Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers.

BACKGROUND: In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. METHODS: In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). RESULTS: 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. CONCLUSIONS: Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.

Pathological complete response in an advance stage IIIB non-small cell lung cancer secondary to neoadjuvant osimertinib targeted therapy: A case report and review of literature.

Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67-year-old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation-positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re-imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC.

The Utility of N-Terminal Pro-Brain Natriuretic Peptide as an Adjunct Diagnostic Tool for Acute Heart Failure in Acute Dyspneic Patients Coming to the Emergency Department: A Retrospective Review of Our Early Experience.

Acute dyspnea is one of the prevalent reasons for admission to the emergency department. The use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an adjunct for assessing acute dyspnea is not a common practice in many public hospitals in Malaysia. This retrospective review is part of our clinical audit to determine the utility of NT-proBNP as an adjunct to non-standardised clinical evaluation in identifying acute heart failure (HF) in patients with persistent dyspnea (24 h) post-admission. In this cohort of 30 patients with acute dyspnea, NT-proBNP was positive in 20 patients (87%) with acute HF. Three patients (13%) who were treated for septic shock recorded a NT-proBNP false-positive. NT-proBNP demonstrated an overall sensitivity of 90%, a specificity of 70%, a positive predictive value of 85.7% and a negative predictive value of 77.8% in identifying acute HF. These results reinforce that age-stratified NT-proBNP cut-off values are useful for ruling-in or -out acute HF. Thus, NT-proBNP should be considered a crucial point of care, testing to decifer the conundrum of acute dyspneic patients.

Bonuses and pitfalls of a paperless drive-through screening and COVID-19: A field report.

As the world witnessed the rapid spread of SARS-CoV-2, the World Health Organization has called for governing bodies worldwide to intensify case findings, contact tracing, monitoring, and quarantine or isolation of contacts with COVID-19. Drive-through (DT) screening is a form of case detection which has recently gain preference globally. Proper implementation of this system can help remediate the outbreak.

Telehealth: "virtual" lifeline for home-ventilated patients during the COVID-19 pandemic.

Telehealth appears useful to fill in the void for home-ventilated patients to maintain the much-needed connectivity with their healthcare team during the #COVID19 pandemic https://bit.ly/3ftvjxW.

Indwelling pleural catheter and successful autopleurodesis of refractory inflammatory lupus effusion.

Indwelling pleural catheter (IPC) is a useful tool for refractory malignant pleural effusions (MPEs). It allows palliation by intermittent symptomatic relief of the effusion and improves quality of life. Its use in benign pleural effusions comes mainly from retrospective studies, case series, and case reports. Lupus effusion is common, causes minimal symptoms, and usually responds to either steroid therapy or immunosuppressants. Refractory lupus effusion is less common and treatment may require invasive surgical pleurectomy. We describe a 52-year-old woman whose first presentation of systemic lupus erythematosus (SLE) was a pleural effusion refractory to steroids and immunosuppressants. She successfully achieved spontaneous pleurodesis with intermittent IPC drainage at three months.

Resolution of refractory chylothorax with a combination of talc pleurodesis and CPAP.

Chylothorax is an uncommon cause of pleural effusion. Recurrent chylous effusions are often resistant to conservative treatment and many need surgical intervention. We report a 69-year-old woman with refractory idiopathic chylothorax resistant to medium-chain triglyceride diet and intermittent thoracentesis. Lymphangiography and lymphoscintigraphy failed to identify the site of leakage. We initiated continuous positive airway pressure (CPAP) 12 h before and 48 hours after talc pleurodesis. Chest drain was removed at day 3 and she was discharged at day 5. To our knowledge, this is the first case of successful resolution of idiopathic refractory chylothorax with CPAP ventilation used in tandem with talc pleurodesis.

What happens when we treat the "Typhoid Mary" of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was declared a pandemic on 11 March 2020. We have since seen its fast spread worldwide. A likely contributing factor was the lack of symptoms of some of the carriers, making them unaware of their risk of spreading to other more vulnerable individuals. The other important finding has been the reported cases of infectivity despite lack of symptoms. We describe the SARS-CoV-2 pneumonia patterns in asymptomatic individuals. The common computed tomography (CT) thorax patterns found are peripheral ground-glass opacification (GGO) with upper or lower lobe predominance. We believe screening for 2019-novel coronavirus (COVID-19) in high-risk individuals may help identify the patients needing longer follow-up.

Silicone pneumonitis after gluteal filler: a case report and literature review.

Liquid silicone (polydimethylsiloxane) is an inert material that is commonly used for cosmetic purpose. Silicone embolization syndrome (SES) can rapidly progress to pneumonitis as a consequence of the injection of nonmedical-grade liquid silicone. We describe a case of severe silicone pneumonitis complicated with acute respiratory distress syndrome and bilateral pneumothorax secondary to silicone gluteal augmentation. In this case report, we aim to discuss our experience and approach in managing an uncommon case of SES.

Endobronchial and endoscopic ultrasound: it only takes an echobronchoscope to tango.

Endobronchial ultrasound (EBUS) is indispensable when it comes to evaluation of mediastinal lesion and staging of lung cancer. The incorporation of endoscopic ultrasound using an echobronchoscope (EUS-B) further extends this capability to the paraoesophageal and subdiaphragmatic structures. When combined, EBUS with EUS-B increases the diagnostic yield. Both procedures can be done in a single session and by a single operator; this translates into an overall reduction in the healthcare cost.

Cluster Analysis Evaluating PM2.5, Occupation Risk and Mode of Transportation as Surrogates for Air-pollution and the Impact on Lung Cancer Diagnosis and 1-Year Mortality.

Objective: Epidemiological studies have reported the close relationship between risk for lung cancers and air pollution in particular, for non-smoking related lung cancers. However, most studies used residential address as proxies which may not estimate accurately an individual's air pollution exposure. Therefore, the aim of this study was to identify risk factors such as occupation and mode of transportation associated with lung cancer diagnosis and death. Methods: Subjects with lung cancer (n=514) were evaluated both by chart reviews for clinical data and interviews to determine residential address for ten years, main occupation and main mode of transportation. Annual particulate matter with diameter size less than 2.5 micrometre (PM2.5) concentration were calculated based on particulate matter with diameter size less than 10 micrometre (PM10) data recorded by Malaysian Department of Environment. Logistic regression analysis, cluster analysis and the Cox regression analysis were performed to the studied variables. Results: This study concurred with previous studies that lung adenocarcinoma were diagnosed in predominantly younger, female non-smokers compared to the other types of lung cancers. Lung adenocarcinoma subjects had annual PM2.5 that was almost twice higher than squamous cell carcinoma, small cell carcinoma and other histological subtypes (p=0.024). Independent of smoking, the κ -means cluster analysis revealed two clusters in which the high risk cluster involves occupation risk with air pollution of more than four hours per day, main transportation involving motorcycle and trucks and mean annual PM2.5 concentration of more than 30 based on residential address for more than ten years. The increased risk for the high-risk cluster was more than five times for the diagnosis of lung adenocarcinoma (OR=5.69, 95% CI=3.14-7.21, p<0.001). The hazard ratio for the high-risk cluster was 3.89 (95% CI=2.12-4.56, p=0.02) for lung adenocarcinoma mortality at 1 year. Conclusion: High-risk cluster including PM2.5, occupation risk and mode of transportation as surrogates for air-pollution exposure was identified and highly associated with lung adenocarcinoma diagnosis and 1-year mortality.

Outcome of advanced lung cancer with central airway obstruction versus without central airway obstruction.

Patients with central airway obstruction (CAO) from advanced lung cancer present with significant morbidity and are assumed to have lower survival. Hence, they are offered only palliative support. We asked if patients who have advanced lung cancer with CAO (recanalised and treated) will behave similarly to those with advanced lung cancer without CAO. This study was a retrospective review of the medical records of the patients managed for advanced lung cancer during 2010 and 2015 at our institution. 85 patients were studied. Median survival and 1-, 2- and 5-year survival were 5.8 months, 30.3%, 11.7% and 2.3% versus 9.3 months, 35.7%, 9.6% and 4.7%, respectively, in the CAO and no CAO groups (p=0.30). More patients presented with respiratory failure (15 (35%) versus none; p=0.0001) and required assisted mechanical ventilation (10 (23.3%) versus none; p=0.001) in the CAO group compared with the no CAO group. Fewer patients received chemotherapy in the CAO group (11 (25.5%)) compared with the no CAO group (23 (54.7%); p=0.008). There was no difference in survival among patients with advanced lung cancer whether they presented with CAO or without CAO. Survival was similar to those without CAO in patients with recanalised CAO despite greater morbidity and lesser use of chemotherapy, strongly advocating bronchoscopic recanalisation of CAO. These findings dispel the nihilism associated with such cases.

Marijuana "bong" pseudomonas lung infection: a detrimental recreational experience.

The use of Cannabis sativa, also known as marijuana, is believed to have dated back to thousands of years B.C. More than 200 decades later, it remains a popular recreational psychoactive substance that can be smoked through a water pipe. We report a case of marijuana smoking via a "bong" device, which has resulted in severe Pseudomonas aeruginosa necrotizing pneumonia treated with conservative medical therapy. This case highlights the importance of recognizing that life-threatening pneumonia can potentially be linked to marijuana and "bong" usage. Complicated cases should be considered for early surgical intervention.

The use of e-cigarettes among university students in Malaysia.

INTRODUCTION: E-cigarette use is an emerging phenomenon with increasing recognition and acceptance globally. This study aims to create a profile of e-cigarette users among university students in Malaysia. METHODS: The study was conducted using a cross-sectional research involving six universities in Malaysia. A semi-structured questionnaire was distributed to 1302 randomly selected students, who either smoked cigarettes and/or e-cigarettes. The 2011 version of Global Adult Tobacco Surveys (GATS) tool was used to record the respondents' sociodemographic data. RESULTS: The study revealed that 74.9% of the respondents smoked e-cigarettes; 40.3% used both cigarettes and e-cigarettes (dual users), and 34.5% were exclusive e-cigarette users. The exclusive use of e-cigarettes was related to gender (OR=0.18, 95% CI: 0.09-0.39). Also, male respondents were the majority users (95%). Of the respondents, 75.2 % were Malays, 98.0% single and most believed they have no health problems (92.1%). Further findings revealed the occurrence of adverse effects, dizziness 14.4%, cough 14.1%, and headaches 12.4%. Overall, 57.8% of the respondents used e-cigarettes as a smoking cessation tool, while others consider e-cigarettes a self-image enhancing tool or as part of social activities. CONCLUSIONS: Further research on the use of e-cigarettes should be conducted on a large number of respondents in other settings to augment the findings of this study, and also guide policy making on and prevention practice of e-cigarette use, among the general student population in Malaysia.

Dental technician pneumoconiosis mimicking pulmonary tuberculosis: a case report.

BACKGROUND: Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported. CASE PRESENTATION: We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation. CONCLUSIONS: This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.

Ambiguous presentations of pulmonary epithelioid hemangioendothelioma: Two case reports of a rare pulmonary malignancy.

Pulmonary epithelioid hemangioendothelioma is an uncommon lung malignancy of endothelial origin. Besides demonstrating unpredictable presentation features and prognosis, the paucity of established treatment guidelines remains a challenge in managing these patients. We present two patients. The first patient presented with chronic productive cough over 1-year duration. He was initially diagnosed and showed partial response to treatment for cardiac failure. A persistent right upper zone consolidation on chest radiograph prompted further investigations which revealed the diagnosis of pulmonary epithelioid hemangioendothelioma. The second patient presented with right-sided hemiparesis for 1-month duration. Initial computer tomography scan of the brain showed findings of distant metastatic foci. Subsequent investigations revealed pulmonary epithelioid hemangioendothelioma as the primary lesion. Both patients succumbed without any treatment due to rapid progression of the disease. We believe that pulmonary epithelioid hemangioendothelioma is undoubtedly rarely reported in south-east Asia region. In these two case reports, the patients were diagnosed in west and east Malaysia, respectively, in the same year (2015). Both cases highlight the increasing prevalence of pulmonary epithelioid hemangioendothelioma. We postulate that this could possibly be secondary to the advancement in diagnostic capabilities and improved healthcare facilities available in this region. Late presentation of pulmonary epithelioid hemangioendothelioma generally results in grave prognosis. Further investigations are required to elucidate the nature of progression and therapeutic options for patients with pulmonary epithelioid hemangioendothelioma.

Recurrent spontaneous pneumothorax during pregnancy managed conservatively: a case report

A 36-year-old lady presented with four episodes of right sided pneumothorax during pregnancy requiring multiple chest drain insertion. It was complicated with persistent air leak despite low pressure high volume suction applied to the chest drainage. She delivered safely through spontaneous vaginal delivery with chest drainage. Further imaging by high resolution computed tomography (HRCT) scan of thorax done revealed bilateral scattered pulmonary cysts and sub pleural bullae and was later followed up with respiratory unit. She had no further episodes of pneumothorax postpartum. This case highlights the vital importance of prompt recognition and management of pneumothorax in pregnancy as the patient involved is at higher risk for acute respiratory failure leading to maternal and/or foetal mortality. It is essential for early involvement of obstetric team and to expedite the delivery for a better perinatal and maternal outcome.

Pulmonary melioidosis presenting with pleural effusion: A case report and review of literature.

Melioidosis is a serious infection, which can involve multiple systems. We report a case of pulmonary melioidosis with the initial presentation mimicking a partially treated pneumonia complicated by right-sided pleural effusion. The patient is a 49-year old man who did not respond to parenteral ceftriaxone and tazobactam/piperacillin therapy. However, upon culture and sensitivity results from blood and pleural samples isolated Burkholderia pseudomallei; antimicrobial therapy was de-escalated to parenteral ceftazidime. Within 72 h duration, his fever subsided and other respiratory symptoms improved tremendously. This case highlights the importance of early recognition of B. pseudomallei in pulmonary infection in order for prompt institution of appropriate antibiotics treatment; thus reducing morbidity and mortality.