Assessment of Advanced Diagnostic Bronchoscopy Outcomes for Peripheral Lung Lesions: A Delphi Consensus Definition of Diagnostic Yield and Recommendations for Patient-centered Study Designs. An Official American Thoracic Society/American College of Chest Physicians Research Statement.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Hypoxemia After Endobronchial Valve Deployment for Persistent Air Leak.

Endobronchial valves (EBVs) are a novel, minimally invasive bronchoscopic management technique for persistent air leaks that fail conservative therapy. Currently, 2 EBVs are available in the United States: the Spiration Valve System (Olympus, Redmond, WA) and the Zephyr Valve (Pulmonx, Redwood, CA). These valves are Food and Drug Administration-approved to reduce hyperinflation in emphysematous patients via bronchoscopic lung-volume reduction. However, more recently, the Spiration Valve has been granted a compassionate use exemption through the Food and Drug Administration for persistent postsurgical air leaks. Despite their popularity, these devices are not free from side effects. As an anesthesiologist, it is vital to be aware of the pathophysiology of this patient population so that safe and effective anesthetics may be provided during valve placement. Here, the use of EBVs is discussed in a patient who presented with a persistent air leak after a transthoracic needle aspiration that failed treatment due to persistent hypoxemia, warranting EBV removal.

Accuracy of a Robotic Endoscopic System in Cadaver Models with Simulated Tumor Targets: ACCESS Study.

BACKGROUND: Bronchoscopy for the diagnosis of peripheral pulmonary lesions continues to present clinical challenges, despite increasing experience using newer guided techniques. Robotic bronchoscopic platforms have been developed to potentially improve diagnostic yields. Previous studies in cadaver models have demonstrated increased reach into the lung periphery using robotic systems compared to similarly sized conventional bronchoscopes, although the clinical impact of additional reach is unclear. OBJECTIVES: This study was performed to evaluate the performance of a robotic bronchoscopic system's ability to reach and access artificial tumor targets simulating peripheral nodules in human cadaveric lungs. METHODS: Artificial tumor targets sized 10-30 mm in axial diameter were implanted into 8 human cadavers. CT scans were performed prior to procedures and all cadavers were intubated and mechanically ventilated. Electromagnetic navigation, radial probe endobronchial ultrasound, and fluoroscopy were used for all procedures. Robotic-assisted bronchoscopy was performed on each cadaver by an individual bronchoscopist to localize and biopsy peripheral lesions. RESULTS: Sixty-seven nodules were evaluated in 8 cadavers. The mean nodule size was 20.4 mm. The overall diagnostic yield was 65/67 (97%) and there was no statistical difference in diagnostic yield for lesions <20 mm compared with lesions measuring 21-30 mm, the presence of a concentric or eccentric radial ultrasound image, or relative distance from the pleura. CONCLUSIONS: The robotic bronchoscopic system was successful at biopsying 97% of peripheral pulmonary lesions 10-30 mm in size in human cadavers. These findings support further exploration of this technology in prospective clinical trials in live human subjects.

Safety and diagnostic performance of pulmonologists performing electromagnetic guided percutaneous lung biopsy (SPiNperc).

BACKGROUND AND OBJECTIVE: Percutaneous lung biopsy for diagnostic sampling of peripheral lung nodules has been widely performed by interventional radiologists under computed tomography (CT) guidance. New technology allows pulmonologists to perform percutaneous lung biopsies using electromagnetic (EM) guided technology. With the adoption of this new technique, the safety, feasibility and diagnostic yield need to be explored. The goal of this study was to determine the safety, feasibility and diagnostic yield of EM-guided percutaneous lung biopsy performed by pulmonologists. METHODS: We conducted a retrospective, multicentre study of 129 EM-guided percutaneous lung biopsies that occurred between November 2013 and March 2017. The study consisted of seven academic and three community medical centres. RESULTS: The average age of participants was 65.6 years, BMI was 26.3 and 50.4% were females. The majority of lesions were in the right upper lobe (37.2%) and left upper lobe (31.8%). The mean size of the lesions was 27.31 mm and the average distance from the pleura was 13.2 mm. Practitioners averaged two fine-needle aspirates and five core biopsies per procedure. There were 23 (17.8%) pneumothoraces, of which 16 (12.4%) received small-bore chest tube placement. The diagnostic yield of percutaneous lung biopsy was 73.7%. When EM-guided bronchoscopic sampling was also performed during the same procedural encounter, the overall diagnostic yield increased to 81.1%. CONCLUSION: In this large multicentred series, the use of EM guidance for percutaneous lung biopsies was safe and feasible, with acceptable diagnostic yield in the hands of pulmonologists. A prospective multicentre trial to validate these findings is currently underway (NCT03338049).

First-in-Human Use of a Hybrid Real-Time Ultrasound-Guided Fine-Needle Acquisition System for Peripheral Pulmonary Lesions: A Multicenter Pilot Study.

BACKGROUND: The ability to successfully perform a biopsy on pulmonary lesions by means of bronchoscopy varies widely due to anatomic and technological limitations. One major limitation is the lack of the ability to utilize real-time guidance during tissue sampling in the periphery. A novel system has been developed that enables real-time visualization and sampling of peripheral lesions by displaying an ultrasound image of the lesion and needle simultaneously. METHODS: We performed a multicenter, prospective pilot in patients with peripheral pulmonary lesions undergoing a clinically indicated bronchoscopy. The purpose of this study was to demonstrate the feasibility of visualizing, accessing, and obtaining specimens adequate for the cytology of lung lesions when using a novel hybrid real-time ultrasound-guided fine-needle aspiration system for peripheral pulmonary lesions. RESULTS: Twenty-three patients underwent bronchoscopic sampling of a peripheral pulmonary lesion with the study device. Mean lesion size was 3.6 (range 1.7-5.7) cm. Targeted lesions were located in all lobes of the lung. All lesions were successfully visualized and sampled under real-time visualization with specimens adequate for cytological evaluation. The needle was visualized in all lesions throughout targeting and sampling. There were no incidents of pneumothorax or moderate-to-severe bleeding. CONCLUSION: In this feasibility study, we report the first-in-human use of a continuous real-time endobronchial ultrasound guidance system to sample peripheral pulmonary lesions. Future generations of this device may improve usability and further studies are needed to determine the true diagnostic capabilities of this novel technique.

A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).

RATIONALE: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months. OBJECTIVES: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe. METHODS: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the ΔEBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores. MEASUREMENTS AND MAIN RESULTS: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a ΔFEV1 greater than or equal to 15% (P < 0.001). ΔEBV-SoC at 12 months was statistically and clinically significant: for FEV1, 0.106 L (P < 0.001); 6-minute-walk distance, +39.31 m (P = 0.002); and St. George's Respiratory Questionnaire, -7.05 points (P = 0.004). Significant ΔEBV-SoC were also observed in hyperinflation (residual volume, -522 ml; P < 0.001), modified Medical Research Council Dyspnea Scale (-0.8 points; P < 0.001), and the BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index (-1.2 points). Pneumothorax was the most common serious adverse event in the treatment period (procedure to 45 d), in 34/128 (26.6%) of EBV subjects. Four deaths occurred in the EBV group during this phase, and one each in the EBV and SoC groups between 46 days and 12 months. CONCLUSIONS: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe. Clinical trial registered with www.clinicaltrials.gov (NCT 01796392).

Guided Bronchoscopy for the Evaluation of Pulmonary Lesions: An Updated Meta-analysis.

BACKGROUND: Guided bronchoscopy is increasingly used to diagnose peripheral pulmonary lesions (PPLs). A meta-analysis published in 2012 demonstrated a pooled diagnostic yield of 70%; however, recent publications have documented yields as low as 40% and as high as 90%. RESEARCH QUESTION: Has the diagnostic yield of guided bronchoscopy in patients with PPLs improved over the past decade? STUDY DESIGN AND METHODS: A comprehensive search was performed of studies evaluating the diagnostic yield of differing bronchoscopic technologies used to reach PPLs. Study quality was assessed using the Quality assessment of diagnostic accuracy of studies (QUADAS-2) assessment tool. Number of lesions, type of technology used, overall diagnostic yield, and yield by size were extracted. Adverse events were recorded. Meta-analytic techniques were used to summarize findings across all studies. RESULTS: A total of 16,389 lesions from 126 studies were included. There was no significant difference in diagnostic yield prior to 2012 (39 studies; 3,052 lesions; yield 70.5%) vs after 2012 (87 studies; 13,535 lesions; yield 69.2%) (P > .05). Additionally, there was no significant difference in yield when comparing different technologies. Studies with low risk of overall bias had a lower diagnostic yield than those with high risk of bias (66% vs 71%, respectively; P = .018). Lesion size > 2 cm, presence of bronchus sign, and reports with a high prevalence of malignancy in the study population were associated with significantly higher diagnostic yield. Significant (P < .0001) between-study heterogeneity was also noted. INTERPRETATION: Despite the reported advances in bronchoscopic technology to diagnose PPLs, the diagnostic yield of guided bronchoscopy has not improved.

Reducing hospital admissions in patients with malignant pleural effusion: a quality improvement study.

BACKGROUND: Malignant pleural effusions (MPE) can cause severe dyspnoea leading to greater than 125 000 hospitalisations per year and cost greater than US$5 billion per year in the USA. Timely insertion of tunnelled pleural catheters (TPCs) is associated with fewer inpatient days and emergency department visits. We conducted a quality improvement study to reduce hospital admissions of patients with MPE. METHODS: Key stakeholders were surveyed, including thoracic and breast oncology teams, general pulmonary and interventional pulmonology (IP) to help identify the underlying causes and solutions. Our preintervention group consisted of 51 patients who underwent TPC placement by our IP service. In our first intervention, we reviewed referrals for MPE with the scheduling team and triaged them based on urgency. In the second intervention, we added a follow-up phone call 1 week after the initial thoracentesis performed by IP to assess for the recurrence of symptoms. RESULTS: Demographic and clinical characteristics were summarised across the three groups. We evaluated the rate ratio (RR) of admissions in the intervention groups with the multivariable Poisson regression and adjusted for race, gender and cancer. Compared with the preintervention group, intervention I showed trends towards a 41% lower hospital admission rate (RR 0.59 (0.33-1.07), p=0.11). Compared with the preintervention group, intervention II showed trends towards a 40% lower hospital admission rate (RR 0.6 (0.36-0.99), p=0.07). The results did not reach statistical significance. Exploratory comparisons in readmission rates between interventions I and II showed no difference (RR 0.89 (0.43-1.79), p=0.75). CONCLUSIONS: Both interventions showed trends toward fewer hospital readmissions although they were not statistically significant. Larger-size prospective studies would be needed to demonstrate the continued effectiveness of these interventions.

Ultrasound guided pulmonary artery catheter insertion: An alternative to fluoroscopic guidance.

Pulmonary artery catheters (PACs) can provide extremely valuable objective data in select patients. They are usually advanced by floatation of balloon tip along the normal blood flow and their placement is confirmed under pressure waveform guidance. Imaging such as fluoroscopy is often employed in low flow states and in cardiac catheterization suite to reduce the failure rate and time to wedge; but is not readily available at bedside. In critically ill patient, bedside insertion is feasible but can be complicated by repeated attempts to float the balloon tip through various cardiac chambers. Point of care ultrasound can be used to visualize the balloon tip of PAC inside the cardiac chambers alongside the confirmatory pressure waveform changes.

Correlation of Vital Signs and Depth of Sedation by Modified Observer's Assessment of Alertness and Sedation (MOAA/S) Scale in Bronchoscopy.

BACKGROUND: With complex, lengthy bronchoscopies, there is a need for safe, effective sedation. Most bronchoscopists strive for moderate sedation, though often difficult without compromising vital signs. The Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale is a validated 6-point scale assessing responsiveness of patients coinciding with the American Society of Anesthesiologists (ASA) continuum of sedation. It is commonly used in studying bronchoscopic sedation, but depth of sedation by MOAA/S and correlation with vital signs and adverse events has not been determined. METHODS: This study was a post hoc analysis of a prospective, double-blind, randomized trial evaluating the safety and efficacy of remimazolam. MOAA/S and corresponding vital signs were used to assess the effect of the level of sedation on vital signs and adverse events. RESULTS: A total of 23,341 MOAA/S scores from 431 patients were recorded. Older and higher ASA class patients spent more time in deeper sedation (MOAA/S 0 to 1) (6% vs. 2%, P=0.01). Oxygen saturation was equal in deep sedation (MOAA/S 0 to 1) (97±3%) compared with moderate sedation (96±3%) (P=0.11). Mean systolic and diastolic blood pressures were significantly lower when comparing MOAA/S 0 to 1 to MOAA/S 5 (systolic blood pressure: 126±19 vs. 147±24 mm Hg, P<0.01; diastolic blood pressure: 68±14 vs. 84±15 mm Hg, P<0.01). There was a nonsignificant trend towards lower heart rate at deep versus moderate sedation (84±15 vs. 94±18 beats/min, P=0.07). Respiratory rate was also comparable with moderate and deep sedation (17±5 vs. 18±6 beats/min, P=0.94). CONCLUSION: There was no clinically meaningful correlation between vital signs and depth of sedation assessed by MOAA/S. Older and higher ASA class patients spend more time in deeper sedation. However, when in deep sedation, there was no difference in vital signs other than a slightly increased incidence of clinically insignificant hypotension.

Robotic Bronchoscopy for Peripheral Pulmonary Lesions: A Multicenter Pilot and Feasibility Study (BENEFIT).

BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects. RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs? STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator. RESULTS: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred. INTERPRETATION: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov.

Association between Tunneled Pleural Catheter Use and Infection in Patients Immunosuppressed from Antineoplastic Therapy. A Multicenter Study.

Rationale: Patients with malignant or paramalignant pleural effusions (MPEs or PMPEs) may have tunneled pleural catheter (TPC) management withheld because of infection concerns from immunosuppression associated with antineoplastic therapy.Objectives: To determine the rate of infections related to TPC use and to determine the relationship to antineoplastic therapy, immune system competency, and overall survival (OS).Methods: We performed an international, multiinstitutional study of patients with MPEs or PMPEs undergoing TPC management from 2008 to 2016. Patients were stratified by whether or not they underwent antineoplastic therapy and/or whether or not they were immunocompromised. Cumulative incidence functions and multivariable competing risk regression analyses were performed to identify independent predictors of TPC-related infection. Kaplan-Meier method and multivariable Cox proportional hazards modeling were performed to examine for independent effects on OS.Results: A total of 1,408 TPCs were placed in 1,318 patients. Patients had a high frequency of overlap between antineoplastic therapy and an immunocompromised state (75-83%). No difference in the overall (6-7%), deep pleural (3-5%), or superficial (3-4%) TPC-related infection rates between subsets of patients stratified by antineoplastic therapy or immune status was observed. The median time to infection was 41 (interquartile range, 19-87) days after TPC insertion. Multivariable competing risk analyses demonstrated that longer TPC duration was associated with a higher risk of TPC-related infection (subdistribution hazard ratio, 1.03; 95% confidence interval [CI], 1.00-1.06; P = 0.028). Cox proportional hazards analysis showed antineoplastic therapy was associated with better OS (hazard ratio, 0.84; 95% CI, 0.73-0.97; P = 0.015).Conclusions: The risk of TPC-related infection does not appear to be increased by antineoplastic therapy use or an immunocompromised state. The overall rates of infection are low and comparable with those of immunocompetent patients with no relevant antineoplastic therapy. These results support TPC palliation for MPE or PMPEs regardless of plans for antineoplastic therapy.

Photodynamic therapy for the treatment of tracheobronchial papillomatosis: A multicenter experience.

OBJECTIVE: Recurrent respiratory papillomatosis (RRP) causes mucosal wart-like growths of the upper aerodigestive tract, which can undergo malignant transformation. These tumors are difficult to treat, often requiring repeated debridement, which can be associated with high morbidity. Photodynamic therapy (PDT) uses a photosensitizing medication and a topically applied light source to treat early stage endobronchial lung cancer. Most data on the use of PDT in RRP pertain to laryngeal disease. Our objective was to evaluate the effectiveness of PDT in treating RRP involving the lower respiratory tract. METHODS: We performed a retrospective multicenter review of adult patients who had a diagnosis of RRP involving the lower airways. We documented details of their disease, treatments, and outcomes. RESULTS: Eight patients underwent PDT for ten RRP lesions. Lesions were located in the trachea and more distal airways. Pathology showed malignant conversion to squamous cell carcinoma in half of the cases. All patient underwent debulking and multimodal treatment concurrently with PDT. Treatment was successful in seven patients with improvement in luminal size. Duration of disease-free recurrence ranged from 4 to 33 months. Five of eight patients have sustained ongoing treatment effect, ranging from 10 to 33 months. Most patient had improved quality of life (83 %) and a reduction in interventions (87 %) after PDT. Complications were minimal. CONCLUSION: PDT can be a safe and effective tool when treating RRP of the lower respiratory tract, including lesions with malignant transformation. A multimodal treatment approach is associated with improved outcomes. Further prospective studies are needed to fully determine its effectiveness.

An Evaluation of Diagnostic Yield From Bronchoscopy: The Impact of Clinical/Radiographic Factors, Procedure Type, and Degree of Suspicion for Cancer.

BACKGROUND: Bronchoscopy is commonly used to evaluate suspicious lung lesions. The yield is likely dependent on patient, radiographic, and bronchoscopic factors. Few studies have assessed these factors simultaneously while also including the preprocedure physician-assessed probability of cancer (pCA) when assessing yield. METHODS: This study is a secondary data analysis from a prospective multicenter trial. Diagnostic yield of standard bronchoscopy with biopsy ± fluoroscopy, endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA), electromagnetic navigation, and combination bronchoscopies was assessed. Definitions for diagnostic and nondiagnostic bronchoscopies were rigorously predefined. The association of diagnostic yield with individual variables was examined by using univariate and multivariate logistic regression analyses where appropriate. RESULTS: A total of 687 patients were included from 28 sites. Overall diagnostic yield was 69%; 80% for EBUS, 55% for bronchoscopy with biopsy ± fluoroscopy, 57% for electromagnetic navigation, and 74% for combination procedures (P < .001). Patients with larger, central lesions with adenopathy were significantly more likely to undergo a diagnostic bronchoscopy. Patients with pCA < 10% and 10% to 60% had lower yields (44% and 42%, respectively), whereas pCA > 60% yielded a positive result in 77% (P < .001). In multivariate logistic regression, the use of EBUS-TBNA, larger sized lesions, and central location were significantly associated with a diagnostic bronchoscopy. Seventeen percent of those with a malignant diagnosis and 28% of those with a benign diagnosis required secondary procedures to establish a diagnosis. CONCLUSIONS: This study is the first to assess the yield of bronchoscopy according to physician-assessed pCA in a large, prospective multicenter trial. The yield of bronchoscopy varied greatly according to physician suspicion that cancer is present, the patients' clinical/radiographic features, and the type of procedure performed. Of the procedures performed, EBUS-TBNA was the most likely to provide a diagnosis.

Assessment of Ergonomic Strain and Positioning During Bronchoscopic Procedures: A Feasibility Study.

BACKGROUND: Poor ergonomics place health care workers at risk for work-related overuse injuries. Repetitive and prolonged hand maneuvers, such as those performed during endoscopic procedures, may lead to musculoskeletal complaints and work-related injuries. However, the prevalence of health care-related work injuries among physicians is thought to be underreported and there is a paucity of literature investigating the impact of ergonomic strain on bronchoscopy. We designed a feasibility study to explore the differences in ergonomic strain and muscle activity of bronchoscopists. MATERIALS AND METHODS: A prospective study of bronchoscopic procedures was performed in a simulated environment. Preselected target areas were identified and airway sampling was performed with real-time ergonomic assessment utilizing electromyogram (EMG), grip strength, and musculoskeletal use and motion analysis. RESULTS: Procedural data was obtained for all procedures (78 bronchoscopies by 13 subjects) for both ergonomic and EMG scores. Experienced bronchoscopists demonstrated less EMG burden (P=0.007) and improved ergonomic positioning (P=0.007) during bronchoscopy when compared with less experienced bronchoscopists. Procedures performed with rotational-head bronchoscopes trended toward improved ergonomics (P=0.15) and lower EMG scores (P=0.88). A significant improvement in ergonomic scores was seen with the rotational-head bronchoscope when targeting the left upper lobe (P=0.036). CONCLUSION: Poor ergonomic positioning and excessive muscle strain appear present within bronchoscopy procedures but may be improved in those with more bronchoscopy experience. Technological advances in bronchoscope design may also have the potential to improve procedural ergonomics. Additional prospective studies are warranted to define the long-term impact on bronchoscopic ergonomics.

Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies: Guideline From the College of American Pathologists in Collaboration With the American College of Chest Physicians, Association for Molecular Pathology, American Society of Cytopathology, American Thoracic Society, Pulmonary Pathology Society, Papanicolaou Society of Cytopathology, Society of Interventional Radiology, and Society of Thoracic Radiology.

CONTEXT.­: The need for appropriate specimen use for ancillary testing has become more commonplace in the practice of pathology. This, coupled with improvements in technology, often provides less invasive methods of testing, but presents new challenges to appropriate specimen collection and handling of these small specimens, including thoracic small biopsy and cytology samples. OBJECTIVE.­: To develop a clinical practice guideline including recommendations on how to obtain, handle, and process thoracic small biopsy and cytology tissue specimens for diagnostic testing and ancillary studies. METHODS.­: The College of American Pathologists convened an expert panel to perform a systematic review of the literature and develop recommendations. Core needle biopsy, touch preparation, fine-needle aspiration, and effusion specimens with thoracic diseases including malignancy, granulomatous process/sarcoidosis, and infection (eg, tuberculosis) were deemed within scope. Ancillary studies included immunohistochemistry and immunocytochemistry, fluorescence in situ hybridization, mutational analysis, flow cytometry, cytogenetics, and microbiologic studies routinely performed in the clinical pathology laboratory. The use of rapid on-site evaluation was also covered. RESULTS.­: Sixteen guideline statements were developed to assist clinicians and pathologists in collecting and processing thoracic small biopsy and cytology tissue samples. CONCLUSIONS.­: Based on the systematic review and expert panel consensus, thoracic small specimens can be handled and processed to perform downstream testing (eg, molecular markers, immunohistochemical biomarkers), core needle and fine-needle techniques can provide appropriate cytologic and histologic specimens for ancillary studies, and rapid on-site cytologic evaluation remains helpful in appropriate triage, handling, and processing of specimens.

A Pilot Study of Simulation Training in Difficult Bag Mask Ventilation Using a Computerized Patient Simulator.

OBJECTIVE: Bag mask ventilation (BMV) is fundamental to airway management. Simulation is effective in airway management training, but its effectiveness for difficult BMV training is less clear. We evaluated the difference between type of training (simulation vs on patients) and the pass rate on a post-test on patients. DESIGN: A single center pilot study was performed with 32 medical students randomized to participate in difficult BMV training on simulators or patients. Pre- and post-training tests on the simulator and on patients were recorded. Surveys of trainee confidence level were collected. The primary goal was to estimate the difference between type of training (simulation vs on patients) and the pass rate on the post-test on patients with an improvement of 10% or more in passing rate considered as a meaningful improvement. Secondary outcomes included whether or not participants passed the simulator post-test, post-test on patient confidence, and pre- and post-test confidence. MEASUREMENTS AND MAIN RESULTS: Participants trained on the simulator had 13% higher passing rate on the post-test on patients compared to participants trained on patients (88% vs 75%). In addition, subjects that passed the simulator post-test had 11 times the odds of passing a post-test on patients relative to subjects that did not pass the simulator post-test (P = 0.023, odds ratio = 11.0, 95% confidence interval [CI] = 1.48-81.6). Post-training confidence levels were higher among those who passed the simulator pre-test and post-test and received simulator training. CONCLUSIONS: Simulation training for difficult BMV led to a higher passing rate on a post-test on patients compared to those trained on patients. This finding will need to be confirmed in larger randomized controlled trials. Successfully completing difficult BMV training on a simulator with a passing grade correlated with passing a test on difficult BMV on patients.

Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy.

BACKGROUND: While the complexity of flexible bronchoscopy has increased, standard options for moderate sedation medications have not changed in three decades. There is a need to improve moderate sedation while maintaining safety. Remimazolam was developed to address shortcomings of current sedation strategies. METHODS: A prospective, double-blind, randomized, multicenter, parallel group trial was performed at 30 US sites. The efficacy and safety of remimazolam for sedation during flexible bronchoscopy were compared with placebo and open-label midazolam. RESULTS: The success rates were 80.6% in the remimazolam arm, 4.8% in the placebo arm (P < .0001), and 32.9% in the midazolam arm. Bronchoscopy was started sooner in the remimazolam arm (mean, 6.4 ± 5.82 min) compared with placebo (17.2 ± 4.15 min; P < .0001) and midazolam (16.3 ± 8.60 min). Time to full alertness after the end of bronchoscopy was significantly shorter in patients treated with remimazolam (median, 6.0 min; 95% CI, 5.2-7.1) compared with those treated with placebo (13.6 min; 95% CI, 8.1-24.0; P = .0001) and midazolam (12.0 min; 95% CI, 5.0-15.0). Remimazolam registered superior restoration of neuropsychiatric function compared with placebo and midazolam. Safety was comparable among all three arms, and 5.6% of the patients in the remimazolam group had serious treatment-emergent adverse events as compared with 6.8% in the placebo group. CONCLUSIONS: Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy. In an exploratory analysis, it demonstrated a shorter onset of action and faster neuropsychiatric recovery than midazolam.

Common problems in critically ill obstetric patients, with an emphasis on pharmacotherapy.

Pharmacological treatment of critically ill obstetric patients can be especially challenging due to the complexity of caring for 2 patients, with a paucity of research to support practice. This review will provide practitioners with primary recommendations for management of the critical illnesses most commonly encountered in pregnancy and will discuss the scientific and clinical merit of these recommendations.