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.
Electromagnetic navigation bronchoscopy (ENB) with biopsy under fluoroscopic guidance has enhanced the yield of flexible bronchoscopy in the diagnosis of peripheral lung lesions. However, the ...accuracy of ENB navigation suggests that the addition of fluoroscopy is redundant.
Data were prospectively collected to determine the yield of ENB without fluoroscopy in the diagnosis of peripheral lung lesions.
ENB was performed via flexible bronchoscopy (superDimension/Bronchus system; superDimension Inc; Plymouth, MN). Biopsy specimens were obtained through the extended working channel after navigation. Fluoroscopy was not utilized, but post-transbronchial biopsy chest radiographs were obtained to exclude pneumothorax. The primary end point was diagnostic yield, and the secondary end points were navigation accuracy, procedure duration, and safety. Analysis by lobar distribution was also performed to assess performance in different lobes of the lung.
Ninety-two peripheral lung lesions were biopsied in the 89 subjects. The diagnostic yield of ENB was 67%, which was independent of lesion size. Total procedure time ranged from 16.3 to 45.0 min (mean ± SD procedure time, 26.9 ± 6.5 min). The mean navigation error was 9 ± 6 mm (range, 1 to 31 mm). There were two incidences of pneumothorax for which no intervention was required. When analyzed by lobar distribution, there was a trend toward a higher ENB yield in diagnosing lesions in the right middle lobe (88%).
ENB can be used as a stand-alone bronchoscopic technique without compromising diagnostic yield or increasing the risk of pneumothorax. This may result in sizable timesaving and avoids radiation exposure.
•Upfront NGS is feasible and cost-effective in an EGFR mutant predominant population.•Characterizing the wider genomic profile may yield important information.•There was a high proportion with ...targetable alterations in the PD-L1 >50 % subgroup.
There is an expanding list of therapeutically relevant biomarkers for non-small cell lung cancer (NSCLC), and molecular profiling at diagnosis is paramount. Tissue attrition in scaling traditional single biomarker assays from small biopsies is an increasingly encountered problem. We sought to compare the performance of targeted next-generation sequencing (NGS) panels with traditional assays and correlate the mutational landscape with PD-L1 status in Singaporean patients.
We identified consecutive patients diagnosed between Jan 2016 to Sep 2017 with residual tissue after standard molecular testing. Tissue samples were tested using a targeted NGS panel for DNA alterations (29 selected genes including BRAF, EGFR, ERBB2 and TP53) and an RNA fusion panel (ALK, ROS1 and RET). PD-L1 immunohistochemistry was also performed. A cost-effectiveness analysis of NGS compared to standard molecular testing was conducted.
A total of 174 samples were evaluated: PD-L1 (n = 169), NGS DNA panel (n = 173) and RNA fusion (n = 119) testing. Median age was 68 years, 53 % were male, 58 % were never smokers, 85 % were Chinese, 66 % had stage IV disease and 95 % had adenocarcinoma histology. In patients profiled with NGS on DNA, EGFR (56 %), KRAS (14 %), BRAF (2 %) and ERBB2 (1 %) mutations were found. RNA fusion testing revealed fusions in ALK (6 %), RET (3 %) and ROS1 (1 %). Cost-effectiveness analysis demonstrated that compared to sequential testing in EGFR negative patients, upfront NGS testing would result in an additional 1 % of patients with actionable alterations for targeted therapy being identified without significant increases in testing cost or turnaround time.
This study demonstrates that even in an EGFR mutant predominant population, upfront NGS represents a feasible, cost-effective method of diagnostic molecular profiling compared with sequential testing strategies. Our results support the implementation of diagnostic NGS in non-squamous NSCLC in Asia to allow patients access to the most appropriate personalized therapy.
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.
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.
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%.
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.
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.
Detection of nonsmall cell lung cancer at the intraepithelial stage is believed to improve cure rates. New bronchoscopic technologies, including white light videobronchoscopy (WLB), autofluorescence ...imaging (AFI), and narrow band imaging (NBI), are aiming to diagnose airway neoplasia at a preinvasive stage.
To evaluate the diagnostic yields of NBI individually and in combination with WLB and AFI.
A 10-month review of patients who were referred for airway screening or surveillance. Patients were randomized as to the order of AFI and NBI examinations. The airway mucosa was graded endoscopically as “normal,” “abnormal,” “suspicious,” or “tumor.” All areas that were not normal were biopsied. Biopsies with a histologic grading of moderate to severe dysplasia or carcinoma in situ were considered positive for intraepithelial neoplasia.
Sixty-two patients with a mean age of 56.2 ± 9.8 years were studied. Five patients had invasive cancers and were excluded from the analysis. The remaining 57 cases had a 30% prevalence of intraepithelial neoplasia. The sensitivity of WLB was 0.18 and the specificity was 0.88. The relative sensitivities (compared with WLB) of AFI and NBI were 3.7 (p = 0.005) and 3.0 (p = 0.03), respectively. The relative specificities of AFI and NBI were 0.5 (p < 0.001) and 1.0 (p = 0.72), respectively. Combining AFI and NBI did not increase diagnostic yield significantly. The sequence of performing AFI and NBI did not impact findings.
NBI is an alternative to AFI in the detection of early lung cancers because it has a comparatively higher specificity without significantly compromising the sensitivity.
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.
ABSTRACT
Background and objective
Bronchial thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations and improving asthma control for patients with severe persistent asthma ...but it is also expensive. Evidence on its cost‐effectiveness is limited and inconclusive. In this study, we aim to evaluate the incremental cost‐effectiveness of BT combined with optimized asthma therapy (BT‐OAT) relative to OAT for difficult‐to‐treat and severe asthma patients in Singapore, and to provide a general framework for determining BT's cost‐effectiveness in other healthcare settings.
Methods
We developed a Markov model to estimate the costs and quality‐adjusted life years (QALYs) gained with BT‐OAT versus OAT from the societal and health system perspectives. The model was populated using Singapore‐specific costs and transition probabilities and utilities from the literature. Sensitivity analyses were conducted to identify the main factors determining cost‐effectiveness of BT‐OAT.
Results
BT‐OAT is not cost‐effective relative to OAT over a 5‐year time horizon with an incremental cost‐effectiveness ratio (ICER) of $US138 889 per QALY from the societal perspective and $US139 041 per QALY from the health system perspective. The cost‐effectiveness of BT‐OAT largely depends on a combination of the cost of the BT procedure and the cost of asthma‐related hospitalizations and emergency department (ED) visits.
Conclusion
Based on established thresholds for cost‐effectiveness, BT‐OAT is not cost‐effective compared with OAT in Singapore. Given its current clinical efficacy, BT‐OAT is most likely to be cost‐effective in a setting where the cost of BT procedure is low and costs of hospitalization and ED visits are high.
Bronchial thermoplasty (BT) combined with optimized asthma therapy (OAT) was not found cost‐effective compared with OAT alone in Singapore. It is most likely to be cost‐effective in a setting where the cost of BT procedure is low and costs of hospitalization and emergency department visits are high.
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.
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