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Lung cancer is the world’s leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n  = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts. Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

Background Bronchoalveolar lavage (BAL) is utilized for diagnosing lung infiltrates in immunocompromised. There is heterogeneity in the data and reported diagnostic yields range from 26 to 69%. Therefore, selection criteria for BAL to maximize yield and minimize complications are unclear. Objectives of this study were to determine the diagnostic yield and complication rate of BAL in immunocompromised patients presenting with lung infiltrates, and identify factors impacting these outcomes. Exploratory aims included characterization of pathogens, rate of treatment modification and mortality. Methods Retrospective study from January 2012 to December 2016. Patients on mechanical ventilation were excluded. Positive diagnostic yield was defined as confirmed microbiological or cytological diagnosis. Results A total of 217 patients were recruited (70.1% male and mean age: 51.7 ± 14.6 years). Diagnostic yield was 60.8% and complication rate 14.7%. Complications (hypoxemia and endobronchial bleeding) were all sell-limiting. Treatment modification based on BAL results was 63.3%. In 97.0% an infectious aetiology was identified. HIV infection (OR 5.304, 95% CI 1.611–17.458, p  = 0.006) and severe neutropenia (OR 4.253, 95% CI 1.288–14.045, p  = 0.018) were associated with positive yield. Leukemia (OR 0.317, 95% CI 0.102–0.982, p  = 0.047) was associated with lower yield. No factors impacted complication rate. Overall mortality (90-day) was 17.5% and in those with hematologic malignancy, it was 28.3%. Conclusion BAL retains utility in diagnosis of immunocompromised patients with lung infiltrates. However, patients with hematologic malignancy have a high mortality and alternative sampling should be considered because of poor results with BAL. Trial registration ClinicalTrials.gov identifier NCT01374542 . Registered June 16, 2011.

Triage becomes necessary when demand for intensive care unit (ICU) resources exceeds supply. Without triage, there is a risk that patients will be admitted to the ICU in the sequence that they present, disadvantaging those who either present later or have poorer access to healthcare. Moreover, if the patients with the best prognosis are not allocated life support, there is the possibility that overall mortality will increase. Before formulating criteria, principles such as maximizing lives saved and fairness ought to have been agreed upon to guide decision-making. The triage process is subdivided into three parts, i.e., having explicit inclusion/exclusion criteria for ICU admission, prioritization of patients for allocation to available beds, and periodic reassessment of all patients already admitted to the ICU. Multi-dimensional criteria offer more holistic prognostication than only using age cutoffs. Appointed triage officers should also be enabled to make data-driven decisions. However, the process does not merely end with an allocation decision being made. Any decision has to be sensitively and transparently communicated to the patient and family. With infection control measures, there are challenges in managing communication and the psychosocial distress of dying alone. Therefore, explicit video call protocols and social services expertise will be necessary to mitigate these challenges. Besides symptom management and psychosocial management, supportive care teams play an integral role in coordination of complex cases. This scoping review found support for the three-pronged, triage-communication-supportive care approach to facilitate the smooth operationalization of the triage process in a pandemic.

The aim of the study was to measure empathy in healthcare professionals in Singapore and to compare the scores between the different professions: doctors, nurses, and allied health professionals. An online survey questionnaire was conducted using the Jefferson Scale of Empathy (JSE) from July 2019 to January 2020. The total JSE score was calculated and compared among the different groups. Multiple linear regression was performed to assess predictors of total empathy scores for groups with statistically lower scores. The survey was completed by 4,188 healthcare professionals (doctors (n=569, 13.6%), nurses (n=3032, 72.4%), and allied health professionals (n=587, 14.0%)) out of the 9,348-strong survey population, with a response rate of 44.8%. The study revealed a mean empathy score (SD) of 103.6 (15.6) for the cohort. The mean empathy score (SD) was 112.3 (14.7), 101.3 (15.2), and 107.0 (15.0), respectively for doctors, nurses, and allied health professionals. These were statistically significantly different among the groups (p< 0.0001), with nurses scoring significantly lower than either doctors (p< 0.0001) or allied health professionals (p< 0.0001). Multiple linear regression showed that age < 30 years old, male gender, Malay ethnicity, and working in a hospital setting were associated with significantly lower empathy scores in the nursing group. Nurses in Singapore had significantly lower empathy scores compared to doctors and allied health professionals. Further research on the underlying causes should be undertaken and measures to improve empathy among Singapore nursing staff should be explored and implemented.

Introduction This case of fenthion poisoning demonstrates the delayed, protracted and yet unpredictable nature of cholinergic effects which are unique to fenthion toxicity. Case Presentation A 36-year-old female presented to the emergency department with drowsiness and vomiting, 8 hours after an unknown pesticide ingestion. She had some cholinergic symptoms (miosis, incontinence, emesis) suspicious of organophosphate toxicity but was initially well with no bronchorrhea or bradycardia. During her admission, she developed increasing salivation and bronchorrhea resulting in respiratory failure requiring intubation 27 h’ post-ingestion. Possible aspiration pneumonitis was initially considered given the delayed nature of deterioration. However, blood toxicology results confirmed fenthion poisoning. Atropine and pralidoxime boluses were administered followed by continuous infusion. She was extubated after initial improvement and stabilization – only to require reintubation for recurring respiratory failure and seizures on Days 4 and 5, each time following apparent recovery. She was eventually weaned off mechanical ventilation only on Day 31. Discussion and Conclusion This case illustrates the importance of physician awareness to potentially innocuous presentations of fenthion poisoning as symptoms at the onset may appear benign and falsely reassuring. Serious toxic manifestations may be significantly delayed over a prolonged, waxing-and-waning clinical course because of the compound’s high lipid solubility and metabolism into potent secondary compounds.

Background and Objective. Intrapleural tissue plasminogen activator/deoxyribonuclease (tPA/DNase) is increasingly being used for pleural infections. Compared to sequential instillation of tPA/DNase, concurrent instillation considerably reduces the complexity of the administration process and reduces workload and the number of times the chest drain is accessed. However, it remains unclear if concurrent intrapleural therapy is as efficacious or safe as sequential intrapleural therapy. Methods. We conducted a retrospective review of patients with pleural infection requiring intrapleural therapy at two tertiary referral centres. Results. We included 84 (62.2%) and 51 (37.8%) patients who received sequential and concurrent intrapleural therapy, respectively. Patient demographics and clinical characteristics, including age, RAPID score, and percentage of pleural opacity on radiographs before intrapleural therapy, were similar in both groups. Treatment failure rates (defined by either in-hospital mortality, surgical intervention, or 30-day readmission for pleural infection) were 9.5% and 5.9% with sequential and concurrent intrapleural therapy, respectively (p=0.534). This translates to a treatment success rate of 90.5% and 94.1% for sequential and concurrent intrapleural therapy, respectively. There was no significant difference in the decrease in percentage of pleural effusion size on chest radiographs (15.1% [IQR 6-35.7] versus 26.6% [IQR 9.9-38.7], p=0.143) between sequential and concurrent therapy, respectively. There were also no significant differences in the rate of pleural bleeding (4.8% versus 9.8%, p=0.298) and chest pain (13.1% versus 9.8%, p=0.566) between sequential and concurrent therapy, respectively. Conclusion. Our study adds to the growing literature on the safety and efficacy of concurrent intrapleural therapy in pleural infection.

Pulmonary alveolar proteinosis (PAP) can be due to primary autoimmune and secondary causes, including e‐cigarette, or vaping, product use‐associated lung injury. We present a 33‐year‐old male presenting with PAP and a history of vaping. Serum anti‐granulocyte‐macrophage colony‐stimulating factor antibodies were present. Vitamin E (VE), but not VE acetate, was detected in bronchoalveolar lavage. This is the first report of potential association between vaping and autoimmune PAP. We present a 33‐year‐old male presenting with pulmonary alveolar proteinosis (PAP) and a history of vaping. Serum anti‐granulocyte‐macrophage colony‐stimulating factor antibodies were present. Vitamin E (VE), but not VE acetate, was detected in bronchoalveolar lavage. This is the first report of potential association between vaping and autoimmune PAP.

This purpose of this study was to examine clinical-pathologic factors--particularly smoking and brain metastases--in EGFR mutation positive (M(+)) lung adenocarcinoma (ADC) to determine their impact on survival in patients treated with first line EGFR TKI. A retrospective review of EGFR mutation reflex testing experience for all ADC diagnosed at a tertiary Asian cancer centre from January 2009 to April 2013. Amongst this cohort, patients with advanced EGFR M(+) ADC treated with first line EGFR TKI were identified to determine factors that influence progression free and overall survival. 444/742 (59.8%) ADC reflex tested for EGFR mutations were EGFR M(+.) Amongst never-smokers (n=468), EGFR M(+) were found in 74.5% of females and 76.3% of males, and amongst ever smokers (n=283), in 53.3% of females and 35.6% of males. Exon 20 mutations were found more commonly amongst heavy smokers (> 50 pack years and > 20 pack years, Pearson's chi square p=0.044, and p=0.038 respectively). 211 patients treated with palliative first line TKI had a median PFS and OS of 9.2 and 19.6 months respectively. 26% of patients had brain metastasis at diagnosis. This was significantly detrimental to overall survival (HR 1.85, CI 1.09-3.16, p=0.024) on multivariate analysis. There was no evidence that smoking status had a significant impact on survival. The high prevalence of EGFR M(+) in our patient population warrants reflex testing regardless of gender and smoking status. Smoking status and dosage did not impact progression free or overall survival in patients treated with first line EGFR TKI. The presence of brain metastasis at diagnosis negatively impacts overall survival.

Background. Conventional flexible bronchoscopy has limited sensitivity in the diagnosis of peripheral lung lesions and is dependent on lesion size. However, advancement of CT imaging offers multiplanar reconstruction facilitating enhanced preprocedure planning. This study aims to report efficacy and safety while considering the impact of patient selection and multiplanar CT planning. Method. Prospective case series of patients with peripheral lung lesions suspected of having lung cancer who underwent flexible bronchoscopy (forceps biopsy and lavage). Endobronchial lesions were excluded. Patients with negative results underwent CT-guided transthoracic needle aspiration, surgical biopsy, or clinical-radiological surveillance to establish the final diagnosis. Results. 226 patients were analysed. The diagnostic yield of bronchoscopy was 80.1% (181/226) with a sensitivity of 84.2% and specificity of 100%. In patients with a positive CT-Bronchus sign, the diagnostic yield was 82.4% compared to 72.8% with negative CT-Bronchus sign (p=0.116). Diagnostic yield was 84.9% in lesions > 20 mm and 63.0% in lesions ≤ 20 mm (p=0.001). Six (2.7%) patients had transient hypoxia and 2 (0.9%) had pneumothorax. There were no serious adverse events. Conclusion. Flexible bronchoscopy with appropriate patient selection and preprocedure planning is more efficacious in obtaining a diagnosis in peripheral lung lesions compared to historical data. This trial is registered with ClinicalTrials.gov Identifier: NCT01374542.

Endobronchial ultrasound (EBUS) and electromagnetic navigation bronchoscopy (ENB) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions. However, the role of combining these modalities to overcome each individual technique's limitations and, consequently, to further increase the diagnostic yield remains untested. A prospective randomized controlled trial involving three diagnostic arms: EBUS only, ENB only, and a combined procedure. All procedures were performed via flexible bronchoscopy and transbronchial forceps biopsies were obtained without fluoroscopic guidance. In the combined group, after electromagnetic navigation, the ultrasound probe was passed through an extended working channel to visualize the lesion. Biopsies were taken if ultrasound visualization showed that the extended working channel was within the target. Primary outcome was diagnostic yield. The reference \"gold standard\" was a surgical biopsy if bronchoscopic biopsy did not reveal a definite histological diagnosis compatible with the clinical presentation. Secondary outcomes were yields by size, lobar distribution, and lesion pathology. Complication rates were also documented. Of the 120 patients recruited, 118 had a definitive histological diagnosis and were included in the final analysis. The diagnostic yield of the combined procedure (88%) was greater than EBUS (69%) or ENB alone (59%; p = 0.02). The combined procedure's yield was independent of lesion size or lobar distribution. The pneumothorax rates ranged from 5 to 8%, with no significant differences between the groups. Combined EBUS and ENB improves the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising safety.