The effect of pleural drainage on pulse oximetry in a post-operative thoracic surgery population.

BACKGROUND: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients. METHODS: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2. RESULTS: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001). CONCLUSIONS: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients.

GRAvity- versus Wall suction-drIven large volume Thoracentesis: a rAndomized controlled Study (GRAWITAS study).

BACKGROUND: Prior studies found no differences in procedural chest discomfort for patients undergoing manual syringe aspiration or drainage with gravity after thoracentesis. However, whether gravity drainage could protect against chest pain due to the larger negative pressure gradient generated by wall suction has not been investigated. RESEARCH QUESTION: Does wall suction drainage result in more chest discomfort compared to gravity drainage in patients undergoing large volume thoracentesis? STUDY DESIGN AND METHODS: In this multicenter, single-blinded, randomized controlled trial, patients with large free-flowing effusions of ≥500 mL were assigned to wall suction or gravity drainage in a 1:1 ratio. Wall suction was performed with suction system attached to the suction tubing and with vacuum pressure adjusted to full vacuum. Gravity drainage was performed with a drainage bag placed 100 cm below the catheter insertion site and connected via straight tubing. Patients rated chest discomfort on a 100-mm visual analog scale before, during, and after drainage. The primary outcome was postprocedural chest discomfort at 5 minutes. Secondary outcomes included measures of post procedure chest discomfort, breathlessness, procedure time, volume of fluid drained and complication rates. RESULTS: Of the 228 patients initially randomized, 221 were included in the final analysis. The primary outcome of procedural chest discomfort did not differ significantly between the groups (p = 0.08), nor did the secondary outcomes of postprocedural discomfort and dyspnea. Similar volumes were drained in both groups, but the procedure duration was longer in the gravity arm by approximately 3 minutes. No differences in rate of pneumothorax or re-expansion pulmonary edema were noted between the two groups. INTERPRETATION: Thoracentesis via wall suction and gravity drainage results in similar levels of procedural discomfort and dyspnea improvement.

Autonomous medical needle steering in vivo.

The use of needles to access sites within organs is fundamental to many interventional medical procedures both for diagnosis and treatment. Safely and accurately navigating a needle through living tissue to a target is currently often challenging or infeasible because of the presence of anatomical obstacles, high levels of uncertainty, and natural tissue motion. Medical robots capable of automating needle-based procedures have the potential to overcome these challenges and enable enhanced patient care and safety. However, autonomous navigation of a needle around obstacles to a predefined target in vivo has not been shown. Here, we introduce a medical robot that autonomously navigates a needle through living tissue around anatomical obstacles to a target in vivo. Our system leverages a laser-patterned highly flexible steerable needle capable of maneuvering along curvilinear trajectories. The autonomous robot accounts for anatomical obstacles, uncertainty in tissue/needle interaction, and respiratory motion using replanning, control, and safe insertion time windows. We applied the system to lung biopsy, which is critical for diagnosing lung cancer, the leading cause of cancer-related deaths in the United States. We demonstrated successful performance of our system in multiple in vivo porcine studies achieving targeting errors less than the radius of clinically relevant lung nodules. We also demonstrated that our approach offers greater accuracy compared with a standard manual bronchoscopy technique. Our results show the feasibility and advantage of deploying autonomous steerable needle robots in living tissue and how these systems can extend the current capabilities of physicians to further improve patient care.

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).

Pleural Fluid Resolution Is Associated with Improved Survival in Patients with Malignant Pleural Effusion.

Malignant pleural effusion is associated with a poor prognosis and, while risk stratification models exist, prior studies have not evaluated pleural fluid resolution and its association with survival. We performed a retrospective review of patients diagnosed with malignant pleural effusion between 2013 and 2017, evaluating patient demographics, pleural fluid and serum composition, and procedural and treatment data using Cox regression analysis to evaluate associations with survival. In total, 123 patients were included in the study, with median survival from diagnosis being 4.8 months. Resolution of malignant pleural fluid was associated with a significant survival benefit, even when accounting for factors such as placement of an indwelling pleural catheter, anti-cancer therapy, pleural fluid cytology, cancer pheno/genotypes, and pleural fluid characteristics. Elevated fluid protein, placement of an indwelling pleural catheter, and treatment with targeted or hormone therapies were associated with pleural fluid resolution. We conclude that the resolution of pleural fluid accumulation in patients with malignant pleural effusion is associated with a survival benefit possibility representing a surrogate marker for treatment of the underlying metastatic cancer. These findings support the need to better understand the mechanism of fluid resolution in patients with malignant pleural effusion as well as the tumor-immune interplay occurring with the malignant pleural space.

Interventional Pulmonary Fellowship Training: End of the Beginning.

Interventional pulmonology (IP) fellowship training has undergone increased popularity and growth. The Accreditation Council of Graduate Medical Education recently recognized IP medicine as a new subspecialty, which leads to new challenges and opportunities for a young subspecialty. Although the specialty-specific requirements are in progress, IP fellowship programs must plan ahead for the known common program requirements and anticipated accreditation process. The educational leadership in IP must identify and execute solutions to sustain continued excellence. This includes transitioning to a new regulatory environment with issues of funding new fellowships, keeping up to date with training/assessment of new procedures, and shaping the future through recruitment of talent to lead the young subspecialty.

Landmark Based Bronchoscope Localization for Needle Insertion Under Respiratory Deformation.

Bronchoscopy is currently the least invasive method for definitively diagnosing lung cancer, which kills more people in the United States than any other form of cancer. Successfully diagnosing suspicious lung nodules requires accurate localization of the bronchoscope relative to a planned biopsy site in the airways. This task is challenging because the lung deforms intraoperatively due to respiratory motion, the airways lack photometric features, and the anatomy's appearance is repetitive. In this paper, we introduce a real-time camera-based method for accurately localizing a bronchoscope with respect to a planned needle insertion pose. Our approach uses deep learning and accounts for deformations and overcomes limitations of global pose estimation by estimating pose relative to anatomical landmarks. Specifically, our learned model considers airway bifurcations along the airway wall as landmarks because they are distinct geometric features that do not vary significantly with respiratory motion. We evaluate our method in a simulated dataset of lungs undergoing respiratory motion. The results show that our method generalizes across patients and localizes the bronchoscope with accuracy sufficient to access the smallest clinically-relevant nodules across all levels of respiratory deformation, even in challenging distal airways. Our method could enable physicians to perform more accurate biopsies and serve as a key building block toward accurate autonomous robotic bronchoscopy.

A Multicenter Study Assessing Interventional Pulmonary Fellow Competency in Electromagnetic Navigation Bronchoscopy.

Background: Current medical society guidelines recommend a procedural number for obtaining electromagnetic navigational bronchoscopy (ENB) competency and for institutional volume for training. Objective: To assess learning curves and estimate the number of ENB procedures for interventional pulmonology (IP) fellows to reach competency. Methods: We conducted a prospective multicenter study of IP fellows in the United States learning ENB. A tool previously validated in a similar population was used to assess IP fellows by their local faculty and two blinded independent reviewers using virtual recording of the procedure. Competency was determined by performing three consecutive procedures with a competency score on the assessment tool. Procedural time, faculty global rating scale, and periprocedural complications were also recorded. Results: A total of 184 ENB procedures were available for review with assessment of 26 IP fellows at 16 medical centers. There was a high correlation between the two blinded independent observers (rho = 0.8776). There was substantial agreement for determination of procedural competency between the faculty assessment and blinded reviewers (kappa = 0.7074; confidence interval, 0.5667-0.8482). The number of procedures for reaching competency for ENB bronchoscopy was determined (median, 4; mean, 5; standard deviation, 3.83). There was a wide variation in the number of procedures to reach competency, ranging from 2 to 15 procedures. There were six periprocedural complications reported, four (one pneumomediastinum, three pneumothorax) of which occurred before reaching competence and two pneumothoraces after achieving competence. Conclusion: There is a wide variation in acquiring competency for ENB among IP fellows. Virtual competency assessment has a potential role but needs further studies.

Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

A Direct Comparative Study of Bronchoscopic Navigation Planning Platforms for Peripheral Lung Navigation: The ATLAS Study.

BACKGROUND: The use of mapping to guide peripheral lung navigation (PLN) represents an advance in the management of peripheral pulmonary lesions (PPL). Software has been developed to virtually reconstruct computed tomography images into 3-dimensional airway maps and generate navigation pathways to target PPL. Despite this there remain significant gaps in understanding the factors associated with navigation success and failure including the cartographic performance characteristics of these software algorithms. This study was designed to determine whether differences exist when comparing PLN mapping platforms. METHODS: An observational direct comparison was performed to evaluate navigation planning software packages for the lung. The primary endpoint was distance from the terminal end of the virtual navigation pathway to the target PPL. Secondary endpoints included distal virtual and segmental airway generations built to the target and/or in each lung. RESULTS: Twenty-five patient chest computed tomography scans with 41 PPL were evaluated. Virtual airway and navigation pathway maps were generated for each scan/nodule across all platforms. Virtual navigation pathway comparison revealed differences in the distance from the terminal end of the navigation pathway to the target PPL (robotic bronchoscopy 9.4 mm vs. tip-tracked electromagnetic navigation 14.2 mm vs. catheter based electromagnetic navigation 17.2 mm, P=0.0005) and in the generation of complete distal airway maps. CONCLUSION: Comparing PLN planning software revealed significant differences in the generation of virtual airway and navigation maps. These differences may play an unrecognized role in the accurate PLN and biopsy of PPL. Further prospective trials are needed to quantify the effect of the differences reported.

Electromagnetic Navigation Transthoracic Nodule Localization for Minimally Invasive Thoracic Surgery.

The increased use of chest computed tomography (CT) has led to an increased detection of pulmonary nodules requiring diagnostic evaluation and/or excision. Many of these nodules are identified and excised via minimally invasive thoracic surgery; however, subcentimeter and subsolid nodules are frequently difficult to identify intra-operatively. This can be mitigated by the use of electromagnetic transthoracic needle localization. This protocol delineates the step-by-step process of electromagnetic localization from the pre-operative period to the postoperative period and is an adaptation of the electromagnetically guided percutaneous biopsy previously described by Arias et al. Pre-operative steps include obtaining a same day CT followed by the generation of a three-dimensional virtual map of the lung. From this map, the target lesion(s) and an entry site are chosen. In the operating room, the virtual reconstruction of the lung is then calibrated with the patient and the electromagnetic navigation platform. The patient is then sedated, intubated, and placed in the lateral decubitus position. Using a sterile technique and visualization from multiple views, the needle is inserted into the chest wall at the prechosen skin entry site and driven down to the target lesion. Dye is then injected into the lesion and, then, continuously during needle withdrawal, creating a tract for visualization intra-operatively. This method has many potential benefits when compared to the CT-guided localization, including a decreased radiation exposure and decreased time between the dye injection and the surgery. Dye diffusion from the pathway occurs over time, thereby limiting intra-operative nodule identification. By decreasing the time to surgery, there is a decrease in wait time for the patient, and less time for dye diffusion to occur, resulting in an improvement in nodule localization. When compared to electromagnetic bronchoscopy, airway architecture is no longer a limitation as the target nodule is accessed via a transparenchymal approach. Details of this procedure are described in a step-by-step fashion.

Silver Nitrate-coated versus Standard Indwelling Pleural Catheter for Malignant Effusions: The SWIFT Randomized Trial.

Rationale: Tunneled, indwelling pleural catheters (IPCs) have been demonstrated to be an effective method of managing malignant pleural effusions. However, they allow pleurodesis and can therefore be removed in only a subset of patients. A novel, silver nitrate-coated IPC was developed with the intention of creating a rapid, effective chemical pleurodesis to allow more frequent and earlier catheter removal. This study represents the pivotal clinical trial evaluating that catheter versus the standard IPC. Objectives: To compare the efficacy of a novel silver nitrate-eluting indwelling pleural catheter (SNCIPC) with that of a standard, uncoated catheter. Methods: The SWIFT [A Pivotal Multi-Center, Randomized, Controlled, Single-Blinded Study Comparing the Silver Nitrate-Coated Indwelling Pleural Catheter (SNCIPC) to the Uncoated PleurX® Pleural Catheter for the Management of Symptomatic, Recurrent, Malignant Pleural Effusions] trial was a multicenter, parallel-group, randomized, controlled, patient-blind trial. Central randomization occurred according to a computer-generated schedule, stratified by site. Recruitment was from 17 secondary or tertiary care hospitals in the United States and 3 in the United Kingdom and included adult patients with malignant pleural effusion needing drainage, without evidence of lung entrapment or significant loculation. The intervention group underwent insertion of an SNCIPC with maximal fluid drainage, followed by a tapering drainage schedule. The control group received a standard, uncoated catheter. Follow-up was conducted until 90 days. The primary outcome measure was pleurodesis efficacy, measured by fluid drainage, at 30 days. Results: A total of 119 patients were randomized. Five withdrew before receiving treatment, leaving 114 (77 SNCIPC, 37 standard IPC) for analysis. The mean age was 66 years (standard deviation, 11). More patients in the SNCIPC group were inpatients (39% vs. 14%; P = 0.009). For the primary outcome, pleurodesis rates were 12 (32%) of 37 in the control group and 17 (22%) of 77 in the SNCIPC group (rate difference, -0.10; 95% confidence interval, -0.30 to 0.09). Median time to pleurodesis was 11 days (interquartile range, 9 to 23) in the control group and 4 days (interquartile range, 2 to 15) in the SNCIPC group. No significant difference in treatment-related adverse event rates was noted between groups. Conclusions: The SNCIPC did not improve pleurodesis efficacy compared with a standard IPC. This study does not support the wider use of the SNCIPC device. Clinical trial registered with www.clinicaltrials.gov (NCT02649894).

Feasibility of a prototype carbon nanotube enabled stationary digital chest tomosynthesis system for identification of pulmonary nodules by pulmonologists.

Background: Screen detected and incidental pulmonary nodules are increasingly common. Current guidelines recommend tissue sampling of solid nodules >8 mm. Bronchoscopic biopsy poses the lowest risk but is paired with the lowest diagnostic yield when compared to CT-guided biopsy or surgery. A need exists for a safe, mobile, low radiation dose, intra-procedural method to localize biopsy instruments within target nodules. This retrospective cross sectional reader feasibility study evaluates the ability of clinicians to identify pulmonary nodules using a prototype carbon nanotube radiation enabled stationary digital chest tomosynthesis system. Methods: Patients with pulmonary nodules on prior CT imaging were recruited and consented for imaging with stationary digital chest tomosynthesis. Five pulmonologists of varying training levels participated as readers. Following review of patient CT and a thoracic radiologist's interpretation of nodule size and location the readers were tasked with interpreting the corresponding tomosynthesis scan to identify the same nodule found on CT. Results: Fifty-five patients were scanned with stationary digital chest tomosynthesis. The median nodule size was 6 mm (IQR =4-13 mm). Twenty nodules (37%) were greater than 8 mm. The radiation entrance dose for s-DCT was 0.6 mGy. A significant difference in identification of nodules using s-DCT was seen for nodules <8 vs. ≥8 mm in size (57.7% vs. 90.9%, CI: -0.375, -0.024; P<0.001). Inter-reader agreement was fair, and better for nodules ≥8 mm [0.278 (SE =0.043)]. Conclusions: With system and carbon nanotube array optimization, we hypothesize the detection rate for nodules will improve. Additional study is needed to evaluate its use in target and tool co-localization and target biopsy.

Accuracy of Pulmonary Nodule Sampling Using Robotic Assisted Bronchoscopy with Shape Sensing, Fluoroscopy, and Radial Endobronchial Ultrasound (The ACCURACY Study).

BACKGROUND: Despite recent advances in guided bronchoscopy, the yield of bronchoscopic biopsy of a peripheral pulmonary nodule (PPN) remains highly variable. OBJECTIVE: The aim of the study was to evaluate which features of robotic assisted bronchoscopy (RAB) contribute to a successful biopsy in a cadaver model. METHODS: A preclinical, prospective, single-blinded trial using a ventilated human cadaveric model assessed the successful puncture of implanted pulmonary nodules using various localization techniques with RAB. The different approaches included positioning the robotic catheter at predefined distances from the target nodule (<10 mm, 10-20 mm, 20-30 mm), bronchoscopist correction of divergence between the software virtual map and bronchoscopic view if observed, and impact of fluoroscopy and radial endobronchial ultrasound (rEBUS). The primary endpoint was a central target hit (defined as an inner 2/3 target puncture) verified by cone-beam computed tomography. RESULTS: Thirty-eight RAB procedures were performed to target 16 PPNs. Median nodule size was 16.2 mm. All targets were located in the outer 1/3 of the lung with a bronchus sign in 31.3%. Central target hit rates were improved when the robotic catheter tip was closer to the nodule (<10 mm 68%, 10-20 mm 66%, 20-30 mm 11%, p < 0.001). Multivariable analysis confirmed the strongest predictor of a central target hit was robotic catheter distance to nodule (OR 0.89 per increase in 1 mm, p < 0.001), independent of the presence of a bronchus sign, divergence or concentric rEBUS view. CONCLUSIONS: Utilizing a RAB platform, closer proximity of the robotic catheter to the target nodule results in an increase in peripheral nodule biopsy success.

Targeting disialoganglioside GD2 with chimeric antigen receptor-redirected T cells in lung cancer.

BACKGROUND: We explored whether the disialoganglioside GD2 (GD2) is expressed in small cell lung cancer (SCLC) and non-SCLC (NSCLC) and can be targeted by GD2-specific chimeric antigen receptor (CAR) T cells. METHODS: GD2 expression was evaluated in tumor cell lines and tumor biopsies by flow cytometry and immunohistochemistry. We used a GD2.CAR that coexpress the IL-15 to promote T-cell proliferation and persistence, and the inducible caspase 9 gene safety switch to ablate GD2.CAR-T cells in case of unforeseen toxicity. The antitumor activity of GD2.CAR-T cells was evaluated using in vitro cocultures and in xenograft models of orthotopic and metastatic tumors. The modulation of the GD2 expression in tumor cell lines in response to an epigenetic drug was also evaluated. RESULTS: GD2 was expressed on the cell surface of four of fifteen SCLC and NSCLC cell lines (26.7%) tested by flow cytometry, and in 39% of SCLC, 72% of lung adenocarcinoma and 56% of squamous cell carcinoma analyzed by immunohistochemistry. GD2 expression by flow cytometry was also found on the cell surface of tumor cells freshly isolated from tumor biopsies. GD2.CAR-T cells exhibited antigen-dependent cytotoxicity in vitro and in vivo in xenograft models of GD2-expressing lung tumors. Finally, to explore the applicability of this approach to antigen low expressing tumors, we showed that pretreatment of GD2low/neg lung cancer cell lines with the Enhancer of zeste homolog 2 inhibitor tazemetostat upregulated GD2 expression at sufficient levels to trigger GD2.CAR-T cell cytotoxic activity. CONCLUSIONS: GD2 is a promising target for CAR-T cell therapy in lung cancer. Tazemetostat treatment could be used to upregulate GD2 expression in tumor cells, enhancing their susceptibility to CAR-T cell targeting.

A Metric for Finding Robust Start Positions for Medical Steerable Needle Automation.

Steerable needles are medical devices with the ability to follow curvilinear paths to reach targets while circumventing obstacles. In the deployment process, a human operator typically places the steerable needle at its start position on a tissue surface and then hands off control to the automation that steers the needle to the target. Due to uncertainty in the placement of the needle by the human operator, choosing a start position that is robust to deviations is crucial since some start positions may make it impossible for the steerable needle to safely reach the target. We introduce a method to efficiently evaluate steerable needle motion plans such that they are safe to variation in the start position. This method can be applied to many steerable needle planners and requires that the needle's orientation angle at insertion can be robotically controlled. Specifically, we introduce a method that builds a funnel around a given plan to determine a safe insertion surface corresponding to insertion points from which it is guaranteed that a collision-free motion plan to the goal can be computed. We use this technique to evaluate multiple feasible plans and select the one that maximizes the size of the safe insertion surface. We evaluate our method through simulation in a lung biopsy scenario and show that the method is able to quickly find needle plans with a large safe insertion surface.

Pleural Interventions in the Management of Hepatic Hydrothorax.

Hepatic hydrothorax can be present in 5% to 15% of patients with underlying cirrhosis and portal hypertension, often reflecting advanced liver disease. Its impact can be variable, because patients may have small pleural effusions and minimal pulmonary symptoms or massive pleural effusions and respiratory failure. Management of hepatic hydrothorax can be difficult because these patients often have a number of comorbidities and potential for complications. Minimal high-quality data are available for guidance specifically related to hepatic hydrothorax, potentially resulting in pulmonary or critical care physician struggling for best management options. We therefore provide a Case-based presentation with management options based on currently available data and opinion. We discuss the role of pleural interventions, including thoracentesis, tube thoracostomy, indwelling tunneled pleural catheter, pleurodesis, and surgical interventions. In general, we recommend that management be conducted within a multidisciplinary team including pulmonology, hepatology, and transplant surgery. Patients with refractory hepatic hydrothorax that are not transplant candidates should be managed with palliative intent; we suggest indwelling tunneled pleural catheter placement unless otherwise contraindicated. For patients with unclear or incomplete hepatology treatment plans or those unable to undergo more definitive procedures, we recommend serial thoracentesis. In patients who are transplant candidates, we often consider serial thoracentesis as a standard treatment, while also evaluating the role indwelling tunneled pleural catheter placement may play within the course of disease and transplant evaluation.

Design Considerations for a Steerable Needle Robot to Maximize Reachable Lung Volume.

Steerable needles that are able to follow curvilinear trajectories and steer around anatomical obstacles are a promising solution for many interventional procedures. In the lung, these needles can be deployed from the tip of a conventional bronchoscope to reach lung lesions for diagnosis. The reach of such a device depends on several design parameters including the bronchoscope diameter, the angle of the piercing device relative to the medial axis of the airway, and the needle's minimum radius of curvature while steering. Assessing the effect of these parameters on the overall system's clinical utility is important in informing future design choices and understanding the capabilities and limitations of the system. In this paper, we analyze the effect of various settings for these three robot parameters on the percentage of the lung that the robot can reach. We combine Monte Carlo random sampling of piercing configurations with a Rapidly-exploring Random Trees based steerable needle motion planner in simulated human lung environments to asymptotically accurately estimate the volume of sites in the lung reachable by the robot. We highlight the importance of each parameter on the overall system's reachable workspace in an effort to motivate future device innovation and highlight design trade-offs.