INTRODUCTION:Endoscopic lung volume reduction with coils is a symptomatic treatment approach for patients with severe pulmonary emphysema and positive collateral ventilation. In this study, we evaluated the safety and feasibility of the new Lung Volume Reduction Reverser (LVR-R) system. METHODS:Prospective, nonrandomized, exploratory, single-center, first-in-man study in 15 patients with chronic obstructive pulmonary disease (COPD) and severe emphysema. Most affected lung lobes were treated sequentially with the LVR-R coils from May 2019 to JUL 2022. Pulmonary function, 6-min walking distance (6-MWD), questionnaires and adverse events were recorded from baseline to 1-year post-procedure. Computer tomography was acquired at baseline and 6 months. RESULTS:A total of 28 procedures were performed, in which 10 (n = 22, 78.6%), 9 (n = 2, 7.1%), or 8 (n = 4, 14.3%) LVR-R coils were implanted, predominantly in the upper lobes (n = 26/28, 92.86%). Two patients refused a second treatment, one of whom refused follow-ups. Adverse events at 3 months included severe pneumonia and/or COPD exacerbations (n = 7), ventilatory failure (n = 2) and 1 pneumothorax requiring thoracic drainage. Mild hemoptysis occurred in 18 and mild pneumonia and/or COPD exacerbations in 9 patients. Overall, neither FEV1, residual volume, 6-MWD, CAT nor mMRC improved within 1-year (n.s. all). In 2 patients, response in FEV1 >500 mL occurred. CONCLUSION:In this severely diseased and small patient cohort, LVR-R implantation was technically feasible. The complication rate was similar to other coil studies and requires a careful pre-procedure benefit-risk evaluation. Two of fourteen bilaterally treated individuals demonstrated a notable improvement in lung function.

Autoimmune-mediated connective tissue diseases such as antisynthetase syndrome (ASyS) and systemic sclerosis (SSc) have a high unmet medical need. Here we report on treatment under compassionate use with the CD19×CD3 T cell engager (TCE) blinatumomab and the BCMA×CD3 TCE teclistamab in five patients with treatment-refractory ASyS and in five patients with treatment-refractory SSc, respectively. Induction therapy with blinatumomab or teclistamab reduced target cells in affected muscle and skin, respectively, and decreased autoantibody titers. Blinatumomab induced rapid clinical, serological and histological improvement of myositis and stabilization of interstitial lung disease (ILD) in patients with ASyS. Teclistamab improved skin fibrosis, stabilized ILD and resolved tendon friction rubs in patients with SSc. Inhibition of B cell redifferentiation by maintenance therapy with rituximab (RTX) enabled prolonged disease control, even for patients previously unresponsive to RTX. Treatment was associated with adverse events including cytokine release syndrome (CRS) up to grade 3, in two patients with ASyS and in all patients with SSc. No immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Respiratory infections treated with antibiotics occurred in six patients. Blinatumomab and teclistamab may offer potential as rescue therapies for patients with treatment-refractory ASyS and SSc.

IntroductionThe necessity of lymph node dissection (LND) as part of curative-intent surgery for ground-glass opacity (GGO)-dominant lung adenocarcinoma has been called into question, given the favorable prognosis and indolent behavior of these tumors. However, the oncological safety of omitting LND in cases of GGO-dominant lung adenocarcinoma remains controversial, and current guidelines continue to recommend it.MethodsThis study was designed as a retrospective, single-center cohort study. Patients with cT1N0M0 lung adenocarcinoma who underwent surgical resection between 2010 and 2023 were categorized as GGO-dominant or solid-dominant cohorts based on consolidation-to-tumor ratios in preoperative computed tomography scans. The primary endpoint was the incidence of occult lymph node (LN) metastasis.ResultsA total of 726 consecutive patients were included in this study, categorized as GGO-dominant in 50 patients and solid-dominant in 676 patients. GGO-dominant tumors were more frequently observed in female patients (p = 0.03), whereas no significant differences were found between the groups with respect to age, smoking status, or ECOG performance status. GGO-dominant morphology was associated with lower pT stage and lower rates of pleural and lymphovascular invasion. The incidence of occult LN metastasis was 4% (n=2) in the GGO-dominant cohort and 11.8% (n=80) in solid-dominant cohort. Only solid tumor size was a significant predictor of occult LN metastasis in multivariable logistic regression (OR 1.39 per 5mm increase, 95% CI 1.10-1.77, p = 0.006). Survival analysis revealed a higher rate of freedom from recurrence (p = 0.04) and favorable trends in overall survival (p = 0.09) and recurrence-free survival (p = 0.086) in the GGO-dominant cohort.ConclusionsThe hypothesis that GGO-dominant morphology reliably predicts negative lymph node involvement was not confirmed. These findings support the continued role of surgical nodal assessment for accurate pathological staging.

Immune checkpoint inhibitors have shown promising results in the neoadjuvant treatment of resectable non-small cell lung cancer. This open-label, single-arm, prospective, monocentric trial evaluated the efficacy and safety of neoadjuvant atezolizumab plus carboplatin/nab-paclitaxel in patients with resectable non-squamous non-small cell lung cancer. Patients with previously untreated, pathologically confirmed, non-squamous non-small cell lung cancer in stage II, IIIA, and select IIIB (T3N2 only) were treated with atezolizumab and carboplatin/nab-paclitaxel for 3 cycles followed by curative intent surgery. Major pathologic response (MPR) was defined as primary endpoint. 20 patients with histologically confirmed pulmonary adenocarcinoma in TNM-stage IIA (n = 1, 5%), stage IIB (n = 7, 35%), and stage IIIA (n = 12, 60%) were enrolled and treated according to the study protocol. 151 treatment-related adverse events were recorded, and 13 patients (65%) had treatment-related adverse events of grade 3 or higher. There were no grade 5 events. All patients underwent complete anatomical resection (R0). MPR was observed in 9 patients (45%), including 5 (25%) patients with complete pathological response. The proportion of remaining viable tumor showed a significant but weak association to the relative tumor size change in CT (p = 0.018) and the relative change in SUVmax (p = 0.006). In conclusion, neoadjuvant chemoimmunotherapy with atezolizumab achieved a promising MPR-rate of 45% while being well tolerated and allowing a safe and complete surgical resection. These results strongly support the further investigation of atezolizumab as preoperative therapy in resectable non-small cell lung cancer and underline the continued need to develop biomarkers of response.

Community-acquired respiratory viruses (CARV), such as influenza-, parainfluenza- or respiratory syncytial virus, pose a significant threat to immunocompromised patients with cancer. Following the COVID-19 pandemic, SARS-CoV-2 has now joined the ranks of endemic respiratory viruses and continues to be a cause of significant morbidity and mortality in patients with cancer. Strategies to protect this vulnerable patient population both by prevention of infection and by early therapeutic intervention in case of infectious disease are therefore of utmost importance. This guideline provides updated evidence-based recommendations on diagnosis, prophylaxis and treatment of CARV infections including COVID-19 in patients with solid tumors or hematologic malignancies to support clinicians in offering optimal care. The guideline is based on a systematic review of currently available data and was developed until the beginning of 2025 by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

Importance:Chemoimmunotherapy followed by immunotherapy maintenance is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), yet data regarding efficacy and safety of consolidative thoracic radiotherapy (TRT) are lacking. Objective:To determine whether combining consolidative TRT with immunotherapy maintenance in ES-SCLC is safe and improves patients' overall survival (OS) and progression-free survival (PFS). Design, Settings, and Participants:This was a multicenter open-label phase 2 randomized clinical trial recruiting patients from September 2020 to August 2022 in Germany and Austria, with the last follow-up visit in September 2024. Eligible patients had ES-SCLC with at least stable disease after induction chemoimmunotherapy (carboplatin-etoposide-atezolizumab). Although the database was locked in April 2025, a post hoc survival update was performed in April 2026. Data were analyzed from April 2025 to April 2026. Interventions:Randomized (1:1) to either atezolizumab maintenance combined with consolidative TRT (30 Gy in 10 fractions) (arm A) or atezolizumab maintenance alone (arm B). Main Outcome and Measure:OS (time from randomization to death due to any cause). Results:Of 96 patients assessed for eligibility, 68 patients were randomized; recruitment was prematurely terminated due to safety concerns. Median OS in the combination arm was numerically shorter compared to atezolizumab only (6.7 months [95% CI, 5.1-9.0] vs 13.4 months [95% CI, 10.7-17.5]; HR, 1.55 [95% CI, 0.90-2.69]; P = .34), while median PFS was similar (2.4 months [95% CI, 1.3-3.9] vs 2.6 months [95% CI, 1.2-3.9]; HR, 0.92 [95% CI, 0.54-1.55]; P = .85). TRT plus atezolizumab was accompanied by higher frequency of severe adverse events (SAEs) (19 patients [61.3%] vs 6 patients [18.2%]; P < .001) and fatal outcomes (6 patients [19.4%] vs 1 patient [3.0%]; P = .04). Safety analysis revealed predominance of infection and respiratory disorder-related SAEs, possibly facilitated by a depletion of lymphocytes observed specifically in patients after TRT, and by a lower single breath diffuse capacity of the lungs for carbon monoxide in patients with fatal AEs in arm A. No further risk factors were identified, given that baseline characteristics were well balanced between both arms and between patients with and without SAEs, including fatal SAEs. Conclusions and Relevance:In this randomized clinical trial, TRT combined with immunotherapy increased toxic effects in unselected patients with ES-SCLC without survival benefit, presumably due to radiation-induced lymphocyte depletion facilitating infections. Cautious patient selection and further investigation to identify those who may benefit without undue risk are required. Trial Registration:ClinicalTrials.gov Identifier: NCT04462276.

Low-dose computed tomography (LDCT) screening can reduce lung cancer (LC)-related mortality, but questions remain about the duration of this effect and differences by sex and tumor histology. Extended follow-up data from the ITALUNG and LUSI trials were pooled to examine screening-related tumor stage-shifts and to estimate relative hazards for LC-related mortality, by sex and histology. Findings were compared to, and additionally combined with, those from the US National Lung Screening Trial (NLST). In ITALUNG-LUSI, screening yielded a 30% reduction of overall LC mortality up to 8 years after final screening (dilution-adjusted HR=0.70[0.51-0.96]). This reduction, however, was more pronounced for women (HR=0.49[0.25-0.96]) than men (HR=0.78[0.54-1.11]), which was confirmed in combined data of ITALUNG-LUSI plus NLST (6 years post-screening, women: HR=0.74[0.61-0.90], men: HR=0.93[0.80-1.06]; pheterogeneity=0.06). Analyses of stage-shifts and relative mortality hazards suggested that screening reduced mortality by non-small cell and non-squamous tumors in both sexes. In women (18-20%), more than among men (5-9%), screening also resulted in frequent detection of adenocarcinomas with lepidic growth. Finally, in both ITALUNG-LUSI and NLST, LDCT screening reduced the incidence and mortality for small-cell lung cancer (SCLC) among women (HR=0.63[0.43-0.94], all trials combined) but not among men (pheterogeneity=0.04). LC-related mortality reduction by LDCT screening may last until 8 or more years after cessation, and appears to be stronger for women than men, due to reduced incidence and mortality of SCLC in women only. The latter might be caused by removal of (likely EGFR-mutated, and slowly growing) adenomatous precursor lesions that over time would transform into SCLC (lineage plasticity). These findings may have major implications for the optimization of screening programs in terms of eligibility criteria and screening intervals Rudolf Kaaks, Francisco O. Cortès-Ibañez, Stefan Delorme, Erna Motsch, Verena Katzke, Claus-Peter Heussel, Hans-Ulrich Kauczor, Giulia Picozzi, Giuseppe Gorini, Francesca Maria Carozzi, Laura Carrozzi, Eugenio Paci, Donella Puliti, Mario Mascalchi. Effectiveness of lung cancer screening by sex and tumor histology: Extended, pooled analysis of the ITALUNG and LUSI trials, with comparison to findings in the NLST [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7409.

Background:The e-Lung weighted reticulovascular score (WRVS) is an automated computed tomography biomarker that quantifies interstitial lung disease (ILD) severity and is associated with prognosis in patients with idiopathic pulmonary fibrosis (IPF). The aims of the present study were to evaluate WRVS as a prognostic factor in patients with non-IPF ILD. Methods:The test cohort comprised patients from the Open Source Imaging Consortium and the validation cohort, patients recruited to the prospective German CoWorker ILD registry. Associations between baseline and serial WRVS with future forced vital capacity (FVC) decline and survival were tested. Results:Median survival was 7.1 and 6.1 years in the test (n=302) and validation (n=378) cohorts, respectively. Baseline WRVS was associated with mortality in test (hazard ratio (HR) 1.11, 95% CI 1.08-1.14; p<0.001, C-index 0.75) and validation (HR 1.12, 95% CI 1.09-1.15; p<0.001, C-index 0.72) cohorts. A threshold WRVS of ≥15% was associated with mortality in both cohorts (HR 4.77, 95% CI 3.11-7.31; p<0.001, C-index 0.71, and HR 3.49, 95% CI 2.48-4.91; p<0.001, C-index 0.63 for test and validation cohorts, respectively). After adjustment for FVC, age and sex, baseline WRVS was associated with future FVC decline or death in test (OR 1.13, 95% CI 1.06-1.21; p<0.001, C-index 0.72) and validation (OR 1.18, 95% CI 1.11-1.25; p<0.001, C-index 0.72) cohorts. A rise in WRVS of 3% on serial computed tomography was associated with mortality in both test (HR 5.69, 95% CI 2.77-11.70; p<0.001, C-index 0.75) and validation cohorts (HR 1.99, 95% CI 1.09-3.65; p=0.026, C-index 0.57). Conclusion:In patients with non-IPF ILD, the e-Lung WRVS biomarker is associated with mortality and FVC decline when applied to baseline high-resolution computed tomography scans replicating previous studies in IPF. Patients with an increase in WRVS of 3% on serial computed tomography scans have significantly increased risk of mortality.

INTRODUCTION:Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated. METHODS:We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31-54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method. RESULTS:In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs. CONCLUSIONS:Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.

Chest quantitative computed tomography (QCT) has been used in clinical trials to monitor patients with alpha-1 antitrypsin deficiency (AATD). There is limited data on the use of quantitative computed tomography (QCT) to phenotype emphysema in AATD. Data from patients with a reduced AATD serum level and/or at least one deficiency mutation, who underwent a chest CT scan at the Thoraxklinik, University of Heidelberg, between 03/2012 and 02/2024, were retrospectively analyzed. The patients were categorized into three groups based on their AAT serum levels: reduced to normal (> 70 mg/dl), moderate (41–70 mg/dl), and severe (≤ 40 mg/dl). The QCT analyses were performed using a fully automated quantitative CT software package (YACTA v2.9.4.98). In this retrospective cohort study, 75 AATD patients were analysed, including 13 with reduced-to-normal AATD, 16 with moderate AATD and 46 with severe AATD. The mean age was 54.3 ± 14.7 years with no differences between groups. Significant differences in pack-years (PY) were found: reduced to normal 14.9 ± 17.2, moderate 39.4 ± 31.9 and severe 15.1 ± 14.6 (p < 0.001). There were no differences in predicted FEV1

The e-Lung weighted reticulovascular score (WRVS) is an automated CT biomarker that quantifies interstitial lung disease (ILD) severity and is associated with prognosis in patients with idiopathic pulmonary fibrosis (IPF). To evaluate WRVS as a prognostic factor in patients with non-IPF fibrotic ILD (fILD). The test cohort comprised patients from the Open Source Imaging Consortium and the validation cohort, patients recruited to the prospective German CoWorker ILD registry. Associations between baseline and serial WRVS with future forced vital capacity (FVC) decline and survival were tested. Median survival was 7.1 and 6.1 years in the test (n=302) and validation (n=378) cohorts respectively. Baseline WRVS was associated with mortality in test (HR 1.11, [1.08–1.14], (p<0.001), C-index 0.75) and validation (HR 1.12, [1.09–1.15], (p<0.001), C-index 0.72) cohorts. A threshold WRVS of ≥15% was associated with mortality in both cohorts (HR 4.77, (3.11–7.31), p<0.001, C-index 0.71) and (HR 3.49, [2.48–4.91], p<0.001, C-index 0.63). After adjustment for FVC, age and sex, baseline WRVS was associated with future FVC decline or death (OR 1.13, [1.06–1.21], p<0.001, C-index 0.72) and (OR 1.18, [1.11–1.25], p<0.001, C-Index 0.72) in test and validation cohorts respectively. A rise in WRVS of 3% on serial CT was associated with mortality in both test (HR 5.69, [2.77–11.70], p<0.001, C-index 0.75) and validation cohorts (HR 1.99, [1.09–3.65], p=0.026), C-index 0.57). In patients with non-IPF fILD, the e-Lung WRVS biomarker is associated with mortality and FVC decline when applied to baseline HRCT scans replicating previous studies in IPF. Patients with an increase in WRVS of 3% on serial CT scans have significantly increased risk of mortality.

Die im Januar 2024 aktualisierte S3-Leitlinie zur „Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie“ bietet evidenzbasierte Empfehlungen zur Verbesserung der Versorgung dieser häufigen Krankenhausinfektion. Sie ersetzt die Version von 2017 und wurde unter Beteiligung von 14 Fachgesellschaften überarbeitet. Die Leitlinie umfasst 26 Empfehlungen, etwa zur differenzierten Diagnostik (inkl. Multiplex-PCR, BAL, Biomarkern) und zur kalkulierten antimikrobiellen Therapie. Sie betont kürzere Therapiedauern, gezielte Einsatzindikationen für Kombinationstherapien und moderne Konzepte wie Antibiotic Stewardship. Neu sind Empfehlungen zu viralen und fungalen Erregern sowie ein Flussdiagramm zur initialen Therapieentscheidung. Die Gültigkeit der Leitlinie reicht bis Februar 2029.

Predicting vertebral height is complex due to individual factors. AI-based medical imaging analysis offers new opportunities for vertebral assessment. Thereby, these novel methods may contribute to sex-adapted nomograms and vertebral height prediction models, aiding in diagnosing spinal conditions like compression fractures and supporting individualized, sex-specific medicine. In this study an AI-based CT-imaging spine analysis of 262 subjects (mean age 32.36 years, range 20-54 years) was conducted, including a total of 3117 vertebrae, to assess sex-associated anatomical variations. Automated segmentations provided anterior, central, and posterior vertebral heights. Regression analysis with a cubic spline linear mixed-effects model was adapted to age, sex, and spinal segments. Measurement reliability was confirmed by two readers with an intraclass correlation coefficient (ICC) of 0.94-0.98. Female vertebral heights were consistently smaller than males (p < 0.05). The largest differences were found in the upper thoracic spine (T1-T6), with mean differences of 7.9-9.0%. Specifically, T1 and T2 showed differences of 8.6% and 9.0%, respectively. The strongest height increase between consecutive vertebrae was observed from T9 to L1 (mean slope of 1.46; 6.63% for females and 1.53; 6.48% for males). This study highlights significant sex-based differences in vertebral heights, resulting in sex-adapted nomograms that can enhance diagnostic accuracy and support individualized patient assessments.

Incidentally detected pulmonary nodules present a challenge in clinical routine with demand for reliable support systems for risk classification. We aimed to evaluate the performance of the lung-cancer-prediction-convolutional-neural-network (LCP-CNN), a deep learning-based approach, in comparison to multiparametric statistical methods (Brock model and Lung-RADS®) for risk classification of nodules in cohorts with different risk profiles and underlying pulmonary diseases. Retrospective analysis was conducted on non-contrast and contrast-enhanced CT scans containing pulmonary nodules measuring 5–30 mm. Ground truth was defined by histology or follow-up stability. The final analysis was performed on 297 patients with 422 eligible nodules, of which 105 nodules were malignant. Classification performance of the LCP-CNN, Brock model, and Lung-RADS® was evaluated in terms of diagnostic accuracy measurements including ROC-analysis for different subcohorts (total, screening, emphysema, and interstitial lung disease). LCP-CNN demonstrated superior performance compared to the Brock model in total and screening cohorts (AUC 0.92 (95

Background Interstitial lung diseases (ILD) represent an interdisciplinary clinical challenge and are not uncommonly associated with rheumatological diseases. Interstitial lung disease multidisciplinary meetings (ILD-MDM) provide a structured platform for interdisciplinary case discussions and decision making. Despite their great importance in patient care, data on the prevalence, structure and function of ILD-MDM in Germany are lacking. Objective The aim of the study was to assess the current status of ILD-MDM in German hospitals to gain insights into their composition, processes and potential for optimization. Material and methods A web-based survey was conducted via SurveyMonkey under the auspices of the German Society for Rheumatology and Clinical Immunology (DGRh) and in collaboration with the German Respiratory Society (DGP) and the German Radiological Society (DRG). A standardized questionnaire captured information on the participating specialist disciplines, organizational structures as well as the content and challenges of local ILD-MDM. The analysis was conducted descriptively. Results A total of 125 physicians from 15 federal states in Germany participated. Pulmonologists (93.6 %), radiologists (86.4 %), rheumatologists (59.2 %) and pathologists (57.6 %) are the most commonly represented members of ILD-MDM. The majority of ILD-MDMs are conducted either in person (50 %) or in a hybrid format (31.5 %) and are held on a weekly basis (41.1 %). Of all patient cases discussed, two thirds receive a definitive diagnosis and treatment recommendation. Conclusion The findings reveal a high acceptance and prevalence of ILD-MDM in Germany but also highlight potential areas for improvement, particularly regarding interdisciplinary participation, technical infrastructure and standardization.

BACKGROUND:Nosocomial pneumonia, encompassing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), remains a major cause of morbidity and mortality in hospitalized adults. In response to evolving pathogen profiles and emerging resistance patterns, this updated S3 guideline (AWMF Register No. 020-013) provides an evidence-based framework to enhance the diagnosis, risk stratification, and treatment of nosocomial pneumonia. METHODS:The guideline update was developed by a multidisciplinary panel representing key German professional societies. A systematic literature review was conducted with subsequent critical appraisal using the GRADE methodology. Structured consensus conferences and external reviews ensured that the recommendations were clinically relevant, methodologically sound, and aligned with current antimicrobial stewardship principles. RESULTS:For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to non-bronchoscopic sampling in terms of main outcomes. Combination antibiotic therapy is now reserved for patients in septic shock and high risk for multidrug-resistant pathogens, while select patients may be managed with monotherapy (e. g., meropenem). In clinically stabilized patients, antibiotic therapy should be de-escalated and focused, as well as duration shortened to 7-8 days. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION:This updated S3 guideline offers a comprehensive, multidisciplinary approach to the management of nosocomial pneumonia in adults. By integrating novel diagnostic modalities and refined therapeutic strategies, it aims to standardize care, improve patient outcomes, and enhance antimicrobial stewardship to curb the emergence of resistant pathogens.