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Jie Pan,1 Qiuyan Li,1 Yan Sun,1 Yingying Gu,1 Yijie Ding,1 Nengzhi Pang,1 Yujia Zhou,1 Lei Pei,1 Mengqi Gao,1 Sixi Ma,1 Ying Xiao,1 Feilong Wu,1 De Hu,1 Yu-Ming Chen,2 Lili Yang1 1Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Lili Yang, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74, Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-87330625, Email yangll7@mail.sysu.edu.cnPurpose: A panel of international experts proposed a new definition of fatty liver in 2020, namely metabolic dysfunction-associated fatty liver disease (MAFLD). As an adipokine, adipsin is closely related to metabolic-related diseases. In this study, we aimed to evaluate the relationship among MAFLD, serum adipsin, and metabolic risk abnormalities.Methods: Our study was a cross-sectional study based on the first follow-up of the Guangzhou Nutrition and Health Study (GNHS). A total of 908 patients with hepatic steatosis were involved in our study. Detailed data of patients were collected based upon questionnaire information, physical examination, and blood biochemical test.Results: Among the 908 patients, 789 patients were diagnosed with MAFLD. The levels of serum adipsin in the MAFLD group and non-MAFLD group were (3543.00 (3187.94– 3972.50) ng/mL) and (3095.33 (2778.71– 3354.77) ng/mL) (P < 0.001), respectively. After adjusting for potential confounders, adipsin levels were found to be associated with MAFLD. The OR was 3.46 (95% CI: 1.57– 7.64) for adipsin when comparing subjects in the highest tertile with those in the lowest tertile. With the increase in the number of metabolic risk abnormalities, both the levels of serum adipsin and the proportion of moderate to severe fatty liver increased (all p-trend < 0.001).Conclusion: Increased serum adipsin correlates with MAFLD. Both adipsin levels as well as fatty liver severity increase with higher numbers of metabolic risk abnormalities.Keywords: metabolic dysfunction-associated fatty liver disease, adipsin, metabolic risk abnormalities, hepatic steatosis

Hwa-Yen Chiu,1– 4 Yung-Yang Liu,1,4 Tsu-Hui Shiao,1,4 Kang-Cheng Su,1,4 Kun-Ta Chou,1,4 Yuh-Min Chen1,4 1Chest Department, Taipei Veterans General Hospital, Taipei, 11217, Taiwan, Republic of China; 2Institute of Biophotonics, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, Republic of China; 3Division of Internal Medicine, Hsinchu Branch, Taipei Veterans General Hospital, Hsinchu, 31064, Taiwan, Republic of China; 4School of Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan, Republic of ChinaCorrespondence: Yung-Yang Liu, Chest Department, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, 11217, Taiwan, Republic of China, Tel +886-2-2871-2121 ext. 3071, Fax +886-2-2875-7858, Email yyliu1103@gmail.comPurpose: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia and sleep fragmentation. While apnea is pronounced with severe desaturation during rapid eye movement (REM) sleep, REM-related OSA is a distinct phenotype of OSA associated with respiratory disturbances predominantly during REM sleep. In this study, we investigated the clinical features of REM-related OSA in Taiwan.Patients and Methods: All patients diagnosed with OSA in the Taipei Veterans General Hospital from 2015 to 2017 were analyzed retrospectively and classified into REM-related OSA (REM-OSA) group, non-REM related OSA (NREM-OSA) group, and non-stage specific-OSA group. The clinical demographics, OSA-related symptoms, polysomnography results, and medical comorbidities of the three groups were analyzed.Results: Among 1331 patients with OSA, 414 (31.1%) were classified as REM-OSA, 808 (60.7%) as NREM-OSA, and 109 (8.2%) as non-stage specific-OSA. After being adjusted for OSA severity, the REM-OSA group was associated with less portion of males, longer desaturation duration, and lower nadir oxygen saturation (SpO2) compared with the NREM-OSA group in mild and moderate OSA. In moderate OSA, the non-stage specific-OSA group featured more OSA severity and more desaturation compared with the other groups. The Epworth Sleepiness Scale scores and the prevalence of comorbidities did not vary among the REM-OSA, NREM-OSA, and non-stage specific-OSA groups. High REM-AHI/NREM-AHI ratio was associated with young age, female gender, high BMI, and low AHI.Conclusion: OSA patients with high REM-AHI/NREM-AHI ratio are related to young age, female gender, high BMI, and low AHI. Patients with REM-related OSA presented with longer desaturation duration and lower nadir SpO2 after being adjusted for OSA severity.Keywords: obstructive sleep apnea, OSA, rapid eye movement, REM, intermittent hypoxia, sleep-disordered breathing

Yi-Ju Liao,1 Tzu-Hung Hsiao,2– 4 Ching-Heng Lin,2,3,5,6 Chun-Sheng Hsu,7– 10 Yen-Lin Chang,1,8 Yu-Wei Chen,11 Chiann-Yi Hsu,2,12 Yi-Ming Chen,2,10,13– 15,&ast; Ming-Fen Wu1,&ast; 1Department of Pharmacy, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan; 4Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan; 5Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; 6Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung, Taiwan; 8Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan; 9School of Medicine, National Defense Medical Center, Taipei, Taiwan; 10Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 11Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan; 12Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan; 13Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 14Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 15School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yi-Ming ChenDivision of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Xitun Dist., Taichung, 407, Taiwan, Tel +886-4-2359-2525 ext. 4400, Fax +886-4-2359-2705, Email ymchen1@vghtc.gov.twPurpose: Clopidogrel is widely used in coronary artery, peripheral arterial, and cerebrovascular disease. We aimed to study the association of the CYP2C19 phenotype with cardiovascular outcomes and interventional procedures in a hospital-based population.Patients and Methods: This cross-sectional, retrospective study enrolled patients with prior exposure to clopidogrel at the Taichung Veterans General Hospital (TCVGH) using data extracted from the Taiwan Precision Medicine Initiative (TPMI). Data on the CYP2C19 phenotype, drug-prescription profile, comorbidities, vascular intervention procedures, and hospitalization due to acute myocardial infarction (AMI) or stroke of clopidogrel users were analyzed.Results: From the 32,728 patients in the TCVGH-TPMI cohort, we selected 2687 clopidogrel users. A total of 400 (14.9%) clopidogrel poor metabolizers (PMs), 1235 (46.0%) intermediate metabolizers (IMs), and 1052 (39.2%) extensive metabolizers (EMs) were identified. The predominant loss-of-function allele is &ast;2. In 2687 patients with clopidogrel exposure, the CYP2C19 PM phenotype was unassociated with hospitalization due to AMI or stroke after adjusting for comorbidities and carotid angiographies. Among the 1554 clopidogrel users who underwent cardiovascular intervention, 193 (12.4%) received two or more types of interventional procedures. Compared with non-PMs, patients with the PM phenotype had a higher risk of multiple carotid interventions (OR: 3.13, 95% CI: 1.19– 8.22).Conclusion: In this hospital-wide cohort, 8.2% were clopidogrel users, of which 14.9% were CYP2C19 PMs. The result of this study does not support universal genotyping of CYP2C19 in all clopidogrel users to identify risks for stroke and AMI. CYP2C19 PMs are more likely to undergo multiple carotid interventions than non-PMs. Prospective studies to investigate the association of the CYP2C19 genotype and carotid interventions and outcomes are needed to validate our results.Keywords: pharmacogenomics, clopidogrel, CYP2C19, Taiwan precision medicine initiative, TPMI, carotid intervention

Hung-Chen Chen,1,2 Yung-Che Chen,1 Tsu-Nai Wang,3 Wen-Feng Fang,1 Ya-Chun Chang,1 Yu-Mu Chen,1 I-Ya Chen,2 Meng-Chih Lin,1 Ming-Yu Yang2,4 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Ming-Yu YangGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No. 259, Wenhua 1st Road, Guishan Dist., Taoyuan City, 33302, TaiwanEmail yangmy@mail.cgu.edu.twMeng-Chih LinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Road Niaosong Dist., Kaohsiung City, 83301, TaiwanEmail mengchih@cgmh.org.twPurpose: Circadian clock is synchronized to the 24-hour day by the daily light–dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma.Patients and Methods: We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ϵ, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals.Results: Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ϵ, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ϵ, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIϵ, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875– 0.958; P< 0.001).Conclusion: Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIϵ, PER3, and TIM could be a potential predictor for bronchial asthma.Keywords: bronchial asthma, nocturnal symptom, circadian clock genes, PER3

Yu-Meng Chen,1 Xue-Qiang Wang2,3 1Department of Rehabilitation, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai, People’s Republic of China; 3Department of Rehabilitation Medicine, Shanghai Shangti Orthopaedic Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xue-Qiang WangDepartment of Sport Rehabilitation, Shanghai University of Sport, 188 Hengren Road, Shanghai 200438, People’s Republic of ChinaEmail qiang897@163.comBackground: Neuropathic pain, a type of chronic pain, is difficult to treat clinically. Mounting evidence suggests that exercise can effectively ease neuropathic pain, and the number of publications related to exercise and neuropathic pain has increased over time. However, bibliometrics is rarely used in analyzing the general aspects of studies on exercise and neuropathic pain. The present study aims to provide a systematic overview of global scientific research related to exercise and neuropathic pain from 2005 to 2019.Methods: Publications on Science Citation Index – Expanded of Web of Science from 2005 to 2019 were searched, and those related to exercise and neuropathic pain were analyzed. Only English papers were included without specific species restrictions.Results: A total of 676 papers were included in accordance with our adopted criteria. Linear regression analysis showed a statistically meaningful increase in the number of publications on exercise and neuropathic pain study over time (p< 0.001). The subject categories of the 676 papers mainly focused on neuroscience (29.88%), clinical neurology (18.79%) and rehabilitation (10.06%) in Web of Science. In terms of contribution to scientific research on exercise and neuropathic pain, the United States led the first echelon and had the largest numbers of published papers, citations and H-index.Conclusion: The findings in our study may provide researchers useful information about research trends and frontiers, cooperators and cooperative institutions.Keywords: exercise, neuropathic pain, bibliometrics, research trends

Xueling Wang,1–3,* Yuming Chen,1–3,* Yong Tao,1–3 Yunge Gao,1–3 Dehong Yu,1–3 Hao Wu1–3 1Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The delivery of treatment agents to inner ear with drug delivery system (DDS) has been under investigation to overcome the limitations of the conventional therapeutic agents in curing or alleviating the cisplatin ototoxicity.Methods: In the present study, a novel targeted dexamethasone (DEX)-loaded DDS, A666-DEX-NP, was constructed for prevention from cisplatin-induced hearing loss. A666-(CLEPRWGFGWWLH) peptides specifically bind to prestin, which is limited to the outer hair cells (OHCs). HEI-OC1 and cisplatin-treated guinea pigs (12 mg/kg, intraperitoneal) were used as in vitro and in vivo models for investigating the targeting and protective efficiency against cisplatin.Results: As expected, compared to A666-unconjugated nanoparticles (NP), A666-conjugated coumarin 6-labeled NP showed active targeting to OHCs. Furthermore, A666-coumarin 6-labeled NP could be significantly internalized by HEI-OC1 cells via the A666–prestin interaction. This facilitated the uptake of cells pretreated with A666-DEX-NP, followed by the cisplatin-treated group, which led to enhanced cell viability, reduced apoptotic properties, and decreased reactive oxygen species levels as compared to cells pretreated with DEX or DEX-NP, 4 hours in advance of cisplatin treatment. In cisplatin-treated guinea pigs, pretreatment with A666-DEX-NP effectively preserved OHCs and showed significant hearing protection at 4, 8, and 16 kHz as compared to pretreatment with saline, DEX, or DEX-NP formulation.Conclusion: This OHC-targeting DDS provides a novel strategy for DEX application that can be potentially used to combat cisplatin ototoxicity. Keywords: A666 peptide, dexamethasone, prestin, cisplatin ototoxicity

Pei-Chao Lin,1,2 Chien-Hsun Li,3,4 Pi-Ling Chou,1,2 Yao-Mei Chen,1,5 Li-Chan Lin6 1School of Nursing, College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 5International Medical Service Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Institute of Clinical Nursing, National Yang-Ming University, Taipei, Taiwan Purposes: To investigate the prevalence of pain-related diagnoses in patients with dementia and evaluate the association of pain-related diagnoses with demographic characteristics and dementia subtypes. Patients and methods: In this population-based retrospective cohort study, participants were recruited from a cohort of 2 million people randomly sampled from the general population in the National Health Insurance Research Database of Taiwan from 2000 to 2013. The index year was defined as the period of 1 year from the date of the first diagnosis of dementia. Results: The study group comprised 28,450 patients with the dementia subtypes of vascular dementia, Alzheimer’s disease, or other dementia subtypes. The mean age of patients with dementia was 76.75 years. Of all patients with dementia, 49.07% had at least one pain-related diagnosis documented in their outpatient or inpatient claim records within the index year. The top three pain-related diagnoses were osteoarthritis (29.27%), headache (12.53%), and osteoporosis (11.43%). Musculoskeletal diagnosis was more likely in female patients with vascular dementia. Although patients with vascular dementia had a significantly lower prevalence of pain-related diagnosis, they had a significantly higher risk of 1-year mortality than patients with other dementia subtypes. Conclusion: During the index year, 49.07% of patients with dementia had at least one pain-related diagnosis. To investigate the differences of the use of pain medication in patients with different dementia subtypes and the difference of pain-related diagnosis and treatment in patients with and without dementia, future studies are recommended. Keywords: Alzheimer’s, dementia, diagnosis, hospital, pain, prevalence

Jui-O Chen,1,2,* Jui-Fang Liu,1,3–5,* Yu-qi Liu,6 Yu-Mu Chen,7 Mei-Lien Tu,4 Hong-Ren Yu,8 Meng-Chih Lin,3,7 Chiu-Chu Lin,2 Shih-Feng Liu3,7 1Department of Nursing, Tajen University, Pingtung, Taiwan; 2College of Nursing, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital-Kaohsiung Medical Center and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Respiratory Care, Chang Gung University of Science and Technology, Taoyuan, Taiwan; 5Department of Education, National Kaohsiung Normal University, Kaohsiung, Taiwan; 6Department of Intensive Care unit, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 8Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan *These authors contributed equally to this work Purpose: It is unclear whether the effectiveness of pulmonary rehabilitation program (PRP) after cardiac surgery differs between patients with and without COPD. This study aimed to compare the effectiveness of PRP between patients with and without COPD undergoing coronary artery bypass graft (CABG) surgery. Patients and methods: We retrospectively included patients who underwent CABG surgery and received 3-week PRP from January 2009 to December 2013. We excluded patients who underwent emergency surgery, had an unstable hemodynamic status, were ventilator dependent or did not complete the PRP. Demographics, muscle strength, degree of dyspnea, pulmonary function and postoperative complications were compared. Results: Seventy-eight patients were enrolled (COPD group, n=40; non-COPD group, n=38). Maximal inspiratory pressure (MIP; −34.52 cmH2O vs −43.25 cmH2O, P

Hsin-Hua Chen,1–7 Der-Yuan Chen,1–6 Chi-Chen Lin,1,2 Yi-Ming Chen,1–4 Kuo-Lung Lai,3,4 Ching-Heng Lin1 1Department of Medical Research, Taichung Veterans General Hospital, 2Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, Chung-Hsing University, Taichung, 3School of Medicine, National Yang-Ming University, Taipei, 4Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, 5School of Medicine, Chung-Shan Medical University, 6Department of Medical Education, Taichung Veterans General Hospital, Taichung, 7Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taipei, Taiwan Purpose: The aim of this study is to investigate the association between the use of disease-modifying antirheumatic drugs (DMARDs) and diabetes mellitus (DM) in patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), or psoriasis/psoriatic arthritis (PS/PSA).Patients and methods: This retrospective cohort study used a nationwide, population-based administrative database to enroll 84,989 cases with AS, RA, or PS/PSA who initiated treatment with anti-tumor necrosis factor (anti-TNF) drugs or nonbiologic DMARDs. Multivariable analysis was used to estimate the effect of different therapies on the risk of DM.Results: The incidence rates of DM per 1,000 person-years were 8.3 for users of anti-TNF drugs, 13.3 for users of cyclosporine (CSA), 8.4 for users of hydroxychloroquine (HCQ), and 8.1 for users of other nonbiologic DMARDs. Compared with the users of nonbiologic DMARDs, the multivariate-adjusted hazard ratios (aHRs) for DM were significantly lower for those who used anti-TNF drugs with HCQ (aHR: 0.49, 95% confidence interval [CI]: 0.36–0.66) and those who used HCQ alone (aHR: 0.70, 95% CI: 0.63–0.78), but not for those who used anti-TNFs without HCQ (aHR: 1.23, 95% CI: 0.94–1.60) or CSA (aHR: 1.14, 95% CI: 0.77–1.70).Conclusion: The aHR for DM was lowest for patients with RA and PS/PSA who initiated treatment with an anti-TNF agent with concomitant HCQ, followed by HCQ users. Those who used anti-TNF agents without HCQ and other nonbiologic DMARDs had a similar risk of DM. Keywords: ankylosing spondylitis, rheumatoid arthritis, psoriasis, psoriatic arthritis, diabetes mellitus

Ching-Chung Hsiao,1,* Cheng-Hao Weng,1,2,* Yi-Jung Li,1 Hsin-Hsu Wu,1,2 Yung-Chang Chen,1 Yu-Ming Chen,1 Hsiang-Hao Hsu,1 Ya-Chung Tian1 1Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Taipei, 2Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Abstract: Hemodialysis (HD) patients are more susceptible to infective endocarditis (IE) due to the increased risk of bacterial invasion through intravascular access. However, it remains unclear whether the causative organisms and outcomes of IE in HD patients differ from those in non-HD patients. This study clarified the differences in clinical presentation and outcomes between HD and non-HD patients. At our hospital, we performed a retrospective study of 39 HD and 51 non-HD patients with echocardiography-confirmed IE between June 2000 and February 2007. No differences in sex, intravenous drug use, previous diagnosis of congestive heart failure, and previous valvular surgery were observed between these two groups. The number of patients with diabetic mellitus in these two groups was significantly different (28.2% HD vs 5.9% non-HD patients). The C-reactive protein levels in the two groups were not significantly different. By contrast, the erythrocyte sedimentation rate was significantly higher in the HD patients (HD vs non-HD: 87.2±33.32 vs 52.96±28.19). The incidence of IE involving the mitral valve (MV; 45.1%) or the aortic valve (AV; 43.1%) was similar among the non-HD patients, whereas a preference of IE involving the MV (79.5%) over the AV (15.4%) was noted among the HD patients. The HD patients had a significantly higher Staphylococcus aureus infection rate (HD: 46.2%; non-HD: 27.5%). The proportion of methicillin-resistant S. aureus (MRSA; 83.8%) infection accounting for S. aureus IE in the HD group was higher than that (28.6%) in the non-HD group. The in-hospital mortality rate did not differ between the two groups. In conclusion, compared with non-HD patients, a propensity of IE involving the MV and a higher MRSA infection rate were observed in HD patients. The in-hospital mortality rate of echocardiography-confirmed IE did not differ between the two groups. Keywords: infective endocarditis, hemodialysis, mitral valve, aortic valve, Staphylococcus aureus

JingLun Li,1 JiaoJiao Deng,2 JinXian Yuan,1 Jie Fu,1 XiaoLing Li,2 AiPing Tong,2 YueLong Wang,2 YangMei Chen,1 Gang Guo2 1Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 2State Key Laboratory of Biotherapy and Cancer Center, and Department of Neurosurgery, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China Abstract: Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(L-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future. Keywords: spinal cord injury, zonisamide, nanomicelles

Shih-Feng Liu,1–3 Ho-Chang Kuo,1,2,4 Guan-Heng Liu,5 Shu-Chen Ho,4 Huang-Chih Chang,1,3 Hung-Tu Huang,6 Yu-Mu Chen,1 Kuo-Tung Huang,1,3 Kuan-Yi Chen,2 Wen-Feng Fang,1–3 Meng-Chih Lin1–3 1Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, 2Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, 3Chang Gung University College of Medicine, 4Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, 5Li-Chih Valuable School, 6Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Background: Whether the use of inhaled corticosteroids (ICSs) in patients with COPD can protect from osteoporosis remains undetermined. The aim of this study is to assess the incidence of osteoporosis in patients with COPD with ICS use and without.Patients and methods: This is a retrospective cohort and population-based study in which we extracted newly diagnosed female patients with COPD between 1997 and 2009 from Taiwan’s National Health Insurance (TNHI) database between 1996 and 2011 (International Classification of Diseases, Ninth Revision – Clinical Modification [ICD-9-CM] 491, 492, 496). The patients with COPD were defined by the presence of two or more diagnostic codes for COPD within 12 months on either inpatient or outpatient service claims submitted to TNHI. Patients were excluded if they were younger than 40 years or if osteoporosis had been diagnosed prior to the diagnosis of COPD and cases of asthma (ICD-9 CM code 493.X) before the index date. These enrolled patients were followed up till 2011, and the incidence of osteoporosis was determined. The Cox proportional hazards regression model was also used to estimate hazard ratios (HRs) for incidences of lung cancer.Results: Totally, 10,723 patients with COPD, including ICS users (n=812) and nonusers (n=9,911), were enrolled. The incidence rate of osteoporosis per 100,000 person years is 4,395 in nonusers and 2,709 in ICS users (HR: 0.73, 95% confidence interval [CI]: 0.63–084). The higher ICS dose is associated with lower risk of osteoporosis (0 mg to ≤20 mg, HR: 0.84, 95% CI: 0.69–1.04; >20 mg to ≤60 mg, HR: 0.78, 95% CI: 0.59–1.04; and >60 mg, HR: 0.72, 95% CI: 0.55–0.96; P for trend =0.0023) after adjusting for age, income, and medications. The cumulative osteoporosis probability significantly decreased among the ICS users when compared with the nonusers (P

Hsin-Hua Chen,1–6 Der-Yuan Chen,1–3,6–8 Yi-Ming Chen,1–3 Chao-Hsiun Tang9 1Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China; 3Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 4Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, Taiwan, Republic of China; 5Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan, Republic of China; 6School of Medicine, Chung-Shan Medical University, Taichung, Taiwan, Republic of China; 7Institute of Biomedical Science, Chung-Hsing University, Taichung, Taiwan, Republic of China; 8Department of Medical Education, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 9School of Health Care Administration, Taipei Medical University, Taipei, Taiwan, Republic of China Objective: To compare drug discontinuation risk between adalimumab (ADA) and etanercept (ETN) treatment among anti-tumor necrosis factor (anti-TNF)-naïve rheumatoid arthritis (RA) patients, in particular the influence of concomitant dose of methotrexate (MTX).Methods: This retrospective nationwide population-based cohort study identified 4,592 anti-TNF-naïve RA patients in whom ETN (n=2,609) or ADA (n=1,983) was initiated using National Health Insurance claims data. After adjustment for prior medication, concomitant medication, and baseline demographic data, the relative risk of drug discontinuation in ADA users compared with ETN users was quantified by calculating adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) using Cox proportional hazard regression analyses, stratified by the follow-up time (≤1 year, >1 year) and/or concomitant MTX dose (≤10 mg/wk, >10 mg/wk).Results: ADA users had a higher risk of drug discontinuation compared with ETN users during the first year of follow-up (aHR, 1.13; 95% CI, 1.01–1.27), but not during all treatment periods (aHR, 1.06; 95% CI, 0.98–1.16) or after 1 year (aHR, 0.99; 95% CI, 0.87–1.13). However, ADA users had a significantly higher risk of drug discontinuation compared with ETN users among patients on concomitant MTX >10 mg/wk during all treatment periods (aHR, 1.27; 95% CI, 1.10–1.47), during the first year of follow-up (aHR, 1.48; 95% CI, 1.22–1.78), or after 1 year (aHR, 1.42; 95% CI, 1.06–1.90), but not among patients on concomitant MTX 0–10 mg/wk.Conclusion: This population-based cohort study demonstrated a modification effect of concomitant MTX dose on the relative risk of anti-TNF discontinuation for ADA compared with ETN among anti-TNF-naïve RA patients. However, the lack of exact cause of anti-TNF discontinuation limited causal inference of such a concomitant MTX dose-related modification effect. Keywords: adalimumab, etanercept, methotrexate, rheumatoid arthritis, treatment disconti­nuation

BackgroundThe Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry.Methods and resultsA total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

An implant was removed 6 months after restoration because of peri-implant pathosis. The implant had been placed adjacent to the mandibular right second premolar and close to a periapical lesion of the endodontically treated adjacent first premolar. Along with removal of the failed implant and an apicoectomy of the problem tooth, guided bone regeneration was used to restore the alveolar ridge defect at the site of the failed implant. A replacement implant was placed 6 months later and successfully restored after healing. [ABSTRACT FROM AUTHOR]