Transbronchial Lung Cryobiopsy and Surgical Lung Biopsy: A Prospective Multi-Centre Agreement Clinical Trial (CAN-ICE).

Rationale: Transbronchial cryobiopsy (TBCB) for the diagnosis of interstitial lung disease (ILD) has shown promising results, but prospective studies with matched surgical lung biopsy (SLB) have yielded conflicting results. Objectives: We aimed to assess within- and between-center diagnostic agreement between TBCB and SLB at both the histopathologic and multidisciplinary discussion (MDD) levels in patients with diffuse ILD. Methods: In a multicenter prospective study, we performed matched TBCB and SLB in patients referred for SLB. After a blinded review by three pulmonary pathologists, all cases were reviewed by three independent ILD teams in an MDD. MDD was performed first with TBCB, then with SLB in a second session. Within-center and between-center diagnostic agreement was evaluated using percentages and correlation coefficients. Measurements and Main Results: Twenty patients were recruited and underwent contemporaneous TBCB and SLB. Within-center diagnostic agreement between TBCB-MDD and SLB-MDD was reached in 37 of the 60 (61.7%) paired observations, resulting in a Cohen's κ value of 0.46 (95% confidence interval [CI], 0.29-0.63). Diagnostic agreement increased among high-confidence or definitive diagnoses on TBCB-MDD (21 of 29 [72.4%]), but not significantly, and was more likely among cases with SLB-MDD diagnoses of idiopathic pulmonary fibrosis than fibrotic hypersensitivity pneumonitis (13 of 16 [81.2%] vs. 16 of 31 [51.6%]; P = 0.047). Between-center agreement for cases was markedly higher for SLB-MDD (κ = 0.71 [95% CI, 0.52-0.89]) than TBCB-MDD (κ = 0.29 [95% CI, 0.09-0.49]). Conclusions: This study demonstrated moderate TBCB-MDD and SLB-MDD diagnostic agreement for ILD, while between-center agreement was fair for TBCB-MDD and substantial for SLB-MDD. Clinical trial registered with www.clinicaltrials.gov (NCT02235779).

Predictors of Episode-of-Care Costs for Ankle Fractures.

Ankle fractures are one of the most resource-consuming traumatic orthopedic injuries. Few studies have successfully evaluated the episode-of-care costs (EOCC) of common traumatic orthopedic injuries. The objective of this study was to determine the EOCC associated with the surgical management of ankle fractures. A retrospective cohort study of 105 consecutive patients who underwent open reduction internal fixation of an isolated ankle fracture at a Canadian Level-1 trauma center was conducted. Episode-of-care costs were generated using an activity-based costing framework. The median global episode-of-care cost for ankle fracture surgeries performed at the studied institution was $3,487 CAD [IQR 880] ($2,685 USD [IQR 616]). Patients aged 60 to 90 years had a significantly higher median EOCC than younger patients (p = .01). Supination-adduction injuries had a significantly higher median EOCC than other injury patterns (p = .01). The median EOCC for patients who underwent surgery within 10 days of their injury ($3,347 CAD [582], $2,577 USD [448]) was significantly lower than the cost for patients who had their surgery delayed 10 days or more after the injury ($3,634 CAD [776], $2,798 USD [598]) (p = .03). Patient sex, anesthesia type, ASA score and surgeon's fellowship training did not affect the EOCC. This study provides valuable data on predictors of EOCC in the surgical management of ankle fractures. Delaying simple ankle fracture cases due to operating time constraints can increase the total cost and burden of these fractures on the healthcare system. In addition, this study provides a framework for future episode-of-care cost analysis studies in orthopedic surgery.

Outcomes Following Surgical Lung Biopsy for Interstitial Lung Diseases: A Monocenter Experience.

BACKGROUND: Surgical lung biopsy (SLB) is considered in the investigation of interstitial lung diseases (ILDs) when a complete clinical evaluation and a multidisciplinary discussion (MDD) do not allow the clinician to make a confident diagnosis. Owing to the risk of the procedure, an appropriate assessment of the risk/benefit ratio prior to the intervention is recommended. We aimed to assess the postoperative outcomes and diagnostic yield of SLB for the investigation of ILD in a tertiary care institution. METHODS: We conducted a retrospective cohort study of consecutive subjects who underwent a SLB for the investigation of ILD in our center from 2009 to 2020. The postoperative mortality and complications rates as well as the diagnostic yield of the procedure were assessed. RESULTS: Of the 1,805 patients newly investigated for ILD in our center from 2009 to 2020, 71 (3.93%) underwent a SLB. At days 30 and 90, the mortality rates were 0 and 2.8%, whereas 4.3 and 7.6% patients experienced an acute ILD exacerbation, respectively. In addition, 4 (5.8%) patients experienced infectious complications and 5 (7.0%) presented prolonged air leaks (all within 30 days). A definite pathological diagnosis was made in 47 (66.2%) patients. Following postoperative MDD, a confident diagnosis was made in 61 patients (85.9%) and resulted in a change of therapy in 49 (69.0%) patients. CONCLUSION: SLB for the diagnosis of unclassifiable ILDs is associated with low mortality but significant morbidity. However, it results in a confident diagnosis and a change in therapy in the majority of patients.

Tracking the rise of United States foreign military training: IMTAD-USA, a new dataset and research agenda.

Training other countries' armed forces is a go-to foreign policy tool for the United States and other states. A growing literature explores the effects of military training, but researchers lack detailed data on training activities. To assess the origins and consequences of military training, as well as changing patterns over time, this project provides a new, global dataset of US foreign military training. This article describes the scope of the data along with the variables collected, coding procedures, and spatial and temporal patterns. We demonstrate the added value of the data in their much greater coverage of training activities, showing differences from both existing datasets and aggregate foreign military aid data. Reanalyzing prior research findings linking US foreign military training to the risk of coups d'état in recipient states, we find that this effect is limited to a single US program representing a small fraction of overall US training activities. The data show comprehensively how the United States attempts to influence partner military forces in a wide variety of ways and suggest new avenues of research.

Trial marketing in the Pan-Canadian Early Detection of Lung Cancer Study.

BACKGROUND: Recruitment to clinical trials is suboptimal, increasing costs, and delaying the potential implementation of clinical advances. Among other barriers, the lack of marketing experience among trialists may limit recruitment. In this observational study, in the context of the Pan-Canadian Early Detection of Lung Cancer Trial, we assessed the value of a motivational survey of study participants in planning a tailored advertising campaign and analysed the value of individual components of advertising in generating telephone calls to the study and recruited subjects. METHODS: The Pan-Canadian Early Detection of Lung Cancer Trial was a single arm study assessing risk modelling for lung cancer screening by low-dose computed tomography scan and autofluorescence bronchoscopy. Individuals were recruited to eight sites across Canada without a central marketing plan. On contact with the study, individuals reported how they heard about the study according to a predefined list. One site, the Juravinski Cancer Centre, worked with a marketing expert to develop a survey to assess participant motivations, source of study awareness, and personal habits. The survey was used to develop a media campaign for recruitment. Media events were collected from all sites. The primary analysis assessed the number of telephone contacts and recruited subjects associated with various media factors. Individual print media characteristics were assessed for their effect on recruitment. RESULTS: At all sites, 7059 individuals contacted the study, and 2537 were eligible and recruited. Among 52 individuals completing the Juravinski Cancer Centre survey, motivation included concern for personal risk of lung cancer (71%), followed by desire to contribute to a cure (67%), followed by personal knowledge of a person with lung cancer (50%). Most reported hearing of the study from the newspaper (58%) despite no print ad yet being distributed. With survey input, a newsprint campaign was executed. The number of media events varied by site (median: 13, range: 3-28). Among all recruits, 56.4% reported referral by newspaper followed by family/friend (14%). Telephone contacts and recruited subjects per event varied significantly by site, while unpaid media events appeared superior to paid events. Print media characteristics associated with increased telephone contacts and recruitment included use of a rational appeal (vs a mixed rational-emotional), less use of white space, and larger headline font. CONCLUSION: A survey of trial candidates provides useful information regarding personal motivation, media use, and lifestyle. Unpaid media events appear superior in generating recruitment, while print media may be superior to radio and television in selecting eligible recruits. The utility of individual print media characteristics appears to differ from the commercial advertising literature. Further research on marketing in clinical trials is encouraged to improve recruitment ( ClinicalTrials.gov registration: NCT00751660, https://clinicaltrials.gov/ct2/show/NCT00751660 ).

A Rare Complication: Development of an Aspergilloma after Endobronchial Coil Placement in a COPD Patient.

Endobronchial coils are a relatively novel endoscopic lung volume reduction modality that aims to increase functional capacity in chronic obstructive pulmonary disease (COPD) patients. Two major trials have studied the safety and efficacy of this therapy, but long-term safety has not been studied. Adverse events reported are mainly periprocedural pneumothoraces and early bacterial infectious complications. We report the case of a patient with severe emphysema (Global Initiative for Chronic Obstructive Lung Disease stage IV COPD) who developed endobronchial coil-associated aspergillomas 3 years after coil placement.

Improving Lung Function in Severe Heterogenous Emphysema with the Spiration Valve System (EMPROVE). A Multicenter, Open-Label Randomized Controlled Clinical Trial.

Rationale: Less invasive, nonsurgical approaches are needed to treat severe emphysema.Objectives: To evaluate the effectiveness and safety of the Spiration Valve System (SVS) versus optimal medical management.Methods: In this multicenter, open-label, randomized, controlled trial, subjects aged 40 years or older with severe, heterogeneous emphysema were randomized 2:1 to SVS with medical management (treatment) or medical management alone (control).Measurements and Main Results: The primary efficacy outcome was the difference in mean FEV1 from baseline to 6 months. Secondary effectiveness outcomes included: difference in FEV1 responder rates, target lobe volume reduction, hyperinflation, health status, dyspnea, and exercise capacity. The primary safety outcome was the incidence of composite thoracic serious adverse events. All analyses were conducted by determining the 95% Bayesian credible intervals (BCIs) for the difference between treatment and control arms. Between October 2013 and May 2017, 172 participants (53.5% male; mean age, 67.4 yr) were randomized to treatment (n = 113) or control (n = 59). Mean FEV1 showed statistically significant improvements between the treatment and control groups-between-group difference at 6 and 12 months, respectively, of 0.101 L (95% BCI, 0.060-0.141) and 0.099 L (95% BCI, 0.048-0.151). At 6 months, the treatment group had statistically significant improvements in all secondary endpoints except 6-minute-walk distance. Composite thoracic serious adverse event incidence through 6 months was greater in the treatment group (31.0% vs. 11.9%), primarily due to a 12.4% incidence of serious pneumothorax.Conclusions: In patients with severe heterogeneous emphysema, the SVS shows significant improvement in multiple efficacy outcomes, with an acceptable safety profile.Clinical trial registered with www.clinicaltrials.gov (NCT01812447).

Chronic obstructive pulmonary disease prevalence and prediction in a high-risk lung cancer screening population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition sharing risk factors with lung cancer. Lung cancer screening may provide an opportunity to improve COPD diagnosis. Using Pan-Canadian Early Detection of Lung Cancer (PanCan) study data, the present study sought to determine the following: 1) What is the prevalence of COPD in a lung cancer screening population? 2) Can a model based on clinical and screening low-dose CT scan data predict the likelihood of COPD? METHODS: The single arm PanCan study recruited current or former smokers age 50-75 who had a calculated risk of lung cancer of at least 2% over 6 years. A baseline health questionnaire, spirometry, and low-dose CT scan were performed. CT scans were assessed by a radiologist for extent and distribution of emphysema. With spirometry as the gold standard, logistic regression was used to assess factors associated with COPD. RESULTS: Among 2514 recruited subjects, 1136 (45.2%) met spirometry criteria for COPD, including 833 of 1987 (41.9%) of those with no prior diagnosis, 53.8% of whom had moderate or worse disease. In a multivariate model, age, current smoking status, number of pack-years, presence of dyspnea, wheeze, participation in a high-risk occupation, and emphysema extent on LDCT were all statistically associated with COPD, while the overall model had poor discrimination (c-statistic = 0.627 (95% CI of 0.607 to 0.650). The lowest and the highest risk decile in the model predicted COPD risk of 27.4 and 65.3%. CONCLUSIONS: COPD had a high prevalence in a lung cancer screening population. While a risk model had poor discrimination, all deciles of risk had a high prevalence of COPD, and spirometry could be considered as an additional test in lung cancer screening programs. TRIAL REGISTRATION: (Clinical Trial Registration: ClinicalTrials.gov, number NCT00751660 , registered September 12, 2008).

Simplified Criteria Using Pleural Fluid Cholesterol and Lactate Dehydrogenase to Distinguish between Exudative and Transudative Pleural Effusions.

BACKGROUND: An important part of the investigation of pleural effusion is the identification of markers that help separate exudate from transudate. OBJECTIVES: The purposes of this study were to compare the accuracy of published and new sets of criteria to distinguish between exudative and transudative pleural effusions, and to determine whether serum biochemical analysis is necessary. METHODS: An externally validated cohort study was performed. Pleural effusions were determined to be transudative or exudative on the basis of an assessment of the medical record by two clinicians blinded to biochemical results. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating characteristic curve were determined for each proposed combination of criteria. RESULTS: Pleural fluid analysis was available for 311 thoracenteses in the main cohort and for 112 thoracenteses in the validation cohort. The best sensitivity (97% [95% CI 94-99]) and negative likelihood ratio (0.04 [95% CI 0.02-0.08]) for identifying exudative effusions were observed with criteria combining pleural fluid lactate dehydrogenase greater than 0.6 the upper limit of normal serum lactate dehydrogenase and pleural fluid cholesterol greater than 1.04 mmol/L (40 mg/dL). The overall diagnostic accuracy was similar to Light's criteria. Findings were similar in the validation cohort. CONCLUSIONS: Our proposed criteria using simultaneously pleural fluid lactate dehydrogenase and pleural fluid cholesterol can identify an exudate with a sensitivity and an overall diagnostic accuracy similar to Light's criteria. It avoids simultaneous blood sampling, thus reducing patient discomfort and potential costs.

Participant selection for lung cancer screening by risk modelling (the Pan-Canadian Early Detection of Lung Cancer [PanCan] study): a single-arm, prospective study.

BACKGROUND: Results from retrospective studies indicate that selecting individuals for low-dose CT lung cancer screening on the basis of a highly predictive risk model is superior to using criteria similar to those used in the National Lung Screening Trial (NLST; age, pack-year, and smoking quit-time). We designed the Pan-Canadian Early Detection of Lung Cancer (PanCan) study to assess the efficacy of a risk prediction model to select candidates for lung cancer screening, with the aim of determining whether this approach could better detect patients with early, potentially curable, lung cancer. METHODS: We did this single-arm, prospective study in eight centres across Canada. We recruited participants aged 50-75 years, who had smoked at some point in their life (ever-smokers), and who did not have a self-reported history of lung cancer. Participants had at least a 2% 6-year risk of lung cancer as estimated by the PanCan model, a precursor to the validated PLCOm2012 model. Risk variables in the model were age, smoking duration, pack-years, family history of lung cancer, education level, body-mass index, chest x-ray in the past 3 years, and history of chronic obstructive pulmonary disease. Individuals were screened with low-dose CT at baseline (T0), and at 1 (T1) and 4 (T4) years post-baseline. The primary outcome of the study was incidence of lung cancer. This study is registered with ClinicalTrials.gov, number NCT00751660. FINDINGS: 7059 queries came into the study coordinating centre and were screened for PanCan risk. 15 were duplicates, so 7044 participants were considered for enrolment. Between Sept 24, 2008, and Dec 17, 2010, we recruited and enrolled 2537 eligible ever-smokers. After a median follow-up of 5·5 years (IQR 3·2-6·1), 172 lung cancers were diagnosed in 164 individuals (cumulative incidence 0·065 [95% CI 0·055-0·075], incidence rate 138·1 per 10 000 person-years [117·8-160·9]). There were ten interval lung cancers (6% of lung cancers and 6% of individuals with cancer): one diagnosed between T0 and T1, and nine between T1 and T4. Cumulative incidence was significantly higher than that observed in NLST (4·0%; p<0·0001). Compared with 593 (57%) of 1040 lung cancers observed in NLST, 133 (77%) of 172 lung cancers in the PanCan Study were early stage (I or II; p<0·0001). INTERPRETATION: The PanCan model was effective in identifying individuals who were subsequently diagnosed with early, potentially curable, lung cancer. The incidence of cancers detected and the proportion of early stage cancers in the screened population was higher than observed in previous studies. This approach should be considered for adoption in lung cancer screening programmes. FUNDING: Terry Fox Research Institute and Canadian Partnership Against Cancer.

Probability of cancer in pulmonary nodules detected on first screening CT.

BACKGROUND: Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography (CT) are the definition of a positive result and the management of lung nodules detected on the scans. We conducted a population-based prospective study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up. METHODS: We analyzed data from two cohorts of participants undergoing low-dose CT screening. The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study (PanCan). The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency (BCCA), sponsored by the U.S. National Cancer Institute. The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked. Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer. RESULTS: In the PanCan data set, 1871 persons had 7008 nodules, of which 102 were malignant, and in the BCCA data set, 1090 persons had 5021 nodules, of which 42 were malignant. Among persons with nodules, the rates of cancer in the two data sets were 5.5% and 3.7%, respectively. Predictors of cancer in the model included older age, female sex, family history of lung cancer, emphysema, larger nodule size, location of the nodule in the upper lobe, part-solid nodule type, lower nodule count, and spiculation. Our final parsimonious and full models showed excellent discrimination and calibration, with areas under the receiver-operating-characteristic curve of more than 0.90, even for nodules that were 10 mm or smaller in the validation set. CONCLUSIONS: Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant. (Funded by the Terry Fox Research Institute and others; ClinicalTrials.gov number, NCT00751660.).

Plasma pro-surfactant protein B and lung function decline in smokers.

Plasma pro-surfactant protein B (pro-SFTPB) levels have recently been shown to predict the development of lung cancer in current and ex-smokers, but the ability of pro-SFTPB to predict measures of chronic obstructive pulmonary disease (COPD) severity is unknown. We evaluated the performance characteristics of pro-SFTPB as a biomarker of lung function decline in a population of current and ex-smokers. Plasma pro-SFTPB levels were measured in 2503 current and ex-smokers enrolled in the Pan-Canadian Early Detection of Lung Cancer Study. Linear regression was performed to determine the relationship of pro-SFTPB levels to changes in forced expiratory volume in 1 s (FEV1) over a 2-year period as well as to baseline FEV1 and the burden of emphysema observed in computed tomography (CT) scans. Plasma pro-SFTPB levels were inversely related to both FEV1 % predicted (p=0.024) and FEV1/forced vital capacity (FVC) (p<0.001), and were positively related to the burden of emphysema on CT scans (p<0.001). Higher plasma pro-SFTPB levels were also associated with a more rapid decline in FEV1 at 1 year (p=0.024) and over 2 years of follow-up (p=0.004). Higher plasma pro-SFTPB levels are associated with increased severity of airflow limitation and accelerated decline in lung function. Pro-SFTPB is a promising biomarker for COPD severity and progression.

Feasibility of using the nasal route for linear endobronchial ultrasound.

PURPOSE: Linear endobronchial ultrasound (EBUS) is a safe and accurate diagnostic test for mediastinal adenopathy. Its feasibility through the nasal route has not been reported. The objective of this study was to document the feasibility of linear EBUS using the nasal route and compare its accuracy and safety with the oral route. METHODS: A retrospective analysis of consecutive subjects who underwent an EBUS procedure under conscious sedation at our center was conducted. Nasal insertion of the bronchoscope was attempted in all subjects; the oral route was used in case of failed nasal insertion. Characteristics of the procedure and the diagnostic accuracy of EBUS were compared between the two insertion routes. RESULTS: From May to October 2012, 209 subjects underwent an EBUS. Complete data were available for 196 subjects. Nasal insertion of the EBUS bronchoscope was possible in 73.5 %. There was no difference between the two insertion routes in the location and number of stations sampled per subject. Procedure duration and complications (epistaxis, bronchial bleeding, desaturation, and pneumothorax) were similar between the two groups (2.1 % for nasal group vs 1.9 % for oral group). Minor epistaxis occurred in one subject in the nasal group. Comparing the nasal and oral groups, rates of adequate specimens were similar (90.5 vs 88.9 %, respectively; p = 0.68), and proportions of diagnostic specimens were not statistically different (51.4 vs 42.3 %, respectively; p = 0.26). CONCLUSION: Linear EBUS can be performed safely and with high accuracy via the nasal route. Controlled studies are required to determine which insertion route provides best patient comfort.

Bronchial Rheoplasty for Chronic Bronchitis: Results from a Canadian Feasibility Study with RheOx®.

Purpose: Chronic bronchitis (CB), a chronic obstructive pulmonary disease (COPD) phenotype defined by persistent mucus hypersecretion and cough, is associated with poor quality of life, exacerbations, and lung function impairment. Bronchial Rheoplasty (BR) delivers non-thermal pulsed electric fields to airway epithelium and submucosa. Preliminary studies demonstrated reduced airway goblet cell hyperplasia and symptom improvement in response to BR. This study aimed to further assess the safety and clinical feasibility of BR in the setting of CB. Patients and Methods: This 3-center, single-arm study evaluated the safety and feasibility of BR in Canadian patients. The major inclusion criteria were the sum of CAT first 2 questions (cough and mucus) ≥ 7 out of 10 and FEV1 ≥ 30% predicted. Right-sided airways were treated first; left, 1 month later. Serious adverse events (SAEs) were tabulated through 12 months. Outcomes were evaluated using the SGRQ and CAT. Results: Ten patients with CB were enrolled and followed for 12 months. The BR procedure was successful in all patients (mean age 69 ± 5.8 years, post-BD FEV1 77.1 ± 28.3, SGRQ 56.2 ± 8.8, CAT 25.4 ± 4.7). Only one SAE, a COPD exacerbation 13 days following the BR procedure, was considered device related. No additional SAEs occurred through 12 months, and 90% of the patients were CAT responders (≥ 2-point improvement) at 3 and 6 months. Similar results were observed in SGRQ. Conclusion: BR was safe and well-tolerated. Meaningful symptom improvement was observed through 12 months, suggesting BR may be a viable treatment option for patients with CB.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

Polygenic inheritance and its interplay with smoking history in predicting lung cancer diagnosis: a French-Canadian case-control cohort.

BACKGROUND: The most near-term clinical application of genome-wide association studies in lung cancer is a polygenic risk score (PRS). METHODS: A case-control dataset was generated consisting of 4002 lung cancer cases from the LORD project and 20,010 ethnically matched controls from CARTaGENE. A genome-wide PRS including >1.1 million genetic variants was derived and validated in UK Biobank (n = 5419 lung cancer cases). The predictive ability and diagnostic discrimination performance of the PRS was tested in LORD/CARTaGENE and benchmarked against previous PRSs from the literature. Stratified analyses were performed by smoking status and genetic risk groups defined as low (<20th percentile), intermediate (20-80th percentile) and high (>80th percentile) PRS. FINDINGS: The phenotypic variance explained and the effect size of the genome-wide PRS numerically outperformed previous PRSs. Individuals with high genetic risk had a 2-fold odds of lung cancer compared to low genetic risk. The PRS was an independent predictor of lung cancer beyond conventional clinical risk factors, but its diagnostic discrimination performance was incremental in an integrated risk model. Smoking increased the odds of lung cancer by 7.7-fold in low genetic risk and by 11.3-fold in high genetic risk. Smoking with high genetic risk was associated with a 17-fold increase in the odds of lung cancer compared to individuals who never smoked and with low genetic risk. INTERPRETATION: Individuals at low genetic risk are not protected against the smoking-related risk of lung cancer. The joint multiplicative effect of PRS and smoking increases the odds of lung cancer by nearly 20-fold. FUNDING: This work was supported by the CQDM and the IUCPQ Foundation owing to a generous donation from Mr. Normand Lord.

Diagnostic utility of peripheral endobronchial ultrasound with electromagnetic navigation bronchoscopy in peripheral lung nodules.

BACKGROUND AND OBJECTIVE: This study aimed to investigate the diagnostic utility of peripheral endobronchial ultrasound (pEBUS) followed by as-needed electromagnetic navigation bronchoscopy (ENB) for sampling peripheral lung nodules. METHODS: The study was a single-arm, prospective cohort study of patients with peripheral lung nodules. Peripheral lung lesion localization was initially performed using a pEBUS probe with guide sheath. If localization failed with pEBUS alone, ENB was used to help identify the lesion. Transbronchial biopsy, bronchial brush, transbronchial needle aspiration and bronchial washings were performed. RESULTS: Sixty patients were enrolled with average lesion size of 27 mm and mean pleural distance of 20 mm. Lesions were found with pEBUS alone in 75% of cases. The addition of ENB improved lesion localization to 93%. However, diagnostic yield for pEBUS alone and pEBUS with ENB were 43% and 50%, respectively. Factors predicting need for ENB use included smaller lesion size and absence of an air bronchus sign on computed tomography. CONCLUSIONS: ENB improves localization of lung lesions after unsuccessful pEBUS but is often not sufficient to ensure confirmation of a specific diagnosis. Technical improvements in sampling methods could improve the diagnostic yield.

Wait Times and Survival in Lung Cancer Patients across the Province of Quebec, Canada.

Lung cancer is the leading cause of cancer death worldwide, with a five-year survival of 22% in Canada. Guidelines recommend rapid evaluation of patients with suspected lung cancer, but the impact on survival remains unclear. We reviewed medical records of all patients with newly diagnosed lung cancer in four hospital networks across the province of Quebec, Canada, between 1 February and 30 April 2017. Patients were followed for 3 years. Wait times for diagnosis and treatment were collected, and survival analysis using a Cox regression model was conducted. We included 1309 patients, of whom 39% had stage IV non-small cell lung cancer (NSCLC). Median wait times were, in general, significantly shorter in patients with stage III-IV NSCLC or SCLC. Surgery was associated with delays compared to other types of treatments. Median survival was 12.9 (11.1-15.7) months. The multivariate survival model included age, female sex, performance status, histology and stage, treatment, and the time interval between diagnosis and treatment. Longer wait times had a slightly protective to neutral effect on survival, but this was not significant in the stage I-II NSCLC subgroup. Wait times for the diagnosis and treatment of lung cancer were generally within targets. The shorter wait times observed for advanced NSCLC and SCLC might indicate a tendency for clinicians to act quicker on sicker patients. This study did not demonstrate the detrimental effect of longer wait times on survival.

Malignant pleural mesothelioma: Comparison of surgery-based trimodality therapy to medical therapy at two tertiary academic institutions.

OBJECTIVES: Medical management based on palliative chemotherapy is currently the standard of care in malignant pleural mesothelioma (MPM). Median survival of 12-16 months has been reported with modern chemotherapy regimens with or without anti-angiogenic agents. Multimodality therapy incorporating cytoreductive surgery, systemic chemotherapy and radiotherapy has been offered for years to fit patients with early-stage disease, but its role remains debated. Our objective was to compare overall survival in patients offered multimodality therapy in a specialized clinic setting in London, UK to that of patients offered exclusively medical treatment at another academic institution in Quebec, Canada. MATERIALS AND METHODS: We retrospectively compared the survival rates of 2 separate cohorts of patients treated consecutively: Cohort 1 (n = 106) received multimodality therapy including systemic chemotherapy, extended pleurectomy/decortication (P/D) and prophylactic radiotherapy in London (United Kingdom) between 2009 and 2016, while Cohort 2 (n = 98) received medical treatment at the Quebec Heart and Lung Institute (Canada) during the same period. RESULTS: In Cohort 1, all patients but two completed trimodality therapy. In cohort 2, 51 % received palliative care only and 40 % received systemic chemotherapy. Median survival was 32 months vs 10 months in Cohort 1 and Cohort 2, respectively (hazard ratio with age, gender, pathology and TNM staging as covariates: 3.81; 95 % CI: 2.67-5.45; p < 0.0001). Similar results were obtained in sensitivity analyses, after excluding those who received best supportive care only and in a propensity score-matched analysis. CONCLUSION: Aggressive therapy of MPM using cancer-directed surgery, systemic chemotherapy and prophylactic radiotherapy may provide a significant survival benefit in selected patients.