Gastrointestinal microbiota profile and clinical correlations in advanced EGFR-WT and EGFR-mutant non-small cell lung cancer.

INTRODUCTION: Difference in clinical responses to cancer therapy in each patient is from several factors. Gastrointestinal microbiota is one of the reasons. However, this correlation remains unknown. This study aims to explore correlation between gastrointestinal microbiota profile and clinical outcomes in Thai advanced non-small cell lung cancer (NSCLC) according to epidermal growth factor receptor (EGFR) status. METHODS: We enrolled 13 patients with advanced EGFR-wild-type (WT) NSCLC who received chemotherapy and 15 patients with EGFR-mutant NSCLC who received EGFR tyrosine kinase inhibitors. We collected fecal samples at baseline and first disease evaluation and performed 16S rRNA gene sequencing by NGS to assess microbiota profile. The correlations between gastrointestinal microbiota and clinical variables were studied. RESULTS: The clinical characteristics were balanced between the cohorts, excluding significantly higher albumin levels in the EGFR-mutant group. Albumin was the only significant clinical factor affecting the treatment response in multivariate analysis (ORR 15.6%, P = 0.03). Proteobacteria counts were higher in the EGFR-WT group, whereas Bacteroidetes and Firmicutes counts were higher in the EGFR-mutant group. The alpha diversity of the gastrointestinal microbiome was significantly higher in the EGFR-mutant group (Shannon index: 3.82 vs. 3.25, P = 0.022). Following treatment, Proteobacteria counts were lower and Bacteroidetes and Firmicutes counts were higher in both cohorts; the changes were more prominent in the EGFR-WT cohort. No significant correlation between microbiota profile and treatment response were demonstrated in our study. However, beta diversity was significantly different according to severity of adverse events. Enrichment of Clostridia and Bacteroidia was associated with higher adverse event risk in the EGFR-WT cohort. CONCLUSIONS: Proteobacteria was dominant in Thai lung cancer patients both EGFR-WT and EGFR-mutant, and this phylum maybe associate with lung cancer carcinogenesis. Chemotherapy altered the gastrointestinal microbiota, whereas EGFR-TKIs had less effects. Our findings highlight the potential predictive utility of the gastrointestinal microbiota for lung cancer carcinogenesis. Studies with larger cohorts and comparison with the healthy Thai population are ongoing to validate this pilot study.

Diaphragmatic parameters by ultrasonography for predicting weaning outcomes.

BACKGROUND: Diaphragmatic dysfunction remains the main cause of weaning difficulty or failure. Ultrasonographic measurement of diaphragmatic function can be used to predict the outcomes of weaning from mechanical ventilation. Our primary objective was to investigate the performance of various sonographic parameters of diaphragmatic function for predicting the success of weaning from mechanical ventilation. METHODS: We prospectively enrolled 68 adult patients requiring mechanical ventilation who were admitted to the intensive care unit from June 2013 to November 2013. The diaphragmatic inspiratory excursion, time to peak inspiratory amplitude of the diaphragm (TPIAdia), diaphragmatic thickness (DT), DT difference (DTD), and diaphragm thickening fraction (TFdi) were determined by bedside ultrasonography performed at the end of a spontaneous breathing trial. A receiver operating characteristic curve was used for analysis. RESULTS: In total, 62 patients were analyzed. The mean TPIAdia was significantly higher in the weaning success group (right, 1.27 ± 0.38 s; left, 1.14 ± 0.37 s) than in the weaning failure group (right, 0.97 ± 0.43 s; left, 0.85 ± 0.39 s) (P <  0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of a TPIAdia of > 0.8 s in predicting weaning success were 92, 46, 89, and 56%, respectively. The diaphragmatic inspiratory excursion, DTD, and TFdi were associated with reintubation within 48 h. The P values were 0.047, 0.021, and 0.028, and the areas under the receiver operating characteristic curve were 0.716, 0.805, and 0.784, respectively. CONCLUSION: Among diaphragmatic parameters, TPIAdia exhibits good performance in predicting the success of weaning from mechanical ventilation. This study demonstrated a trend toward successful use of TPIAdia rather than diaphragmatic inspiratory excursion as a predictor of weaning from mechanical ventilation.

Clinical and chest radiographic features of missed lung cancer and their association with patient outcomes.

PURPOSE: To examine clinical and chest radiographic features of missed lung cancer (MLC) and explore their association with patient outcomes. METHODS: We retrospectively reviewed chest radiographs obtained at least six months before lung cancer (LC) diagnosis in 95 patients to identify the first positive chest radiograph showing MLC. We assessed chest radiographic features of MLC and their association with patient outcomes. RESULTS: Seventy-five (78.9%) patients (39 men, 36 women; mean age, 64.5 ± 10.5 years) had MLC. The median diagnostic delay was 31.3 months (6.6-128.0 months). The median MLC size was 16 mm (5-57 mm), and 54.7%, 68.0%, and 74.7% of MLC were in the left lung, the middle/lower zones, and the outer two-thirds of the lung, respectively. MLC exhibited a round/oval shape, partly/poorly defined margin, irregular/spiculated border, a density less than the aortic knob, and anatomical superimposition in 57.3%, 77.3%, 61.3%, 85.3%, and 88.0% of cases, respectively. Thirty-five (46.7%) patients had stage III + IV LC at diagnosis. Thirty-one (41.3%) patients died. MLC in the inner one-third of the lung, exhibiting a density equal to/greater than the aortic knob, or superimposed by midline structures was significantly associated with stage III + IV LC at diagnosis. The 3-year all-cause mortality significantly increased when MLC was in the upper zone, superimposed by pulmonary vessels, superimposed by pulmonary vessels plus ribs, or superimposed by pulmonary vessels plus in the inner one-third of the lung. CONCLUSION: MLC with some radiographic features pertaining to their location, density, and superimposed structures was found to portend a worse outcome.

A Phase II Study of Osimertinib in Patients with Advanced-Stage Non-Small Cell Lung Cancer following Prior Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) Therapy with EGFR and T790M Mutations Detected in Plasma Circulating Tumour DNA (PLASMA Study).

Epidermal growth factor receptor (EGFR) T790M mutations drive resistance in 50% of patients with advanced non-small cell lung cancer (NSCLC) who progress on first/second generation (1G/2G) EGFR tyrosine kinase inhibitors (TKIs) and are sensitive to Osimertinib. Tissue sampling is the gold-standard modality of T790M testing, but it is invasive. We evaluated the efficacy of Osimertinib in patients with EGFR mutant NSCLC and T790M in circulating tumour DNA (ctDNA). PLASMA is a prospective, open-label, multicentre single-arm Phase II study. Patients with advanced NSCLC harbouring sensitizing EGFR and T790M mutations in plasma at progression from ≥one 1G/2G TKI were treated with 80 mg of Osimertinib daily until progression. The primary endpoint was the objective response rate (ORR); the secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicities. Plasma next-generation sequencing was performed to determine Osimertinib resistance mechanisms and assess serial ctDNA. A total of 110 patients from eight centres in five countries were enrolled from 2017 to 2019. The median follow-up duration was 2.64 (IQR 2.44-3.12) years. The ORR was 50.9% (95% CI 41.2-60.6) and the DCR was 84.5% (95% CI 76.4-90.7). Median PFS was 7.4 (95% CI 6.0-9.3) months; median OS was 1.63 (95% CI 1.35-2.16) years. Of all of the patients, 76% had treatment-related adverse events (TRAEs), most commonly paronychia (22.7%); 11% experienced ≥ Grade 3 TRAEs. The ctDNA baseline load and dynamics were prognostic. Osimertinib is active in NSCLC harbouring sensitizing EGFR and T790M mutations in ctDNA testing post 1G/2G TKIs.

Clinical Course and Outcomes among COVID-19 Patients at the Hospitel in Bangkok: A Retrospective Study.

A hospitel is a hotel that has been designated as an extension of the healthcare facilities during the COVID-19 pandemic in resource-limited settings. However, the clinical course and outcomes of patients with COVID-19 admitted to this unique type of facility have never been studied. We retrospectively reviewed the medical records of adult patients with COVID-19 who were admitted to a single hospitel in Bangkok, Thailand. Risk factors with respect to chest X-ray progression and clinical progression were analyzed using a logistic regression. A total of 514 patients were recruited, with a mean (standard deviation) age of 35.6 (13.4) years, and 58.6% were women. Patients were admitted after a median (interquartile range) of 3 (2−6) days of illness and were classified with mild (12.3%), moderate (86.6%), and severe (1.1%) conditions. Favipiravir and corticosteroids were prescribed in 26.3% and 14.9% of patients, respectively. Chest X-ray progression was found in 7.6% of patients, and hospital transfer occurred in 2.9%, with no deaths. Favipiravir use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4−7.5, p = 0.005), nausea/vomiting after admission (OR 32.3, 95% CI 1.5−700.8, p = 0.03), and higher oxygen saturation on admission (OR 1.99; 95% CI 1.22−3.23, p = 0.005) were factors associated with chest X-ray progression. Additionally, an oxygen requirement on admission was an independent risk factor for hospital transfer (OR 904, 95% CI 113−7242, p < 0.001). In a setting where the hospitel has been proposed as an extension facility for patients with relatively non-severe COVID-19, most patients could achieve a favorable clinical outcome. However, patients who require oxygen supplementation should be closely monitored for disease progression and promptly transferred to a hospital if necessary.

Combined Pulmonary Tuberculosis with Pulmonary and Pleural Cryptococcosis in a Patient Receiving Ruxolitinib Therapy.

With an advance in therapy, there are increasing emerging and re-emerging opportunistic infections among patients with hematologic conditions and malignancy. Herein, we present a 56-year-old woman with primary myelofibrosis who developed combined tuberculosis (TB) and cryptococcosis with extensive pulmonary, pleural, and nodal involvement during ruxolitinib therapy. Marked clinical and radiologic improvements were undoubtedly evident after receiving anti-TB and antifungal therapies and pleural drainage. Hence, the presence of atypical clinical and radiologic manifestations and incomplete responses, despite receiving adequate antimicrobial treatment, should raise concerns regarding the combined emerging and re-emerging opportunistic infections and the possibility of unusual radiologic manifestations of cryptococcosis in a ruxolitinib-treated patient.

Initial diagnosis and successful treatment of pulmonary tumor embolism manifesting as the first clinical sign of prostatic adenocarcinoma.

Although pulmonary tumor embolism (PTE) is a well-recognized end-stage form of pulmonary metastases at postmortem examination, the entity is rarely the first clinical sign of prostate cancer. Diagnosis of this condition in patients who have no previous history of malignancy is a challenge. Herein, we reported a 79-year-old man presented with progressive, unexplained dyspnea on exertion. Microscopic PTE coinciding with pulmonary lymphangitic carcinomatosis were readily recognized based on the presence of multifocal dilatation and beading of the peripheral pulmonary arteries with thickening of the bronchial walls and interlobular septa on the initial thin-section chest CT images. Pathologic examination of the transbronchial lung biopsy specimen revealed tumor emboli occluding both the small muscular pulmonary arteries and lymphatic vessels. These tumor cells were positive for prostatic specific antigen on immunohistochemical staining. The final diagnosis of prostatic adenocarcinoma was confirmed. Remarkable clinical and radiographic improvement was achieved following bilateral orchiectomies and anti-androgen treatment.

Non-Small Cell Lung Carcinoma with Concomitant Localized Pulmonary Melioidosis: A Rare Co-Existing Disease.

Melioidosis is caused by Burkholderia pseudomallei, water-and-soil gram-negative bacteria predominantly found in Southeast Asia and Australia. Herein, we reported a 63-year-old Thai man presenting with prolonged fever, non-productive cough, and weight loss for 3 months. He underwent deceased donor kidney transplantation 4 years ago and was on many immunosuppressive agents after transplantation. At presentation, his chest radiograph showed a mass-like lesion in the left upper lobe. Histopathological examination of a transthoracic needle lung biopsy yielded adenocarcinoma, while tissue culture grew for B. pseudomallei. He was diagnosed with stage IIIA non-small cell lung cancer (T4N0M0) co-existing with localized pulmonary melioidosis. After intensive and eradication therapy for melioidosis, his well-being improved with the resolution of fever. He sequentially underwent left upper lobectomy, but the procedure was not accomplished due to severe adhesions surrounding the left lung and great vessels. After surgery, he received concurrent chemoradiation therapy for his lung cancer. Nevertheless, the disease progressed, and he finally passed away. Since fever is not a common manifestation of lung cancer, co-existing infection, such as tuberculosis, fungal infection, and melioidosis, should always be excluded in patients suspected of having lung cancer presenting with unexplained fever.

Primary polymorphous low-grade adenocarcinoma of the bronchus: complete tumor removal with bronchoscopic resection.

Primary polymorphous low-grade adenocarcinoma (PLGA) is an uncommon malignant tumor arising from the minor salivary glands, but its occurrence as a primary tumor of the tracheobronchial tree is very rare. Herein, we have reported a rare case of endobronchial PLGA in a 56-year-old woman presenting with chronic cough and progressive exertional dyspnea. Chest CT clearly demonstrated an endobronchial tumor obstructing the distal part and bifurcation of the left main bronchus and causing distal atelectasis. She underwent rigid bronchoscope with electrocautery and bronchoscopic resection of the tumor. PLGA was diagnosed histologically. Subsequent left pneumonectomy was performed and showed no evidence of residual tumor.

Bronchial anthracostenosis with mediastinal fibrosis associated with long-term wood-smoke exposure.

Bronchial anthracostenosis describes a disease entity consisting of bronchial destruction, deformity and stenosis related to dark pigmentation on bronchoscopy in patients with a history of coal workers' pneumoconiosis or chronic exposure to biomass smoke. The combined occurrence of bronchial anthracostenosis and mediastinal fibrosis in association with wood-smoke exposure has not been previously reported. This case report describes a non-cigarette smoking elderly woman who developed bronchial anthracostenosis and mediastinal fibrosis after long-term exposure to wood smoke. Clinical and radiological improvements were achieved after treatment with corticosteroid and tamoxifen. Awareness of this unusual entity will help to avoid misdiagnosis of malignancy or unnecessary thoracotomy.

Relationship between the presence of bronchiectasis and acute exacerbation in Thai COPD patients.

Background: The prevalence rate of bronchiectasis in COPD is variable. Coexisting bronchiectasis and COPD may influence COPD severity and exacerbation. Objective: We investigated whether bronchiectasis is associated with frequent or severe COPD exacerbation. Lower airway bacterial and mycobacterial infections are a possible mechanism for bronchiectasis. Materials and methods: A cross-sectional study was conducted in 2013-2014. COPD exacerbations and hospitalizations were reviewed. Spirometry and CT were performed. COPD symptoms were assessed by using the COPD assessment test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Sputum inductions were performed and specimens were sent for microbiology. Results: We recruited 72 patients. Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, B, C, and D, were noted in 20%, 27.1%, 14.3%, and 38.6% of the patients, respectively. Frequent exacerbations (≥2) and/or ≥1 hospitalization in the previous year were observed in 40.3% of patients. Median mMRC of COPD with frequent and non-frequent exacerbations was 1.0 (range 1-2) and 2.0 (range 1-3), (p=0.002), respectively. Median CAT of COPD with frequent and non-frequent exacerbations was 20.5 (3-37) and 11.0 (2-32), (p=0.004), respectively. CT-detected bronchiectasis was observed in 47.2% of patients. Median mMRC of COPD with and without bronchiectasis was 1.0 (0-4) and 1.0 (0-4) (p=0.22), respectively. Median CAT of COPD with and without bronchiectasis was 16.2 (95% CI: 12.9-19.6) and 13.0 (3-37), (p=0.49), respectively. The lower post-bronchodilator forced expiratory volume in 1 second (FEV1) of COPD with frequent exacerbations than those without was noted (p=0.007). The post-bronchodilator forced expiratory volume at 1 second percent in patients with and without bronchiectasis was not different (p=0.91). After adjusting for gender, severity of airflow obstruction, severity of COPD symptoms, the odds ratio for bronchiectasis with frequent and/or severe exacerbation was 4.99 (95% CI: 1.31-18.94), (p=0.018). Neither bacterial nor mycobacterial airway infection was associated with bronchiectasis or frequent exacerbation. Conclusions: Bronchiectasis is common in Thai COPD. It was associated with frequent exacerbation or hospitalization. Mycobacterial tuberculosis in COPD patients with bronchiectasis was uncommon.

Assessment of proximal and peripheral airway dysfunction by computed tomography and respiratory impedance in asthma and COPD patients with fixed airflow obstruction.

OBJECTIVE: To ascertain: (i) if elderly patients with fixed airflow obstruction (FAO) due to asthma and chronic obstructive pulmonary disease (COPD) have distinct airway morphologic and physiologic changes; (ii) the correlation between the morphology of proximal/peripheral airways and respiratory impedance. METHODS: Twenty-five asthma cases with FAO and 22 COPD patients were enrolled. High-resolution computed tomography was used to measure the wall area (WA) and lumen area (LA) of the proximal airway at the apical segmental bronchus of the right upper lobe (RB1) adjusted by body surface area (BSA) and bronchial wall thickening (BWT r ) of the peripheral airways and extent of expiratory air trapping (AT exp ). Respiratory impedance included resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequency (Fres). Total lung capacity (TLC) and residual volume (RV) were measured. RESULTS: Asthma patients had smaller RB1-LA/BSA than COPD patients (10.5 ± 3.4 vs. 13.3 ± 5.0 mm2/m2, P = 0.037). R5(5.5 ± 2.0 vs. 3.4 ± 1.0 cmH2O/L/s, P = 0.02) and R20(4.2 ± 1.7 vs. 2.6 ± 0.7 cmH2O/L/s, P = 0.001) were higher in asthma cases. AT exp and BWT r were similar in both groups. Regression analysis in asthma showed that forced expiratory volume in one second (FEV1) and Fres were associated with RB1-WA/BSA (R2= 0.34, P = 0.005) and BWT r (0.5, 0.012), whereas RV/TLC was associated with AT exp (0.38, 0.001). CONCLUSIONS: Asthma patients with FAO had a smaller LA and higher resistance of the proximal airways than COPD patients. FEV1 and respiratory impedance correlated with airway morphology.

Eosinophilic pleural effusion after gastric variceal obliteration with cyanoacrylate.

Pleuropulmonary complications after endoscopic injection sclerotherapy for treatment of esophagogastric varices are not uncommon but are usually mild and self-limited. Herein we report a male patient with liver cirrhosis who underwent endoscopic injection sclerotherapy, using a mixture of n-butyl-2-cyanoacrylate and ethiodized oil for obliteration of gastric varices. After the procedure, he developed moderate amount of left pleural effusion that persisted for a period of time and required thoracentesis and medical treatment. We believed that the inadvertent retrograde reflux of the embolized glue and ethiodized oil via the portosystemic venous collateral into the left pleura might be the possible mechanism for the development of left pleural effusion as the droplets of ethiodized oil were seen along the left pleura on the imaging studies.

Thin-section CT findings of thoracolithiasis.

PURPOSE: To review thin-section CT findings of thoracolithiasis. MATERIALS AND METHODS: Thirty-three thin-section CT scans of 9 patients with thoracolithiasis diagnosed between 2008 and 2016 were reviewed for the location, shape, longest diameter, and calcification of each freely mobile nodule (thoracolith) and for the presence of coexisting abnormalities. RESULTS: The mean age of 9 patients (5 women) was 65.8 years (SD 14.9; range 37-83 years). Eight were > 50 years of age. Three patients had two thoracoliths, and the remaining 6 patients had one. Thoracoliths were in the left (n = 9) or right (n = 3) pleural cavity, with most in the lower pleural cavity. Nine thoracoliths were found to be larger at follow-up. The median diameters of the 12 thoracoliths were 4.9 mm (range 2.1-10.6 mm) and 6.2 mm (range 3.6-11.0 mm) on the initial and latest follow-up CT scans, respectively. Concomitant old granulomatous disease (n = 6) and diffuse systemic sclerosis-related interstitial lung disease (n = 2) were noted. CONCLUSION: Thoracolithiasis can manifest as one or two small calcified nodules. It tends to occur in the left lower pleural cavity, occur in a patient aged > 50 years, be larger on follow-up, and coincide with other diseases.

Massive hemothorax in a beta-thalassemic patient due to spontaneous rupture of extramedullary hematopoietic masses: diagnosis and successful treatment.

Intrathoracic extramedullary hematopoiesis is an unusual but well-described entity. The condition is typically found in patients who have chronic hemolytic anemias, especially thalassemia. We report a case of a 38-year-old man with underlying beta thalassemia/hemoglobin E who developed intrathoracic extramedullary hematopoiesis. The hematopoietic masses spontaneously ruptured, resulting in massive hemothorax. The condition was confirmed by video-assisted thoracoscopy and successfully treated with surgery, hydroxyurea, and radiation.

A case of recurrent pneumothorax related to oral methylphenidate.

Primary spontaneous pneumothorax (PSP) commonly occurs in young, tall, and thin males, without any identifiable cause except for emphysema-like changes (ELCs). However, other risk factors may be overlooked. Herein, we report the case of a 19-year-old male who presented with recurrent spontaneous pneumothorax while taking oral methylphenidate.

Thoracic manifestations of paradoxical immune reconstitution inflammatory syndrome during or after antituberculous therapy in HIV-negative patients.

Immune reconstitution inflammatory syndrome (IRIS) is a consequence of exaggerated and dysregulated host's inflammatory response to invading microorganism, leading to uncontrolled inflammatory reactions. IRIS associated with tuberculosis (TB) is well recognized among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy, but it is less common among HIV-negative patients. IRIS can manifest as a paradoxical worsening or recurring of preexisting tuberculous lesions or development of new lesions despite successful antituberculous treatment. Hence, the condition might be misdiagnosed as superimposed infections, treatment failure, or relapse of TB. This pictorial essay reviewed diagnostic criteria and various thoracic manifestations of the paradoxical form of TB-associated IRIS (TB-IRIS) that might aid in early recognition of this clinical entity among HIV-negative patients. The treatment and outcomes of TB-IRIS were also discussed.

Chronic Klebsiella pneumonia: a rare manifestation of Klebsiella pneumonia.

K. pneumoniae can present as two forms of community-acquired pneumonia, acute and chronic. Although acute pneumonia may turn into necrotizing pneumonia, which results in a prolonged clinical course, it often has a rapidly progressive clinical course. In contrast, chronic Klebsiella pneumonia runs a protracted indolent course that mimics other chronic pulmonary infections and malignancies. Herein, we present two cases of chronic Klebsiella pneumonia. The diagnosis was made by microorganism identification, as well as absence of other potential causes. Clinical and radiographic findings improved after a prolonged course of antibiotic therapy.