Ultrasensitive Strain Sensor Utilizing a AgF-AgNW Hybrid Nanocomposite for Breath Monitoring and Pulmonary Function Analysis.

Breath monitoring and pulmonary function analysis have been the prime focus of wearable smart sensors owing to the COVID-19 outbreak. Currently used lung function meters in hospitals are prone to spread the virus and can result in the transmission of the disease. Herein, we have reported the first-ever wearable patch-type strain sensor for enabling real-time lung function measurements (such as forced volume capacity (FVC) and forced expiratory volume (FEV) along with breath monitoring), which can avoid the spread of the virus. The noninvasive and highly sensitive strain sensor utilizes the synergistic effect of two-dimensional (2D) silver flakes (AgFs) and one-dimensional (1D) silver nanowires (AgNWs), where AgFs create multiple electron transmission paths and AgNWs generate percolation networks in the nanocomposite. The nanocomposite-based strain sensor possesses a high optimized conductivity of 7721 Sm-1 (and a maximum conductivity of 83,836 Sm-1), excellent stretchability (>1000%), and ultrasensitivity (GFs of 35 and 87 when stretched 0-20 and 20-50%, respectively), thus enabling reliable detection of small strains produced by the body during breathing and other motions. The sensor patching site was optimized to accurately discriminate between normal breathing, quick breathing, and deep breathing and analyze numerous pulmonary functions, including the respiratory rate, peak flow, FVC, and FEV. Finally, the observed measurements for different pulmonary functions were compared with a commercial peak flow meter and a spirometer, and a high correlation was observed, which highlights the practical feasibility of continuous respiratory monitoring and pulmonary function analysis.

Establishing Quality of Life in Southern Taiwan COPD Patients Using Long-Acting Bronchodilator.

Background: To assess the health-related quality of life (HRQoL) of Taiwan patients with different stages of chronic obstructive pulmonary disease (COPD) and using different combination therapies and to explore the factors affecting HRQoL in these patients. Methods: This cross-sectional study included outpatient participants aged 35 years old and older who were receiving long-acting bronchodilator treatment in one of two hospitals in Southern Taiwan. Participants were categorized according to their Global Initiative for Obstructive Lung Disease (GOLD) classification as either their COPD group, based on symptoms and exacerbation risk, or their COPD stage, based on spirometry results. Patients' HRQoL was assessed using the St. George's Respiratory Questionnaire score (SGRQ), World Health Organization Quality of Life Quality of Life-BREF (WHOQOL-BREF), and EQ-5D-5L. The total scores of the SGRQ, WHOQOL-BREF, EQ-5D utility index, and EQ-VAS were presented as mean ± standard deviation (SD) among different combination treatments. Univariate and multivariate analyses were used to explore the association of patients' baseline characteristics and environmental factors with HRQoL. Results: A total of 218 patients were enrolled in the study. The distribution of patients using GOLD group classification were as follows: 73.39% in group A, 20.19% group B, 1.83% group C and 4.59% group D. Triple therapy patients mostly showed a lower quality of life than other combination therapies, regardless of the GOLD classification system. However, only the SGRQ scores of GOLD groups A and B were significantly different when using different drug combinations (p-value = 0.0072 and 0.0430, respectively). The COPD assessment test (CAT) score, a questionnaire to assess impact of COPD on health status, was found to be associated with all the questionnaires. Conclusion: The HRQoL is impaired in patients with COPD, and it deteriorates with an increase of severity. The CAT was the strongest predictor of HRQoL.

Establishing Aspergillus-Specific IgG Cut-Off Level for Chronic Pulmonary Aspergillosis Diagnosis: Multicenter Prospective Cohort Study.

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).

Remdesivir use in the coronavirus disease 2019 pandemic: A mini-review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative viral pathogen of coronavirus disease 2019 (COVID-19), appears to have various clinical presentations and may result in severe respiratory failure. The global SARS-CoV-2-associated viral pneumonia pandemic was first reported in December 2019 in China. Based on known pharmacological mechanisms, many therapeutic drugs have been repurposed to target SARS-CoV-2. Among these drugs, remdesivir appears to be the currently most promising according to several clinical trials and reports of compassionate use. In this mini-review, we summarize the current evidence on the efficacy and challenges of remdesivir for the treatment of coronavirus disease 2019 (COVID-19).

Pin1 coordinates HDAC6 upregulation with cell migration in lung cancer cells.

Histone deacetylase 6 (HDAC6) controls many cellular processes via its catalyzing deacetylation of downstream substrates or interacting with its partner proteins. Dysregulation of HDAC6 signaling links to many diseases. Our previous study has been reported peptidyl-prolyl cis/trans isomerase, and NIMA-interacting 1 (Pin1) involving in HDAC6-mediated cell motility. To gain insight into precisely coordination of HDAC6 and Pin1 in cell migration, shRNA-mediated gene silencing and ectopic expression were applied to manipulate protein expression level to evaluate relationship between HDAC6 and Pin1 expression. Quantitative RT-PCR and the cycloheximide (CHX) chase assay resulted in HDAC6 expression is correlated with Pin1 level in H1299 cells. It hints that the Pin1 increases HDAC6 expression through increased transcripts and posttranslational stabilization. Furthermore, wound healing assay and transwell invasion assay evidenced the contribution of Pin1 on cell motility in H1299 cells. Our data suggest that Pin1 acts as an important regulator to manage HDAC6 expression for cell motility in lung cancer cells.

The extracts of Astragalus membranaceus overcome tumor immune tolerance by inhibition of tumor programmed cell death protein ligand-1 expression.

A polysaccharide isolated from the radix of Astragalus membranaceus, called PG2, used in traditional Chinese medicine, with potential hematopoiesis inducing and immunomodulation activities. PG2 extracted from A. membranaceus has been demonstrated as a novel alternative medicine for cancer patients. Recently, we demonstrated that PG2 enhanced chemotherapy through bystander effect and reduced the expression of indoleamine 2, 3-dioxygenase 1 in tumor cells. Many tumors have been proven to have a high expression of programmed cell death protein ligand-1 (PD-L1), which binds with programmed cell death protein-1(PD-1) in immune cells, thus causing immune tolerance within the tumor microenvironment. With decreased expression of PD-L1, increased immune response can be observed, which might be helpful when developing tumor immunotherapy. The antitumor therapeutic effect mediated by PG2 may associate with an inflammatory immune response at the tumor site. However, the molecular mechanism that by which PG2 inhibits PD-L1 is still incompletely known. The expression of PD-L1 was decreased after tumor cells were treated with PG2. In addition, the cell signaling pathway in tumor cells was evaluated by Western blotting analysis after PG2 treatment. PG2 can downregulate the expression of PD-L1 on the cell surface via the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase beta-1 (p70S6K) pathway. In conclusion, our results indicate that PG2 inhibits PD-L1 expression and plays a crucial role in immunotherapy, which might be a promising strategy combined with other treatments.

Female Asthmatic Patients Have Higher Risk to Develop Gemifloxacin-Associated Skin Rash, Highlighting Unique Delayed Onset Characteristics.

Gemifloxacin is a common oral antibiotic for lower respiratory tract infection worldwide. We noticed an uncommon delayed onset skin rash in patients who received Gemifloxacin. Therefore, we retrospectively reviewed all patients who received Gemifloxacin from 1 January 2011 to 31 May 2016 in a university-affiliated hospital in Taiwan. A total of 1358 patients were enrolled, of whom 36 (2.65%) had skin eruptions. The female patients had a significantly higher odds ratio (OR) 2.24 (95% confidence interval (CI) 1.11-4.53, p = 0.021) of having skin eruptions. A history of asthma was also a significant risk factor (OR 2.04, 95% CI = 1.01-4.14, p = 0.043). Female asthmatic patients had the highest risk of skin eruptions (10/129, 7.2%) with an adjusted OR up to 4.45 (95% CI = 1.81-10.93, p < 0.001) compared to male and non-asthmatic patients. Of note, up to 58.3% (21/36) of the patients experienced a skin rash after they had completed and stopped Gemifloxacin. The median onset time was on the second day (ranging one to five days) after completing treatment. We reported that female asthmatic patients have the highest risk of Gemifloxacin-associated skin eruptions in Asia and that they highlighted a unique delayed onset skin rash.

Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung.

PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. RESULTS: Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. CONCLUSIONS: Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Acute respiratory distress syndrome and acute myocarditis developed in a previously healthy adult with influenza B.

BACKGROUND: Influenza B virus infection is generally considered to be mild and is rarely associated pulmonary cardiovascular involvement in adults. However fatal complications may occur. CASE PRESENTATION: A 43-year-old previously healthy Taiwanese male came to our emergency department due to high fever, chills, general malaise and myalgia for about 4 days. An influenza rapid test from a throat swab was negative. Chest radiography showed mild left lung infiltration and levofloxacin was prescribed. However, progressive shortness of breath and respiratory failure developed 48 h later after hospitalization. Emergent intubation was performed and he was transferred to the intensive care unit where oseltamivir (Tamiflu, Roche) 75 mg orally twice daily was given immediately. In the intensive care unit, cardiac catheterization revealed normal coronary arteries. However, a markedly elevated cardiac enzyme level (Troponin I level was up to 71.01 ng/ml), a positive cardiac magnetic resonance imaging findings and no coronary artery stenosis led to the diagnosis of acute myocarditis. Subsequent real-time polymerase chain reaction of endotracheal aspirates was positive for influenza B. His condition gradually improved and he was successfully weaned from the ventilator on day 22. He was discharged without prominent complications on day 35. CONCLUSION: Influenza B infection is not always a mild disease. Early detection, early administration of antiviral agents, appropriate antibiotics and best supportive care, is still the gold standard for patients such as the one reported.

Port type is a possible risk factor for implantable venous access port-related bloodstream infections and no sign of local infection predicts the growth of gram-negative bacilli.

BACKGROUND: Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial. METHODS: We retrospectively reviewed all patients who received IVAPs at a Hospital in Taiwan from January 1, 2011 to June 31, 2014. Two types of venous port, BardPort® 6.6 fr (Bard port) and Autosuture Chemosite® 7.5 fr (TYCO port) were used. All patients with clinically proven venous port-related BSIs were enrolled. RESULTS: A total of 552 patients were enrolled. There were 34 episodes of IVAP-related BSIs during the study period for a total incidence of 0.177 events/1000 catheter days. Port type (TYCO vs. Bard, HR = 7.105 (95% confidence interval (CI), 1.688-29.904), p = 0.0075), age > 65 years (HR = 2.320 (95 % CI, 1.179-4.564), p = 0.0148), and lung cancer (HR = 5.807 (95% CI, 2.946-11.447), p < 0.001) were risk factors for port infections. We also found that no local sign of infection was significantly associated with the growth of gram-negative bacilli (p = 0.031). CONCLUSIONS: TYCO venous ports, age > 65 years, and lung cancer were all significant risk factors for IVAP-related BSIs, and no sign of infection was significantly associated with the growth of gram-negative bacilli.

Risk factors for venous port migration in a single institute in Taiwan.

BACKGROUND: An implantable port device provides an easily accessible central route for long-term chemotherapy. Venous catheter migration is one of the rare complications of venous port implantation. It can lead to side effects such as pain in the neck, shoulder, or ear, venous thrombosis, and even life-threatening neurologic problems. To date, there are few published studies that discuss such complications. METHODS: This retrospective study of venous port implantation in a single center, a Taiwan hospital, was conducted from January 2011 to March 2013. Venous port migration was recorded along with demographic and characteristics of the patients. RESULTS: Of 298 patients with an implantable import device, venous port migration had occurred in seven, an incidence rate of 2.3%. All seven were male and had received the Bard port Fr 6.6 which had smaller size than TYCO port Fr 7.5 and is made of silicon. Significantly, migration occurred in male patients (P = 0.0006) and in those with lung cancer (P = 0.004). Multivariable logistic regression analysis revealed that lung cancer was a significant risk factor for port migration (odds ratio: 11.59; P = 0.0059). The migration rate of the Bard port Fr 6.6 was 6.7%. The median time between initial venous port implantation and port migration was 35.4 days (range, 7 to 135 days) and 71.4% (5/7) of patients had port migration within 30 days after initial port implantation. CONCLUSIONS: Male sex and lung cancer are risk factors for venous port migration. The type of venous port is also an important risk factor.

The effect of chemotherapy with cisplatin and pemetrexed for choroidal metastasis of non-squamous cell carcinoma.

PURPOSE: Choroidal metastasis from lung cancer is very rare in the clinical setting. Treatment for lung cancer with symptomatic choroidal metastasis remains uncertain because of the rarity of such cases. METHODS: We performed a retrospective study on symptomatic choroidal metastasis from lung cancer at the Kaohsiung Medical University Hospital from January 2010 to August 2011. In addition, we also performed literature review of all such patients (or of cancers with choroidal metastasis) treated with systemic chemotherapy. RESULTS: In our study, a total of 226 lung cancer patients were registered during the study period, and only four had choroidal metastasis (4/226, 1.77 %). Three were female (75 %) and one was male, with a mean age of 40.74 (range 26-60) years. Three patients had marked choroidal tumor regression after treatment with pemetrexed and cisplatin. In the literature reviews, there are only 12 patients (including our patients) received systemic chemotherapy alone instead of local therapy and eight (66.7 %) demonstrated choroidal tumor regression after treatment. CONCLUSIONS: Symptomatic choroidal metastasis from lung cancer is extremely rare. Our findings indicate that systemic chemotherapy with pemetrexed and cisplatin may be a good option for such patients. Further large-scale studies for the treatment of such patients are warranted. However, currently, radiotherapy is still the gold standard for such patients.

The impact of inappropriate antibiotics on bacteremia patients in a community hospital in Taiwan: an emphasis on the impact of referral information for cases from a hospital affiliated nursing home.

BACKGROUND: Evidence for the impact of inappropriate antimicrobial therapy on bacteremia is mainly from studies in medical centers. We investigated the impact of inappropriate antimicrobial therapy on bacteremia in a community hospital. In particular, patients from the hospital's affiliated nursing home were sent to the hospital with adequate referral information. METHODS: We performed a retrospective study to collect data of patients with bacteremia in a community hospital in Taiwan from 2005 to 2007. RESULTS: A total of 222 patients with blood stream infection were diagnosed, of whom 104 patients (46.8%) died. The rate of initial inappropriate antibiotic prescriptions was high (59%). Multivariate analysis revealed that patients with initial inappropriate antibiotics, patients with ventilator support and patients requiring ICU care were the independent predictors for inhospital mortality. Patients referred from the hospital-affiliated nursing home and patients with normal WBC counts had better survival outcome. More than 80% cases infected with methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis received initial inappropriate antimicrobial therapy. With the longer delay to administer appropriate antibiotic, a trend of higher mortality rates was observed. CONCLUSIONS: Bacteremia patients from a hospital-affiliated nursing home had a better prognosis, which may have been due to the adequate referral information. Clinicians should be aware of the commonly ignored drug resistant pathogens, and efforts should be made to avoid delaying the administration of appropriate antibiotic therapy.