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Objectives: In patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD), the response to treatment is evaluated based on microbiological, clinical, and radiological data. However, little is known about the dynamics of CT findings. The aim of this study was to evaluate CT changes in NTM-PD in order to define radiological criteria for treatment success., Methods: Retrospective multicenter study (Hannover, Heidelberg, Gauting). Sixty patients with NTM-PD and at least two consecutive CT scans were included. Scoring for NTM-PD was performed by evaluating variables of bronchiectasis, mucus plugging, bronchiolitis, cavities, nodules, and consolidations on an ordinal scale from 0 to 3. Differences between baseline and follow-up were calculated, and patients with/without cultural conversion were compared using the Mann-Whitney U-test. For paired comparison of the two consecutive CT scans the Wilcoxon test was used., Results: Comparing patients with and without culture conversion, there were significant differences in temporal changes of bronchiectasis (p < 0.001), cavities (p = 0.006), bronchiolitis (p < 0.001), consolidations (p = 0.004), and total score (p < 0.001). Nodules showed no significant differences between groups (p = 0.060). The Wilcoxon test showed significant differences between both CTs in patients with a microbiological cure for the total score (p < 0.001), cavities (p = 0.005), bronchiolitis (p < 0.001), and consolidations (p = 0.021) with a decrease after microbiological cure, whereas bronchiectasis (p = 0.102) and nodules (p = 0.18) stayed stable. In the case of persistently positive cultures, there was an increase in the total score (p = 0.010) which was attributable to progressive bronchiectasis (p < 0.001)., Conclusion: Cavities, consolidations, and bronchiolitis are useful to assess treatment response, whereas bronchiectasis and nodules may remain stable despite successful treatment., Clinical Relevance Statement: Cavities, consolidations, and bronchiolitis can assess treatment response whereas bronchiectasis and nodules may remain stable despite successful treatment. In persistently positive cultures, bronchiectasis showed an increase over time indicating that NTM-PD is a progressive chronic disease., Key Points: Little is known about CT changes in nontuberculous mycobacteria pulmonary disease (NTM-PD) and criteria to evaluate treatment response. In the case of culture conversion, cavities and bronchiolitis decreased whereas bronchiectasis and nodules remained stable. Cavities and bronchiolitis can evaluate treatment response in NTM, but bronchiectasis and nodules may persist despite successful treatment., (© 2024. The Author(s).)

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Limited evidence is available on the most effective diagnostic approaches, management strategies, and long-term outcomes for CAP in patients who have undergone solid organ transplantation., Research Question: What is the acute and long-term morbidity and mortality after CAP in organ transplant recipients?, Study Design and Methods: We retrospectively analyzed hospitalizations for CAP in solid organ recipients at the largest German transplant center. The study included patients admitted between January 1, 2010, and May 31, 2021. The reported outcomes are in-hospital and 1-year mortality, risk of cardiovascular events during hospitalization and at 1 year, admission to the ICU, and risk of pneumonia with Pseudomonas aeruginosa. Multivariable binary logistic regression using stepwise forward selection was performed to determine predictive factors for pneumonia with P aeruginosa., Results: We analyzed data from 403 hospitalizations of 333 solid organ recipients. In > 60% of cases, patients had multiple comorbidities, with cardiovascular and chronic kidney disease being the most prevalent. More than one-half of the patients required oxygen supplementation after admission. In-hospital mortality (13.2%) and the death rate at 1 year postevent (24.6%) were higher than data reported from immunocompetent patients. We also observed high rates of acute cardiovascular events and events occurring 1 year after admission. Early blood cultures and bronchoscopy in the first 24 h significantly increased the odds of establishing an etiology. In our low-resistance setting, the burden of antimicrobial resistance was driven by bacteria from chronically colonized patients, mostly lung transplant recipients., Interpretation: This comprehensive analysis highlights the high morbidity associated with CAP after transplantation. It also emphasizes the need for prospective multicenter studies to guide evidence-based practices and improve outcomes for these vulnerable patients., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical characteristics of refugees with HIV from Ukraine that seek continuation of medical care in Germany., Methods: Fourty-six refugees with HIV that had left Ukraine between 24 February and 30 December 2022 were examined. Information on patients' history was obtained using a standardized questionnaire for clinical care. Interviews were conducted in Russian during their first clinical presentation., Results: Fourty-six persons (41 females and 5 males) were included and their mean age was 39.6 (±8.4) years. The mean time since HIV diagnosis was 8.0 (median, IQR 7.15) years and 70.3% of participants currently received tenfofovir-DF, lamividine and dolutegravir. Most refugees had an undetectable HIV viral load and their current mean CD4 T cell count was 702 (SD ± 289) per μL. Serology revealed previous hepatitis B infection in 50.4% without evidence for replication, with undetectable anti-hepatitis B surface antigen in the remaining refugees. Antibodies against hepatitis C were present in 23 refugees (50%), but only 10 patients had been diagnosed with hepatitis C previously. Five refugees had undergone successful antiviral treatment for hepatitis C. Detectable HCV-RNA was evident in nine patients (19.6%). Sixteen (38.6%) refugees had a positive tuberculosis (TB) interferon gamma release assay, and four were on TB treatment for previously diagnosed infection. One had been diagnosed with multidrug-resistant (MDR) TB, two with pre-extensively drug-resistant (pre-XDR) TB and two with XDR TB and were treated with combinations of second-line and novel agents according to WHO guidelines., Conclusions: Based on this preliminary analysis of a not fully representative cohort, refugees with HIV from Ukraine were young, mostly healthy females highly adherent to antiretroviral therapy. The rate of transmittable co-infections urges early diagnostic evaluation and treatment., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: In clinical routine, voriconazole plasma trough levels ( C min ) out of target range are often observed with little knowledge about predisposing influences., Objectives: To determine the distribution and influencing factors on voriconazole blood levels of patients treated on intensive- or intermediate care units (ICU/IMC)., Patients and Methods: Data were collected retrospectively from patients with at least one voriconazole trough plasma level on ICU/IMC ( n  = 153) to determine the proportion of sub-, supra- or therapeutic plasma levels. Ordinal logistic regression analysis was used to assess factors hindering patients to reach voriconazole target range., Results: Of 153 patients, only 71 (46%) reached the target range at the first therapeutic drug monitoring, whereas 66 (43%) patients experienced too-low and 16 (10%) too-high plasma levels. Ordinal logistic regression analysis identified the use of extra corporeal membrane oxygenation (ECMO), low international normalized ratio (INR) and aspartate-aminotransferase (AST) serum levels as predictors for too-low plasma levels., Conclusion: Our data highlight an association of ECMO, INR and AST levels with voriconazole plasma levels, which should be considered in the care of critically ill patients to optimize antifungal therapy with voriconazole., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Photon counting (PC) detectors allow a reduction of the radiation dose in CT. Chest X-ray (CXR) is known to have a low sensitivity and specificity for detection of pneumonic infiltrates. The aims were to establish an ultra-low-dose CT (ULD-CT) protocol at a PC-CT with the radiation dose comparable to the dose of a CXR and to evaluate its clinical yield in patients with suspicion of pneumonia., Methods: A ULD-CT protocol was established with the aim to meet the radiation dose of a CXR. In this retrospective study, all adult patients who received a ULD-CT of the chest with suspected pneumonia were included. Radiation exposure of ULD-CT and CXR was calculated. The clinical significance (new diagnosis, change of therapy, additional findings) and limitations were evaluated by a radiologist and a pulmonologist considering previous CXR and clinical data., Results: Twenty-seven patients (70% male, mean age 68 years) were included. With our ULD-CT protocol, the radiation dose of a CXR could be reached (mean radiation exposure 0.11 mSv). With ULD-CT, the diagnosis changed in 11 patients (41%), there were relevant additional findings in 4 patients (15%), an infiltrate (particularly fungal infiltrate under immunosuppression) could be ruled out with certainty in 10 patients (37%), and the therapy changed in 10 patients (37%). Two patients required an additional CT with contrast medium to rule out a pulmonary embolism or pleural empyema., Conclusions: With ULD-CT, the radiation dose of a CXR could be reached while the clinical impact is higher with change in diagnosis in 41%., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Exacerbations of COPD are associated with worsening of the airflow obstruction, hospitalisation, reduced quality of life, disease progression and death. At least 70% of COPD exacerbations are infectious in origin, with respiratory viruses identified in approximately 30% of cases. Despite long-standing recommendations to vaccinate patients with COPD, vaccination rates remain suboptimal in this population. Streptococcus pneumoniae is one of the leading morbidity and mortality causes of lower respiratory tract infections. The Food and Drug Administration recently approved pneumococcal conjugate vaccines that showed strong immunogenicity against all 20 included serotypes. Influenza is the second most common virus linked to severe acute exacerbations of COPD. The variable vaccine efficacy across virus subtypes and the impaired immune response are significant drawbacks in the influenza vaccination strategy. High-dose and adjuvant vaccines are new approaches to tackle these problems. Respiratory syncytial virus is another virus known to cause acute exacerbations of COPD. The vaccine candidate RSVPreF3 is the first authorised for the prevention of RSV in adults ≥60 years and might help to reduce acute exacerbations of COPD. The 2023 Global Initiative for Chronic Lung Disease report recommends zoster vaccination to protect against shingles for people with COPD over 50 years., Competing Interests: Conflict of interest: T. Welte reports support for the present manuscript from German Ministry of Research and Education; grants or contracts from Bavaria Nordisk, outside the submitted work; payment or honoraria from Janssen, GSK, MSD and Pfizer, outside the submitted work; and is a current editorial board member for European Respiratory Review. J. Rademacher reports receiving payment or honoraria from GSK and MSD, outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

AMS in chronic lung disease can be challenging. Causal treatment of treatable traits may be the most successful AMS strategy for patients with any chronic pulmonary disease and should be brought into focus. https://bit.ly/3ptrmV8., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2023.)

Background:  Oxygen (O2) therapy is one of the most commonly applied medications in German hospitals and rescue services. Both hypoxemia and hyperoxemia can be associated with complications. There is currently a lack of reliable data on the use, documentation and surveillance of O2-therapy in German hospitals., Methods:  We conducted a cross-sectional study on the use of O2 in three hospitals in Hannover, Germany., Results:  Of 343 patients included in this study, 20 % received O2 therapy. Twenty-nine percent of patients receiving O2 were at increased risk for hypercapnia. A standard operating procedure (SOP) for O2 therapy was available in only 68 % of patients. In 22 % patients the applied O2-therapy was appropriate in the context of the documented vital parameters. A complete documentation of vital parameters was conducted in only 30 % of all patients and 41 % of patients receiving O2-therapy. A surveillance of O2-therapy using capillary or arterial blood gas analysis was performed in 76 % of patients. Here, 64 % of patients showed normoxemia, 17 % showed hyperoxemia and 19 % of patients showed hypoxemia. The only identifiable predictor for an adequate O2-therapy was a previous invasive ventilation., Discussion:  Our data point towards and inadequate prescription, application and documentation of O2 therapy. The recently released German S3-guideline should be used to increase awareness among physicians and nursing staff regarding the use of O2-therapy to improve O2 therapy and consequently patient safety., Competing Interests: Jens Gottlieb und Thomas Fühner sind Autoren der S3-Leitlinie ,Sauerstoff in der Akuttherapie beim Erwachsenen‘; die anderen Autoren geben an, keinen Interessenkonflikt zu haben., (Thieme. All rights reserved.)

Introduction: Chronic obstructive pulmonary disease (COPD) carries a tremendous societal and individual burden, posing significant challenges for public health systems worldwide due to its high morbidity and mortality. Due to aging and multimorbidity but also in the wake of important progress in deciphering the heterogeneous disease endotypes, an individualized approach to the prevention and management of COPD is necessary., Areas Covered: This article tackles relevant immunization strategies that are available or still under development with a focus on the latest evidence but also controversies around different regional immunization approaches. Further, we present the crossover between chronic lung inflammation and lung microbiome disturbance as well as its role in delineating COPD endotypes. Moreover, the article attempts to underline endotype-specific treatment approaches. Lastly, we highlight non-pharmacologic prevention and management programs in view of the challenges and opportunities of the COVID-19 era., Expert Opinion: Despite the remaining challenges, personalized medicine has the potential to offer tailored approaches to prevention and therapy and promises to improve the care of patients living with COPD.

Despite substantial progress in long-term follow-up strategies for lung transplant recipients, morbidity and mortality remain high, mostly because of the elevated infectious risk and the development of chronic lung allograft dysfunction. The high immunosuppressive levels necessary to prevent acute rejection and the graft's constant exposure to the environment come at the high price of frequent infectious complications. Moreover, some infectious agents have been shown to trigger acute rejection or chronic allograft dysfunction. A rapid diagnostic approach followed by an early treatment and follow-up strategy are of paramount importance. However, these are challenging endeavors because of the vast spectrum of possible pathogens and the discrete clinical features resulting form transplant recipients' impaired immune responses. This review proposes a stratified diagnostic strategy and discusses the most relevant pathogens and the corresponding therapeutic approaches, while also offering insight on infection prevention strategies: vaccination, prophylaxis, pre-emptive therapy, and antibiotic stewardship., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Antimicrobial resistance is a major public health issue caused by antibiotic overuse and misuse. Antimicrobial stewardship (AMS) has been increasingly endorsed worldwide, but its effect has been studied scarcely in urologic settings. A before-after study was performed from 2018 through 2020 to evaluate changes in antimicrobial prescription, resistance rates and clinical safety upon implementation of an AMS audit and feedback program in the Urology Department of a large German academic medical center. The primary endpoints were safety clinical outcomes: the rate of infection-related readmissions and of infectious complications after transrectal prostate biopsies. Resistance rates and antimicrobial consumption rates were the secondary endpoints. The AMS team reviewed 196 cases (12% of all admitted in the department). The overall antibiotic use dropped by 18.7%. Quinolone prescriptions sank by 78.8% (p = 0.02) and 69.8% (p > 0.05) for ciprofloxacin and levofloxacin, respectively. The resistance rate of E. coli isolates declined against ceftriaxone (−9%), ceftazidime (−12%) and quinolones (−25%) in the AMS period. No significant increase in infection-related readmissions or infectious complications after prostate biopsies was observed (p = 0.42). Due to the potential to reduce antibiotic use and resistance rates with no surge of infection-related complications, AMS programs should be widely implemented in urologic departments.

Despite advances in lung transplantation (LTx), morbidity, and mortality are high. We hypothesized that pleural effusions requiring thoracocentesis lead to poor outcomes after LTx. We performed a single-center retrospective analysis of thoracocenteses after initial hospital discharge in LTx patients between March 2008 and September 2020 to identify risk factors, etiologies, and outcomes. Of the 1223 patients included, 113 patients (9.2%) required a total of 195 thoracocenteses. The cumulative incidence of thoracocentesis was 10.6% at 1 year and 14.2% at 5 years after transplantation. We observed a bimodal distribution of pleural effusion onset with a threshold at 6 months. Late-onset effusions were mostly of malignant or cardiac origin. We observed a high rate of nonspecific effusions (41.5%) irrespective of the timepoint post-transplantation. Patients with late-onset effusions had significantly lower survival compared to a matched controlled group (HR 2.43; 95% CI (1.27-4.62). All pulmonary function parameters were significantly decreased in patients requiring thoracocentesis compared to matched controls. Male sex and re-transplantation were risk factors for pleural effusions. In conclusion, pleural effusions requiring thoracocentesis occur frequently in LTx patients and lead to a reduced long-term allograft function. Late-onset effusions are associated with a lower survival., (© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Background: Tuberculosis (TB) control is a primary global health priority but the goal to eliminate TB is being threatened by the increase in incidence of multidrug-resistant tuberculosis (MDR-TB). With this series of seven MDR-TB cases in migrant patients with identical Mycobacterium tuberculosis strains we aim to illustrate the challenges encountered during therapy and follow-up: language barriers, access to care for migrant patients, depression due to isolation, adverse reactions to the treatment, management of pediatric TB, further contact tracing. We also discuss best practices for the management of complex MDR-TB cases in settings with low overall TB incidence focusing on modern diagnostic assays and an individualized and an interdisciplinary therapeutic approach., Methods: We describe a case series of seven consecutively diagnosed MDR-TB patients, six of them treated at our tertiary care hospital between May 2018 and March 2020. Epidemiologic data was gained by semi-structured patient interviews and reconstruction of the migration route. The origin of the cluster was confirmed by genotyping of the TB-strains., Results: Six related patients were diagnosed with pulmonary MDR-TB between May and August 2018. All had a positive Interferon-Gamma-Release Assay (IGRA), in five patients sputum microscopy was positive for acid-fast bacilli (AFB). The genetic and phenotypical drug susceptibility test did not match with MDR-TB strains from an East-African origin. The index patient was identified through genetical fingerprinting. By changing the therapy to a modern MDR-TB regime and using an interdisciplinary and culture-sensitive approach, all patients improved clinically and radiologically., Conclusion: Human migration plays an important role for the global spread of MDR-TB in low incidence countries. Early case detection and adequate treatment are key to prevention of outbreaks. Especially language barriers and complex migration routes make genotyping of TB-strains a crucial tool to identify cases clusters, the potential index patient and transmission dynamics. We are fortunate enough to experience times in which new TB-antibiotics were made available and in which molecular assays revolutionized TB-diagnostics. We need to take advantage of that and develop personalized therapies for patients suffering from drug resistant TB.

Generalized lymphadenopathy is a common cause of concern for both patients and clinicians. Possible etiologies include infections, malignancies and autoimmune diseases. Kikuchi Fujimoto disease (KFD) is a hyperergic condition that presents with fever, lymphadenopathy and can include systemic involvement, thus being easily mistaken for the above-mentioned entities. We report the case of a previously healthy 18- year old male who presented with a selflimiting generalized lymphadenopathy, high fevers, skin vasculitis and polyserositis. The lymph-node biopsy revealed a histiocytotic necrotizing lymphadenitis, suggestive of Kikuchi's disease. This case emphasizes the importance of KFD in the differential diagnosis of lymphadenopathy, especially in young adults., Competing Interests: Conflict of interest: the authors declare no potential conflict of interest.

Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.