Majid, Adnan

Abstract 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).

Abstract Rationale Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method used to diagnose suspected mediastinal lymph nodes or masses. However, the accuracy of the diagnosis in patients with suspected lymphoma is unclear. Objectives To evaluate the diagnostic yield of EBUS-TBNA in patients with suspected lymphoma. Methods A literature search including EMBASE, MEDLINE, Cochrane Library, and Google Scholar was performed by two reviewers. Included articles were evaluated using the QUADAS-2 tool and meta-analysis with a binary method model to compare the sensitivity, specificity, and summary receiver operating characteristic curve in patients with suspected lymphoma. Results Fourteen studies (425 participants) were pooled in the analysis. EBUS-TBNA reported an overall sensitivity of 66.2% (confidence interval [CI], 55–75.8%; I 2 = 76.2%) and specificity of 99.3% (CI, 98.2–99.7%; I 2 = 40%). For a new diagnosis of lymphoma, 13 studies including 243 participants reported sensitivity of 67.1% (CI, 54.2–77.9%; I 2 = 66.8%) and specificity of 99.6% (CI, 99.1–99.8%; I 2 = 0%). For recurrence of lymphoma, 11 studies including 166 participants reported sensitivity of 77.8% (CI, 68.1–85.2%; I 2 = 20.2%) and specificity of 99.5% (CI, 98.9–99.8%; I 2 = 0%). In the recurrence group, we found the use of rapid onsite examination, sample size, and flow cytometry increased the sensitivity of EBUS-TBNA, albeit a potential source of heterogeneity. Conclusions EBUS-TBNA has fair sensitivity for identifying a new diagnosis of lymphoma and fair to good sensitivity for identifying recurrence. Trial Registry PROSPERO CRD42018102773 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=102773.

Abstract Rationale Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) are commonly used for the diagnosis and mediastinal staging of lung cancer. Molecular markers are becoming increasingly important in patients with lung cancer to define targetable mutations suitable for personalized therapy, such as epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species proto-oncogene (ROS1), and programmed death-ligand 1 (PD-L1). Objectives To evaluate the adequacy of EBUS-TBNA–derived tissue for molecular analysis. Methods We searched the MEDLINE, LILACS, www.clinicaltrials.gov, and Epistemonikos databases through January 2018. Data Extraction Two independent reviewers performed the data search, quality assessment, and data extraction. We included both prospective and retrospective studies; risk of bias was evaluated using the ROBINS-I tool. The primary outcome was the proportion of adequate samples obtained by EBUS-TBNA for molecular analysis. Data were pooled by using a binary random effects model. Finally, evidence was rated by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Results A total of 33 studies including 2,698 participants were analyzed. In 28 studies that evaluated EBUS-TBNA for the identification of EGFR mutations, the pooled probability of obtaining a sufficient sample was 94.5% (95% confidence interval CI], 93.2–96.4%). For identification of ALK mutations, the pooled probability was 94.9% (95% CI, 89.4–98.8%). Finally, the prevalence of EGFR mutation was 15.8% (95% CI, 12.1–19.4%), and the prevalence of ALK mutation was 2.77% (95% CI, 1.0–4.8%). Data for ROS1 and PD-L1 mutations were not suitable for meta-analysis. Conclusions EBUS-TBNA has a high yield for molecular analysis of both EGFR and ALK mutations. However, the suitability of TBNA samples for next-generation sequencing is uncertain and should be explored in further studies. Clinical trial registered with PROSPERO (CRD42017080008).