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Objectives The purpose of this study was to investigate the value of PET/CT in the preoperative staging of non-small cell lung cancer in predicting long-term survival and diagnostic performance, validated by histopathology following surgical resection. Methods Between 02/2009 and 08/2011, 255 patients with non-small cell lung cancer were included in this single-center prospective study. All underwent 18F FDG-PET/CT for pre-operative staging, and in 243 patients complete surgical resection was possible. Regarding lymph node involvement and extrathoracic metastases, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the histopathological staging as reference. Median follow-up for censored patients was 9.1 years. Results Overall 5-year survival rate of all patients was 55.6%, and of patients who had complete surgical resection it was 58.2%. In multivariate analysis of all surgically resected patients lymph node involvement (p=0.029) and age >61 years (p= Conclusions In this study, tumor 18F FDG-uptake values did not provide additional prognostic information. Age>61 years and lymph node metastasis were associated with worse long-term survival in surgically resected patients. 18F FDG-PET/CT scans allow for improved patient selection. However, in staging mediastinal lymph nodes, there is a high rate of false positives and false negatives, suggesting that tissue biopsy is still indicated in many cases.

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilises the angiotensin-converting enzyme 2 (ACE2) transmembrane peptidase as cellular entry receptor. However, whether SARS-CoV-2 in the alveolar compartment is strictly ACE2-dependent and to what extent virus-induced tissue damage and/or direct immune activation determines early pathogenesis is still elusive.MethodsSpectral microscopy, single-cell/-nucleus RNA sequencing or ACE2 “gain-of-function” experiments were applied to infected human lung explants and adult stem cell derived human lung organoids to correlate ACE2 and related host factors with SARS-CoV-2 tropism, propagation, virulence and immune activation compared to SARS-CoV, influenza and Middle East respiratory syndrome coronavirus (MERS-CoV). Coronavirus disease 2019 (COVID-19) autopsy material was used to validateex vivoresults.ResultsWe provide evidence that alveolar ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation and virus-induced tissue damage in the human alveolus. Instead,ex vivoinfected human lungs and COVID-19 autopsy samples showed that alveolar macrophages were frequently positive for SARS-CoV-2. Single-cell/-nucleus transcriptomics further revealed nonproductive virus uptake and a related inflammatory and anti-viral activation, especially in “inflammatory alveolar macrophages”, comparable to those induced by SARS-CoV and MERS-CoV, but different from NL63 or influenza virus infection.ConclusionsCollectively, our findings indicate that severe lung injury in COVID-19 probably results from a macrophage-triggered immune activation rather than direct viral damage of the alveolar compartment.

Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner’s factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a “do not intubate” order.

The purpose of this study was to investigate the value of PET/CT in the preoperative staging of non-small cell lung cancer in predicting long-term survival and diagnostic performance, validated by histopathology following surgical resection.Between 02/2009 and 08/2011, 255 patients with non-small cell lung cancer were included in this single-center prospective study. All underwent 18F FDG-PET/CT for pre-operative staging, and in 243 patients complete surgical resection was possible. Regarding lymph node involvement and extrathoracic metastases, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the histopathological staging as reference. Median follow-up for censored patients was 9.1 years.Overall 5-year survival rate of all patients was 55.6%, and of patients who had complete surgical resection it was 58.2%. In multivariate analysis of all surgically resected patients lymph node involvement (p=0.029) and age61 years (p=0.001) were significant independent prognostic factors. SUVmax and SUVmean cut-offs between SUV 2 and 11, however, were not associated with better or ;worse survival. The PET-CT sensitivity, specificity, positive predictive value and negative predictive value for predicting lymph node involvement were 57, 95, 88, and 76%, respectively. Furthermore, sensitivity, specificity, positive predictive value, and negative predictive value for detecting extrathoracic metastases were 100, 58, 98, and 100%, respectively.In this study, tumor 18F FDG-uptake values did not provide additional prognostic information. Age61 years and lymph node metastasis were associated with worse long-term survival in surgically resected patients. 18F FDG-PET/CT scans allow for improved patient selection. However, in staging mediastinal lymph nodes, there is a high rate of false positives and false negatives, suggesting that tissue biopsy is still indicated in many cases.

The analysis of circulating cell-free DNA (cfDNA) extracted from peripheral blood can serve as a minimally invasive alternative to tumor tissue biopsies in cases with impaired access to tissue. Its clinical utility has been well demonstrated for EGFR T790M testing in lung cancer patients suffering progress after tyrosine kinase inhibitor treatment. At present, highly sensitive unique molecular identifiers (UMI)-based NGS for liquid biopsy testing is less established compared to single gene assays. However, the critical bottleneck are sufficient cfDNA yields, which are essentially required to obtain meaningful test results. We compared four different cfDNA extraction methods (Qiagen, Promega, Thermo and Stratec) using the same plasma samples in order to evaluate their suitability for further NGS analysis. We managed to draw 60 ml blood from 12 patients each and equally collected 30ml in PAXgene and EDTA tubes at the same time point, sufficient for total of 96 cfDNA extractions. CfDNA concentrations and total amounts were highest for Qiagen and Promega protocols, showing the best read length profiles after sequencing. Known oncogenic driver mutations were identified in 9 out of 12 patients with at least one of the cfDNA extraction methods, again favoring the extraction protocols from Qiagen and Promega. We also uncovered putative sequencing artefacts including known driver genes pointing to a careful consideration for the limit of detection of this methodology. Our study shows that pre-analytical optimization is necessary to achieve the maximum sensitivity of UMI-based sequencing but also highlights the low abundance of tumor-derived cfDNA in lung cancer samples.

Referring to a literature review published recently in this Journal, we report a single-center case series of 45 children and adolescents (age 2-17 years) with suspected tuberculosis (TB) and negative microscopy on repeated sputum or gastric aspirate samples. All subjects underwent flexible airway endoscopy including bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) without adverse events. Among 41 subjects with a final TB diagnosis, Mycobacterium tuberculosis was detected by PCR and/or culture in 20 (49% bacteriological confirmation) with 11 cases relying exclusively on results from TBNA samples. Only 7 of 17 positive culture results related to sputum (17% confirmation rate), and 9 of 17 on the combination of sputum and BAL (22%) respectively. The sampling site of a person’s first positive culture was TBNA in 13 of 17 cases (76%). Bacteriological confirmation was essential for diagnostic accuracy and tailored treatment based on individual drug susceptibility testing. We therefore recommend the inclusion of bronchoscopy and EBUS-TBNA in a comprehensive diagnostic protocol for smear-negative pediatric TB suspects.

Summary Objectives The coronavirus disease 2019 (COVID-19) pandemic situation in Germany is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany. Methods In this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12, and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes. Results We included 1904 patients with a median age of 73 years, and 48.5% (924/1904) were female. The mortality rate was 17% (317/1835; 95% confidence interval [CI] 16-19), the rate of admission to the intensive care unit (ICU) 21% (399/1860; 95% CI 20–23), and the rate of invasive mechanical ventilation 14% (250/1850: 95% CI 12–15). The most prominent risk factors for death were male sex (hazard ratio [HR] 1.45; 95% CI 1.2-1.8), preexisting lung disease (HR 1.61; 95% CI 1.20-2.16), and increased patient age (HR 4.1 [95% CI 2.6–6.6] for age >79 years versus

The majority of research within lung cancer is focused on prevention, diagnosis and treatment rather than examining infrastructure or processes of lung cancer centres. Benchmarking is a systematic method for documenting and comparing processes, functions or performance of organisations against the best in the world. ADVANCE-1 is a European Respiratory Society funded pilot study with the main aim of creating a benchmarking tool that can easily document and reflect the structure and process within a lung cancer centre and its associated registry. By doing this we can then compare centres and generate best practice learning points from each centre in order to learn from each other. The ADVANCE-1 study group was constituted by two ERS fellowship-holders and senior lung cancer specialists from the two participating lung cancer services in Glasgow, Scotland, and Berlin, Germany. The study design and benchmarking tools were reviewed externally. Once the benchmarking tools were created, prospective testing was undertaken in the two participating centres in order to allow comparison to ascertain best practice in a so called 'collaborative benchmarking approach'. We were then able to create personalised learning points for each centre. The next phase of the project will be to expand the benchmarking across several European centres in the ADANCE-2 project.

ZusammenfassungDas Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK) feiert in diesem Jahr seinen 125. Geburtstag. Aus diesem Anlass blickt das DZK als eine der weltweit ältesten TB-Organisationen auf seine Entwicklung in diesen 125 Jahren zurück. Die Ergebnisse werden detailliert in einem umfangreichen Buch geschildert und in diesem Artikel zusammengefasst. Hierin spiegeln sich die vielfältigen politischen Veränderungen mit ihren Auswirkungen auf das DZK wider, angefangen vom Kaiserreich, über die Weimarer Republik, das sog. „Dritte Reich“, die beiden nach dem Zweiten Weltkrieg getrennten deutschen Staaten und die jetzige Bundesrepublik Deutschland. Die Tuberkulose (TB) war zur Gründungszeit noch die beherrschende Volkskrankheit in Deutschland, heute ist sie weltweit die führende Infektionskrankheit. Als Folge von Migration ist davon auch Deutschland betroffen. Nach zwischenzeitlich – speziell 2015/2016 – deutlich angestiegenen Erkrankungszahlen (insbesondere bei den nicht in Deutschland geborenen Neuerkrankten, die 2019 einen Anteil von 72 % hatten), die Auswirkungen der medikamentenresistenten TB (2019 hatten 11,4 % aller Neuerkrankungen irgendeine [jegliche] Resistenz [384 Fälle], darunter 87 Fälle mit einer MDR-TB und von diesen 8 Fälle mit einer XDR-TB und 27 Fälle einer Prä-XDR-TB) sowie auch der hohe Anteil offener und damit hoch infektiöser Lungentuberkulosen (81,5 % in 2019) zeigen eindrücklich, dass die TB nach wie vor ein auch in Deutschland nicht zu unterschätzendes Gesundheitsproblem darstellt, welches sich zunehmend in Risikogruppen konzentriert (sozial benachteiligte Personen, Menschen aus Hochprävalenzländern, Obdachlose, Drogenabhängige, Alkoholkranke, HIV-Infizierte). Dem DZK kommt daher in der Kontrolle der TB auch heute noch eine wichtige Rolle zu als Bindeglied zwischen den mit der Bekämpfung der TB betrauten nationalen und internationalen Institutionen.

Objective The qSOFA (quick sepsis-related organ failure assessment) score shows similarities to the CRB-65 pneumonia score, but its prognostic accuracy in patients with community-acquired pneumonia (CAP) has not been extensively evaluated. Our aim was to validate the qSOFA (-65) score in a large cohort of CAP patients. Methods We conducted a retrospective population-based cohort study including all CAP cases hospitalized between 1st January 2014 and 31st December 2018 from the German nationwide mandatory quality assurance programme. We excluded cases transferred from another hospital, with mechanical ventilation present on admission, and without documented respiratory rate. Predefined outcomes were hospital mortality and need for mechanical ventilation. Results Among the 1,262,250 included cases, hospital mortality was 12.4% and the mechanical ventilation rate was 7.1%. All CRB and qSOFA criteria were associated with both outcomes, but the qSOFA had inferior sensitivity compared to the CRB-65 for mortality prediction. Including the age criterion ≥65 years, qSOFA-65 and CRB-65 performed similarly (AUC 0.69, 95%CI 0.69–0.69 versus 0.68, 95%CI 0.68–0.68). A qSOFA-65 of 0 was associated with fewer missed deaths (3328, 2.0%) compared to a CRB-65 of 0 (5480, 2.4%). The sensitivity of the suggested qSOFA cut-off of ≥2 for sepsis was low (mortality 25.8%, 95%CI 25.6–26.0%; mechanical ventilation 24.1%, 95%CI 23.8–24.4%). Results were similar when frail and palliative patients were excluded. Conclusions The qSOFA parameters show prognostic accuracy similar to the CRB parameters in CAP, but the sepsis cut-off of ≥2 lacked sensitivity. For sensitive mortality prediction, the age criterion ≥65 years should be added to the qSOFA.

We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.

Background In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N1 is a heterogeneous entity, and different forms of lymph node involvement may represent different prognoses. For methodological reasons, the 8th edition of the TNM staging system for NSCLC makes no official changes to the N descriptor. However, there is evidence that different subforms of N1 disease are associated with different prognoses, and it is now recommended that clinicians record the number of affected lymph nodes and nodal stations for further analyses. In this investigation we sought to determine whether patients with different levels and types of N1 lymph node involvement had significantly different 5-year survival rates. Methods We retrospectively identified 90 patients with NSCLC (61 men, 29 women), who were treated between 2008 and 2012 and found to have pathologic N1 lymph node involvement and tumor sizes corresponding to T1 or T2. All patients were treated in curative intent with surgical lung resection and systematic mediastinal and hilar lymph node dissection. Results The overall 5-year survival rate was 56.3%. In the univariate analysis, lower tumor stage and tumor histology other than large-cell carcinoma were significantly associated with better long-term survival. Patients with solitary lymph node metastases also had longer disease-free survival than those with multiple nodal metastases. In the multivariate analysis, large-cell carcinoma and Union for International Cancer Control (UICC) stage IIB were independently associated with worse survival, while pneumonectomy, compared to lobar or sublobar resection, was independently associated with better survival. Conclusions Although we did not observe significant prognostic differences between N1 subcategories within our patient population, other analyses may yield different results. Therefore, these data highlight the need for large, well-designed multicenter studies to confirm the clinical significance of N1 subcategories.

Die Entwicklung von Medikamentenresistenz ist global derzeit eines der größten Hindernisse im Kampf gegen TB. Die Problematik resistenter TB ist auch in Deutschland präsent. Zwar sind die Resistenzraten in den letzten Jahren relativ stabil geblieben, die RKI-Surveillancedaten der letzten 10 Jahre zeigen jedoch, dass bei einem Großteil der Fälle multiresistenter TB (MDR-TB) mehr als nur die beiden wichtigsten TB-Medikamente Isoniazid und Rifampicin unwirksam sind. Um eine Ausbreitung von MDR-TB zu verhindern, sind rechtzeitige und sachgemäße Resistenztestungen sowie eine resistenzgerechte, individualisierte Behandlung durch Experten/-innen unabdingbar. Hierbei sind aktuelle Entwicklungen zur Diagnostik, Behandlungsmöglichkeiten und Medikamenten zu berücksichtigen. In Epidemiologischen Bulletin 11/12 2019 beschreiben Maurer et al. die von der WHO empfohlene Umstellung auf ein orales Behandlungsregime und betonen auch hier, dass die Möglichkeiten der Resistenztestung ausgeschöpft werden sollten.

Hintergrund: In der Rehabilitation stehen im Fachgebiet der Inneren Medizin muskulare Ausdauerbelastungen im Vordergrund des sporttherapeutischen Handelns. Leider ist das ambulante Rehabilitations- und Sportangebot fur viele pneumologische Patienten begrenzt, und Lungensportgruppen sind noch nicht flachendeckend vorhanden. So wurde ein ambulantes Ausdauersportprogramm mit sportmedizinischer Begleitung als sporttherapeutische Masnahme in der Pneumologie entwickelt und auf Effektivitat uberpruft. Methode: In diese Projektstudie wurden konsekutiv 31 Patienten (50 ± 15 Jahre) mit verschiedenen pneumologischen Erkrankungen eingeschlossen. Der ambulanten sporttherapeutischen Intervention (12-wochiges aerobes Ausdauersportprogramm mit ≥ 3 Einheiten a 20 – 60 min/Woche) wurde eine professionelle Leistungsdiagnostik inkl. Spiroergometrie und Laktatstufentest nach Standards der DGP und DGSP vorgeschaltet, und somit wurden die optimalen individuellen Trainingsbereiche festgelegt. Ergebnisse: Nach erfolgreicher Absolvierung des Trainingsprogramms konnten signifikante Verbesserungen in den Bereichen Luftnotempfinden (Borg-Summenwert: 65,7 ± 12,2 vs. 62,2 ± 12,6, Punkte, p = 0,013), Korperkonstitution (BMI: 25,7 ± 3,3 vs. 24,3 ± 3,2 kg/m2, p = 0,018; Korperfettanteil: 24,8 ± 5,8 vs. 23,8 ± 6,4 %, p = 0,043) sowie korperliche Leistungsfahigkeit (VO2 bei 4 mmol/l Laktat: 24,2 ± 6,9 vs. 26,5 ± 7,6 ml/min/kg, p Schlussfolgerung: Das vorgestellte ambulante Ausdauersportprogramm kann als gut durchfuhrbar angesehen werden und erwies sich auch in eigenverantwortlicher Durchfuhrung nach qualifizierter Anleitung als eine effektive sporttherapeutische Masnahme bei Patienten mit unterschiedlichen pneumologischen Erkrankungen.

Approximately 20% of symptomatic patients with SARS-CoV-2 infection progress to severe coronavirus disease (COVID-19) with critical hypoxemia fulfilling the criteria of acute respiratory distress syndrome (ARDS). Consistent with the classic features of ARDS, severe COVID-19 is characterised by ground glass opacities in CT imaging and diffuse alveolar damage post mortem [5] suggesting permeability-type lung edema as driver of respiratory failure. Consistent with this concept, autopsy findings show severe lung endothelial injury in patients who succumbed to COVID-19 [1]., Plasma of COVID-19 patients induces pulmonary microvascular barrier failure which increases with disease severity. Here, we report a versatile high-throughput screening platform to test for involved plasma mediators and the therapeutic potential of barrier stabilising compounds.

These data support the safety and tolerability of delamanid in the treatment of patients with MDR- and XDR-TB, even with drug exposure for longer than 6 monthshttps://bit.ly/3cPQQPS

Background: Pulmonary nocardiosis (PN) is an uncommon but potentially life-threatening infection. Most of our knowledge on PN is derived from case reports and small case series. Increasing incidence rates of PN have been reported recently. The aim of this study was to describe the clinical course of and risk factors for PN in four Western European countries and to estimate population-based annual hospitalization rates. Methods: This was a retrospective evaluation (1995–2011) of the clinical course of and risk factors for PN in patients at 11 hospitals in four European countries (Germany, Austria, Switzerland, and the Netherlands). Population-based estimates of hospitalization rates for PN in Germany (2005 to 2011) were calculated using official German nationwide diagnosis-related groups (DRG) hospital statistics. Results: Forty-three patients fulfilled stringent criteria for proven (n = 8) and probable (n = 35) PN; seven had extrapulmonary dissemination. For these 43 patients, the major risk factors for PN were immunocompromising (83.7%) and/or pulmonary (58.1%; as only comorbidity in 27.9%) comorbidities. The median duration of PN targeted therapy was 12 weeks. Distinctive patterns of resistance were observed (imipenem susceptibility: Nocardia farcinica 33.3%; Nocardia asteroides 66.7%). The overall mortality rate was 18.9% (50% in disseminated PN). Over time, annual PN hospitalization rates remained unchanged at around 0.04/100 000, with the highest rate among men aged 75–84 years (0.24/100 000). Conclusions: PN is a rare, but potentially life-threatening disease, and mainly affects immunocompromised elderly males. Overall, annual hospitalization rates remained stable between 2005 and 2011. Keywords: Nocardiosis, Nocardia, Pulmonary nocardiosis

Early immune responses to Mycobacterium tuberculosis (Mtb) invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host-pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host-pathogen interactions, while animal models have their own limitations. In this study, we have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue-resident cell types. As first cell types confronted with pathogens invading the lung, alveolar macrophages, and epithelial cells displayed rapid proinflammatory chemokine and cytokine responses to Mtb infection. Other tissue-resident innate cells like gamma/delta T cells, mucosal associated invariant T cells, and natural killer cells showed partially similar but weaker responses, with a high degree of variability across different donors. Finally, we investigated the responses of tissue-resident innate lymphoid cells to the inflammatory milieu induced by Mtb infection. Our infection model provides a unique approach toward host-pathogen interactions at the natural port of Mtb entry and site of its implantation, i.e., the human lung. Our data provide a first detailed insight into the early responses of different relevant pulmonary cells in the alveolar microenvironment to contact with Mtb. These results can form the basis for the identification of host markers that orchestrate early host defense and provide resistance or susceptibility to stable Mtb infection.

Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time. We first revealed that bacterially released PLY caused significant changes of the cellular ATP homeostasis and led to morphologic alterations of mitochondria in human alveolar epithelial cells in vitro and, by use of spectral live-tissue imaging, in human alveoli. This was accompanied by strong mitochondrial calcium influx and loss of mitochondrial membrane potential resulting in opening of the mitochondrial permeability transition pore and mtDNA release without activation of intrinsic apoptosis. Moreover, our data indicate cellular mtDNA liberation via microvesicles, which may contribute to S.pn. related pro-inflammatory immune activation in the human alveolar compartment.

Background: In a recent prospective study on pul- monary infections with non-tuberculous myco- bacteria (NTM) led by the WATL group, disease rates in patients with M. kansasii infection were found to be 100%. In the present study we re- evaluated the pathogenicity of M. kansasii infec- tions in a large lung diseases treatment center in

Die kalkulierte Behandlung der multiresistenten (MDR) Tuberkulose (TB) nach molekularer Schnelltestung wird durch die mehrwochige Unkenntnis der Empfindlichkeit gegen Zweitlinienmedikamente erschwert. Durch die Berucksichtigung regionaler Haufungen von Resistenzen bei Migranten konnte die kalkulierte Behandlung mit Zweitlinienmedikamenten zielgerichteter erfolgen. Von 2008 bis 2013 wurden retrospektiv die Ergebnisse der kulturellen Empfindlichkeitstestung aller eingesendeten Mykobakterienstamme des Instituts fur Mikrobiologie, das mit der Lungenklinik Heckeshorn zusammenarbeitet, analysiert und auf regionale Unterschiede untersucht. Unter den Proben fanden sich 39 Mycobacterium tuberculosis-Stamme mit Multiresistenz. Als Zweitrangmedikamente wurden Linezolid (97 %), Clofazimin (95 %), Cycloserin (95 %), Capreomycin (90 %), P-Aminosalicylsaure (82 %), Moxifloxacin (79 %) und Amikacin (79 %) bei mehr als der Halfte der Stamme empfindlich getestet. Der Anteil der empfindlichen Stamme war niedriger fur Pyrazinamid (44 %), Ethambutol (28 %), Protionamid (15 %), Rifabutin (8 %) und Streptomycin (8 %). Bei den Mykobakterienstammen aus Tschetschenien (n = 14) unterschieden sich die Empfindlichkeiten gegen Amikacin (57 %) und Protionamid (36 %) signifikant von denen aus anderen Regionen. Die regional unterschiedlich ausgepragten Empfindlichkeiten gegen Zweitlinienmedikamente legen nahe, dass bei der Wahl der kalkulierten Initialtherapie von MDR TB-Patienten mit Migrationshintergrund differenziert vorgegangen werden muss.

Background Surgical treatment of patients with limited metastatic lesions from non-small cell lung cancer (NSCLC) remains controversial; however, reports suggest that a subset of patients may benefit from complete resection including metastasectomy. Methods Between 1997 and 2009, 99 patients underwent complete solitary synchronous NSCLC metastasis resection in a single center. Only patients who met the potentially curative operation criteria (ie, primary NSCLC and metastasis resection of a solitary pulmonary or solitary extrapulmonary metastases) were included for retrospective analyses within this study. Results The overall 5-year survival rate was 38%. A significantly longer survival was observed in patients without mediastinal (N2 or N3) lymph node involvement (median, 50.0 months) compared with patients who had mediastinal lymph node metastases (median, 19.0 months survival; p = 0.015). In patients with a solitary metastasis in the ipsilateral (not ipsilobar) or contralateral lung, we observed a 5-year survival rate of 48.5%, whereas the rate was 23.6% in patients with extrapulmonary metastases ( p = 0.006). In univariate analysis, a trend for a more favorable long-term survival rate was observed for patients with a histologic grade of G1 or G2 versus G3 primary NSCLC ( p = 0.058). Conclusions We conclude that metastasectomy for synchronous oligometastatic disease in NSCLC can be performed in selected patients. It appears reasonable that such patients should be considered as surgical candidates if mediastinal lymph node involvement is excluded.

In the article by Alsaad et al. [1] in a recent issue of the European Respiratory Journal the authors reviewed six drugs with antimicrobial activity against Mycobacterium tuberculosis (phenothiazine, metronidazole, doxycycline, disulfiram, tigecycline and co-trimoxazole) which are not listed in the World Health Organization guidelines on multidrug-resistant tuberculosis (MDR-TB) treatment, but could be potential candidates for this use. Despite of the release of new drugs (delamanid, bedaquiline), treatment alternatives are still warranted, last but not least because of treatment costs. We would like to extend this list by evaluating the anti-malaria drug mefloquine. Mefloquine has in vitro activity against MDR- and non-MDR-TB and should be evaluated in clinical studies

Die nichttuberkulosen Mykobakteriosen umfassen eine Gruppe von Erkrankungen, die von Mykobakterien verursacht werden, die nicht dem Mycobacterium (M.) tuberculosis-Komplex und nicht M. leprae zugerechnet werden und durch eine breite Vielfalt in Hinsicht auf ihr Vorkommen und ihre Anpassungen an spezifische Umweltbedingungen charakterisiert sind. Einige Spezies konnen definierte Krankheitsbilder insbesondere bei Patienten mit systemischer Immunsuppression, vorbestehenden Lungenerkrankungen oder genetisch bedingter erhohter Empfanglichkeit hervorrufen. Weltweit wird eine Zunahme der Pravalenz und der Bedeutung dieser Erregergruppe beobachtet. Die vorliegenden Empfehlungen fassen aktuelle Aspekte der Epidemiologie, der Pathogenese, Klinik, Diagnostik einschlieslich mikrobiologischer Diagnostik und Resistenztestung, sowie der speziesabhangigen Therapie bei nichttuberkulosen Mykobakteriosen zusammen. Auserdem werden die besonderen Aspekte der Diagnostik und Therapie im Kindesalter und bei HIV-infizierten Patienten dargestellt.

Hintergrund: Die Mode des Tatowierens hat sich in westlichen Gesellschaften in den letzten zwei Dekaden sehr stark ausgebreitet. Uber medizinische Komplikationen nach der Tatowierung wurde in Einzelfalldarstellungen vielfach berichtet. Allerdings wurde eine systemische anaphylaktische Reaktion als Komplikation des Tatowierens bisher nur einmal beschrieben. Hierbei handelte es sich um eine Patientin, die bereits vorher unter schweren Allergien litt. Falldarstellung und Verlauf: Wir stellen den Fall eines 59-jahrigen Mannes vor, der funf Stunden nach einer Tatowierung eine progrediente Schwellung und Rotung entwickelte. Nach einer weiteren Stunde kam es in der Notaufnahme zu einer systemischen Anaphylaxie Schweregrad III. Es zeigte sich eine rapide zunehmende Schwellung und Rotung des tatowierten linken Arms, der linken Wange sowie von Lippen und Zunge. Allergien waren bei dem Patienten in der Vorgeschichte nicht bekannt. Der Patient sprach gut auf eine Therapie mit Prednisolon und Antihistaminika an. Die weitere Abklarung identifizierte Formaldehyd, Nickel und Mangan als Bestandteile der Farben, die als potenzielle chemische Ausloser der Symptome des Patienten infrage kommen. Einer erweiterten allergologischen Abklarung mit Prick-Test stimmte der Patient nicht zu. Schlussfolgerung: Die Kasuistik deutet darauf hin, dass Tattoofarben systemische Anaphylaxien auslosen konnen. Entscheidungstrager in Politik und Verwaltung sollten versuchen, die Anwendung bekannter starker allergener Stoffe in kommerziellen Tattoofarben wirkungsvoller zu beschranken.

The recent introduction of bronchoscopically recovered cryobiopsy of lung tissue has opened up new possibilities in the diagnosis of neoplastic and non-neoplastic lung diseases in various aspects. Most notably the morphological diagnosis of peripheral lung biopsies promises to achieve a better yield with a high quality of specimens. To better understand this phenomenon, its diagnostic options and perspectives, this study morphometrically compares 15 cryobiopsies and 18 transbronchial forceps biopsies of peripheral lung tissue a priori without considering clinical hit ratio or integration of results in the clinical diagnostic processing. Cryotechnically harvested specimens were significantly larger (mean: 17.1 ± 10.7 mm2 versus 3.8 ± 4.0 mm2) and contained alveolar tissue more often. If present, the alveolar part in cryobiopsies exceeded the one of forceps biopsies. The alveolar tissue of crybiopsy specimens did not show any artefacts. Based on these results cryotechnique seems to open up new perspectives in bronchoscopic diagnosis of lung disease.

Background There is only few data available on the use of cryotechnique during medical thoracoscopy. Methods Medical thoracoscopy was performed in consecutive patients with pleural effusion. Prospectively, biopsies were taken by rigid forceps, flexible forceps and cryoprobe. Specimen size, depth and diagnostic yield were compared. Results 80 Patients were included. 408 biopsies were taken (205 rigid biopsies, 104 flexible biopsies, 99 cryobiopsies). Mean surface area of rigid biopsies was 22.6 ± 20.4 mm2 (flexible biopsies: 7.1 ± 9.3 mm2, cryobiopsies: 14.4 ± 12.8 mm2). Rigid biopsies were significantly larger than cryobiopsies (p

3-day mortality from CAP corresponds to 33% of in-hospital deaths; the CRB-65 criteria are independent predictors http://ow.ly/XFMlB

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

C(U)RB-65 (confusion, (urea7 mol · L(-1),) respiratory frequency ≥ 30 breaths · min(-1), systolic blood pressure90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥ 65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe. In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008-2010, different CRB-age groups (≥ 50 and ≥ 60 years) across the total CAP population and three entities of CAP (younger population aged65 years, patients aged ≥ 65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death. 660 594 patients were investigated. Mortality was n=93 958 (14.0%). In the total population, CRB-80 had the optimal area under the curve (0.690, 95% CI 0.688-0.691). However, in the younger cohort, CRB-50 performed best (0.730, 95% CI 0.724-0.736), with good identification of low-risk patients (CRB-50 risk class 1: 1.28% deaths, negative predictive value 98.7%). In the elderly, CRB-80 as the optimal age group performed worse (0.663, 95% CI 0.660-0.655 in patients not residing in nursing homes; 0.608, 95% CI 0.605-0.611 in those with NHAP). In the latter group, all CRB-age groups failed to identify low-risk patients (CRB-80 risk class 1: 22.75% deaths, negative predictive value 81.8%). Patients with hospitalised CAP aged65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.

The diagnostic value of flexible bronchoscopy in the pre-operative work-up of solitary pulmonary nodules (SPN) is still under debate among pneumologists, radiologists and thoracic surgeons. In a prospective observational manner, flexible bronchoscopy was routinely performed in 225 patients with SPN of unknown origin. Of the 225 patients, 80.5% had lung cancer, 7.6% had metastasis of an extrapulmonary primary tumour and 12% had benign aetiology. Unsuspected endobronchial involvement was found in 4.4% of all 225 patients (or in 5.5% of patients with lung cancer). In addition, flexible bronchoscopy clarified the underlying aetiology in 41% of the cases. The bronchoscopic biopsy results from the SPN were positive in 84 (46.5%) patients with lung cancer. Surgery was cancelled due to the results of flexible bronchoscopy in four cases (involvement of the right main bronchus (impaired pulmonary function did not allow pneumonectomy) n=1, small cell lung cancer n=1, bacterial pneumonia n=2), and the surgical strategy had to be modified to bilobectomy in one patient. Flexible bronchoscopy changed the planned surgical approach in five cases substantially. These results suggest that routine flexible bronchoscopy should be included in the regular pre-operative work-up of patients with SPN.

Einfuhrung: Die Behandlung synchroner solitarer Lungenmetastasen beim nicht-kleinzelligen Lungenkarzinom (NSCLC) ist umstritten. So werden Satellitenmetastasen im gleichen Lungenlappen mittlerweile als T3-Tumore klassifiziert und konsequenterweise meist reseziert, da bestenfalls ein Stadium IIB (T3N0M0) resultiert. Im Gegensatz dazu werden ipsilaterale Herde in unterschiedlichen Lappen zwar neuerdings prognostisch als T4-Tumore klassifiziert und somit bestenfalls in ein Stadium IIIA eingeordnet (T4N0 – 1M0), jedoch in der taglichen Praxis meist nicht reseziert. Kontralaterale Lungenmetastasen werden, da prognostisch etwas gunstiger als extrathorakale Fernmetastasen, zwar neuerdings als M1a klassifiziert, eine chirurgische Konsequenz – wie in Einzelfallen bei solitarer Hirn- oder Nebennierenmetastase – ergibt sich hieraus jedoch nicht, da bisher eine begrundende Datenlage fehlt. Aus diesem Grund uberpruften wir in unserer Lungenklinik die Ergebnisse nach Resektion sowohl des Primartumors als auch der synchronen solitaren pulmonalen Metastase auserhalb des tumortragenden Lappens. Methoden: Wir operierten zwischen 1997 und 2007 siebenundfunfzig Patienten mit NSCLC und zeitgleicher zweiter (solitarer) maligner Lasion der Lunge, auserhalb des tumortragenden Lappens, nach entsprechender Aufklarung und Einverstandnis im Rahmen individueller Heilversuche. Der weitere Krankheitsverlauf wurde in einer Datenbank festgehalten und das Uberleben mit Kaplan-Meier-Statistik analysiert. Ergebnisse: Der Primartumor wurde in 67 % der Falle durch Lobektomie, in 9 % durch Pneumonektomie, in 2 % durch Bilobektomie und in 22 % durch Segment- bzw. atypische Resektion behandelt. Die zweite maligne Lasion und somit potenzielle solitare Metastase wurde in 83 % durch Segment- bzw. atypische Resektion, in 6 % der Falle durch Lobektomie, in 9 % durch Restpneumonektomie und in einem Fall durch Thoraxwandteilresektion behandelt. Das Gesamtuberleben aller Patienten (n = 57) betrug im Median 82 Monate (75 – 89 Monate 95 % Konfidenzintervall (KI)). Bei den synchronen Zweitkarzinomen (n = 7) lag das Uberleben im Median bei 76 Monaten (0,1 – 151 Monate 95 % KI), bei den synchronen Metastasen (n = 50) bei 82 Monaten (75 – 88 ± 95 % KI; p = 0,15). Dies entspricht einer 5-Jahres-Uberlebensrate von 56 % bzw. 77 %. Das mediane Uberleben der Patienten mit solitarer ipsilateraler Metastasierung (T4 nach UICC7) lag bei 79 Monaten (76 – 82 Monate 95 % KI), mit kontralateraler Metastase (M1a nach UICC7) bei 84 Monaten (60 – 107 Monate 95 % KI; p = 0,634). Schlussfolgerungen: Diese Auswertung zeigt, dass eine solitare Lungenmetastase (auserhalb des tumortragenden Lappens), bei ansonsten operablem NSCLC, einen kurativen chirurgischen Therapieansatz nicht von vornherein ausschliest. Bei ausgewahlten Patienten kann durch Resektion des Primartumors, Lymphadenektomie und Resektion der solitaren synchronen Lungenmetastase ein gutes Langzeituberleben erreicht werden. Da die vorgestellten Ergebnisse deutlich gunstiger sind als vergleichbare Daten von Patienten mit solitarer Hirn- oder Nebennierenmetastase, sollte entsprechend der deutschen S3-Leitlinienempfehlung fur diese Patienten in Einzelfallen auch ein chirurgisches Vorgehen bei pulmonal metastasierten NSCLC in Betracht gezogen werden.

Hintergrund: Ein 70-jahriger pneumologischer Patient mit seit vielen Jahren bestehender COPD und Sauerstofflangzeittherapie entwickelte im Verlauf seiner Erkrankung ein komplexes Beschwerdebild. Im mehrwochigen stationaren Verlauf erfolgte eine Behandlung von ausgepragten korperlichen Symptomen wie Luftnot, Angst und Schmerzen. Nach Ubernahme auf die Palliativstation war schlieslich nur noch die umfassende finale Begleitung im stationaren Setting moglich. Die in unserem Zentrum vorhandene palliativmedizinische Expertise wurde in diesem Fall zu spat in die therapeutischen Prozesse mit einbezogen. Das fuhrte zu einer schlechteren Kontrolle der oben genannten Symptome. Des Weiteren konnte der Wunsch des Patienten nach umfassender ambulanter Versorgung nicht rechtzeitig umgesetzt werden, da die Schwere des Krankheitsbildes nicht fruhzeitig erfasst wurde. Instrumente zur rechtzeitigen Erfassung eines nicht malignen pneumologischen Krankheitsbildes mit Bedarf einer zusatzlichen palliativmedizinischen Versorgung sind nicht etabliert.

Hintergrund: Das PET/CT mit F-18-Fluordesoxyglukose (FDG) hat eine hohe Sensitivitat (89 – 100 %) und zufriedenstellende Spezifitat (79 – 95 %) fur die Diagnose des NSCLC. Gegenwartig wird es uberwiegend im praoperativen Staging eingesetzt. Dies fuhrt in ca. 15 % aller Falle zu einer Diagnose von Fernmetastasen, die weder klinisch vermutet noch durch eine vorausgegangene konventionelle Bildgebung erkannt wurden. Wir pruften, ob die daraus resultierende Umstadiierung dieser Falle einen Einfluss auf das statistische Gesamtuberleben von Patienten im palliativen Stadium IV haben kann. Ziel: Vergleich des Gesamtuberlebens von Patienten mit Stadium IV NSCLC, die mittels FDG-PET/CT stadiiert wurden, mit Patienten, bei denen ausschlieslich konventionelle Bildtechnologien zum Stadiieren verwendet wurden. Methoden: Wir haben das Gesamtuberleben aller Patienten unserer Klinik mit der Neudiagnose eines NSCLC im Stadium IV aus dem Jahre 2009 ( n = 254) analysiert. 96 /254 (38 %) Patienten wurden mittels FDG-PET/CT stadiiert, 158 /254 (62 %) mittels konventioneller Methoden (CT-Gruppe). Die Uberlebensdaten wurden mittels Kaplan-Meier-Statistik verglichen. Ergebnisse : Die Patienten in der PET/CT-Gruppe waren junger (65 ± 11) als die der CT-Gruppe (68 ± 10 Jahre, p = 0,008). Das mediane Gesamtuberleben aller Patienten lag bei 246 Tagen (Bereich: 217 – 275 Tage); 338 Tage fur die PET/CT-Gruppe (Bereich: 247 – 429 Tage) und 207 fur die CT-Gruppe (Bereich: 161 – 253 Tage, p = 0,001), entsprechend einem Unterschied im medianen Gesamtuberleben von 131 Tagen (4,4 Monate). Schlussfolgerung : Der heutige Einsatz des FDG-PET/CT im Rahmen des uberwiegend praoperativen Stagings beim NSCLC identifiziert eine prognostisch gunstigere Gruppe an fernmetastasierten Patienten. Deren konsequente Umstadiierung in ein palliatives Stadium IV fuhrt zu einer therapieunabhangigen Verlangerung des mittleren Gesamtuberlebens innerhalb dieses Stadiums.

Die Datenlage zur Versorgungsqualitat von Patienten mit Lungenkrebs in Deutschland ist unzureichend. Zwar existiert mit der S3-Leitlinie Lungenkarzinom aus dem Jahr 2010 eine gute wissenschaftliche Handlungsgrundlage fur die mitunter komplexen Behandlungspfade, jedoch ist nicht belegt, inwieweit die entsprechenden Leitlinienempfehlungen bundesweit umgesetzt werden oder welche Therapien uberhaupt bei einer der prognostisch schlechtesten Tumorentitaten zur Anwendung kommen. Im Rahmen des Nationalen Krebsplans aus dem Jahr 2008 wurden konkrete Handlungsziele zur systematischen Verbesserung der onkologischen Versorgung in Deutschland formuliert. Als ein wesentliches Ziel wird eine bundesweite Neugestaltung und Vereinheitlichung von Tumordokumentation und Qualitatssicherung zur nachhaltigen Steigerung der Versorgungsqualitat gefordert. Dieser Ubersichtsartikel erlautert die zentralen Begrifflichkeiten und untersucht, inwieweit die Handlungsziele des Nationalen Krebsplanes beim Lungenkarzinom bislang umgesetzt wurden.