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Abstract 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 2 (93.2% vs. 36.6%, p 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.

Abstract 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.

Abstract Chronic pulmonary aspergillosis (CPA) often manifests in patients with a history of pulmonary tuberculosis and is typically characterized by recurrent hemoptysis, weight loss, and frequently coexists with poorly controlled diabetes. While weight gain is acknowledged as a valuable clinical marker for monitoring therapeutic responses in CPA, there is a scarcity of case reports exploring this aspect. Furthermore, the impact of stringent blood sugar management in diminishing CPA activity and preventing the recurrence of hemoptysis is also underreported. In this context, we present the case of a 64‐year‐old male who experienced massive hemoptysis. He had a background of uncontrolled diabetes and a history of fully treated pulmonary tuberculosis. Following therapeutic embolization, he was diagnosed with CPA that had transformed into invasive pulmonary aspergillosis (IPA) and underwent antifungal therapy for 9 months. Notably, we observed an inverse correlation between the patient's improved blood sugar control and weight gain with the serum IgG levels for Aspergillosis. This case highlights the potential benefits of non‐invasive monitoring of CPA activity and the identification of treatment responders through effective blood sugar management and weight gain.

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.

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.

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.

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.

Abstract 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

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

Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient’s signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

We fabricated a gas sensor with a wide-bandgap ZnGa2O4 (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 μm2. 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 μm2 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.

Diffuse alveolar hemorrhage (DAH) secondary to anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is rare in clinical practice and may present as severe acute respiratory distress syndrome (ARDS) with high mortality. Extracorporeal membrane oxygenation (ECMO) has been reported to be a salvage treatment providing the time necessary for immunosuppressive treatment in cases accompanied by severe ARDS. Prone positioning (PP) has been proven to reduce the mortality in patients with severe ARDS. However, there is no consensus about choosing PP or ECMO in severe ARDS due to DAH secondary to ANCA-associated vasculitis. We reported a case of microscopic polyangiitis (MPA)-related DAH and severe ARDS treated with PP successfully providing the time necessary for early glucocorticoids and plasma exchange to control the underlying disease. Since anticoagulation therapy is not necessary in PP, it does not increase the risk of bleeding tendency unlike ECMO. PP has a life-saving role in the management of patients with severe ARDS due to ANCA-associated pulmonary vasculitis.

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.

Anti-melanoma differentiation-associated protein 5 (MDA5)-positive rapidly progressive interstitial lung disease (RP-ILD) is associated with poor prognosis, and the most effective therapeutic intervention has not been established. Herein we report a case of a 45-year-old female patient who presented with myalgia, Gottron’s papules with ulceration, and dyspnea on exertion which became aggravated within weeks. Laboratory examination and electromyography confirmed myopathy changes, and a survey of myositis-specific antibodies was strongly positive for anti-MDA5 antibody. High-resolution chest tomography suggested organizing pneumonia with rapidly progressive changes within the first month after diagnosis of the disease. Anti-MDA5-associated dermatomyositis with RP-ILD was diagnosed. Following combination therapy with rituximab, tofacitinib and pirfenidone, clinical symptoms, including cutaneous manifestation, respiratory conditions and radiographic changes, showed significant and sustainable improvement. To our knowledge, this is the first reported case of anti-MDA5-associated dermatomyositis with RP-ILD successfully treated with the combination of rituximab, tofacitinib, and pirfenidone.

Abstract 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.

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.

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.

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).

Objective(s): Carthamus tinctorius L. (CT) or saffloweris 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.

Angiosarcomas are rare soft‐tissue sarcomas of endothelial cell origin and have a poor prognosis. Diffuse alveolar haemorrhage (DAH) is a syndrome characterized by the accumulation of intra‐alveolar red blood cells. However, neoplastic diseases are not commonly considered in the differential diagnosis of DAH. We report a case of a 27‐year‐old female with the diagnosis of primary breast angiosarcoma developing DAH. This raised our concern that angiosarcoma with lung metastasis may present with DAH and should be considered as an important fatal differential diagnosis of DAH.

Acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH) are accompanied with poor outcome and high mortality when miliary tuberculosis is a causative pathogen for both of them. A patient complicated with ARDS and HLH is unusual in critical care, and few case reports are present in PudMed. Besides, the relationship between HLH and ARDS is still unknown and has not been reviewed in the literature. In this report, we present the case of a 74-year-old Taiwanese woman suffering from pulmonary tuberculosis and miliary tuberculosis, and she developed ARDS and HLH on the 3rd day after admission. We arranged serial laboratory examination, various serum markers, bone marrow aspiration, and bronchoscopy with alveolar lavage for survey; we prescribed empirical antibiotics and antituberculosis medication soon after alveolar lavage showing positive acid-fast stain. She was extubated on hospital day 31 and discharged on hospital day 73. In conclusion, early diagnosis and intervention for underlying disease and intensive bundle care for multiorgan failure are crucial for both ARDS and HLH.

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 PaO2/FiO2 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 PaO2/FiO2 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 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 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.

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.

To evaluate whether the use of traditional Chinese medicine (TCM; 中醫 zhōng yī) influences symptoms or functional outcomes in patients with osteoarthritis (OA) of the knee (膝關節炎 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 (針灸 zhēn jiǔ) on pain, which was measured using a visual analogue scale, and physical function, which was measured using qigong (氣功 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 (藥布 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.

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.

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.

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.

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.

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. [ABSTRACT FROM AUTHOR]

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 falsepositives, 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. [ABSTRACT FROM AUTHOR]

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 AIassisted 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. [ABSTRACT FROM AUTHOR]