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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.

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.

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.

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.

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.

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.

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.