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ZusammenfassungIn den vergangenen Jahren hat der Einsatz mechanischer Unterstützungssysteme für Patienten mit Herz- und Kreislaufversagen kontinuierlich zugenommen, sodass in Deutschland mittlerweile jährlich etwa 3000 ECLS/ECMO-Systeme implantiert werden. Vor dem Hintergrund bislang fehlender umfassender Leitlinien bestand ein dringlicher Bedarf an der Formulierung evidenzbasierter Empfehlungen zu den zentralen Aspekten der ECLS/ECMO-Therapie.Im Juli 2015 wurde daher die Erstellung einer S3-Leitlinie durch die Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie (DGTHG) bei der zuständigen Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) angemeldet. In einem strukturierten Konsensusprozess mit Einbindung von Experten aus Deutschland, Österreich und der Schweiz, delegiert aus 11 AWMF-Fachgesellschaften, 5 weiteren Fachgesellschaften sowie der Patientenvertretung, entstand unter Federführung der DGTHG die Leitlinie „Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen“, die im Februar 2021 publiziert wurde.Die Leitlinie fokussiert auf klinische Aspekte der Initiierung, Fortführung, Entwöhnung und Nachsorge und adressiert hierbei auch strukturelle und ökonomische Fragestellungen. Dieser Artikel präsentiert eine Übersicht zu der Methodik und den konsentierten Empfehlungen.

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.In den vergangenen Jahren hat der Einsatz mechanischer Unterstützungssysteme für Patienten mit Herz- und Kreislaufversagen kontinuierlich zugenommen, sodass in Deutschland mittlerweile jährlich etwa 3000 ECLS-/ECMO-Systeme implantiert werden. Vor dem Hintergrund bislang fehlender umfassender Leitlinien bestand ein dringlicher Bedarf an der Formulierung evidenzbasierter Empfehlungen zu den zentralen Aspekten der ECLS-/ECMO-Therapie. Im Juli 2015 wurde daher die Erstellung einer S3-Leitlinie durch die Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie (DGTHG) bei der zuständigen Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF) angemeldet. In einem strukturierten Konsensusprozess mit Einbindung von Experten aus Deutschland, Österreich und der Schweiz, delegiert aus 11 AWMF-Fachgesellschaften, 5 weiteren Fachgesellschaften sowie der Patientenvertretung, entstand unter Federführung der DGTHG die Leitlinie „Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen“, die im Februar 2021 publiziert wurde. Die Leitlinie fokussiert auf klinische Aspekte der Initiierung, Fortführung, Entwöhnung und Nachsorge und adressiert hierbei auch strukturelle und ökonomische Fragestellungen. Dieser Artikel präsentiert eine Übersicht zu der Methodik und den konsentierten Empfehlungen.

Objectives: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). Design: Multicenter retrospective, observational study. Setting: Ten tertiary referral university and community hospitals. Participants: Patients with confirmed severe COVID-19-related ARDS. Interventions: Venovenous or venoarterial ECMO. Measurements and Main Results: One hundred thirty-two patients (mean age 51.1 +/- 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 +/- 4.4, mean pH was 7.23 +/- 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 +/- 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 +/- 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. Conclusions: The present findings suggested that about half of adult patients with severe COVID-19 -related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. (C) 2021 The Authors. Published by Elsevier Inc.

Pandemic outbreaks of viruses such as influenza virus or SARS-CoV-2 are associated with high morbidity and mortality and thus pose a massive threat to global health and economics. Physiologically relevant models are needed to study the viral life cycle, describe the pathophysiological consequences of viral infection, and explore possible drug targets and treatment options. While simple cell culture-based models do not reflect the tissue environment and systemic responses, animal models are linked with huge direct and indirect costs and ethical questions.

SARS-CoV-2 is the causative agent of the immune response-driven disease COVID-19 for which new antiviral and anti-inflammatory treatments are urgently needed to reduce recovery time, risk of death and long COVID development. Here, we demonstrate that the immunoregulatory kinase p38 MAPK is activated during viral entry, mediated by the viral spike protein, and drives the harmful virus-induced inflammatory responses. Using primary human lung explants and lung epithelial organoids, we demonstrate that targeting p38 signal transduction with the selective and clinically pre-evaluated inhibitors PH-797804 and VX-702 markedly reduced the expression of the pro-inflammatory cytokines IL6, CXCL8, CXCL10 and TNF-α during infection, while viral replication and the interferon-mediated antiviral response of the lung epithelial barrier were largely maintained. Furthermore, our results reveal a high level of drug synergism of both p38 inhibitors in co-treatments with the nucleoside analogs Remdesivir and Molnupiravir to suppress viral replication of the SARS-CoV-2 variants of concern, revealing an exciting and novel mode of synergistic action of p38 inhibition. These results open new avenues for the improvement of the current treatment strategies for COVID-19.

Aims Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. Methods A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. Results Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. Conclusion The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.Seit einigen Jahren ist eine stetige Zunahme des Einsatzes von mechanischen extrakorporalen Herz-Kreislauf- und Lungenunterstützungssystemen (ECLS/ECMO) zu verzeichnen. So wurden seit 2015 in Deutschland jährlich bei etwa 3000 Patienten ECLS/ECMO-Systeme implantiert. Trotz dieser häufigen Anwendung der passageren Unterstützungssysteme existieren zurzeit national und international nur Leitlinien zum Einsatz der ECMO/ECLS, die erkrankungsbezogene Teilaspekte komplexer Therapiekaskaden adressieren. Vor diesem Hintergrund erschien es notwendig, evidenzbasierte Empfehlungen zur ECLS/ECMO-Therapie im Hinblick auf Indikationen und das komplexe Patientenmanagement zu verfassen, in denen personelle, prozessuale und infrastrukturelle Anforderungen definiert werden. Aus diesem Grund erfolgte im Juli 2015 durch die Deutsche Gesellschaft für Thorax‑, Herz- und Gefäßchirurgie (DGTHG) die Anmeldung einer diesbezüglichen S3-Leitlinie bei der zuständigen Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF). Im Mittelpunkt der Leitlinie steht die klinische Anwendung der ECLS/ECMO-Therapie; ergänzend werden auch strukturelle und ökonomische Aspekte adressiert. Unter Federführung der DGTHG wurde mit Einbindung von Experten aus Deutschland, Österreich und der Schweiz, delegiert aus 11 AWMF-Fachgesellschaften, 5 weiteren Fachgesellschaften sowie der Patientenvertretung, die S3-Leitlinie im Februar 2021 publiziert. Dieser Artikel stellt eine kurze Zusammenfassung des methodischen Konzepts sowie aller konsentierten Empfehlungen für jede bearbeitete Fragestellung der Leitlinie dar.

Influenza is an acute respiratory infection causing high morbidity and mortality in annual outbreaks worldwide. Antiviral drugs are limited and pose the risk of resistance development, calling for new treatment options. IFN-α subtypes are immune-stimulatory cytokines with strong antiviral activities against IAV in vitro and in vivo. However, the clinical use of IFN-α2, the only licensed subtype of this multi-gene family, could not prevent or limit IAV infections in humans. However, the other subtypes were not investigated. Therefore, this study evaluated the induction and antiviral potential of all human IFN-α subtypes during H3N2 IAV infection in human lung explants. We found that subtypes with weak antiviral activities were preferentially induced during IAV infection in human lungs. Intriguingly, non-induced subtypes α16, α5 and α4 suppressed viral replication up to 230-fold more efficiently than α2. Furthermore, our results demonstrate that subtypes with stronger antiviral activities induce higher expression of IAV-specific restriction factors and that MxA expression is a determinant of the subtype-specific antiviral activity towards H3N2 IAV. These results corroborate that IFN-α subtypes exhibit differential antiviral activities and emphasize that subtypes α16, α5 and α4 should be further investigated for the prevention and treatment of severe infections with seasonal H3N2 IAV.

Objectives: With the occurrence of the COVID-19 pandemic in the year of 2020 the number of patients in need ofintensive care medicine increased dramatically in many countries. Several of them developed an acute respiratory distresssyndrome (ARDS) linked to the COVID-19 infection and many required the use of extracorporeal membrane oxygenation(ECMO). Methods: We are retrospectively reviewing 141 patients who underwent ECMO for severe COVID-19-related ARDS in amulticenter study at 10 European ECMO centers. Result: A total of 141 patients (67.4% male, median age was 55.4 years (interquartile range [IQR]: 44-67.5) were treatedwith ECMO for confirmed (132) or suspected (9) severe COVID-19-related ARDS. Before ECMO, the median SequentialOrgan Failure Assessment (SOFA) score was 9.0 (IQR: 7.0-11.5), median pH was 7.25 (IQR: 7.20-7.30), and medianPaO /FiO ratio was 70 mm Hg (IQR: 60-77). Venovenous ECMO was provided in 130 patients (92%) and venoarterial ECMO in 11 patients (8%) The median duration ofECMO treatment by now was 11 days, IQR: 7-17). At the time of reporting, 71 confirmed COVID-19 patients (53.8%) arealive, of whom 33 (43.4%) are still in the intensive care unit (9 on ECMO, 24 weaned from ECMO and extubated). Overallmortality so far occurred in 62 patients (46.2%). By now advanced age, low arterial pH, and low platelet count before ECMO were independent risk factors for increasedmortality during the intensive care treatment. Conclusion: Despite a substantial overall mortality of over 40%, approximately half of the patients with severe COVID-19-related ARDS, refractory to conventional treatment, may be successfully managed with ECMO therapy.

// Djeda Belharazem 1 , Albert Grass 1 , Cornelia Paul 1 , Mario Vitacolonna 2 , Berthold Schalke 3 , Ralf J. Rieker 4, 5 , Daniel Korner 6 , Philipp Jungebluth 6 , Katja Simon-Keller 1 , Peter Hohenberger 2 , Eric M. Roessner 2 , Karsten Wiebe 7 , Thomas Grater 8 , Thomas Kyriss 9 , German Ott 10, 11 , Peter Geserick 12 , Martin Leverkus 12, 13, * , Philipp Strobel 14 and Alexander Marx 1 1 Institute of Pathology and Medical Research Center (ZMF), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany 2 Department of Thoracic Surgery, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany 3 Department of Neurology, University of Regensburg, Regensburg, Germany 4 Institute of Pathology, University Hospital Heidelberg, University of Heidelberg, Heidelberg, Germany 5 Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany 6 Department of Thoracic Surgery, Thorax Clinic, University of Heidelberg, Heidelberg, Germany 7 Department of Thoracic Surgery, University of Munster, Munster, Germany 8 Department of Thoracic Surgery, Clinic Lowenstein, Lowenstein, Germany 9 Department of Thoracic Surgery, Clinic Schillerhohe, Robert-Bosch-Hospital, Gerlingen, Germany 10 Department of Clinical Pathology, Robert-Bosch-Hospital, Stuttgart, Germany 11 Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany 12 Department of Dermatology, Venereology, and Allergology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany 13 Department for Dermatology and Allergology, University Hospital Aachen, RWTH Aachen, Aachen, Germany 14 Institute of Pathology, University Medical Center Gottingen, University of Gottingen, Gottingen, Germany * Deceased Correspondence to: Djeda Belharazem, email: djeda.belharazem@medma.uni-heidelberg.de Keywords: thymic tumors, cFLIP, NF-κB, senescence, autophagy Received: September 01, 2016 Accepted: December 26, 2016 Published: February 06, 2017 ABSTRACT The anti-apoptotic cellular FLICE-like inhibitory protein cFLIP plays a pivotal role in normal tissues homoeostasis and the development of many tumors, but its role in normal thymus (NT), thymomas and thymic carcinomas (TC) is largely unknown. Expression, regulation and function of cFLIP were analyzed in biopsies of NT, thymomas, thymic squamous cell carcinomas (TSCC), thymic epithelial cells (TECs) derived thereof and in the TC line 1889c by qRT-PCR, western blot, shRNA techniques, and functional assays addressing survival, senescence and autophagy. More than 90% of thymomas and TSCCs showed increased cFLIP expression compared to NT. cFLIP expression declined with age in NTs but not in thymomas. During short term culture cFLIP expression levels declined significantly slower in neoplastic than non-neoplastic primary TECs. Down-regulation of cFLIP by shRNA or NF-κB inhibition accelerated senescence and induced autophagy and cell death in neoplastic TECs. The results suggest a role of cFLIP in the involution of normal thymus and the development of thymomas and TSCC. Since increased expression of cFLIP is a known tumor escape mechanism, it may serve as tissue-based biomarker in future clinical trials, including immune checkpoint inhibitor trials in the commonly PD-L1 high thymomas and TCs.

Summary Background The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50–0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II–IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. Findings Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. Interpretation At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. Funding National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Functional and technical operability has to be evaluated and defined prior to thoracic surgical procedures. Sometimes patients assigned to thoracic surgery procedures have to be declared inoperable due to functional und technical limitations. Extracorporeal lung support is an important tool to establish functional and technical operability in patients undergoing thoracic surgical procedures. This ensures perioperative safety and minimises the risk during extended lung resection.Funktionelle und technische Operabilität müssen vor thoraxchirurgischen Eingriffen evaluiert und definiert werden. Nicht selten gelten Patienten aufgrund funktioneller Einschränkung und/oder aufgrund einer ungünstigen Lokalisation des Tumors als inoperabel. Die extrakorporale Lungenunterstützung stellt in der Thoraxchirurgie ein wichtiges Verfahren zur Etablierung funktioneller und technischer Operabilität dar. Sie ermöglicht eine perioperative Sicherheit und minimiert das Risiko während anspruchsvoller Resektionen.

ZusammenfassungFunktionelle und technische Operabilität müssen vor thoraxchirurgischen Eingriffen evaluiert und definiert werden. Nicht selten gelten Patienten aufgrund funktioneller Einschränkung und/oder aufgrund einer ungünstigen Lokalisation des Tumors als inoperabel. Die extrakorporale Lungenunterstützung stellt in der Thoraxchirurgie ein wichtiges Verfahren zur Etablierung funktioneller und technischer Operabilität dar. Sie ermöglicht eine perioperative Sicherheit und minimiert das Risiko während anspruchsvoller Resektionen.

Background The Interdisciplinary Tumor Board (ITB) of the Cooperative Ewing Sarcoma Study (CESS) Group was investigated to assess its impact on the overall survival (OAS) of Ewing sarcoma (EwS) patients. The ITB functions as a reference center for the international institutions participating in the clinical trials of the CESS group, but is also available internationally to patients who have not been treated within an appropriate clinical trial. The value of tumor boards in terms of benefit for the patients and the health care system in general is not well documented and is also the subject of controversial discussions. A review of the representative literature is included. Methods Data were analyzed from 481 patients who had been registered into the European Ewing Tumor Working Initiative of National Groups (EURO E.W.I.N.G.-99) clinical trial via the CESS data center between 2006 and 2009; this included 331 patients with localized disease and another 150 individuals with metastases at diagnosis. Median follow-up time was 3.2 years. Results Improved OAS was observed for patients with metastases who had received recommendations from the ITB compared with those who had not received recommendations. In patients with localized disease, a recommendation from the ITB had no influence on OAS. Conclusion As a reference center for a rare disease, recommendations from our ITB impacted local therapy and led to higher OAS in patients with metastatic disease. To our knowledge, this is the first analysis that examines the value of a reference tumor board on a rare disease.

Objectives In patients with testicular Germ Cell Tumors (GCT) noncaseating granulomatous diseases such as Sarcoid Like Lesions (SLL) or Sarcoidosis can mimic metastasis due to hilar or mediastinal lymphadenopathy. Due to the clinical and prognostic impact, exclusion of malignant diseases is mandatory. Material and methods Retrospectively, data from 636 GCT patients, who were seen in the course of tumor surveillance/follow-up were collected. Focus was put on the detection of tumor relapse vs. noncaseating granulomatous reactions. For the differential diagnosis of thoracic lymphadenopathy or pulmonary infiltrates either bronchoscopy (e.g., endobronchial ultrasound-guided transbronchial needle aspiration, endobronchial ultrasound-guided transbronchial needle aspiration) or thoracic surgery was performed. Both GCT patients with either tumor relapse or coexisting SLL were compared to GCT patients without SLL and tumor relapse. Results Twenty-nine patients suffered from suspected tumor relapse. Whereas thoracic relapses were suspected in 15 patients on chest computed tomography, thoracic relapse was confirmed in 5 cases by open surgery. In 2 cases open surgery yielded reactive lymphadenitis, and in 8 cases SLL was diagnosed either via EBUS-TBNA (n = 7) or thoracoscopic wedge resection plus lymphadenectomy (n = 1). With focus on overall survival, no relevant difference was found between all tested subgroups (P = 0.265; logrank test). Conclusions In GCT patients, the coexistence of noncaseating granulomatous disease is common. Minimal invasive bronchoscopic techniques can serve for the cytopathologic exclusion of malignant thoracic manifestations. In our monocenter patient group the coexistence of SLL did not have any prognostic impact on overall survival.

Background The ascertainment of brain death (the irreversible, total loss of brain function) gives the physician the opportunity to limit or stop further treatment. Alternatively, if the brain-dead individual is an organ donor, the mode of treatment can be changed from patient-centered to donationcentered. Consensus-derived recommendations for the organ-protective treatment of brain-dead organ donors are not yet available in Germany. Methods This review is based on pertinent publications retrieved by a selective search in PubMed, and on the authors' clinical experience. Results Brain death causes major pathophysiological changes, including an increase in catecholamine levels and a sudden drop in the concentration of multiple hormones, among them antidiuretic hormone, cortisol, insulin, and triand tetraiodothyronine. These changes affect the function of all organ systems, as well as the hemodynamic state and the regulation of body temperature. The use of standardized donor management protocols might well increase the rate of transplanted organs per donor and improve the quality of the transplanted organs. In addition, the administration of methylprednisolone, desmopressin, and vasopressin could be a useful supplement to treatment in some cases. Randomized controlled trials have not yet demonstrated either improved organ function or prolonged survival of the transplant recipients. Conclusion The evidence base for organ-protective intensive care is weak; most of the available evidence is on the level of expert opinion. There is good reason to believe, however, that the continuation of intensive care, in the sense of early donor management, can make organ transplantation more successful both by increasing the number of transplantable organs and by improving organ quality.

Einleitung: Nach offen-chirurgischer Resektion ist die Verdrehung und Verlagerung von benachbarten Lungenlappen als seltene Komplikation bekannt. Für thorakoskopische Lappenresektion wurde sie nicht als typische Komplikation aufgeführt. Material und Methoden: Bei einer 73 jährigen[zum vollständigen Text gelangen Sie über die oben angegebene URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

Einleitung: Die fibröse Dysplasie (FD) ist eine gutartige Tumorbildung des Knochens, die sehr selten auch die Rippen betreffen kann. FD ist häufig asymptomatisch und wird akzidentell oder im Rahmen einer Fraktur entdeckt. Die Diagnose lässt sich radiologisch in der Regel nicht eindeutig[zum vollständigen Text gelangen Sie über die oben angegebene URL], 133. Kongress der Deutschen Gesellschaft für Chirurgie

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%-86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. peerReviewed

Introduction The new strain of influenza A (H1N1) 2009, often referred to colloquially as “swine flu”, which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people. Patients In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support. Results Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support. Conclusions The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people.

Introduction: The functions of large noncoding RNAs (ncRNAs) have remained elusive in many cases. Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types. Methods: Overexpression and RNA interference (RNAi) approaches were used for the analysis of the biological functions of MALAT-1 RNA. Tumor growth was studied in nude mice. For prognostic analysis, MALAT-1 RNA was detected on paraffin-embedded non-small cell lung cancer (NSCLC) tissue probes ( n = 352) using in situ hybridization. Results: MALAT-1 was highly expressed in several human NSCLC cell lines. MALAT-1 expression was regulated by an endogenous negative feedback loop. In A549 NSCLCs, RNAi-mediated suppression of MALAT-1 RNA suppressed migration and clonogenic growth. Forced expression of MALAT-1 in NIH 3T3 cells significantly increased migration. Upon injection into nude mice, NSCLC xenografts with decreased MALAT-1 expression were impaired in tumor formation and growth. In situ hybridization on paraffin-embedded lung cancer tissue probes revealed that high MALAT-1 RNA expression in squamous cell carcinoma of the lung was associated with a poor prognosis. On genetic level, MALAT-1 displays the strongest association with genes involved in cancer like cellular growth, movement, proliferation, signaling, and immune regulation. Conclusions: These data indicate that MALAT-1 expression levels are associated with patient survival and identify tumor-promoting functions of MALAT-1.

Die chirurgische Therapie des nicht kleinzelligen Lungenkarzinoms (NSCLC) ist streng stadienorientiert. Eine exakte, gegebenenfalls auch invasive, Diagnostik ist Voraussetzung fur die richtige Behandlung. Fur die fruhen Stadien der Erkrankung (Stadium I, II und IIIA (T3, N1)) ist die chirurgische Resektion in kurativer Intention die Behandlung der Wahl. Im Rahmen von multimodalen Konzepten konnen aber auch gut selektionierte Patienten in fortgeschrittenen Stadien von einer chirurgischen Therapie profitieren. Kontrovers diskutiert wird die Rolle der Chirurgie dagegen bei lokal fortgeschrittenem oder metastasiertem NSCLC. Die chirurgische Therapie erfordert die Lobektomie mit einer systematischen Lymphadenektomie. Als Alternative zur Thorakotomie hat sich fur das Stadium I die thorakoskopische Lobektomie (VATS-Lobektomie) etabliert. Auch im fortgeschrittenen Alter oder bei stark eingeschrankter Lungenfunktion kann eine chirurgische Resektion eine praktikable und sichere Behandlungsoption sein, die mit einer annehmbaren Lebensqualitat einhergeht. Beim kleinzelligen Lungenkarzinom (SCLC) ist die Operation nur in wenigen Fallen gerechtfertigt.