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Bronchoscopy has changed considerably in recent years as a result of technical innovations and health economic pressure. There is little current information available on the reality of bronchoscopy care in Germany., Methodology: In September 2022, sites where bronchoscopy was carried out were systematically surveyed regarding structural and process quality features in an anonymized DGP survey with 33 questions. The data collected were analyzed descriptively., Results: Of the 196 participating sites, bronchoscopies were performed regularly at 180 sites. The majority were standard secondary care (n=51) and tertiary care (n=43) hospitals (range of services: diagnostic bronchoscopy, predominantly (80%) including endobronchial ultrasound-guided transbronchial needle aspiration, EBUS-TBNA). Extended treatment options were guaranteed for acute cases at >90% of these locations. University hospitals (n=24) and specialist pulmonary hospitals (n=35) also offered more complex diagnostic procedures and therapeutic-interventional techniques. The performance figures were significantly higher in the specialist pulmonary hospital (specialist pulmonary hospitals: 62%: >2000 bronchoscopies/year; university hospitals: 25%: >2000 bronchoscopies/year; p<0.001). In the practice setting (n=21, partly in co-operation with hospitals) , <500 bronchoscopies/year were performed.Intensive care units were available in 97% of the hospitals; 88% of the hospitals had fluoroscopy facilities in the bronchoscopy room. Propofol (91%) and/or midazolam (62%) were the preferred drugs for sedation. At 21% of the sites, >200 bronchoscopies under ventilation/year were performed. BAL and transbronchial forceps biopsies were mainly performed via the nasal or oral approach, EBUS-TBNA via a bronchoscopy tube or the oral approach, the EBUS mini-probe/navigation, cryotechnique or more complex interventions via the rigid tube or a bronchoscopy tube. ASA >2 led to involvement of a second physician at 46% of clinical sites, at 47% of sites at an ASA classification >3., Conclusion: The majority of bronchoscopic examinations are performed in respiratory departments at secondary care centres as well as maximum care hospitals. For more complex procedures, cooperation with hospitals specialized in bronchoscopy (e.g. university hospital or a specialist lung clinic) is advisable., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Both tobacco cessation and low-dose CT screening in at-risk individuals reduce lung cancer-specific and all-cause mortality. As part of a national screening program for the early detection of lung cancer, smoking cessation must be a mandatory part of the counseling given to participants. This increases the cost-benefit effectiveness of the screening program. As part of the initial consultation evidence-based measures for smoking cessation must be offered to smoking participants of the screening program in form of a minimal intervention. If participants do not want to participate in a quit smoking measure they must actively refuse (opt-out rule). The costs of quitting smoking, including the costs of withdrawal-inhibiting medication, have to be fully covered by statutory health insurance for participants in the lung cancer screening program., Competing Interests: Alexander Rupp ist Berater der Firma Sanero Medical GmbH Stuttgart, die eine Internetplattform und eine digitale Gesundheitsanwendung (DiGA) zur Tabakentwöhnung betreibt.Christa Rustler ist Leiterin des Büros des Deutschen Netz rauchfreier Krankenhäuser und Gesundheitseinrichtungen (DNRfK), welches zur Implementierung des „rauchfrei tickets“ Zuwendungen der Bundeszentrale für gesundheitliche Aufklärung (BZgA) erhält.Die anderen Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Since the onset of the war in Ukraine until November 2022, nearly 1 million people sought refuge in Germany. Despite efforts to reduce tuberculosis (TB) cases, Ukraine had a high TB incidence in 2020, with increased rates of multidrug-resistant TB. Conflict and war have historically been associated with TB spread due to delays in diagnosis, treatment interruptions, and increased transmission risks. The World Health Organization (WHO) estimated a rise in TB cases in the EU region due to refugee movements. In Germany, screening methods used in testing individuals in communal housing involving chest X-rays or immunological tests were variable. A survey conducted by the DZK within the nationwide TB working group evaluated TB screening methods and results for Ukrainian refugees. Out of 26,196 individuals aged over 15, 48 TB cases were detected, with a higher-than-expected incidence. About 42% of cases were multidrug-resistant TB. The screening findings differed from both the WHO's estimates as well as TB cases reported to the Robert Koch Institut (RKI) in 2022. A preliminary comparison of the numbers is presented here. The differing results emphasize the need for ongoing data collection and analysis to adapt resources and interventions to the evolving TB situation among Ukrainian refugees in Germany, especially considering the ongoing conflict and potential for increased TB cases in the future., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction:  The ambulantization of patient care that were previously provided as inpatient service is one of the goals of the current reform in the German healthcare system. In pulmonology, this particularly applies to endoscopic procedures. However, the real costs of endoscopic services, which form the basis for the calculation of a future so called hybrid DRG or in the AOP catalog, are unclear., Methods:  After selection of use cases including endoscopic procedures which can be performed on an outpatient basis by a committee of experts the appropriate DRGs were identified from the § 21-KHEntgG data for 2022 published by the Institute for the Hospital Remuneration System (InEK). The costs were calculated from the respective InEK cost matrix added by the calculated material costs., Results:  The use cases suitable for outpatient treatment were systematic endobronchial ultrasound (EBUS) with transbronchial needle aspiration (calculated costs € 2,175.60 without or € 3,315.60 including PET/CT), navigation-assisted bronchoscopy for peripheral lesions (depending on the methodology € 2,870.23 to €4,120.23) and diagnostic (flexible) bronchoscopy (€ 1,121.02)., Conclusion:  Outpatient treatment of endoscopic procedures that were previously performed inpatient is possible and necessary, and the costs calculated in this publication can form a reliable basis for appropriate reimbursement. Together with a structural quality that has been transformed to outpatient service and cross-sector cooperation, continued high-quality care for pneumological patients can be ensured., Competing Interests: Keiner der Autoren erklärte einen Interessenkonflikt. Die inspiring-health GmbH (M. Rathmayer, M. Tiefgraber, M. Wilke) hat als Berater für die Moderation der Arbeitsgruppensitzungen und die Durchführung der Kostenkalkulationen ein Beratungshonorar von der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V. erhalten., (Thieme. All rights reserved.)

Based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB) in December 2022. The new recommendations and the latest study data made it necessary to update the existing guideline on the treatment of at least rifampicin-resistant TB (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published in 2022. A shortened treatment of proven RR-TB and multidrug-resistant TB for at least 6 months using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Austria, Germany, and Switzerland under certain conditions considering the existing barriers for the implementation of the new treatment regimen. For the treatment of pre-extensively drug-resistant (pre-XDR-) TB, an individualized treatment for 18 months continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in selected pre-XDR-TB cases, provided that all prerequisites are met. The necessary requirements for using BPaLM and BPaL are presented in detail in this amendment to the consensus-based TB treatment guideline for adult patients., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'., Competing Interests: Informationen zu Interessenkonflikten finden Sie auf den Seiten der AWMF (http://www.awmf.org/leitlinien/awmf-regelwerk.html)., (Thieme. All rights reserved.)

Preventing the spread of the disease is an essential goal in the care and treatment of tuberculosis. In addition to early diagnosis and effective therapies, isolation of infectious patients and adequate hygiene measures are of particular importance for infection prevention. The present recommendations replace the previous recommendations "tuberculosis infection control" from 2012 and take into account the current national and international recommendations and as well as new scientific findings. After a description of the infection and the transmission pathways, the necessary prevention and hygiene measures in health care facilities are comprehensively presented. Since the last revision of the recommendations on infection prevention, international recommendations and the KRINKO recommendation on ending isolation have been changed. In accordance with this, under certain conditions in the case of sensitive tuberculosis, de-isolation in health care facilities can take place after 14 days without taking the sputum findings into account. The second part of the recommendations explains in detail the measures to be taken in special situations and areas, such as general practitioners, ambulance services and care facilities. Here, the recommendations on respiratory protection have been simplified; for staff, an FFP2 mask is now generally considered sufficient., Competing Interests: Inna Friesen: Institutionelle Förderung durch Bruker/Hain Lifescience und INSTAND, Vortragshonorar durch GSK.Martin Kuhns: Institutionelle Förderung durch Bruker/Hain Lifescience und INSTAND.Roland Diel: Honorare und/oder Reisekostenunterstützung für Vorträge bei Veranstaltungen, die von Hain Lifescience, Insmed, Mikrogen, Oxford Immunotec oder Qiagen gesponsert wurden.Ralf Otto-Knapp: Vortragshonorar durch MSD., (Thieme. All rights reserved.)

The aim of contact tracing for tuberculosis is in addition to active case finding the detection of chains of infection and the prevention of the further spread of the disease. In this context, a careful selection of contact persons is necessary, depending on the type and duration of contact, to identify persons who are recently infected and therefore to increase the benefit of a preventive therapy and to avoid unnecessary testing of persons who are not at risk of infection. Since the last update of the recommendations on contact tracing, data on the use of interferon-y release assays (IGRAs) in children has been improved markedly. These are the preferred test in contact tracing of adults. For children, both IGRAs and the tuberculin skin test can be used equivalently. Rifampicin for 4 months, rifampicin and isoniazid for 3 months, or isoniazid for 9 months are recommended as preventive therapy in cases of confirmed infection.The implementation of the contact tracing in different age groups as well as legal framework conditions and socio-medical aspects and challenges are dealt with in detail. In addition, special cases, such as environmental screening in day-care centers, schools, or other community facilities, are discussed separately., Competing Interests: R. D. erhielt Honorare und/oder Reisekostenunterstützung für Vorträge bei Veranstaltungen, die von Hain Lifescience, Insmed, Mikrogen, Oxford Immunotec oder Qiagen gesponsert wurden. Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

The aim of contact tracing for tuberculosis is in addition to active case finding the detection of chains of infection and the prevention of the further spread of the disease. In this context, a careful selection of contact persons is necessary, depending on the type and duration of contact, to identify persons who are recently infected and therefore to increase the benefit of a preventive therapy and to avoid unnecessary testing of persons who are not at risk of infection. Since the last update of the recommendations on contact tracing, data on the use of interferon-y release assays (IGRAs) in children has been improved markedly. These are the preferred test in contact tracing of adults. For children, both IGRAs and the tuberculin skin test can be used equivalently. Rifampicin for 4 months, rifampicin and isoniazid for 3 months, or isoniazid for 9 months are recommended as preventive therapy in cases of confirmed infection.The implementation of the contact tracing in different age groups as well as legal framework conditions and socio-medical aspects and challenges are dealt with in detail. In addition, special cases, such as environmental screening in day-care centers, schools, or other community facilities, are discussed separately., Competing Interests: R. D. erhielt Honorare und/oder Reisekostenunterstützung für Vorträge bei Veranstaltungen, die von Hain Lifescience, Insmed, Mikrogen, Oxford Immunotec oder Qiagen gesponsert wurden. Alle weiteren Autorinnen und Autoren haben keine potenziellen COI angegeben., (Thieme. All rights reserved.)

Pneumocystis jirovecii , a fungus causing severe Pneumocystis pneumonia (PCP) in humans, has long been described as non-culturable. Only isolated short-term experiments with P. jirovecii and a small number of experiments involving animal-derived Pneumocystis species have been published to date. However, P. jirovecii culture conditions may differ significantly from those of animal-derived Pneumocystis , as there are major genotypic and phenotypic differences between them. Establishing a well-performing P. jirovecii cultivation is crucial to understanding PCP and its pathophysiological processes. The aim of this study, therefore, was to develop an axenic culture for Pneumocystis jirovecii . To identify promising approaches for cultivation, a literature survey encompassing animal-derived Pneumocystis cultures was carried out. The variables identified, such as incubation time, pH value, vitamins, amino acids, and other components, were trialed and adjusted to find the optimum conditions for P. jirovecii culture. This allowed us to develop a medium that produced a 42.6-fold increase in P. jirovecii qPCR copy numbers after a 48-day culture. Growth was confirmed microscopically by the increasing number and size of actively growing Pneumocystis clusters in the final medium, DMEM-O3. P. jirovecii doubling time was 8.9 days (range 6.9 to 13.6 days). In conclusion, we successfully cultivated P. jirovecii under optimized cell-free conditions in a 70-day long-term culture for the first time. However, further optimization of the culture conditions for this slow grower is indispensable.

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor ( p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS ( p < 0.02). The effect was also maintained when only advanced tumour stages were considered ( p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy ( p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.

Introduction: Checkpoint-inhibitor pneumonitis (CIP) represents a major immune-related adverse event (irAE) in patients with lung cancer. We aimed for the clinical characterization, diagnostics, risk factors, treatment and outcome in a large cohort of patients from everyday clinical practice., Patients and Methods: For this retrospective analysis, 1,376 patients having received checkpoint inhibitors (CPI) in any line of therapy from June 2015 until February 2020 from three large-volume lung cancer centers in Berlin, Germany were included and analyzed., Results: With a median follow-up of 35 months, all-grade, high-grade (CTCAE ≥ 3) and fatal CIP were observed in 83 (6.0%), 37 (2.7%) and 12 (0.9%) patients, respectively, with a median onset 4 months after initiation of CPI therapy. The most common radiologic patterns were organizing pneumonia (OP) and non-specific interstitial pneumonia (NSIP) (37% and 31%). All except 7 patients with G1-2 CIP interrupted treatment. Corticosteroids were administered to 74 patients with a median starting dose of 0.75 mg/kg. After complete restitution (n = 67), re-exposure to CPI (n = 14) led to additional irAE in 43% of the cases. Thoracic radiotherapy targeting the lung was the only independent risk factor for CIP (odds ratio 2.8, p < 0.001) and pretherapeutic diffusing capacity for carbon monoxide inversely correlated with CIP severity. Compared with patients without CIP and non-CIP irAE, CIP was associated with impaired overall survival (hazard ratios 1.23, p = 0.24 and 2.01, p = 0.005)., Conclusions: High-grade CIP accounts for almost half of all CIP cases in an allcomer lung cancer population. A continuous vigilance, rapid diagnostics and adequate treatment are key to prevent disease progression associated with impaired survival., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Frost reports consulting fees for being an advisory board member from AbbVie, Amgen, AstraZeneca, BeiGene, Berlinchemie, Boehringer Ingelheim, Bristol Myers&Squibb, Lilly, Merck Sharp&Dohme, Merck, Novartis, Pfizer, Roche, Sanofi and Takeda; Support for attending meetings and/or travel from Amgen, AstraZeneca, BMS, Janssen, Lilly and Takeda; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for the “Deutsche Gesellschaft für Pneumologie (DGP)” and the “Deutsche Krebsgesellschaft (DKG): Arbeitsgemeinschaft Internistische Onkologie, Sektion Thoraxonkologie”. Mrs. Unger has nothing to disclose. Dr. Blum has nothing to disclose. Dr. Misch has nothing to disclose. Dr. Kurz has nothing to disclose. Dr. Lüders has nothing to disclose. Dr. Olive has nothing to disclose. Dr. Raspe has nothing to disclose. Dr. Hilbrandt has nothing to disclose. Dr. Koch reports consulting fees for AstraZeneca and Roche, travel support from Boehringer Ingelheim and participation on a data safety monitoring board or advisory board for Roche and Janssen-Cilag. Dr. Böhmer reports consulting fees from Varian Medical Systems. Dr. Senger has nothing to disclose. Dr. Witzenrath reports having received research grants from the „Deutsche Forschungsgemeinschaft“, „Bundesministerium für Bildung und Forschung“, „Deutsche Gesellschaft für Pneumologie“, European Respiratory Society, Marie Curie Foundation, Else Kröner Fresenius Foundation, Capnetz Foundation, International Max Planck Research School, personal fees for lectures or consulting from: Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotest, Boehringer Ingelheim, Chiesi, Gilead, Glaxo Smith Kline, Hexal, Insmed, Novartis, Noxxon, Pantherna, Roche, Teva, Vaxxilon; Patents planned, issued or pending: EPO 12181535.1: IL-27 for modulation of immune response in acute lung injury (Issued 2012), WO/2010/094491: Means for inhibiting the expression of Ang-2 (Issued 2010); PCT/EP2021/066543: A pharmaceutical combination comprising an anti-viral protonophore and a serine protease inhibitor (Issued 2021); PCT/EP2021/075627: New medical use of cystic fibrosis transmembrane conductance regulator (CFTR) modulators (Issued 2021). Dr. Grohé reports having received research grants from AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda and Siemens; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Ariad, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda and Siemens; Participation on a Data Safety Monitoring Board or Advisory Board for AbbVie, Ariad, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda and Siemens; Dr. Bauer has nothing to disclose. Dr. Modest reports consulting fees from Amgen, Merck Serono, Servier, Pierre Fabre, BMS, MSD, Lilly, AstraZeneca, Onkowissen, Sanofi, Taiho, G1 and Transgene; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, Merck Serono, Servier, Pierre Fabre, BMS, MSD, Lilly, AstraZeneca, Onkowissen, Sanofi, Taiho, G1 and Transgene; Support for attending meetings and/or travel from Amgen. Dr. Kollmeier has nothing to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: At the beginning of the COVID-19 pandemic, SARS-CoV-2 was often compared to seasonal influenza. We aimed to compare the outcome of hospitalized patients with cancer infected by SARS-CoV-2 or seasonal influenza including intensive care unit admission, mechanical ventilation and in-hospital mortality., Methods: We analyzed claims data of patients with a lab-confirmed SARS-CoV-2 or seasonal influenza infection admitted to one of 85 hospitals of a German-wide hospital network between January 2016 and August 2021., Results: 29,284 patients with COVID-19 and 7442 patients with seasonal influenza were included. Of these, 360 patients with seasonal influenza and 1625 patients with COVID-19 had any kind of cancer. Cancer patients with COVID-19 were more likely to be admitted to the intensive care unit than cancer patients with seasonal influenza (29.4% vs 24.7%; OR 1.31, 95% CI 1.00-1.73 p < .05). No statistical significance was observed in the mechanical ventilation rate for cancer patients with COVID-19 compared to those with seasonal influenza (17.2% vs 13.6% OR 1.34, 95% CI 0.96-1.86 p = .09). 34.9% of cancer patients with COVID-19 and 17.9% with seasonal influenza died (OR 2.45, 95% CI 1.81-3.32 p < .01). Risk factors among cancer patients with COVID-19 or seasonal influenza for in-hospital mortality included the male gender, age, a higher Elixhauser comorbidity index and metastatic cancer., Conclusion: Among cancer patients, SARS-CoV-2 was associated with a higher risk for in-hospital mortality than seasonal influenza. These findings underline the need of protective measurements to prevent an infection with either COVID-19 or seasonal influenza, especially in this high-risk population., (© 2022. The Author(s).)

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-019, (Thieme. All rights reserved.)

Precision oncology and immunotherapy have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Emerging studies show that targeted therapies are also beneficial for patients with driver alterations such as epidermal growth factor receptor (EGFR) mutations in early-stage NSCLC (stages I-IIIA). Furthermore, patients with elevated programmed death-ligand 1 (PD-L1) expression appear to respond favorably to adjuvant immunotherapy. To determine the frequency of genomic alterations and PD-L1 status in early-stage NSCLC, we retrospectively analyzed data from 2066 unselected, single-center patients with NSCLC diagnosed using next-generation sequencing and immunohistochemistry. Nine-hundred and sixty-two patients (46.9%) presented with early-stage NSCLC. Of these, 37.0% had genomic alterations for which targeted therapies have already been approved for advanced NSCLC. The frequencies of driver mutations in the early stages were equivalent to those in advanced stages, i.e., the rates of EGFR mutations in adenocarcinomas were 12.7% (72/567) and 12.0% (78/650) in early and advanced NSCLC, respectively ( p = 0778). In addition, 46.3% of early-stage NSCLC cases were PD-L1-positive, with a tumor proportion score (TPS) of ≥1%. With comparable frequencies of driver mutations in early and advanced NSCLC and PD-L1 overexpression in nearly half of patients with early-stage NSCLC, a broad spectrum of biomarkers for adjuvant and neoadjuvant therapies is available, and several are currently being investigated in clinical trials.

Since we first described Mycobacterium heckeshornense, a rare species of mycobacteria in 2000, only 21 cases of infection with this mycobacterium have been described in humans. We relate the diagnosis and therapy of another case of this uncommon nontuberculous mycobacterium in an immune-suppressed patient., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Rapid and reliable diagnostic work-up of tuberculosis (TB) remains a major healthcare goal. In particular, discrimination of TB infection from TB disease with currently available diagnostic tools is challenging and time consuming. This study aimed at establishing a standardised blood-based assay that rapidly and reliably discriminates TB infection from TB disease based on multiparameter analysis of TB antigen-reactive CD4 + T-cells acting as sensors for TB stage-specific immune status., Methods: 157 HIV-negative subjects with suspected TB infection or TB disease were recruited from local tertiary care hospitals in Berlin (Germany). Peripheral blood mononuclear cells were analysed for CD4 + T-cells reactive to the Mycobacterium tuberculosis antigens purified protein derivative and early secretory antigenic target 6 kDa/culture filtrate protein 10. The activation state of TB antigen-reactive T-cells, identified by surface expression of CD154, was evaluated according to the expression profile of proliferation marker Ki-67 and activation markers CD38 and HLA-DR. Using data from 81 subjects with clinically confirmed TB infection (n=34) or culture-proven pulmonary or extrapulmonary TB disease (n=47), 12 parameters were derived from the expression profile and integrated into a scoring system., Results: Using the scoring system, our assay (TB-Flow Assay) allowed reliable discrimination of TB infection from both pulmonary and extrapulmonary TB disease with high sensitivity (90.9%) and specificity (93.3%) as was confirmed by Monte-Carlo cross-validation., Conclusion: With low time requirement, ease of sample collection, and high sensitivity and specificity both for pulmonary and extrapulmonary TB disease, we believe this novel standardised TB-Flow Assay will improve the work-up of patients with suspected TB disease, supporting rapid TB diagnosis and facilitating treatment decisions., Competing Interests: Conflict of interest: A. Scheffold and P. Bacher are advisors to Miltenyi Biotec who own IP rights on the use of CD154 for antigen-specific T-cell detection. A. Scheffold, C. Meisel, H-D. Volk, P. Bacher, T. Meyer and A. Mantei are listed as inventors in a patent (10 2018 131 696.8) that has been issued and a patent (PCT/EP2019/084392) that is pending on the discrimination of TB infection and TB disease using the method described herein. The remaining authors declare no competing financial interests., (Copyright ©The authors 2022.)

Background: Immune checkpoint inhibitors (ICIs) are currently one of the most promising therapy options in the field of oncology. Although the first pivotal ICI trial results were published in 2011, few biomarkers exist to predict their therapy outcome. PD-L1 expression and tumor mutational burden (TMB) were proven to be sometimes-unreliable biomarkers. We have previously suggested the analysis of processing escapes, a qualitative measurement of epitope structure alterations under immune system pressure, to provide predictive information on ICI response. Here, we sought to further validate this approach and characterize interactions with different forms of immune pressure., Methods: We identified a cohort consisting of 48 patients with advanced non-small cell lung cancer (NSCLC) treated with nivolumab as ICI monotherapy. Tumor samples were subjected to targeted amplicon-based sequencing using a panel of 22 cancer-associated genes covering 98 mutational hotspots. Altered antigen processing was predicted by NetChop, and MHC binding verified by NetMHC. The NanoString nCounter® platform was utilized to provide gene expression data of 770 immune-related genes. Patient data from 408 patients with NSCLC were retrieved from The Cancer Genome Atlas (TCGA) as a validation cohort., Results: The two immune escape mechanisms of PD-L1 expression (TPS score) (n = 18) and presence of altered antigen processing (n = 10) are mutually non-exclusive and can occur in the same patient (n = 6). Both mechanisms have exclusive influence on different genes and pathways, according to differential gene expression analysis and gene set enrichment analysis, respectively. Interestingly, gene expression patterns associated with altered processing were enriched in T cell and NK cell immune activity. Though both mechanisms influence different genes, they are similarly linked to increased immune activity., Conclusion: Pressure from the immune system will lay the foundations for escape mechanisms, leading to acquisition of resistance under therapy. Both PD-L1 expression and altered antigen processing are induced similarly by pronounced immunoactivity but in different context. The present data help to deepen our understanding of the underlying mechanisms behind those immune escapes., (© 2022. The Author(s).)

Assessing the risk for specific patient groups to suffer from severe courses of COVID-19 is of major importance in the current SARS-CoV-2 pandemic. This review focusses on the risk for specific patient groups with chronic respiratory conditions, such as patients with asthma, chronic obstructive pulmonary disease, cystic fibrosis (CF), sarcoidosis, interstitial lung diseases, lung cancer, sleep apnea, tuberculosis, neuromuscular diseases, a history of pulmonary embolism, and patients with lung transplants. Evidence and recommendations are detailed in exemplary cases. While some patient groups with chronic respiratory conditions have an increased risk for severe courses of COVID-19, an increasing number of studies confirm that asthma is not a risk factor for severe COVID-19. However, other risk factors such as higher age, obesity, male gender, diabetes, cardiovascular diseases, chronic kidney or liver disease, cerebrovascular and neurological disease, and various immunodeficiencies or treatments with immunosuppressants need to be taken into account when assessing the risk for severe COVID-19 in patients with chronic respiratory diseases., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

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., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: In Germany the coronavirus disease 2019 (COVID-19) pandemic situation 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, 48.5% (924/1904) of whom were female. The mortality rate was 17% (317/1835; 95% confidence interval (95%CI) 16-19), the rate of admission to the intensive care unit (ICU) was 21% (399/1860; 95%CI 20-23), and the rate of invasive mechanical ventilation was 14% (250/1850: 95%CI 12-15). The most prominent risk factors for death were male sex (hazard ratio (HR) 1.45; 95%CI 1.15-1.83), pre-existing lung disease (HR 1.61; 95%CI 1.20-2.16), and increased patient age (HR 4.11 (95%CI 2.57-6.58) for age >79 years versus <60 years). Among patients admitted to the ICU, the mortality rate was 29% (109/374; 95%CI 25-34) and higher in ventilated (33% [77/235; 95%CI 27-39]) than in non-ventilated ICU patients (23%, 32/139; 95%CI 16-30; p < 0.05)., Conclusions: In this nationwide series of patients hospitalized with COVID-19 in Germany, in-hospital and ICU mortality rates were substantial. The most prominent risk factors for death were male sex, pre-existing lung disease, and greater patient age., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Immune checkpoint inhibition, especially the blockade of PD-1 and PD-L1, has become one of the most thriving therapeutic approaches in modern oncology. Immune evasion caused by altered tumor epitope processing (so-called processing escapes) may be one way to explain immune checkpoint inhibition therapy failure. In the present study, we aim to demonstrate the effects of processing escapes on immunotherapy outcome in NSCLC patients., Patients and Methods: Whole exome sequencing data of 400 NSCLC patients (AdC and SCC) were extracted from the TCGA database. The ICB cohort was composed of primary tumor probes from 48 NSCLC patients treated with nivolumab. Mutations were identified by targeted amplicon-based sequencing including hotspots and whole exomes of 22 genes. The effect of mutations on proteasomal processing was evaluated by deep learning methods previously trained on 1260 known MHC-I ligands. Cox regression modelling was used to determine the influence on overall survival., Results: In the TCGA cohort, processing escapes were associated with decreased overall survival (p= 0.0140). In the ICB cohort, patients showing processing escapes in combination with high levels of PD-L1 (n=8/48) also showed significantly decreased overall survival, independently of mutational load or PD-L1 status., Conclusion: The concept of altered epitope processing may help to understand immunotherapy failure. Especially when combined with PD-L1 status, this method can be used as a biomarker to identify patients not suitable for immunotherapy., Competing Interests: Wilfried EE Eberhardt reports grants and personal fees from BMS and Astra Zeneca and personal fees from MSD/Merck and Roche, outside the submitted work. Jens Kollmeier reports being an Advisory Board Member (no personal fees) for Roche, Boehringer Ingelheim, Bristol-Meyers Squibb, MSD, and Takeda, outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Wessolly et al.)

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., (© 2020 S. Karger AG, Basel.)

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., Competing Interests: Conflicts of interest V.E. is a consultant/advisory board member for ThermoFisher and received lecture fees from AstraZeneca and Novartis. Al.S. is a consultant/advisory board member of Bayer, AstraZeneca, Bristol-Myers Squibb, Novartis, ThermoFisher and Illumina, and received speaker’s honoraria from Bayer, BMS, MSD, Roche, Illumina, AstraZeneca, Novartis and ThermoFisher, Takeda as well as research funding from Chugai and BMS. P.S. received advisory board honoraria from Pfizer, Roche, Novartis and AstraZeneca as well as speaker’s honoraria and research funding from Roche, AstraZeneca and Novartis. O.L. is the owner of TIB Molbiol., (Copyright: © 2019 Streubel et al.)

Since 2015 a significant increase in tuberculosis cases is notified in Germany, mostly due to rising numbers of migrants connected to the recent refugee crisis. Because of the low incidence in previous years, knowledge on tuberculosis is more and more limited to specialized centers. However, lung specialist and healthcare workers of other fields have contact to an increasing number of tuberculosis patients. In this situation, guidance for the management of standard therapy and especially for uncommon situations will be essential. This new guideline on tuberculosis in adults gives recommendations on diagnosis, treatment, prevention and prophylaxis. It provides a comprehensive overview over the current knowledge, adapted to the specific situation in Germany. The German Central Committee against Tuberculosis (DZK e. V.) realized this guideline on behalf of the German Respiratory Society (DGP). A specific guideline for tuberculosis in the pediatrics field will be published separately. Compared to the former recommendations of the year 2012, microbiological diagnostics and therapeutic drug management were given own sections. Chapters about the treatment of drug-resistant tuberculosis, tuberculosis in people living with HIV and pharmacological management were extended. This revised guideline aims to be a useful tool for practitioners and other health care providers to deal with the recent challenges of tuberculosis treatment in Germany., Competing Interests: Interessenkonflikt: Siehe Interessenkonflikterklärung auf www.awmf.org, (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Malignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin., Methods: For a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype., Results: Calretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10-3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30-4.00)., Conclusions: Calretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.

C(U)RB-65 (confusion, (urea >7 mol · L(-1),) respiratory frequency ≥ 30 breaths · min(-1), systolic blood pressure <90 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 aged <65 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 aged <65 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.

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Background: Pneumonia accounts for almost half of intensive care unit (ICU) infections and nearly 60% of deaths from nosocomial infections. It increases hospital stay by 7-9 days, crude mortality by 70% and attributable mortality by 30%., Objective: Our purpose was to assess the impact of standard operating procedures adapted to the local resistance rates in the initial empirical treatment for pneumonia on duration of first pneumonia episode, duration of mechanical ventilation, and length of ICU stay., Design: Prospective observational cohort study with retrospective expert audit., Setting: Five anesthesiologically managed ICUs at University hospital (one cardio-surgical, one neurosurgical, two interdisciplinary, and one intermediate care)., Patients: Of 524 consecutive patients with > or = 36 hr ICU treatment 131 patients with pneumonia on ICU were identified. Their first pneumonia episode was evaluated daily for adherence to standard operating procedures. Pneumonia was diagnosed according to the American Thoracic Society guidelines. Patients with > 70% compliance were assigned to high adherence group (HAG), patients with < or = 70% to low adherence group (LAG)., Measurements and Results: HAG consisted of 45 (49 first episode) patients, LAG of 86 (82 first episode) patients, respectively. Mean duration of treatment of the first pneumonia episode was 10.11 +/- 7.95 days in the LAG and 6.22 +/- 3.27 days in the HAG (p = 0.001). Duration of mechanical ventilation was 317.59 +/- 336.18 hrs in the LAG and 178.07 +/- 191.33 hrs in the HAG (p = 0.017). Length of ICU stay was 20.24 +/- 16.59 days in the LAG and 12.04 +/- 10.42 days in the HAG (p = 0.001)., Limitations: Barriers in compliance need further evaluation., Conclusion: Adherence to standard operating procedure is associated with a shorter duration of treatment of first pneumonia episode, a shorter duration of mechanical ventilation, and a shorter ICU stay.

Introduction: To date, the resistance of infectious agents has been assessed by widely varying criteria in different countries. Therefore, published data on resistance often cannot be meaningfully compared. In Germany, different laboratories can potentially report different results for identical microorganisms, since there is no uniform system for categorization. This situation is unsatisfactory., Methods: Selective literature review and evaluation of committee reports., Results: The new ISO standard 20776 for determination of the resistance of infectious agents and the harmonized evaluation system of the European Society for Clinical Microbiology and Infectious Diseases provide a new basis for susceptibility testing. The categorization of infectious agents as "susceptible," "intermediate," or "resistant" to particular antibiotics will become more reliable and will be consistent throughout Europe., Discussion: For a number of antibiotics, the criteria for evaluation of infectious agents as "susceptible," "intermediate", or "resistant" will change. Comparability with earlier resistance data will be compromised. However, the new evaluation criteria reflect current knowledge on the pharmacokinetics and pharmacodynamics of antimicrobial substances.

Purpose of Review: Dust-induced occupational lung diseases comprise a vast variety of causative agents. These largely preventable illnesses not only afflict lung parenchyma but also bronchi, bronchioles, as well as mediastinal and pleural structures. Chest radiography undisputedly has value in screening thoracic manifestations of occupational diseases, but also has its limitations. Obviously, modern high-resolution computed tomography improves the visibility of tissue changes, in particular in early disease stages; however, the crucial correlation of radiologic and clinical findings in this heterogeneous group of patients has been seldom addressed in the past., Recent Findings: The most encouraging results of a Medline search for the years 2004-2007 are presented. Beside an international standardized high-resolution computed tomography classification for pneumoconiosis, several other innovative scoring systems are highlighted. Furthermore, the clinical impact of high-resolution computed tomography is stressed in the context of the limited applicability of conventional radiography., Summary: High-resolution computed tomography is a powerful diagnostic and prognostic tool for assessment of dust-induced occupational lung diseases in compliance with promising recent findings. Novel evidence, however, is limited for these occupational diseases.

The effect of food components on degradation of DNA by DNase I (EC 3.1.21.1) was monitored by electrotransformation of Escherichia coil, making it possible to determine the number of plasmid molecules capable of giving rise to transformed cells. The transformation frequency increased linearly with the plasmid number within the range of 2 x 10(6) to 2 x 10(10). DNA degradation was reduced by one order of magnitude in the presence of 0.05% (w.v(-1)) maltol or 1 mM putrescine. Complete inhibition of degradation was observed with > or = 0.2% (w.v(-1)) maltol, > or = 0.01% (w.v(-1)) octyl gallate or > or = 0.5 mM of spermine. To monitor degradation of plant DNA during food processing, a real-time PCR system was established. The ratio of copy numbers of a potato gbss DNA fragment of 325 bp and a nested 96 bp fragment was determined. The latter served as internal reference for normalization. The system made it possible to exclude process-dependent changes of DNA concentration in the food matrix. Processing of genetically modified potatoes to dried potato sticks, crisps or flakes was studied and drying steps were shown to exert the strongest effect on DNA degradation, resulting in a drop of the ratio from 0.73 to 0.16.

Soymilk, tofu, corn masa, and cooked potato were produced from transgenic raw materials and the effect of processing on the degradation of DNA was studied. Major degrading factors were for soymilk and tofu the mechanical treatment of soaked soybeans and for corn masa and cooked potatoes the thermal treatment. In the processed foods no DNA fragments > 1.1 kb were detected. We included in our studies the effect of the size of donor DNA and length of the homologous sequence on the marker rescue transformation of B. subtilis LTH 5466, which was monitored by restoration of deleted nptII. When DNA fragments (168, 414, 658, and 792 bp) of nptII and linearized plasmid DNA (pGEM-T-1, 3168 bp and pGEM-T-2, 3792 bp) containing the 168 bp or 792 bp fragments, respectively, were used as donor DNA, it was observed that the efficiency of marker rescue decreased with decreasing length of homologous sequence. The use of a larger plasmid (pMR2, 5786 bp) containing the 792 bp fragment revealed higher efficiency of marker rescue compared to pGEM-T-2. The nptII fragments resulted in lower efficiencies compared to plasmid DNA containing the same fragment. For the 792 bp fragment and the linearized plasmid pMR2 a first-order dependency of the frequency of marker rescue transformation on the DNA concentration was observed. Based on the acquired data, the hypothetical frequency of transformation of transgenic DNA to B. subtilis in cooked potatoes was calculated to be equal to 8.5 x 10(-19) and 1.2 x 10(-27) for homologous and illegitimate recombination, respectively. These data permit to roughly estimate the time after which a person (10(8) years) or the world population (15 days) is exposed to one transformant generated by homologous recombination event, when the daily consumption per person is 130 g of cooked potatoes.