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Aspergillus fumigatus -specific IgG is often used as a diagnostic test for chronic pulmonary aspergillosis (CPA), but few studies have evaluated the performance and serology of IgGs from species other than A. fumigatus . In this study, we evaluated the serology and performance of different Aspergillus species-specific IgG antibodies in patients with CPA and at-risk populations and whether different Aspergillus species-specific IgGs could be of clinical utility and aid in the diagnosis of CPA caused by all Aspergillus species . A total of 187 participants were included between 2020 and 2022 (12 with CPA, 75 with old tuberculosis [TB], 45 with active TB and 55 with bronchiectasis). We measured the serum Aspergillus fumigatus, flavus, terreus , niger -specific, and mixed Aspergillus IgG levels (Phadia ImmunoCap). The correlation was the strongest between A. fumigatus and A. niger (Spearman's rank: 0.940), followed by A. niger and A. flavus (Spearman's rank: 0.915). A. terreus -specific IgG was less strongly correlated with the other three Aspergillus species-specific IgG (Spearman's rank: 0.828-0.849). A. flavus (4 of 6, 67%) was the dominant species. Using the at-least-one-positive approach, the highest performance was obtained when A. fumigatus and A. flavus IgGs were used (sensitivity, 0.75; specificity, 0.84). Significant cross-reactivity exists among different Aspergillus- species IgGs although the correlation may be less significant for A. terreus . In addition to the commonly used A. fumigatus IgG test, IgGs specific to local prevalent Aspergillus species may provide additional clinical utility.

Background: This study aimed to assess the diagnostic and prognostic value of Aspergillus-specific IgG (Asp-IgG) for invasive pulmonary aspergillosis (IPA) in non-neutropenic non-hematologic patients., Methods: Between November 2019 and February 2022, we recruited 40 non-neutropenic, non-hematologic IPA patients from Taiwan and measured serum Asp-IgG levels using Phadia, Thermofisher. A positive Asp-IgG test was defined as a level > 40 mgA/L. We evaluated the association between Asp-IgG levels and overall survival, as well 90-day mortality rate of IPA patients., Results: Of the 40 participants, 11 (27.5%) tested positive for Asp-IgG, while 16 (40%) had positive galactomannan antigen (optical density > 1). Higher Asp-IgG levels were associated with improved overall survival (HR: 0.22, 95% CI: 0.05-0.99, p = 0.035) in multivariable Cox regression. The overall 90-day mortality rate was 65% (26/40). We found that patients with low Asp-IgG levels (≤ 40 mgA/L) had a borderline higher 90-day mortality rate compared to patients with high Asp-IgG levels (OR: 3.15, 95% CI: 0.75-13.28, p = 0.118). Stratifying by serum galactomannan and Aspergillus IgG levels, patients with elevated serum GM and low Asp-IgG had the highest 90-day mortality (80%, 8/10), followed by patients with low serum GM and low Asp-IgG (68.4%, 13/19)., Conclusions: Asp-IgG was positive in approximately one-fourth of non-neutropenic IPA patients. Asp-IgG may hold potential as a clinical prognostic factor for IPA. Further studies are required to validate this finding., (© 2024. The Author(s).)

Background: Lower extremity peripheral artery disease (LE-PAD) has been linked to unfavorable cardiovascular outcomes. The impact of potentially undiagnosed LE-PAD, suspected by abnormal ankle-brachial index (ABI), on the survival of sepsis patients admitted to the intensive care unit (ICU) remains uncertain., Methods: We conducted a prospective cohort study and recruited adult patients admitted to the ICU with a primary diagnosis of sepsis (defined by a quick Sepsis-Related Organ Failure Assessment score of ≥ 2) between November 23, 2017 and July 22, 2018. ABI measurements were obtained within 24 hours of admission. The study compared the 30-day and 1-year all-cause mortality rates as well as the incidence of major adverse cardiovascular events (MACEs) between the groups with normal and abnormal ABI values., Results: Of the 102 sepsis patients admitted to the ICU, 38 (37%) were diagnosed with LE-PAD based on their ABI measurements. The overall 30-day mortality rate was 30.0% in patients with LE-PAD and 25.8% in those with normal ABI (p = 0.56). At 1 year, the overall mortality rate was 52.6% in the patients with abnormal ABI and 40.6% in those with normal ABI (p = 0.24). Additionally, the incidence of MACEs was significantly higher in the patients with abnormal ABI compared to those with normal ABI at 1-year follow-up (21.1% vs. 3.1%, respectively; p = 0.003)., Conclusions: The patients with abnormal ABI had a higher incidence of MACEs within one year following hospital discharge. Future studies are needed to improve cardiovascular outcomes among sepsis survivors (ClinicalTrials.gov number, NCT03372330)., Competing Interests: All the authors declare no conflict of interest.

Isoniazid is an early bactericidal anti-tuberculosis (TB) agent and isoniazid mono-resistance TB is the most prevalent drug-resistant TB worldwide. Concerns exist regarding whether resistance to isoniazid would lead to delayed culture conversion and worst outcomes. From January 2008 to November 2017, adult culture-positive pulmonary TB patients receiving isoniazid, rifampicin, pyrazinamide, and ethambutol were identified through Taiwan Center for Disease Control database and were followed until the end of 2017. Primary outcomes included time to sputum culture conversion (SCC) within two months. Secondary outcomes included death and unfavourable outcomes at the end of 2nd month. A total of 37,193 drug-susceptible and 2,832 isoniazid monoresistant pulmonary TB patients were identified. Compared with no resistance, isoniazid monoresistance was not associated with a delayed SCC (HR: 0.99, 95% CI: 0.94─1.05, p  = 0.8145), a higher risk of 2-month mortality (HR: 1.19, 95% CI: 0.92─1.53, p  = 0.1884), and unfavourable outcomes at 2nd month (OR: 1.05, 95% CI: 0.97─1.14, p  = 0.2427). Isoniazid monoresistance was associated with delayed SCC (HR: 0.90, 95% CI: 0.83─0.98, p  = 0.0099) and a higher risk of unfavourable outcomes (OR:1.18, 95% CI: 1.05─1.32, p  = 0.0053) in patients aged between 20 and 65, and delayed SCC in patients without underlying comorbidities (HR: 0.90, 95% CI: 0.81─0.98, p  = 0.0237). Isoniazid mono-resistant TB had a comparable outcome with drug-susceptible TB at the end of the intensive phase. Healthy, and non-elderly patients were more likely to had culture persistence, raising concerns about disease transmission in these subgroups and warranting early molecular testing for isoniazid resistance.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chung, Su, Wang, Budiarto, Yeh, Cheng, Keng, Chen, Lu, Juan, Nakahira, Ruan, Chien, Chang, Jerng, Huang, Chen and Yu.)

Background: Studies comparing the effectiveness of either adjuvant oral uracil-tegafur (UFT) or intravenous chemotherapy on early-stage (stage I and II) non-small cell lung cancer (NSCLC) patients treated with complete surgical treatment remain limited., Methods: From January 2011 to December 2017, patients with early-stage NSCLC (defined as tumor size >3 cm without mediastinal lymph node involvement or any distant metastasis) receiving either adjuvant oral UFT or intravenous chemotherapy after surgical resection were identified from the Taiwan Cancer Registry. Overall survival (OS) and relapse-free survival (RFS) were the primary and secondary outcomes, respectively. Propensity matching was used for controlling confounders., Results: A total of 840 patients receiving adjuvant therapy after surgery (including 595 oral UFT and 245 intravenous chemotherapy) were enrolled. Before matching, patients using oral UFT had significantly longer OS (HR: 0.69, 95% CI: 0.49-0.98, p = 0.0387) and RFS (HR: 0.79, 95% CI: 0.61-0.97, p = 0.0392) than those with intravenous chemotherapy. A matched cohort of 352 patients was created using 1:1 propensity score-matching. In the Cox regression analysis, the UFT and the matched chemotherapy groups had similar OS (HR: 0.80, 95% CI: 0.48-1.32, p = 0.3753) and RFS (HR: 0.98, 95% CI: 0.72-1.34, p = 0.9149). Among subgroup analysis, oral UFT use was associated with longer RFS among the subgroups of non-drinker (HR: 0.66, 95% CI: 0.34-0.99, p = 0.0478) and patients with stage IB disease (HR: 0.67, 95% CI: 0.42-0.97, p = 0.0341)., Conclusions: This population-based study in the real-world setting of Taiwan demonstrates comparable effectiveness between oral UFT and intravenous chemotherapy in terms of clinical outcomes for early-stage NSCLC patients after surgery., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Acute kidney injury (AKI) is occasionally detected in patients receiving anti-tuberculosis (TB) treatment. This prospective cohort study is the first to investigate the incidence, risk factors, and renal outcomes of AKI during anti-TB treatment., Methods: This study was conducted from January 1, 2016, to May 31, 2018. Patients with a new diagnosis of TB and on standard anti-TB treatment were enrolled, and the patients received regular laboratory monitoring. AKI was defined according to the Kidney Disease: Improving Global Outcome (KDIGO) criteria. Urinalysis, renal ultrasonography, blood erythrocyte morphology, and fractional excretion of sodium were performed at AKI onset. The TB treatment regimen was adjusted by the primary physician if necessary. Risk factors for AKI were identified through Cox regression., Results: In total, 106 patients were recruited (mean age 52.6 years, 71.7% men). Eleven (10.3%) patients experienced AKI. Increased serum uric acid and hemoglobin levels were noted at AKI onset. All patients with AKI achieved renal recovery and completed anti-TB treatment containing rifampin. Age [hazard ratio (HR) 1.06 (1.02-1.11)], a higher baseline estimated glomerular filtration rate [eGFR; HR 1.04 (1.02-1.06)], and a blood eosinophil count > 350 (10 9 /L) [HR 10.99 (2.28-53.02)] were associated with a higher risk of AKI during TB treatment., Conclusion: Regular pharmacovigilant monitoring revealed an incidence of renal impairment during anti-TB treatment that was higher than expected. AKI was more common in older patients with a higher eGFR and blood eosinophil count. However, the complications had no influence on TB treatment completion, and no permanent renal impairment occurred., (© 2023. The Author(s).)

Background: Rapid developments in medical care-such as monitoring devices, medications, and working hours restrictions for intensive care personnel-have dramatically increased the demand for intensive care physicians. Therefore, nurse practitioner (NP)-staffed care is becoming increasingly important. This study was aimed to compare the outcomes of daytime NP-staffed and daytime resident-staffed nonsurgical intensive care units (ICU)., Methods: We retrospectively assessed patients admitted to a nonsurgical ICU from March 2017 to December 2017. We collected basic patient data, including age, sex, admission diagnosis, transferring unit, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Primary endpoints were ICU mortality, hospital mortality, and 30-day mortality. Secondary endpoints were 48-h readmission, discharge to nonhome locations, and lengths of ICU and hospital stay., Results: A total of 838 subjects were analysed: 334 subjects in the NP-staffed group and 504 in the resident-staffed group. The NP-staffed group was more likely to come from inpatient units (38.3% vs 16.5% for resident-staffed group; p < 0.001) and had lower disease severity (APACHE II score, 13.9 ± 8.4 vs 15.1 ± 8.2 for resident-staffed group; p = 0.047). After adjusting for age, sex, location before ICU admission, APACHE II score, and significantly different basic characteristics, there were no differences in ICU mortality, hospital mortality, or 30-day mortality between the two groups. Secondary analysis showed the NP-staffed group had a lower discharge rate to nonhome locations (2.1% vs 6.3%; p = 0.023) and shorter hospital stay (12.1 ± 14.1 vs 14.2 ± 14.3 days; p = 0.015)., Conclusions: We observed no difference in mortality between daytime NP-staffed and resident-staffed nonsurgical ICUs. Daytime NP-staffed care is an effective, safe, feasible method for staffing nonsurgical ICUs., (Copyright © 2021 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with influenza-associated acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (vv-ECMO) support have a high mortality rate. Ventilator settings have been known to have a substantial impact on outcomes. However, the optimal settings of mechanical ventilation during vv-ECMO are still unknown., Methods: This multicenter retrospective cohort study was conducted in the intensive care units (ICUs) of three tertiary referral hospitals in Taiwan between July 2009 and December 2019. It aims to describe the effect of ventilator settings during vv-ECMO on patient outcomes., Results: A total of 93 patients with influenza receiving ECMO were screened. Patients were excluded if they: were receiving venoarterial ECMO, died within three days of vv-ECMO initiation, or were transferred to the tertiary referral hospital >24 hours after vv-ECMO initiation. A total of 62 patients were included in the study, and 24 (39%) died within six months. During the first three days of ECMO, there were no differences in tidal volume (5.1 vs. 5.2 mL/kg, p  = 0.833), dynamic driving pressure (15 vs. 14 cmH2O, p  = 0.146), and mechanical power (11.3 vs. 11.8 J/min, p  = 0.352) between survivors and non-survivors. However, respiratory rates were significantly higher in non-survivors compared with survivors (15 vs . 12 breaths/min, p  = 0.013). After adjustment for important confounders, a higher mean respiratory rate of >12 breaths/min was still associated with higher mortality (adjusted hazard ratio = 3.31, 95% confidence interval = 1.10-9.97, p  = 0.034)., Conclusions: In patients with influenza-associated ARDS receiving vv-ECMO support, we found that a higher respiratory rate was associated with higher mortality. Respiratory rate might be a modifiable factor to improve outcomes in this patient population., Competing Interests: The authors declare there are no competing interests., (©2022 Liao et al.)

Background: Microorganisms of tuberculosis (TB) are frequently difficult to identify from the airway specimen; therefore, lung biopsy for further histologic and microbiologic study is required. Endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) is used for the diagnosis of pulmonary malignancy, but is rarely in the TB population. The purpose of this study was to verify the effectiveness and safety of EBUS-TBB with histologic study and tissue culture in the diagnosis of sputum smear-negative pulmonary TB., Methods: Patients who underwent EBUS-TBB with histologic study and TB tissue culture for clinically suspected, but sputum smear-negative pulmonary TB from January 2016 to December 2018, were included. The accuracy of each diagnostic modality was calculated, respectively. Factors that might influence the positive rate of TB culture (washing fluid and tissue specimen) were also evaluated., Results: One hundred sixty-one patients who underwent EBUS-TBB for clinically suspected, but sputum smear-negative pulmonary TB, were enrolled, and 43 of them were finally diagnosed as having pulmonary TB. The sensitivity of washing fluid (a combination of smear, culture, and polymerase chain reaction for TB) and tissue specimen (a combination of pathology and tissue culture) via EBUS-TBB for TB diagnosis were 48.8 and 55.8%, respectively. The sensitivity for TB diagnosis would be elevated to 67.4% when both washing fluid and tissue specimens are used. The positive TB culture rate would not statistically increase with a combination of tissue specimens and washing fluid. Univariate analysis revealed that TB microorganisms would be more easily cultivated when lesions had an abscess or cavity on the computed tomography (CT) image (presence vs. absence; 62.5 vs. 26.3%, p = 0.022), heterogeneous echogenicity on the EBUS finding (heterogeneous vs. homogeneous; 93.3 vs. 21.4%, p = 0.001), or a necrotic pattern via histologic study (presence vs. absence; 70.6 vs. 30.8%, p = 0.013). Heterogeneous echogenicity in the EBUS finding was the independent predictor according to the results of multivariate analysis. None of our patients encountered major adverse events or received further intensive care after EBUS-TBB., Conclusion: Endobronchial ultrasound-guided transbronchial biopsy is safe and effective for use in diagnosing sputum smear-negative pulmonary TB. EBUS echoic feature is also a predictor of the positive TB culture rate in pulmonary TB. However, tissue culture via EBUS-TBB has little effect in improving the positive TB culture rate., 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 Lin, Fan, Yu, Chang, Wen, Keng and Ho.)

Competing Interests: Competing interests: None declared.

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).

Background: Comprehensive rehabilitation programs are recommended for patients with prolonged mechanical ventilation (PMV) to facilitate functional recovery and ventilator weaning, but whether the functional status after rehabilitation influences outcome has not been clearly evaluated. This study aimed to investigate the association between post-rehabilitation functional status and weaning and survival outcome in PMV patients. Methods: We retrospectively enrolled PMV patients admitted to the respiratory care center (RCC), a post-ICU weaning facility with protocolized rehabilitation program, from January 2016 through December 2017. Functional status was measured by the de Morton Mobility Index (DEMMI), with a cut-off value set at 20 points. The primary outcomes were the weaning status at RCC discharge and hospital survival. The secondary outcomes were overall survival and survival at 3 months after RCC discharge. We followed patients until 3 months after RCC discharge or death. Logistic and Cox regressions were performed to identify significant parameters associated with weaning success and survival. Results: In total, 320 patients were enrolled. The weaning success rate was 71.6%. The survival rate at RCC discharge, hospital discharge, and 3 months after RCC discharge was 89.1, 77.5, and 66.6%, respectively. Post-rehabilitation DEMMI ≥ 20 (odds ratio [OR], 3.514; 95% confidence interval [CI], 1.436-8.598; P = 0.006) was the most significantly associated with weaning success. The weaning success and higher post-rehabilitation DEMMI were the two most significant independent factors associated with both hospital survival (weaning success, OR, 12.272; 95% CI, 5.281-28.517; P < 0.001; post-rehabilitation DEMMI ≥ 20, OR, 6.298; 95% CI, 1.302-30.477; P = 0.022) and survival at 3 months after RCC discharge (weaning success, OR, 38.788; 95% CI, 11.505-130.762; P < 0.001; post-rehabilitation DEMMI ≥ 20, OR, 4.830; 95% CI, 1.072-21.756; P = 0.040). Post-rehabilitation DEMMI ≥ 20 remained significantly association with overall survival at 3 months after RCC discharge (hazard ratio, 0.237; 95% CI, 0.072-0.785; P = 0.018). Conclusions: Post-rehabilitation functional status of PMV patients was independently associated with weaning success, as well as hospital and 3-month overall survival after RCC discharge. Post-rehabilitation, but not pre-rehabilitation, functional status was a significant parameter associated with weaning success and survival in patients requiring PMV., Competing Interests: S-KL received speaking honoraria from Norvatis, Pfizer, Roche, and Boehringer Ingelheim. The remaining 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 © 2021 Keng, Liang, Tseng, Wen, Tsou, Chang, Chang, Yu, Lee and Ko.)

(1) Background: Lung cancer is silent in its early stages and fatal in its advanced stages. The current examinations for lung cancer are usually based on imaging. Conventional chest X-rays lack accuracy, and chest computed tomography (CT) is associated with radiation exposure and cost, limiting screening effectiveness. Breathomics, a noninvasive strategy, has recently been studied extensively. Volatile organic compounds (VOCs) derived from human breath can reflect metabolic changes caused by diseases and possibly serve as biomarkers of lung cancer. (2) Methods: The selected ion flow tube mass spectrometry (SIFT-MS) technique was used to quantitatively analyze 116 VOCs in breath samples from 148 patients with histologically confirmed lung cancers and 168 healthy volunteers. We used eXtreme Gradient Boosting (XGBoost), a machine learning method, to build a model for predicting lung cancer occurrence based on quantitative VOC measurements. (3) Results: The proposed prediction model achieved better performance than other previous approaches, with an accuracy, sensitivity, specificity, and area under the curve (AUC) of 0.89, 0.82, 0.94, and 0.95, respectively. When we further adjusted the confounding effect of environmental VOCs on the relationship between participants' exhaled VOCs and lung cancer occurrence, our model was improved to reach 0.92 accuracy, 0.96 sensitivity, 0.88 specificity, and 0.98 AUC. (4) Conclusion: A quantitative VOCs databank integrated with the application of an XGBoost classifier provides a persuasive platform for lung cancer prediction.

Objectives: Large-scale, population-based real-world studies on the treatment outcomes of first-line tyrosine kinase inhibitors (TKIs) and subsequent systemic chemotherapy agents for lung adenocarcinoma (with activating epidermal growth factor receptor [EGFR] mutations) remain limited., Materials and Methods: From March 2014 to December 2016, patients with advanced lung adenocarcinoma, identified from the Taiwan Cancer Registry were included in this study if they received any of the three TKIs as first-line treatment. The primary outcome was overall survival (OS). The secondary outcome was time-to-treatment discontinuation (TTD)., Results: A total of 4,889 patients (median age: 67 years and two-thirds with distant metastasis) were recruited (1,778 gefitinib, 1,599 erlotinib, and 1,512 afatinib users). A 1:1 propensity score (PS)-matched cohorts of 1,228 afatinib/erlotinib and 1054 afatinib/gefitinib was created. After PS matching, it was found that afatinib was not associated with better OS (afatinib vs. erlotinib, HR: 0.96, 95% CI: 0.86-1.07; afatinib vs. gefitinib, HR: 0.91, 95% CI: 0.81-1.02). In the subgroup analysis, afatinib demonstrated a survival benefit in patients with active smoking (afatinib vs. erlotinib, HR: 0.69, 95% CI: 0.51-0.93; afatinib vs. gefitinib, HR: 0.67, 95% CI: 0.48-0.94) and ECOG > 1 (afatinib vs. erlotinib, HR: 0.79, 95% CI: 0.63-0.99; afatinib vs. gefitinib, HR: 0.78, 95% CI: 0.62-0.98). A total of 41.1% (n = 1992) of first-line TKI users received subsequent chemotherapy. Among the three TKI groups, pemetrexed usage was associated with better OS compared with other chemotherapy agents, with the exception of gemcitabine in the afatinib and gefitinib groups. Pemetrexed and gemcitabine had the longest TTD of 3-4 months., Conclusions: Among patients with EGFR mutant lung adenocarcinoma, afatinib use may not provide longer OS compared with first-generation TKIs. Afatinib may be preferably considered among patients with active smoking and should not be withheld among those with worse performance status. With 40% of patients receiving subsequent chemotherapy, pemetrexed may be the preferred agent, while gemcitabine can be a reasonable alternative., Competing Interests: S-KL has received honoraria for speeches from Roche, AstraZeneca, Pfizer, Merck Sharp & Dohme, Novartis, and Boehringer Ingelheim. M-RL has received honoraria for speeches from Roche, Pfizer, and Daiichi Sankyo. J-YS has received speaking honoraria from AstraZeneca, Roche, Boehringer Ingelheim, Pfizer, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, and Eli Lilly, and has been paid for fulfilling a consulting or advisory role by AstraZeneca, Roche, Boehringer Ingelheim, Novartis, Merck Sharp & Dohme, AbbVie, and Chugai Pharmaceutical. The remaining 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 © 2021 Liang, Keng, Chang, Wen, Lee, Yang, Wang, Ko, Shih and Yu.)

Background/purpose: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been gradually introduced in the diagnosis of mediastinal tuberculous (TB) lymphadenitis. The purposes of this study were to evaluate the utility of polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA rinse fluid and to explore the factors that influence the accuracy of EBUS-TBNA., Methods: A retrospective study with prospective data collection was carried out with patients with unselected mediastinal lymphadenopathy who underwent EBUS-TBNA and a TB-PCR study from April 2010 to July 2017. Patients without TB were excluded. The diagnostic accuracy rate for each diagnostic modality (pathology, smear, culture, and TB-PCR) was calculated respectively. The characteristics of the lymph node (LN) and the pathologic findings were analyzed as possible impact factors., Results: 240 consecutive patients who received EBUS-TBNA were enrolled, and in the end, 21 patients with a diagnosis of TB lymphadenitis were included. When combined with histologic results and traditional microbiologic studies, the diagnostic accuracy of EBUS-TBNA was 57.1%. If TB-PCR was also utilized, the diagnostic accuracy would significantly increase to 71.4% (p < 0.001). Univariate and multivariate regression analysis revealed that pathology showing necrosis had a higher positive microbiologic result when using EBUS-TBNA rinse fluid., Conclusion: EBUS-TBNA is a valuable tool for diagnosis of mediastinal TB lymphadenitis. Using TB-PCR assay and targeting LNs with a necrotic component would improve the diagnostic performance of EBUS-TBNA., (Copyright © 2019 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None.

We evaluated the real-world efficacy and side effects of afatinib as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. The medical records of patients receiving afatinib as a first-line therapy after National Health Insurance reimbursement between May 2014 and January 2016 were reviewed, and information on patient characteristics and treatment courses were collected consecutively. Rebiopsy tissue was collected for EGFR mutation and MET amplification analyses. MET amplification was detected by fluorescence in situ hybridization and immunohistochemistry. In total, 140 patients were enrolled (median follow-up, 18.0 months). No significant differences in side effects, treatment responses, progression-free survival, or brain metastasis control were observed between patients receiving 40 mg versus < 40 mg of afatinib during the first 6 months. Patients with significant pretreatment weight loss (> 10.0% in 6 months) had a shorter median progression-free survival. Patients with brain metastases had a poorer Eastern Cooperative Oncology Group performance status and were associated with a shorter median progression-free survival. Nine patients (32.1%) had a p.T790M mutation and only 1 patient gained MET amplifications after disease progression. Afatinib is effective as a first-line therapy for advanced EGFR mutation-positive lung adenocarcinoma. Afatinib dosage does not affect clinical efficacy and drug-related side effects., Competing Interests: CONFLICTS OF INTEREST Sheng-Kai Liang has received honoraria for speeches from Pfizer and Boehringer Ingelheim, and Jen-Chung Ko has received honoraria for speeches from Boehringer Ingelheim, AstraZeneca, and Roche, and Jin-Yuan Shih has received speaking honoraria from AstraZeneca, Roche, Pfizer, Boehringer Ingelheim, Merck Sharp & Dohme, and Eli Lilly.

The current standard care for acute mesenteric ischemia (AMEI) involves urgent revascularization and resection of the necrotic bowel. Since 2012, we have used an AMEI protocol of our own design, which focused on early treatment and allowed interventional cardiologists to become involved when interventional radiologist was not available. A total of 8 patients were treated, and two interventional cardiologists performed all the stenting procedures. The procedure success rate was 100% in patients with non-calcified lesions (6/8). The 30-day survival rate was 100% in patients with angiographic success, and was 0% in patients with failed procedure. In two patients with total occlusion of the superior mesenteric artery, laparotomy was avoided when interventions were successful and completed within six hours of protocol activation. Four surviving patients were discharged after short intensive care unit stays (less than 48 hours); these patients returned to and remained at home throughout their 90-day follow-up. The overall procedure success rate and 30-day survival rate were both 75%. There was no access site or intervention-related complications. Using our protocol, we believe that primary endovascular treatment for AMEI is feasible. In geographic regions where healthcare resources are lacking, a time-efficient strategy adopted by interventional cardiologists should be considered for the purpose of saving lives and possibly even avoiding open laparotomy.

Studies about prognostic assessment in cancer patients requiring prolonged mechanical ventilation (PMV) for post-intensive care are scarce. We retrospectively enrolled 112 cancer patients requiring PMV support who were admitted to the respiratory care center (RCC), a specialized post-intensive care weaning facility, from November 2009 through September 2013. The weaning success rate was 44.6%, and mortality rates at hospital discharge and after 1 year were 43.8% and 76.9%, respectively. Multivariate logistic regression showed that weaning failure, in addition to underlying cancer status, was significantly associated with an increased 1-year mortality (odds ratio, 6.269; 95% confidence interval, 1.800-21.834; P = 0.004). Patients who had controlled non-hematologic cancers and successful weaning had the longest median survival, while those with other cancers who failed weaning had the worst. Patients with low maximal inspiratory pressure, anemia, and poor oxygenation at RCC admission had an increased risk of weaning failure. In conclusion, cancer status and weaning outcome were the most important determinants associated with long-term mortality in cancer patients requiring PMV. We suggest palliative care for those patients with clinical features associated with worse outcomes. It is unknown whether survival in this specific patient population could be improved by modifying the risk of weaning failure.

Patients with rheumatoid arthritis (RA) often have pulmonary involvement, and interstitial lung disease (ILD) is the primary manifestation, in which diffuse alveolar damage (DAD) is a rare histopathologic pattern. Leflunomide (LEF) is a frequently prescribed disease-modifying antirheumatic drug for treating RA. LEF-related ILD in the form of DAD has been reported in patients with RA, with the duration of LEF treatment before symptom onset ranging from 6 to 1204 days.We present a case of elderly woman with RA under prolonged LEF treatment for >9 years (3291 days), who had acute respiratory failure with the initial presentation of exertional dyspnea, fever, chills, and productive cough for 2 days. The histopathologic result of surgical lung biopsy was compatible with DAD. She was diagnosed as having LEF-related ILD, based on correlated clinical history, compatible histopathologic examination and excluding possible infection after extensive survey.Although the causative role of LEF cannot be confirmed, this case still hints that LEF-related DAD may occur even if LEF has been prescribed for a prolonged period.

Background: Both procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been investigated separately as indicators of infection in patients with autoimmune diseases. Our study simultaneously evaluated both PCT and sTREM-1 along with C-reactive protein (CRP) in febrile patients with autoimmune diseases., Methods: Fifty-nine patients were enrolled in the study. The patients were categorized into the infection group (n=24) or the disease flare group (n=35). sTREM-1, PCT and CRP concentrations at fever onset were compared between the two groups of patients., Results: sTREM-1 and CRP did not differ between the two groups. PCT [median (range), ng/ml] was higher in the infection group than in the disease flare group [0.53 (0.02-12.85) vs. 0.12 (0.02-19.23), p=0.001]. The area under the receiver-operating characteristic (ROC) for diagnosis of infection was 0.75 for PCT (p=0.001), 0.63 for CRP (p=0.09) and 0.52 for sTREM-1 (p=0.79). Using 0.2 ng/ml as the cutoff value for PCT, sensitivity was 0.75 and specificity was 0.77. Negative predictive values for PCT were 92%, 87% and 82% for a prevalence of infection of 20%, 30%, and 40%, respectively. Neither immunosuppressants nor biomodulators affected the level of the three biomarkers. However, in patients treated with corticosteroids, the levels of sTREM-1 and CRP were significantly decreased compared with the untreated patients., Conclusions: Setting PCT at a lower cutoff value could provide useful information on excluding infection in febrile patients with autoimmune diseases. The possible effect of corticosteroids on the level of sTREM-1 as an infection marker deserves further study.

Background and Objective: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. While some inflammatory markers in pleural effusion (PE) are helpful in diagnosis, the roles of anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes have not been investigated., Methods: Lymphocyte-predominant exudative PE samples were assayed for inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes. Logistic regression analysis was used to predict the probability of TPE and identify independently associated factors. Receiver operating characteristic (ROC) curve analysis was applied to determine the optimal cut-off value for the predicted probability., Results: Of 95 patients enrolled, 35 had TPE, 46 had malignant PE and 14 had PE due to other aetiologies. Interferon-γ (IFN-γ), adenosine deaminase (ADA), decoy receptor (DcR) 3, monocyte chemo-attractant protein (MCP)-1, IFN-induced protein (IP)-10, granzyme A and perforin were higher in TPE than in PE of other aetiologies. By logistic regression analysis, IFN-γ ≥ 75 pg/mL, ADA ≥ 40 IU/mL, DcR3 ≥ 9.3 ng/mL and soluble tumour necrosis factor receptor 1 (TNF-sR1) ≥ 3.2 ng/mL were independent factors associated with TPE. The predicted probability based on the four predictors had an area under the ROC curve of 0.920, with 82.9% sensitivity and 86.7% specificity under the cut-off value of 0.303. In the TPE group, patients with positive PE/pleural culture for Mycobacterium tuberculosis had higher pleural IFN-γ, MCP-1, IP-10 and perforin than those with positive sputum but negative PE culture., Conclusions: While pleural interferon-γ and ADA are conventional markers for diagnosing TPE, simultaneous measurements of DcR3 and TNF-sR1 can improve the diagnostic efficacy., (© 2014 Asian Pacific Society of Respirology.)

Objective: Conventional methods for diagnosing tuberculous pleurisy (TB pleurisy) are either invasive or have a long turn-around-time. Performances of pleural adenosine deaminase (ADA), ADA2, interferon-gamma (IFN-γ), and interferon-gamma release assays (IGRA) as diagnostic tools for TB pleurisy were evaluated., Methods: Eighty-eight patients with lymphocyte-predominant pleural exudates between June 2010 and March 2011, including 31 with clinically diagnosed TB pleurisy, were prospectively studied. Pleural ADA and ADA2 activity were measured by colorimetric method, IFN-γ levels by enzyme-linked immuno-sorbent assay, and IGRA by enzyme-linked immuno-spot (T-SPOT.TB) assay., Results: Pleural ADA, ADA2, and IFN-γ levels, but not the proportion of positive T-SPOT.TB assay, were significantly higher in patients with TB pleurisy than in those without TB pleurisy. The area under the receiver-operating-characteristic (ROC) curve was 0.920, 0.893, 0.875, and 0.544 for IFN-γ, ADA2, ADA, and T-SPOT.TB assay, respectively. The combination of ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL yielded a specificity of 100%., Conclusions: Pleural ADA, ADA2 and IFN-γ, but not T-SPOT.TB assay, are all sensitive and specific for TB pleurisy. In patients with lymphocyte-predominant pleural exudates, ADA ≥ 40 IU/L and IFN-γ ≥ 75 pg/mL in pleural effusion imply a very high probability of TB pleurisy., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: There is paucity of risk factors on lung function decline among patients with non-tuberculous mycobacteria (NTM) pulmonary disease in literature., Methods: Patients with NTM pulmonary disease between January 2000 and April 2011 were retrospectively selected. Sixty-eight patients had at least two pulmonary function tests within a mean follow-up period of 47 months., Results: Sixty-eight patients were included. They had a median age of 65 years and 65% had impaired lung function (Forced expiratory volume in 1 second [FEV1] <80% of predicted value). The mean FEV1 decline was 48 ml/year. By linear regression, younger age (beta: 0.472, p<0.001), initial FEV1>50% of predicted value (beta: 0.349, p = 0.002), male sex (beta: 0.295, p = 0.018), bronchiectasis pattern (beta: 0.232, p = 0.035), and radiographic score >3 (beta: 0.217, p = 0.049) were associated with greater FEV1 decline. Initial FEV1>50% of predicted value (beta: 0.263, p = 0.032) was also associated with greater FVC annual decline, whereas M. kansasii pulmonary disease was marginally associated with greater annual FVC decline (beta: 0.227, p = 0.062)., Conclusions: NTM pulmonary disease is associated with greater decline in lung function in patients who are young, male, with bronchiectasis, and with a high radiographic score. Special attention should be given to patients with these risk factors.