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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

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

Shin-Hong Chen,1 I-Shiang Tzeng,2– 4 Chou-Chin Lan,5,6 Jau-Yuan Chen,7 Chau Yee Ng,8 Yao-Chin Wang,9 Wen-Lin Su,5 Giou-Teng Yiang,10 Tsu-Yi Chen,10 Chih-Wei Wu,5 Po-Chun Hsieh,11 Chan-Yen Kuo,4 Meng-Yu Wu10 1Department of Education and Research, Taiwan Adventist Hospital, Taipei 10556, Taiwan; 2Department of Statistics, National Taipei University, Taipei 10478, Taiwan; 3Department of Applied Mathematics; Department of Exercise and Health Promotion, Chinese Culture University, Taipei 11114, Taiwan; 4Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; 5Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; 6School of Medicine, Tzu-Chi University, Hualien 97004, Taiwan; 7Department of Family Medicine, Chang-Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan; 8Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Linkou and Keelung 10507, Taiwan; 9Department of Emergency Medicine, Min-Sheng General Hospital, Taoyuan 33044, Taiwan; 10Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan; 11Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, TaiwanCorrespondence: I-Shiang Tzeng No. 289, Jianguo Road, Xindian Dist, New Taipei City 231, TaiwanTel +886-2-6628-9779 ext. 3119Email istzeng@gmail.comBackground: Emergency room (ER) physicians need to face clinically suspected pneumonia patients in the front line of medical care and must do to give major medical interventions if patients show severity in pneumonia.Methods: The data of pneumonia-related ER visit rates were categorized based on the International Classification of Disease (ICD) Codes (480– 486) between 1998 and 2012. We use an age-period-cohort (APC) model to separate the pneumonia-related ER visit rates to identify the effects of age, time period, and cohort for a total of 1,813,588 patients.Results: The age effect showed high risk for pediatric and elder populations. There is a significant increasing period effect, which increased from 1998 to 2012. The cohort effect tended to show an oscillation from 1913 to 1988 and the reverse in a recent cohort. Furthermore, the visit rate of pneumonia showed an increase from 1998 to 2012 for both genders.Conclusion: Age is a risk factor for pneumonia-related ER visits, especially for children and adolescents and older patients. Period and cohort effects were also found to increase the pneumonia visit rates. An APC model used to provide an advance clue for trend of pneumonia-related ER visit rates diversified.Keywords: age-period-cohort, age-adjusted emergency rooms visit rates, pneumonia

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

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.)

Alcohol dependence (AD) and gambling disorder (GD) are common addiction disorders with significant physical and mental health consequences. AD and GD are associated with dysregulated responses to reward which could be due to a common mechanism of dysregulated endogenous opioid signalling. We explored associations between reward anticipation responses, using the Monetary Incentive Delay (MID) functional magnetic resonance imaging (fMRI) task, and mu-opioid receptor (MOR) availability and endogenous opioid release capacity using [ 11 C]carfentanil positron emission tomography (PET), in 13 AD, 15 GD and 14 heathy control (HC) participants. We also examined differences in MID task reward anticipation responses between AD, GD and HC participants. These were secondary exploratory analysis of data collected to examine differences in MOR PET in addiction. We did not find significant differences in MID win > neutral anticipation BOLD responses compared between participant groups in a priori ROIs (ventral striatum, putamen, caudate) or whole brain analyses. We found no significant correlations between MID win > neutral anticipation BOLD responses and [ 11 C]carfentanil PET measures, except for limited negative correlations between putamen MOR availability and MID win > neutral anticipation BOLD response in AD participants. Previous research has suggested a limited role of endogenous opioid signalling on MID task reward anticipation responses in AD and HCs as these responses are not modulated by opioid receptor blockade and this may explain our lack of significant correlations in HC and AD or GD participants. Our results, particularly the lack of differences in MID win > neutral anticipation BOLD responses across participants groups, may be limited due to only including AD or GD participants who are abstinent or in active treatment., Competing Interests: Prof Luke Clark is the Director of the Centre for Gambling Research at 10.13039/501100005247UBC, which is supported by funding from the Province of British Columbia and the British Columbia Lottery Corporation (BCLC), a Canadian Crown Corporation. The Province of BC government and the BCLC had no role in the design, analysis, or interpretation of the study, and impose no constraints on publishing. LC has received remuneration from the International Center for Responsible Gaming (travel; speaker honoraria; academic services), the Institut fur Glucksspiel und Gesellschaft (Germany; travel; speaker honoraria), GambleAware (UK; academic services), Gambling Research Australia (academic services), Alberta Gambling Research Institute (Canada; travel; academic services), German Foundation for Gambling Research (advisory board; travel). He has been remunerated for legal consultancy by the BCLC. He has not received any further direct or indirect payments from the gambling industry or groups substantially funded by gambling. LC receives an honorarium for his role as Co-Editor-in-Chief for International Gambling Studies from Taylor & Francis, and he has received royalties from Cambridge Cognition Ltd. relating to neurocognitive testing. Prof David Nutt is the CRO of Awakn Life Sciences, chair of DrugScience [UK] and PAREA Europe, a member of the Lundbeck Foundation Neurotorium programme and chair of its editorial board, advisor to the British National Formulary and a member of the International Centre for Science in Drug Policy. He has received grants or clinical trial payments from Wellcome Trust, MRC, COMPASS Pathways and Usona, speaking honoraria from Janssen, Lundbeck, Otsuka and Rovi, has share options in P1vital, Awakn, Psyched Wellness and Neurotherapeutics and is a director of Equasy Enterprises and GABA Labs. He has been an expert witness in a number of legal cases relating to psychotropic drugs, is editor of the Drug Science Policy and Law Journal and has edited/written 38 books, some of which have been purchased by pharmaceutical companies.Prof Anne Lingford-Hughes reports honoraria for speaking engagements and/or attendance at conferences from 10.13039/501100013327Lundbeck, 10.13039/501100013327Lundbeck Institute UK, 10.13039/100004319Pfizer and Servier; she has received research grants or support from Alcarelle and Lundbeck; she is a member of the 10.13039/501100000544British Association for Psychopharmacology and receives honoraria for speaking at educational events and led their ‘addiction’ guidelines, which received support from Archimedes Pharma, 10.13039/501100013327Lundbeck, 10.13039/100004319Pfizer and Schering.The other authors declare no conflicts of interest in relation to this paper., (© 2024 The Authors.)

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).)

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca 2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular Ca 2+ . WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied., Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed., Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [ P = .03%] and 1.0% vs 3.8% [ P = .05], respectively)., Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Finding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown., Objective: We therefore assessed the available literature on DR-TB case-finding strategies., Methods: We looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp)., Results: We screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information., Conclusions: Existing descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies., (©Susanna S van Wyk, Marriott Nliwasa, Fang-Wen Lu, Chih-Chan Lan, James A Seddon, Graeme Hoddinott, Lario Viljoen, Gunar Günther, Nunurai Ruswa, N Sarita Shah, Mareli Claassens. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.06.2024.)

Background: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB)., Methods: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores., Results: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality., Conclusion: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB., (© 2024. The Author(s).)

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer., Methods: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT)., Results: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05)., Conclusions: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer., (© 2024. The Author(s).)

Esophageal cancer, ranked as the eighth most prevalent cancer globally, is characterized by a low survival rate and poor prognosis. Concurrent chemoradiation therapy (CCRT) is the standard therapy in the non-surgical treatment of localized carcinoma of the esophagus. Nevertheless, the radiation doses employed in CCRT remain notably lower compared to the curative definite chemoradiation therapy utilized in the management of other carcinomas. In order to increase the local control rates and enhance the treatment outcomes, several clinical trials have used high-dose radiation to analyze the effect of dose escalation. Despite the integration of technically advanced RT schemes such as intensity-modulated radiation therapy (IMRT), the results of these trials have failed to demonstrate a significant improvement in overall survival or local progression-free survival. In this review, we investigated previous clinical trials to determine the ineffectiveness of radiation dose escalation in the context of CCRT for esophageal cancer. We aim to clarify the factors contributing to the limited efficacy of escalated radiation doses in improving patient outcomes. Furthermore, we delve into recent research endeavors, exploring prospective radiation dose modifications being altered based on the histological characteristics of the carcinoma. The exploration of these recent studies not only sheds light on potential refinements to the existing treatment protocols but also seeks to identify novel approaches that may pave the way for more efficacious and personalized therapeutic strategies for esophageal cancer management.

Objectives: Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma., Materials and Methods: Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO 2 )., Results: Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO 2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters., Conclusion: HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Background and Objective: This study evaluated the predictive roles of hematologic inflammatory biomarkers including neutrophil-percentage-to-albumin ratio (NPAR), neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-lymphocyte ratio (ELR) for mortality in community-dwelling individuals with chronic obstructive pulmonary disease (COPD)., Methods: This longitudinal study extracted data of adults 40-79 years who had physician-diagnosed COPD from the United States (US) National Health and Nutrition Examination Survey (NHANES) 1999-2018. Cox regressions determined the associations between NPAR, NLR, ELR and their components, with all-cause mortality, cardiovascular disease (CVD) mortality and mortality from chronic lower respiratory disease (CLRD). Receiver operating characteristic (ROC) curve analysis estimated the predictive performances of these biomarkers for 5-year all-cause mortality., Results: Data of 1158 subjects were analysed. After adjustment, higher NPAR was significantly associated with increased all-cause and CVD mortality, and mortality from CLRD (adjusted hazard ratio [aHR] = 1.14, 1.15 and 1.16). Higher NLR was associated with an increased all-cause and CVD mortality (aHR = 1.16 and 1.29). Higher neutrophil was associated with increased all-cause mortality and mortality from CLRD (aHR = 1.13 and 1.34). Albumin was associated with decreased all-cause and CVD mortality (aHR = 0.91 and 0.86). ELR, eosinophil or lymphocyte was not significantly associated with either mortality outcomes. Adjusted AUC of NPAR and NLR in predicting 5-year all-cause mortality were 0.808 (95% CI: 0.722-0.845) and 0.799 (95% CI: 0.763-0.835), respectively., Conclusion: In community-dwelling US adults with COPD, increased NPAR and NLR are associated with mortality risks. NPAR outperforms the other hematologic inflammatory biomarkers in predicting 5-year all-cause mortality., (© 2023 Asian Pacific Society of Respirology.)

Background: Chronic obstructive pulmonary disease (COPD) often causes cardiopulmonary dysfunction, which deteriorates exercise capacity. Cardiopulmonary exercise testing (CPET) and echocardiography are common tools for evaluating cardiovascular function. No studies have analyzed the correlation between echocardiography-derived parameters and cardiopulmonary response during exercise., Objectives: We analyzed the correlation between echocardiographic parameters such as tricuspid regurgitation peak gradient (TRPG), tricuspid annular plane systolic excursion (TAPSE), TRPG/TAPSE and CPET-derived parameters., Methods: Seventy-seven patients with COPD were evaluated. We analyzed the correlation between parameters derived from echocardiography, exercise capacity, cardiovascular and ventilatory parameters derived from CPET., Results: The correlation between TRPG/TAPSE and work rate (WR) was moderate and negative (-0.4423, p = 0.0003), while TRPG had a weak negative correlation with WR (r= -0.3099, p = 0.0127). Oxygen uptake at peak exercise was weakly negatively correlated with TRPG/TAPSE (-0.3404, p = 0.0059), TRPG (r= -0.3123, p = 0.0120), and the ratio of early mitral inflow velocity to early mitral annular diastolic velocity (E/E'). The correlation between TRPG/TAPSE and exercise capacity was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE exhibited a moderate negative correlation with cardiac index, whereas TRPG and TAPSE showed a weak correlation. The correlation between TRPG/TAPSE and cardiac function during exercise was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE, TRPG, TAPSE, and E/E' were weakly negatively correlated with lung function., Conclusions: In assessing exercise capacity, cardiac function, and gas exchange, TRPG/TAPSE proves to be superior to other cardiac parameters. Higher TRPG/TAPSE levels corresponded to lower exercise capacity, cardiovascular and ventilatory function., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest, (Copyright © 2023. Published by Elsevier Inc.)

Functional near infrared spectroscopy (fNIRS) is a neuroimaging technique that has grown vigorously in recent years. With noticeable attention, machine learning methods have also been applied to fNIRS. However, the current approach lacks interpretability of the results. In recent years, the utilization and investigation of fNIRS have experienced significant growth and are now being utilized in clinical research. However, the collection of clinical fNIRS data is limited in sample size. Therefore, our aim is to utilize the collected fNIRS data from all channels and achieve interpretable analysis results with minimal human manipulation, channel selection or feature extraction. We developed an fNIRS-based interpretable model and used class-specific gradient information to visualize the biomarkers captured by the model via locating the important region. The accuracy of our model's classification was 6% higher than that of the conventional SVM method under within-subject classification. The model focuses on signals from the left brain in the classification of right-hand finger tapping task, while in the task of classifying left-handed movements, the model relies on signals from the right brain. These results were consistent with current understanding of physiology.Clinical Relevance- The machine learning-based fNIRS model has the potential to be used for the diagnosis and prediction of therapeutic efficacy in clinical settings.

Background: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39-51%, and β-blockers and amlodipine are commonly used drugs for these patients., Objectives: We aimed to study the impact of β-blockers and amlodipine on cardiopulmonary responses during exercise., Methods: A total 81 patients with COPD were included and the patients underwent spirometry, cardiopulmonary exercise tests, and symptoms questionnaires., Results: There were 14 patients who took bisoprolol and 67 patients who did not. Patients with COPD taking ß-blockers had lower blood oxygen concentration (SpO2) and more leg fatigue at peak exercise but similar exercise capacity as compared with patients not taking bisoprolol. There were 18 patients treated with amlodipine and 63 patients without amlodipine. Patients taking amlodipine had higher body weight, lower blood pressure at rest, and lower respiratory rates during peak exercise than those not taking amlodipine. Other cardiopulmonary parameters, such as workload, oxygen consumption at peak exercise, tidal volume at rest or exercise, cardiac index at rest or exercise were not significantly different between patients with or without bisoprolol or amlodipine. Smoking status did not differ between patients with or without bisoprolol or amlodipine., Conclusions: COPD is often accompanied by hypertension, and β-blockers and amlodipine are commonly used antihypertensive drugs for these patients. Patients with COPD taking bisoprolol had lower SpO2 and more leg fatigue during peak exercise. Patients taking amlodipine had lower respiratory rates during exercise than those not taking amlodipine. Exercise capacity, tidal volume, and cardiac index during exercise were similar between patients with and without bisoprolol or amlodipine., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non-small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC., Materials and Methods: The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2)., Results: Thirty-three patients were included (25 women; median age: 63 [45-82] years). The median follow-up of the included patients was 17 months (range 6-89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2-74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6-33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9-39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2., Conclusions: Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further., (© 2023. The Author(s).)

Long-term respirator users admitted to intensive care units need to be transferred to a respiratory care center (RCC) for weaning. It may cause malnutrition in critical care patients, which may manifest as a reduction in respiratory muscle mass, lower ventilatory capacity, and decreased respiratory tolerance. This study aimed to assess that if the patients' nutritional status were improved, it could help RCC patients to wean from respirators. All participants were recruited from the RCC of a medical foundation in the city and Taipei Tzu Chi Hospital. The indicators include serum albumin level, respirator detachment index, maximum inspiratory pressure (PImax), rapid shallow breathing index, and body composition measurements. We recorded the length of hospital stay, mortality, and RCW (respiratory care ward) referral rate for these participants and analyzed the differences in relevant research indicators between those who were and weren't weaned off. 43 of 62 patients were weaned from respirators, while 19 failed. The resuscitation rate was 54.8%. Patients with respirator weaning had a lower number of RCC admission days (23.1 ± 11.1 days) than respirator-dependent patients (35.6 ± 7.8 days, P < 0.05). The PImax of successfully weaned patients had a greater reduction (- 27.09 ± 9.7 cmH 2 O) than unsuccessful ones (- 21.4 ± 10.2 cmH 2 O, P < 0.05). The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of successfully weaned patients (15.8 ± 5.0) were lower than those who were not (20.4 ± 8.4, P < 0.05). There was no significant difference in serum albumin levels between the two groups. In the successfully weaned patients, the serum albumin concentration was increased from 2.2 ± 0.3 to 2.5 ± 0.4 mg/dL, P < 0.05. Improved nutritional status can help RCC patients to wean from respirators., (© 2023. The Author(s).)

A previous study of an animal model with tumor suppressor gene von Hippel-Lindau (VHL) conditional knockdown suggested that tissue inflammation and fibrosis play important roles in the development of clear-cell renal cell carcinoma (ccRCC), which is consistent with the epidemiological evidence linking inflammatory kidney disease and renal cancer. Ferroptosis and inflammation have been linked in a recent study, but the exact mechanism remains unclear. This study is aimed at investigating the mechanism of lipocalin-2- (LCN-2-) mediated ferroptosis and inflammation in vhl -mutated HK-2 cells and mouse primary proximal tubule cells (mRTCs) and the polarization of macrophage RAW 264.7 cells. Based on the levels of lipid reactive oxygen species (ROS) and the expression of glutathione peroxidase 4 (GPX4) in HK-2 cells, we observed that a VHL mutation increased ROS production and depressed GPX4 expression, whereas LCN-2 knockdown reversed these effects. Accordingly, VHL appears to affect ferroptosis in an LCN-2-dependent manner. We also revealed that LCN-2 sensitizes HK-2 cells to inflammation and macrophage RAW 264.7 cells to M1-like polarization. This study provides novel insights into the potential therapeutic target and strategy for attenuating the progression of ccRCC by revealing the role of VHL in regulating chronic inflammation within the LCN-2-ferroptosis pathway., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 Chan-Yen Kuo et al.)

Purpose: Limited data exist on asthma medication patterns in Taiwan. The objectives of the SABINA III cross-sectional study in Taiwan were thus, to describe patient demographics and clinical features and estimate short-acting β 2 -agonist (SABA) and inhaled corticosteroids (ICS) prescriptions per patient., Methods: Patients (≥18 years) with asthma were classified by investigator-defined asthma severity per the 2017 Global Initiative for Asthma (GINA) recommendations. Data on asthma symptom control (per GINA 2017 recommendations), severe exacerbation history, and prescribed treatments in the 12 months before study visit were collected using electronic case-report forms. Analyses were descriptive., Results: Overall, all 294 analyzed patients (mean [SD] age, 57.9 [15.6] years; female, 69%) were enrolled by specialists and had fully reimbursed healthcare. Most patients were classified with moderate-to-severe asthma (93.2%; GINA steps 3-5), were obese (53.4%) and nonsmokers (79.6%), reported high school or university and/or postgraduate education (61.9%), and had ≤2 comorbidities (89.1%). Mean (SD) asthma duration was 8.3 (10.0) years, with 37.8% of patients experiencing ≥1 severe exacerbation 12 months before the study visit. Overall, 62.2%, 26.2%, and 11.6% of patients had well-controlled, partly controlled, and uncontrolled asthma, respectively. Crucially, 19.3% of patients were prescribed ≥3 SABA canisters in the preceding 12 months (overprescription). ICS, ICS + long-acting β 2- agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 6.5%, 97.3%, and 31.6% of patients, respectively., Conclusion: Despite treatment by specialists and fully reimbursed healthcare, findings indicate room for improvement in asthma control and SABA prescription practices in Taiwan, emphasizing the need to adhere to latest evidence-based guidelines., Competing Interests: Declaration of competing interest CWC received grants, personal fees for advisory board participation, and traveling fees from AstraZeneca. SYS, TCL, CYW, MHC, YJC, CCL, JMS, CML, SHW, and HCW do not report any conflicts of interests. LY is an employee of AstraZeneca. MB was an employee of AstraZeneca during the conduct of the study., (Copyright © 2022. Published by Elsevier B.V.)

Nuss surgery is effective in correcting pectus excavatum (PE), with a recurrence rate of 1.2-27%. Re-do surgery is successful but still has a 6% failure rate. Patients with obstructive sleep apnea (OSA) experience repetitive PE-associated sternal depression during sleep. As the prevalence of OSA among PE patients is higher than the average, co-existing OSA in PE patients might negatively affect the efficacy of Nuss surgery. This study aimed to evaluate the impact of co-existing OSA on Nuss surgery in patients with PE. In total, 20 adult patients with PE only and 9 patients with PE and OSA were analyzed. Polysomnography was performed before Nuss surgery to evaluate OSA. Sternovertebral distance (SVD) and radiographic Haller index (RHI) were recorded before surgery and at 3, 6, and 24 months postoperatively. The results showed that percentage changes in SVD in patients with PE only at 3, 6, and 24 months postoperatively were significantly increased compared with those in the patients with PE and OSA (31.1% vs. 14.1% at 3 months; 37.5% vs. 21.4% at 6 months; 42.5% vs. 19.2% at 24 months). Meanwhile, percentage changes in RHI were significantly lower in patients with PE alone than in the patients with PE and OSA (-22.9% vs. -9.3% at 3 months; -27.9% vs. -18.7% at 6 months; -30.6% vs. -16.7% at 24 months). This study showed that co-existing OSA might reduce the efficacy of Nuss surgery for patients with PE. We recommend that patients with PE should be evaluated and treated for OSA before surgery to prevent surgical failure after bar removal., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

When patient with coronavirus disease 2019 (COVID-19) are hospitalized, the limited space for activity, disease itself causes fever, muscle aches, fatigue, respiratory failure with mechanical ventilation, or medications such as steroids or neuromuscular blocking can cause muscle dysfunction. Pulmonary rehabilitation (PR) should be arranged for these patients with COVID-19. However, the literature on early PR within 1 week of admission on patients with COVID-19 are limited. This review focuses on early PR in COVID-19 patients admitted to isolation wards or intensive care units. The essential components of early PR programs include education, breathing exercise, airway clearance, and physical activity training. Breathing exercises, including diaphragmatic and pursed-lip breathing, are known to improve lung function in chronic obstructive pulmonary disease and are also recommended for COVID-19 patients. Poor airway clearance can further aggravate pneumonia. Airway clearance techniques help patients to clear sputum and prevent the aggravation of pneumonia. Early physical activity training allows patients to maintain limb muscle function during hospitalization. It is recommended to design appropriate indoor exercise training for patients with frequency 1-2 times a day, and intensity should not be too high (dyspnea Borg Scale ≤3) in the acute stage. In order to achieve safe training, criteria for selecting stable patients and training termination are important. Early PR may help reduce the length of hospital stay, maintain functional status, improve symptoms of dyspnea, relieve anxiety, and maintain health-related quality of life in these patients after discharge., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Tzu Chi Medical Journal.)

Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Acute lung injury (ALI) is characterized by diffuse pulmonary infiltrates and causes great mortality. ALI presents with overproduction of proinflammatory cytokines, cell death, destruction of alveoli-endothelial barriers, and neutrophil infiltration in lung tissues. Damage-associated molecular patterns (DAMPs) are molecules released from damaged cells due to infection, trauma, etc. DAMPs activate innate and adaptive immunity, trigger inflammatory responses, and are important in the initiation and development of ALI. We reviewed the literatures on DAMPs in ALI. Alveolar macrophages (AMs), neutrophils, and epithelial cells (AECs) are important in the pathogenesis of ALI. We comprehensively analyzed the interaction between DAMPs and AMs, alveolar neutrophils, and AECs. During the initial stage of ALI, ruptured cell membranes or destroyed mitochondria release DAMPs. DAMPs activate the inflammasome in nearby sentinel immune cells, such as AMs. AMs produce IL-1β and other cytokines. These mediators upregulate adhesion molecules of the capillary endothelium that facilitate neutrophil recruitment. The recruited neutrophils detect DAMPs using formyl peptide receptors on the membrane, guiding their migration to the injured site. The accumulation of immune cells, cytokines, chemokines, proteases, etc., results in diffuse alveolar damage and pulmonary hyperpermeability with protein-rich fluid retention. Some clinical studies have shown that patients with ALI with higher circulating DAMPs have higher mortality rates. In conclusion, DAMPs are important in the initiation and progression of ALI. The interactions between DAMPs and AMs, neutrophils, and AECs are important in ALI. This review comprehensively addresses the mechanisms of DAMPs and their interactions in ALI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Non-small-cell lung cancer (NSCLC) causes significant mortality worldwide. Patients with chronic renal failure have an increased risk of developing lung cancer. NSCLC Patients with chronic renal failure undergoing hemodialysis (HD) often exhibit poor performance, and chemotherapy is generally contraindicated. Oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective treatment agents for NSCLC patients. However, the benefits and adverse effects of EGFR-TKIs in NSCLC undergoing HD are known. There are no clinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD. We reviewed all previous case reports about EGFR-TKIs in NSCLC patients undergoing HD. It is difficult to design studies about the effects of EGFR-TKIs in patients undergoing HD, and this review is quite important. EGFR-TKIs are well tolerated in patients undergoing HD. The main routes of elimination of EGFR-TKIs are metabolism via the liver, and renal elimination is minor. The recommended doses and pharmacokinetics of these EGFR-TKIs for patients undergoing HD are similar to those for patients with normal renal function. The plasma protein binding of EGFR-TKIs is very high, and it is not necessary to adjust the dose after HD. In conclusion, EGFR-TKIs are effective and well tolerated in patients undergoing HD., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities., Methods: We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis., Results: AEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells., Conclusions: AEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI., 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 © 2022 Hsieh, Peng, Liu, Kuo, Tzeng, Wang, Lan and Huang.)

Obstructive sleep apnea syndrome (OSAS) is one of the most common comorbidities in patients with Prader-Willi syndrome (PWS) and causes significant consequences. This observational study was conducted to investigate the progression of OSAS in pediatric patients with PWS, who had not undergone upper airway surgery, through a longitudinal follow-up of their annual polysomnography results. Annual body mass index (BMI), BMI z-score, sleep efficiency and stages, central apnea index (CAI), obstructive apnea-hypopnea index (OAHI), and oxygen saturation nadir values were longitudinally analyzed. At enrollment, of 22 patients (10 boys and 12 girls) aged 11.7 ± 3.9 years, 20 had OSAS. During the 4-year follow-up, only two patients had a spontaneous resolution of OSAS. The average BMI and BMI z-score increased gradually, but CAI and OAHI showed no significant differences. After statistical adjustment for sex, age, genotype, growth hormone use, and BMI z-score, OAHI was associated with the BMI z-score and deletion genotype. In conclusion, OSAS is common in patients with PWS, and rarely resolved spontaneously. Watchful waiting may not be the best OSAS management strategy. Weight maintenance and careful selection of surgical candidates are important for OSAS treatment in patients with PWS.

Continuous positive airway pressure (CPAP) therapy can spread infections if the equipment is not cleaned properly. We report a case of Pneumocystis jirovecii pneumonia likely spread by unclean CPAP equipment and accessories. A 48-year-old man with severe obstructive sleep apnea was using CPAP equipment that had never been cleaned for 5 years. He experienced intermittent mild fever for 6 weeks. His chest images showed a solitary pulmonary granuloma. Pneumocystis jirovecii was identified from the bronchoalveolar fluid, the CPAP mask, and the air tubing. The fever subsided immediately after changing to a clean CPAP device. We prescribed sulfamethoxazole 400 mg and trimethoprim 80 mg twice daily for 1 month. Three months later, the pulmonary granuloma disappeared, and P. jirovecii was absent in the bronchoalveolar fluid. Poorly cleaned CPAP devices could harbor P. jirovecii and spread pulmonary infection in immunocompetent persons. Appropriate cleaning of CPAP equipment is essential to minimize infection risk., Citation: Jao L-Y, Su W-L, Chang H-C, Lan C-C, Wu Y-K, Yang M-C. Pneumocystis jirovecii pneumonia presenting as a solitary pulmonary granuloma due to unclean continuous positive airway pressure equipment: a case report. J Clin Sleep Med . 2022;18(6):1717-1721., (© 2022 American Academy of Sleep Medicine.)

Background: Pectus excavatum (PE) negatively impacts psychological function, but its effect on autonomic nervous system (ANS) function has not been investigated. We evaluated ANS function following postural changes in patients with PE., Methods: The participants were 14 healthy men (control group) and 20 men with PE (study group). Psychological function was assessed using the visual analog scale for pain, Brief Symptom Rating Scale-5, and Beck Depression Inventory-II. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). ANS regulation in response to postural change was measured in the supine position and immediately after sitting. All measurements were compared between the control and study groups at baseline and between the study groups before and after Nuss surgery., Results: At baseline, upon postural change, symptomatic activity increased in the control group (50.3-67.4%, p = 0.035) but not in the study group (55.0-54.9%, p = 0.654); parasympathetic activity decreased in the control group (49.7-32.6%, p = 0.035) but not in the study group (45.1-45.1%, p = 0.654); and overall ANS regulation increased in the control group (1.02-2.08, p = 0.030) but not in the study group (1.22-1.22, p = 0.322). In response to postural change after Nuss surgery in the study group, sympathetic activity increased (48.7-70.2%, p = 0.005), parasympathetic activity decreased (51.3-29.8%, p = 0.005), and overall ANS regulation increased (0.95-2.36, p = 0.012)., Conclusion: ANS function in response to postural change is dysregulated in patients with PE, which improved after Nuss surgery. Trial registration ClinicalTrials.gov, ID: NCT03346876, November 15, 2017, retrospectively registered, https://register., Clinicaltrials: gov/prs/app/action/SelectProtocol?sid=S0007KGI&selectaction=Edit&uid=U0003JZU&ts=2&cx=cstxeg., (© 2022. The Author(s).)

Microglial cells are well-known phagocytic cells that are resistant to the central nervous system (CNS) and play an important role in the maintenance of CNS homeostasis. Activated microglial cells induce neuroinflammation under hypoxia and typically cause neuronal damage in CNS diseases. In this study, we propose that wild bitter melon extract (WBM) has a protective effect on hypoxia-induced cell death via regulation of ferroptosis, ER stress, and apoptosis. The results demonstrated that hypoxia caused microglial BV-2 the accumulation of lipid ROS, ferroptosis, ER stress, and apoptosis. In this study, we investigated the pharmacological effects of WBM on BV-2 cells following hypoxia-induced cell death. The results indicated that WBM reversed hypoxia-downregulated antiferroptotic molecules Gpx4 and SLC7A11, as well as upregulated the ER stress markers CHOP and Bip. Moreover, WBM alleviated hypoxia-induced apoptosis via the regulation of cleaved-caspase 3, Bax, and Bcl-2. Our results suggest that WBM may be a good candidate for preventing CNS disorders in the future., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Chih-Hung Lin et al.)