 0.007). Hemodynamic data were available in 11 patients after ≥3 BPA sessions. Both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 44.6 ± 11.7 mmHg to 32.6 ± 5.1 mmHg (P = 0.005) and 745 ± 389 dyn·s·cm -5 to 366 ± 120 dyn·s·cm -5 (P = 0.002), respectively. Cardiac output also increased from 3.69 ± 1.12 L/min to 4.33 ± 0.94 L/min (P = 0.021)., Conclusion: BPA improved both clinical symptoms and hemodynamic data in inoperable CTEPH Taiwanese patients without major periprocedural complications., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To develop a deep learning image assessment software VeriSee™ and to validate its accuracy in grading the severity of diabetic retinopathy (DR)., Methods: Diabetic patients who underwent single-field, nonmydriatic, 45-degree color retinal fundus photography at National Taiwan University Hospital between July 2007 and June 2017 were retrospectively recruited. A total of 7524 judgeable color fundus images were collected and were graded for the severity of DR by ophthalmologists. Among these pictures, 5649 along with another 31,612 color fundus images from the EyePACS dataset were used for model training of VeriSee™. The other 1875 images were used for validation and were graded for the severity of DR by VeriSee™, ophthalmologists, and internal physicians. Area under the receiver operating characteristic curve (AUC) for VeriSee™, and the sensitivities and specificities for VeriSee™, ophthalmologists, and internal physicians in diagnosing DR were calculated., Results: The AUCs for VeriSee™ in diagnosing any DR, referable DR and proliferative diabetic retinopathy (PDR) were 0.955, 0.955 and 0.984, respectively. VeriSee™ had better sensitivities in diagnosing any DR and PDR (92.2% and 90.9%, respectively) than internal physicians (64.3% and 20.6%, respectively) (P < 0.001 for both). VeriSee™ also had better sensitivities in diagnosing any DR and referable DR (92.2% and 89.2%, respectively) than ophthalmologists (86.9% and 71.1%, respectively) (P < 0.001 for both), while ophthalmologists had better specificities., Conclusion: VeriSee™ had good sensitivity and specificity in grading the severity of DR from color fundus images. It may offer clinical assistance to non-ophthalmologists in DR screening with nonmydriatic retinal fundus photography., (Copyright © 2020 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

The geriatric nutritional risk index (GNRI) is a simple and efficient tool to assess the nutritional status of patients with malignancies or after surgery. Because trauma patients constitute a specific population that generally acquires accidental and acute injury, this study aimed to identify the association between the GNRI at admission and mortality outcomes of older trauma patients in the intensive care unit (ICU)., Methods: The study population included 700 older trauma patients admitted to the ICU between 1 January 2009 and 31 December 2019. The collected data included age, sex, body mass index (BMI), albumin level at admission, preexisting comorbidities, injury severity score (ISS), and in-hospital mortality. Multivariate logistic regression analysis was conducted to identify the independent effects of univariate predictive variables resulting in mortality in our study population. The study population was categorized into four nutritional risk groups: a major-risk group (GNRI < 82; n = 128), moderate-risk group (GNRI 82 to <92; n = 191), low-risk group (GNRI 92-98; n = 136), and no-risk group (GNRI > 98; n = 245)., Results: There was no significant difference in sex predominance, age, and BMI between the mortality ( n = 125) and survival ( n = 575) groups. The GNRI was significantly lower in the mortality group than in the survival group (89.8 ± 12.9 vs. 94.2 ± 12.0, p < 0.001). Multivariate logistic regression analysis showed that the GNRI (odds ratio-OR, 0.97; 95% confidence interval (CI) 0.95-0.99; p = 0.001), preexisting end-stage renal disease (OR, 3.6; 95% CI, 1.70-7.67; p = 0.001), and ISS (OR, 1.1; 95% CI, 1.05-1.10; p < 0.001) were significant independent risk factors for mortality. Compared to the patients in group of GNRI > 98, those patients in group of GNRI < 82 presented a significantly higher mortality rate (26.6% vs. 13.1%; p < 0.001) and length of stay in hospital (26.5 days vs. 20.9 days; p = 0.016)., Conclusions: This study demonstrated that GNRI is a significant independent risk factor and a promising simple screening tool to identify the subjects with malnutrition associated with higher risk for mortality in those ICU elderly trauma patients.

Background: Cancer has been the leading cause of death in the past decade in Taiwan, with breast cancer being the most common type of cancer in females. Very few studies looked at the risk of recurrence in patients who received multidisciplinary team (MDT) care. We analyzed the influence of MDT on the risk of recurrence and death in breast cancer patients., Method: In this retrospective study, we included newly diagnosed patients from 2004 to 2010. The study included 9,266 breast cancer patients who were enrolled in MDT care and 9,266 patients who were not. The study used log-rank test to analyze patients' characteristics, hospital characteristics, cancer staging, and treatment methods to compare the recurrence rates in MDT care and non-MDT care participants. We used Cox proportional hazards model to examine the effect of MDT and associated factors on the risk of recurrence and mortality of breast cancer patients., Results: Relative risk of recurrence was lower for patients who received MDT care than for patients who did not (HR, 0.84; 95%CI: 0.70-0.99) after matching. The mortality risk for breast cancer patients with relapse was 8.48 times (95%CI: 7.53-9.54) than that for patients without relapse., Conclusions: The relative risk of recurrence and death was significantly lower for breast cancer patients who received MDT care than for those who did not. We suggest that MDT care be implanted in the National Health Policy settings of breast cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest in this study., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Research on social distancing from patients with depression has primarily focused on individual-level factors rather than context-level factors. This study aimed to investigate the relationship between individual-level and context-level factors and social distancing from depressive patients. Methods: Sample data were collected via computer-assisted telephone interviews with 800 Taiwanese adults aged 20 to 65 years in 2016. All effects were tested using multilevel analysis. Results: With regard to individual-level variables, male sex, older age, people with more perceived dangerousness and those with more emotional reaction of fear were associated with greater social distancing from depressive patients. After controlling for individual-level variables, a positive association was found between the degree of urbanization and social distancing. We also found the interaction between the density of psychiatric rehabilitation services and perceived dangerousness to be associated with social distance. This finding revealed that persons with more perceived dangerousness and living in a region with higher density of psychiatric rehabilitation services were associated with greater social distance. Conclusions: We found that social distancing from depressive patients is not only determined by individual-level factors but influenced by the surroundings. This study provides useful directions for the implementation of optimal anti-stigma interventions for patients with depression.

Heart failure (HF) is a major cardiovascular disease worldwide, and the early detection and diagnosis remain challenges. Recently, heart rhythm complexity analysis, derived from non-linear heart rate variability (HRV) analysis, has been proposed as a non-invasive method to detect diseases and predict outcomes. In this study, we aimed to investigate the diagnostic value of heart rhythm complexity in HF patients. We prospectively analyzed 55 patients with symptomatic HF with impaired left ventricular ejection fraction and 97 participants without HF symptoms and normal LVEF as controls. Traditional linear HRV parameters and heart rhythm complexity including detrended fluctuation analysis (DFA) and multiscale entropy (MSE) were analyzed. The traditional linear HRV, MSE parameters and DFAα1 were significantly lower in HF patients compared with controls. In regression analysis, DFAα1 and MSE scale 5 remained significant predictors after adjusting for multiple clinical variables. Among all HRV parameters, MSE scale 5 had the greatest power to differentiate the HF patients from the controls in receiver operating characteristic curve analysis (area under the curve: 0.844). In conclusion, heart rhythm complexity appears to be a promising tool for the detection and diagnosis of HF.

Background: Up to 20% of proximal humeral fractures need to be treated operatively. However, numerus complications were reported by using fixed angled locking plates. The ALPS Proximal Humerus Plating System is a new design implant with novel design features. The aim of this study was to compare the preliminary clinical outcomes and complications of proximal humeral fractures treated with either ALPS or the proximal humeral internal locking system (PHILOS) in Asian patients in Taiwan., Methods: Between January 2016 and December 2018, 66 patients with displaced proximal humeral fractures were analyzed retrospectively, of whom 31 underwent ALPS implant treatment and 35 underwent PHILOS implant treatment. Intraoperative blood loss and operation time, postoperative Constant-Murley Shoulder Outcome (Constant-Murley) score, and complications variables were recorded for the comparison. All cases were regularly followed up for at least 1 year., Results: The mean follow-up period was 400.8 days (range, 367-446 days). Union was achieved in 98.5% of patients (65/66). The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for treating displaced proximal humeral fractures, including operation time, intraoperative blood loss, the Constant-Murley score, and varus malunion (P > 0.05, respectively). However, the incidence of total postoperative complications in the ALPS group was significantly lower than in the PHILOS group (P < 0.05). There was a trend of a lower complication rate of screws/pegs protrusion, avascular necrosis, subacromial impingement, postoperative infection, and reoperation in the ALPS group, although it was not statistically significant (P > 0.05, respectively)., Conclusion: The ALPS group yielded similar radiologic and clinical outcomes to the PHILOS plating group for displaced proximal humeral fractures, but the ALPS group had a significantly lower total rate of complications. Therefore, ALPS may be a better option for treating proximal humeral fractures. Further larger clinical studies are needed to confirm the findings presented here., Trial Registration: Retrospective study.

Objectives: According to the data of Organisation for Economic Cooperation and Development, almost all the countries got increased medical expenditures in these years. Among the diseases, migraine is a condition that affects predominantly young and middle-aged people. It results in great economic losses. So we perform this research to investigate the acupuncture effect of reducing medical expenditure and medical resources use., Perspective: Acupuncture is a non-pharmacologic treatment and it became popular in recent years. In Taiwan, about 13% migraine patients visited acupuncture doctor. We hypothesized that the acupuncture had the additional effect than the medical treatment., Setting: We analysed the economic cost and medical visits in the real word., Methods: We used national cohort data from Taiwan, retrospectively gathered between 2000 and 2010. We selected newly diagnosed migraine patients who were diagnosed by registered neurologists formally licensed by the Taiwan Neurological Society. We divided these patients into two groups: with and without acupuncture treatment. The main outcome was medical expenditures and visits within 1 year after acupuncture., Results: In migraine patients who received acupuncture treatment, medical expenditures on emergency care and hospitalization were significantly lower than the group without acupuncture treatment., Conclusion: According to our real-world data, acupuncture can reduce the medical expenditure in migraine patients within 1 year after diagnosis. For the health policy maker, it is cost effective to encourage combining acupuncture and western medicine to treat migraine patients. For the doctors in routine clinical practice, who may consider to consult acupuncture doctors to deal with the migraine patients together.

Introduction: Being able to predict functional outcomes after a stroke is highly desirable for clinicians. This allows clinicians to set reasonable goals with patients and relatives, and to reach shared after-care decisions for recovery or rehabilitation. The aim of this study was to apply various machine learning (ML) methods for 90-day stroke outcome predictions, using a nationwide disease registry., Methods: This study used the Taiwan Stroke Registry (TSR) which has prospectively collected data from stroke patients since 2006. Three known ML models (support vector machine, random forest, and artificial neural network), and a hybrid artificial neural network were implemented and evaluated by 10-time repeated hold-out with 10-fold cross-validation., Results: ML techniques present over 0.94 AUC in both ischemic and hemorrhagic stroke using preadmission and inpatient data. By adding follow-up data, the prediction ability improved to 0.97 AUC. We screened 206 clinical variables to identify 17 important features from the ischemic stroke dataset and 22 features from the hemorrhagic stroke dataset without losing much performance. Error analysis revealed that most prediction errors come from more severe stroke patients., Conclusion: The study showed that ML techniques trained from large, cross-reginal registry datasets were able to predict functional outcome after stroke with high accuracy. The follow-up data is important which can further improve the predictive models' performance. With similar performances among different ML techniques, the algorithm's characteristics and performance on severe stroke patients will be the primary focus when we further develop inference models and artificial intelligence tools for potential medical., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Published by Elsevier B.V.)

Background & Aims: Acute HEV infection causes varying degrees of liver damage. Although liver-related death due to HEV infection alone is rare in healthy individuals, it is unclear whether HEV superinfection is associated with worse outcomes in patients with chronic HBV infection. Thus, we explored whether HEV superinfection was associated with increased incidence of liver-related death, cirrhosis, and hepatocellular carcinoma (HCC)., Methods: Serum and data were collected from 2 independent retrospective cohorts of patients with chronic HBV infection, comprising 2,123 patients without cirrhosis and 414 with cirrhosis at baseline, respectively. All the patients were negative for HEV-IgG at enrolment and HEV superinfection was defined by the presence of HEV-IgG seroconversion., Results: In the non-cirrhotic cohort, 46 of 2,123 patients developed HEV superinfection. Though HEV superinfection was only associated with increased incidence of liver-related death in the overall cohort, it was a risk factor for all 3 endpoints (liver-related death, cirrhosis, and HCC) in a subgroup of 723 HBeAg-negative patients with chronic HBV infection. In addition, the 1-year mortality rate after HEV superinfection was higher in 4 patients who developed cirrhosis during the follow-up than in those who did not (50% vs. 2.4%, p = 0.001). To elucidate the perceived relationship between HEV superinfection and risk of mortality, an independent cohort of cirrhotic patients (n = 414) was further analyzed to control for the inherent increase in mortality risk due to cirrhosis. The 10 cirrhotic patients with HEV superinfection had a higher 1-year mortality rate than those without (30% vs. 0%, p <0.001)., Conclusions: In both cohorts of patients with chronic HBV infection, acute HEV superinfection increases the risk of liver-related death, especially in those with cirrhosis., Lay Summary: The mortality caused by acute hepatitis E virus infection is usually low in the healthy population, but it is unclear how it affects patients with chronic hepatitis B virus infection, as they already have compromised liver function. Our data show that the 1-year mortality rate is 35.7% in patients with hepatitis B-related cirrhosis who contract hepatitis E virus. Hepatitis E may accelerate disease progression in patients with chronic hepatitis B., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Context: Human height is an inheritable, polygenic trait under complex and multilocus genetic regulation. Familial short stature (FSS; also called genetic short stature) is the most common type of short stature and is insufficiently known., Objective: To investigate the FSS genetic profile and develop a polygenic risk predisposition score for FSS risk prediction., Design and Setting: The FSS participant group of Han Chinese ancestry was diagnosed by pediatric endocrinologists in Taiwan., Patients and Interventions: The genetic profiles of 1163 participants with FSS were identified by using a bootstrapping subsampling and genome-wide association studies (GWAS) method., Main Outcome Measures: Genetic profile, polygenic risk predisposition score for risk prediction., Results: Ten novel genetic single nucleotide polymorphisms (SNPs) and 9 reported GWAS human height-related SNPs were identified for FSS risk. These 10 novel SNPs served as a polygenic risk predisposition score for FSS risk prediction (area under the curve: 0.940 in the testing group). This FSS polygenic risk predisposition score was also associated with the height reduction regression tendency in the general population., Conclusion: A polygenic risk predisposition score composed of 10 genetic SNPs is useful for FSS risk prediction and the height reduction tendency. Thus, it might contribute to FSS risk in the Han Chinese population from Taiwan., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: This study aimed to determine if treatment delay after non-small cell lung cancer (NSCLC) diagnosis impacts patient survival rate., Study Design: This study is a natural experiment in Taiwan. A retrospective cohort investigation was conducted from 2004 to 2010, which included 42 962 patients with newly diagnosed NSCLC., Methods: We identified 42 962 patients with newly diagnosed NSCLC in the Taiwan Cancer Registry from 2004 to 2010. We calculated the time interval between diagnosis and treatment initiation. All patients were followed from the index date to death or the end of 2012. Cox proportional hazard models were used to examine the relationship between mortality and time interval., Results: We included 42 962 patients (15 799 men and 27 163 women) with newly diagnosed NSCLC. The mortality rate exhibited a significantly positive correlation to time interval from cancer diagnosis to treatment initiation. The adjusted HRs ranged from 1.04 to 1.08 in all subgroups time interval more than 7 days compared with the counterpart subgroup of the interval from cancer diagnosis to treatment ≤7 days. The trend was also noted regardless of the patients with lung cancer in stage I, stage II and stage III., Conclusions: There is a major association between time to treat and mortality of patients with NSCLC, especially in stages I and II. We suggest that efforts should be made to minimise the interval from diagnosis to treatment while further study is ongoing to determine causation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Accumulating evidence has linked prolonged exposure to heavy metals to cancer occurrence in the urinary system. However, the specific biological mechanisms responsible for the association of heavy metals with the unusually high incidence of upper tract urothelial carcinoma in Taiwan are complex and incompletely understood., Methods: To elucidate the specific biological mechanism and identify molecular indicators of the unusually high association of upper tract urothelial carcinoma with heavy metal exposure, protein expression following the treatment of T24 human bladder carcinoma and RT4 human bladder papilloma cell line models with arsenic (As) and cadmium (Cd) was studied. Proteomic changes in these cell models were integrated with data from a human bladder cancer (BLCA) tissue proteome to identify possible protein indicators of heavy metal exposure., Results: After mass spectrometry based proteomic analysis and verification by Western blotting procedures, we identified 66 proteins that were up-regulated and 92 proteins that were down-regulated in RT4 cell extracts after treatment with As or Cd. Some 52 proteins were up-regulated and 136 proteins were down-regulated in T24 cell extracts after treatment with Cd. We further confirmed that down-expression of the PML (promyelocytic leukemia) protein was sustained for at least 75 days after exposure of bladder cells to As. Dysregulation of these cellular proteins by As was associated with three biological pathways. Immunohistochemical analyses of paraffin-embedded BLCA tissue slides confirmed that PML protein expression was decreased in BLCA tumor cells compared with adjacent noncancerous epithelial cells., Conclusions: These data suggest that PML may play an important role in the pathogenesis of BLCA and may be an indicator of heavy metal exposure in bladder cells., (© 2019 John Wiley & Sons, Ltd.)

Background Primary aldosteronism (PA) is associated with higher atrial fibrillation prevalence and other cardiovascular complications. However, the effect of target treatment to prevent new-onset atrial fibrillation (NOAF) remains unclear. This study investigated incidence of NOAF under different treatment strategies in patients with PA. Methods and Results We analyzed longitudinal data for patients with PA without atrial fibrillation history from 1997 to 2009 within the National Health Insurance Research Database in Taiwan. Patients with essential hypertension matched by propensity score were enrolled as controls. The primary outcome measurement was NOAF, and secondary outcome measurements were mortality, major cardiac and cardiac/cerebrovascular events, and a combined end point of NOAF and mortality. We identified 2202 patients with PA (534 adrenalectomy, 1668 mineralocorticoid receptor antagonist [MRA] therapy) and 8808 essential hypertension controls with mean follow-up of 4.4 years. In primary outcome measurement, patients with PA who underwent adrenalectomy had a lower incidence of NOAF (adjusted hazard ratio; 0.28, P =0.011) than controls. In contrast, the patients with PA who received MRA therapy had comparable risk of NOAF (adjusted hazard ratio, 1.20; P =0.224). In secondary outcome measurement, patients with PA who underwent adrenalectomy had a lower rate of mortality and combined end point of NOAF and mortality than controls. Patients with PA who received MRA therapy had a higher risk of mortality, major cardiac and cardiac/cerebrovascular events, and combined NOAF with mortality than the essential hypertension controls. Conclusions Compared with patients with essential hypertension, patients with PA who underwent adrenalectomy had a lower incidence of NOAF. However, this finding was not observed in patients with PA who received MRA therapy with a lower dose. Differences between the 2 strategies may reduce with a higher dose of MRA therapy.

Estimated glomerular filtration rate (eGFR) is an important topic in patients with primary aldosteronism (PA). However, the relationship between left ventricular structure and eGFR is unclear. We conducted a prospective, observational, and cross-sectional study to analyze 168 patients with PA and 168 propensity score-matched patients with essential hypertension (EH) as the control group, matched by age, gender, and systolic blood pressure. In the patients with PA, the eGFR was not correlated with left ventricular mass index (LVMI; r=-0.065, p=0.404), while in the patients with EH, the eGFR was negatively correlated with LVMI (r=-0.309, p<0.001). To test whether eGFR had a non-linear relationship with LVMI among the patients with PA, we stratified the patients with PA according to the tertile of eGFR (low, medium, and high tertile). The medium tertile of patients had a significantly lower LVMI than those in the other two tertiles (LVMI: 143.5±41.6, 120.5±40.5, and 133.1±34.3 g/m 2 , from the lowest to highest tertile of eGFR; analysis of covariance p=0.032). The medium tertile of eGFR is associated with lowest LVMI. Patients with PA with high and low eGFR were associated with higher LVMI. The findings implied that the reasons for an increased LVMI in patients with PA may be different to those in patients with EH., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients must adhere to their prescribed warfarin regimens and regularly monitor the anticoagulation effect to maintain therapeutic levels. The ability to evaluate regimen adherence accurately is crucial to the success of patient coaching. However, prevention of thromboembolic events is challenging when the association between medication adherence and the actual amount of anticoagulant agent taken cannot be determined., Purpose: This study used self-reported medication taken and prescription refills to (a) verify warfarin medication adherence and (b) assist clinicians to determine the discrepancy between medication adherence and anticoagulant control efficacy., Methods: This study was conducted at a national-university-affiliated hospital in Yilan County, Taiwan. Structured questionnaires and medical record reviews were adopted. A 100-point visual analog scale was used to measure the reported adherence of participants, whereas medication refill adherence was compared against self-reported adherence. Finally, degree of adherence was evaluated based on time in therapeutic range., Results: This study included 192 participants. Half (n = 94, 49%) were women, and the mean age was 69.6 years. Mean scores were 92.2% for the visual analog scale and 87.3% for medication refill adherence. Medication adherence correlated significantly with age, as reflected in the visual analog scale scores (p < .05). The participants who were receiving polypharmacy with five types of medicines or less attained higher visual analog scale scores, whereas participants who were on warfarin for 2-12 months exhibited higher medication refill adherence. Time in therapeutic range correlated negatively with age, although stability improved with therapy duration., Conclusions/implications for Practice: Despite their high self-reported adherence levels, patients of advanced age require careful monitoring of their time in therapeutic range. The participants in this study who were on warfarin for a relatively longer time exhibited higher stability in the therapeutic range, despite their low medication refill adherence. The results of this study suggest that patient age, duration of warfarin therapy, and polypharmacy are factors associated with medication adherence. The findings may facilitate future assessments of warfarin adherence in patients as well as the implementation of more effective clinical nursing procedures and management practices.

Carpal tunnel syndrome (CTS) is a common cause of compression neuropathy of the upper extremities. This retrospective nationwide matched cohort study was conducted using the data from the Taiwan National Health Insurance Research Database between January 2003 and December 2012. The incidence rate of CTS was 975.84 and 544.12/100,000 person-years, respectively, yielding an incidence rate ratio of 1.79 (95% confidence interval, 1.68-1.91, P < 0.0001). CTS patients with End-stage renal disease (ESRD) in the dialysis group were more likely to receive surgical intervention than those the control group (62.41% vs 12.89%, P < 0.0001). The risk of CTS was significantly higher in the ESRD on dialysis cohort (10-year cumulative incidence, 8.0%) than in the control cohort (5.1%), which yielded an adjusted hazard ratio of 13.95 (95% confidence interval, 10.95-17.76, P < 0.0001). The high risk of CTS in ESRD patients on dialysis suggests that timely referral to hand surgeons with appropriate treatment should prevent permanent median nerve damage by CTS and may possibly improve patients' quality of life.

Objectives: The study aimed to investigate the timeline association with specific dental therapy and osteoradionecrosis (ORN) in oral cancer patients., Materials and Methods: A total of 7394 oral cancer patients, including 198 ORN subjects, were retrieved from a Longitudinal Health Insurance Database for Catastrophic Illness Patients of Taiwan and were analyzed with the Cox proportional hazard regression to compare the ORN risk of individual dental treatments under different dental treatments., Results: The initial dental treatment time significantly impacted on the risk of ORN in oral cancer patients (P<0.05). Pre-radiotherapy endodontic treatment and post-radiotherapy scaling or subgingival curettage increased ORN prevalence (hazard ratio [HR], 2.28 and 1.77, respectively). Endodontic treatment within 2 weeks to 1 month prior to radiotherapy increased the ORN risk by 5.83-fold. Dental scaling or subgingival curettage initialized from three to 6 months post-radiotherapy raised the ORN prevalence by 2.2-fold. Exodontia initialized within 2 weeks before radiotherapy (HR=1.49) or 1 to 3 months after radiotherapy (HR=2.63) greatly increased ORN prevalence. To perform oral surgery from 3 months pre-radiotherapy to 6 months after radiotherapy increased the 1.85-fold ORN risk. The chemotherapy combined oral surgery increased the ORN prevalence by 2.55-fold., Conclusions: Timing of dental treatment, including pre-radiotherapy endodontic treatment, post-radiotherapy scaling or subgingival curettage, and oral surgery or exodontia before and after radiotherapy, could closely relate to ORN development in oral cancer patients., Clinical Relevance: Choosing right time to perform appropriate dental treatment could effectively reduce oral infection and ORN risk.

Background/aim: Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk., Materials and Methods: A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology., Results: The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location., Conclusion: MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This observational study on adult Taiwanese cadavers focused mainly on the intersection of buccal branches of the facial nerve with Stensen's duct, using the emergence of Stensen's duct as the reference landmark., Materials and Methods: Thirty-five cadaveric hemifaces were included in our research. Samples with facial defects due to tumor, trauma, or surgery were all excluded. Buccal branches of the facial nerve were identified according to the Gray's Anatomy 40th edition definition. The distance was measured from the intersection to the emergence of Stensen's duct, running from the anterior border of the parotid gland., Results: In the 35 hemifaces, the number of buccal branch/Stensen's duct intersections ranged from 1 to 5 (average 2.49 ± 1.15). Two-point intersections accounted for 37% (13 hemifaces) of the sample, forming the largest group. Samples of facial nerve buccal branches were divided into four types: Type 1, with two buccal branches, accounted for 37.15% (13/35); Type 2, with three buccal branches, made up 48.59% (17/35) of our samples - the biggest group (Type 2-a was the most frequent pattern among our samples, with two superior buccal branches and one inferior buccal branch, accounting for 34.31% of our samples); Type 3, with four buccal branches, accounted for only 5.7%. Three cases of double Stensen's duct were classified as Type 4, though this is supposed to be a very rare anatomical variation. With Type 2a, the most frequent pattern among our specimens, the distance from the emergence of the Stensen's duct to the emergence point of the first superior buccal branch along the anterior border of the parotid gland was 9.58 ± 5.68 mm. The distance from the emergence point to the emergence of the inferior buccal branch along the anterior border of the parotid gland was 11.03 ± 5.38 mm. The distance (D1) from Stensen's duct to the emergence of the first superiorly located buccal branch of the group Type 2-a was statistically different from the distance (D1) of the other groups (p = 0.02). No direct anastomoses or communicating fibers between upper and lower buccal branches were noted in 11 hemifaces (31%)., Conclusion: The distribution of buccal branches was described using the emergence of Stensen's duct as a reference landmark. According to our observations, the relationship between the buccal branches and Stensen's duct was much more complicated than described in previous studies. This was the first study to investigate the complete distribution of buccal branches of the facial nerve emerging from the anterior of the parotid gland, and their relative locations and branching numbers., (Copyright © 2018. Published by Elsevier Ltd.)

Hodgkin lymphoma (HL) is a highly curable hematologic malignancy. Relapsed/refractory (R/R) HL is an important clinical challenge, despite advances in treatment. Brentuximab vedotin (BV) is highly effective in R/R HL in the western world. However, there are no real-world data on the use of BV in the Asian population. Our study aimed to evaluate the efficacy and safety of BV as salvage therapy in R/R HL patients in Taiwan. We recruited 20 R/R HL patients who received BV at National Taiwan University Hospital. BV was administered at 1.8 mg/kg once every 3 weeks. The median number of systemic treatment received before BV was three. The overall response rate was 73.7% with a complete remission rate of 21.1% in R/R HL. Overall survival was not reached and progression-free survival was 6.8 months. BV could strengthen disease control before transplantation and improve post-transplant outcomes, even among those heavily pretreated patients, without significant overlapping toxicities with prior therapies. Our data suggest that BV is well tolerated and effective in the treatment of Asian patients with R/R HL. BV may offer long-term disease control in selected patients., (Copyright © 2019. Published by Elsevier B.V.)

Air pollution is a modifiable and preventable factor, and it is a possible risk factor for dementia. However, evidence from epidemiological studies is still limited. We conducted a systematic review and meta-analysis to summarize the epidemiological evidence for long-term effects of particulate matter with an aerodynamic diameter ≤2.5 μm (PM 2.5 ) on dementia/Alzheimer's disease (AD). Our inclusion criteria for eligible studies were: longitudinal cohort study design, no overlap in study population, age of study subject ≥50 years, detailed description of exposure assessment for PM 2.5 , outdoor assessment of exposure to PM 2.5 , usage of a clear definition of dementia/AD, and accessibility of sufficient information for meta-analysis. Six databases were searched for eligible studies. The random-effect model was used to synthesize the associations between PM 2.5 and dementia. After exclusion of all irrelevant studies, we analyzed the results of four cohort studies conducted in Canada, Taiwan, the UK, and the US during 2015-2018 among more than 12 million elderly subjects aged ≥50 years (N = 12,119,853). Our meta-analysis reveals that exposure to a 10 μg/m 3 increase in PM 2.5 was significantly and positively associated with dementia (pooled HR = 3.26, 95% CI: 1.20, 5.31). In subgroup analyses, exposure to a 10 μg/m 3 increase in PM 2.5 was found to be positively associated with AD (pooled HR = 4.82, 95% CI: 2.28, 7.36). Analysis of current epidemiological research on PM 2.5 and dementia confirmed that exposure to PM 2.5 was positively associated with a higher risk for dementia. However, it is to be noted that the included studies mainly relied on claim-based diagnosis and showed large differences in methods of exposure assessment, hence further epidemiological studies with well validated outcomes and with standardized exposure assessment models are required to ascertain the relationship between PM 2.5 and dementia/AD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings., Aims: This study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study., Methods: A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC., Results: The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection., Conclusions: Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)