Increased Tuberculosis Reactivation Risk in Patients Receiving Immune Checkpoint Inhibitor-Based Therapy.

OBJECTIVE: Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI). METHODS: To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI. RESULTS: In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression. CONCLUSION: The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection.

Real-world effectiveness of second-line Afatinib versus chemotherapy for the treatment of advanced lung squamous cell carcinoma in immunotherapy-naïve patients.

BACKGROUND: Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. METHODS: In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1-7.5] vs. 2.6 months [95% CI, 0.9-6.7]; hazard ratio (HR) 0.53 [95% CI 0.32-0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1-22.0] vs. 12.3 months [6.2-33.9]; HR 0.65 [95% CI 0.38-1.11], p = 0.112). CONCLUSIONS: Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

Comparative chest computed tomography findings of non-tuberculous mycobacterial lung diseases and pulmonary tuberculosis in patients with acid fast bacilli smear-positive sputum.

BACKGROUND: Early diagnosis and treatment of nontuberculous mycobacterial lung diseases (NTM-LD) and pulmonary tuberculosis (PTB) are important clinical issues. The present study aimed to compare and identify the chest CT characteristics that help to distinguish NTM lung disease from PTB in patients with acid-fast bacilli (AFB) smear-positive sputum. METHODS: From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained from the 159 patients were analyzed, 75 scans were from patients with PTB and 20 scans from NTM-LD. The typical chest CT findings of mycobacterial diseases were analyzed. RESULTS: In patients with PTB, the prevalence of pleural effusion (38.7% vs. 15.0%; P = 0.047), nodules < 10 mm in size (76.0% vs. 25.0%; P < 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P = 0.021), and cavities (31.1% vs. 5.0%; P = 0.018) were significantly higher than patients with NTM. Of the 20 patients with NTM lung diseases, bronchiectasis and cystic changes were significantly higher than patients with PTB (20.0% vs. 4.0%; P = 0.034). In multivariate analysis, CT scan findings of nodules was independently associated with patients with diagnoses of PTB (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02-0.30). Presence of bronchiectasis and cystic changes in CT scans was strongly associated with patients with NTM-LD (OR, 33.04; 95% CI, 3.01-362.55). CONCLUSIONS: The CT distinction between NTM-LD and PTB may help radiologists and physicians to know the most likely diagnoses in AFB-smear positive patients and avoid unnecessary adverse effects and the related costs of anti-TB drugs in endemic areas.

Exploring the evolution of T cell function and diversity across different stages of non-small cell lung cancer.

The immune system plays a key role in detecting and fighting cancerous tumors. T cells are a crucial component in both natural and therapeutic cancer immunoediting responses, but it is unclear if they are the primary agents of these processes. In this study, patients with lung lesions detected by CT scan were selected, and their peripheral blood samples were analyzed for T cell population and serum cytokines/chemokines. T cell subtypes (CD3, CD4, CD8, CD27, CD28, CD45, CD45RA, CD57, CCR7, and PD1) and serum cytokines/chemokines (IL-2, IL-6, IL-10, IFN-γ, TGF-ß, TNFα, CXCL1, CXCL9, and CXCL12) were measured by flow cytometry and analysis before surgical resection or other cancer treatments. The frequency of T cell subpopulations in patients with lung cancer (n = 111) corresponded to those seen in patients with T cell exhaustion. As lung cancer progressed, the proportion of effector memory T cells decreased, while the proportion of naive T cells, PD-1, CD57+, CD28+CD27+, CD45RA+, and CD3+CD4+CCR7 increased. Circulating CD8+PD1+ T cells were positively correlated with intra-tumoral PD-L1 expression. Concurrently, serum levels of IL-2, TGF-ß, and CXCL9 decreased, while IL-6, IL-10, IFN-γ, and CXCL12 increased during the progression of lung cancer. In conclusion, T cell dysfunction is associated with cancer progression, particularly in advanced-stage lung cancer, and cancer immunoediting will provide early-stage cancer detection and further therapeutic strategies.

Pain prediction model based on machine learning and SHAP values for elders with dementia in Taiwan.

INTRODUCTION: Pain conditions are common in elderly individuals, including those with dementia. However, symptoms associated with dementia may lead to poor recognition, assessment and management of pain. In this study, we incorporated the variables based on questionnaires into a machine learning algorithm to build a prediction model for the pain index of elderly individuals with dementia. MATERIALS AND METHODS: In this study, 113 cases were collected through questionnaires and used to build prediction models for the patient's pain index. Three machine learning algorithms were incorporated for comparison in this study. To interpret the prediction model, SHapley additive explanations values were used to depict the ranking importance of variables and the relationship between features and pain index. RESULTS: In the comparison of models, random forests with feature selection outperformed in terms of root mean square error and mean absolute error. A total of 11 features were selected based on embedded method. The results showed that the Karnofsky scale played a key role in predicting pain index for elderly individuals with dementia and was positively associated with pain index. Arthritis is the most important disease to predicting the pain index. CONCLUSIONS: Our findings provided the key insights to predict the pain index of elderly patients with dementia. In the future, it can be used to develop an application system or webpage, which can reduce the use of labour and improve the efficiency.

Capmatinib­associated interstitial lung disease in a patient with lung adenocarcinoma harboring a skipping mutation of mesenchymal­epithelial transition exon 14: A case report.

Capmatinib is a medication used to treat patients with non-small cell lung cancer (NSCLC) who have a specific genetic mutation known as a mesenchymal-epithelial transition exon 14 skipping mutation. Previous clinical trials have reported that capmatinib treatment has a high objective response rate in patients with this genetic mutation. However, there have also been rare reports of patients developing interstitial lung disease (ILD) following capmatinib treatment, which can be life-threatening. The present case study reports the treatment of a patient who developed ILD after 6 weeks of capmatinib treatment for NSCLC, which was resolved following application of corticosteroids. The present case demonstrated that early recognition of the onset of ILD and discontinuation of capmatinib treatment, along with the prompt initiation of corticosteroid administration, can lead to complete resolution of ILD.

The Benefits of Molnupiravir Treatment in Healthcare Facilities Patients with COVID-19.

Background: Molnupiravir (MOL) is an oral antiviral medication that has recently been treated for COVID-19. Objectively: We perform a prospective and observational study to elucidate the efficacy and safety of MOL in healthcare patients with COVID-19. Materials and Methods: A observational, non-randomized study of patients diagnosed with COVID-19 in 46 healthcare facilities and treated with MOL started within 5 days after the onset of signs or symptoms. We recorded data for all patients, including demographic data, clinical features, and symptoms. Treatment response was classified into cure, stable, hospitalization and death. Multivariate analysis was performed with stepwise logistic regression for hospitalization and death risk factors. Results: In total, 856 patients were diagnosed as having COVID-19 and treated with MOL during the study period. Of those, 496 patients (57.9%) were cured, 256 patients (29.9%) in stable condition, 104 patients (12.2%) hospitalized, and 22 patients (2.6%) died, respectively. There was significant effectiveness (87.8%) in COVID-19 patients using MOL. Multivariate analysis was performed to confirm the risk factors for hospitalization and death and included elder age (>80 years old) (odds ratio (OR) 2.2, 95% confidence interval (CI): 1.1-6.9), old cerebrovascular accident (CVA) (OR=4.1, 95% CI: 1.3-9.9), the presence of diabetes mellitus (DM) (OR=2.6, 95% CI: 1.2-9.1) and chronic respiratory diseases (OR=2.4, 95% (CI): 1.3-8.1). Limitations: This is an observational study, neither randomized study nor control group study. Conclusion: Initial treatment with MOL has the treatment benefits and is well tolerated for patients with COVID-19 in healthcare facilities. Older age, old CVA, DM, and chronic respiratory diseases were independent risk factors for hospitalization and mortality. The results demonstrate there are important clinical benefits of MOL beyond the reduction in hospitalization or death for these patients with more comorbidities in Taiwan.

Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment.

Purpose: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated. Materials and methods: From January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB-IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis. Results: The univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR <5.0 (p = 0.008). Conclusion: The benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients.

Real world experience on the effectiveness and safety of pirfenidone in patients with idiopathic pulmonary fibrosis in Taiwan.

Introduction: Randomized controlled trials have demonstrated a reduction in the decline of lung function and a reduced risk of acute exacerbation in patients with idiopathic pulmonary fibrosis treated with the antifibrotic prifenidone. The present study aimed to investigate the real-world effectiveness and safety profile of pirfenidone treatment for patients with IPF in Taiwan. Methods: Between January 1, 2019 and December 31, 2020, we enrolled 50 patients who were newly diagnosed with IPF and had at least 12 months follow-up period after pirfenidone administration. Result: The primary outcome of pharmacologic effect showed that the mean differences in the absolute values of forced vital capacity from baseline were 0.2 liter (n = 36), 0.13 liter (n = 32), 0.04 liter (n = 26), and - 0.004 liter (n = 26) after 3, 6, 9, and 12 months of administration, respectively. A slight improvement in quality of life, including scores of chronic obstructive pulmonary disease assessment test and St. George's respiratory questionnaire scores. The most common adverse effects were gastrointestinal upset and dermatological problems. No new safety concerns were observed in the present study. Conclusion: Our real-world study describe for the first time in Taiwan, the use of pirfenidone over a 12 months period. This drug preserves the lung function and improves quality of life with tolerable side effects.

Successful treatment of severe heatstroke with therapeutic hypothermia by a noninvasive external cooling system.

Heatstroke is a life-threatening disease; however, no pharmacologic treatment has proven to be effective. In severe cases with multiple organ dysfunction, the mortality remains high and many patients inevitably develop permanent neurologic damage. We report a near-fatal case of exertional heatstroke with multiple organ dysfunction, including generalized convulsions, acute lung injury, and disseminated intravascular coagulation, successfully treated with induced therapeutic hypothermia (33°C [91.4°F]) by a noninvasive external cooling system. After treatment, the patient completely recovered, without any neurologic sequelae during 1 year of follow-up. To our knowledge, this is the first reported case of using therapeutic hypothermia in heatstroke.

SnCl2/TiCl3-mediated deoximation of oximes in an aqueous solvent.

A simple procedure for SnCl(2)/TiCl(3)-mediated deoximation of ketoximes in an aqueous solvent is reported. Under the conditions developed in this effort, various ketones and aldehydes are produced in good to excellent yields.

Implementing the evidence translation-based resilience care model on family caregivers of stroke patients: a best-practice implementation project.

OBJECTIVES: The aim of this project was to promote for the family caregivers of stroke patients the resilience evidence translation care model in the community. INTRODUCTION: Stroke is the main cause of disability among many patients with chronic diseases. Resilience helps family caregivers facing the consequences of adversity and stress to have a positive outcome. METHODS: The study utilized clinical audit strategies under the JBI Practical Application of Clinical Evidence System module. Three audit criteria for the caregivers of stroke patients were considered. A preimplementation audit was conducted with eight nurses and 30 caregivers to measure compliance between current practice and best practice. From that audit we identified barriers and facilitators to practice change by undertaking a Getting Research into Practice analysis. A postimplementation audit was conducted using the same number of samples at 8 weeks for the caregivers to evaluation, and the outcomes using follow-up audit. RESULTS: The three criteria showed an improvement: nurses who received education about resilience care protocols, criterion 1 from 0 to 100%, criterion 2 from 0 to 100%, criterion 3 from 0 to 90%. The results showed that the average resilience of caregivers increased from 17.47 (SD ±â€Š1.94) to 18.33 (SD ±â€Š1.54). The resilience scale of pretest and posttest scores were significantly improved ( P  ≤ 0.001). CONCLUSION: The implementation of best practice for enhancing resilience of the family caregivers of stroke patients on the resilience evidence translation care model: a best practice implementation project in community settings is possible. The results indicate that evidence-based practice is an effective method for enhancing the resilience of family caregivers. The strategies contributed to the success of this project, such as scenario simulation education, Objective Structured Clinical Examination, regular weekly audits, and collaboration with project leaders when carrying out caregiver case discussion during clinical practice.

Klebsiella pneumoniae bacteremia and capsular serotypes, Taiwan.

Capsular serotypes of 225 Klebsiella pneumoniae isolates in Taiwan were identified by using PCR. Patients infected with K1 serotypes (41 isolates) had increased community-onset bacteremia, more nonfatal diseases and liver abscesses, lower Pittsburgh bacteremia scores and mortality rates, and fewer urinary tract infections than patients infected with non-K1/K2 serotypes (147 isolates).

Conservative treatment of severe tracheal laceration after endotracheal intubation.

Endotracheal intubation can lead to iatrogenic trauma to the upper airways. Superficial mucosal tears in the mouth, pharynx, or larynx are common and can cause secondary infection and acute respiratory distress due to massive air leak. We report a patient who sustained a severe 5-cm tracheal laceration and subcutaneous emphysema after intubation. She was successfully weaned from the ventilator after adjustment of the endotracheal cuff, therapy with broad-spectrum antibiotics, and continuous airway humidification.

Adenoid cystic carcinoma of trachea treated with tumor curettage and adjuvant intensity modulated radiation therapy.

Primary tracheal tumors are rare, accounting for only 0.2% of all thoracic cancers. Adenoid cystic carcinoma (ACC) is the second most common tracheal malignancy. Most ACC patients present with dyspnea, and the symptoms often mimic those of asthma or chronic bronchitis. We report the case of a 79-year-old female patient who presented with dyspnea and wheezing, but showed poor response to bronchodilator treatment. Bronchoscopy revealed a lobulated tumor over the lower third of the trachea, and biopsy revealed adenoid cystic carcinoma. Tumor curettage followed by intensity modulated radiation therapy was performed, and the patient eventually recovered. This case demonstrates that such less invasive management also leads to a favorable outcome.

Efficacy and Prognosis of First-Line EGFR-Tyrosine Kinase Inhibitor Treatment in Older Adults Including Poor Performance Status Patients with EGFR-Mutated Non-Small-Cell Lung Cancer.

INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutated non-small-cell lung cancer (NSCLC) patients. The efficacy of EGFR-TKIs in older patients including poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) is seldom investigated. METHODS: We enrolled patients 65 years or older with EGFR-mutated Stage IIIB-IV NSCLC and evaluated the efficacy and prognosis of first-line EGFR-TKI treatment. Clinical and demographic characteristics were reviewed and analyzed, including age, sex, PS, smoking history, EGFR mutation type, treatment regimen, progression-free survival (PFS), and overall survival (OS). RESULTS: From January 2015 to December 2019, a total of 237 patients were included, 205 of whom were eligible for efficacy and outcome analyses. Among them, 91 (44.4%) were categorized as poor PS (2-4). Compared with patients categorized as good PS (0-1), those with poor PS were older (79 versus 75 years), had a higher proportion of brain metastases (41.8% versus 25.4%), more comorbidities (74.7% versus 54.4%), and more likely to be treated with first-generation TKIs (74.7% versus 57.0%). The PFS and OS were 17.1 and 26.7 months respectively in patients with good PS and 12.7 and 18.2 months in those with poor PS (both p < 0.001). In the multivariate analysis, good PS, <3 metastatic sites, and first-line treatment with afatinib compared with erlotinib and gefitinib were associated with longer PFS. A relatively younger age, good PS, < 3 metastatic sites, and no brain metastasis at diagnosis were associated with better OS. CONCLUSION: In older patients with EGFR-mutated NSCLC and receive EGFR-TKI treatment, a good PS and <3 metastatic sites at diagnosis were associated with a longer PFS and OS. In addition, afatinib as first-line treatment was associated with a longer PFS whereas a relatively younger age and no brain metastasis at diagnosis were associated with better OS.

PD-L1 Expression and Outcome in Patients with Metastatic Non-Small Cell Lung Cancer and EGFR Mutations Receiving EGFR-TKI as Frontline Treatment.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are most common in Eastern Asia, and frequencies of 30-50% have been reported. EGFR-tyrosine kinase inhibitors (TKIs) are recommended as first-line therapeutic options for non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. Several immune checkpoint inhibitors have been successful in improving the outcomes of advanced lung cancer. The expression of programmed cell death-ligand 1 (PD-L1) on tumor cells plays an important role in predicting the efficacy of programmed cell death protein 1/PD-L1 inhibitors. The role of PD-L1 expression in tumors with EGFR mutation and its influence on clinical outcomes remain controversial. METHODS: Patients with newly diagnosed metastatic NSCLC with sensitizing EGFR mutations who received the standard treatment, ie, EGFR-TKIs for mutant adenocarcinoma as the first-line treatment, were enrolled in this retrospective study. EGFR mutations and PD-L1 expression levels were detected by Cobas RT-PCR and Dako 22C3 immunohistochemistry staining, respectively. RESULTS: From January 2011 to February 2019, 114 patients were enrolled. The average age was 62 years (range 34-92), and 45 (39.5%) patients were male. Among these patients, EGFR mutation analysis revealed exon 19 in-frame deletion in 55 (48.2%) patients, exon 21 L858R in 53 (46.5%) patients, and uncommon mutations in 6 (5.3%) patients. Among these patients with EGFR mutations, PD-L1 expression levels by tumor proportion score (TPS) were <1% in 54 (46.9%) patients, 1-49% in 50 (44.2%) patients, and ≥50% in 10 (8.8%) patients. All patients received EGFR-TKIs as first-line treatment, and in the Kaplan-Meier analysis, progression-free survival was not significantly different among groups with different PD-L1 expression status. CONCLUSION: For patients with metastatic NSCLC and EGFR mutations, PD-L1 expression is not uncommon, but no significant influence on clinical outcomes was observed in patients receiving standard initial treatment.

Oral glutamine supplements reduce concurrent chemoradiotherapy-induced esophagitis in patients with advanced non-small cell lung cancer.

BACKGROUND: Complications related to concurrent chemoradiotherapy (CCRT) such as acute radiation-induced esophagitis (ARIE) may cause significant morbidity and unplanned treatment delays in patients with advanced non-small cell lung cancer (NSCLC). We designed a prospective randomized study to assess the impact of glutamine (GLN) supplementation in preventing CCRT-induced toxicities of advanced NSCLC patients. METHODS: From September 2014 to September 2015, 60 patients diagnosed with NSCLC were included to the study. Thirty patients (50%) received prophylactic powdered GLN orally at a dose of 10 g/8 h. The prescribed radiation dose to the planning target volume was 30 Gy in 2-Gy fractions. The endpoints were radiation-induced esophagitis, mucositis, body weight loss, overall survival and progression-free survival. RESULTS: The 60 patients with NSCLC included 42 men and 18 women with a mean age ±â€Šstandard deviation of 60.3 years ±â€Š18.2 (range, 44-78 years).At a median follow-up of 26.4 months (range 10.4-32.2), all patients tolerated GLN well. A administration of GLN was associated with a decrease in the incidence of grade 2 or 3 ARIE (6.7% vs 53.4% for Gln+ vs Gln-; P = .004). GLN supplementation appeared to significantly delay ARIE onset for 5.8 days (18.2 days vs 12.4 days; P = .027) and reduced incidence of weight loss (20% vs 73.3%; P = .01). DISCUSSION: Our study suggests a beneficial effect of oral glutamine supplementation for the prevention from radiation-induced injury and body weight loss in advanced NSCLC patients who receiving CCRT.

Factors for the Early Revision of Misdiagnosed Tuberculosis to Lung Cancer: A Multicenter Study in A Tuberculosis-Prevalent Area.

BACKGROUND: Lung cancer misdiagnosed as tuberculosis (TB) is not rare, but the factors associated with early diagnosis revision remain unclear. METHODS: We screened the cases with TB notification from 2007 to 2018 and reviewed those with misdiagnosis with a revised diagnosis to lung cancer. We analyzed the factors associated with early diagnosis revision (≤1 months) and early obtained pathology (≤1 months) using multivariable Cox regression. RESULTS: During the study period, 45 (0.7%) of 6683 patients were initially notified as having TB, but later diagnosed with lung cancer. The reasons for the original impression of TB were mostly due to image suspicion (51%) and positive sputum acid-fast stain (AFS) (27%). Using multivariable Cox proportional regression, early diagnosis revision was associated with obtaining the pathology early, lack of anti-TB treatment, and negative sputum AFS. Furthermore, the predictors for early obtained pathology included large lesion size (>3 cm), presence of a miliary radiological pattern, no anti-TB treatment, and a culture-negative result when testing for nontuberculous mycobacteria (NTM) using multivariable Cox regression. CONCLUSION: In patients who are suspected to have TB but no mycobacterial evidence is present, lung cancer should be kept in mind and pathology needs to be obtained early, especially for those with small lesions, radiological findings other than the miliary pattern, and a culture positive for NTM.

Concomitant Genetic Alterations are Associated with Worse Clinical Outcome in EGFR Mutant NSCLC Patients Treated with Tyrosine Kinase Inhibitors.

Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKI) are recommended first-line therapy for advanced non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. It is of clinical interest to identify concurrent genetic mutations in NSCLC patients with EGFR mutations in the hopes of discovering predictive biomarkers towards EGFR-TKI treatment. We retrospectively analyzed a cohort of patients with advanced EGFR mutant NSCLC who underwent treatment with first generation TKIs at our hospital by a multi-gene panel via next generation sequencing. A total of 33 patients with mutant EGFR were enrolled. Up to 26 (78.8%) patients had at least one concomitant genetic alteration coexisting with mutant EGFR. Among the concomitant genetic alterations discovered, TP53 mutation was most common (n = 10,30.3%), followed by CDK4 (n = 8, 24.2%) and CDKN2A (n = 7, 21.2%)copy number variation (CNV). Progression-free survival was shorter in patients with concomitant FGFR3 mutation (1.6 vs. 12.6 months, P = .003) and CDKN2A CNV loss (6.5 vs. 13.4months, P = .019). Patients with any concomitant genetic alterations also had significant worse overall survival (24.1 vs. 40.8 months, P = .029). In summary, our study revealed an unfavorable association between concomitant genetic mutations and treatment response towards EGFR-TKI. FGFR3 mutation and CDKN2A CNV loss may be potential predictive markers for treatment outcome and warrant further investigation.