GLI-12 Reference Values versus Fixed 0.7 Ratio for the Detection of Airflow Obstruction in the Presence of Lung Hyperinflation.

Introduction: Airflow obstruction (AO) is evidenced by reduced forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) with the threshold for diagnosis often being set at <0.7. However, currently the ATS/ERS standards for interpretation of lung function tests recommend the lower limit of normal (LLN), calculated by reference equations of the Global Lung Initiative from 2012 (GLI-12), as a threshold for AO diagnosis. The present study aims to investigate phenotypes, with focus on hyperinflation, which influence AO prevalence defined by FEV1/FVC < LLN when compared to the fixed 0.7 threshold. Methods: Data from 3,875 lung function tests (56.4% men, aged 18-95) including 3,824 body plethysmography recordings performed from July 2021 to June 2022 were analysed. The difference between both classifiers was quantified, before and after stratification by sex, age, and hyperinflation. Results: AO diagnosis was significantly less frequent with the LLN threshold (18.2%) compared to the fixed threshold (28.0%) (p < 0.001) with discordance rate of 10.5%. In the presence of mild or moderate hyperinflation, there was substantial agreement (Cohen's kappa: 0.616, 0.718) between the classifiers compared to near perfect agreement in the presence of severe hyperinflation (Cohen's kappa: 0.896). In addition, subgroup analysis after stratification for sex, age, and hyperinflation showed significant differences between both classifiers. Conclusion: The importance of using the LLN threshold instead of the fixed 0.7 threshold for the diagnosis of AO is highlighted. When using the fixed threshold AO, misdiagnosis was more common in the presence of mild to moderate hyperinflation.

SARS-CoV-2 particles promote airway epithelial differentiation and ciliation.

Introduction: The Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which caused the coronavirus disease 2019 (COVID-19) pandemic, enters the human body via the epithelial cells of the airway tract. To trap and eject pathogens, the airway epithelium is composed of ciliated and secretory cells that produce mucus which is expelled through a process called mucociliary clearance. Methods: This study examines the early stages of contact between SARS-CoV-2 particles and the respiratory epithelium, utilizing 3D airway tri-culture models exposed to ultraviolet light-irradiated virus particles. These cultures are composed of human endothelial cells and human tracheal mesenchymal cells in a fibrin hydrogel matrix covered by mucociliated human tracheal epithelial cells. Results: We found that SARS-CoV-2 particles trigger a significant increase in ciliation on the epithelial surface instructed through a differentiation of club cells and basal stem cells. The contact with SARS-CoV-2 particles also provoked a loss of cell-cell tight junctions and impaired the barrier integrity. Further immunofluorescence analyses revealed an increase in FOXJ1 expression and PAK1/2 phosphorylation associated with particle-induced ciliation. Discussion: An understanding of epithelial responses to virus particles may be instrumental to prevent or treat respiratory infectious diseases such as COVID-19.

Dual Labeling of Primary Cells with Fluorescent Gadolinium Oxide Nanoparticles.

The interest in mesenchymal stromal cells as a therapy option is increasing rapidly. To improve their implementation, location, and distribution, the properties of these must be investigated. Therefore, cells can be labeled with nanoparticles as a dual contrast agent for fluorescence and magnetic resonance imaging (MRI). In this study, a more efficient protocol for an easy synthesis of rose bengal-dextran-coated gadolinium oxide (Gd2O3-dex-RB) nanoparticles within only 4 h was established. Nanoparticles were characterized by zeta potential measurements, photometric measurements, fluorescence and transmission electron microscopy, and MRI. In vitro cell experiments with SK-MEL-28 and primary adipose-derived mesenchymal stromal cells (ASC), nanoparticle internalization, fluorescence and MRI properties, and cell proliferation were performed. The synthesis of Gd2O3-dex-RB nanoparticles was successful, and they were proven to show adequate signaling in fluorescence microscopy and MRI. Nanoparticles were internalized into SK-MEL-28 and ASC via endocytosis. Labeled cells showed sufficient fluorescence and MRI signal. Labeling concentrations of up to 4 mM and 8 mM for ASC and SK-MEL-28, respectively, did not interfere with cell viability and proliferation. Gd2O3-dex-RB nanoparticles are a feasible contrast agent to track cells via fluorescence microscopy and MRI. Fluorescence microscopy is a suitable method to track cells in in vitro experiments with smaller samples.

Influence of Aerosolization on Endothelial Cells for Efficient Cell Deposition in Biohybrid and Regenerative Applications.

The endothelialization of gas exchange membranes can increase the hemocompatibility of extracorporeal membrane oxygenators and thus become a long-term lung replacement option. Cell seeding on large or uneven surfaces of oxygenator membranes is challenging, with cell aerosolization being a possible solution. In this study, we evaluated the endothelial cell aerosolization for biohybrid lung application. A Vivostat® system was used for the aerosolization of human umbilical vein endothelial cells with non-sprayed cells serving as a control. The general suitability was evaluated using various flow velocities, substrate distances and cell concentrations. Cells were analyzed for survival, apoptosis and necrosis levels. In addition, aerosolized and non-sprayed cells were cultured either static or under flow conditions in a dynamic microfluidic model. Evaluation included immunocytochemistry and gene expression via quantitative PCR. Cell survival for all tested parameters was higher than 90%. No increase in apoptosis and necrosis levels was seen 24 h after aerosolization. Spraying did not influence the ability of the endothelial cells to form a confluent cell layer and withstand shear stresses in a dynamic microfluidic model. Immunocytochemistry revealed typical expression of CD31 and von Willebrand factor with cobble-stone cell morphology. No change in shear stress-induced factors after aerosolization was reported by quantitative PCR analysis. With this study, we have shown the feasibility of endothelial cell aerosolization with no significant changes in cell behavior. Thus, this technique could be used for efficient the endothelialization of gas exchange membranes in biohybrid lung applications.

Effervescent Atomizer as Novel Cell Spray Technology to Decrease the Gas-to-Liquid Ratio.

Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4−33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing.

Bone Marrow Derived Mesenchymal Stromal Cells Promote Vascularization and Ciliation in Airway Mucosa Tri-Culture Models in Vitro.

Patients suffering from irresectable tracheal stenosis often face limited treatment options associated with low quality of life. To date, an optimal tracheal replacement strategy does not exist. A tissue-engineered tracheal substitute promises to overcome limitations such as implant vascularization, functional mucociliary clearance and mechanical stability. In order to advance a tracheal mucosa model recently developed by our group, we examined different supporting cell types in fibrin-based tri-culture with primary human umbilical vein endothelial cells (HUVEC) and primary human respiratory epithelial cells (HRE). Bone marrow-derived mesenchymal stromal cells (BM-MSC), adipose-derived mesenchymal stromal cells (ASC) and human nasal fibroblasts (HNF) were compared regarding their ability to promote mucociliary differentiation and vascularization in vitro. Three-dimensional co-cultures of the supporting cell types with either HRE or HUVEC were used as controls. Mucociliary differentiation and formation of vascular-like structures were analyzed by scanning electron microscopy (SEM), periodic acid Schiff's reaction (PAS reaction), two-photon laser scanning microscopy (TPLSM) and immunohistochemistry. Cytokine levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interleukin-6 (IL6), interleukin-8 (IL8), angiopoietin 1, angiopoietin 2, fibroblast growth factor basic (FGF-b) and placenta growth factor (PIGF) in media supernatant were investigated using LEGENDplex™ bead-based immunoassay. Epithelial morphology of tri-cultures with BM-MSC most closely resembled native respiratory epithelium with respect to ciliation, mucus production as well as expression and localization of epithelial cell markers pan-cytokeratin, claudin-1, α-tubulin and mucin5AC. This was followed by tri-cultures with HNF, while ASC-supported tri-cultures lacked mucociliary differentiation. For all supporting cell types, a reduced ciliation was observed in tri-cultures compared to the corresponding co-cultures. Although formation of vascular-like structures was confirmed in all cultures, vascular networks in BM-MSC-tri-cultures were found to be more branched and extended. Concentrations of pro-angiogenic and inflammatory cytokines, in particular VEGF and angiopoietin 2, revealed to be reduced in tri-cultures compared to co-cultures. With these results, our study provides an important step towards a vascularized and ciliated tissue-engineered tracheal replacement. Additionally, our tri-culture model may in the future contribute to an improved understanding of cell-cell interactions in diseases associated with impaired mucosal function.

Suitability of Bronchoscopic Spraying for Fluid Deposition in Lower Airway Regions: Fluorescence Analysis on a Transparent In Vitro Airway Model.

Introduction: Bronchoscopic spraying has potential for the application of therapeutic drugs in distal regions of the lung by bypassing the upper airways. However, there is a lack of understanding about the underlying fluid transport phenomena that are responsible for the intrapulmonary propagation of applied liquid. Methods: By using a transparent airway model, this study provides first experimental insights into relevant transport phenomena of bronchoscopic spraying. Furthermore, the penetration depth of the application is quantitatively evaluated. Laser-induced fluorescence is used to analyze fluid propagation in the transparent channels. Potential influencing factors such as the positioning in different airways, application number, breathing pattern, and lung obstructions are varied within this study to determine their influence on liquid deposition. Findings: This study shows that the method of bronchoscopic spraying allows the application of liquid in distal regions of the airway model. The position of the bronchoscope is a key influencing factor in increasing the penetration depth. We found that fluid transport along the distal airways essentially occurs by the film and plug flow phenomenon during application, which is similar to the transport mechanisms during instillation. Liquid plugs in lower airways are responsible for the reorganization of liquid during proximal movements and thereby influence the penetration depth in subsequent applications.

Broncho-alveolar lavage in patients with acute respiratory distress syndrome due to COVID-19.

As data about microbiological testing and the cellular composition of the broncho-alveolar lavage (BAL) fluid in patients ventilated due to coronavirus disease 2019 (COVID-19) are lacking, this was investigated in a retrospective analysis (n = 58). Co-infection with pathogens was detected in 31 patients, whereas the analysis of BAL cellularity showed an increased total cell count and an alveolitis dominated by neutrophils. None of the physicians performing bronchoscopies in COVID-19 patients had serological evidence of severe acute respiratory syndrome coronavirus 2 infection.

Endoscopic atomization of mesenchymal stromal cells: in vitro study for local cell therapy of the lungs.

BACKGROUND AIMS: Cell-based therapies of pulmonary diseases with mesenchymal stromal cells (MSCs) are increasingly under experimental investigation. In most of these, MSCs are administered intravenously or by direct intratracheal instillation. A parallel approach is to administer the cells into the lung by endoscopic atomization (spraying). In a previous study, the authors developed a flexible endoscopic atomization device that allows administration of respiratory epithelial cells in the lungs with high survival. METHODS: In this study, the authors evaluated the feasibility of spraying MSCs with two different endoscopic atomization devices (air and pressure atomization). Following atomization, cell viability was evaluated with live/dead staining. Subsequent effects on cytotoxicity, trilineage differentiation and expression of MSC-specific markers as well as on MSC metabolic activity and morphology were analyzed for up to 7 days. RESULTS: MSC viability immediately after spraying and subsequent metabolic activity for 7 days was not influenced by either of the devices. Slightly higher cytotoxicity rates could be observed for pressure-atomized compared with control and air-atomized MSCs over 7 days. Flow cytometry revealed no changes in characteristic MSC cell surface marker expression, and morphology remained unchanged. Standard differentiation into osteocytes, chondrocytes and adipocytes was inducible after atomization. CONCLUSIONS: In the literature, a minimal survival of 50% was previously defined as the cutoff value for successful cell atomization. This is easily met with both of the authors' devices, with more than 90% survival. Thus, there is a potential role for atomization in intrapulmonary MSC-based cell therapies, as it is a feasible and easily utilizable approach based on clinically available equipment.

Clinical course of COVID-19 patients needing supplemental oxygen outside the intensive care unit.

Patients suffering from CVOID-19 mostly experience a benign course of the disease. Approximately 14% of SARS-CoV2 infected patients are admitted to a hospital. Cohorts exhibiting severe lung failure in the form of acute respiratory distress syndrome (ARDS) have been well characterized. Patients without ARDS but in need of supplementary oxygen have received much less attention. This study describes the diagnosis, symptoms, treatment and outcomes of hospitalized patients with COVID-19 needing oxygen support during their stay on regular ward. All 133 patients admitted to the RWTH Aachen university hospital with the diagnosis of COVID-19 were included in an observational registry. Clinical data sets were extracted from the hospital information system. This analysis includes all 57 patients requiring supplemental oxygen not admitted to the ICU. 57 patients needing supplemental oxygen and being treated outside the ICU were analyzed. Patients exhibited the typical set of symptoms for COVID-19. Of note, hypoxic patients mostly did not suffer from clinically relevant dyspnea despite oxygen saturations below 92%. Patients had fever for 7 [2-11] days and needed supplemental oxygen for 8 [5-13] days resulting in an overall hospitalization time of 12 [7-20] days. In addition, patients had persisting systemic inflammation with CRP levels remaining elevated until discharge or death. This description of COVID-19 patients requiring oxygen therapy should be taken into account when planning treatment capacity. Patients on oxygen need long-term inpatient care.

Comparison of the SARS-CoV-2 Rapid antigen test to the real star Sars-CoV-2 RT PCR kit.

There is an ongoing need for reliable antigen assays for timely and easy detection of individuals with acute SARS-CoV-2 infection. Using 75 swabs from patients previously tested positive by SARS-CoV-2 PCR and 75 swabs from patients previously tested negative by SARS-CoV-2 PCR, we investigated the sensitivity and specificity of the SARS-CoV-2 Rapid Antigen Test (Roche). We determined a specificity of 96 %. The assay's sensitivity with samples with a cycle threshold of < 25, 25 - <30, 30 - <35, and> = 35 was 100 %, 95 %, 44.8 % and 22.2 %, respectively. We conclude that sensitivity and specificity of the antigen assay is inferior to the PCR assay. However, the antigen assay may be a quick and easy to perform alternative for differentiation of individuals contagious for SARS-CoV-2 from non-contagious individuals.

Determination of SARS-CoV-2 antibodies with assays from Diasorin, Roche and IDvet.

There is an ongoing need for highly reliable serological assays to detect individuals with past SARS-CoV-2 infection. Using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR, we investigated the sensitivity and specificity of the Liaison SARS-CoV-2 S1/S2 IgG assay (DiaSorin), the Elecsys Anti-SARS-CoV-2 assay (Roche), and the ID Screen SARS-CoV-2-N IgG indirect kit (IDVet). We determined a sensitivity of 95.5 %, 95.5 %, and 100 % and a specificity of 90.5 %, 96.2 %, and 92.5 % for the DiaSorin assay, the Roche assay, and the IDVet assay, respectively. We conclude that serologic assays combining very high sensitivity and specificity are still not commercially available for SARS-CoV-2. For maximizing sensitivity and specificity of SARS-CoV-2 serological diagnostics, the combination of two assays may be helpful.

Comparison of four new commercial serologic assays for determination of SARS-CoV-2 IgG.

BACKGROUND: Facing the ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for serological assays identifying individuals with past coronavirus disease 2019 (COVID-19). STUDY DESIGN: Our study is the first to compare four new commercially available assays using 75 sera from patients tested positive or negative by SARS-CoV-2 PCR: the anti SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany), the EDI New Coronavirus COVID-19 IgG ELISA, (Epitope diagnostics (EDI), USA), the recomWell SARS-CoV-2 IgG ELISA (Mikrogen, Germany), and the SARS-CoV-2 Virachip IgG (Viramed, Germany). RESULTS: We found a sensitivity of 86.4 %, 100 %, 86.4 %, and 77.3 % and a specificity of 96,2 %, 88,7 %, 100 %, and 100 % for the Euroimmun assay, the EDI assay, the Mikrogen assay, and the Viramed assay, respectively. CONCLUSIONS: Commercially available SARS-CoV-2 IgG assays have a sufficient specificity and sensitivity for identifying individuals with past SARS-CoV-2 infection.

EndOxy: Mid-term stability and shear stress resistance of endothelial cells on PDMS gas exchange membranes.

Endothelialized oxygenator devices (EndOxy) with a physiological, nonthrombogenic, and anti-inflammatory surface offer the potential to overcome current shortcomings of conventional extracorporeal membrane oxygenation such as complications like thromboembolism and bleeding that deteriorate adequate long-term hemocompatibility. The approach of endothelialization of gas exchange membranes, and thus the formation of a nonthrombogenic and anti-inflammatory surface, is promising. In this study, we investigated the mid-term shear stress resistance as well as gas transfer rates and cell densities of endothelial cells seeded on RGD-conjugated polydimethylsiloxane (RGD-PDMS) gas exchange membranes under dynamic conditions. Human umbilical vein endothelial cells were seeded on RGD-PDMS and exposed to defined shear stresses in a microfluidic bioreactor. Endothelial cell morphology was assessed by bright field microscopy and immunocytochemistry. Furthermore, gas transfer measurement of blank, RGD-conjugated, and endothelialized PDMS oxygenator membranes was performed. RGD-PDMS gas exchange membranes proved suitable for the dynamic culture of endothelial cells for up to 21 days at a wall shear stress of 2.9 dyn/cm2 . Furthermore, the cells resisted increased wall shear stresses up to 8.6 dyn/cm2 after a previous dynamic preculture of each one hour at 2.9 dyn/cm2 and 5.7 dyn/cm2 . Also, after a longer dynamic preculture of three days at 2.9 dyn/cm2 and one hour at 5.7 dyn/cm2 , increased wall shear stresses of 8.6 dyn/cm2 were tolerated by the cells and cell integrity could be remained. Gas transfer (GT) tests revealed that neither RGD conjugation nor endothelialization of RGD-PDMS significantly decrease the gas transfer rates of the membranes during short-term trials. Gas transfer rates are stable for at least 72 hours of dynamic cultivation of endothelial cells. Immunocytochemistry showed that the cell layer stained positive for typical endothelial cell markers CD31 and von Willebrand factor (VWF) after all trials. Cell density of EC on RGD-PDMS increased between 3 and 21 days of dynamic culture. In this study, we show the suitability of RGD-PDMS membranes for flow resistant endothelialization of gas-permeable membranes, demonstrating the feasibility of this approach for a biohybrid lung.

Choosing the Right Differentiation Medium to Develop Mucociliary Phenotype of Primary Nasal Epithelial Cells In Vitro.

In vitro differentiation of airway epithelium is of interest for respiratory tissue engineering and studying airway diseases. Both applications benefit from the use of primary cells to maintain a mucociliated phenotype and thus physiological functionality. Complex differentiation procedures often lack standardization and reproducibility. To alleviate these shortfalls, we compared differentiation behavior of human nasal epithelial cells in four differentiation media. Cells were differentiated at the air-liquid interface (ALI) on collagen-coated inserts. Mucociliary differentiation status after five weeks was analyzed by electron microscopy, histology and immunohistochemistry. The amount of ciliation was estimated and growth factor concentrations were evaluated using ELISA. We found that retinoic-acid-supplemented mixture of DMEM and Airway Epithelial Cell Growth Medium gave most promising results to obtain ciliated and mucus producing nasal epithelium in vitro. We discovered the balance between retinoic acid (RA), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and fibroblast growth factor ß (FGF-ß) to be relevant for differentiation. We could show that low VEGF, EGF and FGF-ß concentrations in medium correspond to absent ciliation in specific donors. Therefore, our results may in future facilitate donor selection and non-invasive monitoring of ALI cultures and by this contribute to improved standardization of epithelial in vitro culture.

EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung.

In the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today's oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n = 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future.

Cardiac stress after electroconvulsive therapy and spontaneous generalized convulsive seizures: A prospective echocardiographic and blood biomarker study.

AIM: Knowledge about cardiac stress related to seizures in electroconvulsive therapy (ECT) and spontaneously occurring generalized convulsive seizures (GCS) is limited. The aim of the present study was to analyze cardiac function and circulating markers of cardiac stress in the early postictal period after ECT and GCS. METHODS: Patients undergoing ECT in the Department of Psychiatry, Psychotherapy and Psychosomatics and patients undergoing diagnostic video-EEG monitoring (VEM) in the Department of Neurology were prospectively enrolled between November 2017 and November 2018. Cardiac function was examined twice using transthoracic echocardiography within 60 min and >4 h after ECT or GCS. Established blood markers (troponin T high-sensitive, N-terminal pro brain natriuretic peptide) of cardiac stress or injury were collected within 30 min, 4 to 6 h, and 24 h after ECT or GCS. In the ECT group, the troponin T values were also correlated with periprocedural heart rate and blood pressure values. Because of organizational or technical reasons, the measurement was not performed in all patients. RESULTS: Twenty patients undergoing ECT and 6 patients with epilepsy with a GCS during VEM were included. Postictal echocardiography showed no wall motion disorders and no change in left ventricular and right ventricular functions. Four of 17 patients displayed a transient increase in high-sensitive cardiac troponin T 4-6 h after the seizure (3 patients with ECT-induced seizure). None of these 4 patients had signs of an acute cardiac event, and periprocedural blood pressure or heart rate peaks during ECT did not significantly differ in patients with and without troponin T elevation. CONCLUSIONS: Signs of mild cardiac stress can occur in some patients following ECT or GCS without clinical complications, probably related to excessive catecholamine release during the seizure.

Comparison of Covered Laser-cut and Braided Respiratory Stents: From Bench to Pre-Clinical Testing.

Lung cancer patients often suffer from severe airway stenosis, the symptoms of which can be relieved by the implantation of stents. Different respiratory stents are commercially available, but the impact of their mechanical performance on tissue responses is not well understood. Two novel laser-cut and hand-braided nitinol stents, partially covered with polycarbonate urethane, were bench tested and implanted in Rhön sheep for 6 weeks. Bench testing highlighted differences in mechanical behavior: the laser-cut stent showed little foreshortening when crimped to a target diameter of 7.5 mm, whereas the braided stent elongated by more than 50%. Testing also revealed that the laser-cut stent generally exerted higher radial resistive and chronic outward forces than the braided stent, but the latter produced significantly higher radial resistive forces at diameters below 9 mm. No migration was observed for either stent type in vivo. In terms of granulation, most stents exerted a low to medium tissue response with only minimal formation of granulation tissue. We have developed a mechanical and in vivo framework to compare the behavior of different stent designs in a large animal model, providing data, which may be employed to improve current stent designs and to achieve better treatment options for lung cancer patients.

Endobronchial ultrasound-guided transbronchial needle aspiration under general anesthesia versus bronchoscopist-directed deep sedation: A retrospective analysis.

BACKGROUND: Different sedation strategies are used during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnostic workup of lung cancer including general anesthesia (GA) and moderate sedation. However, no data are available about EBUS-TBNA under deep sedation (DS) with fiberoptic intubation directed by the investigator. MATERIALS AND METHODS: A retrospective analysis of EBUS-TBNAs under GA (n = 160) or DS (n = 105) was performed. RESULTS: Unadjusted diagnostic yield did not differ significantly between the groups (GA: 42.5% vs. DS: 53.3%P= 0.1018). Similar results were obtained when only patients with a final diagnosis of malignancy were analyzed (GA: 53.6% vs. DS: 61.5%P= 0.2675). Adverse events (AEs) occurred more often under DS (GA: 27.5% vs. DS: 59.1%P< 0.0001) due to more sedation-related problems whereas severe AEs tended to be higher under GA (GA: 7.5% vs. DS: 1.9%P= 0.0523). CONCLUSION: In summary, our data show that the diagnostic yield and the complication rate of EBUS-TBNA performed under DS are similar compared to GA. Hence, in an appropriate setting, EBUS-TBNA can be performed safely under DS.