Treatment of MDR, pre-XDR, XDR and rifampicin-resistant tuberculosis or in case of intolerance to at least rifampicin in Austria, Germany and Switzerland - Amendment to the 2022 consensus-based guideline: Tuberculosis in adulthood by the German Central Committee against Tuberculosis (DZK) on behalf of the German Respiratory Society (DGP) dated 19.09.2023.

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- (RR-TB) for the German-speaking countries, replacing the respective chapters of the treatment guidelines published 2022. A shortened treatment of proven RR-TB and multidrug-resistant (MDR)-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.

[Statement Paper on the Implementation of a National Organized Program in Germany for the Early Detection of Lung Cancer in Risk Populations Using Low-dose CT Screening Including Management of Screening Findings]. / Positionspapier zur Implementierung eines nationalen organisierten Programms in Deutschland zur Früherkennung von Lungenkrebs in Risikopopulationen mittels Low-Dose-CT-Screening inklusive Management von abklärungsbedürftigen Screening-Befunden.

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process.

[Statement paper on the implementation of a national organized program in Germany for the early detection of lung cancer in risk populations using low-dose CT screening including management of screening findings]. / Positionspapier zur Implementierung eines nationalen organisierten Programms in Deutschland zur Früherkennung von Lungenkrebs in Risikopopulationen mittels Low-dose-CT-Screening inklusive Management von abklärungsbedürftigen Screeningbefunden.

The process of implementing early detection of lung cancer with low-dose CT (LDCT) in Germany has gained significant momentum in recent years. It is expected that the ordinance of the Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) on early detection of lung cancer, which has been commented on by the professional societies, will come into effect by the end of 2023. Based on this regulation, the Federal Joint Committee (G-BA) will set up a program for early lung cancer detection with LDCT in the near future. In this position paper, the specialist societies involved in lung cancer screening present concrete cornerstones for a uniform, structured and quality-assured early detection program for lung cancer in Germany to make a constructive contribution to this process.

[Outpatient care in pulmonology - a scientific analysis and a position paper of the German Society of Respiratory Medicine (DGP)]. / Ambulantisierung in der Pneumologie ­ eine wissenschaftliche Analyse und ein Positionspapier der DGP.

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 §â€Š21-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 €â€Š2,175.60 without or €â€Š3,315.60 including PET/CT), navigation-assisted bronchoscopy for peripheral lesions (depending on the methodology €â€Š2,870.23 to €4,120.23) and diagnostic (flexible) bronchoscopy (€â€Š1,121.02). 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.

[Treatment of MDR, pre-XDR, XDR and rifampicin resistant tuberculosis or in case of intolerance to at least rifampicin in Austria, Germany and Switzerland - Amendment dated 19.09.2023 to the Sk2-Guideline: Tuberculosis in adulthood of the German Central Committee against Tuberculosis (DZK) on behalf of the German Respiratory Society (DGP)]. / Therapie bei MDR-, prä-XDR-, XDR-Tuberkulose und Rifampicin-Resistenz oder bei Medikamentenunverträglichkeit gegenüber mindestens Rifampicin.

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'.

Mortality in cancer patients with SARS-CoV-2 or seasonal influenza: an observational cohort study from a German-wide hospital network.

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.

[Recommendations for Contact Tracing for Tuberculosis - Update 2023]. / Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose ­ Update 2023.

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.

Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies.

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.

[Recommendations for contact tracing for tuberculosis - update 2023]. / Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose ­ Update 2023.

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.

[Tuberculosis Infection Control & Hygiene - Recommendations of the DZK]. / Infektionsprävention & Hygiene bei Tuberkulose ­ Empfehlungen des DZK.

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.

M ycobacterium tuberculosis-specific CD4 T-cell scoring discriminates tuberculosis infection from disease.

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.

Human lungs show limited permissiveness for SARS-CoV-2 due to scarce ACE2 levels but virus-induced expansion of inflammatory macrophages.

BACKGROUND: Severe 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. METHODS: Spectral 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 validate ex vivo results. RESULTS: We 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 vivo infected 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. CONCLUSIONS: Collectively, 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.

Digital gene expression analysis of NSCLC-patients reveals strong immune pressure, resulting in an immune escape under immunotherapy.

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.

Risk Assessment for Patients with Chronic Respiratory Conditions in the Context of the SARS-CoV-2 Pandemic Statement of the German Respiratory Society with the Support of the German Association of Chest Physicians.

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.

Is Adjuvant Radiochemotherapy Always Mandatory in Patients with Resected N2 Non-Small Cell Lung Cancer?

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.

Landscape of Genomic Alterations and PD-L1 Expression in Early-Stage Non-Small-Cell Lung Cancer (NSCLC)-A Single Center, Retrospective Observational Study.

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.

[Cavernous Nontuberculous Mycobacterial Lung Infection in an HIV-positive Patient]. / Kavernöse nichttuberkulöse Mykobakteriose der Lunge durch M. heckeshornense bei einem HIV-infizierten Patienten.

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.

[Tuberculosis in adulthood - The Sk2-Guideline of the German Central Committee against Tuberculosis (DZK) and the German Respiratory Society (DGP) for the diagnosis and treatment of adult tuberculosis patients]. / Tuberkulose im Erwachsenenalter.

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.

Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19.

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.

[Adequate Perioperative Use of Antibiotics in Thoracic Surgery]. / Rationale perioperative Antibiotikatherapie in der Thoraxchirurgie.

INTRODUCTION: Infectious complications after lung resections pose a high burden of perioperative morbidity and mortality. Among other factors, perioperative antibiotic prophylaxis and management of a postoperative pneumonia have an impact on patient outcome. We developed a local clinical pathway for adequate perioperative use of antibiotics. METHODS: We analysed respiratory samples of 200 patients taken before and after lung resection performed in our lung clinic from October 2013 till October 2014. The clinical pathway was based on our local pathogen and resistance pattern as well as on current guidelines and on the principals of antibiotic stewardship. RESULTS: Gram negative bacteria were the predominant pathogens that grew from the samples in the preoperative phase (62%), as well as in the postoperative phase (78%). A significant number of these bacteria showed intrinsic resistance against the commonly used antibiotics for perioperative prophylaxis. This was the case for both the preoperative phase (21%) and the postoperative phase (39%). These findings were integrated into the local clinical pathway. CONCLUSION: The commonly used antibiotics for perioperative prophylaxis in thoracic surgery cover only some of the pathogens responsible for preoperative airway colonisation and postoperative pneumonia. Therefore, perioperative antibiotic prophylaxis should be given as a single shot just before surgery and postoperative pneumonia should be treated as a hospital acquired pneumonia with respect to the local pathogen and resistance pattern.