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Pin-Kuei Fu,1–4 Yu-Chi Tung,1 Chen-Yu Wang,2 Sheau-Feng Hwang,5,6 Shin-Pin Lin,7 Chiann-Yi Hsu,8 Duan-Rung Chen9 1Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan; 2Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Biotechnology, Hungkuang University, Taichung, Taiwan; 4School of Chinese Medicine, China Medical University, Taichung, Taiwan; 5Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan; 6Palliative Care Unit, Taichung Veterans General Hospital, Taichung, Taiwan; 7Computer and Communications Center, Taichung Veterans General Hospital, Taichung, Taiwan; 8Biostatistics Task Force, Taichung Veterans General Hospital, Taichung, Taiwan; 9Institute of Health Behaviors and Community Sciences, National Taiwan University, Taipei, Taiwan Purpose: The unpredictable trajectory of COPD can present challenges for patients when faced with a decision regarding a do-not-resuscitate (DNR) directive. The current retrospective analysis was conducted to investigate factors associated with an early DNR decision (prior to last hospital admission) and differences in care patterns between patients who made DNR directives early vs late. Patients and methods: Electronic health records (EHR) were reviewed from 271 patients with terminal COPD who died in a teaching hospital in Taiwan. Clinical parameters, patterns of DNR decisions, and medical utilization were obtained. Those patients who had a DNR directive earlier than their last (terminal) admission were defined as “Early DNR” (EDNR). Results: A total of 234 (86.3%) patients died with a DNR directive, however only 30% were EDNR. EDNR was associated with increased age (OR=1.07; 95% CI: 1.02–1.12), increased ER visits (OR=1.22; 95% CI: 1.10–1.37), rapid decline in lung function (OR=3.42; 95% CI: 1.12–10.48), resting heart rate ≥100 (OR=3.02; 95% CI: 1.07–8.51), and right-sided heart failure (OR=2.38; 95% CI: 1.10–5.19). The median time period from a DNR directive to death was 68.5 days in EDNR patients and 5 days in “Late DNR” (LDNR) patients, respectively (P

Background: Cardiopulmonary exercise testing (CPET) is a unique diagnostic tool that assesses the functional capacity of the heart, lungs, and peripheral oxidative system in an integrated manner. However, the clinical utility of CPET for evaluating interstitial lung disease (ILD) remains uncertain. The objective of this study was to determine the predictive value of CPET for mortality in subjects with ILD., Methods: We prospectively enrolled subjects with ILD who underwent CPET at a tertiary medical center in Taiwan and followed up their survival status for 12 months. Mortality prediction was based on comparing CPET parameters between subjects who survived and those who died. We further analyzed CPET parameters that showed significant differences using receiver operating characteristic curves to identify their optimal cutoff values., Results: A total of 106 newly diagnosed subjects with ILD underwent CPET, and the 1-y mortality rate was 7.5%. Six CPET variables were found to be significant predictors of mortality: peak oxygen consumption, oxygen pulse, end-tidal partial pressure of carbon dioxide, heart rate recovery 1 min after CPET, minute ventilation to carbon dioxide output slope, and functional aerobic impairment. We calculated a summed score by adding the number of CPET variables that exceeded their cutoff values. Subjects with a summed score of 6 had a 1-y survival rate of only 25%, whereas subjects with scores of 0-5 had a survival rate of 98%., Conclusions: In conclusion, the summed score represents a useful tool for screening patients with ILD who can undergo a CPET to determine their prognosis., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2024 by Daedalus Enterprises.)

Background/aim: In this study, we introduce an innovative deep-learning model architecture aimed at enhancing the accuracy of detecting and classifying organizing pneumonia (OP), a condition characterized by the presence of Masson bodies within the alveolar spaces due to lung injury. The variable morphology of Masson bodies and their resemblance to adjacent pulmonary structures pose significant diagnostic challenges, necessitating a model capable of discerning subtle textural and structural differences. Our model incorporates a novel architecture that integrates advancements in three key areas: Semantic segmentation, texture analysis, and structural feature recognition., Materials and Methods: We employed a dataset of whole slide imaging from 20 patients, totaling 100 slides of OP, segmented into training, validation, and testing sets to reflect real-world application scenarios. Our approach utilizes a modified multi-head self-attention mechanism combined with ResUNet for semantic segmentation, enhanced by superpixel concepts. This method facilitates the generation of representative token features through iterative super-token blocks, creating high-resolution token maps that leverage local and high-level feature information for improved accuracy., Results: Benefiting from token features and distribution for enhanced texture alignment with fewer false-positives, the super-token transformer (STT) model achieved a mean intersection over union (mIOU) of 72.42%, with a sensitivity of 47.81%, specificity of 99.83%, positive predictive value of 64.03%, and negative predictive value of 99.94%, highlighting superior efficacy in Masson body segmentation in complex cross-tissue analyses., Conclusion: Our team developed an iterative learning model based on the STT approach, emphasizing token features of super token, including texture and distribution, that enable enhanced alignment with the unique textures of Masson bodies to improve sensitivity and mIOU, The development of this STT model presents a significant advancement in the field of medical image analysis for OP that offers a promising avenue for improving diagnostic precision and patient outcomes in pulmonary pathology., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The pathological diagnosis of organizing pneumonia (OP) relies on conventional traditional histopathological analysis, which involves examining stained thin slices of tissue. However, this method often results in suboptimal diagnostic objectivity due to low tissue sampling rates. This study aimed to assess the efficacy of tissue-clearing and infiltration-enhanced 3D spatial imaging techniques for elucidating the tissue architecture of OP., Materials and Methods: H&E staining, 3D imaging technology, and AI-assisted analysis were employed to facilitate the construction of a multidimensional tissue architecture using six OP patient specimens procured from Taichung Veterans General Hospital, enabling a comprehensive morphological assessment., Results: Specimens underwent H&E staining and exhibited Masson bodies and varying degrees of interstitial fibrosis. Furthermore, we conducted a comprehensive study of 3D images of the pulmonary histology reconstructed through an in-depth pathology analysis, and uncovered heterogenous distributions of fibrosis and Masson bodies across different depths of the OP specimens., Conclusion: Integrating 3D imaging for OP with AI-assisted analysis permits a substantially enhanced visualization and delineation of complex histological pulmonary disorders such as OP. The synergistic application of conventional histopathology with novel 3D imaging elucidated the sophisticated spatial configuration of OP, revealing the presence of Masson bodies and interstitial fibrosis. This methodology transcends conventional pathology constraints and paves the way for advanced algorithmic approaches to enhance precision in the detection, classification, and clinical management of lung pathologies., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD)., Methods: We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender-age-physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model., Results: We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0-2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28-85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07-15.5; p = 0.039) were significantly associated with overall mortality., Conclusion: The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients., (© 2024. The Author(s).)

Background: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients., Methods: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction., Results: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis., Conclusion: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients., (© 2024. The Author(s).)

The influence of inhaled corticosteroids (ICS) on COVID-19 outcomes remains uncertain. To address this, we conducted a systematic review and meta-analysis, analyzing 30 studies, to investigate the impact of ICS on patients with COVID-19. Our study focused on various outcomes, including mortality risk, hospitalization, admission to the intensive care unit (ICU), mechanical ventilation (MV) utilization, and length of hospital stay. Additionally, we conducted a subgroup analysis to assess the effect of ICS on patients with chronic obstructive pulmonary disease (COPD) and asthma. Our findings suggest that the prior use of ICS did not lead to significant differences in mortality risk, ICU admission, hospitalization, or MV utilization between individuals who had used ICS previously and those who had not. However, in the subgroup analysis of patients with COPD, prior ICS use was associated with a lower risk of mortality compared to non-users (OR, 0.95; 95% CI, 0.90-1.00). Overall, while the use of ICS did not significantly affect COVID-19 outcomes in general, it may have beneficial effects specifically for patients with COPD. Nevertheless, more research is needed to establish a definitive conclusion on the role of ICS in COVID-19 treatment. PROSPERO registration number: CRD42021279429., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen 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.)

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The effect of inhaled corticosteroid (ICS) on the risk of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection is unclear., Methods: We performed a systematic review and meta-analysis of clinical studies that assessed the association between the use of ICS and the risk of SARS-COV-2 infection. PubMed, Web of Science, Scopus, Cochrane Library and Google Scholar were searched to January 1st, 2023. ROBINS-I was used to assess risk of bias of included studies. The outcome of interest was the risk of SARS-COV-2 infection in patients and odds ratio (OR) with 95% confidence interval (95% CI) were calculated using Comprehensive Meta-analysis software version 3., Results: Twelve studies involving seven observational cohort studies, three case-control studies, and two cross-sectional studies were included in this meta-analysis. Overall, compared to non-ICS use, the pooled odds ratio (OR) of the risk of SARS-COV-2 infection was 0.997 (95% confidence interval [CI] 0.664-1.499; p = 0.987) for patients with ICS use. Subgroup analyses demonstrated no statistical significance in the increased risk of SARS-COV-2 infection in patients with ICS monotherapy or in combination with bronchodilators (pooled OR=1.408; 95% CI=0.693-2.858; p = 0.344 in ICS monotherapy, and pooled OR=1.225; 95% CI=0.533-2.815; p = 0.633 in ICS combination, respectively). In addition, no significant association was observed between ICS use and the risk of SARS-COV-2 infection for patients with COPD (pooled OR=0.715; 95% CI=0.415-1.230; p = 0.225) and asthma (pooled OR=1.081; 95% CI=0.970-1.206; p = 0.160)., Conclusions: The use of ICS, either monotherapy or in combination with bronchodilators, does not have impact on the risk of SARS-COV-2 infection., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to pose threats to public health. The clinical manifestations of lung pathology in COVID-19 patients include sustained inflammation and pulmonary fibrosis. The macrocyclic diterpenoid ovatodiolide (OVA) has been reported to have anti-inflammatory, anti-cancer, anti-allergic, and analgesic activities. Here, we investigated the pharmacological mechanism of OVA in suppressing SARS-CoV-2 infection and pulmonary fibrosis in vitro and in vivo. Our results revealed that OVA was an effective SARS-CoV-2 3CLpro inhibitor and showed remarkable inhibitory activity against SARS-CoV-2 infection. On the other hand, OVA ameliorated pulmonary fibrosis in bleomycin (BLM)-induced mice, reducing inflammatory cell infiltration and collagen deposition in the lung. OVA decreased the levels of pulmonary hydroxyproline and myeloperoxidase, as well as lung and serum TNF-ɑ, IL-1β, IL-6, and TGF-β in BLM-induced pulmonary fibrotic mice. Meanwhile, OVA reduced the migration and fibroblast-to-myofibroblast conversion of TGF-β1-induced fibrotic human lung fibroblasts. Consistently, OVA downregulated TGF-β/TβRs signaling. In computational analysis, OVA resembles the chemical structures of the kinase inhibitors TβRI and TβRII and was shown to interact with the key pharmacophores and putative ATP-binding domains of TβRI and TβRII, showing the potential of OVA as an inhibitor of TβRI and TβRII kinase. In conclusion, the dual function of OVA highlights its potential for not only fighting SARS-CoV-2 infection but also managing injury-induced pulmonary fibrosis., Competing Interests: Conflict of interest statement The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Masson SAS.)

Aim: In order to investigate the effect of cycling wheelchair training as an exercise for aged 65+ disabled patients on cognitive function, quality of life, aerobic capacity and physiological parameters., Methods: Participants in nursing home performed cycling wheelchair training for 30 min a day, 5 days a week, for a total of 4 weeks. The main outcome measure was the short form 12 survey (SF-12). Other outcome measures included the Mini-Mental State Examination (MMSE), aero bike work rate test, resting blood pressure, and heart rate., Results: In this study, 41 volunteers were recruited and no participants dropped out of the study voluntarily during training, and no serious adverse effect was identified. Physical and mental component summary total scores of SF-12 were significantly higher after training with statistical significance ( p = 0.001). 8 subscales also showed significant improvements after training ( p = 0.025 ~ <0.001). Total MMSE score has no difference before and after training. Attention/calculation ( p = 0.018), short term memory ( p = 0.041), and aerobic capacity ( p < 0.001) as measured by subscales of MMSE and aero bike test showed marked improvements, while resting systolic blood pressure ( p = 0.931) and heart rate ( p = 0.793) did not change., Conclusions: Cycling wheelchair is practical for the disabled elderly to exercise, and a 4-week exercise program enhanced their quality of life and aerobic capacity.

We fabricated a gas sensor with a wide-bandgap ZnGa 2 O 4 (ZGO) epilayer grown on a sapphire substrate by metalorganic chemical vapor deposition. The ZGO presented (111), (222) and (333) phases demonstrated by an X-ray diffraction system. The related material characteristics were also measured by scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. This ZGO gas sensor was used to detect nitric oxide (NO) in the parts-per-billion range. In this study, the structure effect on the response of the NO gas sensor was studied by altering the sensor dimensions. Two approaches were adopted to prove the dimension effect on the sensing mechanism. In the first approach, the sensing area of the sensors was kept constant while both channel length (L) and width (W) were varied with designed dimensions (L × W) of 60 × 200, 80 × 150, and 120 ×100 μm 2 . In the second, the dimensions of the sensing area were altered (60, 40, and 20 μm) with W kept constant. The performance of the sensors was studied with varying gas concentrations in the range of 500 ppb~10 ppm. The sensor with dimensions of 20 × 200 μm 2 exhibited a high response of 11.647 in 10 ppm, and 1.05 in 10 ppb for NO gas. The sensor with a longer width and shorter channel length exhibited the best response. The sensing mechanism was provided to explain the above phenomena. Furthermore, the reaction between NO and the sensor surface was simulated by O exposure of the ZGO surface in air and calculated by first principles.

Purpose: To compare the clinical effectiveness of branded versus generic piperacillin-tazobactam for treating severe community-acquired pneumonia (CAP)., Patients and Methods: We identified patients with severe CAP who received piperacillin-tazobactam based on a nine-center registry database. Furthermore, we classified the patients in three hospitals, which used only branded piperacillin-tazobactam as the study group, and the patients in six other hospitals, which used both branded and generic products as the control group., Results: A total of 472 patients (n = 263 in the study group and n = 209 in the control group) with severe CAP were included. The study group using branded piperacillin-tazobactam had higher odds of clinical cure (adjusted odds ratio [OR] = 3.77, 95 % confidence interval [CI], 1.93-7.37) and lower odds of treatment failure (adjusted OR = 0.28, 95 % CI, 0.13-0.58) than the control group receiving either branded or generic piperacillin-tazobactam. In addition, the study group was associated with higher odds of clinical effectiveness (adjusted OR = 2.95, 95 % CI, 1.46-6.11), less odds of clinical ineffectiveness (adjusted OR = 0.39, 95 % CI, 0.18-0.81), and lower risk of in-hospital mortality (adjusted OR = 0.39, 95 % CI, 0.21-0.73)., Conclusion: Based on the findings of the present study using indirect comparison, the clinical effectiveness of generic piperacillin-tazobactam for treating patients with severe CAP might not be as good as that of brand-name products., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with chronic obstructive pulmonary disease (COPD) are frequently comorbid with mild cognitive impairment (MCI). Whether respiratory muscle training (RMT) is helpful for patients with COPD comorbid MCI remains unclear. Inspiratory muscle training (IMT) with or without expiratory muscle training (EMT) was performed. Patients were randomly assigned to the full training group (EMT + IMT) or the simple training group (IMT only). A total of 49 patients completed the eight-week course of RMT training. RMT significantly improved the maximal inspiratory pressure (MIP), the diaphragmatic thickness fraction and excursion, lung function, scores in the COPD assessment test (CAT), modified Medical Research Council (mMRC) scale scores, and MMSE. The between-group difference in the full training and single training group was not significant. Subgroup analysis classified by the forced expiratory volume in one second (FEV1) level of patients showed no significant differences in MIP, lung function, cognitive function, and walking distance. However, a significant increase in diaphragmatic thickness was found in patients with FEV1 ≥ 30%. We suggest that patients with COPD should start RMT earlier in their disease course to improve physical activity.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Previous studies have addressed the impact of comorbidity on short-term mortality in patients with COPD. However, the prevalence of cardiovascular disease (CVD) and the association of statins prescription with mortality for aged COPD patients remains unclear. We enrolled 296 aged, hospitalized patients who were monitored in the pay-for-performance (P-4-P) program of COPD. Factors associated with long-term mortality were identified by Cox regression analysis. The median age of the study cohort was 80 years old, and the prevalence of coronary artery disease (CAD) and statins prescriptions were 16.6% and 31.4%, respectively. The mortality rate of the median 3-year follow-up was 51.4%. Through multivariate analysis, body mass index (BMI), statin prescription, and events of respiratory failure were associated with long-term mortality. A Cox analysis showed that statins prescription was associated with lower mortality (hazard ratio (HR): 0.5, 95% Confident interval, 95% CI: 0.34-0.73, p = 0.0004) and subgroup analysis showed that rosuvastatin prescription had protective effect on long-term mortality (HR: 0.44; 95% CI: 0.20-0.97; p < 0.05). Statin prescriptions might be associated with better long-term survival in aged COPD patients, especially those who experienced an acute exacerbation of COPD (AECOPD) who require hospitalization.

Lower respiratory tract sampling from endotracheal aspirate (EA) and bronchoalveolar lavage (BAL) are both common methods to identify pathogens in severe pneumonia. However, the difference between these two methods in microbiota profiles remains unclear. We compared the microbiota profiles of pairwise EA and BAL samples in ICU patients with respiratory failure due to severe pneumonia. We prospectively enrolled 50 ICU patients with new onset of pneumonia requiring mechanical ventilation. EA and BAL were performed on the first ICU day, and samples were analyzed for microbial community composition via 16S rRNA metagenomic sequencing. Pathogens were identified in culture medium from BAL samples in 21 (42%) out of 50 patients. No difference was observed in the antibiotic prescription pattern, ICU mortality, or hospital mortality between BAL-positive and BAL-negative patients. The microbiota profiles in the EA and BAL samples are similar with respect to diversity, microbial composition, and microbial community correlations. The antibiotic treatment regimen was rarely changed based on the BAL findings. The samples from BAL did not provide more information than EA in the microbiota profiles. We suggest that EA is more useful than BAL for microbiome identification in mechanically ventilated patients.

Several factors have been found to be predictors of a good response following omalizumab treatment in patients with severe allergic asthma (SAA). However, it remains unclear whether clinical characteristics can predict a minimal clinically important difference (MCID) following omalizumab treatment in this population. Therefore, the aim of this study was to investigate the features associated with an MCID following omalizumab treatment in adult patients with SAA. Of the 124 participants enrolled in this retrospective, cross-sectional study, 94, 103, 20 and 53 achieved the MCID following treatment with omalizumab and were considered to be responders of exacerbation reduction (no exacerbation during the 1-year follow-up period or ≧50% reduction in exacerbations from baseline), oral corticosteroid (OCS) sparing (no use of OCS to control asthma during the study period or a reduction of the monthly OCS maintenance dose to <50% of baseline), lung function (an increase of ≧230 ml in the forced expiratory volume in 1 s from baseline) and asthma control (an increase of ≧3 points in the asthma control test score from baseline), respectively. Normal weight [<25 vs. ≧30 kg/m 2 , odds ratio (OR) = 3.86, p = 0.024] was predictive of a responder of reduction in exacerbations following omalizumab treatment while subjects with a blood eosinophil level of <300 cells/μL (<300 vs. ≧300 cells/μL, OR = 5.81, p = 0.001) were more likely to exhibit an MCID in OCS sparing. No factor was found to be a predictor of lung function or asthma control. When choosing treatment for adult patients with SAA, our findings may help to select those who may benefit the most from omalizumab treatment., 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 Huang, Fu, Chan, Chin, Huang, Lai, Wang, Hung, Wu, Hsieh, Wu, Chen and Hsu.)

Nutritional status could affect clinical outcomes in critical patients. We aimed to determine the prognostic accuracy of the modified Nutrition Risk in Critically Ill (mNUTRIC) score for hospital mortality and treatment outcomes in patients with severe community-acquired pneumonia (SCAP) compared to other clinical prediction rules. We enrolled SCAP patients in a multi-center setting retrospectively. The mNUTRIC score and clinical prediction rules for pneumonia, as well as clinical factors, were calculated and recorded. Clinical outcomes, including mortality status and treatment outcome, were assessed after the patient was discharged. We used the receiver operating characteristic (ROC) curve method and multivariate logistic regression analysis to determine the prognostic accuracy of the mNUTRIC score for predicting clinical outcomes compared to clinical prediction rules, while 815 SCAP patients were enrolled. ROC curve analysis showed that the mNUTRIC score was the most effective at predicting each clinical outcome and had the highest area under the ROC curve value. The cut-off value for predicting clinical outcomes was 5.5. By multivariate logistic regression analysis, the mNUTRIC score was also an independent predictor of both clinical outcomes in SCAP patients. We concluded that the mNUTRIC score is a better prognostic factor for predicting clinical outcomes in SCAP patients compared to other clinical prediction rules.

Background: Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients., Methods: We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up., Results: A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality., Conclusions: Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

Positioning patients in the prone position leads to reduced hospital mortality rates for those with severe acute respiratory distress syndrome (ARDS). What constitutes the optimal feeding strategy for prone patients with ARDS is controversial. We conducted a retrospective study that enrolled 110 prone patients with ARDS in two medical intensive care units (ICUs) from September 2015 to November 2018. Inclusion criteria were as follows: age ≥20 years, diagnosis of respiratory failure requiring mechanical ventilation, diagnosis of ARDS within 72 h of ICU admission, placement in a prone position within the first 7 days of ICU admission, and ICU stay of more than 7 days. Exclusion criteria were as follows: nil per os orders because of gastrointestinal bleeding or hemodynamic instability, and ventilator dependency because of chronic respiratory failure. The consecutive daily enteral nutrition(EN)/EN + parenteral nutrition(PN) ratio could predict hospital mortality rates within the first 7 days of admission when using generalized estimating equations ( p = 0.013). A higher average EN/EN + PN ratio within the first 7 days predicted (hazard ratio: 0.97, confidence interval: 0.96-0.99) lower hospital mortality rates. To reduce hospital mortality rates, caloric intake with a higher EN ratio may be considered for patients in prone positions with ARDS.

Early enteral nutrition (EN) and a nutrition target >60% are recommended for patients in the intensive care unit (ICU), even for those with acute respiratory distress syndrome (ARDS). Prolonged prone positioning (PP) therapy (>48 h) is the rescue therapy of ARDS, but it may worsen the feeding status because it requires the heavy sedation and total paralysis of patients. Our previous studies demonstrated that energy achievement rate (EAR) >65% was a good prognostic factor in ICU. However, its impact on the mortality of patients with ARDS requiring prolonged PP therapy remains unclear. We retrospectively analyzed 79 patients with high nutritional risk (modified nutrition risk in the critically ill; mNUTRIC score ≥5); and identified factors associated with ICU mortality by using a Cox regression model. Through univariate analysis, mNUTRIC score, comorbid with malignancy, actual energy intake, and EAR (%) were associated with ICU mortality. By multivariate analysis, EAR (%) was a strong predictive factor of ICU mortality (HR: 0.19, 95% CI: 0.07-0.56). EAR >65% was associated with lower 14-day, 28-day, and ICU mortality after adjustment for confounding factors. We suggest early EN and increase EAR >65% may benefit patients with ARDS who required prolonged PP therapy.

Objective: The aim of this study was to compare the usefulness of cefoperazone-sulbactam and that of piperacillin-tazobactam in the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP)., Methods: This retrospective study included the adult patients receiving cefoperazone-sulbactam or piperacillin-tazobactam against HAP/VAP in nine hospitals in Taiwan from March 1, 2018 to May 30, 2019. Primary outcome was clinical cure rate., Results: A total of 410 patients were enrolled. Among them, 209 patients received cefoperazone-sulbactam and 201 patients received piperacillin-tazobactam. Overall, cefoperazone-sulbactam group had similar distribution of age, sex, or SOFA scores as piperacillin-tazobactam group. However, cefoperazone-sulbactam had higher comorbidity score and disease severity than piperacillin-tazobactam group (Charlson score: 6.5 ± 2.9 vs 5.7 ± 2.7, p < 0.001; APACHE II score: 21.4 ± 6.2 vs 19.3 ± 6.0, p = 0.002). Regarding clinical outcomes, no significant difference in clinical cure and failure rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical cure rate: 80.9% vs 80.1% and clinical failure rate: 17.2% vs 18.4%, p = 0.943). Moreover, no significant difference in clinical effectiveness and ineffectiveness rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical effective rate: 80.9% vs 80.6% and clinical ineffective rate: 17.7% vs 18.9%, p = 0.711). The all-cause mortality rates of the cefoperazone-sulbactam and piperacillin-tazobactam groups were similar (23.9% vs 20.9%, p = 0.48). After adjustment of Charlson score and APACHE II score, the similarities in these clinical outcomes did not change in overall patients and patients with HAP or VAP., Conclusion: For treating adult patients with nosocomial pneumonia, cefoperazone-sulbactam was as effective as piperacillin-tazobactam., Competing Interests: The authors declare that they have no competing interests., (© 2021 Chen et al.)

Objectives: Aspergillus -specific IgG ( Asp -IgG) cut-off level in diagnosing chronic pulmonary aspergillosis (CPA) remains unknown., Methods: We prospectively recruited participants with clinical suspicion of CPA in three centers in Taiwan during 2019 June to 2020 August. Serum Aspergillus fumigatus -specific IgG ( Asp -IgG) (Phadia, Uppsala, UPPS, Sweden) was examined. Optimal cut-off level was determined by Youden's index and validated., Results: A total of 373 participants were recruited. In the derivation cohort ( n = 262), Asp -IgG had an area under the receiver-operating-characteristic curve (AUC) of 0.832. The optimal cut-off level was 40.5 mgA/L. While applying this cut-off level to the validation cohort ( n = 111), the sensitivity and specificity were 86.7% and 80.2%. Lowering the cut-off level from 40.5 to 27 mgA/L, the sensitivity was steady (30/36, 83.3% to 31/36, 86.1%) while specificity dropped from 81.9% (276/337) to 63.5% (214/337). Restricting CPA diagnosis to only chronic cavitary pulmonary aspergillosis (CCPA) and chronic fibrosing pulmonary aspergillosis (CFPA) yielded a cut-off level of 42.3 mgA/L in the derivation cohort with a sensitivity of 100% and specificity of 84.4% in the validation cohort., Conclusions: Serum Asp -IgG performs well for CPA diagnosis and provides a low false-positive rate when using a higher cut-off level (preferably around 40 mgA/L).

Early and prolonged prone positioning (PP) therapy improve survival in advanced ARDS; however, the predictors of mortality remain unclear. The study aims to identify predictive factors correlated with mortality and build-up the prognostic score in patients with severe ARDS who received early and prolonged PP therapy. A total of 116 patients were enrolled in this retrospective cohort study. Univariate and multivariate regression models were used to estimate the odds ratio (OR) of mortality. Factors associated with mortality were assessed by Cox regression analysis and presented as the hazard ratio (HR) and 95% CI. In the multivariate regression model, renal replacement therapy (RRT; OR: 4.05, 1.54-10.67), malignant comorbidity (OR: 8.86, 2.22-35.41), and non-influenza-related ARDS (OR: 5.17, 1.16-23.16) were significantly associated with ICU mortality. Age, RRT, non-influenza-related ARDS, malignant comorbidity, and APACHE II score were included in a composite prone score, which demonstrated an area under the curve of 0.816 for predicting mortality risk. In multivariable Cox proportional hazard model, prone score more than 3 points was significantly associated with ICU mortality (HR: 2.13, 1.12-4.07, p = 0.021). We suggest prone score ≥3 points could be a good predictor for mortality in severe ARDS received PP therapy.

The implications of boosting Omalizumab treatment (OT) in patients with severe allergic asthma (SAA) remain unclear. The study aimed to explore and compare the 12-month effectiveness between continuous, at least 10-month OT (continuation group) and four-month boost of Omalizumab (boost group) in adult patients with SAA. In this retrospective cohort study, clinical data were collected for further analysis. Of all participants ( n = 124), a significant reduction in annual exacerbations (baseline = 0.8 ± 1.5, follow-up = 0.5 ± 1.0, p = 0.047 *) and improvement in small airway ventilation as evaluated by forced expiratory flow at 25-75% (baseline = 55.1 ± 11.1%, follow-up = 59.4 ± 8.4%, p < 0.001 *) were found in the continuation group ( n = 110). By contrast, the boost group ( n = 14) had significantly increased annual exacerbations (baseline = 0.7 ± 1.4, follow-up = 2.9 ± 3.6, p = 0.031 *) and impaired small airway function (baseline = 55.3 ± 12.9, follow-up = 52.1 ± 12.5, p = 0.026 *). Furthermore, the continuation group rather than the boost group had significant decreases in the frequency of oral corticosteroid (OCS) use as controllers (baseline = 32.7%, follow-up = 20.0%, p = 0.047 *; baseline = 50.0%, follow-up = 21.4%, p = 0.237, respectively) and OCS maintenance dose (mg/month) (baseline = 85.9 ± 180.8, follow-up = 45.8 ± 106.6, p = 0.020 *; baseline = 171.4 ± 221.5, follow-up = 50.0 ± 104.3, p = 0.064, respectively), and increases in asthma control test scores (baseline = 16.0 ± 3.0, follow-up = 19.8 ± 4.4, p < 0.001 *; baseline = 14.6 ± 3.8, follow-up = 19.7 ± 4.7, p = 0.050, respectively). Continuous OT would be beneficial for adult patients with SAA, while boost of Omalizumab would worsen their long-term outcomes.

Background: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood., Method: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model., Results: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO 2 , and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality., Conclusions: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Background and Objectives: Stress hyperglycemia is a common condition in critically ill patients. Inappropriate nutritional supplementation may worsen blood glucose control in these patients. The present study aimed to investigate the outcome of blood glucose control status when using various enteral formulas., Methods and Study Design: This retrospective study was conducted at the intensive care unit of a tertiary medical center in central Taiwan. Patients meeting the following inclusion criteria were enrolled in the study: age ≥20 years, respiratory failure requiring mechanical ventilation, and two consecutive blood glucose concentration measurements of ≥180 mg/dL. Demographic data, blood glucose samples, and hospital mortality were collected for analysis., Results: A total of 4,604 blood glucose samples from 48 patients were analyzed. Results demonstrated no significant difference in mortality rate or blood glucose control between patients fed semi-elemental formulas and those fed polymer formulas. Serum HbA1C of <7.5% was a risk factor for hospital mortality (OR: 0.18, 95% CI: 0.04-0.89). Enteral formulas containing less carbohydrate were associated with better blood glucose control., Conclusions: No significant difference in the outcome of blood glucose control was observed between patients fed semi-elemental formula and those fed polymer formula. To achieve better blood glucose control in critically ill patients, formulas with lower carbohydrate content should be considered.

The effects of tiotropium bromide soft mist inhalers (SMIs) in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation remain unexplored. This study investigated the dynamic effects of a tiotropium SMI on lung mechanics and gas exchange in these patients. We analyzed 11 mechanically ventilated and hemodynamically stable patients with COPD who experienced acute exacerbation and were ready to be weaned from the ventilator. Two puffs of tiotropium (2.5 μg/puff) were administered with a T-adaptor connected to the ventilator circuit. Lung mechanics-peak inspiratory pressure, plateau pressure, mean airway pressure, maximum respiratory resistance (Rrs), and gas exchange function-were analyzed. The two-puff tiotropium SMI treatment led to the greatest reduction in Rrs at 6 h, with the Rrs returning to baseline gradually, and significantly improved the PaO 2 /FiO 2 ratio at 24 h. Compared with baseline values, tiotropium SMI had the strongest effect on Rrs between hours 3 and 6 but did not significantly affect hemodynamic parameters. Tiotropium SMI administration in mechanically ventilated patients with COPD achieved the greatest reduction in Rrs at 6 h and significantly improved the PaO 2 /FiO 2 ratio at 24 h. Future studies should investigate whether the bronchodilation effect can be improved with increased dosage or frequency.

Although energy intake might be associated with clinical outcomes in critically ill patients, it remains unclear whether full or trophic feeding is suitable for critically ill patients with high or low nutrition risk. We conducted a prospective study to determine which feeding energy intakes were associated with clinical outcomes in critically ill patients with high or low nutrition risk. This was an investigator-initiated, single center, single blind, randomized controlled trial. Critically ill patients were allocated to either high or low nutrition risk based on their Nutrition Risk in the Critically Ill score, and then randomized to receive either the full or the trophic feeding. The feeding procedure was administered for six days. No significant differences were observed in in-hospital, 14-day and 28-day mortalities, the length of ventilator dependency, or ICU and hospital stay among the four groups. There were no associations between energy and protein intakes and in-hospital, 14-day and 28-day mortalities in any of the four groups. However, protein intake was positively associated with the length of hospital stay and ventilator dependency in patients with low nutrition risk receiving trophic feeding. Full or trophic feeding in critically ill patients showed no associations with clinical outcomes, regardless of nutrition risk., Competing Interests: The authors have no conflicts of interest.

Nasogastric tube enteral nutrition (NGEN) should be initiated within 48 h for patients at high nutritional risk. However, whether small bowel enteral nutrition (SBEN) should be routinely used instead of NGEN to improve hospital mortality remains unclear. We retrospectively analyzed 113 critically ill patients with modified Nutrition Risk in Critically Ill (mNUTRIC) score ≥ 5 and feeding volume < 750 mL/day in the first week of their stay in the intensive care unit (ICU). Age, sex, mNUTRIC score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were matched in the SBEN ( n = 48) and NGEN ( n = 65) groups. Through a univariate analysis, factors associated with hospital mortality were SBEN group (hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.31-1.00), Simplified Organ Failure Assessment (SOFA) score on day 7 (HR, 1.12; 95% CI, 1.03-1.22), and energy intake achievement rate < 65% (HR, 2.53; 95% CI, 1.25-5.11). A multivariate analysis indicated that energy intake achievement rate < 65% on the third follow-up day (HR, 2.29; 95% CI, 1.12-4.69) was the only factor independently associated with mortality. We suggest initiation of SBEN on the seventh ICU day before parenteral nutrition initiation for critically ill patients at high nutrition risk.

Context: Nearly 70% of do-not-resuscitate (DNR) directives for chronic obstructive pulmonary disease (COPD) patients are established during their terminal hospitalization. Whether patient use of end-of-life resources differs between early and late establishment of a DNR is unknown., Objectives: The objective of this study was to compare end-of-life resource use between patients according to DNR directive status: no DNR, early DNR (EDNR) (established before terminal hospitalization), and late DNR (LDNR) (established during terminal hospitalization)., Methods: Electronic health records from all COPD decedents in a teaching hospital in Taiwan were analyzed retrospectively with respect to medical resource use during the last year of life and medical expenditures during the last hospitalization. Multivariate linear regression analysis was used to determine independent predictors of cost., Results: Of the 361 COPD patients enrolled, 318 (88.1%) died with a DNR directive, 31.4% of which were EDNR. COPD decedents with EDNR were less likely to be admitted to intensive care units (12.0%, 55.5%, and 60.5% for EDNR, LDNR, and no DNR, respectively), had lower total medical expenditures, and were less likely to undergo invasive mechanical ventilator support during their terminal hospitalization. The average total medical cost during the last hospitalization was nearly twofold greater for LDNR than for EDNR decedents. Multivariate linear regression analysis revealed that nearly 60% of medical expenses incurred were significantly attributable to no EDNR, younger age, longer length of hospital stay, and more comorbidities., Conclusion: Although 88% of COPD decedents died with a DNR directive, 70% of these directives were established late. LDNR results in lower quality of care and greater intensive care resource use in end-of-life COPD patients., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Pulmonary embolism is a life-threatening disease. Its development is generally thought to be due to causes collectively known as the Virchow's triad. Chronic inflammations are associated with the activation of coagulation and increased risks of venous thromboembolic events. Asthma is one of the chronic inflammatory diseases associated with procoagulants and antifibrinolytic activities in the airways. Coagulation is activated in patients with asthma with the following steps of pathophysiology: Increased tissue factor expression in various cell types, decreased activity of the anticoagulant protein C system and inhibition of fibrinolysis through over-production of plasminogen activator inhibitor type 1 (PAI-1). Asthma is therefore likely a risk factor for pulmonary embolism, especially in those patients with severe disease conditions together with frequent exacerbation. Here we present a case of severe asthma associated with coagulopathy and complicated by massive pulmonary embolism, presented with typical S1Q3T3 on electrocardiography (ECG) and massive thrombosis on computed tomography angiography, successfully treated with directed catheter thrombolytic therapy., Competing Interests: The authors declare no conflict of interest.

Small bowel enteral nutrition (SBEN) may improve nutrient delivery to critically ill patients intolerant of gastric enteral nutrition. However, the optimal time and target for evaluating SBEN efficacy are unknown. This retrospective cohort study investigates these parameters in 55 critically ill patients at high nutrition risk (modified NUTRIC score ≥ 5). Daily actual energy intake was recorded from 3 days before SBEN initiation until 7 days thereafter. The energy achievement rate (%) was calculated as follows: (actual energy intake/estimated energy requirement) × 100. The optimal time was determined from the day on which energy achievement rate reached >60% post-SBEN. Assessment results were as follows: median APACHE II score, 27; SOFA score, 10.0; modified NUTRIC score, 7; and median time point of SBEN initiation, ICU day 8. The feeding volume, energy and protein intake, and achievement rate (%) of energy and protein intake increased significantly after SBEN ( p < 0.001). An energy achievement rate less than 65% 3 days after SBEN was significantly associated with increased mortality after adjusting for confounding factors (odds ratio, 4.97; 95% confidence interval, 1.44⁻17.07). SBEN improves energy delivery in critically ill patients who are still at high nutrition risk after 1 week of stomach enteral nutrition.

Background : The incidence of stroke after kidney transplantation is poorly understood. Our study aimed to determine the incidence and predictors of stroke as well as mortality from stroke in kidney transplant recipients (KTRs). Methods : This retrospective cohort study used the National Health Insurance Research Database in Taiwan to study KTRs ( N = 4635), patients with end-stage renal disease (ESRD; N = 69,297), and patients from the general population who were chronic kidney disease (CKD)-free and matched by comorbidities ( N = 69,297) for the years 2000 through 2010. The risk of stroke was analyzed using univariate and multivariate Cox regression models and compared between study cohorts. Findings : Compared with the ESRD subgroup, KTRs had a significantly lower risk of overall stroke (adjusted hazard ratio (aHR) = 0.37, 95% confidence interval (CI) = 0.31⁻0.44), ischemic stroke (aHR = 0.45, 95% CI = 0.37⁻0.55), and hemorrhagic stroke (aHR = 0.20, 95% CI = 0.14⁻0.29). The risk patterns for each type of stroke in the KTR group were not significantly different than those of the CKD-free control subgroup. The predictors of stroke were age and diabetes in KTRs. All forms of stroke after transplantation independently predicted an increased risk of subsequent mortality, and the strongest risk was related to hemorrhagic events. Interpretation : KTRs had a lower risk of stroke than ESRD patients, but this risk was not significantly different from that of the CKD-free comorbidities-matched general population group. Although stroke was relatively uncommon among cardiovascular events, it predicted unfavorable outcome in KTRs.

The clinical conditions of critically ill patients are highly heterogeneous; therefore, nutrient requirements should be personalized based on the patient's nutritional status. However, nutritional status is not always considered when evaluating a patient's nutritional therapy in the medical intensive care unit (ICU). We conducted a retrospective cross-sectional study to assess the effect of ICU patients' nutrition risk status on the association between energy intake and clinical outcomes (i.e., hospital, 14-day and 28-day mortality). The nutrition risk of critically ill patients was classified as either high- or low-nutrition risk using the modified Nutrition Risk in the Critically Ill score. There were 559 (75.3%) patients in the high nutrition risk group, while 183 patients were in the low nutrition risk group. Higher mean energy intake was associated with lower hospital, 14-day and 28-day mortality rates in patients with high nutrition risk; while there were no significant associations between mean energy intake and clinical outcomes in patients with low nutrition risk. Further examination of the association between amount of energy intake and clinical outcomes showed that patients with high nutrition risk who consumed at least 800 kcal/day had significantly lower hospital, 14-day and 28-day mortality rates. Although patients with low nutrition risk did not benefit from high energy intake, patients with high nutrition risk are suggested to consume at least 800 kcal/day in order to reduce their mortality rate in the medical ICU.

Background: Patients with polycystic kidney disease (PKD) might have a risk of cardiovascular diseases because several cardiovascular risk factors are occasionally associated with PKD patients. Data on the association between PKD and the risk of cardiovascular events, including acute coronary syndrome (ACS), stroke, and congestive heart failure (CHF), are scant. Methods: Patients aged &ge;20 years who were newly diagnosed with PKD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 753.12 and 753.13) between 2000 and 2011 were selected as a PKD cohort (N = 5157). The association between PKD and cardiovascular events was analyzed. Results: We randomly selected a comparison cohort of people without PKD, who were frequency-matched by sex, age, and index date of diagnosis. At the end of 2011, the PKD cohort had a 1.40-fold greater incidence of ACS compared with the comparison cohort (8.59 vs. 6.17 per 1000 person-years), in addition to a 1.40-fold greater incidence of stroke, a 1.49-fold greater incidence of CHF, and a 1.64-fold greater incidence of mortality. Conclusions: This retrospective cohort study shows that patients with PKD have an increased risk of cardiovascular events including ACS, stroke, and CHF as well as mortality, particularly in younger patients. Early identification is necessary to attenuate the risk of cardiovascular complications in patients with PKD.

Background: Claims data are currently widely used as source data in asthma studies. However, the insufficient information in claims data related to level of asthma severity may negatively impact study findings. The present study develops and validates an asthma severity classification model that uses medication utilization in Taiwan National Health Insurance claims data., Methods: The National Health Insurance Research Database was used for the years 2006-2012 and included a total of 7221 patients newly diagnosed with asthma in 2007 for model development and in 2008 for model validation. The medication utilization of patients during the first year after the index date was used to classify level of severity, and the acute exacerbation of asthma during the second through fourth years after the index date was used as the outcome variable. Three models were developed, with subjects classified into four, three, and two groups, respectively. The area under the receiver operating characteristic curve (AUC) and the Kaplan-Meier survival curve were used to compare the performances of the classification models., Results: In development data, the distribution of subjects and acute exacerbation rate among the stage 1 to stage 4 were: 62.71%, 5.54%, 22.79%, and 8.96%, and 8.17%, 9.55%, 11.97%, and 14.91%, respectively. The results also showed the higher severity groups to be more prone to being prescribed oral corticosteroids for asthma control, while lower severity groups were more likely to be prescribed short-acting medication and inhaled corticosteroid treatment. Furthermore, the results of survival analysis showed two-group classification was recommended and yield moderate performance (AUC = 0.671). In validation data, the distribution of subjects, acute exacerbation rates, and medication uses among stages were similar to those in development data, and the results of survival analysis were also the same., Conclusions: Understanding asthma severity is critical to conducting effective, scholarly research on asthma, which currently uses claims data as a primary data source. The model developed in the present study not only overcomes a gap in the current literature but also provides an opportunity to improve the validity and quality of claims-data-based asthma studies.

Paeonol is a key phenolic compound in the root bark of Moutan Cortex Radicis that has been used in traditional Chinese Medicine to ameliorate inflammation. A series of aminothiazole-paeonol derivatives (APDs) were synthesized in this work and subjected to preliminary evaluation in cells followed by verification in animals. Quantification of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) in culture media of LPS-activated A549 cells, a lung epithelial adenocarcinoma cell line, were used to investigate the anti-inflammatory capability of APDs. ALI-bearing rats were employed to verify therapeutic efficacy of APDs according to observations of total cells, protein amounts, MCP-1 and IL-6 in bronchoalveolar lavage fluid (BALF). Histopathological examinations of lung tissues were consequently applied for validation of APDs. Among these compounds, 2-(2-aminothiazol-4-yl)-5-methoxyphenol ( 4 ) had the most potent activity, showing comparable inhibition of MCP-1/IL-6 and superior elimination of neutrophil infiltration and protein exudation in lungs compared to others as well as dexamethasone. This study demonstrated a comprehensive strategy to evaluate APDs through integration of cell-based screening and animal-based verification. In order to fulfill unmet needs of treating acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), APDs introduced in this work could be promising lead compounds to develop high potent anti-inflammation agents., Competing Interests: The authors declare no conflict of interest.

Objectives: Carthamus tinctorius L. (CT) or safflower is widely used in traditional Chinese medicine. This study investigated the effects of CT extract (CTE) on ischemia-reperfusion (I/R) brain injury and elucidated the underlying mechanism., Materials and Methods: The I/R model was conducted by occlusion of both common carotid arteries and right middle cerebral artery for 90 min followed by 24 hr reperfusion in Sprague-Dawley rats. CTE (0.2-0.6 g/kg) was administered intraperitoneally before and during ischemia, and during reperfusion period. The cerebral infarction area, neurological deficit scores, free radicals (lucigenin chemiluminescence counts) and pro-inflammatory cytokines expression were measured., Results: Pretreatment and treatment with CTE significantly reduced the cerebral infarction area and neurological deficits. CTE (0.4 g/kg) also reduced blood levels of free radicals and expression of tumor necrosis factor-α and interleukin-1β in the cerebral infarction area., Conclusion: The reduction in I/R cerebral infarction caused by CTE is possibly associated with its antioxidation and anti-inflammatory properties.

The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production. It is different from the non-hydrolyzing enzymes for bacterial cell wall biosynthesis, and it is feed-back inhibited by the downstream product CMP-Neu5Ac. Here the complex crystal structure of the N-terminal epimerase part of human GNE shows a tetramer in which UDP binds to the active site and CMP-Neu5Ac binds to the dimer-dimer interface. The enzyme is locked in a tightly closed conformation. By comparing the UDP-binding modes of the non-hydrolyzing and hydrolyzing UDP-GlcNAc epimerases, we propose a possible explanation for the mechanistic difference. While the epimerization reactions of both enzymes are similar, Arg113 and Ser302 of GNE are likely involved in product hydrolysis. On the other hand, the CMP-Neu5Ac binding mode clearly elucidates why mutations in Arg263 and Arg266 can cause sialuria. Moreover, full-length modelling suggests a channel for ManNAc trafficking within the bifunctional enzyme.

To evaluate whether the use of traditional Chinese medicine (TCM; zhōng yī) influences symptoms or functional outcomes in patients with osteoarthritis (OA) of the knee ( xī guān jié yán). A systematic review of randomized control trials was conducted. Searches for studies in PubMed that were performed between 1965 and August 2013, and retrieved studies were subjected to reference screening. The types of studies included in our review were 1) placebo-based or comparative studies; 2) open label, single-blinded or double-blinded studies; 3) studies evaluating the efficacy of TCM for treating OA of the knee; and 4) studies evaluating only TCM or combination preparations. Trials were conducted with participants over 18 years of age with knee pain and at least three of the following characteristics: 1) an age greater than 50 years; 2) morning stiffness lasting for fewer than 30 min; 3) a crackling or grating sensation; 4) bony tenderness of the knee; 5) bony enlargement of the knee; or 6) no detectable warmth of the joint to the touch. Studies were rated for risk of bias and graded for quality. After screening, 104 studies that satisfied the eligibility requirements were identified, and only 18 randomized control trials were included in the quantitative and qualitative synthesis. Upon review, we found "moderate-quality" evidence of effects from acupuncture ( zhēn jiǔ) on pain, which was measured using a visual analogue scale, and physical function, which was measured using qigong ( qì gōng) with motion. "Low-quality" evidence was found regarding the effects of acupuncture on physical function, and no evidence was found regarding the effects of herbal medicine on pain or physical function. Herbal patches ( yào bù) appeared to affect pain and physical and function, but these effects were not found to be significant. The initial findings included in this review suggest that acupuncture is a promising intervention according to the primary outcome measure, pain, and qigong with motion is an effective method for treating physical function. However, according to the Grades of Recommendation, Assessment, Development, and Evaluation criteria, only moderate-quality evidence was found in these studies. Further rigorous studies are warranted to investigate the application of TCM in treating OA of knee.

Streptosporangium sibiricum SibL catalyzes the methyl transfer from S-adenosylmethionine (SAM) to 3-hydroxykynurenine (3-HK) to produce S-adenosylhomocysteine (SAH) and 3-hydroxy-4-methyl-kynurenine for sibiromycin biosynthesis. Here, we present the crystal structures of apo-form Ss-SibL, Ss-SibL/SAH binary complex and Ss-SibL/SAH/3-HK ternary complex. Ss-SibL is a homodimer. Each subunit comprises a helical N-terminal domain and a Rossmann-fold C-terminal domain. SAM (or SAH) binding alone results in domain movements, suggesting a two-step catalytic cycle. Analyses of the enzyme-ligand interactions and further mutant studies support a mechanism in which Tyr134 serves as the principal base in the transferase reaction of methyl group from SAM to 3-HK.

Moutan cortex radicis (MCR) is a Chinese herbal medicine that was widely used over a long period as an analgesic, antipyretic, and anti-inflammatory agent in China. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rat models is considered similar to adult respiratory distress syndrome (ARDS) in humans. Therefore, the present study investigates the effect of MCR on ALI. The ALI model was developed through the intra-tracheal (IT) administration of LPS (16mg/kg) to Sprague-Dawley (SD) rats, which formed the LPS group. MCR was orally administered before and after LPS was introduced into rats (MCR-LPS group and LPS-MCR group, respectively). In the MCR-LPS group, rats received MCR 2g/kg/times 3 times before LPS challenge; the LPS-MCR group received MCR 2g/kg/times 3 times after LPS challenge. The results of this experiment indicate that the number of total cells and neutrophils and the concentration of protein exudation in bronchoalveolar lavage fluid (BALF) significantly decreased in the MCR-LPS group. Cytokine levels, including levels of interleukin (IL)-1β, macrophage-inflammatory peptide (MIP)-2, IL-6, and IL-10, in BALF were also significantly inhibited at 16h after LPS administration in the MCR-LPS group. Myeloperoxidase (MPO) activity in lung tissue was reduced in the MCR-LPS and LPS-MCR groups at 16h after LPS administration. Furthermore, leukocyte infiltration and protein exudation in the alveolar space were less severe in the MCR-LPS group than in the LPS group. Therefore, the findings of this study suggest that the administration of MCR prior to LPS improves ALI, possibly mediating ALI through anti-inflammation., (Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.)