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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.

Influenza A virus (IAV) causes pandemics and annual epidemics of severe respiratory infections. A better understanding of the molecular regulation in tissue and cells upon IAV infection is needed to thoroughly understand pathogenesis. We analyzed IAV replication and gene expression induced by IAV strain H3N2 Panama in isolated primary human alveolar epithelial type II cells (AECIIs), the permanent A549 adenocarcinoma cell line, alveolar macrophages (AMs) and explanted human lung tissue by bulk RNA sequencing. Primary AECII exhibit in comparison to AM a broad set of strongly induced genes related to RIG-I and interferon (IFN) signaling. The response of AECII was partly mirrored in A549 cells. In human lung tissue, we observed induction of genes unlike in isolated cells. Viral RNA was used to correlate host cell gene expression changes with viral burden. While relative induction of key genes was similar, gene abundance was highest in AECII cells and AM, while weaker in the human lung (due to less IAV replication) and A549 cells (pointing to their limited suitability as a model). Correlation of host gene induction with viral burden allows a better understanding of the cell-type specific induction of pathways and a possible role of cellular crosstalk requiring intact tissue.

ZusammenfassungDieser Übersichtsartikel stellt detailliert die derzeitigen Einsatzgebiete der Positronen-Emissions-Tomografie/Computertomografie (PET/CT) bei dem Management von Lungenkarzinom-Patient*innen dar. Hierbei werden Indikationen, Wertigkeit bei Dignitätsbeurteilung und Stadiierung sowie Nutzen, Limitationen und prognostische Relevanz dieses diagnostischen Hybridverfahrens beleuchtet.Darüber hinaus bietet diese Publikation einen Ausblick auf neue Radiotracer und mehrschichtige maschinelle Lernverfahren als konsequente Weiterentwicklungen der PET/CT, welche deren diagnostischen, prädiktiven und prognostischen Zusatznutzen zukünftig noch vergrößern wird.

ZusammenfassungDas Lungenkarzinom ist weltweit die häufigste Todesursache unter den Krebserkrankungen. 1 In Deutschland erkrankten im Jahr 2016 etwa 21 500 Frauen und 36 000 Männer an bösartigen Tumoren der Lunge, 16 481 Frauen und 29 324 Männer verstarben an dieser Erkrankung. 2 In den letzten Jahren ist die Bedeutung molekularer Testung von Tumorgewebe bei Patienten mit metastasierten nichtkleinzelligen Lungenkarzinom (NSCLC) immer weiter in den Vordergrund gerückt und bestimmt nunmehr unser therapeutisches Handeln. Neue zielgerichtete Therapiestrategien wie die Tyrosinkinase-Inhibitoren und die Immuntherapie rücken immer weiter in den Fokus und haben die Diagnostik und das Management der Erkrankung über die Jahre revolutioniert. Durch den gezielten Einsatz dieser neuen Substanzen hat sich die Prognose des metastasierten NSCLC dramatisch gewandelt. Besonders Patienten mit aktivierenden Treibermutationen haben von den Entwicklungen der letzten Jahre enorm profitiert. Am Beispiel der EGFR-Mutation und der ALK- Fusion sehen wir Überlebensdaten, die noch vor wenigen Jahren utopisch erschienen.

Background In patients with non-small cell lung cancer (NSCLC), the pathologic union for international cancer control (UICC) stage IIIA is a heterogeneous entity, with different forms of N2-lymph node involvement representing different prognoses. Although a multimodality treatment approach, including surgery, systemic therapy, and/or radiotherapy, is almost always recommended, in this retrospective observational study, we sought to determine whether long-term survival might be possible in selected patients who are treated with complete surgical resection alone. Methods Between 2013 and 2018, we retrospectively identified 24 patients with NSCLC (16 men and 8 women), who were found to have pathologic N2-lymph node involvement, and were treated with complete surgical lung resection and systematic mediastinal and hilar lymph node dissection but no neoadjuvant or adjuvant treatment. Results The most frequent reason (n = 14) for forgoing adjuvant treatment was patient refusal. The mean overall survival (OS) was 34.5 months (interquartile range [IQR]: 15.5–53.5 months). The mean disease-free survival (DFS) was 18 months (IQR: 4.75–46.75 months). We identified five patients who survived at least 5 years without recurrence (21%). In each of these cases, the nodal metastases were restricted to a single level and no extracapsular lymph node involvement were detected. Additionally, worse DFS was associated with pT3/4 (vs. a lower T-stage), as well as microscopic lymphovascular invasion. Conclusion Although the small sample size precludes any definitive conclusions, it was possible to demonstrate that long-term survival without neoadjuvant and adjuvant treatment is possible in some patients if complete tumor and nodal resection is performed.

ZusammenfassungDie erfreulicherweise zunehmende Evidenz hat in den letzten Jahren mehrfache Änderungen der internationalen Empfehlungen für die Diagnostik und Therapie der resistenten Tuberkulose notwendig gemacht. In diesem Jahr hat die WHO umfassende Empfehlungen veröffentlicht, die die Entwicklungen der letzten Jahre berücksichtigen. Die aktuelle deutsche Tuberkuloseleitlinie erschien im Jahr 2017 und weicht in einigen Bereichen von diesen Empfehlungen ab. Hier werden die Neuerungen der WHO-Empfehlungen von 2020 für schnelle Diagnostik und die Therapie resistenter Tuberkulose zusammengefasst und relevante Abweichungen für Deutschland, Österreich und die Schweiz kommentiert. Eine Neubewertung der Literatur findet derzeit im Rahmen der Aktualisierung der deutschsprachigen AWMF-2k-Leitlinie statt.

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.

Zusammenfassung Hintergrund Infektiöse Komplikationen nach lungenresezierenden Eingriffen sind mit erheblicher perioperativer Morbidität und Mortalität verbunden. Neben anderen Faktoren beeinflusst sowohl die perioperative Antibiotikaprophylaxe als auch das Management der postoperativen Pneumonie das Behandlungsergebnis. Ein lokaler Behandlungspfad soll helfen, eine rationale perioperative Antibiotikatherapie zu realisieren. Methoden Wir analysierten mikrobiologische Ergebnisse von 200 Patienten vor und nach lungenresezierenden Eingriffen von Oktober 2013 bis Oktober 2014. Unter Berücksichtigung der aktuellen Leitlinien, der lokalen Erreger- und Resistenzsituation sowie Prinzipien der Antibiotic Stewardship wurde ein Behandlungspfad für die perioperative Antibiotikatherapie entwickelt. Ergebnisse Mehrheitlich wurden in der präoperativen (62%) und in der postoperativen Phase (78%) gramnegative Erreger nachgewiesen. Der Anteil der Erreger mit intrinsischer Resistenz gegenüber der gängigen perioperativen Antibiotikaprophylaxe war sowohl in der präoperativen (21%) als auch in der postoperativen Phase (39%) bedeutsam. Diese Erkenntnisse wurden in den lokalen Behandlungspfad integriert. Schlussfolgerung Die gängige perioperative Antibiotikaprophylaxe erfasst nur teilweise das Erregerspektrum der präoperativen tracheobronchialen Besiedelung sowie der postoperativen Pneumonie. Sie sollte daher nicht über den Operationszeitpunkt hinaus fortgeführt werden. Eine postoperative Pneumonie sollte nach den Grundsätzen einer nosokomialen Pneumonie therapiert werden und die lokale Erreger- und Resistenzsituation berücksichtigen.

The Purple Urine Bag Syndrome (PUBS) is a rare condition in which the urine turns purple. It may occur in Urinary Tract Infections (UTIs) when bacteria metabolize dietary tryptophan to indole resulting in indigo (blue) and indirubin (red). This condition is mostly seen in elderly female patients with permanent urinary bladder catheterization. Patients, relatives and health professionals may be concerned about this discolouration, which is usually harmless. Medical management of PUBS involves frequent urinary bag change, antibiotic therapy and most importantly reassurance. We report an 89-years-old long-term catheterized female nursing home resident who was admitted to the emergency room because of a Community Acquired Pneumonia (CAP). After a few days of inpatient treatment her urine bag turned purple. Antibiotic therapy continued and the indwelling urinary catheter was changed resulting in clear urine. Keywords: Purple urine bag syndrome (PUBS); purple discolouration; urinary tract infection (UTI); long-term catheterization.

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.

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.

SARS-CoV-2 utilizes the ACE2 transmembrane peptidase as essential cellular entry receptor. Several studies have suggested abundant ACE2 expression in the human lung, inferring strong permissiveness to SARS-CoV-2 infection with resultant alveolar damage and lung injury. Against this expectation, we provide evidence that ACE2 expression must be considered scarce, thereby limiting SARS-CoV-2 propagation in the human alveolus. Instead, spectral imaging of ex vivo infected human lungs and COVID-19 autopsy samples depicted that alveolar macrophages were frequently positive for SARS-CoV-2, indicating viral phagocytosis. Single-cell transcriptomics of SARS-CoV-2 infected human lung tissue further revealed strong inflammatory and anti-viral activation responses in macrophages and monocytes, comparable to those induced by MERS-CoV, but with virus-specific gene expression profiles. Collectively, our findings indicate that severe lung injury in COVID-19 likely results from an overwhelming immune activation rather than direct viral damage of the alveolar compartment. Funding: ACH, LES, SH were supported by Berlin University Alliance GC2 Global Health (Corona Virus Pre-Exploration Project). ACH, SH, TW and CD were supported by BMBF (RAPID) and ACH, SH by BMBF (alvBarriereCOVID-19). KH, LB, SL, SH, CD, TW, ACH were funded by BMBF (NFN-COVID 19, Organo-Strat). KH, NS, LES, MW, SH, ADG, CD, TW and ACH were supported by DFG (SFB-TR 84). ACH was supported by BIH, Charite 3R, and Charite-Zeiss MultiDim. KH was supported by BMBF (Camo-COVID-19). MW, NS and SH was supported by BMBF (PROVID). MW and NS was supported by BIH and BMBF (SYMPATH, CAPSyS, NAPKON). BO and DB were funded through the BIH Clinical Single Cell Bioinformatics Pipeline. LB was supported by the BMBF (CoIMMUNE), the DFG (KFO 342) and the IZKF of the Medical Faculty of the WWU. Conflict of Interest: The authors declare no competing interests. Ethical Approval: The study was approved by the ethics committee at the Charite clinic (projects EA2/079/13) and Arztekammer Westfalen-Lippe and of the Westfalischen Wilhelms-Universitat (AZ: 2016-265-f-S). Written informed consent was obtained from all patients.

The majority of the people suffering from tuberculosis in Germany are migrants. The treatment of this demographic still presents certain challenges. Only up to a quarter to a fifth of tuberculosis cases in migrants is being diagnosed by the screening methods that were implemented by The German Protection against Infection Act (Infektionsschutzgesetz, IfSG). Reactivation of latent tuberculosis is the most common cause for tuberculosis in migrants. Easy access to health care is vital for the testing and treatment of latent tuberculosis in people with a high risk of reactivation. The level of infection risk, comorbidities and presentation of disease vary depending on the country of origin. Especially during migration people are more susceptible to somatic and mental maladies. Extrapulmonary tuberculosis is frequent in migrants and requires specific diagnostic approaches. Where risk factors for a multi-drug-resistant tuberculosis are present, this condition has to be actively excluded. To facilitate diagnosis and therapy of tuberculosis in migrants a high level of trust has to be established in the doctor-patient relationship. Therefore and despite of cultural and linguistic differences empathy and time are key. Patients need to be encouraged to complete their treatment rather than terminate it prematurely. To that end comorbidities have also to be diagnosed and treated, social and legal aspects have to be considered.

Autoimmunerkrankungen mit Lungenbeteiligung sind gut charakterisiert. In der Praxis gibt es diffuse Lungenparenchymerkrankungen unklarer Ursache, aber mit moglichen Hinweisen auf eine Autoimmunerkrankung, ohne dass eine definitive rheumatologische Diagnose gestellt werden kann. In 2015 veroffentlichte eine Arbeitsgruppe der European Respiratory Society (ERS) und der American Thoracic Society (ATS) einen Klassifikationskatalog zur IPAF („interstitial pneumonia with autoimmune features“), nachdem zuvor unterschiedliche Klassifikationssysteme existierten. Diese Arbeit bietet einen Uberblick uber aktuelle Evidenz zum Thema IPAF sowie einen Ausblick auf das im Aufbau befindliche Berlin-Brandenburger IPAF-Register. Die Evidenz wurde mittels narrativer PubMed-Recherche gesucht. Zielsetzung und Projektdesign des Registers werden dargestellt. Die Evidenz zu IPAF ist limitiert. Nach Veroffentlichung der ERS/ATS-Kriterien wurden nur wenige, retrospektive Evaluationsstudien publiziert. Der Parameterkatalog des Berlin-Brandenburger IPAF-Registers bildet IPAF-Krankheitsverlaufe umfassend ab. Eine Online-Datenplattform fur prospektive, multizentrische Langzeitbeobachtungen wurde programmiert. Nach einer Pilotphase ist eine Ausweitung des Datenregisters auf die Region Berlin-Brandenburg geplant. Eine exakte Abgrenzung von idiopathischen interstitiellen Pneumonien (IIP), IPAF und Kollagenosen („connective tissue diseases“, CTD) mit pulmonalen Manifestationen ist weiterhin schwierig. Eine noch intensivere multidisziplinare Zusammenarbeit von Rheumatologen, Pneumologen, Radiologen, Pathologen und Labormedizinern ist daher anzustreben. Zur Verbesserung der Evidenzbasis konnen prospektive Patientenregister wie das Berlin-Brandenburger IPAF-Register eine wertvolle Hilfe darstellen.

Zwar ist die Tuberkulose mit knapp 6.000 Neuinfektionen pro Jahr noch immer eine eher seltene Erkrankung, aber weltweit ist die Tuberkulose mit uber 10 Millionen Neuinfektionen pro Jahr unter den 10 haufigsten Todesursachen zu finden. In unserer globalisierten Welt sollten Sie die Symptome sicher erkennen, bezuglich der Risikofaktoren informiert sein und wissen, welche diagnostischen und therapeutischen Schritte einzuleiten sind.

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.

Die Tuberkulose (TB) ist weltweit eine der haufigsten Infektionserkrankungen und unter den zehn haufigsten Todesursachen. In Deutschland ist vor allem migrationsbedingt ein Anstieg der Fallzahlen seit 2015 zu beobachten. Dadurch ist der Informationsbedarf bezuglich der Infektionskontrolle sowie der richtigen Diagnostik und Therapie dieser in Deutschland selten gewordenen Erkrankung merklich gestiegen. Vor diesem Hintergrund hat das Deutsche Zentralkomitee zur Bekampfung der TB (DZK) im Auftrag der Deutschen Gesellschaft fur Pneumologie (DGP) und in Zusammenarbeit mit den hierfur relevanten Fachgesellschaften die Empfehlungen zur TB-Therapie von 2012 uberarbeitet. Konsensbasiert wurde der derzeitige Wissenstand bei der Diagnostik und Therapie der verschiedenen TB-Formen unter Berucksichtigung der Situation in Deutschland zusammengestellt. Im Juni 2017 wurde die S2k-Leitlinie „Tuberkulose im Erwachsenenalter“ veroffentlicht. Gesondert erscheint eine eigenstandige Leitlinie der entsprechenden Fachgesellschaften fur die TB im Kindesalter. Die Leitlinien sollen den an der Behandlung der TB beteiligten Fachgruppen eine Hilfestellung bei der komplexen und strukturell aufwandigen Patientenbetreuung bieten. In dieser Ubersicht werden wichtige Aspekte der neuen Leitlinie fur die Behandlung von medikamentensensiblen und -resistenten TB-Patienten zusammengefasst.

ZusammenfassungIn Deutschland ist seit 2015 ein deutlicher Anstieg der gemeldeten Tuberkulosefälle zu verzeichnen. Zurückzuführen ist dieser vor allem auf die aktuell vermehrte Migration. Durch die niedrige Inzidenz in den vorhergehenden Jahren konzentriert sich die Erfahrung im Umgang mit Tuberkulose immer mehr auf spezialisierte Zentren. Pneumologen wie auch andere Fachbereiche sind nun aber wieder häufiger an der Behandlung einer Tuberkulose beteiligt, sodass Fachwissen zur Standardtherapie wie auch zu selteneren Therapiesituationen benötigt wird. Die aktuelle Leitlinie zur Diagnostik und Therapie, einschließlich Chemoprävention und -prophylaxe im Erwachsenenalter fasst den derzeitigen Wissensstand zusammen und passt die Empfehlungen an die Situation in Deutschland an. Realisiert wurde die AWMF S2k-Leitlinie durch das Deutsche Zentralkomitee zur Bekämpfung der Tuberkulose e. V. (DZK) im Auftrag der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. (DGP). Zur Behandlung der Tuberkulose im pädiatrischen Bereich wird in Kürze eine eigenständige Leitlinie der entsprechenden Fachgesellschaften veröffentlicht. Im Vergleich zu den Empfehlungen von 2012 sind eigenständige Kapitel zur Labordiagnostik und zum therapeutischen Medikamentenmanagement entstanden. Die Kapitel Mehrfachresistenzen gegen Medikamente der Standardtherapie, HIV-Koinfektion und die Übersicht der Arzneimittel wurden erweitert. Die umfangreiche Überarbeitung der Empfehlungen soll Ärzten und auch anderen Beschäftigten im Gesundheitswesen helfen, den aktuellen Herausforderungen im Umgang mit dem selten gewordenen Tuberkuloseerreger zu begegnen.

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.

Introduction: Tumours with chest wall invasion form a distinct sub-entity in the heterogeneuous group of locally advanced NSCLC. Despite some available evidence, the best sequence of recommended multimodal therapeutic approaches continues to be subjet of clinical research in view of the improved possibilities of radiation and systemic therapies. Material and Methods: In our mono-centric, retrospective observational study, all NSCLC pts. with chest wall infiltration or pancoast tumour (N0-2, M0), diagnosed between 01/2009 and 12/2013, were analyzed using our hospital information system and cancer registry. Clinical, radiological, tumour biological, therapeutic and follow-up data were recorded for this study. Results: In the 5 year period, 81 pts. were detected with chest wall invasion and pancoast in 72 and 9 pts., respectively. Mean age was 66.4 yrs. (45.7-84,7 yrs.). Histology was dominated by squamous cell (53.1%) and adenocarcinoma (32.1%), followed by large cell carc. (6.2%). Theraputic regimes were: 1. neoadjuvant Tx.+resection (22 pts., 27.2%), 2. planned neoadj. Tx. with change to definite chemoradiotherapy due to progression (13. pts., 16.0%), 3. resection+adjuv. Tx (25 pts., 30.8%), 4. primary definite chemoradiotherapy (19 pts., 23.5%) and 5. best-supportive care only (2 pts., 2.5%). Best median 5-year overall survival was seen in the cohort with neoadjuvant Tx.+resection (11.6-153.4 months) (fig. 1). Discussion: Our retrospective data underline the prognostic significance of neoadjuvant tx followed by resection as treatment regimen in NSCLC with chest wall invasion. However, patient and tumour characteristics havinfluence the choice of treatment.

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.

Objectives Surgery has been available for the treatment of mono-metastatic, non-small cell lung cancer (NSCLC) and promising overall survival was observed in some retrospective studies with selected patients. This study investigated whether the preoperative 18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) scan influences survival in this patient group. Furthermore we tried to identify other prognostic factors associated with survival and aimed to clarify if synchronous metastases are different from metachronous disease. Methods Between 1994 and 2012, 181 patients underwent resection for solitary metastases. Sixty-six patients underwent surgery after an initial FDG-PET/CT scan, whereas 115 patients underwent conventional preoperative staging by a spiral CT scan. Results The overall 5-year survival rate was 38.8%. The 5-year survival rates after preoperative evaluation by FDG-PET/CT and by conventional CT were 58% and 33%, respectively ( p = 0.01). A higher 5-year survival rate was observed in patients without thoracic lymph node involvement (pN0: 44% vs. pN1-3: 33%, p = 0.028). In patients with a solitary pulmonary metastasis, we observed a 5-year survival rate of 45.7%, whereas in patients with extrapulmonary metastases, the 5-year survival rate was 27.1% ( p = 0.001). In patients with a locally limited primary lung cancer according to the pT descriptor, we observed a 5-year survival rate of 53.1%, whereas in patients with a pT > 1 descriptor, the 5-year survival rate was 33.6% ( p = 0.016). By multivariate analyses, we showed that preoperative FDG-PET/CT evaluation, no thoracic lymph node metastases, and sole pulmonary metastatic disease were favorable predictors of survival, whereas the time of metastasis (synchronous vs. metachronous) and maximum standardized uptake value was not. Conclusions We conclude that resection of the primary tumor and metastasectomy for mono-metastatic NSCLC can be performed after a comprehensive evaluation with FDG-PET/CT. N-stage and the site of the oligometastases have a significant influence on overall survival.

Based on the results of studies from the 1960s-1980s the current four drug combination therapy was established as standard or short course tuberculosis therapy worldwide. The regional epidemiology and the often unique conditions within a national health system create the need for specific adjustments. Over the last years these were realized by the German central committee against tuberculosis (DZK) in the recommendations for tuberculosis therapy. Because of the recent development of migration into Germany from countries with higher tuberculosis incidences an increase in tuberculosis cases is to be expected. The expected increase in tuberculosis cases will lead to more contact with tuberculosis patients even in the outpatient setting. New S2k guidelines guided by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) for the treatment of tuberculosis for children and adults are under development. Before the release of the comprehensive guidelines, practical evidence for the diagnosis and treatment of uncomplicated tuberculosis is summarized in this document to meet the challenges of the recent developments.

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

Due to an increase of drug resistant TB, alternative drugs that are not currently listed in the WHO guidelines on MDR TB treatment are currently being evaluated. Our group tested 100 susceptible, 20 MDR and 2 XDR Mtb strains against the phenothiazine derivatives thioridazine, trifluoperazine and triflupromazine. MIC testing was performed on Middlebrook 7H10 agar and was defined as the lowest drug concentration that inhibits ≥99% of the bacterial population. We confirm very good in vitro activity of phenothiazines against Mycobacterium tuberculosis. In >77% of all strains MICs of ≤10 μg/ml were found.

Loss of alveolar barrier function with subsequent respiratory failure is a hallmark of severe pneumonia. Although junctions between endo- and epithelial cells regulate paracellular fluid flux, little is known about their composition and regulation in the human alveolar compartment. High autofluorescence of human lung tissue in particular complicates the determination of subcellular protein localization. By comparing conventional channel mode confocal imaging with spectral imaging and linear unmixing, we demonstrate that background fluorescent spectra and fluorophore signals could be rigorously separated resulting in complete recovery of the specific signal at a high signal-to-noise ratio. Using this technique and Western blotting, we show the expression patterns of tight junction proteins occludin, ZO-1 as well as claudin-3, -4, -5 and -18 and adherence junction protein VE-cadherin in naive or Streptococcus pneumoniae-infected human lung tissue. In uninfected tissues, occludin and ZO-1 formed band-like structures in alveolar epithelial cells type I (AEC I), alveolar epithelial cells type II (AEC II) and lung capillaries, whereas claudin-3, -4 and -18 were visualised in AEC II. Claudin-5 was detected in the endothelium only. Claudin-3, -5, -18 displayed continuous band-like structures, while claudin-4 showed a dot-like expression. Pneumococcal infection reduced alveolar occludin, ZO-1, claudin-5 and VE-cadherin but did not change the presence of claudin-3, -4 and -18. Spectral confocal microscopy allows for the subcellular structural analysis of proteins in highly autofluorescent human lung tissue. The thereby observed deterioration of lung alveolar junctional organisation gives a structural explanation for alveolar barrier disruption in severe pneumococcal pneumonia.

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.

Die Ausbildung von Bronchiektasen entsteht in einem „circulus vitiosus“ aus verminderter Sekretclearance, bakterieller Besiedlung, chronischer Entzundung und Gewebezerstorung. Die chronisch-progressive Lungendestruktion fuhrt zu erhohter Morbiditat und Mortalitat. Die Diagnose wird mittels hochauflosender Computertomographie („high-resolution computed tomography“, HRCT) gestellt. Bei Bestatigung von Bronchiektasen muss eine weitere Abklarung in Richtung einer moglichen Grunderkrankung begonnen werden. Aufgrund der Vielzahl der in Frage kommenden Erkrankungen ist eine strukturierte Differentialdiagnostik notwendig. Dieser Artikel erlautert die verschiedenen Ursachen von Non-CF-Bronchiektasie (NCFB) und stellt einen diagnostischen Algorithmus sowie Therapieoptionen vor. Diese Ubersicht soll Kinder- und Jugendarzten sowie Internisten als Leitfaden dienen und zur verbesserten Diagnose und Therapie von Patienten aller Altersgruppen mit Bronchiektasen beitragen.