Oxidative stress leads to impaired T cell activation. A central integrator of T cell activation is the actin-remodelling protein cofilin. Cofilin is activated through dephosphorylation at Ser3. Activated cofilin enables actin dynamics through severing and depolymerization of F-actin. Binding of cofilin to actin is required for formation of the immune synapse and T cell activation. Here, we showed that oxidatively stressed human T cells were impaired in chemotaxis- and costimulation-induced F-actin modulation. Although cofilin was dephosphorylated, steady-state F-actin levels increased under oxidative stress conditions. Mass spectrometry revealed that cofilin itself was a target for oxidation. Cofilin oxidation induced formation of an intramolecular disulfide bridge and loss of its Ser3 phosphorylation. Importantly, dephosphorylated oxidized cofilin, although still able to bind to F-actin, did not mediate F-actin depolymerization. Impairing actin dynamics through oxidation of cofilin provides a molecular explanation for the T cell hyporesponsiveness caused by oxidative stress.
Stent placement has been established as a standard procedure for treating airway obstructions. Other indications are localized malacias and fistulas. Though many different stents with various diameters and lengths are available, the shapes are hardly ever ideal because of the distorted anatomy in patients with diseased airways. There are technical and legal limitations for customizing purchased airway stents. Individually tailored stents would be preferable. New techniques of additive manufacturing such as 3D printing make it possible to produce optimized stents for a particular patient. Using CT data and bronchoscopic images, stents can be constructed that match a particular anatomical situation and apply the optimized expansion force. We give an overview of the currently available manufacturing techniques for polymeric stents and report about our own experience. Direct on-site printing of polyurethane stents in a hospital and printing individual extrusion molds for silicone stents in a certified cleanroom are both feasible. Furthermore, there are promising attempts of combining mechanically customized stents with surface modifications, drug-eluting features, biodegradability, and time-dependent adaptation (4D printing). Truly optimized airway stents with the potential of solving the well-known stent problems such as granulation tissue formation, remodeling, mucostasis, and infections are in reach. The technical hurdles are probably easier to overcome than the legal constraints. The legal situations are discussed from a physician's and a manufacturer's perspective.
Background. Pneumothorax is a common side effect in interventional pulmonology. The ideal moment for detection with chest X-ray or ultrasound has not yet been defined. Earlier studies demonstrated the utility of performing these tests with a certain delay, which always results in a potentially dangerous gap. Methods. We prospectively enrolled patients with pulmonary interventions at increased risk of pneumothorax. Thoracic ultrasound was performed immediately after the intervention and at the moment of chest X-ray with a delay up to two hours. Results: Overall, we detected four pneumothoraxes in 115 procedures. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 75%, 100%, 100%, 99%, 99% for ultrasound and 75%, 90%, 21%, 99% und 89% for chest X-ray respectively. All pneumothoraces requiring chest tube were sufficiently detected by both methods. Conclusion. Thoracic ultrasound when performed immediately can more accurately exclude pneumothorax after interventional bronchoscopy when compared to chest X-ray. Further ultrasound examinations are unnecessary.
<b><i>Background:</i></b> Endobronchial ultrasound (EBUS) with transbronchial needle aspiration increases the diagnostic yield of lung cancer staging. The left adrenal gland (LAG) is a common site for lung cancer metastasis. The modality of transesophageal examination with an EBUS bronchoscope (EUS-B) routinely for LAG has not been assessed. <b><i>Objective:</i></b> The aim of this study was to prospectively assess if evaluation and tissue sampling of the LAG could routinely be implemented in an EBUS procedure. <b><i>Methods:</i></b> Patients referred for EBUS between March and August 2017 had assessment of the LAG via EUS-B. Fine-needle aspiration (FNA) was performed in cases with a suspicious LAG. The detection rate, procedure time, and learning curve of four experienced EBUS-bronchoscopists was assessed, plus the diagnostic accuracy and complication rate of FNA. <b><i>Results:</i></b> In total, 313 consecutive patients were included. The overall LAG detection rate was 87.5%. After the initial learning curve, the detection rate for all four bronchoscopists was >93%. The detection rate did not correlate with any patient characteristics. EUS-B-FNA revealed nine LAG metastases, with a sensitivity, specificity, and accuracy of 75%, 100%, and 99%, respectively. The mean EUS-B operation time was 194.4 s, with 594.8 s for FNA. There were no FNA-associated complications. <b><i>Conclusions:</i></b> Evaluation of the LAG with EUS-B could routinely be included in an EBUS procedure if necessary. A high detection rate can be achieved after an initial learning period. FNA of the LAG was feasible and safe. EUS-B of the LAG could be integrated into the usual EBUS/EUS-B procedure in lung cancer staging workup.
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