Das schwere Thoraxtrauma gehört zu den häufigsten und potenziell letalen Verletzungen beim Schwerverletzten. Fast 50

Purpose:Accurate mediastinal staging of non-small cell lung cancer is essential for guiding curative treatment strategies, particularly regarding the indication for neoadjuvant therapy. This study evaluated pretherapeutic predictive factors for mediastinal lymph node metastases based on routinely collected clinico-pathological data. Patients and Methods:We retrospectively analysed data from all patients who underwent video-assisted mediastinoscopic lymphadenectomy for mediastinal staging before curatively-intended treatment during a 12-year period. Logistic regression and ROC analyses were used to identify independent risk factors for histologically confirmed N2/N3 involvement. Results:Clinical N2 status based on PET/CT was the strongest independent predictor of mediastinal metastasis. However, even patients with cN1 status showed a significantly increased risk. Adenocarcinoma histology (OR 2.3; p < 0.01) and central tumour location (OR 2.1; p < 0.01) were also independently associated with mediastinal involvement. ROC analysis identified a tumour size ≥ 3 cm as a potential cutoff, although discrimination was limited (AUC 0.588). Conclusion:Mediastinal lymph node involvement in NSCLC is not restricted to patients with abnormal PET/CT findings. Central tumours, adenocarcinoma or lesions > 3 cm should undergo invasive staging, regardless of imaging appearance.

Severe thoracic trauma is among the most frequent and potentially lethal injuries in severely injured patients. Almost 50% of polytrauma patients present with relevant chest trauma (AIS >= 3). The spectrum ranges from chest wall instability and pulmonary contusions to life-threatening injuries of the heart, great vessels, and tracheobronchial tree. While initial ATLS-based management is well established, treatment strategies for severe chest wall injuries have shifted in recent years from predominantly non-operative care towards early surgical stabilization. This paradigm change is driven by growing evidence that rapid restoration of chest wall integrity and biomechanics significantly reduces morbidity (e.g. pneumonia, ventilation time, ICU stay) and mortality. This CME article summarises current diagnostics and therapy, outlines indications and contraindications for operative interventions, and reviews complication management in severe thoracic trauma management.

Introduction Video-assisted thoracoscopic surgery (VATS) lobectomy is a commonly employed surgical technique for the management of operable early stage non-small cell lung cancer (NSCLC). This procedure, however, is dependent on the patient’s ability to tolerate surgery. In light of this, stereotactic ablative radiotherapy (SABR) has emerged as a viable alternative treatment strategy for patients who are inoperable or who refuse surgery. Considering the lack of randomised controlled trials and the increased risk of bias in observational cohort studies, this study protocol proposes an emulated target trial design to investigate the causal effect of SABR, in comparison to VATS, on overall survival in operable early stage NSCLC patients.Methods and analysis Data on NSCLC patients will be collected from routinely collected university hospital records linked with German cancer registry data. This study protocol was developed using the target trial methodology outlined by Hernan et al. The protocol establishes specific parameters for key trial components in order to mitigate bias in the analysis of observational data and to facilitate the calculation of causal estimands. The target trial design that would be emulated is a multicentre open-label two-parallel arm superiority randomised trial. Mediators and confounding variables were determined through the use of a directed acyclic graph. The statistical analysis aims to measure the per-protocol and intention to treat effect of SABR versus VATS within 3 months of diagnosis, on survival, through the difference in restricted mean survival times, using weighted non-parametric Kaplan-Meier curves.Ethics and dissemination The Ethics Committee of the Medical Faculty of Martin Luther University Halle-Wittenberg with an approved addendum with Dnr 2023–112 has approved this study. The study uses anonymised routinely collected hospital and cancer registry data in accordance with applicable data protection regulations. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

ABSTRACT Innate defenses of the respiratory epithelium are the first barrier against incoming respiratory viruses. To understand the contribution of both basal (tonic) and induced interferon (IFN) to antiviral defenses in a physiologically relevant system, we established air-liquid interface (ALI) cultures of primary human bronchial epithelium (HBE) and small airway epithelium (HSE). Via an organoid intermediate stage, the limited healthy donor material was expanded while preserving stemness, and subsequently differentiated. Characterization by immunofluorescent profiling and transcriptomic analyses showed that the cellular diversity and architecture of our ALI cultures were comparable to native human lung epithelium. Infection with human rhinovirus (HRV16) induced a strong and early IFN response, whereas human coronavirus (HCoV-229E and HCoV-NL63) infection caused a more subdued and delayed response. HRV16, but not HCoV-229E, infection was eventually cleared from the cultures after more than 30 days. Depletion of tonic or early type I/III IFNs using neutralizing antibodies or scavengers increased infectious HRV production by ~10- or ~1,000-fold, respectively, suggesting a role of IFNs in clearance. Taken together, we present a method for generating primary lung epithelial air-liquid interface cultures that retain effective IFN responses, demonstrate clearance of HRV by innate defenses, and highlight the importance of tonic and early IFN.IMPORTANCEMild respiratory viral infections, for example, with human common cold coronaviruses or rhinoviruses, are a massive cause of human morbidity. The respiratory tract is the primary entry route for these viruses and also the contact site for initial innate immune defenses. Here, we show that primary human lung epithelial cell-derived air-liquid interface cultures mimic the architecture and cell composition of native human lung epithelium, and retain both induced and tonic interferon (IFN) responses. Notably, our data show that the model’s innate immune defense, characterized by rapid and robust IFN responses, are sufficient to clear human rhinovirus (HRV) infections but not human coronavirus 229E. Finally, depletion of induced or tonic IFNs led to a marked increase in HRV infection. Thus, our data suggest that tonic low levels of IFNs contribute to the epithelial defense against viruses, maintaining the tissue’s immune readiness.

Digital learning resources are in increasing demand, especially in the light of the planned reform of the medical licensing regulations for 2028. In a pilot project, we digitised and evaluated a logbook for students in their practical year (PJ).The aim of this study is to evaluate the digital and non-digital PJ logbooks.Based on a printed PJ logbook, a digital PJ logbook was developed as a web app. The implementation was performed using the commercial enterprise knowledge management system Confluence (Atlassian Corporation, Sydney, Australia), which allows responsive design, integration with the university's user directory, and incorporation of corporate design. Student satisfaction (n = 34) was assessed using questionnaires and a 5-level Likert scale. Additionally, students self-assessed their skills at the beginning and end of the rotation before (n = 49) and after (n = 34) the introduction of the digital logbook by grade points.The majority of students found the digital logbook to be an intuitive and a valuable addition. In the stationary setting, the introduction of the digital logbook led to a significant improvement in self-assessed skills by 0.73 grade points at the beginning (p < 0.001) and 0.78 grade points at the end of the rotation (p < 0.001). In the operating theatre, there was only a significant improvement of 0.47 grade points at the beginning of the rotation (p = 0.027).The evaluation demonstrates that the digital PJ logbook is well-received by students and significantly improves their self-assessed skills. The observed increase in self-assessed skills could be attributed to the introduction of the digital logbook and its contents, although other factors, such as the engagement of the instructors, cannot be excluded. Future modifications are planned to make the logbook more appealing.

Lung cancer is the leading cause for cancer related death worldwide. One treatment option for patients with pulmonary adenocarcinoma is the targeted therapy gefitinib (Iressa®, ZD1839). As with other promising targeted therapies, desired in vivo effects of gefitinib came short to in vitro expectations, as preclinical testing is hampered by an inaccuracy of existing models and resistances develop frequently. We analysed the pharmacodynamics of gefitinib in a 3D tissue engineered human lung cancer model of HCC827 cells, as well as a resistant subpopulation of HCCres A2 cells. In 2D cell culture, a cell viability of 50 % was reached after treatment with 0.01-0.05 μM gefitinib. In the 3D model administering higher doses of gefitinib did not lead to a further reduction in viability and proliferation, or an increase in apoptosis. This shows that the pharmacodynamic effect of promising new therapies can often be overestimated in 2D versus 3D models. The results we obtained for gefitinib testing in the 3D models reflect astonishing well the efficacy of priorly published clinical data, suggesting that our 3D tumor models can display in vivo conditions more accurately, bridging the gap to living organisms. To mimic the clinical setting further, the lung cancer cells were cultivated under dynamic conditions in a bioreactor. The exploration of a resistant subpopulation confirmed an epithelial-mesenchymal transition. The described 3D lung cancer model can be used as a refined, preclinical testing platform for targeted therapies and with clinically relevant pharmacodynamic properties as shown exemplary for gefitinib.

The covid 19 pandemic has had a significant impact on healthcare worldwide, yet the effects on the surgical treatment of lung cancer patients in Germany have not yet been adequately studied.This retrospective analysis used data from the German Thoracic Register. The surgical treatment of 2989 patients with bronchial carcinoma was analysed in two periods: 2020-2021 (pandemic phase: 1297 patients) and 2018-2019 (pre-pandemic phase: 1692 patients) across 8 German hospitals.During the pandemic phase, the number of complex surgeries decreased, and the need for intensive care dropped from 39.7% to 19.4% (p < 0.001). The rates of neoadjuvant chemotherapy and radiation therapy decreased from 44% to 17% and 20% to 5%, respectively (both p < 0.001). Simultaneously, a significant reduction in postoperative complications, particularly pneumonia (8.5% to 6.2%, p = 0.020), was observed.The lower complication rates may be attributed to stricter hygiene measures and reduced visitor access during the pandemic. Consideration of these risk factors in postoperative patient care may help improve the prognosis of surgically treated lung cancer patients in the future.

Background The optimal management for spontaneous pneumothorax (SP) remains contentious, with various proposed approaches. This joint clinical practice guideline from the ERS, EACTS and ESTS societies provides evidence -based recommendations for the management of SP. Methods This multidisciplinary Task Force addressed 12 key clinical questions on the management of pneumothorax, using ERS methodology for guideline development. Systematic searches were performed in MEDLINE and Embase. Evidence was synthesised by conducting meta -analyses, if possible, or narratively. Certainty of evidence was rated with GRADE (Grading of Recommendations, Assessment, Development and Evaluations). The Evidence to Decision framework was used to decide on the direction and strength of the recommendations. Results The panel makes a conditional recommendation for conservative care of minimally symptomatic patients with primary spontaneous pneumothorax (PSP) who are clinically stable. We make a strong recommendation for needle aspiration over chest tube drain for initial PSP treatment. We make a conditional recommendation for ambulatory management for initial PSP treatment. We make a conditional recommendation for early surgical intervention for the initial treatment of PSP in patients who prioritise recurrence prevention. The panel makes a conditional recommendation for autologous blood patch in secondary SP patients with persistent air leak (PAL). The panel could not make recommendations for other interventions, including bronchial valves, suction, pleurodesis in addition to surgical resection or type of surgical pleurodesis. Conclusions With this international guideline, the ERS, EACTS and ESTS societies provide clinical practice recommendations for SP management. We highlight evidence gaps for the management of PAL and recurrence prevention, with research recommendations made.