Shape-sensing robotic-assisted bronchoscopy for pulmonary nodules: initial multicenter experience using the Ion™ Endoluminal System.

BACKGROUND: Traditional bronchoscopy provides limited approach to peripheral nodules. Shape-sensing robotic-assisted bronchoscopy (SSRAB, Ion™ Endoluminal System) is a new tool for minimally invasive peripheral nodule biopsy. We sought to answer the research question: Does SSRAB facilitate sampling of pulmonary nodules during bronchoscopists' initial experience? METHODS: The lead-in stage of a multicenter, single-arm, prospective evaluation of the Ion Endoluminal System (PRECIsE) is described. Enrolled subjects ≥ 18 years old had recent computed tomography evidence of one or more solid or semi-solid pulmonary nodules ≥ 1.0 to ≤ 3.5 cm in greatest dimension and in any part of the lung. Subjects were followed at 10- and 30-days post-procedure. This stage provided investigators and staff their first human experience with the SSRAB system; safety and procedure outcomes were analyzed descriptively. Neither diagnostic yield nor sensitivity for malignancy were assessed in this stage. Categorical variables are summarized by percentage; continuous variables are summarized by median/interquartile range (IQR). RESULTS: Sixty subjects were enrolled across 6 hospitals; 67 nodules were targeted for biopsy. Median axial, coronal and sagittal diameters were < 18 mm with a largest cardinal diameter of 20.0 mm. Most nodules were extraluminal and distance from the outer edge of the nodule to the pleura or nearest fissure was 4.0 mm (IQR: 0.0, 15.0). Median bronchial generation count to the target location was 7.0 (IQR: 6.0, 8.0). Procedure duration (catheter-in to catheter-out) was 66.5 min (IQR: 50.0, 85.5). Distance from the catheter tip to the closest edge of the virtual nodule was 7.0 mm (IQR: 2.0, 12.0). Biopsy completion was 97.0%. No pneumothorax or airway bleeding of any grade was reported. CONCLUSIONS: Bronchoscopists leveraged the Ion SSRAB's functionality to drive the catheter safely in close proximity of the virtual target and to obtain biopsies. This initial, multicenter experience is encouraging, suggesting that SSRAB may play a role in the management of pulmonary nodules. Clinical Trial Registration identifier and date NCT03893539; 28/03/2019.

Safety and Efficacy of the Tracheobronchial Bonastent: A Single-Center Case Series.

BACKGROUND: Tracheobronchial stents are widely used devices in interventional pulmonology; however, the current literature on the effectiveness and complication rates of the different types of stents is limited. OBJECTIVE: We report the largest case series of airway Bonastent placement and describe the efficacy and early (<30 days) and late (≥30 days) complication rates. METHODS: We performed a retrospective review of our prospectively collected database of patients who underwent therapeutic bronchoscopy with stent placement. All adult patients who had a tracheal/bronchial Bona-stent placed between July 1, 2017, and July 30, 2019, for any indication at our institution were included. The efficacy as well as intraoperative and short- and long-term complications of Bonastent placement were evaluated. RESULTS: Sixty Bonastents were placed in 50 patients. The etiology was malignant in 90% of the cases, while 2 patients had a tracheoesophageal fistula. All procedures were performed via rigid bronchoscopy. The most common location for stent placement was the bronchus intermedius, followed by the trachea, in 32 and 30% of the cases, respectively. Seventy percent of the patients (35/50) had improvement of respiratory symptoms within 30 days. Twenty-eight stents (48%) were removed at a mean of 74 days. Seventeen patients (34%) died within 30 days of stent placement. The overall complication rate was 54% (27/50 patients) at a mean follow-up of 111 days. The stent-related complication rate was 23.3% (14/60 cases) within <30 days and 53% (18/34 cases) at ≥30 days. CONCLUSIONS: The tracheobronchial Bonastent is effective for the treatment of patients with central airway obstruction and tracheoesophageal fistulae with an acceptable safety profile.

Interventional Pulmonology: The Role of Simulation Training and Competency-Based Evaluation.

Medical education and training are becoming more complex endeavors as technological and research advancements lead to new tools and methods to care for patients. In recent years, there has been a paradigm shift in medical education to competency-based assessments. Another important recent development in medical education has been the increasing use of simulation-based learning for procedural training. Interventional pulmonology (IP) is a relatively young and rapidly evolving procedural-based subspecialty. There are several well-validated competency-based assessment tools available to measure training adequacy in many of the most commonly performed procedures in IP. These tools have been shown to improve learning curves and training outcomes. The extent of how widely these tools are being used in clinical and educational spheres, however, remains unclear. Moreover, several commonly performed procedures in IP have no or limited validation tools currently available. Standardized training using simulation has also been shown to lead to positive training outcomes as compared with more traditional training models. However, widespread adoption of simulators has been limited due to the cost and availability.

Preoperative Workup of Patients With Excessive Central Airway Collapse: Does Stent Evaluation Serve a Role?

BACKGROUND: Tracheobronchoplasty (TBP) is a definitive anatomic intervention for patients with severe symptomatic expiratory central airway collapse. Although stent evaluations have been described for surgical workup, current literature does not address if improvement during stent evaluation is sustained after TBP. We compared health-related quality of life (HRQOL) and functional status responses after airway stenting to those post-TBP. METHODS: A retrospective review was performed in patients with severe expiratory central airway collapse who underwent stent evaluation followed by TBP from January 2004 to December 2019. Baseline, poststent, 3- and 12-month postoperative HRQOL scores, and functional status were analyzed with statistical tests as appropriate. RESULTS: One hundred twenty patients underwent a stent evaluation and TBP. Baseline and stent evaluation measurements were compared with statistically and clinically significant differences in the Cough Quality-of-life Questionnaire (CQLQ) (55 vs. 68, P <0.01), Modified Medical Research Council (mMRC) 0 to 2 (90% vs. 47%, P <0.01), 6-minute walk test (6MWT) (1301 ft vs. 1138 ft, P <0.01). Improvements in the HRQOL and functional status were maintained from stent evaluation to 3 months postoperatively [CQLQ 55 vs. 54, P =0.63; mMRC 0 to 2 (87% vs. 84%), P =0.39; 6MWT 1350 ft vs. 1314 ft, P =0.33], and 12 months postoperatively [CQLQ 54 vs. 54, P =0.91; mMRC 0 to 2 (95% vs. 86%), P =0.74; 6MWT 1409 ft vs. 1328 ft, P =0.13]. The magnitude of change between the data was not significantly different between the stent evaluation, 3-, and 12 months postoperative. Predicted forced expiratory volume in 1-second measurements at baseline, after stent placement, 3 months, and 12 months post-TBP were 74%, 79%, 73%, and 73%, respectively, and not clinically significant. CONCLUSIONS: Improvement after stent evaluation and the magnitude of improvement may be predictive of postoperative outcomes up to 1 year after surgery.

Does aspirin use make it harder to collect seizures during elective video-EEG telemetry?

Aspirin has shown promise as an anticonvulsant drug in animal models. Whether aspirin alters seizure frequency in humans remains unstudied. We retrospectively looked at adults with focal onset epilepsy who took aspirin daily while undergoing elective video-EEG monitoring and compared them with similar age- and sex-matched controls to see if seizure frequencies were different between those two populations. Significantly fewer seizures were seen on day two of monitoring for patients on aspirin therapies. Higher aspirin doses were correlated with fewer seizures collected during the monitoring stay. Further prospective study is needed to determine whether aspirin affects more robust seizure control.

Stent Evaluation for Expiratory Central Airway Collapse: Does the Type of Stent Really Matter?

BACKGROUND: Careful selection of patients with expiratory central airway collapse (ECAC) that may benefit from tracheobronchoplasty (TBP) can be aided by a short-term airway stent evaluation. This can be performed with either silicone Y-stents (SYSs) or uncovered self-expanding metallic airway-stents (USEMAS). No direct comparison has been made between these 2 stent types. METHODS: This was a small retrospective review of consecutive patients that underwent a stent evaluation. A propensity score was used to match patients in the USEMAS and SYS groups. Outcomes included complications, changes in the health-related quality-of-life (HR-QoL), and changes in exercise capacity. Baseline measurements were compared with those obtained during stent evaluation and after TBP. RESULTS: Forty-two patients with severe ECAC underwent USEMAS placement, while 18 patients had an SYS placed. Propensity score matching resulted in 13 matched SYS and USEMAS pairs. The SYS group had an increased rate of mucus plugging (38.5% vs. 0%, P <0.047). Although not statically significant, a clinical improvement was observed in HR-QoL and exercise capacity in the USEMAS group during stent placement. In patients who underwent TBP, both USEMAS and SYS groups had a statistically significant change in the Modified Medical Research Council Dyspnea Scale during stent evaluation and after TBP. CONCLUSION: In patients with severe ECAC, short-term evaluation with airway stents appears to be safe and improves respiratory symptoms, HR-QoL, and exercise capacity. The use of USEMAS led to a lower complication rate, a greater improvement in HR-QoL and exercise capacity, and appeared to better predict how the patients would respond to TBP.

Tracheobronchoplasty yields long-term anatomy, function, and quality of life improvement for patients with severe excessive central airway collapse.

OBJECTIVES: This study examines the long-term anatomic and clinical effects of tracheobronchoplasty in severe excessive central airway collapse. METHODS: Included patients underwent tracheobronchoplasty for excessive central airway collapse (2002-2016). The cross-sectional area of main airways on dynamic airway computed tomography was measured before and after tracheobronchoplasty. Expiratory collapse was calculated as the difference between inspiratory and expiratory cross-sectional area divided by inspiratory cross-sectional area ×100. The primary outcome was improvement in the percentage of expiratory collapse in years 1, 2, and 5 post-tracheobronchoplasty. Secondary outcomes included mean response profile for the 6-minute walk test, Cough-Specific Quality of Life Questionnaire, Karnofsky Performance Status score, and St George Respiratory Questionnaire. Repeated-measures analysis of variance was used for statistical analyses. RESULTS: The cohort included 61 patients with complete radiological follow-up at years 1, 2, and 5 post-tracheobronchoplasty. A significant linear decrease in the percentage of expiratory collapsibility of the central airways after tracheobronchoplasty was present. Anatomic repair durability was preserved 5 years after tracheobronchoplasty, with decrease in percentage of expiratory airway collapse up to 40% and 30% at years 1 and 2, respectively. The St George Respiratory Questionnaire (74.7 vs 41.8%, P < .001) and Cough-Specific Quality of Life Questionnaire (78 vs 47, P < .001) demonstrated significant improvement at year 5 compared with baseline. Similar results were observed in the 6-minute walk test (1079 vs 1268 ft, P < .001) and Karnofsky score (57 vs 82, P < .001). CONCLUSIONS: Tracheobronchoplasty has durable effects on airway anatomy, functional status, and quality of life in carefully selected patients with severe excessive central airway collapse.

Obese Patients Undergoing Tracheobronchoplasty Have Excellent Outcomes.

BACKGROUND: Tracheobronchoplasty (TBP) is the gold-standard treatment for severe symptomatic excessive central airway collapse; however outcomes among obese patients are unknown. METHODS: A retrospective, single-center analysis was conducted on consecutive patients undergoing TBP for severe symptomatic excessive central airway collapse from 2003 to 2020. Demographics, comorbidities, functional status, and perioperative complications were collected. Functional status was assessed with a 6-minute walk test (6MWT). Health-related quality of life (HRQOL) was assessed with the St George's Respiratory Questionnaire (SGRQ), Cough-specific Quality of Life Questionnaire, and modified Medical Research Council dyspnea scale (mMRC) at baseline and postoperatively. Wilcoxon rank-sum and χ2 tests were used to compare outcomes between groups. A mixed-effects regression model compared 6MWT and HRQOL over time. RESULTS: One hundred three patients underwent TBP with complete follow-up data. Thirty-four patients (33%) were obese (body mass index ≥ 35 kg/m2). Baseline demographics were similar between obese and nonobese groups, but obese patients had worse preoperative SGRQ and mMRC scores. Overall complication rates were similar (52.9% vs 43.5%, P = .36). At 3 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, or 6MWT scores; however mMRC scores were higher in obese patients (P = .04). At 12 months there was no significant difference in SGRQ, Cough-specific Quality of Life Questionnaire, mMRC, or 6MWT scores. Correcting for age, sex, and Charlson Comorbidity Index a mixed-effects regression model demonstrated obesity was not an independent predictor for lower 6MWT scores or HRQOL. CONCLUSIONS: Obese patients achieve similar improvement in HRQOL and functional capacity with comparable morbidity after TBP as nonobese patients. Obesity should not preclude patients with severe symptomatic excessive central airway collapse from TBP.

Ion: Technology and Techniques for Shape-sensing Robotic-assisted Bronchoscopy.

PURPOSE: This report describes the Ion Endoluminal System (Intuitive Surgical, Inc, Sunnyvale, CA) and practices for safe and effective use in patients with small peripheral pulmonary nodules (PPNs). DESCRIPTION: This shape-sensing robotic-assisted bronchoscopy system allows airway visualization and navigation to reach and biopsy small PPNs through a stable platform. The system provides 3-dimensional mapping and visualization of the airways, a flexible and fully articulating 3.5-mm (outer diameter) catheter, a peripheral vision probe, and system-specific biopsy needles. EVALUATION: The Ion Endoluminal System was evaluated in an ongoing prospective, multicenter trial including 241 patients with 270 PPNs (largest mean cardinal measurement, 18.8 ± 6.5 mm). Mean time to register and navigate decreased from 10 minutes in the first 10 cases to 7 minutes in the subsequent cases. Asymptomatic pneumothorax occurred in 8 patients (3.3%), 1 (0.4%) with pigtail catheter placement. Two patients (0.8%) experienced airway bleeding; both cases of bleeding resolved within 5 minutes of tamponade. CONCLUSIONS: The Ion Endoluminal System's unique shape-sensing technology can be leveraged to facilitate localization and sampling of PPNs and potentially improve diagnostic accuracy.

Comparison of Flexible 3D Printed Stenotic Airway Model Versus Standard Model for Therapeutic Bronchoscopy Training a Proof of Concept.

AIM: This study aimed to determine operator impressions of an airway obstruction procedure using a custom silicone model of low cost and high accuracy. BACKGROUND: Current procedural education for therapeutic bronchoscopy relies on animal models, supervised in-patient training, and inanimate artificial models. Model manufacturing via lost-wax casting allows for the flexibility of the material selection and reproduction of complex airway shapes. METHODS: A patient computed tomography scan was anonymized and segmented into a stereolithographic (STL) file. The water dissolvable interior airway mold was 3-dimensional (D) printed using polyvinyl alcohol and the exterior mold was printed with polylactic acid. Flexible silicone was injected into the mold. During advanced bronchoscopy courses (2017-2018) at Beth Israel Deaconess Medical Center, participants were asked to evaluate both standard bronchoscopy manikin and the manikin with 3D customization. RESULTS: We evaluated 17 participants with different levels in training in the pulmonary field. All of them reported that they previously have performed >100 bronchoscopies, 88% having treated patients with airway stenosis. In total, 77% of participants thought the 3D model was better or much better for airway inspection when compared with Broncho-Boy. Overall, 94% of participants reported the 3D model was accurate or very accurate for realism. In total, 69% of trainees reported the overall experience as excellent. All of them reported 3D model would improve their skills on stent placement. CONCLUSION: 3D printing with silicone lost wax casting can be used to reproduce airway abnormalities for tactile simulation bronchoscopy. Reproducible custom airway models can be created for a relatively low cost.

Psychopharmacology of aggression in children and adolescents with autism: a critical review of efficacy and tolerability.

BACKGROUND: Autism is characterized by a clinical triad of symptoms that affect social, language, and behavioral domains. Aggression and self-injury may be associated symptoms of autism and can result in significant harm to those affected as well as marked distress for their families. The precise nature of the relationship between aggressive or self-injurious behavior (SIB) and autism remains unclear and as a result, these symptoms are treated with a broad range of pharmacological approaches. This review seeks to systematically and critically examine the evidence for the pharmacological management of aggression and SIB in children with autism spectrum disorders. METHOD: The entire PubMed database was searched for English language biomedical articles on clinical trials with medication in autism spectrum disorders. Studies were selected based on the following inclusion criteria: (1) randomized placebo-controlled trials; (2) a sample population that included children and adolescents; (3) at least one standardized assessment of aggression as a primary outcome measure of the study. RESULTS: Twenty one trials with 12 medications were identified. Five medications produced significant improvement as compared to placebo, including tianeptine, methylphenidate, risperidone, clonidine, and naltrexone. Only risperidone and methylphenidate demonstrate results that have been replicated across at least two studies. CONCLUSIONS: Although many medications have been studied under placebo-controlled conditions, few produce significant improvement. Additional placebo-controlled trials are needed to increase the number of therapeutic options available in the treatment of aggression in autism.

Tumor biomarker testing in non-small-cell lung cancer: A decade of change.

INTRODUCTION: Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice. METHODS: We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics. RESULTS: The majority of 1009 NSCLC patients had advanced stages of adenocarcinoma with most tissues obtained from the lung, mediastinal/hilar nodes, or pleura. The majority of testing was performed on cytology or small biopsy specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing at our institution for EGFR, ALK, ROS1 and PD-L1 all occurred within the first year following evidence of clinical activity or regulatory body approval of an associated inhibitor. The overall testing failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene identified (EGFR/ALK/ROS1/BRAF V600E) with an approved oral targeted therapy, with the highest prevalence in those patients with no or light (≤15 pack-years) history of tobacco use. CONCLUSIONS: Tumor biomarker testing using clinical NSCLC specimens in routine oncologic care evolves rapidly following approval of targeted therapies linked to diagnostic assays. Our practice's decade plus experience highlights the rapid evolution of biomarker testing and confirms the therapeutic relevance of such testing in all patients-particularly those patients with light/no history of tobacco use.

Frailty Characteristics Predict Respiratory Failure in Patients Undergoing Tracheobronchoplasty.

BACKGROUND: Respiratory complications are the leading cause of morbidity in patients undergoing tracheobronchoplasty, yet risk stratification systems on this population are insufficient. We investigated the association between frailty and risk of major respiratory complications after tracheobronchoplasty. METHODS: A retrospective review was made of 161 consecutive tracheobronchoplasties (October 2002 to September 2016). A frailty index was developed by the deficit-accumulation approach comprising 26 multidomain preoperative variables. The main outcome was a composite endpoint of major respiratory complications within 30 days of surgery. Odds ratio (OR) and 95% confidence interval (CI) were estimated using logistic regression. RESULTS: The cohort consisted of 103 women (64%), median age of 58 years (interquartile range, 51 to 66) and median FI of 0.25 (interquartile range, 0.1 to 0.3). Forty-eight patients (30%) had respiratory complications, the most common being respiratory failure (n = 27, 16.8%) and pneumonia (n = 25, 15.5%). Severe frailty (frailty index ≥0.33) was strongly associated with major respiratory complications (73.8% versus 2.5%; OR 58.8, 95% CI: 9.6 to 358.3). The association with severe frailty appeared stronger for respiratory failure (47.6% versus 2.5%; OR 30, 95% CI: 4.7 to 189.9) than for pneumonia (40.5% versus 0%; OR 35.2. 95% CI: 2.0 to 599.8). Further adjustment for intraoperative crystalloid volume or forced expiratory volume in 1 second moderately attenuated the association between frailty with major respiratory complications (OR 17.4. 95% CI: 2.0 to 150.8), respiratory failure (OR 13.1, 95% CI: 1.7 to 95.8), and pneumonia (OR 20.1, 95% CI: 1.1 to 341.8). CONCLUSIONS: Frailty, as indicated by frailty index, was associated with major respiratory complications, particularly respiratory failure after tracheobronchoplasty. Preoperative identification of frailty may help guide decision making for patients considering this effective, although arduous procedure.

Electromagnetic Navigational Bronchoscopy Spares a Drunken Crab From the Surgeon's Knife.

Surgical resection is traditionally the preferred treatment for fluorodeoxyglucose-avid peripheral pulmonary nodules that grow over time. However, new technologies, including electromagnetic navigational bronchoscopy (ENB), provide an opportunity to confirm or possibly exclude a cytologic cancer diagnosis, before resection. We present a case of a 56-year-old North American man who presented with a fluorodeoxyglucose-avid pulmonary nodule and sought a second opinion after being recommended thoracotomy with lobectomy. The peripheral nodule was biopsied using ENB and pathologic evaluation of the lesion demonstrated parasitic eggs with features of Paragonimus westermani. No evidence of malignancy was found. The radiographic abnormalities resolved after treatment with praziquantel. Using a minimally invasive procedure with ENB, we successfully diagnosed pulmonary infection with P. westermani, a rare infectious cause of peripheral pulmonary lesions in a patient without travel to an endemic area. Furthermore, an alternative diagnosis to cancer was established, sparing this patient an unnecessary thoracotomy with right middle lobectomy.

Endobronchial Ultrasound-guided Transbronchial Needle Injection of Liposomal Amphotericin B for the Treatment of Symptomatic Aspergilloma.

Surgical treatment with lung resection has traditionally been the treatment of choice for pulmonary cavities containing aspergillomas that cause hemoptysis. Endobronchial ultrasound (EBUS) is a minimally invasive bronchoscopic technique that is commonly used for transbronchial needle aspiration of hilar and mediastinal lymph nodes as well as centrally located parenchymal lesions. Here, we describe a case of a 71-year-old woman who was found to have a cavitary lesion in the lung containing aspergillomas. Under direct ultrasound visualization with EBUS, liposomal amphotericin B was injected into the aspergillomas. These aspergillomas regressed after treatment. To our knowledge, this is the first reported treatment of aspergilloma with EBUS-guided transbronchial needle injection of liposomal amphotericin B.