ZusammenfassungDie Deutsche Gesellschaft für Pneumologie hat die AWMFS1-Leitlinie Post-COVID/Long-COVID initiiert. In einem breiten interdisziplinären Ansatz wurde diese S1-Leitlinie basierend auf dem aktuellen Wissensstand gestaltet.Die klinische Empfehlung beschreibt die aktuellen Post-COVID/Long-COVID-Symptome, diagnostische Ansätze und Therapien.Neben der allgemeinen und konsentierten Einführung wurde ein fachspezifischer Zugang gewählt, der den aktuellen Wissensstand zusammenfasst.Die Leitlinie hat einen expilzit praktischen Anspruch und wird basierend auf dem aktuellen Wissenszugewinn vom Autorenteam stetig weiterentwickelt und adaptiert.

<b><i>Background:</i></b> COVID-19 survivors face the risk of long-term sequelae including fatigue, breathlessness, and functional limitations. Pulmonary rehabilitation has been recommended, although formal studies quantifying the effect of rehabilitation in COVID-19 patients are lacking. <b><i>Methods:</i></b> We conducted a prospective observational cohort study including consecutive patients admitted to an outpatient pulmonary rehabilitation center due to persistent symptoms after COVID-19. The primary endpoint was change in 6-min walk distance (6MWD) after undergoing a 6-week interdisciplinary individualized pulmonary rehabilitation program. Secondary endpoints included change in the post-COVID-19 functional status (PCFS) scale, Borg dyspnea scale, Fatigue Assessment Scale, and quality of life. Further, changes in pulmonary function tests were explored. <b><i>Results:</i></b> Of 64 patients undergoing rehabilitation, 58 patients (mean age 47 years, 43% women, 38% severe/critical COVID-19) were included in the per-protocol-analysis. At baseline (i.e., in mean 4.4 months after infection onset), mean 6MWD was 584.1 m (±95.0), and functional impairment was graded in median at 2 (IQR, 2–3) on the PCFS. On average, patients improved their 6MWD by 62.9 m (±48.2, <i>p</i> &#x3c; 0.001) and reported an improvement of 1 grade on the PCFS scale. Accordingly, we observed significant improvements across secondary endpoints including presence of dyspnea (<i>p</i> &#x3c; 0.001), fatigue (<i>p</i> &#x3c; 0.001), and quality of life (<i>p</i> &#x3c; 0.001). Also, pulmonary function parameters (forced expiratory volume in 1 s, lung diffusion capacity, inspiratory muscle pressure) significantly increased during rehabilitation. <b><i>Conclusion:</i></b> In patients with long COVID, exercise capacity, functional status, dyspnea, fatigue, and quality of life improved after 6 weeks of personalized interdisciplinary pulmonary rehabilitation. Future studies are needed to establish the optimal protocol, duration, and long-term benefits as well as cost-effectiveness of rehabilitation.

STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting STAT3 is currently proposed as therapeutic intervention. Here we demonstrate that STAT3 plays an unexpected tumour-suppressive role in KRAS mutant lung adenocarcinoma (AC). Indeed, lung tissue-specific inactivation of Stat3 in mice results in increased KrasG12D-driven AC initiation and malignant progression leading to markedly reduced survival. Knockdown of STAT3 in xenografted human AC cells increases tumour growth. Clinically, low STAT3 expression levels correlate with poor survival and advanced malignancy in human lung AC patients with smoking history, which are prone to KRAS mutations. Consistently, KRAS mutant lung tumours exhibit reduced STAT3 levels. Mechanistically, we demonstrate that STAT3 controls NF-κB-induced IL-8 expression by sequestering NF-κB within the cytoplasm, thereby inhibiting IL-8-mediated myeloid tumour infiltration and tumour vascularization and hence tumour progression. These results elucidate a novel STAT3–NF-κB–IL-8 axis in KRAS mutant AC with therapeutic and prognostic relevance.

No abstract

ZusammenfassungDie Deutsche Gesellschaft für Pneumologie hat 2021 die AWMF S1-Leitlinie Long-/Post-COVID initiiert. In einem breiten interdisziplinären Ansatz wurde diese S1-Leitlinie basierend auf dem aktuellen Wissensstand gestaltet.Die klinische Empfehlung beschreibt die aktuellen Long- bzw. Post-COVID-Symptome, diagnostische Ansätze und Therapien.Neben der allgemeinen und konsentierten Einführung wurde ein fachspezifischer Zugang gewählt, der den aktuellen Wissensstand zusammenfasst.Die Leitlinie hat einen explizit praktischen Anspruch und wird basierend auf dem aktuellen Wissenszugewinn vom Autorenteam weiterentwickelt und adaptiert.