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Meng-Jer Hsieh,1 Ning-Hung Chen,2 Shih-Lung Cheng,3,4 Chi-Wei Tao,5 Yu-Feng Wei,6,7 Yao-Kuang Wu,8 Ming-Cheng Chan,9,10 Shih-Feng Liu,11– 13 Wu-Huei Hsu,14 Tsung-Ming Yang,15 Ming-Shian Lin,16,17 Ching-Lung Liu,18 Ping-Hung Kuo,19 Ying-Huang Tsai1,20 1Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 4Department of Chemical Engineering and Materials Science, Yuan Ze University, Zhongli, Taoyuan, Taiwan; 5Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 6School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan; 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 9Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 10National Chung Hsing University, Taichung, Taiwan; 11Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 13College of Medicine, Chang Gung University, Taoyuan, Taiwan; 14Critical Medical Center, China Medical University Hospital, Taichung, Taiwan; 15Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 16Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 17Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan; 18Division of Chest Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 19Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 20Department of Pulmonary and Critical Care Medicine, Xiamen Chang Gung Hospital, Xiamen, 361028, People’s Republic of ChinaCorrespondence: Ying-Huang Tsai, Department of Pulmonary and Critical Care Medicine, Linkou Chang Gung Memorial Hospital, Chang Gung Medical Foundation and Department of Respiratory Therapy, College of Medicine, Chang Gung University, No. 5 Fu-Xin St, Kweishan District, Taoyuan, Taiwan, Email chestmed@cgmh.org.twBackground: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan.Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics.Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period.Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.Keywords: tiotropium/olodaterol, umeclidinium/vilanterol, indacaterol/glycopyrronium, LABA/LAMA therapy, Taiwan, cohort study, propensity score matching, chronic obstructive pulmonary disease, moderate-to-severe exacerbation

Chun-Hao Chen,1 Ming-Chyi Huang,2 Yi-Hang Chiu,3 I-Ming Chen,1,4 Chun-Hsin Chen,3,5 Mong-Liang Lu,3,5 Tsung-Yang Wang,1 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 3Department of Psychiatry, Wan-Fang Hospital, Taipei, Taiwan; 4Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 5Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen, Department of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, Taiwan, Tel +886-2-2312-3456 ext. 66787, Fax +886-2-2381-3208, Email hsichungchen@ntu.edu.twObjective: This study aimed to investigate the relationship between eveningness preference and poor sleep quality and eventually examine the moderation effect of stress susceptibility.Methods: Individuals with non-acute major depressive disorder or bipolar affective disorder and healthy participants were recruited. The Composite Scale of Morningness (CSM) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate chronotype and sleep quality, respectively. Eysenck Personality Questionnaire, Tridimensional Personality Questionnaire, Perceived Stress Scale, and Beck Anxiety Inventory were used to formulate stress susceptibility and as indicator variables for empirical clustering by latent class analysis (LCA). Linear regression models were used to examine the relationship between chronotype preference and sleep quality. The interaction terms of CSM and stress susceptibility were examined for the moderation effect.Results: A total of 887 individuals were enrolled in this study, with 68.2% female and 44.1% healthy participants. Three subgroups were derived from LCA and designated as low stresssusceptibility (40.2%), moderate stress susceptibility (40.9%), and high stress susceptibility (18.8%) groups. After controlling for covariates, the CSM scores inversely correlated with PSQI scores [b (se)=− 0.02 (0.01), p=0.01], suggesting that individuals with eveningness preferences tend to have poor sleep quality. Moreover, stress susceptibility moderated the relationship between CSM and PSQI scores (p for interaction term = 0.04). Specifically, the inverse association between CSM and PSQI was more robust in the high stress susceptibility group than that in the low stress susceptibility group.Conclusion: Eveningness preference was associated with poor sleep quality, and this relationship was moderated by stress susceptibility.Keywords: chronotype, empirical clustering, moderation effect, stress susceptibility, sleep quality

Hsi-Chung Chen,1,2 Nai-Wei Hsu,3– 5 Po-Jung Pan,6 Po-Hsiu Kuo,1,7 Meng-Yueh Chien,8 Pesus Chou9 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 3Division of Cardiology, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan; 4Department of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 5Public Health Bureau of Yilan County, Yilan, Taiwan; 6Department of Physical Medicine and Rehabilitation & Community Medicine Center, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan; 7Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 8College of Medicine, National Taiwan University and the Physical Therapy Center of National Taiwan University Hospital, Taipei, Taiwan; 9Community Medicine Research Center & Institute of Public Health, National Yang-Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Hsi-Chung ChenDepartment of Psychiatry, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei, 10002, TaiwanTel +886-2-2312-3456 ext. 66787Fax +886-2-2381-320Email hsichungchen@ntu.edu.twObjective: Poor sleep quality is prevailing, deleterious, but heterogeneous in older adults. This study aimed to develop a simplified instrument to screen and classify poor sleep quality in community-dwelling older adults, by which stepped care with needs-based interventions could be implemented.Methods: Cohorts of adults aged 65 years and older were used to develop the Rapid Classification Scale for Sleep Quality (RCSSQ). Poor sleep quality was defined with the Pittsburgh Sleep Quality Index (PSQI). Established subgroups of poor sleep quality in the development dataset (n = 2622) were used as the criterion standard. Two independent validation datasets (n = 964 and 193, respectively) were used to examine the external validity. Questions in the PSQI were examined by the stepwise multinomial logistic regressions to determine the optimal numbers of items in the RCSSQ. On the premise of item parsimony and instrument validity, the optimal combination of reduced items was determined.Results: In the development dataset, the 4-item RCSSQ (RCSSQ-4) was the optimal predictive model. In terms of internal validity, the accuracy rates to identify PSQI-defined poor sleep quality and its subgroups in the developmental dataset by the RCSSQ-4 were 89.0% and 79.9%, respectively. Meanwhile, the RCSSQ-4 also had good external validity in the validation datasets to detect PSQI-defined poor sleep quality (accuracy rates: 89.1– 90.7%). Furthermore, the profiles of PSQI component scores and comorbid conditions for the predicted subgroups in the validation dataset were comparable with the criterion standard.Conclusion: The RCSSQ-4 is a valid instrument for screening and subgrouping poor sleep quality in community-dwelling older adults. The RCSSQ-4 may help guide tailored interventions under the context of stepped care in the community.Keywords: older adults, screen, sleep quality, subgroup, scale, the Yilan study

Wen-Yin Chen,1,2 Hsing-Cheng Liu,1,3 Ying-Chih Cheng,2,4 Hua Li,2 Chi-Chieh Huang,2 Yu-Wei Ding,2 Ming-Chyi Huang,1,3 Chih-Chiang Chiu,1,3 Yu-Kang Tu,2,5 Po-Hsiu Kuo2,5,6 1Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan; 2Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 3Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Psychiatry, China Medical University Hsinchu Hospital, China Medical University, Hsinchu, Taiwan; 5Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; 6Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Yu-Kang Tu; Po-Hsiu KuoDepartment of Public Health, College of Public Health, National Taiwan University, Room 521, No. 17, Xuzhou Road, Taipei City, 100, TaiwanEmail yukangtu@ntu.edu.tw; phkuo@ntu.edu.twIntroduction: The priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis.Methods: The PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044).Results: Total 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00– 1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03– 1.13), and galantamine (SMD = 1.22, 95% CI = 0.10– 2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined.Conclusion: Considerable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients’ cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.Keywords: cognitive function, systematic review, network meta-analysis, Hasse diagram, partially ordered set

Sze-Yu Chen,1 Chun-Hao Chen,1 Chen Lo,1 Mong-Liang Lu,2 Cheng-Dien Hsu,3 Yi-Hang Chiu,2 Chun-Hsin Chen,2 Shih-Ku Lin,4,5 Ming-Chyi Huang,5 Hsi-Chung Chen,1,6 Po-Hsiu Kuo1,7 1Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; 2Department of Psychiatry, Wan-Fang Hospital & School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Psychosomatic Medicine, Taiwan Adventist Hospital, Taipei, Taiwan; 4Department of Psychiatry, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 5Department of Psychiatry, Taipei City Hospital, Songde Branch, Taipei, Taiwan; 6Center of Sleep Disorders, National Taiwan University Hospital, Taipei, Taiwan; 7Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Hsi-Chung Chen Email hsichungchen@ntu.edu.twPurpose: This study aimed to elucidate the various co-occurring patterns of depressive symptomatology and sleep-wake-related disturbances (SWRDs) in patients with mood disorders.Patients and Methods: Individuals in non-acute states of major depressive disorder or bipolar disorder were recruited. The Beck Depression Inventory II (BDI-II) was utilized to evaluate depressive symptoms. BDI-II items were classified into three domains: cognitive, affective, and somatic. Between-domain differences with various SWRDs were examined. Latent class analysis was used to empirically classify participants using BDI-II items as indicator variables. Co-occurring patterns between domains of BDI-II items and SWRDs were re-examined in each subgroup to elucidate inter-individual differences.Results: In total, 657 participants were enrolled. Of participants, 66.8% were female, and 52.4% were diagnosed with major depressive disorder. Each BDI-II domain exhibited different co-occurring patterns. The somatic domain was most likely to co-occur with various SWRDs. Three subgroups were derived from latent class analysis and were designated as poor sleep quality and high insomnia (n=150), poor sleep quality and moderate insomnia (n=248), and poor sleep quality and low insomnia (n=159). The group with more severe insomnia presented with more severe depressive and anxiety symptoms. The three subgroups further differed in co-occurring patterns. From the low insomnia to high insomnia group, the associations with various SWRDs appeared in the sequence of somatic, affective, and cognitive domains.Conclusion: Co-occurring patterns between domains of depressive symptomatology with various SWRDs differ and may vary among individuals.Keywords: co-occurring, latent class analysis, mood disorders, sleep-wake-related disturbance, depression

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

Yu-Feng Wei,1,2 Ying-Huang Tsai,3 Chin-Chou Wang,4 Ping-Hung Kuo5 On behalf of the TOLD Study Group 1Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 2Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 4Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China Purpose: A low body mass index (BMI) is a poor prognostic marker of acute exacerbations and mortality in patients with COPD. However, the impact of overweight and obesity on COPD-related outcomes is uncertain. The aim of this study was to examine whether a high BMI is associated with the frequent exacerbator phenotype (≥2/year) in Taiwanese patients with COPD. Patients and methods: Data were obtained from the Taiwan Obstructive Lung Disease study, a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals in Taiwan. Multivariate logistic regression models were used to explore the association between BMI and other factors with the frequency of COPD exacerbations in these patients. Results: Among the whole study cohort (n=1,096), 735 (67.1%) had no exacerbations and 148 (13.5%) were frequent exacerbators in the previous year. The BMI values of the patients with 0, 1, and ≥2 exacerbations were 23.6, 23.5, and 22.6 kg/m2, respectively. In all, 256 (23.4%) and 196 (17.9%) patients were overweight (27 kg/m2 > BMI ≥24 kg/m2) and obese (BMI ≥27 kg/m2), respectively. Even after adjusting for multiple factors, overweight and obesity were associated with the frequency of exacerbations (odds ratio [95% confidence interval] 0.49 [0.28–0.87, P=0.015] and 0.49 [0.26–0.94, P=0.033], respectively). Conclusion: Our results suggest that overweight and obesity are associated with a lower frequency of COPD exacerbations in Taiwan. Keywords: acute exacerbation, COPD, obesity, overweight

We present a case of an immunocompetent 27-year-old African American man who was initially diagnosed with diffuse pulmonary coccidioidomycosis and started on oral fluconazole. While his symptoms improved, he began to develop tender cutaneous lesions. Biopsies of the cutaneous lesions grew Coccidioides immitis. Subsequent 18F-FDG PET/CT revealed extensive multisystem involvement including the skin/subcutaneous fat, lungs, spleen, lymph nodes, and skeleton. This case demonstrates the utility of obtaining an 18F-FDG PET/CT to assess the disease extent and activity in patients with disseminated coccidioidomycosis who initially present with symptoms involving only the lungs.

While various modalities exist for the diagnosis of pulmonary embolism (PE), CT pulmonary angiography (CTPA) is the most widely used and can establish the diagnosis quickly and reliably. We report a patient who presented with syncope who developed pulseless electrical activity (PEA) arrest in the emergency department. Given the presence of acute renal injury, CTA was felt to be contraindicated. A ventilation-perfusion lung (VQ) scan demonstrated low probability for PE; however, echocardiography revealed evidence for right heart strain. Subsequent cardiac magnetic resonance imaging (CMR) unexpectedly revealed a saddle PE. This case highlights the potential role for MR for the diagnosis of PE when high clinical suspicion is discordant with results of conventional imaging.

Wan-Chun Huang,1 Ying-Huang Tsai,2 Yu-Feng Wei,3 Ping-Hung Kuo,4 Chi-Wei Tao,5 Shih-Lung Cheng,6 Chao-Hsien Lee,7 Yao-Kuang Wu,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Chin-Chou Wang,12 Ming-Shian Lin1,131Division of Pulmonary Medicine, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 2Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, 3Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, 4Department of Internal Medicine, National Taiwan University Hospital, 5Department of Internal Medicine, Cheng-Hsin General Hospital, 6Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, 7Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, 8Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, 9Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, 11Division of Chest Medicine, Taichung Veterans Genera Hospital, Taichung, 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 13Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi, Taiwan, Republic of ChinaBackground: COPD is an important public health challenge with significant heterogeneity of clinical presentation and disease progression. Clinicians have been trying to find phenotypes that may be linked to distinct prognoses and different therapeutic choices. Not all patients with COPD present with wheezing, a possible clinical phenotype that can help differentiate patient subgroups.Methods: The Taiwan Obstructive Lung Disease study was a retrospective, multicenter research study to investigate the treatment patterns of COPD after the implementation of the Global Initiative for Chronic Obstructive Lung Disease 2011 guidelines. Between November 2012 and August 2013, medical records were retrieved from patients with COPD aged ≥40 years; patients diagnosed with asthma were excluded. Demographic data, lung function, symptom scores, and acute exacerbation were recorded and analyzed, and the differences between patients with and without wheezing were evaluated.Results: Of the 1,096 patients with COPD, 424 (38.7%) had the wheezing phenotype. The wheezing group had significantly higher COPD Assessment Test scores (12.4±7.8 versus 10.5±6.7, P

Yu-Feng Wei,1 Ping-Hung Kuo,2 Ying-Huang Tsai,3 Chi-Wei Tao,4 Shih-Lung Cheng,5,13 Chao-Hsien Lee,6 Yao-Kuang Wu,7 Ning-Hung Chen,8 Wu-Huei Hsu,9 Jeng-Yuan Hsu,10 Ming-Shian Lin,11 Chin-Chou Wang12 1Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan; 4Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Thoracic Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan; 6Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan; 8Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University and China Medical University Hospital, Taichung, Taiwan; 10Division of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Pulmonary and Critical Care Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan; 12Division of Pulmonary and Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 13Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan Background and objective: The overprescription of inhaled corticosteroids (ICS) in the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A and B patients with chronic obstructive pulmonary disease (COPD) is not uncommon in clinical practice. The aim of this study was to explore the factors associated with the use of ICS in these patients. Methods: The Taiwan obstructive lung disease (TOLD) study was a retrospective, observational nationwide survey of COPD patients conducted at 12 hospitals (n=1,096) in Taiwan. Multivariate logistic regression models were used to explore the predictors of ICS prescription in GOLD group A and B patients. Results: Among the group A (n=179) and group B (n=398) patients, 198 (34.3%) were prescribed ICS (30.2% in group A and 36.2% in group B, respectively). The wheezing phenotype was present in 28.5% of group A and 34.2% of group B patients. Wheezing was the most significant factor for an ICS prescription in group A (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.14–4.75; P=0.020), group B (OR, 1.93; 95% CI, 1.24–2.99; P=0.004), and overall (OR, 2.04; 95% CI, 1.40–2.96; P

Previous studies on acetaldehyde dehydrogenase 2 (ALDH2) focused on drinking behavior or alcoholism because the ALDH2*2 allele protects against the risk of developing alcoholism. The mechanism provides that the ALDH2 gene's protective effect is also involved in dopamine metabolism. The interaction of the ALDH2 gene with neurotransmitters, such as dopamine, is suggested to be related to alcoholism. Because alcoholism is often co-morbid with antisocial personality disorder (ASPD), previous association studies on antisocial alcoholism cannot differentiate whether those genes relate to ASPD with alcoholism or ASPD only. This study examined the influence of the interaction effect of the ALDH2*1*1, *1*2 or *2*2 polymorphisms with the dopamine 2 receptor (DRD2) Taq I polymorphism on ASPD. Our 541 Han Chinese male participants were classified into three groups: antisocial alcoholism (ASPD co-morbid with alcohol dependence, antisocial ALC; n = 133), ASPD without alcoholism (ASPD not co-morbid with alcohol dependence, antisocial non-ALC; n = 164) and community controls (healthy volunteers from the community; n = 244). Compared with healthy controls, individuals with the DRD2 A1/A1 and the ALDH2*1/*1 genotypes were at a 5.39 times greater risk for antisocial non-ALC than were those with other genotypes. Our results suggest that the DRD2/ANKK1 and ALDH2 genes interacted in the antisocial non-ALC group; a connection neglected in previous studies caused by not separating antisocial ALC from ASPD. Our study made this distinction and showed that these two genes may be associated ASPD without co-morbid alcoholism. [ABSTRACT FROM AUTHOR]

Background. Although alcohol dependence (AD) and major depression (MD) are highly co-morbid, their causal relationship is unclear. In this longitudinal study, we used a genetically informative population-based twin sample to examine the age-at-onset distributions and the temporal relationship of AD and MD.Method. Our sample included 7477 twins, whose diagnoses of AD and MD and age-at-onset information were obtained from structured interviews. Individual-level survival analyses were conducted based on 2603 monozygotic (MZ) twins, and co-twin diagnosis was included in models as an index of familiar liability to AD and MD.Results. The age-at-onset distributions of AD and MD differed substantially. Most onsets of AD were in young adulthood, whereas MD had a flatter distribution across age. Most subjects, especially women, had an onset of MD preceding AD. Prior MD significantly affected risk for developing AD, and this risk decreased over time. By contrast, preceding AD had negligible effects on the risk for future MD. Familial risk was transmitted within disorders but there was little evidence of additional familial liability shared across disorders.Conclusions. Risk for developing AD was substantially increased by a prior episode of MD. The association was only partially accounted for by familial factors, providing support for a direct causal effect such as self-medication. The etiologic path from AD to MD was insignificant. [ABSTRACT FROM AUTHOR]

This work reports Ag(I)-catalyzed oxidative cyclizations of 1,4-diynamide-3-ols with 8-methylquinoline oxide to form 2-substituted furan-4-carboxamides. The reaction chemoselectivity is distinct from that reported in previous work by Hashmi. We performed density functional theory calculations to elucidate our proposed mechanism after evaluation of the energy profiles of two possible pathways. In this Ag(I) catalysis, the calculations suggest that the amide and alkyne groups of the 3,3-dicarbonyl-2-alkyne intermediates tend to chelate with the Ag(I) catalyst, further inducing a formyl attack at the Ag(I)-π-alkyne moiety to deliver the observed products.

Background: Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups., Methods: The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed., Results: Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study., Conclusions: The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) is a serious, progressive lung disease for which treatments are scarce. Pirfenidone has been approved for the treatment of IPF in Taiwan since 2016. This study aimed to gain a better insight into pirfenidone's real-world safety and effectiveness in adult IPF patients in Taiwan., Methods: We conducted a prospective, multicenter, post-marketing surveillance study, and analyzed data from a small sample of 50 IPF patients treated with pirfenidone., Results: Most patients were men, with a mean age of 72.8 years (±10.3). They were in physiology stage I or II with a baseline mean forced vital capacity (FVC) of 2.236 L (73.8% of predicted value). After treatment with pirfenidone, the mean FVC decreased by 0.088 L at week 24 and 0.127 L at week 52. The mean 6 min walk test was 325.5 m at baseline, increased by 8.1 m at week 24, but then decreased by 23.0 m at week 52. These changes from baseline did not reach statistical significance. Pirfenidone prevented worsening of cough but did not stabilize dyspnea. During 52 weeks of treatment, the incidence of total adverse drug reactions was 62.0%, with decreased appetite (32.0%) and pruritis (10.0%) being the most common. The adverse events leading to treatment discontinuation were decreased appetite (8.0%), nausea (4.0%), and respiratory failure (4.0%). No safety concern was raised by the study. Treatment with pirfenidone stabilized both FVC and the subjective symptom of cough in most patients., Conclusions: This post-marketing surveillance study demonstrated that pirfenidone is an effective, safe, and well-tolerated treatment in patients with IPF in Taiwan.

Background: Quantitative thresholds are helpful to define an abnormal DaT SPECT in patients with suspected nigrostriatal degenerative diseases (NSDD). The optimal DaTQUANT threshold for diagnostic accuracy of DaT SPECT across combined movement and cognitive disorder populations has been previously described. Methods : We established optimal DaTQUANT thresholds that enhance the discrimination between dementia with Lewy bodies (DLB) and non-DLB dementia types, as well as between Parkinsonian syndromes (PS) and conditions not characterized by nigrostriatal degeneration (non-PS). Results: Data from a total of 303 patients were used in this retrospective analysis. Posterior putamen of the more affected hemisphere (MAH) was shown to be an accurate single-variable predictor for both DLB and PS and was comparable to the most accurate multi-variable models. Conclusions: Automated quantification with DaTQUANT can accurately aid in the differentiation of DLB from non-DLB dementias and PS from non-PS. Optimal thresholds for assisting a diagnosis of DLB are striatal binding ratio (SBR) ≤ 0.65, z-score ≤ -2.36, and a percent deviation ≤ -0.54 for the posterior putamen of the MAH. Optimal posterior putamen thresholds for assisting a diagnosis of PS are SBR ≤ 0.92, z-score ≤ -1.53, and a percent deviation ≤ -0.33, which are similar to our previously reported posterior putamen threshold values using a blended patient pool from multiple study populations.

This study employed machine learning techniques to predict the rate of feline infectious peritonitis (FIP) diagnoses, with a specific focus on mutations in the spike protein gene of the feline coronavirus (FCoV). FIP is a fatal viral disease affecting the peritoneum of cats and is primarily caused by mutations in FCoV. Its diagnosis largely relies on evaluations of various biomarkers and clinical symptoms. The current analysis of FCoV spike protein gene mutations exhibits certain limitations. To address this problem, the present study employed a large dataset-comprising information on FCoV copy numbers, spike protein mutation outcomes, and related clinical data-and used machine learning models to analyze the association between spike protein gene mutations and FIP diagnosis. Various algorithms were used to establish highly accurate predictive models, namely logistic regression, random forest, decision tree, neural network, support vector machine, gradient boosting tree, and categorical boosting (CatBoost) algorithms. The model obtained using the CatBoost algorithm was discovered to have accuracy of 0.9541. Accordingly, a highly accurate predictive model was developed to enable early diagnosis of FIP and improve the rate of survival in cats. The application of machine learning technology in this study yielded research findings that provide veterinarians with effective tools for managing and preventing FIP, a painful and deadly disease for cats. This study is a pioneering work in the systematic application of multiple machine learning models to the prediction of FIP and comparison of performance results to improve diagnostic accuracy and efficiency. This study is the first of its kind in the field of FIP., 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 Ltd. All rights reserved.)

Raman spectrum preprocessing method for automatic denoising and suppression of the fluorescent background. In this method, noise is reduced using wavelet transform, and a modified polynomial curve fitting method is implemented such that an algorithm can independently identify the optimal curve parameters for fluorescent background suppression. To address the problem of imbalanced datasets, the present study employed a synthetic minority oversampling technique to increase the volume of data in minority classes. This technique enables the prediction of pesticides that are otherwise difficult to detect, and the prediction accuracy is comparable to that of detection with large data volumes. The proposed convolutional neural network model was verified to accurately identify the type of single pesticides and composition of mixed pesticides. The prediction accuracy for mixed pesticides reached 99.1%., 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.)

Background: Reports on the efficacy of omega-3 fatty acids (n-3 PUFAs) for the treatment of late-life depression (LLD) are mixed, and most studies focus on the modification of depressive symptoms rather than depression prevention. The aim of the present study was to investigate the efficacy of n-3 PUFAs in preventing depressive recurrence in patients with late-life depression. In addition, we investigated the effects of n-3 PUFAs on changes in depressive and anxiety symptoms and inflammatory markers in LLD., Methods: A 52-week, double-blind, randomized, controlled trial was conducted. We enrolled a total of 39 euthymic patients with LLD. They were randomized to receive either n-3 PUFAs (1.2 g per day of eicosapentaenoic acid and 1 g of docosahexaenoic acid) or placebo for 52 weeks. Recurrence of depression and severity of depression symptoms were assessed at baseline and weeks 4, 8, 16, 24, 32, 40, and 52., Results: A total of 39 patients completed the trial with 19 in the n-3 PUFAs group and 20 in the placebo group. Cox proportional hazard regression indicated that n-3 PUFAs had significant protective effect on depression recurrence (Hazard Ratio: 0.295, 95 % Confidence Interval: 0.093-0.931, p value =0.037). But n-3 PUFAs intervention had no significant effect in reducing depressive or anxiety symptoms, inflammatory markers over the placebo group., Limitation: The results should be interpreted with consideration of the modest sample size., Conclusion: These findings suggest that n-3 PUFAs may have a prophylactic effect in currently euthymic patients with LLD., 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.)

Although guidelines for the use of 177 Lu-PSMA-617 published by various organizations are important, they do not include all the essential, practical points necessary for a complete institutional protocol. Therefore, a brief survey was performed to assess key components of the 177 Lu-PSMA-617 protocol before, during, and after delivery of therapy. This survey demonstrated the wide variability in many aspects of institutional protocols regarding determination of eligibility for and administration of 177 Lu-PSMA-617 therapy. The real-world protocol details provided here from a variety of institutions may help new and established theranostic programs., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Major depressive disorder (MDD) is a complex mental disorder, potentially linked to the gut-microbiota-brain axis. Probiotics like Lactobacillus plantarum PS128 (PS128) may improve depressive symptoms by modulating the gut microbiota based on our previous open trial. We conducted an 8-week double-blind, placebo-controlled trial to investigate the impact of PS128 on depression severity, markers of inflammation and gut permeability, and the gut microbiota composition in 32 patients with MDD with stable antidepressant treatment but moderate symptom severity. Following the 8-week intervention, both the Hamilton Depression Rating Scale-17 score (HAMD), and Depression and Somatic Symptoms Scale (DSSS) showed a significant decrease in both groups (p<0.001). However, there was no significant difference in the change of depression severity between groups (p=0.203). Moreover, alterations in serum levels of high sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, and intestinal fatty acid binding protein, as well as changes in the gut microbiota composition, did not exhibit significant differences before and after intervention or between the groups. In comparison to the placebo group, our study did not find significant effects of PS128 on depressive symptoms, biomarkers of inflammation and gut permeability, and the overall gut microbiota composition. Nonetheless, we observed a potential impact of PS128 on the symbiosis of specific taxa. To comprehensively understand the psychophysiological effects of PS128 in patients with MDD, further research with a larger sample size is imperative., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background Lutetium 177 [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) is a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC). Quantitative PSMA PET/CT analysis could provide information on 177 Lu-PSMA-617 treatment benefits. Purpose To explore the association between quantitative baseline gallium 68 [ 68 Ga]Ga-PSMA-11 ( 68 Ga-PSMA-11) PET/CT parameters and treatment response and outcomes in the VISION trial. Materials and Methods This was an exploratory secondary analysis of the VISION trial. Eligible participants were randomized (June 2018 to October 2019) in a 2:1 ratio to 177 Lu-PSMA-617 therapy (7.4 GBq every 6 weeks for up to six cycles) plus standard of care (SOC) or to SOC only. Baseline 68 Ga-PSMA-11 PET parameters, including the mean and maximum standardized uptake value (SUV mean and SUV max ), PSMA-positive tumor volume, and tumor load, were extracted from five anatomic regions and the whole body. Associations of quantitative PET parameters with radiographic progression-free survival (rPFS), overall survival (OS), objective response rate, and prostate-specific antigen response were investigated using univariable and multivariable analyses (with treatment as the only other covariate). Outcomes were assessed in subgroups based on SUV mean quartiles. Results Quantitative PET parameters were well balanced between study arms for the 826 participants included. The median whole-body tumor SUV mean was 7.6 (IQR, 5.8-9.9). Whole-body tumor SUV mean was the best predictor of 177 Lu-PSMA-617 efficacy, with a hazard ratio (HR) range of 0.86-1.43 for all outcomes (all P < .001). A 1-unit whole-body tumor SUV mean increase was associated with a 12% and 10% decrease in risk of an rPFS event and death, respectively. 177 Lu-PSMA-617 plus SOC prolonged rPFS and OS in all SUV mean quartiles versus SOC only, with no identifiable optimum among participants receiving 177 Lu-PSMA-617. Higher baseline PSMA-positive tumor volume and tumor load were associated with worse rPFS (HR range, 1.44-1.53 [ P < .05] and 1.02-1.03 [ P < .001], respectively) and OS (HR range, 1.36-2.12 [ P < .006] and 1.04 [ P < .001], respectively). Conclusion Baseline 68 Ga-PSMA-11 PET/CT whole-body tumor SUV mean was the best predictor of 177 Lu-PSMA-617 efficacy in participants in the VISION trial. Improvements in rPFS and OS with 177 Lu-PSMA-617 plus SOC were greater among participants with higher whole-body tumor SUV mean , with evidence for benefit at all SUV mean levels. ClinicalTrials.gov identifier: NCT03511664 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Interreader and intrareader reproducibility of 18 F-flotufolastat PET/CT scans in newly diagnosed and recurrent prostate cancer patients was assessed from masked image evaluations from two phase 3 studies. Methods: 18 F-flotufolastat PET/CT images of newly diagnosed ( n = 352) or recurrent ( n = 389) patients were evaluated by 3 masked readers. Cohen κ was used to assess pairwise patient- and region-level interreader agreement. Agreement among all readers was assessed using Fleiss κ. Intrareader agreement between the first and repeat read (20% of images, ≥4 wk later) was assessed using Cohen κ. Results: Pairwise interreader agreement was 95% or better (newly diagnosed) and 75% or better (recurrent). The κ coefficients were impacted by the high-agreement-low-κ paradox: Cohen κ ranged from not estimable to 0.55, whereas Fleiss κ was 0.50 (newly diagnosed) and 0.41 (recurrent). Agreement was highest in the prostate of newly diagnosed patients (≥95%) and in the pelvic lymph nodes in recurrent patients (≥87%). Intrareader agreement was 86% or better across both populations. Conclusion: 18 F-flotufolastat PET/CT images can be reliably interpreted, with a high degree of inter- and intrareader agreement., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: The symptom variability in major depressive disorder (MDD) complicates treatment assessment, necessitating a thorough understanding of MDD symptoms and potential biomarkers., Methods: In this prospective study, we enrolled 54 MDD patients and 39 controls. Over the course of weeks 1, 2, and 4 participants underwent evaluations, with electroencephalograms (EEG) recorded at baseline and week 1. Our investigation considered five previously identified syndromal factors derived from the 17-item Hamilton Depression Rating Scale (17-item HAMD) for assessing depression: core, insomnia, somatic anxiety, psychomotor-insight, and anorexia. We assessed treatment response and EEG characteristics across all syndromal factors and total scores, all of which are based on the 17-item HAMD. To analyze the topology of brain networks, we employed functional connectivity (FC) and a graph theory-based method across various frequency bands., Results: The healthy control group had notably higher values in delta band EEG FC compared to the MDD patient group. Similar distinctions were observed between the responder and non-responder patient groups. Further exploration of baseline FC values across distinct syndromal factors revealed significant variations among the core, psychomotor-insight, and anorexia subgroups when using a specific graph theory-based approach, focusing on global efficiency and average clustering coefficient., Limitations: Different antidepressants were included in this study. Therefore, the results should be interpreted with caution., Conclusions: Our findings suggest that delta band EEG FC holds promise as a valuable predictor of antidepressant efficacy. It demonstrates an ability to adapt to individual variations in depressive symptomatology, offering insights into personalized treatment for patients with depression., Competing Interests: Declaration of competing interest There were no conflicts of interest from funding sources. All authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1 H -pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33 , exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8 + T-cells, and helper CD4 + T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 ( BPR5K230 ) with excellent oral bioavailability ( F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.

Background: Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature., Case Presentation: A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections., Conclusions: To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG., (© 2024. The Author(s).)

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II., Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism., Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II., (© 2024. The Author(s).)

Objective. Single-photon emission computed tomography (SPECT) with pinhole collimators can provide high-resolution imaging, but is often limited by low sensitivity. Acquiring projections simultaneously through multiple pinholes affords both high resolution and high sensitivity. However, the overlap of projections from different pinholes on detectors, known as multiplexing, has been shown to cause artefacts which degrade reconstructed images. Approach. Multiplexed projection sets were considered here using an analytic simulation model of AdaptiSPECT-C-a brain-dedicated multi-pinhole SPECT system. AdaptiSPECT-C has fully adaptable aperture shutters, so can acquire projections with a combination of multiplexed and non-multiplexed frames using temporal shuttering. Two strategies for reducing multiplex artefacts were considered: an algorithm to de-multiplex projections, and an alternating reconstruction strategy for projections acquired with a combination of multiplexed and non-multiplexed frames. Geometric and anthropomorphic digital phantoms were used to assess a number of metrics. Main results. Both de-multiplexing strategies showed a significant reduction in image artefacts and improved fidelity, image uniformity, contrast recovery and activity recovery (AR). In all cases, the two de-multiplexing strategies resulted in superior metrics to those from images acquired with only mux-free frames. The de-multiplexing algorithm provided reduced image noise and superior uniformity, whereas the alternating strategy improved contrast and AR. Significance. The use of these de-multiplexing algorithms means that multi-pinhole SPECT systems can acquire projections with more multiplexing without degradation of images., (© 2024 Institute of Physics and Engineering in Medicine.)

We present the case of a young woman with Hodgkin lymphoma exhibiting physiologic 18 F-FDG uptake in brown adipose tissue and lactating breast on consecutive 18 F-FDG PET/CT scans. Both entities are common imaging interpretation pitfalls and should be recognized in oncologic 18 F-FDG PET/CT practice. We review the imaging features and differential diagnosis of these 2 entities and discuss the radiation safety precautions during breastfeeding., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Importance: Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge., Objective: To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs., Design, Setting, and Participants: This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022., Exposure: In-hospital use of LAIs with or without early discontinuation., Main Outcome and Measures: Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model., Results: Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model., Conclusions and Relevance: The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.

Diagnostic evaluation of a patient with dizziness or vertigo is complicated by a lack of standardized nomenclature, significant overlap in symptom descriptions, and the subjective nature of the patient's symptoms. Although dizziness is an imprecise term often used by patients to describe a feeling of being off-balance, in many cases dizziness can be subcategorized based on symptomatology as vertigo (false sense of motion or spinning), disequilibrium (imbalance with gait instability), presyncope (nearly fainting or blacking out), or lightheadedness (nonspecific). As such, current diagnostic paradigms focus on timing, triggers, and associated symptoms rather than subjective descriptions of dizziness type. Regardless, these factors complicate the selection of appropriate diagnostic imaging in patients presenting with dizziness or vertigo. This document serves to aid providers in this selection by using a framework of definable clinical variants. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: The RECOVERY trial demonstrated that the use of dexamethasone is associated with a 36% lower 28-day mortality in hospitalized patients with COVID-19 on invasive mechanical ventilation. Nevertheless, the optimal timing to start dexamethasone remains uncertain., Methods: We conducted a quasi-experimental study at National Taiwan University Hospital (Taipei, Taiwan) using propensity score matching to simulate a randomized controlled trial to receive or not to receive early dexamethasone (6 mg/day) during the first 7 days following the onset of symptoms. Treatment was standard protocol-based, except for the timing to start dexamethasone, which was left to physicians' decision. The primary outcome is 28-day mortality. Secondary outcomes include secondary infection within 60 days and fulfilling the criteria of de-isolation within 20 days., Results: A total of 377 patients with COVID-19 were enrolled. Early dexamethasone did not decrease 28-day mortality in all patients (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.97-1.10) or in patients who required O2 for severe/critical disease at admission (aOR, 1.05; 95%CI, 0.94-1.18); but is associated with a 24% increase in superinfection in all patients (aOR, 1.24; 95% CI, 1.12-1.37) and a 23% increase in superinfection in patients of O2 for several/critical disease at admission (aOR, 1.23; 95% CI, 1.02-1.47). Moreover, early dexamethasone is associated with a 42% increase in likelihood of delayed clearance of SARS-CoV-2 virus (adjusted hazard ratio, 1.42; 95% CI, 1.01-1.98)., Conclusion: An early start of dexamethasone (within 7 days after the onset of symptoms) could be harmful to hospitalized patients with COVID-19., (Copyright © 2024. Published by Elsevier B.V.)