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Yi-Ling Lai,1,2 Wen-Yi Chen,3,* Shiuan-Shinn Lee,1,* Yung-Po Liaw1,4,5 1Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, 402367, Taiwan; 2Community Health Center, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, 427213, Taiwan; 3Department of Senior Citizen Service Management, National Taichung University of Science and Technology, Taichung, 403301, Taiwan; 4Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, 402367, Taiwan; 5Institute of Medicine, Chung Shan Medical University, Taichung, 402367, Taiwan*These authors contributed equally to this workCorrespondence: Wen-Yi Chen, Department of Senior Citizen Service Management, National Taichung University of Science and Technology, 193 Sec 1, San-Min Road, Taichung, 403301, Taiwan, Tel +886 4 22196932, Email chenwen@nutc.edu.tw Shiuan-Shinn Lee, Department of Public Health, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung, 402367, Taiwan, Tel +886 4 24730022 Ext 12185, Email shinn@csmu.edu.twPurpose: This study investigates the influence of demographic changes on the effectiveness of hospital nurse staffing policy, measured by the cumulative response of inpatient care quality to adjustments in hospital nurse staffing levels in Taiwan.Methods: The research design utilized in this study aligns with the observational time-series methodology, and a total of 99 monthly time-series observations were collected from multiple databases administered by the Taiwan government over the period from January 2015 to March 2023. Specifically, the time-varying parameter vector autoregressive and autoregressive distributed lag models were employed to investigate the association between age distribution and nurse staffing policy effectiveness.Results: The time-varying impulse responses of the unplanned 14-day readmission rate after discharge to changes in nurse staffing levels indicate a positive association between patient-to-nurse ratios and unplanned 14-day readmission rates across various types of hospitals. Nevertheless, the effectiveness of hospitals’ nurse staffing policy is observed to diminish with population aging, particularly evident in medical centers and regional hospitals.Conclusion: Policymakers should establish lower mandated patient-to-nurse ratios, grounded in practical nurse workforce planning, to address the needs of an aging society and enhance inpatient care quality through improved nurse staffing in hospitals.Keywords: demographic structural change, nurse staffing, inpatient care quality, time-varying parameter vector autoregressive model, autoregressive distributed lags model

Shadi Chamseddine,1,* Michael LaPelusa,2,* Lianchun Xiao,3 Yehia I Mohamed,1 Sunyoung S Lee,1 Zishuo Ian Hu,1 Rikita I Hatia,4 Manal Hassan,4 James C Yao,1 Dan G Duda,5 Saumil Datar,6 Hesham M Amin,7,8 Ahmed O Kaseb1 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 6Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA; 7Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 8MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Hesham M Amin, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston, TX, 77030, USA, Tel +1 713 794-1769, Fax +1 713 792-7273, Email hamin@mdanderson.org Ahmed O Kaseb, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA, Tel +1-713-792-2828, Fax +1 713-745-1163, Email akaseb@mdanderson.orgIntroduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T).Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤ 3.7 μg/L and ≤ 0.9 μg/L, respectively. The Kaplan–Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups.Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036).Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.Keywords: hepatocellular carcinoma, growth hormone, durvalumab, tremelimumab, overall survival, progression-free survival

Zunirah Ahmed,1 Sunyoung S Lee,2 David W Victor 3rd,1,3 Sudha Kodali1,3 1Department of Medicine, Division of Gastroenterology and Hepatology, Houston Methodist Hospital, Houston, TX, USA; 2Department of Gastrointestinal (GI) Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USACorrespondence: David W Victor, 3 rd, Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, 6445 Main, Suite OPC 22.001, Houston, TX, 77030, USA, Email dwvictor@houstonmethodist.orgAbstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide and is associated with significant health care costs and burden. Management of HCC is guided based on the Barcelona Clinic Liver Cancer (BCLC) system and includes liver transplantation, surgical resection, and liver-directed and systemic therapies. In recent years, there have been significant advancements in understanding the immunogenicity of HCC and this has led to approval of different targeted agents as well as immunotherapy for advanced HCC. Tremelimumab is a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) blocking antibody and has recently been approved in combination with durvalumab (a programmed death-ligand 1 [PDL1] inhibitor) as first-line therapy for advanced (Barcelona Clinic Liver Cancer Stage C) HCC. In this article, we review the different available systemic therapies for advanced HCC with special focus on the clinical utility of tremelimumab for the treatment of unresectable HCC.Keywords: unresectable hepatocellular carcinoma, immunotherapy, CTLA4 antibody, targeted therapy

Jee Youn Oh,1 Sung-Soon Lee,2 Hyung Woo Kim,3 Jinsoo Min,4 Yousang Ko,5 Hyeon-Kyoung Koo,2 Yun-Jeong Jeong,6 Hyeon Hui Kang,7 Ji Young Kang,8 Ju Sang Kim,3 Jae Seuk Park,9 Yunhyung Kwon,10 Jiyeon Yang,10 Jiyeon Han,10 You Jin Jang,10 Min Ki Lee,11 Yangjin Jegal,12 Young-Chul Kim,13 Yun Seong Kim14 1Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; 7Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 9Division of Pulmonary Medicine, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea; 10Division of Tuberculosis Prevention and Control, Korea Disease Control and Prevention Agency, Cheongju, Republic of Korea; 11Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Pusan, Republic of Korea; 12Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ulsan University Hospital, Ulsan University College of Medicine, Ulsan, Republic of Korea; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Republic of Korea; 14Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of KoreaCorrespondence: Sung-Soon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea, Tel +82-10-7173-6575, Fax +82-2-2626-1166, Email sungsoonlee@gmail.comPurpose: Bronchoscopy is widely used for microbiological diagnosis of patients with minimal sputum production. However, the usefulness of bronchoscopy in patient groups who benefit from subsequent microbiological confirmation has not been established.Patients and Methods: We retrospectively analyzed Korean tuberculosis (TB) cohort data from September 2018 to October 2019 to evaluate the usefulness of bronchoscopy in patients with microbiologically negative pulmonary TB (based on initial sputum polymerase chain reaction and culture results). The primary outcome was the proportion of microbiological diagnoses made after bronchoscopy. Secondary outcomes were the predictors of microbiological confirmation and the percentage of additional resistance detection after bronchoscopy.Results: A total of 5194 patients were diagnosed with pulmonary TB, 937 of whom were microbiologically negative for pulmonary TB based on the initial sputum findings. Of these, 319 patients underwent bronchoscopy, and further microbiological confirmation was achieved in 157 (49.1%) patients. The predictors of microbiological confirmation after bronchoscopy were age > 65 years, female sex, and low body mass index (BMI). The rate of additional resistance detection was 10.5% (multidrug resistant/rifampin-resistant 3.8%; isoniazid-resistant 5.7%).Conclusion: Bronchoscopy can be used for the detection of resistant pathogens. Bronchoscopy should be considered for microbiologically negative pulmonary TB in women aged > 65 years and with low BMI for subsequent microbiological confirmation.Keywords: tuberculosis, pulmonary, bronchoscopy, cohort studies

Yu-Ting Tseng,1,2 Pei-Yun Chou,1 Ming-Hong Tai,2,3 Chia-Yen Dai,4– 6 Susan Shin-Jung Lee,1,7 Yao-Shen Chen,1,7 Hung-Chin Tsai,1,3,7,8,* Yen-Hsu Chen2,6,9– 13,* 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 8Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanEmail hctsai1011@yahoo.com.twYen-Hsu ChenGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanEmail infchen@gmail.comBackground: The Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.Methods: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.Results: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986– 19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033– 26,150 ng/mL] vs 3489 ng/mL [IQR 924– 160,640] ng/mL, p = 0.0059, 95% CI 4002– 17,098 ng/mL, area under the curve 0.799, 95% CI 0.632– 0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).Conclusion: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.Keywords: C-reactive protein, Jarisch-Herxheimer reaction, syphilis

Ahmed Omar Kaseb,1 S Cheenu Kappadath,2 Sunyoung S Lee,1 Kanwal Pratap Raghav,1 Yehia I Mohamed,1 Lianchun Xiao,3 Jeffrey S Morris,4 Chimela Ohaji,1 Rony Avritscher,5 Bruno C Odisio,5 Joshua Kuban,5 Mohamed E Abdelsalam,5 Beth Chasen,6 Khaled M Elsayes,7 Mohamed Elbanan,7 Robert A Wolff,1 James C Yao,1 Armeen Mahvash2 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 5Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 6Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Department of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Ahmed Omar Kaseb Email akaseb@mdanderson.orgPurpose: The most common cause of death in advanced/metastatic hepatocellular carcinoma (HCC) is liver failure due to tumor progression. While retrospective studies and meta-analyses of systemic therapy combined with liver-directed therapy have been performed, prospective studies of safety/efficacy of antiangiogenesis followed by intra-arterial therapies are lacking. We tested our hypothesis that sorafenib followed by yttrium 90 glass microspheres (90Y GMs) is safe and that survival outcomes may improve by controlling hepatic tumors.Methods: We enrolled 38 Child–Pugh A patients with advanced/metastatic HCC. In sum, 34 received sorafenib, followed after 4 weeks by 90Y GMs. Analysis of safety and survival outcomes was performed to assess adverse events, median progression-free survival, and overall survival.Results: A total of 34 patients were evaluable: 14 (41.2%) with chronic hepatitis, nine (26.5%) with vascular invasion, and eleven (32.4%) with extrahepatic diseases. Safety analysis revealed that the combination therapy was well tolerated. Grade III–IV adverse events comprised fatigue (n=3), diarrhea (n=2), nausea (n=1), vomiting (n=2), hypertension (n=4), thrombocytopenia (n=1), hyperbilirubinemia (n=1), proteinuria (n=1), hyponatremia (n=1), and elevated alanine or aspartate aminotransferase (n=5). Median progression-free and overall survival were 10.4 months (95% CI 5.8– 14.4) and 13.2 months (95% CI 7.9– 18.9), respectively. Twelve patients (35.3%) achieved partial responses and 16 (47.0%) stable disease. Median duration of sorafenib was 20 (3– 90) weeks, and average dose was 622 (466– 800) mg daily. Dosimetry showed similar mean doses between planned and delivered calculations to normal liver and tumor:normal liver uptake ratio, with no significant correlation with adverse events at 3 and 6 months post-90Y treatment.Conclusion: This is the first prospective study to evaluate sorafenib followed by 90Y in patients with advanced HCC. The study validated our hypothesis of safety with encouraging efficacy signals of the sequencing treatment, and provides proof of concept for future combination modalities for patients with advanced or metastatic HCC.Clinical Trial Registration Number: NCT01900002.Keywords: HCC, sorafenib, yttrium 90, BCLC, hepatocellular carcinoma

Betul Gok Yavuz,1 Elshad Hasanov,2 Sunyoung S Lee,1 Yehia I Mohamed,1 Michael A Curran,3 Eugene J Koay,4 Vittorio Cristini,5,6 Ahmed O Kaseb1 1Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 4Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, TX, USA; 6Department of Imaging Physics, University of Texas MD Anderson Cancer Center, Houston, TX, USACorrespondence: Ahmed O Kaseb Email akaseb@mdanderson.orgAbstract: Hepatocellular carcinoma (HCC) is the most common liver cancer and one of the leading causes of cancer-related deaths in the world. Multiple immunotherapeutic approaches have been investigated to date, and immunotherapy has become the new standard of care therapy in HCC. However, the current role of immunotherapy in HCC remains non-curative. Given this context, a high priority for oncology is understanding the biomarkers that predict clinical response to immunotherapy, have the potential to improve patient selection to maximize the clinical benefit, and spare unnecessary toxicity. In this review, we summarize the key predictive and prognostic biomarkers investigated in immunotherapy clinical trials in HCC and the emerging biomarkers to serve as a roadmap for future clinical trials. Biomarkers from tumoral tissues including PDL-1 expression, tissue infiltrating lymphocytes, tumor mutational burden (TMB) and specific immune signatures, and from peripheral blood including neutrophil-to-lymphocytes ratio, platelet-to-lymphocytes ratio, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and specific cytokines, along with gut microbiota are among the studied biomarkers to date in the HCC era. More integrative approaches, including mathematical biomarkers to predict immunotherapy outcomes, are yet to be studied in HCC.Keywords: hepatocellular carcinoma, immunotherapy, biomarker

Chun-Sheng Hsu,1– 4 Shin-Tsu Chang,1,5,6 Oswald Ndi Nfor,2 Kuan-Jung Lee,2 Chien-Chang Ho,7,8 Chuan-Ching Liu,1 Shiuan-Shinn Lee,2 Yung-Po Liaw2,9 1Department of Physical Medicine and Rehabilitation, Taichung Veterans General Hospital, Taichung City, 40201, Taiwan; 2Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung City, 40201, Taiwan; 3School of Medicine, National Defense Medical Center, Taipei City, 11490, Taiwan; 4College of Medicine, National Chung Hsing University, Taichung City, 402, Taiwan; 5Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, School of Medicine, National Defense Medical Centre, Taipei City, 11490, Taiwan; 6Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, Kaohsiung City, 813414, Taiwan; 7Department of Physical Education, Fu Jen Catholic University, New Taipei, 24205, Taiwan; 8Research and Development Center for Physical Education, Health, and Information Technology, Fu Jen Catholic University, New Taipei, 24205, Taiwan; 9Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung City, 40201, TaiwanCorrespondence: Yung-Po Liaw; Shiuan-Shinn LeeDepartment of Public Health and Institute of Public Health, Chung Shan Medical University, No. 110 Sec. 1 Jianguo N. Road, Taichung City, 40201, TaiwanTel +886 424730022 ext. 11838; +886 424730022 ext.12185Fax +886 423248179Email Liawyp@csmu.edu.tw; shinn@csmu.edu.twPurpose: The Lipoprotein lipase (LPL) gene is a significant contributor to dyslipidemia. It has shown associations with several conditions including atherosclerosis, obesity, and metabolic syndrome (MetS). We assessed the interactive association between MetS and rs3779788 of the LPL gene based on aerobic exercise.Materials and Methods: Data were available for 7532 Taiwan Biobank (TWB) participants recruited between 2008 and 2016. We used multiple logistic regression to determine the odds ratios (OR) for MetS and their 95% confident intervals (C.I.). Potential variables included LPL rs3779788, aerobic exercise, sex, age, education, marital status, body mass index (BMI), smoking, alcohol consumption, midnight snacking, vegetarian diet, coffee, dietary fat, and tea drinking.Results: Aerobic exercise was protective against MetS (OR, 0.858; 95% C.I., 0.743– 0.991). Compared to CC/CT genotype, the OR for developing MetS was 0.875, (95% C.I., 0.571– 1.341) in TT individuals. The test for interaction was significant for the rs3779788 variant and aerobic exercise (p = 0.0484). In our group analyses, the OR for MetS was 0.841 (95% C.I., 0.727– 0.974) in CC/CT and 4.076 (95% C.I., 1.158– 14.346) in TT individuals who did aerobic exercise compared to those who did not.Conclusion: Our study indicated that aerobic exercise improved metabolic syndrome in Taiwanese adults with rs3779788 CC/CT genotype relative to those with TT genotype.Keywords: polymorphisms, variant, physical activity, metabolic disorders

Pin-Chieh Wu,1,2,* Jiun-Ling Wang,3,4,* Po-Ren Hsueh,5 Po-Hsiang Lin,6 Ming-Fang Cheng,7–10 I-Fei Huang,7 Yao-Shen Chen,8,11 Susan Shin-Jung Lee,8,11 Mar Guang-Yuan,1,11 Hsien-Chung Yu,1,8,11–12 Chiao-Lin Hsu,1,2 Fu-Wei Wang,2,13 Chi-Shen Chen,1 Chih-Hsin Hung,9 Wen-Chien Ko3,41Department of Physical Examination Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Department of Nursing, Meiho University, Pingtung, Taiwan; 3Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 4Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Departments of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Department of Pediatrics, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8School of Medicine, National Yang-Ming University, Taipei, Taiwan; 9Department of Chemical Engineering and Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 10Department of Nursing, Fooyin University, Kaohsiung, Taiwan; 11Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 12Institute of Health Care Management, Department of Business Management, National Sun Yat-sen University, Kaohsiung, Taiwan; 13Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan*These authors contributed equally to this workPurpose: Fecal carriage of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is common in Asia, especially in China and Southeast Asia. There are no data about fecal carriage of ESBL-EC and mcr-1-positive E. coli in Taiwan, and few studies focusing on the risk factors of asymptomatic fecal carriage of epidemic ST131 E. coli have been published.Patients and methods: From healthy inhabitants attending health examinations at a medical center in southern Taiwan in 2017, we collected 724 stool samples, which were examined for ESBL-EC fecal carriage using chromogenic medium. ST131 and mcr1-positive E. coli were also investigated using multiplex PCR. Clinical data from all participating adults were collected to analyze the risk factors for fecal ESBL-EC or ST131 E. coli carriage.Results: The prevalence rate of asymptomatic ESBL-EC fecal carriage in adults was 1.9% (14/724). ST131 was found in 22 (3.0%) adults and mcr-1-positive E. coli was found in three (0.4%) adults. A multivariate analysis showed that the risk factors associated with ESBL-EC carriage were diabetes mellitus (adjusted odds ratio [aOR]: 5.5, 95% confidence interval [CI]: 1.3–22.7), a history of colonic polyps (aOR: 6.4, 95% CI: 1.6–24.9), and chronic renal insufficiency (aOR: 20.7, 95% CI: 1.4–305.7). Underlying cancer (aOR: 4.8, 95% CI: 1.0–22.5) and stroke (aOR: 18.0, 95% CI: 1.6–207.5) were associated with ST131 E. coli fecal carriage. In our cohort, travel to Asian countries and food habit were not associated with ST131 or ESBL-EC fecal carriage.Conclusions: The ESBL-EC or ST131 E. coli fecal carriage rate is low among asymptomatic adults in Taiwan. Certain underlying medical conditions were associated with their fecal carriage.Keywords: fecal colonization, extended-spectrum β-lactamase, sequence type, MCR1, Escherichia coli

Hung-Chin Tsai,1–3 I-Tzu Chen,1 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan Purpose: Sparse data are available on the prevalence of resistance among HIV-1-infected patients with virological failure to a single-tablet regimen (STR). This study aimed to evaluate the prevalence of HIV genotypic drug resistance in HIV-1-infected patients with virological failure to STRs in southern Taiwan. Patients and methods: This retrospective study investigated drug resistance in patients with virological failure to STR from January 2016 to September 2017. Antiretroviral resistance mutations were defined using the 2017 International AIDS Society-USA HIV drug resistance algorithm, and drug resistance was compared using the HIVdb program of the Stanford University HIV Drug Resistance Database. Variables between resistance and non-resistance groups were compared. Results: Thirty-nine HIV-1-infected patients with treatment failure were tested for resistance, of whom 89% were infected by men who have sex with men. Subtype B HIV-1 strains were found in 90% of the patients. Eight patients were treatment naïve and initiated STRs, while 31 patients experienced treatment failure after switching to STRs. Eighty-seven percent of the patients harbored any of four classes of resistance (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors (PIs), and integrase strand transfer inhibitors). The prevalence rates of nucleoside reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, PI, and integrase strand transfer inhibitor resistance were 72%, 82%, 10%, and 3%, respectively. Patients with PI resistance were more likely to respond to treatment with a non-tenofovir disoproxil fumarate/emtricitabine/efavirenz-based STR (P=0.004) and a longer duration of antiretroviral therapy (101 months [72.0–123.3] vs 11 months [7–44], P=0.007). There were no associations between different STRs and transmission risk factors, HIV subtype, duration of antiretroviral therapy, and resistance to tenofovir disoproxil fumarate. Conclusion: A high rate of antiretroviral drug resistance was found in the patients who failed STR treatment. The presence of PI resistance in these patients represented an inappropriate switch from a multiple tablet regimen to an STR. These findings should remind clinicians that detailed drug resistance history and close monitoring are mandatory after switching to an STR. Keywords: HIV, single-tablet regimen, drug resistance, treatment failure, antiretroviral therapy

Hung-Chin Tsai,1–3 I-Tzu Chen,1 Kuan-Sheng Wu,1,2 Yu-Ting Tseng,1 Cheng-Len Sy,1 Jui-Kuang Chen,1 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Department of Medicine, Division of Infectious Diseases, Kaohsiung Veterans General Hospital, Kaohsiung, 2Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) has been associated with loss of viral suppression measured by a rise in HIV-1 RNA levels, a decline in CD4 cell counts, persistence on a failing treatment regimen, and lack of adherence to combination antiretroviral therapy. Objectives: This study aimed to monitor the prevalence and risk factors associated with drug resistance in Taiwan after failure of first-line therapy.Materials and methods: Data from the Veterans General Hospital Surveillance and Monitor Network for the period 2009–2014 were analyzed. Plasma samples from patients diagnosed with virologic failure and an HIV-1 RNA viral load >1000 copies/mL were analyzed by the ViroSeq™ HIV-1 genotyping system for drug susceptibility. Hazard ratios (HRs) for drug resistance were calculated using a Cox proportional hazard model.Results: From 2009 to 2014, 359 patients were tested for resistance. The median CD4 count and viral load (log) were 214 cells/µL (interquartile range [IQR]: 71–367) and 4.5 (IQR: 3.9–5.0), respectively. Subtype B HIV-1 strains were found in 90% of individuals. The resistance rate to any of the three classes of antiretroviral drugs (NRTI, NNRTI, and PI) was 75.5%. The percentage of NRTI, NNRTI, and PI resistance was 58.6%, 61.4%, and 11.4%, respectively. The risk factors for any class of drug resistance included age ≤35 years (adjusted HR: 2.30, CI: 1.48–3.56; p

Moa Jeong,1 Hyung Koo Kang,1 Pamela Song,2 Hye Kyeong Park,1 Hoon Jung,1 Sung-Soon Lee,1 Hyeon-Kyoung Koo1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, 2Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea Purpose: Hand grip strength (HGS) is a simple way of predicting the risk of cardiovascular disease and all-cause mortality in the general population. However, the practical significance of grip strength in patients with COPD is uncertain. The aim of this study was to compare HGS between subjects with and without COPD and to evaluate its clinical relevance in patients with COPD by using a national survey.Methods: Data were collected from the Korean National Health and Nutrition Examination Survey. The study included 421 adults with COPD and 2,542 controls who completed questionnaires, spirometry, and a HGS test. HGS was compared between subjects with and without COPD, and the association between grip strength, lung function, and quality of life (QoL) was evaluated.Results: The mean HGS was 33.3±9.1 kg in the COPD group and 29.9±9.5 kg in the non-COPD group; adjusted HGS was 30.9±0.33 kg and 30.9±0.11 kg, respectively (P=0.99). HGS was not related to forced vital capacity (β=0.04, P=0.70) or forced expiratory volume in 1 second (β=0.11, P=0.24) in multivariable analysis. HGS was independently associated with the EQ-5D index, but the relationship was stronger in the COPD group (β=0.30, P

Remanence magnetization plots (e.g., Henkel or δM plots) have been extensively used as a straightforward way to determine the presence and intensity of dipolar and exchange interactions in assemblies of magnetic nanoparticles or single domain grains. Their evaluation is particularly important in functional materials whose performance is strongly affected by the intensity of interparticle interactions, such as patterned recording media and nanostructured permanent magnets, as well as in applications such as hyperthermia and magnetic resonance imaging. Here, we demonstrate that δM plots may be misleading when the nanoparticles do not have a homogeneous internal magnetic configuration. Substantial dips in the M plots of γ-Fe2O3 nanoparticles isolated by thick SiO2 shells indicate the presence of demagnetizing interactions, usually identified as dipolar interactions. Our results, however, demonstrate that it is the inhomogeneous spin structure of the nanoparticles, as most clearly evidenced by Mössbauer measurements, that has a pronounced effect on the δM plots, leading to features remarkably similar to those produced by dipolar interactions. X-ray diffraction results combined with magnetic characterization indicate that this inhomogeneity is due to the presence of surface structural (and spin) disorder. Monte Carlo simulations unambiguously corroborate the critical role of the internal magnetic structure in the δM plots. Our findings constitute a cautionary tale on the widespread use of remanence plots to assess interparticle interactions as well as offer new perspectives in the use of Henkel and δM plots to quantify the rather elusive inhomogeneous magnetization states in nanoparticles.

Onychomadesis is presented in four patients as a result of hand-foot-mouth disease.