Epidemiology and outcomes of multidrug-resistant bacterial infection in non-cystic fibrosis bronchiectasis.

PURPOSE: Multidrug-resistant (MDR) bacteria impose a considerable health-care burden and are associated with bronchiectasis exacerbation. This study investigated the clinical outcomes of adult patients with bronchiectasis following MDR bacterial infection. METHODS: From the Chang Gung Research Database, we identified patients with bronchiectasis and MDR bacterial infection from 2008 to 2017. The control group comprised patients with bronchiectasis who did not have MDR bacterial infection and were propensity-score matched at a 1:2 ratio. The main outcomes were in-hospital and 3-year mortality. RESULTS: In total, 554 patients with both bronchiectasis and MDR bacterial infection were identified. The types of MDR bacteria that most commonly affected the patients were MDR- Acinetobacter baumannii (38.6%) and methicillin-resistant Staphylococcus aureus (18.4%), Extended-spectrum-beta-lactamases (ESBL)- Klebsiella pneumoniae (17.8%), MDR-Pseudomonas (14.8%), and ESBL-E. coli (7.5%). Compared with the control group, the MDR group exhibited lower body mass index scores, higher rate of chronic bacterial colonization, a higher rate of previous exacerbations, and an increased use of antibiotics. Furthermore, the MDR group exhibited a higher rate of respiratory failure during hospitalization (MDR vs. control, 41.3% vs. 12.4%; p < 0.001). The MDR and control groups exhibited in-hospital mortality rates of 26.7% and 7.6%, respectively (p < 0.001); 3-year respiratory failure rates of 33.5% and 13.5%, respectively (p < 0.001); and 3-year mortality rates of 73.3% and 41.5%, respectively (p < 0.001). After adjustments were made for confounding factors, the infection with MDR and MDR bacteria species were determined to be independent risk factors affecting in-hospital and 3-year mortality. CONCLUSIONS: MDR bacteria were discovered in patients with more severe bronchiectasis and were independently associated with an increased risk of in-hospital and 3-year mortality. Given our findings, we recommend that clinicians identify patients at risk of MDR bacterial infection and follow the principle of antimicrobial stewardship to prevent the emergence of resistant bacteria among patients with bronchiectasis.

Afatinib treatment in a large real-world cohort of nonsmall cell lung cancer patients with common and uncommon epidermal growth factor receptor mutation.

The epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) afatinib improves survival in nonsmall cell lung cancer (NSCLC) patients with EGFR mutation. We analysed the outcome between EGFR mutation subtypes in a large afatinib-treated cohort in which 516 EGFR-mutated NSCLC patients receiving afatinib as front-line treatment. EGFR uncommon mutations include exon 20 insertion, de novo T790M of high or low allele frequency (dT790MHAF /dT790MLAF ), non-T790M compound mutation and others, where EGFR exon 20 insertion and dT790MHAF were defined as type-I and the rest as type-II uncommon mutation. Four hundred and sixty-one (89.3%) and 55 (10.7%) patients were common and uncommon mutation, respectively. Exon 20 insertion and dT790MHAF patients demonstrated a significantly shortened progression-free survival (PFS) (2.6 and 4.1 months) compared to EGFR common mutation, dT790MLAF and other uncommon mutation patients (15.1, 27.0 and 18.4 months; P = 3 × 10-8 ). Type-I uncommon mutation was an independent predictor of PFS (HR 4.46 [95% CI, 2.60-7.64]; P < .001) and OS (HR 2.56 [95% CI, 1.37-4.75]; P = .003). EGFR L858R patients demonstrated a significantly higher CNS progression (cause-specific HR, 3.16; 95% CI 1.24-8.08; P = .016), and type-I uncommon mutation patients exhibited a significantly higher systemic progression (cause-specific HR, 4.95; 95% CI 2.30-10.60; P = 4.3 × 10-5 ). Tendencies of higher CNS and lower systemic progression were observed in type-II uncommon mutation patients. A PFS ≥ 12 months (OR 2.38 [95% CI, 1.18-4.89]; P = .016) and uncommon EGFR mutation (OR 0.08 [95% CI, 0.01-0.48]; P = .021) were independent predictors of secondary T790M. Afatinib-treated NSCLC patients presented an EGFR genotype-specific pattern of disease progression and outcome.

Comparison of Clinical Characteristics and Outcomes of Hospitalized Patients Infected with the D614G Strain or Alpha Variant of COVID-19 in Taiwan: A Multi-Center Cohort Study.

Objective: Direct comparison of the clinical traits of coronavirus disease 2019 (COVID-19) in strain D614G, which originated from Wuhan, China, and the Alpha variant, which contains 17 mutations, infected patients could help physicians distinguish between strains and make clinical decisions accordingly. This study sought to compare the clinical characteristics and outcomes of the D614G strain and Alpha variant of SARS-COV-2 and identify the predictors for viral RNA clearance and in-hospital mortality in patients with COVID-19. Methods: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were determined. Results: Among the 239 enrolled patients, 11.2% (27/239) were infected with strain D614G and 88.7% (212/239) were infected with the Alpha variant. There were no significant differences in disease progression, rate of respiratory failure, subsequent development of acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, duration of stay in the intensive care unit or hospital, discharge rate, mortality rate, or viral RNA clearance time between the two groups. Multivariate Cox regression revealed that antibiotic therapy reduced the risk of delayed viral RNA clearance (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.13-0.55), while autoimmune disease increased the risk of delayed viral RNA clearance (HR, 3.98; 95% CI, 1.21-13.04). Elderly patients (age > 65 years) and patients with a history of cerebrovascular accident (CVA) were at increased risk of in-hospital mortality (HR, 5.14; 95% CI, 1.06-24.72 and HR, 3.62; 95% CI, 1.25-10.42, respectively). Conclusions: There were no significant differences between the D614G strain and Alpha variant of COVID-19 in terms of clinical characteristics and outcomes. However, factors affecting viral RNA clearance and the risk of in-hospital mortality were identified. These results could help to inform the future prioritization of resource allocation and identify patients in need of intense monitoring.

The Clinical Experience of Mycobacterial Culture Yield of Pleural Tissue by Pleuroscopic Pleural Biopsy among Tuberculous Pleurisy Patients.

Background and Objectives: Tuberculous pleurisy is a common extrapulmonary TB that poses a health threat. However, diagnosis of TB pleurisy is challenging because of the low positivity rate of pleural effusion mycobacterial culture and difficulty in retrieval of optimal pleural tissue. This study aimed to investigate the efficacy of mycobacterial culture from pleural tissue, obtained by forceps biopsy through medical pleuroscopy, in the diagnosis of TB pleurisy. Materials and Methods: This study retrospectively enrolled 68 TB pleurisy patients. Among them, 46 patients received semi-rigid pleuroscopy from April 2016 to March 2021 in a tertiary hospital. We analyzed the mycobacterial culture from pleural tissue obtained by forceps biopsy. Results: The average age of the study participants was 62.8 years, and 64.7% of them were men. In the pleuroscopic group, the sensitivity of positive Mycobacterium tuberculosis (M. TB) cultures for sputum, pleural effusion, and pleural tissue were 35.7% (15/42), 34.8% (16/46), and 78.3% (18/23), respectively. High sensitivities of M. TB culture from pleural tissue were up to 94.4% and 91.7% when pleural characteristic patterns showed adhesion lesions and both adhesion lesions and presence of micronodules, respectively. Conclusions: M. TB culture from pleural tissue should be considered a routine test when facing unknown pleural effusion during pleuroscopic examination.

A retrospective study of alectinib versus ceritinib in patients with advanced non-small-cell lung cancer of anaplastic lymphoma kinase fusion in whom crizotinib treatment failed.

BACKGROUND: Crizotinib is the approved treatment for advanced non-small cell lung cancers (NSCLCs) of anaplastic lymphoma kinase (ALK) fusion. Failure of crizotinib treatment frequently involves drug intolerance or resistance. Comparison of using second-generation ALK inhibitors in this setting remains lacking. METHODS: Sixty-five ALK-positive advanced NSCLC patients receiving second-generation ALK inhibitors following treatment failure of crizotinib were retrospectively analyzed for the therapeutic efficacy. RESULTS: Forty-three (66.2%) and 22 (33.8%) patients received alectinib and ceritinib, respectively. Comparing alectinib to ceritinib treatment: the 12-month progression-free survival (PFS) rate (61.0% [95% confidence interval, 47.1 to 78.9%] vs. 54.5% [95% CI, 37.3 to 79.9%]); the hazard ratio (HR) for disease progression or death, 0.61 (95% CI, 0.31-1.17; p = 0.135). Multivariate Cox regression showed ECOG PS (0-1 vs. 2-3 HR 0.09 [95% CI, 0.02-0.33]; p < 0.001) and cause of crizotinib treatment failure (resistance vs. intolerance HR 2.75 [95% CI, 1.26-5.99]; p = 0.011) were the independent predictors for the PFS of second-generation ALK inhibitors. Treatment of alectinib, compared to ceritinib, was associated with a lower incidence of CNS progression (cause-specific HR, 0.10; 95% CI 0.01-0.78; p = 0.029) and a higher efficacy in patients whose cause of crizotinib treatment failure was intolerance (HR 0.29 [95% CI, 0.08-1.06]; p = 0.050). The most commonly noted adverse events were elevated AST/ALT in 10 (23.3%) patients treated with alectinib and diarrhea in 8 (36.4%) patients treated with ceritinib. CONCLUSION: Second-generation ALK inhibitors in crizotinib-treated patients showed a satifactory efficacy. Alectinib treatment demonstrated a CNS protection activity and a higher PFS in selected patients failing crizotinib treatment.

Cardiorespiratory coupling is associated with exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: The interaction between the pulmonary function and cardiovascular mechanics is a crucial issue, particularly when treating patients with chronic obstructive pulmonary disease (COPD). Synchrogram index is a new parameter that can quantify this interaction and has the potential to apply in COPD patients. Our objective in this study was to characterize cardiorespiratory interactions in terms of cardiorespiratory coupling (CRC) using the synchrogram index of the heart rate and respiratory flow signals in patients with chronic obstructive pulmonary disease. METHODS: This is a cross-sectional and preliminary data from a prospective study, which examines 55 COPD patients. K-means clustering analysis was applied to cluster COPD patients based on the synchrogram index. Linear regression and multivariable regression analysis were used to determine the correlation between the synchrogram index and the exercise capacity assessed by a six-minute walking test (6MWT). RESULTS: The 55 COPD patients were separated into a synchronized group (median 0.89 (0.64-0.97), n = 43) and a desynchronized group (median 0.23 (0.02-0.51), n = 12) based on K-means clustering analysis. Synchrogram index was correlated significantly with six minutes walking distance (r = 0.42, p = 0.001) and distance saturation product (r = 0.41, p = 0.001) assessed by 6MWT, and still was an independent variable by multivariable regression analysis. CONCLUSION: This is the first result studying the heart-lung interaction in terms of cardiorespiratory coupling in COPD patients by the synchrogram index, and COPD patients are clustered into synchronized and desynchronized groups. Cardiorespiratory coupling is associated with exercise capacity in patients with COPD.

Emphysema-Predominant COPD Had a Greater 5-Year Mortality and a Worse Annual Decline in Lung Function Than Airway Obstruction-Predominant COPD or Asthma at Initial Same Degree of Airflow Obstruction.

Background and Objectives: We studied whether the extent of exertional oxygen desaturation and emphysema could cause greater mortality in COPD and asthma independent of airflow obstruction. Materials and Methods: We performed a 5-year longitudinal observational study in COPD and asthma patients who matched for airflow obstruction severity. All subjects performed a 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) and followed spirometry and oxygen saturation (SpO2) during the 6MWT every 3-6 months. Overall survival was recorded. Cumulative survival curves were performed according to the Kaplan-Meier method and compared with the log-rank test. Results: The COPD group had higher emphysema scores, higher Δinspiratory capacities (ICs) and lower SpO2 during the 6MWT, which showed a greater yearly decline in FEV1 (40.6 mL) and forced vital capacity (FVC) (28 mL) than the asthma group (FEV1, 9.6 mL; FVC, 1.2 mL; p < 0.05). The emphysema-predominant COPD group had an accelerated annual decline in lung function and worse survival. The nadir SpO2 ≤ 80% and a higher emphysema score were the strong risk factors for mortality in COPD patients. Conclusions: The greater structural changes with a higher emphysema score and greater desaturation during the 6MWT in COPD may contribute to worse yearly decline in FEV1 and higher five-year mortality than in asthma patients with a similar airflow obstruction. The lowest SpO2 ≤ 80% during the 6MWT and emphysema-predominant COPD were the strong independent factors for mortality in chronic obstructive airway disease patients.

Etiology and characteristics of patients with bronchiectasis in Taiwan: a cohort study from 2002 to 2016.

BACKGROUND: Bronchiectasis is a chronic infectious respiratory disease with diverse causes and ethnic or geographic differences. However, few large-scale studies of its etiology have been conducted in Asia. This study aimed to determine the etiology and clinical features of bronchiectasis in Taiwan. METHODS: This longitudinal cohort study investigated the etiology and clinical features of newly diagnosed non-cystic fibrosis bronchiectasis patients from January 2002 to December 2016. The clinical, functional and microbiological data of patients were retrieved from the Chang Gung Research Database, which includes seven medical facilities throughout Taiwan. The index date was the date of the first bronchiectasis diagnosis. Known diseases that were diagnosed before the index date were regarded as etiologies of bronchiectasis. RESULTS: The cohort comprised 15,729 adult patients with bronchiectasis. Idiopathic (32%) was the most common cause, followed by post-pneumonia (24%). Other causes included post-tuberculosis (12%), chronic obstructive pulmonary disease (14%), asthma (10%), gastroesophageal reflux disease (2%) and rheumatic diseases (2%). At diagnosis, 8487 patients had sputum culture. Pseudomonas aeruginosa (5.3%) was the most common bacteria, followed by non-tuberculosis mycobacteria (3.6%), Haemophilus influenzae (3.4%) and Klebsiella pneumoniae (3.1%), but 6155 (72.1%) had negative sputum cultures. Patients with post-tuberculosis had a higher sputum isolation rate of non-tuberculosis mycobacteria than P. aeruginosa. Patients with post-tuberculosis and post-pneumonia bronchiectasis had a higher frequency of chronic lung infection than other groups (p < 0.05). Clinical characteristics, such as gender, lung function, comorbidities and microbiology, were significantly different between idiopathic and known etiologies. CONCLUSIONS: Idiopathic, post-infection and tuberculosis constitute major bronchiectasis etiologies in Taiwan. Clinical characteristics and sputum microbiology were distinct among separate etiology phenotypes.

Oxygen desaturation during the 6-min walk test as a risk for osteoporosis in non-cystic fibrosis bronchiectasis.

BACKGROUND: Osteoporosis is a common comorbidity in non-cystic fibrosis (non-CF) bronchiectasis patients. We determined whether desaturation during 6-min walk test (6MWT) can be a predictor for osteoporosis risk. METHODS: This was a retrospective cross-sectional study. Sixty-six non-CF bronchiectasis patients were enrolled. Lung function, walking distance, the lowest oxygen saturation (SpO2), the fall in SpO2 (ΔSpO2), and the distance-saturation product (DSP) were determined during the 6MWT. Desaturators (n = 45) were defined as those with ΔSpO2 > 10% or the lowest SpO2 < 88%. Bone mineral density (BMD) was determined through dual-energy X-ray absorptiometry. The severity of non-CF bronchiectasis was evaluated using high-resolution computed tomography. RESULTS: Osteoporosis was evident in more desaturators (82%) than non-desaturators (43%, p < 0.01). BMD at the level of the femoral neck was significantly lower in desaturators than in non-desaturators (- 3.6 ± 1.1 vs. - 2.4 ± 0.9, p < 0.01). BMD was correlated positively with the lowest SpO2 and negatively with ΔSpO2 and severe exacerbations. In multivariate linear regression analysis, desaturation during 6MWT was the most significant predictive factor for osteoporosis (95% confidence interval - 1.60 to - 0.26, p = 0.01). Other risk factors included old age, low body mass index and severe exacerbation. CONCLUSIONS: Exertional desaturation during the 6MWT was a significant predictive factor for osteoporosis in Asian non-CF bronchiectasis patients. The 6MWT may be useful in identifying the osteoporotic phenotype of non-CF bronchiectasis and increasing clinician awareness to promote early intervention.

Factors affecting survival in patients with endobronchial malignant mass after flexible Bronchoscopic cryotherapy: a cohort study.

BACKGROUND: Malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly to diagnose MEM, however, the therapeutic role of cryotherapy impacts on survival has not be well addressed. METHODS: Cohort data on post-cryotherapy MEM patients in a university-affiliated hospital between 2007 and 2012 were evaluated. Factors that impact survival of these subjects were analyzed using multivariate regression analysis. RESULTS: During study period, 67 patients (47 males), with median age was 63 years (range, 50-77 and median performance status of 2 (inter-quartile range [IQR], 2-3). Twenty-five had primary lung squamous cell carcinoma, 14 primary had lung adenocarcinoma, seven had metastatic colon adenocarcinoma, four had sarcoma, four had non-small cell lung cancer, four had small cell lung cancer, three had large cell carcinoma, two had lymphoma, one had muco-epidermoid carcinoma, two had esophageal squamous cell carcinoma, and one had metastatic renal cell carcinoma. MEM were observed as follows: 15 at the trachea, 14 at the left main bronchus, 12 at the right main bronchus, 12 at the right upper lobe bronchus, five at the right intermediate bronchus, three at the right lower lobe bronchus, three at the left upper lobe bronchus, two at the left lower lobe bronchus, and one at the right middle lobe bronchus Post-cryotherapy complications included minor bleeding (n = 14) and need for multiple procedures (n = 12); outcomes were relief of symptoms (n = 56), improved performance status (n = 49) and ability to receive chemotherapy (n = 43). After controlling for other variables, performance status improved after cryotherapy (odds ratio [OR] 3.7; p = 0.03; 95% confidence interval [CI] 1.2~10.7) and ability to receive chemotherapy (OR 4.3; p = 0.02; 95% CI 1.4~13.7) remained significant survival factor. Patients who received chemotherapy and cryotherapy had better survival than patients who received only cryotherapy (median, 472 vs. 169 days; log-rank test, p = 0.02; HR 0.37; 95% CI 0.16-0.89). CONCLUSION: Cryotherapy could be useful management of MEM by flexible bronchoscopy. The performance status after cryotherapy improved and caused further chemotherapy possible for the study patients and thereby, improved survival. However, the mechanism in detail of cryotherapy improve survival should be explored in the future.

Different perceptions of narrative medicine between Western and Chinese medicine students.

BACKGROUND: Western medicine is an evidence-based science, whereas Chinese medicine is more of a healing art. To date, there has been no research that has examined whether students of Western and Chinese medicine differentially engage in, or benefit from, educational activities for narrative medicine. This study fills a gap in current literature with the aim of evaluating and comparing Western and Chinese Medicine students' perceptions of narrative medicine as an approach to learning empathy and professionalism. METHODS: An initial 10-item questionnaire with a 5-point Likert scale was developed to assess fifth-year Western medical (MS) and traditional Chinese medical (TCMS) students' perceptions of a 4-activity narrative medicine program during a 13-week internal medicine clerkship. Exploratory factor analysis was undertaken. RESULTS: The response rate was 88.6% (412/465), including 270 (65.5%) MSs and 142 (34.5%) TCMSs, with a large reliability (Cronbach alpha = 0.934). Three factors were extracted from 9 items: personal attitude, self-development/reflection, and emotional benefit, more favorable in terms of enhancement of self-development/reflection. The perceptions of narrative medicine by scores between the two groups were significantly higher in TCMSs than MSs in all 9-item questionnaire and 3 extracted factors. CONCLUSIONS: Given the different learning cultures of medical education in which these student groups engage, this suggests that undertaking a course in Chinese medicine might enhance one's acceptance to, and benefit from, a medical humanities course. Alternatively, Chinese medicine programmes might attract more humanities-focused students.

Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure.

OBJECTIVES: Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells. DESIGN: Open-label prospective randomized controlled trial. SETTING: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment. CONCLUSIONS: In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

Overall response to first-line tyrosine kinase inhibitor and second-line chemotherapy is predictive of survival outcome in epidermal growth factor receptor-mutated adenocarcinoma.

BACKGROUND: First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for the treatment of lung adenocarcinoma with an EGFR-sensitizing mutation, but resistance is inevitable. Chemotherapy is widely used in the second-line setting. The outcome following this treatment scheme has not been thoroughly evaluated. METHODS: From 2007 to 2011, consecutive patients with mutated EGFR receiving first-line TKI and second-line chemotherapy were retrospectively reviewed. The overall response was categorized into double responder, single responder and double nonresponder. RESULTS: Following this treatment scheme, baseline Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (HR 0.60; 95% CI 0.37-0.98; p = 0.041) and double responder (HR 0.24; 95% CI 0.07-0.78; p = 0.018) were independent predictors of overall survival. Absence of pleural metastasis independently predicted the response to first-line TKI (OR 2.60; 95% CI 1.13-5.99; p = 0.025). In TKI responders, ECOG performance status 0-1 before chemotherapy (OR 4.95; 95% CI 1.15-21.28; p = 0.006), an exon 19 deletion (OR 4.74; 95% CI 1.30-17.21; p = 0.018) and progression-free survival (PFS) on first-line TKI (OR 1.02; 95% CI 1.01-1.09; p = 0.049) independently predicted the response to second-line chemotherapy. A moderate linear relationship (Pearson's r = 0.441; p = 0.001) existed between the PFS of this treatment scheme in TKI responders. CONCLUSION: The status of double responder to first-line TKI and second-line chemotherapy was predictive of improved survival in EGFR-mutated adenocarcinoma.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BACKGROUND: Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. METHODS: To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. RESULTS: Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. CONCLUSIONS: A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).

Algorithmic approach by endobronchial ultrasound-guided transbronchial needle aspiration for isolated intrathoracic lymphadenopathy: a study in a tuberculosis-endemic country.

BACKGROUND/PURPOSE: Isolated intrathoracic lymphadenopathy (IT-LAP) is clinically challenging because of the difficult anatomic location and wide range of associated diseases, including tuberculosis (TB). Although sampling via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for histopathology is a major development, there is still room for improvement. This study aimed to investigate an algorithmic approach driven by EBUS-TBNA and conventional bronchoscopy to streamline the management of IT-LAP. METHODS: Eighty-three prospectively enrolled patients with IT-LAP were subjected to an EBUS-TBNA diagnostic panel test (histopathology, cytology, and microbiology) and underwent conventional bronchoscopy for bronchoalveolar lavage. The results were structured into an algorithmic approach to direct patient treatment, workup, or follow-up. RESULTS: The diagnostic yields of EBUS-TBNA based on histopathology were similar for each disease entity: 77.8% for malignancy, 70.0% for TB, 75.0% for sarcoidosis, 80.0% for anthracosis, and 70.0% for lymphoid hyperplasia (p = 0.96). The incidence of malignancy was 10.8% for total IT-LAP patients, and 12.0% and 33.7% for patients with TB and sarcoidosis, respectively. Thirty-five (42.2%) patients were symptomatic. The leading diagnosis was sarcoidosis (60%), followed by TB (20%), malignancy (11.4%), lymphoid hyperplasia (5.7%), and anthracosis (2.9%). By logistic regression analysis, granulomatous disease (odds ratio: 13.45; 95% confidence interval: 4.45-40.67, p < 0.001) was an independent predictor of symptoms. Seven (8.4%) and three (3.6%) IT-LAP patients diagnosed active TB and suggestive of TB with household contact history, respectively, were all placed on anti-TB treatment. CONCLUSION: The algorithmic approach streamlines patient management. It enables early detection of malignancy, correctly places nonmalignant patients on an appropriate treatment regimen, and particularly identifies candidates at high risk of TB reactivation for anti-TB chemoprophylaxis.

Removal of endobronchial malignant mass by cryotherapy improved performance status to receive chemotherapy.

Although malignant endobronchial mass (MEM) has poor prognosis, cryotherapy is reportedly a palliative treatment. Clinical data on postcryotherapy MEM patients in a university-affiliated hospital between 2007 and 2011 were evaluated. Survival curve with or without postcryotherapy chemotherapy and performance status (PS) improvement of these subjects were analyzed using the Kaplan-Meier method. There were 59 patients (42 males), with median age of 64 years (range, 51-76, and median performance status of 2 (interquartile range [IQR], 2-3). Postcryotherapy complications included minor bleeding (n = 12) and need for multiple procedures (n = 10), while outcomes were relief of symptoms (n = 51), improved PS (n = 45), and ability to receive chemotherapy (n = 40). The survival of patients with chemotherapy postcryotherapy was longer than that of patients without such chemotherapy (median, 534 versus 106 days; log-rank test, P = 0.007; hazard ratio, 0.25; 95% confidence interval, 0.10-0.69). The survival of patients with PS improvement postcryotherapy was longer than that of patients without PS improvement (median, 406 versus 106 days; log-rank test, P = 0.02; hazard ratio, 0.28; 95% confidence interval, 0.10-0.81). Cryotherapy is a feasible treatment for MEM. With better PS after cryotherapy, further chemotherapy becomes possible for patients to improve survival when MEM caused dyspnea and poor PS.

Chronic obstructive pulmonary disease in stage I non-small cell lung cancer that underwent anatomic resection: the role of a recurrence promoter.

BACKGROUND: Despite the use of anatomic resection, the post-surgical recurrence rate remains high in early-stage non-small cell lung cancer (NSCLC). Chronic inflammation plays a role in the mechanism that promotes tumor initiation. This study aimed to investigate the association between recurrence outcome and chronic inflammation-related co-morbidities in early-stage resected NSCLC. METHODS: A review of medical records for recurrence outcome and co-morbidities, in terms of chronic obstructive pulmonary disease (COPD), DM, asthma and cardiovascular diseases, was performed with 181 patients with stage I NSCLC that underwent anatomic resection. RESULTS: Subjects with T descriptors as T2a disease (49.5 vs. 28.0%, p < 0.05) and the presence of COPD (42.4 vs. 20.7%, p < 0.01) had a higher risk of tumor recurrence. Univariate analysis for recurrence-free survival showed T descriptor as T2a (21.5 months vs. NR, p < 0.05) and the presence of COPD (20.5 months vs. NR, p < 0.01) as significant factors predicting reduced survival. The presence of COPD (HR: 1.98; 95% CI, 1.29-.02, p < 0.01) and T descriptor as T2a (HR: 2.01; 95% CI, 1.04-3.91, p < 0.05) remain independent predictors of reduced recurrence-free survival in the Cox regression model. Patients with COPD were at higher risk of brain recurrence (OR: 7.88; 95% CI, 1.50-41.3, p < 0.01). In contrast, patients without COPD showed a tendency toward recurrence in bone and liver (OR: 4.13; 95% CI, 1.08-15.8, p = 0.05). CONCLUSION: Subjects with COPD and T2a disease had a higher risk of recurrence. The role of COPD as a recurrence promoter merits further prospective investigation.

Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC.

Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47-2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10-5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44-2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.

Different prognostic meaning of tumor resistant gene detected from tumor or blood in patients with EGFR-mutant lung cancer The study demonstrates that patients with EGFR-mutant lung cancer who develop resistance due to a secondary T790M mutation, defined by tumor or blood T790M positivity, achieve better survival than patients without secondary T790M mutation; this association was mainly contributed by tumour T790M positivity. Oismertinib and chemotherapy led to similar survival in tumour T790M-positive patients. However, compared to osimertinib, chemotherapy was associated with longer survival in blood T790M-positive patients.

CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer.

RATIONALE: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T-cell immunity in tumor-bearing hosts. Their clinical relevance remains unclear. OBJECTIVES: To identify subtypes of myeloid-derived suppressor cells in patients with non-small cell lung cancer (NSCLC) and their clinical relevance. METHODS: CD11b(+)CD14(-) and CD11b(+)CD14(+) cells, determined and phenotyped by fluorescence-activated cell sorter analysis, in the peripheral blood mononuclear cells (PBMCs) of treatment-naive patients with advanced NSCLC were correlated with clinical data. T-cell activation in response to CD3/CD28 costimulation was determined by carboxy-fluorescein diacetate succinimidyl ester (CFSE) staining and ELISA analysis of IFN-γ. The percentage of CD11b(+)CD14(+)S100A9(+) cells in PBMCs was correlated with and tested as a predictor for treatment response in a cohort of patients prospectively receiving first-line cisplatin-based chemotherapy. MEASUREMENTS AND MAIN RESULTS: Patients with NSCLC had a significantly higher ratio of CD11b(+)CD14(+) cells than healthy subjects, which was correlated with poor performance status and poor response to chemotherapy. The depletion of these cells in the PBMC reversed the suppression of CD8(+) and CD4(+) T cells. Isolated CD11b(+)CD14(+) cells suppressed CD8(+) T-cell proliferation and IFN-γ production, and the former effect was attenuated by the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine hydrochloride, arginase inhibitor N-hydroxy-nor-l-arginine (nor-NOHA), and blocking antibodies for IL-4Rα(+) and IL-10. CD11b(+)CD14(+) cells were monocyte-like, expressing CD33(+), CD15(-/low), IL-4Rα(+), and S100A9(+) and producing iNOS, arginase, and several cytokines. The ratio of S100A9(+) cells positively correlated with the suppressive ability of the CD11b(+)CD14(+) cells, was associated with poor response to chemotherapy, and predicted shorter progression-free survival. CONCLUSIONS: CD14(+)S100A9(+) inflammatory monocytes in patients with NSCLC are a distinct subset of MDSCs, which suppress T cells by arginase, iNOS, and the IL-13/IL-4Rα axis. The amount of these inflammatory monocytes is associated with poor response to chemotherapy. Clinical trial registered with www.clinicaltrials.gov (NCT 01204307).

Thrombin worsens extravascular lung water and outcomes of septic patients with acute respiratory distress syndrome: A case control study.

Endothelial cell (EC) activation may increase systemic vascular permeability, causing extravascular lung water (EVLW) in sepsis with acute respiratory distress syndrome (ARDS). However, the correlation between thrombin and EVLW in sepsis and ARDS has not yet been addressed. Patients with sepsis and ARDS were prospectively enrolled between 2014 and 2016, and EVLW and serum thrombin levels on days 1 and 3 were measured and compared between surviving and non-surviving patients. Additionally, morphological changes in human umbilical vein endothelial cells (HUVECs) in the serum of patients with high and low EVLW were evaluated. The levels of EVLW, endothelial cells, and thrombin may positively correlate with the survival of patients with severe sepsis and ARDS. Twenty-seven patients were enrolled, and baseline characteristics, including age, sex, Acute Physiology and Chronic Health Evaluation (APACHE) II, prior 24-h fluid balance, body mass index, and shock status, were similar between survivors and non-survivors; however, day 1 EVLW was higher in non-survivors (27.5 ±â€…8.4 vs 22 ±â€…6.5 mL/kg, P = .047). EVLW of survivors improved from day 1 to day 3 (22 ±â€…6.5 vs 11 ±â€…3.8 mL/kg, P < .001), but did not improve in non-survivors (27.5 ±â€…8.4 vs 28 ±â€…6.7 mL/kg, P = .086), which means that patients had significantly lower EVLW on day 3 than on day 1. Thrombin levels of survivors significantly improved (1.03 ±â€…0.55 vs 0.87 ±â€…0.25 U/mL, P = .04) but did not improve in non-survivors (1.97 ±â€…0.75 vs 2.2 ±â€…0.75 U/mL, P = .08) from day 1 to day 3. EVLW and thrombin levels were positively correlated (r2 = 0.71, P < .0001). In vitro, the morphology and junctions of HUVECs changed when the serum from patients with high EVLW was added. The intercellular distances among the control, high EVLW, and low EVLW groups were 5.25 ± 1.22, 21.33 ± 2.15, and 11.17 ± 1.64 µm, respectively (P < .05).