Search

Wei-Chun Huang,1,2 Chih-Yu Chen,1 Wei-Chih Liao,1,2 Biing-Ru Wu,1,3,4 Wei-Chun Chen,1,3,4 Chih-Yen Tu,1,2 Chia-Hung Chen,1,2 Wen-Chien Cheng1– 4 1Division of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 3Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 4Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, TaiwanCorrespondence: Wen-Chien Cheng; Chia-Hung ChenDivision of Pulmonary and Critical Care, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, North District, Taichung City, 40402, TaiwanEmail wcchengdr@gmail.com; hsnu758@gmail.comObjective: This real world study evaluated the effectiveness of switching to closed triple therapy from mono/dual combination or open triple therapy in patients with chronic obstructive pulmonary disease (COPD).Methods: We conducted this retrospective study at a single medical center from December 2014 to September 2020. Patients with COPD who were stepped up to triple therapy were enrolled. We analyzed the duration from initial COPD management to open or closed triple therapy and identified the clinical predictors of the patients who needed triple therapy early. We also evaluated the effectiveness of triple therapy after switching from initial management, and closed triple therapy after switching from open triple therapy.Results: A total 115 COPD patients who were stepped up to triple therapy from initial treatment were analyzed. The duration from initial treatment to triple therapy was 22.4 months. The baseline peripheral blood eosinophil counts of the patients who switched to triple therapy early (n=63, less than 22 months) and those who switched to triple therapy later (n=52, more than 22 months) were similar (489.6 vs 434.5 cells/uL; p=0.589). After univariate and multivariate analysis, the patients who were older had more acute exacerbations (AEs) in the previous year, asthma and COPD overlap (ACO), and initial dual bronchodilator therapy were stepped up to triple therapy early. The FEV1 of the patients was significantly increased after switching to open triple therapy from mono bronchodilator therapy. In addition, switching from initial or open triple therapy to closed triple therapy significantly reduced the incidence of AEs.Conclusion: COPD patients with high blood eosinophilia, older age, more AEs in the previous year, ACO, and initial dual bronchodilator therapy were stepped up to triple therapy early. Triple therapy showed improvements in lung function of most patients switching from mono bronchodilator therapy. After switching to closed triple therapy further reduced the incidence of AEs.Keywords: COPD, chronic obstructive pulmonary disease, closed triple therapy, open triple therapy, ACO, asthma COPD overlap

Wen-Chien Cheng,1– 6 Biing-Ru Wu,1,3,5,6 Wei-Chih Liao,1,2,4,7 Chih-Yu Chen,1 Wei-Chun Chen,1,3– 6 Te-Chun Hsia,1,4,8 Chih-Yen Tu,1– 3 Chia-Hung Chen,1,2,7 Wu-Huei Hsu1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University, Taichung, Taiwan; 3Department of Life Science, National Chung Hsing University, Taichung, Taiwan; 4Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University Hospital, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 8Department of Respiratory Therapy, China Medical University, Taichung, TaiwanCorrespondence: Chia-Hung Chen; Chih-Yu ChenDepartment of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung, TaiwanEmail hsnu758@gmail.com; cychen0808@gmail.comPurpose: Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function. Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.Patients and Methods: This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL. The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Composite CID was used in assessing the response to treatment after 24 weeks of therapy.Results: This study included 110 patients, of which 49 patients reportedly experienced CID. The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥  100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA). Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA. Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID. A baseline FEV1 of ≤ 42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.Conclusion: Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥ 100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18).Keywords: inhaled corticosteroid, ICS, long-acting muscarinic antagonist, LAMA, long-acting β2 agonist, LABA, triple therapy, chronic pulmonary obstructive disease, COPD, clinically important deterioration, CID

Abstract Overexpression of HER-2/Neu occurs in about 25–30% of breast cancer patients and is indicative of poor prognosis. While Her2/Neu overexpression is primarily a result of erbB2 amplification, it has recently been recognized that erbB2 levels are also regulated on the protein level. However, factors that regulate Her2/Neu protein stability are less well understood. The prolyl isomerase Pin1 catalyzes the isomerization of specific pSer/Thr-Pro motifs that have been phosphorylated in response to mitogenic signaling. We have previously reported that Pin1-catalyzed post-phosphorylational modification of signal transduction modulates the oncogenic pathways downstream from c-neu. The goal of this study was to examine the expression of prolyl isomerase Pin1 in human Her2+ breast cancer, and to study if Pin1 affects the expression of Her2/Neu itself. Methods Immunohistochemistry for Her2 and Pin1 were performed on two hundred twenty-three human breast cancers, with 59% of the specimen from primary cancers and 41% from metastatic sites. Pin1 inhibition was achieved using siRNA in Her2+ breast cancer cell lines, and its effects were studied using cell viability assays, immunoblotting and immunofluorescence. Results Sixty-four samples (28.7%) stained positive for Her2 (IHC 3+), and 54% (122/223) of all breast cancers stained positive for Pin1. Of the Her2-positive cancers 40 (62.5%) were also Pin1-positive, based on strong nuclear or nuclear and cytoplasmic staining. Inhibition of Pin1 via RNAi resulted in significant suppression of Her2-positive tumor cell growth in BT474, SKBR3 and AU565 cells. Pin1 inhibition greatly increased the sensitivity of Her2-positive breast cancer cells to the mTOR inhibitor Rapamycin, while it did not increase their sensitivity to Trastuzumab, suggesting that Pin1 might act on Her2 signaling. We found that Pin1 interacted with the protein complex that contains ubiquitinated erbB2 and that Pin1 inhibition accelerated erbB2 degradation, which could be prevented by treatments with the proteasome inhibitor ALLnL. Conclusion Pin1 is a novel regulator of erbB2 that modulates the ubiquitin-mediated degradation of erbB2. The overexpression of Pin1 in a majority of Her2-overexpressing breast cancer may contribute to maintain erbB2 levels. Pin1 inhibition alone and in conjunction with mTOR inhibition suppresses the growth of Her2+ breast cancer cells.

Abstract Background Stat3 has been classified as a proto-oncogene and constitutive Stat3 signaling appears to be involved in oncogenesis of human cancers. However, whether constitutive Stat3 signaling plays a role in the survival and growth of osteosarcomas, rhabdomyosarcomas, and soft-tissue sarcomas is still unclear. Methods To examine whether Stat3 is activated in osteosarcomas, rhabdomyosarcomas and other soft-tissue sarcomas we analyzed sarcoma tissue microarray slides and sarcoma cell lines using immunohistochemistry and Western blot analysis, respectively, with a phospho-specific Stat3 antibody. To examine whether the activated Stat3 pathway is important for sarcoma cell growth and survival, adenovirus-mediated expression of a dominant-negative Stat3 (Y705F) and a small molecule inhibitor (termed STA-21) were used to inhibit constitutive Stat3 signaling in human sarcoma cell lines expressing elevated levels of Stat3 phosphorylation. Cell viability was determined by MTT assays and induction of apoptosis was analyzed by western blotting using antibodies that specifically recognize cleaved caspases-3, 8, and 9. Results Stat3 phosphorylation is elevated in 19% (21/113) of osteosarcoma, 27% (17/64) of rhabdomyosarcoma, and 15% (22/151) of other soft-tissue sarcoma tissues as well as in sarcoma cell lines. Expression of the dominant-negative Stat3 and treatment of STA-21 inhibited cell viability and growth and induced apoptosis through caspases 3, 8 and 9 pathways in human sarcoma cell lines expressing elevated levels of phosphorylated Stat3. Conclusion This study demonstrates that Stat3 phosphorylation is elevated in human rhabdomyosarcoma, osteosarcomas and soft-tissue sarcomas. Furthermore, the activated Stat3 pathway is important for cell growth and survival of human sarcoma cells.

Cancer prognosis requires precision to identify high-risk patients and improve survival outcomes. Conventional methods struggle with the complexity of genetic biomarkers and diverse medical data. Our study uses deep learning to distil high-dimensional medical data into low-dimensional feature vectors exploring shared patterns across cancer types. We developed a multi-task bimodal neural network integrating RNA Sequencing and clinical data from three The Cancer Genome Atlas project datasets: Breast Invasive Carcinoma, Lung Adenocarcinoma, and Colon Adenocarcinoma. Our approach significantly improved prognosis prediction, especially for Colon Adenocarcinoma, with up to 26% increase in concordance index and 41% in the area under the precision-recall curve. External validation with Small Cell Lung Cancer achieved comparable metrics, indicating that supplementing small datasets with data from other cancers can improve performance. This work represents initial strides in using multi-task learning for prognosis prediction across cancer types, potentially revealing shared mechanisms among cancers and contributing to future applications in precision medicine., (© 2024. The Author(s).)

GeSn alloy has emerged as an attractive active material for Si-based mid-infrared (MIR) lasers due to its direct bandgap nature at higher Sn concentrations. Here, we report on an optically-pumped GeSn MIR lasers based on planar slab waveguide with a top Si ridge structure. The inclusion of 10% Sn transforms the GeSn active layer into a direct bandgap material. The Si ridge structure ensures appropriate optical confinements with reduced scattering loss from the waveguide sidewall. Lasing action was achieved under optical pumping with a low threshold of 60.85 kW/cm 2 and an emission wavelength of 2238 nm at T = 40 K. Lasing action was also observed up to T = 90 K with a threshold of 170 kW/cm 2 .

Background: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control., Methods: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment., Results: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group., Conclusions: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART., (© 2024. The Author(s).)

Bacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25 cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14 Streptococcus pneumoniae or 5 Streptococcus agalactiae serotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM + ) memory B cells and vaccine-inefficient S. pneumoniae serotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence of S. agalactiae invasive disease, compared to Dutch donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy., (© 2023. The Author(s).)

Background: We conducted a retrospective observational study to explore the potential application of impulse oscillometry (IOS) as an alternative to high-resolution computed tomography (HRCT) for detecting pulmonary involvement in patients with rheumatoid arthritis (RA) because clinically evident interstitial lung disease (ILD) and airway involvement are common in this population., Methods: We enrolled 72 patients with RA who underwent pulmonary function tests (PFTs) and IOS between September 2021 and September 2022. We aimed to identify the PFT and IOS variables associated with lung diseases shown on HRCT images., Results: In our cohort of 72 patients, 48 underwent HRCT; of these, 35 had airway disease or ILD and 13 showed no obvious abnormalities on HRCT. Abnormal IOS and PFT parameters were observed in 34 and 23 patients, respectively, with abnormal HRCT images. The predicted percentages for forced vital capacity, the ratio of forced expiratory volume in the first one second to forced vital capacity, and forced mid-expiratory flow value were significantly lower in patients with abnormal HRCT. Lung resistance at 5 Hz, difference in resistance between 5 and 20 Hz, resonant frequency (Fres), and reactance area were higher in these patients and reactance at 5 Hz was lower. Compared to other parameters, Fres > 14.14 was significantly associated with alterations in HRCT and may be used as an indicator for monitoring disease., Conclusion: Fres > 14.14 is significantly associated with lung involvement in RA patients. Performance of spirometry with IOS is more beneficial than spirometry alone for evaluating lung involvement in RA patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Marginal spectrum (MS) feature information of humpback whale vocalization (HWV) signals is an interesting and significant research topic. Empirical mode decomposition (EMD) is a powerful time-frequency analysis tool for marine mammal vocalizations. In this paper, new MS feature innovation information of HWV signals was extracted using the EMD analysis method. Thirty-six HWV samples with a time duration of 17.2 ms were classified into Classes I, II, and III, which consisted of 15, 5, and 16 samples, respectively. The following ratios were evaluated: the average energy ratios of the 1 first intrinsic mode function (IMF1) and residual function (RF) to the referred total energy for the Class I samples; the average energy ratios of the IMF1, 2nd IMF (IMF2), and RF to the referred total energy for the Class II samples; the average energy ratios of the IMF1, 6th IMF (IMF6), and RF to the referred total energy for the Class III samples. These average energy ratios were all more than 10%. The average energy ratios of IMF1 to the referred total energy were 9.825%, 13.790%, 4.938%, 3.977%, and 3.32% in the 2980-3725, 3725-4470, 4470-5215, 10,430-11,175, and 11,175-11,920 Hz bands, respectively, in the Class I samples; 14.675% and 4.910% in the 745-1490 and 1490-2235 Hz bands, respectively, in the Class II samples; 12.0640%, 6.8850%, and 4.1040% in the 2980-3725, 3725-4470, and 11,175-11,920 Hz bands, respectively, in the Class III samples. The results of this study provide a better understanding, high resolution, and new innovative views on the information obtained from the MS features of the HWV signals.

Erectile dysfunction is a common disease of the male reproductive system, which seriously affects the life quality of patients and their partners. At present, erectile dysfunction is considered as a social-psychological-physiological disease with complex etiology and various treatment methods. Oral PDE5I is the first-line treatment for erectile dysfunction with the advantages of high safety, good effect and non-invasiveness. But intracavernosal injection, hormonal replacement therapy, vacuum erection device, penile prosthesis implantation can also be alternative treatments for patients have organic erectile dysfunction or tolerance to PDE5I. With the rapid development of technologies, some new methods, such as low-intensity extracorporeal shock wave and stem cell injection therapy can even repair the organic damage of the corpora cavernosa. These are important directions for the treatment of male erectile dysfunction in the future. In this mini-review, we will introduce these therapies in detail., 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 © 2023 Wang, Wu, Xiang, Xiao and Hu.)

Patients with hematologic malignancies (HMs) have a significantly elevated risk of mortality compared to other cancer patients treated in the intensive care unit (ICU). The prognostic impact of numerous poor outcome indicators has changed, and research has yielded conflicting results. This study aims to determine the ICU and hospital outcomes and risk factors that predict the prognosis of critically ill patients with HMs. In this retrospective study, conducted at a referral hospital in Taiwan, 213 adult patients with HMs who were admitted to the medical ICU were evaluated. We collected clinical data upon hospital and ICU admission. Using a multivariate regression analysis, the predictors of ICU and hospital mortality were assessed. Then, a scoring system (Hospital outcome of critically ill patients with Hematological Malignancies (HHM)) was built to predict hospital outcomes. Most HMs (76.1%) were classified as high grade, and more than one-third of patients experienced a relapsed or refractory disease. The ICU and hospital mortality rates were 55.9% and 71.8%, respectively. Moreover, the disease severity was high (median Sequential Organ Failure Assessment (SOFA) score: 11 and Acute Physiology and Chronic Health Evaluation (APACHE II) score: 28). The multivariate analysis revealed that high-grade HMs, invasive mechanical ventilation requirement, renal replacement therapy initiation in the ICU, and a high SOFA score correlated with ICU mortality. Furthermore, a higher HHM score predicted hospital mortality. This study demonstrates that ICU mortality primarily correlates with the severity of organ dysfunction, whereas the disease status markedly influences hospital outcomes. Furthermore, the HHM score significantly predicts hospital mortality.

This real-world study evaluated the efficacy of once-daily long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) for improving lung function in patients with chronic obstructive pulmonary disease (COPD). Patients with COPD who were treated with once-daily LABA/LAMA FDCs for 12 months were included. We evaluated their lung function improvement after 12 months of treatment with different LABA/LAMA FDCs. A total of 198 patients with COPD who were treated with once-daily LABA/LAMA FDCs were analyzed. A total of 114 patients were treated with umeclidinium/vilanterol (UMEC/VIL); 34 patients were treated with indacaterol/glycopyrronium (IND/GLY); and 50 patients were treated with tiotropium/olodaterol (TIO/OLO). The forced expiratory volume in 1 s (FEV1) was significantly increased in the patients treated with all three once-daily FDCs (55.2% to 60.9%, p = 0.012 for UMEC/VIL, 58.2% to 63.6%, p = 0.023 for IND/GLY, and 54.1% to 57.7%, p = 0.009 for TIO/OLO). The treatment of COPD patients with TIO/OLO resulted in a significant improvement in both forced vital capacity (FVC%) (71.7% to 77.9%, p = 0.009) and residual volume (RV%) (180.1% to 152.5%, p < 0.01) compared with those treated with UMEC/VIL (FVC%: 75.1% to 81.5%, p < 0.001; RV%:173.8% to 165.2%, p = 0.231) or IND/GLY (FVC%: 73.9% to 79.3%, p = 0.08; RV%:176.8% to 168.3%, p = 0.589). Patients treated with UMEC/VIL or TIO/OLO showed significant improvement in FVC. In addition, those receiving TIO/OLO also showed significant improvement in RV reduction.

Element doping is a universal way to improve the electronic and optical properties of two-dimensional (2D) materials. Here, we investigate the influence of group-ⅣA element (C, Si, Ge, Sn, and Pb) doping on the electronic and optical properties of the ZnS monolayer with a tetragonal phase by using first-principles calculations. The results indicate that the doping atoms tend to form tetrahedral structures with neighboring S atoms. In these doped models, the formation energies are all negative, indicating that the formation processes of the doped models will release energy. The formation energy is smallest for C-doped ZnS and gradually increases with the metallicity of the doping element. The doped ZnS monolayer retains a direct band gap, with this band gap changing little in other element doping cases. Moreover, intermediate states are observed that are induced by the sp 3 hybridization from the doping atoms and S atoms. Such intermediate states expand the optical absorption range into the visible spectrum. Our findings provide an in-depth understanding of the electronic and optical properties of the ZnS monolayer and the associated doping structures, which is helpful for application in optoelectronic devices.

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38-0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia.

Background: Although lung protective strategy and adjunctive intervention are associated with improved survival in patients with acute respiratory distress syndrome (ARDS), the implementation of effective therapies remains low. This study aimed to evaluate whether the use of business intelligence (BI) for real-time data visualization is associated with an improvement in lung protective strategy and adjunctive therapy., Methods: A retrospective observational cohort study was conducted on patients with ARDS admitted between September 2020 and June 2021 at two intensive care units (ICUs) of a tertiary referral hospital in Taiwan. BI was imported for data visualization and integration to assist in clinical decision in one of the ICUs. The primary outcomes were the implementation of low tidal volume ventilation (defined as tidal volume/predicted body weight ≤ 8 mL/kg) within 24 h from ARDS onset. The secondary outcomes included ICU and hospital mortality rates., Results: Among the 1201 patients admitted to the ICUs during the study period, 148 (12.3%) fulfilled the ARDS criteria, with 86 patients in the BI-assisted group and 62 patients in the standard-of-care (SOC) group. Disease severity was similar between the two groups. The application of low tidal volume ventilation strategy was significantly improved in the BI-assisted group compared with that in the SOC group (79.1% vs. 61.3%, p = 0.018). Despite their ARDS and disease severity, the BI-assisted group tended to achieve low tidal volume ventilation. The ICU and hospital mortality were lower in the BI-assisted group., Conclusions: The use of real-time visualization system for data-driven decision support was associated with significantly improved compliance to low tidal volume ventilation strategy, which enhanced the outcomes of patients with ARDS in the ICU., (© 2022. The Author(s).)

Background: The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB., Methods: This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67)., Results: The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan-Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups., Conclusions: The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB., (© 2022. The Author(s).)

Modulation of the electronic and optical properties of two-dimensional (2D) materials is of great significance for their practical applications. Here, by using first-principles calculations, we study a tetragonal phase of monolayer ZnS, and explore its associated electronic and optical properties under biaxial strain. The results from phonon dispersion and molecular dynamics simulation demonstrate that the tetragonal phase of monolayer ZnS possesses a very high stability. The monolayer ZnS has a direct band gap of 4.20 eV. It changes to an indirect band gap under both compression and tension, exhibiting a decrease in band gap. However, the band gap decreases more slowly under compression compared to the tension process such that the direct band gap remains within -8%, demonstrating excellent endurance under pressure. Fortunately, tetragonal ZnS exhibits a good absorption ability in the ultraviolet (UV) range regardless of strain. Our research results enrich the understanding of monolayer ZnS, which is helpful for the design and application of optoelectronic devices using the material., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC ( n = 62) and CT ( n = 59) groups. After propensity score matching ( n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria ( p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.

Objective: To study the value of airway pH monitoring in determining the association between chronic cough and laryngopharyngeal reflux (LPR) in children., Methods: A total of 274 children with chronic cough who were treated from January 2016 to December 2019 were enrolled. The DX-pH detection system was used to conduct 24-hour airway pH monitoring. The association between chronic cough and LPR was analyzed., Results: Among the 274 children, there were 168 boys and 106 girls, with a median age of 62.8 months and a median airway pH value of 7.3. Of all the 274 children, 99 (36.1%) had LPR, and the incidence rate of LPR was 36.9% (62/168) in boys and 34.9% (37/106) in girls ( P =0.737). The comparison of the incidence rate of LPR among children aged < 1 year, 1-6 years, and > 6 years showed that the younger children had a significantly higher incidence rate of LPR than the older ones ( P =0.003). There was no significant difference in the incidence of LPR between the two groups with chronic cough of unknown etiology and definite etiology. The incidence of chronic cough was positively correlated with that of LPR ( r s =0.861, P < 0.01). Among the 99 children with positive RYAN index, 65 (66%) suffered from simple LPR., Conclusions: LPR is highly associated with the development of chronic cough, and airway pH monitoring may be a safe and effective method for the diagnosis of LPR.

Aberrant composition of glycans in the tumor microenvironment (TME) and abnormal expression of extracellular matrix proteins are hallmarks of hepatocellular carcinoma (HCC); however, the mechanisms responsible for establishing the TME remain unclear. We demonstrate that the chondroitin polymerizing factor (CHPF), an enzyme that mediates the elongation of chondroitin sulfate (CS), is a critical elicitor of the malignant characteristics of HCC as it modifies the potent tumor suppressor, decorin (DCN). CHPF expression is frequently downregulated in HCC tumors, which is associated with the poor overall survival of HCC patients. We observed that restoring CHPF expression suppressed HCC cell growth, migration, and invasion in vitro and in vivo. Mechanistic investigations revealed that TGF-β signaling is associated with CHPF-induced phenotype changes. We found that DCN, as a TGF-β regulator, is modified by CHPF, and that it affects the distribution of DCN on the surface of HCC cells. Importantly, our results confirm that CHPF and DCN expression levels are positively correlated in primary HCC tissues. Taken together, our results suggest that CHPF dysregulation contributes to the malignancy of HCC cells, and our study provides novel insights into the significance of CS, which affects DCN expression in the TME.

Electronic properties of monolayer tellurium (Te) with three proposed atomic configurations under external electric field were investigated through first-principles calculations. The calculated results demonstrate that α-Te and γ-Te have indirect band gaps, whereas β-Te, when no electric field is applied, can be considered as a direct semiconductor. An interesting structural change occurs in α- and γ-phase Te under a specific electric field strength, as does a change in structural chirality. In the presence of a perpendicular electric field, the band gaps can be modified and drawn close to 0 eV at a certain critical electric field strength. Before that, the band gaps of α-Te and γ-Te are nearly constant, while that of β-Te shows a quadratic relationship to electric field strength. These findings not only enrich our understanding of the electronic properties of monolayer tellurium but also show that monolayer tellurium has tremendous potential in nanoscale electronic devices owing to its tunable band gaps., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer was introduced in 2017 and included major revisions, especially of stage III. For the subgroup stage IIIA-N2 non-small-cell lung cancer (NSCLC), surgical resection remains controversial due to heterogeneous disease entity. The aim of this study was to evaluate the clinicopathologic features and prognostic factors of patients with completely resected stage IIIA-N2 NSCLC. We retrospectively evaluated 77 consecutive patients with pathologic stage IIIA-N2 NSCLC (AJCC eighth edition) who underwent surgical resection with curative intent in China Medical University Hospital between 2006 and 2014. Survival analysis was conducted, using the Kaplan-Meier method. Prognostic factors predicting overall survival (OS) and disease-free survival (DFS) were analyzed, using log-rank tests and multivariate Cox proportional hazards models. Of the 77 patients with pathologic stage IIIA-N2 NSCLC examined, 35 (45.5%) were diagnosed before surgery and 42 (54.5%) were diagnosed unexpectedly during surgery. The mean age of patients was 59 years, and the mean length of follow-up was 38.1 months. The overall one-, three-, and five-year OS rates were 91.9%, 61.3%, and 33.5%, respectively. Multivariate analysis showed that tumor size <3 cm (hazards ratio (HR): 0.373, p = 0.003) and video-assisted thoracoscopic surgery (VATS) approach (HR: 0.383, p = 0.014) were significant predictors for improved OS. For patients with surgically treated, pathologic stage IIIA-N2 NSCLC, tumor size <3 cm and the VATS approach seemed to be associated with better prognosis.

This paper presents a design for silicene quantum dots (SiQDs) embedded in silicane. The shape and size of an embedded SiQD are managed by hydrogen atoms. A first-principles method was used to evaluate the magnetism as well as the electronic and structural properties of embedded SiQDs of various shapes and sizes. The shape of the embedded SiQD determined its electronic structure as well as the dot size. Moreover, the magnetic properties of SiQDs in silicane were highly shape dependent. The triangular SiQDs were all magnetic, some small parallelogram SiQDs were nonmagnetic, and all others were antiferromagnetic; almost all hexagonal SiQDs were nonmagnetic. An unequal number of bare Si atoms at the A and B sites was identified as a critical factor for establishing magnetism in embedded SiQDs. The tip of a triangular SiQD enhanced the magnetic moment of the dot. The parallelogram SiQD with two tip atoms appeared as a magnetic needle and has potential for use in spintronic applications. SiQDs embedded in silicane can be used in the design of silicon-based nanoelectronic devices and binary logic based on nanoscale magnetism., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Hepatitis C virus (HCV) is one of very few viruses that are either naturally cleared, or alternatively persist to cause chronic disease. Viral diversity and escape, as well as host adaptive immune factors, are believed to control the outcome. To date, there is limited understanding of the critical, early host-pathogen interactions. The asymptomatic nature of early HCV infection generally prevents identification of the transmitted/founder (T/F) virus, and thus the study of host responses directed against the autologous T/F strain. In this study, 14 rare subjects identified from very early in infection (4-45 days) with varied disease outcomes (n = 7 clearers) were examined in regard to the timing, breadth, and magnitude of the neutralizing antibody (nAb) response, as well as evolution of the T/F strain. Clearance was associated with earlier onset and more potent nAb responses appearing at a mean of 71 days post-infection (DPI), but these responses were narrowly directed against the autologous T/F virus or closely related variants. In contrast, a delayed onset of nAbs (mean 425 DPI) was observed in chronic progressors that appear to have targeted longitudinal variants rather than the T/F strain. The nAb responses in the chronic progressors mapped to known CD81 binding epitopes, and were associated with rapid emergence of new viral variants with reduced CD81 binding. We propose that the prolonged period of viremia in the absence of nAbs in these subjects was associated with an increase in viral diversity, affording the virus greater options to escape nAb pressure once it emerged. These findings indicate that timing of the nAb response is essential for clearance. Further investigation of the specificities of the early nAbs and the factors regulating early induction of protective nAbs is needed.

Background: According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited., Methods: This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment ( vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year., Results: The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients' difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for <1 year due to successful step-down treatment according to Global Initiative for Asthma (GINA) score. All clinical characteristics of these two groups were collected and analyzed. Univariate and multivariate analyses showed that asthma-and-chronic obstructive pulmonary disease (COPD)-overlap (ACO), initial forced expiratory volume-one second (FEV1) % predicted <80%, or body mass index (BMI) >30 kg/m 2 were predictors for asthmatics requiring long-term tiotropium add-on therapy., Conclusions: Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted <80%, or BMI >30 kg/m 2 require long-term tiotropium add-on therapy for asthma control., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Background: Patients with advanced esophageal cancer and airway involvement have a poor prognosis. Self-expandable metallic stent (SEMS) implantation via bronchoscopy can immediately relieve airway stenosis and improve survival. The purpose of this study was to determine the factors that predict survival in patients with airway involvement due to advanced esophageal cancer after SEMS implantation., Methods: We conducted this retrospective study from February 2007 to October 2013 at a university hospital. Forty-two patients with advanced esophageal cancer and airway involvement were included. The patients underwent flexible bronchoscopy with electrosurgery and SEMS implantation under bronchoscopic visualization and local anesthesia with no fluoroscopic guidance throughout the procedure., Results: Acute respiratory failure (ARF) occurred in 14 patients (33.3%). After SEMS implantation, 28 patients (66.7%) received additional anti-cancer therapy. The median survival after the procedure was 83 days. A longer survival was seen in the patients who received further anti-cancer therapy [hazard ratio (HR), 0.146; 95% confidence interval (CI), 0.06-0.34; P<0.001]. Persistent pneumonia and poor performance status (PS) were potential factors for not receiving further therapy. The patients who received anti-cancer therapy before the procedure (HR, 3.429; 95% CI, 1.54-7.60; P=0.002) and those with ARF (HR, 5.224; 95% CI, 2.23-12.26; P<0.001) had worse survival., Conclusions: SEMS insertion with flexible bronchoscopy without fluoroscopic guidance in the patients with airway involvement due to advanced esophageal cancer was safe and feasible. The patients who received anti-cancer therapy before the procedure and those with ARF had a poor prognosis. Post-airway stenting therapy had the positive impact on survival in these patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

Background: Carbon monoxide (CO), a colorless and odorless gas, is one of the common causes of poisoning-related deaths worldwide. CO poisoning can result in hypoxic brain damage and death, but intensive care can improve the likely outcome for critically ill patients. However, there is a paucity of clinical data regarding the prognostic factors and association between organ dysfunction and clinical outcome of patients treated for CO poisoning in the intensive care unit (ICU)., Methods: We performed a retrospective study of patients admitted to a university affiliated hospital ICU between July 2001 and December 2010 following CO poisoning. Outcomes were survival to ICU discharge and to hospital discharge., Results: Seven hundred and eighty-seven patients were admitted to the university hospital following CO poisoning, of which 140 (17.8%) were admitted to the hospital ICU. The overall mortality rate of the patients admitted to the ICU was 14.3% (20/140). Univariate analysis indicated that non-surviving patients with CO poisoning were more likely to have initial blood carboxyhemoglobin (COHb) level > 30%, shock, acute respiratory failure, Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 25, Glasgow coma scale (GCS) score of 3, acute renal failure, dysfunction or failure of more than 3 organs, low blood pH, low HCO3- level, high potassium level, and high glucose level. They were also more likely to have not received hyperbaric oxygen (HBO) intervention. Multivariate logistical regression analysis indicated that the mortality rate of patients treated in the ICU for CO poisoning was higher if their initial APACHE II score was ≥25, GCS was 3, and more than 3 organs were dysfunctional. Moreover, HBO intervention in ICU significantly decreased patients' risk of mortality due to CO poisoning., Conclusion: In conclusion, we observed that APACHE II score >25, GCS 3, and dysfunction of more than 3 organ systems on admission to emergency department was associated with a significant mortality risk in patients treated in the ICU for CO poisoning. Moreover, HBO therapy could reduce the risk of mortality in patients with CO poisoning in ICU., (Copyright © 2018. Published by Elsevier B.V.)

Background: Long-acting muscarinic antagonist (LAMA) tiotropium improved lung function and reduced risks of exacerbation when added on to inhaled corticosteroids (ICS) with or without long-acting B 2 agonists (LABAs) in patients with uncontrolled asthma. However, studies predicting the effectiveness of tiotropium based on patients' clinical characteristics were limited., Methods: We conducted this retrospective study at a single medical center from July 2016 to July 2017, and used asthma control test (ACT) to evaluate the effectiveness of tiotropium add-on therapy in patients with uncontrolled asthma. The effectiveness was shown by an increase in ACT score from baseline of 3 or greater after 3 months of tiotropium add-on therapy., Results: Patients with uncontrolled asthma despite the use of low- or medium- to high-dose of ICS plus LABA (n=160) were analyzed. Among patients having good response (n=112, ACT score increased ≥3 points) to tiotropium (TGR group) and patients having poor response (n=48, ACT increased <3 points) to tiotropium (TPR group), their baseline characteristics including age, asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), cigarette use, initial FEV1, serum IgE level, eosinophil count, and BMI were significantly different. Univariate analysis showed that old age, ACO, cigarette use, initial FEV1 <80%, and BMI >30 were predictors of the effectiveness of tiotropium. Patients with high serum total IgE level >430 µg/L and eosinophil count >0.6×10 9 /L had a negative impact on response to tiotropium. Multivariate logistic regression analysis demonstrated that the independent factor of poor response to tiotropium was high serum IgE level >430 µg/L., Conclusions: Tiotropium add-on therapy in patients with uncontrolled asthma was effective. However, patients with serum total IgE level >430 µg/L were less likely to benefit from tiotropium., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Pleuroscopy, also known as medical thoracoscopy (MT), is an important tool for pleural disease management. Removal of foreign body (FB) by MT was reported in a few reports because it can identify the position of a FB in the pleural cavity and can be used for its urgent removal. In this study, we describe the case of a male patient with a ruptured lung abscess and a rare complication of self-expandable metallic stent (SEMS) migration into the pleural cavity via a bronchopleural fistula after the management of obstructive airway disease. An experienced pulmonologist successfully removed the SEMS from the pleural cavity using semi-rigid pleuroscopy under local anesthesia and conscious sedation in a bronchoscopy suite., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Purpose: Radiomics, which extract large amount of quantification image features from diagnostic medical images had been widely used for prognostication, treatment response prediction and cancer detection. The treatment options for lung nodules depend on their diagnosis, benign or malignant. Conventionally, lung nodule diagnosis is based on invasive biopsy. Recently, radiomics features, a non-invasive method based on clinical images, have shown high potential in lesion classification, treatment outcome prediction., Methods: Lung nodule classification using radiomics based on Computed Tomography (CT) image data was investigated and a 4-feature signature was introduced for lung nodule classification. Retrospectively, 72 patients with 75 pulmonary nodules were collected. Radiomics feature extraction was performed on non-enhanced CT images with contours which were delineated by an experienced radiation oncologist., Result: Among the 750 image features in each case, 76 features were found to have significant differences between benign and malignant lesions. A radiomics signature was composed of the best 4 features which included Laws&#95;LSL&#95;min, Laws&#95;SLL&#95;energy, Laws&#95;SSL&#95;skewness and Laws&#95;EEL&#95;uniformity. The accuracy using the signature in benign or malignant classification was 84% with the sensitivity of 92.85% and the specificity of 72.73%., Conclusion: The classification signature based on radiomics features demonstrated very good accuracy and high potential in clinical application.

Introduction: Patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR)-activating mutations have good response rate and longer progression-free survival (PFS) when treated with the tyrosine kinase inhibitors (TKI) compared with platinum-based chemotherapy. However, studies comparing the effectiveness of these drugs as first-line therapy in such patients are limited., Results: We analyzed 422 patients with EGFR-mutated advanced lung adenocarcinoma receiving first-line gefitinib ( n = 195, 46.2%), erlotinib ( n = 123, 29.1%), or afatinib ( n = 104, 24.6%). The PFS of the afatinib group was longer (12.2 months) than that of the gefitinib group (9.8 months) ( p = 0.035) but similar to that of the erlotinib group (11.4 months) ( p = 0.38). In patients without brain metastasis (BM), subgroup analysis showed that the afatinib group had significantly longer PFS (13.1 months) than erlotinib (11.7 months) and gefitinib (9.8 months) groups ( p = 0.010). Patients with exon 19 deletions in the afatinib and erlotinib groups had potentially long PFS ( p = 0.073). Efficacy of afatinib was similar between the 30 mg and 40 mg arms (median PFS 16.1 months vs. 10.3 months; p = 0.923)., Conclusions: Afatinib may be the optimal EGFR-TKI for advanced lung adenocarcinoma harboring EGFR-activating mutations, particularly in the absence of BM. Patients with exon 19 deletions taking afatinib had potentially long PFS. An afatinib dose of 30 and 40 mg has similar effect., Methods: We conducted this retrospective study at a single medical center from January 2013 to March 2017 and used PFS to evaluate the effectiveness of gefitinib, erlotinib, and afatinib in patients with advanced lung adenocarcinoma harboring EGFR mutations., Competing Interests: CONFLICTS OF INTEREST None.

Background: The aim of this study was thus to evaluate the feasibility and safety of taking biopsy specimens by cryoprobe from the parietal pleura during semirigid pleuroscope., Methods: In a single-center, observational, prospective study, patients with exudative pleural effusion (EPE) were evaluated with a semirigid pleuroscope between January 2015 and July 2017. Each patient underwent pleural biopsy using flexible forceps and flexible cryoprobe through pleuroscope following diagnostic thoracentesis and closed pleural biopsy (CPB)., Results: A total of 92 patients (median age 64 years) were included in the study, most of whom were men (65.2%). Cytological cell block (CCB) and CPB made definitive diagnoses in 32/92 (34.8%) and 25/92 (27.5%), respectively; flexible forceps biopsy (FFB) and cryoprobe biopsy (CB) established definitive diagnoses in 84/92 (91.3%) and 91/92 (98.9%), respectively. The sample obtained by CB (9.4 ± 4.9 mm) was significantly larger than the other two methods: FFB (4.2 ± 2.3 mm) or CPB (1.9 ± 1.0 mm) ( P < 0.0001). The immunohistochemical (IHC) staining was more easily performed with CB (98.9%) compared to either FFB (87.0%) or CPB (13.0%). There were no significant complications or procedure-related deaths., Conclusions: Based on these results, CB during semirigid pleuroscope has a high diagnostic yield, differentiating EPE of unknown etiology with satisfactory effectiveness and safety.

Background/purpose: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated., Methods: Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load ≥ 200 copies/mL within 96 weeks., Results: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure., Conclusion: Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring., (Copyright © 2016. Published by Elsevier B.V.)

Patients with central airway obstruction (CAO) may need endobronchial intervention to relieve their symptoms. This report is on a single-center experience of using interventional bronchoscopy in terms of complications and survival. This retrospective study was conducted in a university hospital and involved 614 patients (464 men, 150 women; mean age, 60.2 years) with benign (n = 133) and malignant (n = 481) tracheobronchial disease who received 756 endobronchial intervention procedure during the period 2008 to 2015. Survival was analyzed using the Kaplan-Meier method, while the log-rank test was used for comparisons. A total of 583 patients (95%) achieved endoscopic success after interventional bronchoscopy. Four (0.7%) died within 24 hours of the procedure, while the major morbidities were halitosis (n = 41, 6.7%) and iatrogenic pneumonia (n = 24, 3.9%). Repeat procedures due to recurrent airway obstruction were done on 45 patients with benign conditions and on 60 with malignancies. The median survival after the procedure in patients with lung cancer, other metastatic cancer, and esophageal cancer was 166, 228, and 86 days, respectively. Between patients with inoperable lung cancer and CAO after therapeutic bronchoscopy and patients without CAO, there was no statistically significant difference in survival (P = 0.101). Interventional bronchoscopy is a safe and effective procedure that may be recommended for CAO. Patients with lung metastases have similar lengths of survival as patients with primary lung cancer. Patients with advanced lung cancer and CAO have similar survival as those without CAO., Competing Interests: The authors have no funding and conflicts of interest to disclose.

No large-scale population-based cohort study has ever investigated the risk of developing chronic obstructive pulmonary disease (COPD) in patients with Sjögren syndrome (SS). This study evaluated the risk of COPD in women with primary SS (pSS) in a nationwide population.We used the data of the National Health Insurance Research Database of Taiwan to establish a pSS group consisting of 3013 female adults diagnosed between 2000 and 2005, and a non-SS group consisting of 12,052 women without SS matched by a propensity score. Incident COPD cases were identified to the end of 2011. The pSS group to non-SS group adjusted hazard ratios (aHRs) of COPD were estimated using multivariable Cox proportional hazards regression analysis.After a mean follow-up period of 7.99 years, the incidence of COPD was 1.4-fold greater in the pSS group than in the non-SS group (3.87 vs 2.77 per 1000 person-years) with an aHR of 1.39 (95% confidence interval [CI] = 1.10-1.75, P = 0.007). The COPD incidence was 7-fold greater for women aged 50 years and above than women aged 20 to 49, with the aHR of 4.24 (95% CI = 3.06-5.88, P < 0.001). Comorbidity increased the COPD risk further for women with pSS. Women with both pSS and comorbidity had an aHR of 3.11 (95% CI = 2.23-4.33, P < 0.001) for COPD, compared to those free of both pSS and comorbidity.Women with pSS are at a greater risk of developing COPD than those without SS. Patients with SS require close monitoring to prevent COPD development, particularly for those with comorbidity., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Rapid on-site evaluation (ROSE) of cytologic specimens is a useful ancillary technique in needle aspiration procedures of pulmonary/mediastinal lesions, but few reports had been carried out to confirm the utility in the diagnosis of peripheral pulmonary lesions (PPLs) by radial probe endobronchial ultrasound (R-EBUS)., Methods: To evaluate the impact of ROSE on the diagnostic yield of R-EBUS for PPLs, we retrospectively analyzed the diagnostic yields of transbronchial biopsy (TBB) or brushing using R-EBUS for patients with PPLs in a tertiary university hospital from December 2012 to December 2014., Results: A total of 815 patients with PPLs were included. A definite diagnosis was made by R-EBUS-guided TBB or brushing for 627 patients (76.9%). A total of 279 patients (34.2%) were examined by a ROSE technique. The combination of R-EBUS guided TBB or brushing with ROSE raised the diagnostic yield in the diagnosis of PPLs, especially difficult cases: right apical and left apical-posterior segment locations, small PPLs <3 cm without bronchus signs on computed tomography (CT) scan, PPLs with pleural effusions, and the position of probe is not within., Conclusions: ROSE can improve the PPLs diagnostic yield when using R-EBUS guided TBB or brushing.

Objectives: The role of advanced bronchoscopic diagnostic techniques in the detection and staging of lung cancer has increased sharply in recent years. The development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions (PLLs). We investigated the impact of using EBUS as a diagnostic method for tissue acquisition in lung cancer patients., Methods: In a single center observational retrospective study, 3712 subjects were diagnosed with lung cancer from 2003 to 2013 (EBUS was introduced in 2008). Thus, we divided the data into two periods: the conventional bronchoscopy period (2003 to 2007) and the EBUS period (2008 to 2013)., Results: A total of 3712 patients were included in the analysis. Comparing the conventional bronchoscopy period with the EBUS period data, there has been a significant reduction in the use of diagnostic modalities: CT-guided biopsy (P < 0.0001) and pleural effusion cytology (P < 0.0001). The proportion of subjects diagnosed using bronchoscopy significantly increased from 39.4% in the conventional period to 47.4% in the EBUS period (P < 0.0001). In the EBUS period, there has also been a significant increase in the proportion of patients proceeding directly to diagnostic surgery (P < 0.0001). Compared to bronchoscopy, the incidence of complications was higher in those who underwent CT guide biopsy. The incidence of iatrogenic pneumothorax significantly decreased in the EBUS period., Conclusions: Advanced bronchoscopic techniques are widely used in the diagnosis of lung cancer. At our institution, the increasing use of EBUS for providing lung cancer diagnosis has led to a significant reduction in other diagnostic modalities, namely CT-guided biopsy and pleural effusion cytology. These changes in practice also led to a reduction in the incidence of complications.

Hydrogen vacancies in graphane are products of incomplete hydrogenation of graphene. The missing H atoms can alter the electronic structure of graphane and therefore tune the electronic, magnetic, and optical properties of the composite. We systematically studied a variety of well-separated clusters of hydrogen vacancies in graphane, including the geometrical shapes of triangles, parallelograms, hexagons, and rectangles, by first-principles density functional calculation. The results indicate that energy levels caused by the missing H are generated in the broad band gap of pure graphane. All triangular clusters of H vacancies are magnetic, the larger the triangle the higher the magnetic moment. The defect levels introduced by the missing H in triangular and parallelogram clusters are spin-polarized and can find application in optical transition. Parallelograms and open-ended rectangles are antiferromagnetic and can be used for nanoscale registration of digital information.

Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/245 (40.0%)) (p = 0.01). In multivariate analysis, secondary syphilis (adjusted OR 6.79; 95% CI 1.97-23.28) and rapid plasma reagin (RPR) titres of ≥1: 32 (adjusted OR 2.23; 95% CI 1.02-4.89) were independently associated with the presence of treponemal DNA in patients without oral ulcers. We conclude that detection of treponemal DNA in the oral cavity with PCR assays is not uncommon in MSM, most of whom reported having unprotected oral sex. Although the presence of oral ulcers is significantly associated with detection of treponemal DNA, treponemal DNA is more likely to be identified in patients without oral ulcers who present with secondary syphilis and RPR titres of ≥1: 32., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Atrial fibrillation (AF), the most common sustained arrhythmia requiring treatment worldwide, is one of the major causes of ischemic stroke. Although amiodarone is commonly used for rhythm control in AF, its relationship with stroke has rarely been addressed.We evaluated 16,091 patients who were diagnosed with AF (Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] 427.31 and 427.32) between 1998 and 2011; the date of AF diagnosis was set as the index date. Patients with a history of stroke (ICD-9-CM 430-438) who received amiodarone before the index date or during the following 30 days, or who experienced stroke within 30 days of receiving amiodarone were excluded. Finally, 7548 patients with AF were included in this study and divided into 2 groups according to whether they received amiodarone (Anatomical Therapeutic Chemical code C01BD01) during the study period.The risk of ischemic stroke in AF patients receiving amiodarone was 1.81-fold (95% confidence interval [CI] 1.52-2.16), 1.79-fold (95% CI 1.50-2.14), and 1.78-fold (95% CI 1.49-2.13) higher than in those who did not receive amiodarone, according to crude, Model 1, and Model 2 Cox proportional hazard regression models, respectively. In a demographically stratified analysis, the risk of ischemic stroke was significantly higher in patients aged <65 years, with no comorbidities, who were also taking digoxin or had a low CHA2DS2VASc score.Amiodarone treatment is associated with an increased risk of stroke in patients with AF, especially in those who have an initial low risk of stroke. Antiplatelet drugs and warfarin could reduce the stroke risk in AF patients receiving amiodarone. However, as the combination of digoxin and amiodarone increases the risk of stroke in these patients, the combination of these 2 drugs should be avoided.

Background/purpose: Little is known about the factors associated with syphilis among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) with access to combination antiretroviral therapy (cART) in Taiwan, where MSM has re-emerged as the leading risk group for HIV transmission., Methods: From March to October 2011, MSM who regularly attended HIV clinics at a university hospital were invited to participate in the study. A structured questionnaire interview was conducted to collect information on sociodemographic characteristics, immunologic and virologic status, sexual partners and patterns of sexual behavior, and use of recreational drugs., Results: During the study period, 310 HIV-infected MSM with a mean age of 35.5 years were enrolled, of which 82.3% (n = 255) were sexually active and 37.4% (n = 116) used recreational drugs in the past 6 months. Syphilis was self-reported in 46.5% (n = 144) of the participants after HIV infection was diagnosed and 37.5% (112/299) had serologic evidence of syphilis within 1 year before enrollment. Multivariate logistic regression analysis limited to those who were receiving cART showed that higher CD4 counts [adjusted odds ratio (AOR): 1.17; 95% confidence interval (CI): 1.02-1.34], lower educational achievement (AOR: 1.95; 95% CI: 1.05-3.63), serosorting (AOR: 3.32; 95% CI: 1.04-10.63), and use of recreational drugs (AOR: 2.55; 95% CI: 1.26-5.13) were associated with syphilis., Conclusion: Improved immune status, lower educational achievement, serosorting, and use of recreational drugs were associated with syphilis among HIV-infected MSM who were receiving cART. These findings suggest that strengthening client-specific counseling is needed to reduce risks for syphilis among HIV-infected MSM in Taiwan., (Copyright © 2013. Published by Elsevier B.V.)

Introduction: Wide inter-patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV-positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV-containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)-guided strategy to optimize the EFV dose in HIV-positive Taiwanese patients., Materials and Methods: The plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV-positive adults who had received EFV-containing cART with viral suppression (plasma HIV RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4-12 weeks after switch using high-performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase-chain-reaction restriction fragment-length polymorphism., Results: Between April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4% HBsAg-positive and 7.5% anti-HCV-positive) with plasma C12 efavirenz >2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62-4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53-2.33) for 64 patients who had completed follow-up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9-57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow-up of PVL achieved undetectable PVL (<40 copies/ml) following switch to a reduced dose of EFV after a mean observation of 13 weeks (IQR, 7-15 weeks)., Conclusions: Switch to cART containing a half tablet of EFV (1/2#) in HIV-positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful viral suppression with the guidance of TDM.

Background and Aim: The purpose of this study was to assess the relationship of pleural adenosine deaminase (P-ADA) and non-Hodgkin's lymphoma (NHL)., Design and Methods: We retrospectively analysed 63 NHL patients with pleural effusions who accepted a diagnostic thoracentesis and who had P-ADA available at the China Medical University Hospital (Taichung, Taiwan) between January 2003 and April 2012., Results: There were 46 exudates [40 malignant pleural effusions (MPE), 5 complicated para-pneumonic effusions and 1 undiagnosed effusion] and 17 transudates. The P-ADA activity was significantly different between the two groups (P < 0.005). Among 40 MPE cases, 29 were due to B-cell and 11 due to T-cell NHL. There was no pleural transudative effusion with P-ADA value higher than 26 U/l in our study, but simultaneously 48% (22/46) of exudative pleural effusions showed a P-ADA value under that cut-off point. The P-ADA level reached the diagnostic cut-off for tuberculosis (40 IU/l) in 11 cases of MPE (11/40 = 27.5%): 9 B-cell NHL (9/29 = 31%) and 2 T-cell NHL (2/11 = 18%). The median levels (25th, 75th percentiles) of P-ADA were 28 IU/l (14-50) in the MPE of B-cell NHL and 26 IU/l (14-28) in the T-cell NHL (P = 0.693)., Conclusions: The use of P-ADA in NHL effusion could aid the separation of transudates from exudates. Around one-quarter MPE of NHL had abnormal P-ADA ( > 40 IU/l). There was no difference in the P-ADA activity in T-cell and B-cell NHL., (© Crown copyright 2014.)

Resistance mutations A2058G and A2059G, within the 23S rRNA gene of Treponema pallidum, have been reported to cause treatment failures in patients receiving azithromycin for syphilis. Genotyping of T. pallidum strains sequentially isolated from patients with recurrent syphilis is rarely performed. From September 2009 to August 2013, we collected 658 clinical specimens from 375 patients who presented with syphilis for genotyping to examine the number of 60-bp repeats in the acidic repeat protein (arp) gene, T. pallidum repeat (tpr) polymorphism, and tp0548 gene, and to detect A2058G and A2059G point mutations by restriction fragment length polymorphism. Treponemal DNA was identified in 45.2% (n = 298) of the specimens that were collected from 216 (57.6%) patients; 268 (40.7%) specimens tested positive for the 23S rRNA gene, and were examined for macrolide resistance. Two isolates (0.7%) harboured the A2058G mutation, and no A2059G mutation was identified. A total of 14 strains of T. pallidum were identified, with 14f/f (57.5%) and 14b/c (10.0%) being the two predominant strains. Forty patients who presented with recurrent episodes of syphilis had T. pallidum DNA identified from the initial and subsequent episodes, with five cases showing strain discrepancies. One patient had two strains identified from different clinical specimens collected in the same episode. Our findings show that 14f/f is the most common T. pallidum strain in Taiwan, where the prevalence of T. pallidum strains that show A2058G or A2059G mutation remains low. Different genotypes of T. pallidum can be identified in patients with recurrent episodes of syphilis., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Between 2009 and 2013, polymerase-chain-reaction assay was used to detect Treponema pallidum in the blood samples collected from 296 patients with early syphilis (241 being HIV infected) and 102 patients (34.5%) had spirochetemia. The presence of spirochetemia was associated with lower CD4 counts (per 10-cell/mm(3) decrease, adjusted odds ratio (AOR), 1.020; 95% CI, 1.006-1.036) and secondary syphilis (AOR, 4.967; 95% CI, 2.016-12.238). Patients with early latent syphilis were less likely to achieve serological response compared with those with primary or secondary syphilis (AOR, 0.317; 95% CI, 0.142-0.708). However, serological response was not affected by presence of spirochetemia or antibiotic regimens., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: Plasma efavirenz concentrations in HIV-infected patients with tuberculosis (TB) may be affected by cytochrome P450 (CYP) 2B6 single-nucleotide polymorphisms and concurrent rifampicin use. We aimed to investigate the effects of CYP2B6 G516T polymorphisms and concomitant rifampicin use on the plasma efavirenz concentrations in HIV-infected Taiwanese., Methods: HIV-infected patients with or without TB who had received combination antiretroviral therapy containing efavirenz (600 mg daily) for two weeks or greater were enrolled for determinations of CYP2B6 G516T polymorphism and plasma efavirenz concentrations with the use of polymerase-chain-reaction restriction fragment-length polymorphism and high-performance liquid chromatography, respectively., Results: From October 2009 to August 2012, 171 HIV-infected patients, including 18 with TB, were enrolled 113 (66.1%) with CYP2B6 G516G, 55 (32.2%) GT, and 3 (1.8%) TT genotype. Patients receiving rifampicin had a significantly lower median plasma efavirenz concentration than the control group (2.16 vs 2.92 mg/L, P = 0.003); however, all patients achieved target plasma concentration (>1 mg/L). Patients with GT or TT genotype had a significantly higher plasma concentration than those with GG genotype (2.50 vs 3.47 mg/L for GT genotype and 8.78 mg/L for TT genotype, P<0.001). Plasma efavirenz concentration >4 mg/L was noted in 38 (22.2%) patients, which was associated with a lower weight (per 10-kg increase, odds ratio, 0.52; 95% confidence interval, 0.33-0.83) and GT or TT genotype (odds ratio, 4.35; 95% confidence interval, 1.97-9.59) in multivariate analysis., Conclusions: Despite combination with rifampicin, sufficient plasma efavirenz concentrations can be achieved in HIV-infected Taiwanese with TB who receive efavirenz 600 mg daily. Carriage of CYP2B6 516 GT and TT genotypes and a lower weight are associated with higher plasma efavirenz concentrations.