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Ya-Ru Liang,1,2,* Chou-Chin Lan,1,3,* Wen-Lin Su,1,3 Mei-Chen Yang,1,3 Sin-Yi Chen,1 Yao-Kuang Wu1,3 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, TaoYuan City, Taiwan; 3School of Medicine, Tzu-Chi University, Hualien, Taiwan*These authors contributed equally to this workCorrespondence: Yao-Kuang Wu, Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian Dist, New Taipei City, Taiwan, Tel +886-2-66289779 ext 5709, Fax +886-2-66289009, Email drbfci@yahoo.com.twBackground: The decision guild for non-invasive positive pressure ventilation (NPPV) application in acute respiratory failure (ARF) patients still needs to work out.Methods: Adult patients with acute hypoxemic or hypercapnic respiratory failure were recruited and treated with NPPV or primary invasive mechanical ventilation (IMV). Patients’ characteristic and clinical outcomes were recorded. Logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals for baseline characteristics and clinical outcomes. Subgroup analyses by reason behind successful NPPV were conducted to ascertain if any difference could influence the outcome.Results: A total of 4525 ARF patients were recruited in our facility between year 2015 and 2017. After exclusion, 844 IMV patients, 66 patients with failed NPPV, and 74 patients with successful NPPV were enrolled. Statistical analysis showed APACHE II score (aOR = 0.93), time between admission and start NPPV (aOR = 0.92), and P/F ratio (aOR = 1.04) were associated with successful NPPV. When comparing with IMV patients, failed NPPV patients displayed a significantly lower APACHE II score, higher Glasgow Coma Scale, longer length of stay in hospital, longer duration of invasive ventilation, RCW/Home ventilator, and some comorbidities.Conclusion: APACHE II score, time between admission and start NPPV, and PaO2 can be predictors for successful NPPV. The decision of NPPV application is critical as ARF patients with failed NPPV have various worse outcomes than patients receiving primary IMV.Keywords: acute respiratory failure, hospital stay, invasive mechanical ventilation, non-invasive positive pressure ventilation

Yao-Kuang Wu,1,2 Wen-Lin Su,1,2 Mei-Chen Yang,1,2 Sin-Yi Chen,1 Chih-Wei Wu,1 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu-Chi University, Hualien, TaiwanCorrespondence: Chou-Chin Lan, Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian Dist., New Taipei City, Taiwan, Tel +886-2-66289779 ext 5709, Fax +886-2-66289009, Email bluescopy@yahoo.com.twBackground: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with an increased mortality rate in recent years, mainly caused by exposure to tobacco smoke. Regular physical activity is thought to diminish the risk of COPD exacerbation, while very few studies investigate the interaction between smoking and physical activity on COPD development. This study aims to investigate the association between smoking status, physical activity and prevalent COPD.Methods: This study analyzed data of adults 20 to 79 years old from the National Health and Nutrition Examination Survey (NHANES) 2007– 2012.Results: A total of 6404 participants aged 20– 79 were included and divided into four groups by their physical activity levels and smoking status. Amongst, 2819 (43.7%) were physically active non-smokers, 957 (14.8%) were physically inactive non-smokers, 1952 (30.3%) were physically active smokers, and 717 (11.1%) were physically inactive smokers. Prevalence of airflow obstruction were 5.7%, 7.1%, 17.7% and 18.6%, respectively. After adjustment, physically active smokers (aOR=2.71, 95% CI=1.94– 3.80) and physically inactive smokers (aOR=2.70, 95% CI=1.78– 4.09) but not physically active non-smokers were more likely to have airflow obstruction than physically active non-smokers. These associations were similar among most subgroups by age, sex, or BMI. Among smokers, being physically inactive was not significantly associated with a greater chance for prevalent airflow obstruction than being physically active.Conclusion: Smokers, regardless of their physical activity level, are more likely to have airflow obstruction as compared with physically active non-smokers. Within smokers, being physically inactive poses no excess chance to be airflow obstructed. The findings indicate that physical activity level seem not altering the relationship between smoking and airflow obstruction.Keywords: chronic obstructive pulmonary disease, smoking, physical activity, airflow obstruction

Lun-Yu Jao,1,2 Po-Chun Hsieh,3 Yao-Kuang Wu,1,2 Mei-Chen Yang,1,2 Chih-Wei Wu,1,2 Chung Lee,1,2 I-Shiang Tzeng,4 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu-Chi University, Hualien, Taiwan; 3Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan; 4Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanCorrespondence: Chou-Chin Lan, Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian District, New Taipei City, Taiwan, 23142, Tel +886-2-6628-9779 ext. 2259, Fax +886-2-6628-9009, Email bluescopy@yahoo.com.twBackground: Chronic obstructive pulmonary disease (COPD) often involves the cardiopulmonary dysfunction that deteriorates health-related quality of life (HRQL) and exercise capacity. Work efficiency (WE) indicates the efficiency of overall oxygen consumption (VO2) during exercise. This study investigated whether different WEs have different effects on pulmonary rehabilitation (PR).Methods: Forty-five patients with stable COPD were scheduled for PR. The PR programs consisted of twice-weekly sessions for three months. These patients were comprehensively evaluated by cardiopulmonary exercise testing and COPD assessment test (CAT) before and after PR. We compared these parameters between patients with a normal versus poor WE.Results: Twenty-one patients had a normal WE and twenty-four patients had a poor WE (< 8.6 mL/min/watt). Patients with a poor WE had earlier anaerobic metabolism, a poorer oxygen pulse, lower exercise capacity, more exertional dyspnea, and a poorer HRQL than those with a normal WE. PR improved exercise capacity, HRQL, anaerobic threshold, exertional dyspnea and leg fatigue in patients with either normal or poor WE. However, significant improvement of WE, oxygen pulse, respiratory frequency (Rf) during exercise, chest tightness, activity and sleepiness by CAT were noted only in patients with a poor WE. Among the patients with a poor WE, 29% patients had WE returned to normal after PR.Conclusion: Patients with different WE had different responses to PR. PR improved exercise capacity and HRQL regardless of a normal or poor WE. However, WE, oxygen pulse, Rf during exercise, chest tightness, activity and sleepiness were only improved in patients with a poor WE.Keywords: chronic obstructive pulmonary disease, exercise intolerance, pulmonary rehabilitation, work efficiency

Mu-Chun Yang,1,2 Yao-Kuang Wu,2,3 Chou-Chin Lan,2,3 Mei-Chen Yang,2,3 Sheg-Kang Chiu,2,4 Ming-Yieh Peng,4 Wen-Lin Su2,3 1Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan, Republic of China; 2School of Medicine, Tzu Chi University, Hualien, Taiwan, Republic of China; 3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan, Republic of China; 4Division of Infectious Disease, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan, Republic of ChinaCorrespondence: Wen-Lin Su, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289 Jianguo Road, Xindian District, New Taipei City, 23142, Taiwan, Republic of China, Tel +886-2-66289779, Fax +886-2-66289009, Email williamsu2007@gmail.comPurpose: Patients with septicemia caused by vancomycin-resistant Enterococcus (VRE) bacteremia have higher mortality rates than patients infected by VSE. Vancomycin or teicoplanin is selected as the antibiotic stewardship intervention to cover methicillin-resistant Staphylococcus aureus infections before blood culture reveals VRE bacteremia in critically ill patients with Gram-positive cocci (GPC) bacteremia; this may require linezolid or daptomycin treatment instead. We thus evaluated antibiotic stewardship practices, such as appropriate timing of antibiotic use in GPC bacteremia, and clinical outcomes of critically ill patients with VRE infection.Patients and Methods: This retrospective study enrolled 191 critically ill patients with enterococcal bacteremia at the Taipei Tzu Chi Hospital during January 1, 2019–December 31, 2020. Demographic and clinical characteristics, as well as disease outcomes and appropriate antibiotic use after GPC bacteremia diagnosis, were compared between the VRE and VSE groups.Results: Of 191 patients, 55 had VRE bacteremia (case group) and 136 had VSE bacteremia (control group). The rate of antibiotic change after initial antibiotic use for GPC bacteremia was higher in the VRE bacteremia group (100% vs 10.3%; p< 0.001). The time to appropriate antibiotic administration after GPC bacteremia diagnosis was longer in the VRE bacteremia group (3.3± 2.1 vs 1.5± 1.8 days; p< 0.001). Patients with VRE bacteremia had higher 28-day mortality rates (relative risk, 1.997; 95% confidence interval [CI], 1.041– 3.83). Multivariate Cox regression analysis showed that delayed appropriate antibiotic administration of > 3 days after GPC bacteremia diagnosis increased the risks of 28-day all-cause mortality (adjusted hazard ratio, 2.045; 95% CI, 1.089– 3.84; p=0.026) in patients with VRE infection.Conclusion: Patients with VRE bacteremia with delayed appropriate antibiotic administration of > 3 days after GPC bacteremia diagnosis had increased 28-day mortality risks. New strategies for early VRE detection in GPC bacteremia may shorten the time to administer appropriate antibiotics and lower mortality rates.Keywords: VRE bacteremia, sepsis, early detection, appropriate antibiotic use, GPC bacteremia

Meng-Chang Yang,1,&ast; Peng Li,1,&ast; Wen-Jie Su,1 Rong Jiang,1 Jia Deng,1 Ru-Rong Wang,2 Chao-Li Huang3 1Department of Anesthesiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ru-Rong WangDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18140049936Fax +86 28-87393632Email wangrurong@scu.edu.cnChao-Li HuangDepartment of Internal Medicine, Eastern Hospital, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 585, Damian, Honghe North Road, Longquanyi District, Chengdu, People’s Republic of ChinaTel +86 13350855681Fax +86 28-87775681Email chaoli_huang@126.comPurpose: Several randomized clinical trials (RCTs) investigated the effects of the manual placental removal on hemorrhage or other hemorrhage-related complications compared with the spontaneous placental removal during cesarean section (CS), while the results remained controversial and were inconsistent. The purpose of this meta-analysis was to quantify the pooled effects of the methods of placental removal on hemorrhage during CS.Patients and Methods: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Heterogeneity was tested by I2 statistics and Q-statistic. The random-effects model or fixed-effects model were used to calculate the pooled effect for the included studies according to heterogeneity. And the term of standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled and estimated the effects across all studies.Results: A total of nine RCTs were included in this meta-analysis. Compared with spontaneous group, manual placental removal increased the amount of hemorrhage (SMD = 0.53, 95% CI [0.12, 0.94]; Z = 2.54, P = 0.011) and increased the risk of endometritis (OR = 1.84, 95% CI [1.31, 2.58]; Z = 3.52, P < 0.0001). In contrast, there was no significant difference concerning the operating time (SMD = − 0.30, 95% CI [− 0.85, 0.24]; Z = 1.09, P = 0.276), the length of hospital stays (SMD = 0.11, 95% CI [− 0.08, 0.30]; Z = 1.11, P = 0.265), and blood transfusion requirement (OR = 1.36, 95% CI [0.91, 2.04]; Z = 1.52, P = 0.129), respectively.Conclusion: Comparing with spontaneous placental removal, manual placental removal appeared to be less positive effect during CS. Because of the limitations of this meta-analysis, more high-quality RCTs are needed to confirm our findings.Keywords: cesarean section, manual placental removal, spontaneous placenta removal, hemorrhage, meta-analysis

Ching-Ju Chiu,1 Min-Chia Yang,2 Chi-Chang Huang,3 Chia-Ming Chang1,3 1Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 2Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan; 3Division of Geriatrics and Gerontology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Min-Chia YangDepartment of Medicine, College of Medicine, National Cheng Kung University, No.1, University Road, Tainan, 70101, TaiwanTel +886-6-2353535 ext. 5739Fax +886-6-3028175Email kh9531023@gmail.comBackground: In this study, factors associated with the duration of a disability before death in older adults who are moderately to severely disabled in Taiwan are investigated.Methods: A nationally representative sample of older adults (65+) in 1996 who died before 2016 (n = 1139) were analyzed to calculate their disability status and the length of time they were disabled before death.Results: The mean period during which the participants experienced moderate to severe disability before death for older adults in Taiwan was 5.53 years (SD = 3.15). Men who were overweight had an average of 1.17 more survival years (βoverweight = 1.17, p < 0.05) as compared to those who were normal weight, and in the case of those who were cognitively impaired (SPMSQ ≤ 7), years of survival were decreased by an average of 1.70 years as compared to those who were cognitively intact before death (βcognition = − 1.70, p < 0.01). The aforementioned effects were independent of age. In women, the number of diseases was the most dominant independent correlate for survival years (βdisease = − 0.34, p < 0.05).Conclusion: Disability distribution at various time points before death among the elderly in Taiwan was revealed in the study. At 10 years before death, 93% of the elderly were free from any ADL disabilities, and only 4% reported more than three ADL disabilities. At 6 years before death, an average of 10% of the participants had more than three ADL disabilities, and at one year before death, moderate to severe disability increased to 38%. Factors associated with the survival years among those who were moderately to severely disabled showed distinct gender differences.Keywords: disability, duration before death, elderly, risk factor

Yao-Kuang Wu,1,2 Wen-Lin Su,1,2 Mei-Chen Yang,1,2 Sin-Yi Chen,1 Chih-Wei Wu,1 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2School of Medicine, Tzu-Chi University, Hualien, TaiwanCorrespondence: Chou-Chin LanDivision of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian District, New Taipei City, TaiwanTel +886-2-66289779 ext 5709Fax +886-2-66289009Email bluescopy@yahoo.com.twBackground: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease with exacerbations causing hospitalizations, morbidity, and mortality. COPD exacerbation causes a substantial health impact, and its subtypes might differ in prognosis and treatment response.Methods: This study evaluated the factors of COPD exacerbations and explored the probabilities of frequent severe COPD exacerbations. Categorical and continuous variables between groups were compared. The hazard ratio (HR) and the probability of no hospital readmission were also estimated.Results: A total of 617 COPD patients were enrolled and comprised the frequent exacerbator (N = 226) and the non-frequent exacerbator (N = 391) groups. The frequent exacerbator group significantly displayed a higher eosinophil count (EC; p=0.004), a higher percentage of the frequent severe acute exacerbation history before the index hospitalization (IH; p < 0.001), a lower FEV1 value (p=0.001), and a higher triple combination inhaler prior and following the IH (p < 0.001 and p=0.002) than the non-frequent exacerbator one. Increasing age (aOR of 1.02), higher EC (aOR of 1.09), and lower FEV1 value (aOR of 0.72) were significantly associated with an increased hospital readmission risk. The readmission rate and risk were higher in patients with a history of frequent severe acute exacerbation (aHR of 3.38) than those without severe acute exacerbation. Cases treated with the triple combination inhaler before the IH had a higher readmission rate and risk than non-users.Conclusion: Patients with EC ≥ 2%, FEV1 < 50%, or frequent severe acute exacerbation history before the IH have a higher risk of being diagnosed with a frequent exacerbator phenotype. Besides, higher age, triple combination inhaler before the IH, and smoking might be independently correlated with the frequent readmission risk within 1-year post-exacerbation. A better comprehension of the COPD exacerbation mechanism may further identify the best course of preventative strategy and lead to novel interventions.Keywords: chronic obstructive pulmonary disease, COPD, forced expiratory volume in one second, FEV1, forced vital capacity, FVC, index hospitalization, eosinophil count

Shih-Hsing Yang,1 Mei-Chen Yang,2,3 Yao-Kuang Wu,2,3 Chih-Wei Wu,2,3 Po-Chun Hsieh,4 Chan-Yen Kuo,5 I-Shiang Tzeng,5 Chou-Chin Lan2,3 1Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan; 2Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 3School of Medicine, Tzu-Chi University, Hualien, Taiwan; 4Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan; 5Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanCorrespondence: Chou-Chin LanDivision of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289, Jianguo Road, Xindian City, New Taipei City, 23142, TaiwanTel +886-2-6628-9779 Ext. 2259Fax +886-2-6628-9009Email bluescopy@yahoo.com.twIntroduction: Chronic obstructive pulmonary disease (COPD) is a progressive disease with deteriorating cardiopulmonary function that decreases the health-related quality of life (HRQL) and exercise capacity. Patients with COPD often have cardiovascular and muscular problems that hinder oxygen uptake by peripheral tissues, resulting in poor oxygen consumption efficiency. It is important to develop new physiological parameters to evaluate oxygen consumption efficiency during activities and to evaluate its association with exercise capacity and HRQL. Work efficiency (WE) measures oxygen consumption efficiency during exercise. We hypothesize that patients with poor WE should have exercise intolerance and poor HRQL. Therefore, we aimed to evaluate the association between WE and exercise capacity, HRQL and other cardiopulmonary parameters.Patients and Methods: Seventy-eight patients with COPD were evaluated with spirometry, cardiopulmonary exercise testing, and assessment of dyspnea score and HRQL (using the St. George’s Respiratory Questionnaire [SGRQ]). Cardiopulmonary exercise testing was performed using a cycle ergometer with an incremental protocol and exhaled breath analysis to assess oxygen consumption. WE was defined as the relationship between oxygen consumption and workload.Results: There were 31 patients with normal WE (group I) and 47 patients (group II) with poor WE. Patients with poor WE had lower exercise capacity (maximal oxygen consumption, group I vs II as 1050± 53 vs 845 ± 34 mL/min, p=0.0011), poorer HRQL (SGRQ score 41.1± 3.0 vs 55± 2.2, p=0.0002), higher exertional dyspnea score (5.1± 0.2 vs 6.1± 0.2, p= 0.0034) and early anaerobic metabolism during exercise (anaerobic threshold, 672± 27 vs 583 ± 18 mL/min, p=0.0052).Conclusion: WE is associated with exercise capacity and HRQL. Here, patients with poor WE also had exercise intolerance, poorer HRQL, and more exertional dyspnea.Keywords: chronic obstructive pulmonary disease, exercise physiology, work efficiency

Chih-Wei Wu,1,2 Po-Chun Hsieh,3,4 Mei-Chen Yang,1,2 I-Shiang Tzeng,5 Yao-Kuang Wu,1,2 Chou-Chin Lan1,2 1Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 2Faculty of Medicine, School of Medicine, Tzu Chi University, Hualien, Taiwan; 3Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 4Department of Post-Baccalaureate Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan; 5Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, TaiwanCorrespondence: Chou-Chin Lan; Yao-Kuang WuDivision of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jianguo Road, Xindian District, New Taipei City 23142, TaiwanTel +886-2-6628-9779 ext. 2259Fax +886-2-6628-9009Email bluescopy@yahoo.com.tw; drbfci@yahoo.com.twIntroduction: Patients with chronic obstructive pulmonary disease (COPD) are at an increased risk of cardiovascular comorbidities such as pulmonary hypertension or heart failure. Impaired cardiovascular function often has a significant impact on patients with COPD. Oxygen pulse (O2P) is a surrogate for stroke volume. However, studies regarding O2P, health-related quality of life (HRQL), and exercise capacity in patients with COPD are lacking. We aimed to confirm the association between O2P, HRQL, exercise capacity, severe exacerbation of COPD, and other parameters in exercise testing.Materials and methods: This study included 79 patients with COPD who underwent lung function testing, a cardiopulmonary exercise test (CPET), Borg Dyspnea Scale evaluation, completion of the St. George’s Respiratory Questionnaire, and echocardiography. Cardiovascular comorbidities, COPD-related hospitalizations, and emergency room visits were recorded. We compared these parameters between two groups of patients: those with normal peak O2P and those with impaired peak O2P. The relationships of peak O2P with CPET and lung function were analyzed using simple linear regression.Results: Patients with normal peak O2P had higher exercise capacity (peak oxygen uptake and work rate), better HRQL, lower dyspnea score, lower COPD-related hospitalizations, and higher circulatory and ventilator parameters than patients with impaired peak O2P. According to a simple linear regression analysis, the anaerobic threshold (AT) and forced expiratory volume in one second (FEV1) showed a significant association with peak O2P, and the Pearson correlation coefficients (Pearson’s r) were 0.756 and 0.461, respectively.Conclusion: Peak O2P has a significant impact on exercise capacity, HRQL, dyspnea, COPD-related hospitalization, and circulatory and ventilatory functions in patients with COPD. The AT and FEV1 have strong and moderate associations with peak O2P, respectively. Therefore, peak O2P is an important indicator of disease severity for patients with COPD.Keywords: cardiopulmonary exercise test, chronic obstructive pulmonary disease, hospitalization, oxygen pulse, health-related quality of life

Ming-Cheng Chan,1,* Elise Chia-Hui Tan,2 Ming-Chin Yang3,* 1Section of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; 2National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, Republic of China; 3Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan, Republic of China *These authors contributed equally to this work Objective: The aim of this study was to evaluate the cost-effectiveness of the long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator indacaterol/glycopyrronium (IND/GLY) as a maintenance treatment for COPD patients from the perspective of health care payer in Taiwan. Patients and methods: We adopted a patient-level simulation model, which included a cohort of COPD patients aged ≥40 years. The intervention used in the study was the treatment using IND/GLY, and comparators were tiotropium or salmeterol/fluticasone combination (SFC). Data related to the efficacy of drugs, incidence of exacerbation, and utility were obtained from clinical studies. Direct costs were estimated from claims data based on the severity of COPD. The cycle length was 6 months (to match forced expiratory volume in 1 second [FEV1] data), and the time horizons included 1, 3, 5, 10 years, and lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results. Costs were expressed in US dollars with a discount rate of 3.0%. Results: Compared to tiotropium and SFC, the incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) gained of patients treated with IND/GLY were US$5,987 and US$14,990, respectively. One-way sensitivity analysis revealed that the improvement in FEV1 provided by IND/GLY, the distribution of patients with regard to the severity of COPD, and acute exacerbation rate ratio were the key drivers behind cost-effectiveness. Adopting a willingness to pay of US$60,000 per QALY gained as the threshold, there was a 98.7% probability that IND/GLY was cost-effective compared to tiotropium. Similarly, there was a 99.9% probability that IND/GLY was cost-effective compared to SFC. Conclusion: As a maintenance treatment for COPD, we consider the dual bronchodilator IND/GLY as a cost-effective strategy when compared to either tiotropium or SFC. Keywords: COPD, LABA/LAMA dual bronchodilator, indacaterol/glycopyrronium, maintenance therapy, cost-effectiveness, ICS/LABA combination

Yi-Chih Huang,1,2 Mei-Chen Yang1,2 1Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, 2The School of Medicine, Tzu-Chi University, Hualien, Taiwan Purpose: To investigate associations between occupational inhalation risks and fractional exhaled nitric oxide (FeNO) levels in patients with chronic obstructive pulmonary disease (COPD).Patients and methods: Data of 16,486 subjects who had undergone spirometry with pre-bronchodilator and post-bronchodilator lung function assessment were retrieved from the National Health and Nutrition Examination Survey, 2007–2012 database. After excluding 2,638 subjects with missing spirometry values, data of 13,336 subjects were included for analysis. Factors associated with occupational inhalation, FeNO levels and COPD were analyzed using logistic regression analysis.Results: COPD was associated with occupational exposures to mineral dusts, organic dusts, exhaust fumes, other fumes, and second-hand smoking (P50 ppb (ORs 0.058 and 0.210, respectively).Conclusion: Occupational exposures to airborne pollutants carries higher risk of COPD than non-exposure and the risk is higher the longer the duration of exposure. Exposure–response relationships are inconsistent in subjects with suspected asthmatic airway inflammation (FeNO ≥50 ppb). More careful risk assessment is needed in occupational inhalation exposure, since COPD with asthmatic airway inflammation, or asthma-COPD overlapping syndrome, may have the distinguishing features of both COPD and asthma. Keywords: chronic obstructive pulmonary disease, COPD, fractional exhaled nitric oxide, FeNO, occupational inhalation risk

Cheng-I Hsieh,1–3 Kuo-Piao Chung,3 Ming-Chin Yang,3 Tsai-Chung Li4–61Division of Hematology and Oncology, Department of Internal Medicine, Taipei Medical University Hospital, 2Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, 3Institute of Health Policy and Management, College of Public Health, National Taiwan University, Taipei, 4Graduate Institute of Biostatistics, College of Public Health, China Medical University, 5Graduate Institute of Chinese Medicine Science, College of Chinese Medicine, China Medical University, 6Department of Healthcare Administration, College of Health Science, Asia University, Taichung, TaiwanBackground: A variety of unfulfilled needs may trigger doctor-shopping behavior (DSB) in patients. In oncology, treatment results usually cause patients the most concern. This study investigated the association of DSB with active treatments received by patients with hepatocellular carcinoma (HCC) and outcomes.Methods: With approval from the institutional review board, all patients registered in the cancer database of a teaching hospital and diagnosed as having HCC by self-referral from outside hospitals or by in-house diagnosis were retrospectively identified. Patient data were then reviewed and analyzed via electronic medical records.Results: Hepatitis B carriers were significantly more likely than noncarriers to show first-time DSB. Recurrent disease was less likely to result in DSB than predicted. Patients from outside hospitals not receiving upfront first treatment after diagnosis were significantly more likely to show more frequent DSB than those receiving it. Male patients eligible for salvage treatment were less likely to have frequent occurrences of DSB than their female counterparts. Receiving first salvage treatment was not associated with more frequent DSB. Treatment recommendations offered in the study hospital did not influence patients' decisions to leave or stay. Only elderly patients (>70 years) were less likely to show DSB.Conclusion: DSB can occur throughout the entire course of treatment for HCC for a variety of reasons. Active treatments, disease status, and patient characteristics all exerted an influence on DSB.Keywords: doctor-shopping behavior, second opinion, hepatocellular carcinoma

The maturation of inhibitory circuits in juvenile visual cortex triggers a critical period in the development of the visual system. Although several manipulations of inhibition can alter the timing of the critical period, none have demonstrated the creation of a new critical period in adulthood. We developed a transplantation method to reactivate critical period plasticity in the adult visual cortex. Transplanted embryonic inhibitory neurons from the medial ganglionic eminence reinstate ocular dominance plasticity inadult recipients. Transplanted inhibitory cells develop cell-type-appropriate molecular characteristics and visually evoked responses. In adult mice impaired by deprivation during the juvenile critical period, transplantation also recovers both visual cortical responses and performance on a behavioral test of visual acuity. Plasticity and recovery are induced when the critical period would have occurred in the donor animal. These results reveal that the focal reactivation of visual cortical plasticity using inhibitory cell transplantation creates a new critical period that restores visual perception after childhood deprivation.

Purpose: As certain vaccine serotypes are still circulating within the community during the PCV13 era, we aimed to delineate the clinical features and assess the immunity following breakthrough infections in children., Methods: 101 PCVs-vaccinated children < 18 years with culture confirmed PCV13 serotype breakthrough infection (25/101, invasive pneumococcal disease [IPD]) was identified in Taiwan in 2015-2019. Immunoglobulin G (IgG) antibody levels, IgM + memory B cells (MBCs), and isotype-switched immunoglobulin (sIg + ) MBC specific to serotypes 3, 14, 19 A were assessed prior to and one month after an additional PCV13 booster in 9 patients. A cohort of 89 previously vaccinated, healthy children were enrolled as controls., Results: The majority (88%) of the breakthrough infection occurred in children under 7 years old. Infection by serotypes 3 and 19 A increased in children aged 5-17 years in 2018-2019. The pre-booster serotype 3- and 19 A-specific IgG in both children with breakthrough infection and controls were lower than the IPD protective thresholds (2.83 µg/mL for 3; 1.00 µg/mL for 19 A). Breakthrough infected children showed higher geometric mean ratio in serotype-specific IgG, IgM + MBCs and sIg + MBC after an additional PCV13 booster, compared to the controls., Conclusions: Most breakthrough infections occurred in previously healthy preschool-aged children, but such infections may still occur in school-aged children due to waning immunity. Breakthrough infections may also enhance the anamnestic response elicited by PCV13., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

ABCA12 is crucial for skin barrier function and traditionally linked to severe congenital ichthyosis, such as harlequin ichthyosis. However, its genotype-phenotype relationship may be more nuanced. Using whole-exome sequencing and Sanger sequencing, we identified four cases of mild ichthyosis with biallelic ABCA12 pathogenic variants. In addition to a milder phenotype, the palmoplantar keratoderma (PPK) in these cases had a distinct "mosaic-tile like" pattern. Two cases with missense variants in the N-terminus of ABCA12 also presented an annular ichthyosis pattern resembling erythrokeratodermia variabilis et progressiva (EKVP). Our findings suggest a correlation between ABCA12 missense variant location and clinical presentation, expanding the phenotype spectrum associated with ABCA12 variants and highlighting the potential for annular patterns or "mosaic-tile like" PPK in these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: To examine the relative importance of social cognitive predictors (ie, performance accomplishment, vicarious learning, verbal persuasion, affective state) on health promotion self-efficacy among older adults during COVID-19., Design: Cross-sectional., Setting: Data collected online from participants in British Columbia (BC), Canada., Subjects: Seventy-five adults (n = 75) aged ≥65 years., Measures: Health promotion self-efficacy was measured using the Self-Rated Abilities for Health Practices Scale. Performance accomplishment was assessed using the health directed behavior subscale of the Health Education Impact Questionnaire; vicarious learning was measured using the positive social interaction subscale of the Medical Outcomes Survey - Social Support Scale (MOS-SSS); verbal persuasion was assessed using the informational support subscale from the MOS-SSS; and affective state was assessed using the depression subscale from the Depression Anxiety Stress Scale (DASS-21)., Analysis: Multiple linear regression was used to investigate the relative importance of each social cognitive predictor on self-efficacy, after controlling for age., Results: Our analyses revealed statistically significant associations between self-efficacy and performance accomplishment (health-directed behavior; β = .20), verbal persuasion (informational support; β = .41), and affective state (depressive symptoms; β = -.44) at P < .05. Vicarious learning (β = -.15) did not significantly predict self-efficacy. The model was statistically significant ( P < .001) explaining 43% of the self-efficacy variance., Conclusion: Performance accomplishment experiences, verbal persuasion strategies, and affective states may be the target of interventions to modify health promotion self-efficacy among older adults, in environments that require physical and social distancing., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aimed to identify clinical characteristics to differentiate multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) in Taiwan, an island with a delayed cluster of MIS-C and a high incidence of KD. Additionally, we studied risk factors for developing severe complications in patients with MIS-C., Methods: We conducted a retrospective, multicenter, cohort, and observational study that linked data on patients with MIS-C between May and December 2022 and patients with KD between 2019 and 2021 from 12 medical centers. Hemodynamic compromise, defined as the need for inotropic support or fluid challenge, was recorded in patients with MIS-C. We also evaluated maximal coronary Z-scores before treatment and one month after disease onset., Results: A total of 83 patients with MIS-C and 466 patients with KD were recruited. A 1:1 age and gender-matched comparison of 68 MIS-C and KD pairs showed that MIS-C patients had a lower percentage of positive BCG red halos, lower leukocyte/platelet counts, more gastrointestinal symptoms, and a higher risk of hemodynamic compromise. In Taiwan, 38.6% of MIS-C patients experienced hemodynamic compromise, with presence of conjunctivitis and elevated levels of procalcitonin (>1.62 ng/mL) identified as independent risk factors., Conclusion: We identified two independent risk factors associated with hemodynamic compromise in MIS-C patients. The comparison between matched MIS-C and KD patients highlighted significant differences in clinical presentations, like BCG red halos, which may aid in the differential diagnosis of the two disease entities, especially in regions with a high incidence rate of KD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

As the prevalence of obesity continues to rise globally, the research on adipocytes has attracted more and more attention. In the presence of nutrient overload, adipocytes are exposed to pressures such as hypoxia, inflammation, mechanical stress, metabolite, and oxidative stress that can lead to organelle dysfunction. Endoplasmic reticulum (ER) is a vital organelle for sensing cellular pressure, and its homeostasis is essential for maintaining adipocyte function. Under conditions of excess nutrition, ER stress (ERS) will be triggered by the gathering of abnormally folded proteins in the ER lumen, resulting in the activation of a signaling response known as the unfolded protein responses (UPRs), which is a response system to relieve ERS and restore ER homeostasis. However, if the UPRs fail to rescue ER homeostasis, ERS will activate pathways to damage cells. Studies have shown a role for disturbed activation of adipocyte ERS in the pathophysiology of obesity and its complications. Prolonged or excessive ERS in adipocytes can aggravate lipolysis, insulin resistance, and apoptosis and affect the bioactive molecule production. In addition, ERS also impacts the expression of some important genes. In view of the fact that ERS influences adipocyte function through various mechanisms, targeting ERS may be a viable strategy to treat obesity. This article summarizes the effects of ERS on adipocytes during obesity., (© The Author(s), 2024.)

Background: Coronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients., Methods: This study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT., Results: Most post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1 s to forced vital capacity ratio (<70%) was initially 2% in Group 4, it increased to 29% after MCT. No significant differences in allergic history or underlying diseases were observed between the groups., Conclusions: These findings provide comprehensive insights into the AHR and respiratory symptoms of post-COVID-19 individuals, highlighting the characteristics and potential exacerbations in patients with positive MCT results. This emphasises the need of MCT to address respiratory dynamics in post-COVID-19 individuals., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to declare., (Copyright ©The authors 2024.)

Decellularised extracellular matrix (dECM) produced by mesenchymal stromal cells (MSCs) is a promising biomaterial for improving the ex vivo expansion of MSCs. The dECMs are often deposited on high modulus surfaces such as tissue culture plastic or glass, and subsequent differentiation assays often bias towards osteogenesis. We tested the hypothesis that dECM deposited on substrates of varying modulus will produce cell culture environments that are tailored to promote the proliferation and/or lineage-specific differentiation of MSCs. dECM was produced on type I collagen-functionalised polyacrylamide hydrogels with discrete moduli (∼4, 10, and 40 kPa) or in a linear gradient of modulus that spans the same range, and the substrates were used as culture surfaces for MSCs. Fluorescence spectroscopy and mass spectrometry characterization revealed structural compositional changes in the dECM as a function of substrate modulus. Softer substrates (4 kPa) with dECM supported the largest number of MSCs after 7 days (∼1.6-fold increase compared to glass). Additionally, osteogenic differentiation was greatest on high modulus substrates (40 kPa and glass) with dECM. Nuclear translocation of YAP1 was observed on all surfaces with a modulus of 10 kPa or greater and may be a driver for the increased osteogenesis on the high modulus surfaces. These data demonstrate that dECM technology can be integrated with environmental parameters such as substrate modulus to improve/tailor MSC proliferation and differentiation during ex vivo culture. These results have potential impact in the improved expansion of MSCs for tailored therapeutic applications and in the development of advanced tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE: Mesenchymal stromal cells (MSCs) are extensively used in tissue engineering and regenerative medicine due to their ability to proliferate, differentiate, and modulate the immune environment. Controlling MSC behavior is critical for advances in the field. Decellularised extracellular matrix (dECM) can maintain MSC properties in culture, increase their proliferation rate and capacity, and enhance their stimulated differentiation. Substrate stiffness is another key driver of cell function, and previous reports have primarily looked at dECM deposition and function on stiff substrates such as glass. Herein, we produce dECM on substrates of varying stiffness to create tailored environments that enhance desired MSC properties such as proliferation and differentiation. Additionally, we complete mechanistic studies including quantitative mass spec of the ECM to understand the biological function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Prehospital telemedicine triage systems combined with machine learning (ML) methods have the potential to improve triage accuracy and safely redirect low-acuity patients from attending the emergency department. However, research in prehospital settings is limited but needed; emergency department overcrowding and adverse patient outcomes are increasingly common., Objective: In this scoping review, we sought to characterize the existing methods for ML-enhanced telemedicine emergency triage. In order to support future research, we aimed to delineate what data sources, predictors, labels, ML models, and performance metrics were used, and in which telemedicine triage systems these methods were applied., Methods: A scoping review was conducted, querying multiple databases (MEDLINE, PubMed, Scopus, and IEEE Xplore) through February 24, 2023, to identify potential ML-enhanced methods, and for those eligible, relevant study characteristics were extracted, including prehospital triage setting, types of predictors, ground truth labeling method, ML models used, and performance metrics. Inclusion criteria were restricted to the triage of emergency telemedicine services using ML methods on an undifferentiated (disease nonspecific) population. Only primary research studies in English were considered. Furthermore, only those studies using data collected remotely (as opposed to derived from physical assessments) were included. In order to limit bias, we exclusively included articles identified through our predefined search criteria and had 3 researchers (DR, JS, and KS) independently screen the resulting studies. We conducted a narrative synthesis of findings to establish a knowledge base in this domain and identify potential gaps to be addressed in forthcoming ML-enhanced methods., Results: A total of 165 unique records were screened for eligibility and 15 were included in the review. Most studies applied ML methods during emergency medical dispatch (7/15, 47%) or used chatbot applications (5/15, 33%). Patient demographics and health status variables were the most common predictors, with a notable absence of social variables. Frequently used ML models included support vector machines and tree-based methods. ML-enhanced models typically outperformed conventional triage algorithms, and we found a wide range of methods used to establish ground truth labels., Conclusions: This scoping review observed heterogeneity in dataset size, predictors, clinical setting (triage process), and reported performance metrics. Standard structured predictors, including age, sex, and comorbidities, across articles suggest the importance of these inputs; however, there was a notable absence of other potentially useful data, including medications, social variables, and health system exposure. Ground truth labeling practices should be reported in a standard fashion as the true model performance hinges on these labels. This review calls for future work to form a standardized framework, thereby supporting consistent reporting and performance comparisons across ML-enhanced prehospital triage systems., (©Daniel Raff, Kurtis Stewart, Michelle Christie Yang, Jessie Shang, Sonya Cressman, Roger Tam, Jessica Wong, Martin C Tammemägi, Kendall Ho. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 11.09.2024.)

Introduction: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU)., Methods: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth., Results: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia., Conclusion: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size., Trial Registration: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered)., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Benja-ummarit (BU), a traditional Thai herbal formula, has been prescribed by traditional Thai practitioners for the treatment of liver cancer. Clinical trials of BU have shown an increase in overall survival in hepatocellular carcinoma (HCC) patients, including stage 1-3 (with or without prior standard chemotherapy) and terminal stage. The clinical outcomes differ from those of other apoptosis-based conventional chemotherapies. The molecular mechanisms underlying the anti-cancer properties of BU remain unclear., Aim of Study: To investigate BU-induced ferroptosis through morphological and molecular analyses of HCC cell lines and HCC rat tissues., Methodology: Cytotoxicity of BU extract in HepG2 and HuH-7 cells, with or without LX-2 in 2D and 3D cultures, was determined through MTT assay and by observing spheroid formation, respectively, as compared to sorafenib. Morphological changes and the cellular ultrastructure of the treated cells were evaluated by light microscopy and transmission electron microscopy (TEM), respectively. In addition, alterations in ferroptosis protein markers in both cell lines and rat liver tissue were determined using western blot analysis and immunohistochemical staining, respectively. To investigate the pathways mediating ferroptosis, cells were pretreated with an iron chelator to confirm the iron-dependent ferroptosis induced by the BU extract. Intracellular ROS, a mediator of ferroptosis, was measured using a scanning ion conductance microscope (SICM). SICM was also used to determine cellular stiffness. The lipid profiles of BU-treated cells were studied using LC-MS/MS., Results: The BU extract induced cell death under all HCC cell culture conditions. The BU-IC 50 in HepG2 and HuH-7 were 31.24 ± 4.46 μg/mL and 23.35 ± 0.27 μg/mL, respectively as determined by MTT assay. In co-culture with LX-2, BU exhibited a similar trend of cytotoxicity in both HepG2 and HuH-7 cells. Light microscopy showed cell ballooning features with intact plasma membranes, and TEM microscopy showed mitochondrial swelling and reduced mitochondrial cristae in BU-treated cells. BU promotes intracellular iron levels by increasing DMT1 and NCOA4 expression and decreasing FTH1 expression. BU also suppressed the cellular antioxidant system by lowering CD98, NRF2, and GPX4 expression, and promoting KEAP1 expression. IHC results of HCC rat liver tissues showed the absence of DMT1 and high expression of GPX4 in the tumor area. Pre-treatment with an iron chelator partially restored cell viability and shifted the mode of cell death to a more apoptosis-like morphology in the BU-treated group. The SICM showed increased intracellular ROS levels and cellular stiffness 24 h after BU treatment. In more detail of BU-mediated ferroptosis, cellular lipid profiling revealed increased expression of 3 polyunsaturated lipids, which are highly susceptible to lipid peroxidation, in BU-treated cells., Discussion: Alterations in intracellular iron levels, ROS levels, and cellular lipid composition have been previously reported in cancer cells. Therefore, targeting the iron-dependent ROS pathway and polyunsaturated lipids via BU-induced ferroptosis may be more cancer-specific than apoptosis-based cancer drugs. These observations are in accordance with the clinical outcomes of BU. The ferroptosis-inducing mechanism of BU makes it an extremely promising novel drug candidate for the treatment of HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy., Materials and Methods: Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value., Results: Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement ( p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms., Conclusion: The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Liu, Zhang, Guo, Yang, Zhang, Cui, Zhou, Guo and Hou.)

Background: Fiberglass has a larger aerodynamic diameter and is less likely to be inhaled into the lungs. Further, it will be cleared even if it is mechanically broken into smaller pieces and inhaled into the lungs. Fiberglass lung disease has been well documented if long term exposure but was thought reversible and would not cause severe diseases. The diagnosis of fiberglass lung disease depends on exposure history and histopathological findings. However, the exact occupational exposure history is often difficult to identify because mixed substance exposure often occurs and fiberglass disease is not as well-known as asbestosis., Case Presentation: A 66-year-old man had unexplained transudative pericardial effusion requiring pleural pericardial window operation twice at another medical center where asbestosis was told because of his self-reported long-term asbestosis exposure and the histopathological finding of a ferruginous body in his lung. Constrictive pericarditis developed two years later and resulted in congestive heart failure. Radical pericardiectomy combined with lung biopsy was performed following chest computed tomography imaging and the transudative nature of pericardial effusion not compatible with asbestosis. However, the histopathologic findings of his lung and pericardium at our hospital only showed chronic fibrosis without any asbestosis body. The patient's lung was found to be extremely fragile during a lung biopsy; histopathologic specimens were reviewed, and various fragments of fiberglass were found in the lung and pericardium. The patient's occupational exposure was carefully reevaluated, and he restated that he was only exposed to asbestosis for 1-2 years but was heavily exposed to fiberglass for more than 40 years. This misleading exposure history was mainly because he was only familiar with the dangers of asbestos. Since most fiberglass lung diseases are reversible and the symptoms of heart failure resolve soon after surgery, only observation was needed. Ten months after radical pericardiectomy, his symptoms, pleural effusion, and impaired pulmonary function eventually resolved., Conclusion: Fiberglass could cause inflammation of the pericardium, resulting in pericardial effusion and constrictive pericarditis, which could be severe and require radical pericardiectomy. Exact exposure history and histopathological examinations are the key to diagnosis., (© 2024. The Author(s).)

Purpose: To describe the use of an amniotic membrane graft (AMG) with fibrin sealant to address an overfiltering trabeculectomy flap encountered intraoperatively., Observations: A 35-year-old female with severe primary open angle glaucoma underwent trabeculectomy with mitomycin C due to uncontrolled intraocular pressure (IOP). Intraoperatively, the elastic nature of the scleral flap led to overfiltration, causing persistent anterior chamber shallowing despite numerous sutures. To decrease but not completely shut down aqueous outflow through the trabeculectomy flap, we utilized AMG and fibrin sealant to stabilize the flap. Postoperatively, the patient had a formed anterior chamber, elevated bleb and significantly reduced IOP, without the need for additional glaucoma medications., Conclusions and Importance: Amniotic membrane grafts (AMG) with fibrin sealant may help regulate aqueous flow efflux, maintain anterior chamber stability, and mitigate the risk of postoperative hypotony in trabeculectomy surgery. AMG was chosen in this setting given its anti-inflammatory, anti-fibrotic properties, as well as its optically clear nature to allow for post-operative visualization of the flap. AMG allows for early postoperative stabilization of the scleral flap without complete obstruction, and may be useful in patients at risk of early postoperative hypotony., Competing Interests: 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., (© 2024 The Authors.)

Gastroesophageal reflux disease (GERD) is associated with an incompetent lower esophageal sphincter (LES), resulting in the reflux of gastric contents into the esophagus. U46619, a thromboxane A2 (TXA2) receptor agonist, induces contractions in various smooth muscles. Therefore, this study aimed to investigate the effects and mechanisms of action of U46619 on the porcine LES. To achieve this, contractions of the clasp and sling strips of the porcine LES, induced by U46619, were measured using isometric transducers. Furthermore, the contractile mechanism of U46619 in the porcine LES was investigated by pretreating the strips with atropine (a muscarinic receptor antagonist), tetrodotoxin (a neuronal sodium channel blocker), nifedipine (a calcium channel blocker), and Ca 2+ -free Krebs-Henseleit solution. Additionally, reverse transcription polymerase chain reaction (PCR) and immunohistochemistry (IHC) were performed to determine the presence of the TXA2 receptor in porcine LES. The results of this study demonstrated that U46619 caused marked concentration-dependent contractions in both porcine sling and clasp strips. The mechanism of U46619-induced contraction of the porcine LES was found to be related to calcium channels. Furthermore, the reverse transcription PCR analysis and IHC revealed that the TXA2 receptor was expressed in the clasp and sling fibers of porcine LES. Consequently, this study suggests that U46619 mediates the contraction of porcine LES through calcium channels and has potential as a therapeutic approach for treating GERD. SIGNIFICANCE STATEMENT: This study establishes that U46619 induces concentration-dependent contractions in porcine LES, primarily mediated by calcium channels. The presence of the TXA2 receptor in LES clasp and sling fibers is confirmed. These findings highlight U46619's potential as a GERD therapeutic by targeting calcium channels for LES contraction modulation., (Copyright © 2024 by The Author(s).)

Background: Sciaenidae is one of the most important coastal fisheries in Taiwan, both in production and economic value. It is also significant as the main targetted diet of Chinese white dolphins, Sousachinensis , especially for the genus Johnius , such as J.taiwanensis , J.belangerii and J.distinctus , which is primarily found in central-western Taiwan coastal waters. Despite an abundance of Johnius species occurrences reported in the Global Biodiversity Information Facility (GBIF) and the Taiwan Biodiversity Information Facility (TaiBIF) data portals (Mozambique, Australia, Taiwan, Korea, India, Indonesia, South Africa, Pakistan, Vietnam and China), there are no specific datasets that properly document the regional distribution of this genus, especially in Taiwanese waters. Thus, this paper describes a dataset of genus Johnius occurrences in waters on the central-western coast of Taiwan. The data collection for the present study was conducted from 2009 until 2020 and comprised 62 sampling events and 133 occurrence records. All fish specimens were collected by trawling in Miaoli, Changhwa and Yunlin Counties, Taiwan and brought back to the lab for identification, individual number count and body weight measurement. These processing data have been integrated and established in the Taiwan Fish Database and published in GBIF. This dataset contains six Johnius species and 2,566 specimens, making it comprehensive Johnius fish fauna and spatial distributional data on the coastal habitat in central-western Taiwanese waters., New Information: This dataset contains 133 occurrence records of Johnius species (Sciaenidae) with 2,566 specimens, making it the most extensive public dataset of Johnius distribution records in Taiwan. The publication of this dataset through the TaiBIF and GBIF dataset platforms demonstrated that the number of Johnius spatial and temporal records in Taiwan waters is influenced by the topographical structure of the Changyun Rise (CYR) in combination with the cold current of the China Coastal currents and bound with the warm currents of the Kuroshio and the South China Sea on the central-western coast of Taiwan. The data serve as the foundation for understanding the biogeography and Johnius species ecology in Taiwan's coastal waters, which present a 2°C water temperature difference split at the CYR., (Norhafiz Hanafi, Meng-Hsien Chen, Ming-Che Yang, Chien-Cheng Lai, Chih-Wei Chang.)

A digermanium(III) 1,2-dication comprises two cationic centers located at two interconnected Ge atoms. The strong Coulombic repulsion between two positively charged germanium cations hinders their bond formation. Balancing these two oppositions was achieved by using amidinate and cyclic (alkyl)amino carbene (cAAC)-phosphinidenide ligands, where an amidinato cAAC-phosphinidenidogermylene complex, [LGeP(cAAC Me )] ( 2 , where L = PhC(N t Bu) 2 , cAAC Me = :C{C(Me) 2 CH 2 C(Me) 2 NAr}, and Ar = 2,6- i Pr 2 C 6 H 3 ), underwent one-electron oxidation with a bis(phosphinidene) radical cation, [(cAAC Me )P] 2 •+ , to form a digermanium(III) 1,2-dication, [LGeP(cAAC Me )] 2 2+ , in compound 4 .

Objectives: Endotracheal tube (ETT) intubation is a life-saving procedure in patients with respiratory failure. However, the presence of an ETT can cause significant discomfort. A tracheostomy tube is used to administer a mechanical ventilator, resulting in a more stable airway and fewer serious injuries. Noninvasive ventilators (NIPPVs) administer ventilation through masks and must be tightly fixed to the face. ETT, tracheostomy, and NIPPV are the most common methods of ventilator maintenance. However, these interventions often cause discomfort to patients. This study aimed to compare discomfort associated with ETT, tracheostomy, and NIPPV., Materials and Methods: Forty-nine conscious patients with postextubation NIPPV and eight conscious patients who underwent postextubation tracheotomy were evaluated for discomfort. A questionnaire survey on discomfort was performed before and after NIPPV or tracheostomy. These patients reported their level of discomfort on a visual analog scale., Results: The levels of sore throat, nasal pain, body pain, activity limitation, respiratory discomfort, oral discomfort, difficulty coughing sputum, worry about respiratory tube disconnection, back pain, anxiety, worry about long-term admission, sleep disturbance, and general discomfort during ETT intubation were higher than during tracheostomy or NIPPV (all P < 0.05). The mean level of discomfort was approximately 5-6 points (moderate) in patients with ETT and 2-3 points (mild) in patients with NIPPV or tracheostomy., Conclusion: The level of discomfort was higher in patients who underwent ETT intubation than in those who underwent NIPPV or tracheostomy. However, the level of discomfort was similar between the patients with NIPPV and those who underwent tracheostomy., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Background: Subdural empyema is one of the more serious complications of bacterial meningitis and therapeutic challenges to clinicians. We aimed to evaluate the clinical characteristics, treatment, and outcome of subdural empyema in neonates with bacterial meningitis. Methods: A retrospective cohort study was conducted in two medical centers in Taiwan that enrolled all cases of neonates with subdural empyema after bacterial meningitis between 2003 and 2020. Results: Subdural empyema was diagnosed in 27 of 153 (17.6%) neonates with acute bacterial meningitis compared with cases of meningitis without subdural empyema. The demographics and pathogen distributions were comparable between the study group and the controls, but neonates with subdural empyema were significantly more likely to have clinical manifestations of fever (85.2%) and seizure (81.5%) (both p values < 0.05). The cerebrospinal fluid results of neonates with subdural empyema showed significantly higher white blood cell counts, lower glucose levels and higher protein levels ( p = 0.011, 0.003 and 0.006, respectively). Neonates with subdural empyema had a significantly higher rate of neurological complications, especially subdural effusions and periventricular leukomalacia. Although the final mortality rate was not increased in neonates with subdural empyema when compared with the controls, they were often treated much longer and had a high rate of long-term neurological sequelae. Conclusions: Subdural empyema is not uncommon in neonates with acute bacterial meningitis and was associated with a high risk of neurological complications, although it does not significantly increase the final mortality rate. Close monitoring of the occurrence of subdural empyema is required, and appropriate long-term antibiotic treatment after surgical intervention may lead to optimized outcomes.

Background/purpose: Healthy states of human microbiota depend on a stable community of symbiotic microbes irrespective of external challenges from the environment. Thus, long-term stability of the oral microbiota is of importance, particularly for older patient populations., Materials and Methods: We used next-generation sequencing (NGS) to examine the tongue microbiota of 18 individuals receiving long-term care over a 10-month period., Results: Beta diversity analysis demonstrated temporal stability of the tongue microbiota, as microbial compositions from all time points were indistinguishable from each other ( P  = 0.0887). However, significant individual variation in microbial composition ( P  = 0.0001) was observed, underscoring the presence of a unique microbial profile for each patient., Conclusion: The temporal dynamics of tongue microbiota exhibit long-term stability, providing diagnostic implications for oral diseases within older patient populations., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

The objective of this study was to investigate gut dysbiosis and its metabolic and inflammatory implications in pediatric metabolic dysfunction-associated fatty liver disease (MAFLD). This study included 105 children and utilized anthropometric measurements, blood tests, the Ultrasound Fatty Liver Index, and fecal DNA sequencing to assess the relationship between gut microbiota and pediatric MAFLD. Notable decreases in Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. were found in the MAFLD group. Lachnospira spp. was particularly reduced in children with MAFLD and hepatitis compared to controls. Both MAFLD groups showed a reduction in flavone and flavonol biosynthesis sequences. Lachnospira spp. correlated positively with flavone and flavonol biosynthesis and negatively with insulin levels and insulin resistance. Body weight, body mass index (BMI), and total cholesterol levels were inversely correlated with flavone and flavonol biosynthesis. Reduced Lachnospira spp. in children with MAFLD may exacerbate insulin resistance and inflammation through reduced flavone and flavonol biosynthesis, offering potential therapeutic targets.