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Abstract Background The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. Methods One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1–4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. Results One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p

Abstract Background The COVID-19 pandemic has caused significant disruptions in the implementation of programs across educational institutions. Nursing students, being both young adults and by practical training, part of the health care system, may be particularly vulnerable during the COVID-19 pandemic. The purpose of this study was to explore the associations between self-reported fear of COVID-19, general health, psychological distress and overall quality of life (QoL) in a sample of Norwegian baccalaureate nursing students compared to reference data. Methods The survey targeted baccalaureate nursing students from five universities in February 2021. An electronic questionnaire consisted of the Fear of COVID-19 Scale (FCV-19S), the Hopkins Symptom Checklist 5 (SCL-5), one general health and one overall QoL question. The respondents’ mean scores were compared to reference data. Hierarchical regression analyses were conducted, and effect sizes (Cohen’s d) were evaluated. Results In total, 2605 out of 6088 (43%) students responded. Their FCV-19S scores (mean 2.45, CI 2.42, 2.48) were significantly higher than those of the reference population (mean 1.8, P

Pneumococcal disease can be divided into invasive disease, i.e. when bacteria are detected in normally sterile body fluids, and noninvasive disease. Pneumococcal disease occurs more frequently in younger children and older adults. It is estimated that, in 2050, 30.3% of the European population will be ≥65 yrs old, compared with 15.7% in 2000. Preventive medicine, including vaccination, is essential for the promotion of healthy ageing. Uptake rates for influenza vaccination in the elderly are generally low, despite recommendations in many countries. In addition, it has been reported that influenza infections can make people more susceptible to pneumococcal infections. Despite pneumococcal vaccination, case fatality rates for patients hospitalised with invasive pneumococcal disease have remained at around 12% since the 1950s. Even when effective antibiotic therapy is administered, mortality can be high amongst immunocompetent patients in intensive care. Timely and accurate diagnosis of pneumococcal disease and identification of patients at high risk of poor outcome is essential to ensure that adequate treatment, including hospitalisation when necessary, is implemented as early as possible. Improved diagnostic techniques and more efficacious treatments may help to reduce the burden of pneumococcal disease, but preventive measures, such as influenza and pneumococcal vaccination, should be promoted in order to avoid preventable disease, particularly in the elderly.

Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Nevertheless, its importance is often underestimated. Large cohorts of patients with CAP have been established worldwide and improved our knowledge about CAP by far. Therefore, current guidelines are much more evidence-based than ever before. This article discusses recent major studies and concepts on CAP such as the role of biomarkers, appropriate risk stratification to identify patients in need of hospitalisation or intensive care, appropriate empiric antibiotic therapy (including the impact of macrolide combination therapy and antibiotic stewardship), and CAP prevention with novel influenza and pneumococcal vaccines.

The formation and 29SiNMR spectroscopic characterizationof silicon cations that are intramolecularly stabilized by a dialkylthioether are described. The chemical stability of the silicon–sulfurLewis pair and, hence, the viability of the approach, were probedwith a 2-[(alkylthio)methyl]phenyl-substituted hydrosilaneas a proxy before three different motifs with chiral binaphthyl backboneswere prepared in multistep sequences. The degree of shielding of thesilicon atom in these cations was found to depend on the substitutionpattern at the silicon atom and the ring size generated by the silicon–sulfurinteraction. These sulfur-stabilized silicon cations are sufficientlyreactive to promote Diels–Alder reactions of cyclohexa-1,3-dienewith various dienophiles; the same set of reactions with cyclopentadieneis also reported. One of the three chiral Lewis acids induces low,but promising, enantioselectivity, and 24% ee is the highest valueso far obtained with a cationic tetracoordinate silicon catalyst. [ABSTRACT FROM AUTHOR]

Introduction Antipsychotics (AP) are used as the primary pharmaceutical treatment for schizophrenia. Randomised clinical trials (RCT) show that the initiation of AP treatment often induces side effects such as substantial weight gain and metabolic disturbances, including an increased risk of type-2 diabetes (DM). However, the limitations of RCTs are often small cohorts that only represent a minority of patients with schizophrenia seen in everyday clinical settings leading to selection bias. Many RCTs are also limited by a short follow-up time, as evaluation of metabolic disturbances requires months to years of observation. Objectives Within a large cohort of real-world patients with long-term follow-up, we aim to study the differential metabolic side effects of specific antipsychotic drugs. Methods We performed a retrospective cohort study using the electronic patient record system “MidtEPJ”, which contains data from blood samples and medication usage from all patients registered with a schizophrenia diagnosis (ICD-10 code DF20) in the central region of Denmark from 2016-2022. Patients were followed from September 2016 (for patients with a schizophrenia diagnosis before this date) or their first schizophrenia diagnosis. The exposure is treatment with AP medication. Outcomes of interest are the development of DM, defined as a diagnosis of DM or usage of anti-diabetic medication, and changes in HbA1c, glucose, and cholesterol levels (high-density lipoprotein [HDL], low-density lipoprotein [LDL], total cholesterol and triglycerides). We performed cox regression analyses to study the associations between specific AP compounds with the differential risk for developing DM and changes in metabolic markers. Results We identified 4909 individual patients with a schizophrenia diagnosis from October 1st, 2016, to September 30th, 2022. AP was subscribed to 4609 of these patients. The results will be presented at the 2023 EPA Congress. Conclusions Our results will be discussed at the conference. Disclosure of Interest None Declared

Impaired interferon (IFN) production has been observed in various obstructive respiratory diseases. This contributes to enhanced sensitivity towards viral infections triggering acute exacerbations. To compensate for this impaired host IFN response, there is need to explore new therapeutic strategies, like exogenous administration of IFNs as prophylactic treatment. In the present study, we examined the protective potential of IFN-λ1 and compared it with the previously established protecting effect of IFN-β. A549 cells and human primary bronchial epithelial cells were first treated with either IFN-β (500 IU/ml) or IFN-λ1 (500 ng/ml) for 18 h. For infection, two approaches were adopted: i) Continuous scenario: after pre-treatment, cells were infected immediately for 24 h with human rhinovirus 1B (HRV1B) in IFN-containing medium, or were cultured for another 72 h in IFN-containing medium, and then infected for 24 h with HRV1B, ii) Pre-treatment scenario: IFN-containing medium was replaced after 18 h and cells were infected for 4 h either immediately after pre-treatment or after additional culturing for 72 h in IFN-free medium. The protective effect was evaluated in terms of reduction in the number of viral copies/infectious progeny, and enhanced expression of IFN-stimulated genes (ISGs). In both cell types and in both approaches, IFN-λ1 and IFN-β treatment resulted in pronounced and long-lasting antiviral effects exemplified by significantly reduced viral copy numbers and diminished infectious progeny. This was associated with strong up-regulation of multiple ISGs. However, in contrast to the IFN-β induced expression of ISGs, which decreased over time, expression of ISGs induced by IFN-λ1 was sustained or even increased over time. Here we demonstrate that the protective potential of IFN-λ1 is comparable to IFN-β. Yet, the long-lasting induction of ISGs by IFN-λ1 and most likely less incitement of side effects due to more localized expression of its receptors could make it an even more promising candidate for prophylactic treatment than IFN-β.

Four fungicides were tested for control of rust on greenhouse carnations. The most effective fungicides were Plantvax and Systhane; the latter is not currently registered for control of this disease in California.

Eski çağın bir insanı birdenbire karşımıza çıksa, herhalde ona evvela hürmetle, hayretle bakarız. Biraz sonra merak ederiz, bu harikulade fırsattan istifade etmek, geçmiş zamanlar hakkında birçok şeyler öğrenmek isteriz. Kitabeler de eski çağlardan kalma insanlara benzemez mi? Onlara mazinin şahitleri dersek, boş bir söz söylemiş olmayız: ömrü boyunca kitabelerle uğraşmış bir alim de bu taşların gözü önünde nice tarihi hadiselerin cereyan ettiğini düşünüp durur. Böylece kitabe, tarihle doğrudan doğruya temasa girmemizi temin eder. Zaten eski çağ da onları bu niyetle dikmiştir : kitabenin sadece sessiz bir anıt değil, geçen yolcuyu selâmlıyarak ona bir şey anlatmasını, aklına gelen suallere cevap verebilmesini istemişti.

Community-acquired pneumonia (CAP) has a significant impact on public health, especially in light of the recent SARS-CoV-2 pandemic. To enhance disease characterization and improve understanding of the underlying mechanisms, a comprehensive analysis of the plasma lipidome, metabolome and proteome was conducted in patients with viral and bacterial CAP infections, including those induced by SARS-CoV-2. Lipidomic, metabolomic and proteomic profiling were conducted on plasma samples of 69 patients suffering either from viral or bacterial CAP. Lipid and metabolite analyses were LC-MS-based, while proteomic analyses were performed using multiple panels of the Olink platform. Statistical methods, machine learning and pathway analyses were conducted investigating differences between the infection types. Through comparison of the bacterial and viral pathogen groups, distinct signatures were observed in the plasma profiles. Notably, linoleic acid-derived inflammation signaling metabolites (EpOME and DiHOME) were increased in viral CAP compared to bacterial CAP. Similarly, proteins involved in cellular immune response and apoptosis (LAG-3 and TRAIL) showed elevated levels in viral CAP, while bacterial CAP exhibited notable elevation in pattern-recognizing receptors (CLEC4D and EN-RAGE). Additionally, within the lipidomic profile at baseline, several lipids displayed notable differences between viral and bacterial pneumonia, including bile acids (GCA, TCA, TCDCA), various tri- and diglycerides (TGs and DGs), and several phosphatidylcholines (PCs). These findings hold promise for facilitating the differential diagnosis of viral and bacterial pulmonary infections based on the systemic lipidome, metabolome and proteome, enabling timely treatment decisions. Additionally, they highlight potential targets for drug research, advancing therapeutic interventions in CAP. By providing valuable insights into the molecular characterization of CAP, this study contributes to the improvement of understanding the disease and, ultimately, the development of effective treatment strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was conducted on plasma samples from adult, fully consenting participants. All protocols adhered to the Declaration of Helsinki, as well as guidelines of good clinical practice (GCP) and good epidemiological practice (GEP). Informed consent was obtained from all participants. This study was approved by the institutional ethics board of the Hannover Medical School (Ethics approval No. 301–2008) and local responsible review boards of participating centers., (© 2025. The Author(s).)

Psychiatric symptoms are frequent in neurocognitive disorders and dementias. Psychotic symptoms, mainly hallucinations and delusions, may appear in up to 50% of cases, influencing morbidity and mortality. Genetic, neurobiological, and environmental factors are involved in their onset. We conducted a narrative review of primary articles developed in humans that analyzed the genetic and neurobiological basis of psychosis in dementias. Evidence suggests that there are genetic risk variants for presenting psychosis in dementia. How genetic variants are related to schizophrenia, dementia, and other neurodegenerative disorders is under discussion. Candidate gene studies have found and genetic variants are associated with psychosis in dementia while genome-wide association studies have shown variants located in y . Epigenetic studies are scarce but have detected differences in the methylome of people with dementia and psychosis. On the other hand, alterations of the cholinergic, serotonergic, dopaminergic, and gabaergic neurotransmitter systems and the excitatory-inhibitory balance have been described in dementia. From a functional and anatomical point of view, there are alterations in several regions, mainly in the frontal area and other sensory processing and integration areas. Finally, we describe the influence of cognitive alterations in the genesis and maintenance of delusions and discuss the phenomenological overlap with confabulations. Multiple genetic, neurobiological, structural, and cognitive factors influence the occurrence of delusions and hallucinations in persons with dementia. Further research is needed to understand the pathophysiology of psychosis in dementias. This approach would support the understanding of psychosis as a transdiagnostic entity., Competing Interests: The authors completed the ICMJE conflict of interest statement and declared that they received no funds for the completion of this article; they have no financial relationships with organizations that may have an interest in the published article in the last three years; and they have no other relationships or activities that may influence the publication of the article. Forms can be requested by contacting the responsible author or the Editorial Committee of the Journal., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Introduction: Endometriosis is the leading cause of chronic pelvic pain among women. The pain associated with endometriosis significantly impacts various aspects of patients' quality of life. A notable void in the literature is the absence of a systematic review exploring pain communication between patients with endometriosis and healthcare professionals. Hence, the aim of this qualitative systematic review was to synthesize findings on how patients with endometriosis experience communicating with healthcare professionals about pain and how healthcare professionals experience these interactions., Material and Methods: A systematic literature search was conducted related to patients with endometriosis and pain communication in CINAHL PLUS with full text and MEDLINE (via EBSCO host) on May 12, 2023, and updated January 26, 2024. Searches were supplemented by backward searching reference lists and forward searching citations of included reports in Scopus and Google Scholar. The review was guided by the four-step meta-synthesis methodology by Sandelowski and Barosso. Critical appraisal of included studies was conducted using Critical Appraisal Skill Program (CASP). Findings were analyzed thematically, using the approach described by Thomas and Harden. The meta-synthesis was based on a registered protocol in PROSPERO (CRD 42023425430), and the study is reported adhering to the PRISMA 2020 checklist., Results: Overall, 37 reports published from 2003 until 2023 contributed to the review, including 4842 participants. Through thematic analysis, we developed the following themes: "Navigating the double burden," "Lack of mutual understanding," and "The complexities of conveying pain.", Conclusions: The communication of pain between patients with endometriosis and healthcare professionals is complex, encompassing patterns of disbelief, normalization, and psychological attribution. Engaging in discussions about pain presents diverse challenges stemming from insufficient communication skills and assessment tools. Further research is warranted to comprehensively explore the perspectives of both patients and healthcare professionals, aiming to devise strategies that enhance communication and patient care., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Axial spondyloarthritis (ax-SpA) causes pain, fatigue, stiffness, loss of physical function, and poor health status, which can influence sexual activity and enjoyment. To explore whether patients with ax-SpA perceive that their health status effects their sexual activity and to identify predictors of these perceived effects on sexual activity after a 5-year follow-up. Data about demographics, disease, medication, health-related quality of life (HRQOL), and sexual quality of life (SQOL) were collected at the baseline and 5-year follow-up. The perceived effect of health status on sexual activity was measured by question 15 in the 15D questionnaire. Data were analysed using the McNemar and independent paired t tests and logistic regression. In the 244 patients with ax-SpA (30% women, 70% men; mean age, 46 years), measures reflecting disease activity decreased and comorbidities increased, and more patients were treated with biological drugs at 5 years. Compared with patients whose health status had little/no effect on sexual activity (n = 200), those who perceived that their health status had a large effect on sexual activity (n = 44) were older, exercised less, fewer were employed, had more comorbidities, higher disease activity, and lower HRQOL and SQOL. The baseline predictors of a negative effect of health status on sexual activity were old age and low SQOL. Patients reporting that their health status had a large effect on sexual activity at 5 years were older, had more disease activity, and lower HRQOL and SQOL., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Compliance with ethical standards: The study was approved Ethics by the Regional Committee for Medical Research Ethics, Norway (REK #4.2007.2152). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual respondents included in the study. Informed consent: Written informed consent was obtained from all individual participants included in the study. Data in the study were anonymized., (© 2024. The Author(s).)

The aim was to identify predictors for early identification of HFNC failure risk in patients with severe community-acquired (CAP) pneumonia or COVID-19. Data from adult critically ill patients admitted with CAP or COVID-19 and the need for ventilatory support were retrospectively analysed. HFNC failure was defined as the need for invasive ventilation or death before intubation. 60 patients with CAP and 185 with COVID-19 were included. 27 (45%) patients with CAP and 69 (37.3%) patients with COVID-19 showed HFNC failure. Lower oxygenation index, lower respiratory oxygenation (ROX) index, and higher respiratory rate at the start of HFNC were significantly associated with HFNC failure. ROC-analysis identified a respiratory rate of 27/min as the optimal cut-off for predicting HFNC failure, with a specificity of 59% and a sensitivity of 75%, and an oxygenation index after HFNC initiation of 99.6 (specificity 81%, sensitivity 74%). In COVID-19, an elevated CRB65-score at hospital admission and at HFNC-initiation was significantly associated with HFNC failure. In CAP and COVID patients an oxygenation index < 99.6, a respiratory rate > 27/min and a ROX index < 4.88 were predictors for HFNC failure whereas a CRB65 score > 3 at hospital admission and > 2 at HFNC start was predictive for HFNC failure in COVID-19., Competing Interests: Declarations. Conflict of interest: A. Grünewaldt reports personal fees from Boehringer Ingelheim for lectures and GSK for consultancy during advisory board meetings. G. Rohde reports personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Solvay, Takeda, Novartis, Pfizer and Vertex for consultancy during advisory board meetings, furthermore personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures. M. Gaillard reports no competing interests. Ethical approval: The study protocol was endorsed by the local ethics committee of the university hospital, Goethe university Frankfurt (study number 22-785)., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Community-acquired pneumonia (CAP) is a major global health concern as it is a leading cause of morbidity, mortality and economic burden to the health care systems. In Germany, more than 15,000 people die every year from CAP. Climate change is altering weather patterns, and it may influence the probability and severity of CAP. The increasing frequency and intensity of extreme weather events necessitate the study of their impact on CAP hospitalizations. In this regard, we examine the influence of absolute values and changes in various meteorological and air quality conditions on the frequency of CAP hospitalizations. We matched weather data to the German CAPNETZ-Cohort of 10,660 CAP patients from 22 healthcare facilities between 2003 and 2017. Our findings show that daily fluctuations in meteorological conditions (maximum temperature, 99th percentile precipitation), apart from relative humidity, are likely to result in triggering CAP hospitalizations than absolute conditions. In contrast, the absolute values of air quality (CO, NO 2 , O 3 , PM 2.5 , SO 2 , and total aerosols) are found to exert a greater influence on CAP hospitalizations than changes in air quality. The study outcomes have implications for public health measures, early warning systems, and public awareness, with the aim of mitigating the risk of CAP., Competing Interests: Declarations. Ethics approval: Patient data was acquired from CAPNETZ-Cohort which received ethical approval by the local ethical committees of the centers participating in CAPNETZ, ensuring compliance with relevant guidelines and regulations., (© 2024. The Author(s).)

The airway epithelium provides a crucial barrier against infection with respiratory pathogens. This barrier can be impaired following viral infection, paving the way for bacterial superinfections. Type I interferons (IFNs) are important antiviral mediators, and inhaled formulations of these glycoproteins are considered a potential approach for the treatment of respiratory viral infections. To investigate if type I IFNs can also protect against virus-induced epithelial barrier dysfunction, differentiated primary bronchial epithelial cells were pre-treated with IFN-β1a and subsequently infected with human rhinovirus (HRV) for 24 to 72h. Moreover, to functionally assess the effects of IFN-β1a pre-treatment on barrier integrity, we conducted co-infection experiments, in which cells were initially infected with HRV, and superinfected with Streptococcus pneumoniae 24 to 72 h later. In untreated cells, HRV infection significantly damaged ZO-1 positive tight junctions and cilia, and transiently increased permeability, whereas the barrier of cultures pre-treated with IFN-β1a remained intact. In co-infection experiments, bacteria were able to penetrate deeper into the cell layers of HRV-infected cultures than into those of uninfected cells. IFN-β1a pre-treatment abrogated virus-induced damage to the epithelial barrier. Taken together, these data demonstrate a beneficial effect of IFN-β in protecting epithelial barrier function in addition to its antiviral effects., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Prior studies have reported lower effectiveness of XBB.1.5-adapted vaccines against hospitalization related to the Omicron JN.1 variant than the XBB variant. This study evaluated the effectiveness and durability of the BNT162b2 XBB.1.5-adapted vaccine against JN.1-related hospitalization during the 2023-2024 season in Europe., Methods: A test-negative case-control study was carried out in adults (≥18 y) hospitalized between 2 October 2023 and 2 April 2024 with severe acute respiratory infection (SARI) within the id.DRIVE partnership. This study included nine sites across Belgium, Germany, Italy, and Spain. Cases had a laboratory-confirmed JN.1 infection or a positive SARS-CoV-2 test with symptom onset during JN.1 predominance; controls had a negative SARS-CoV-2 test and symptom onset during JN.1 predominance. The primary objective was to estimate BNT162b2 XBB.1.5-adapted vaccine effectiveness (VE) against COVID-19 hospitalization. One case was matched with up to four controls, according to symptom onset date and site. Multivariable analyses were adjusted for symptom onset date, age, sex, and number of chronic conditions., Findings: Among 308 test-positive cases and 1117 test-negative controls, BNT162b2 XBB.1.5-adapted VE against hospitalization compared to no vaccination this season was 53.8% (95% CI 38.4-65.4) after a median of 63 days following vaccination. Protection was sustained through five months; VE was 52.2% (95% CI 41.3-61.1) 2 to <4 weeks after vaccination, 48.9% (95% CI 17.9-68.2) at 4 to <8 weeks, and ranged from 54.6% to 59.5% at 4-week intervals from 8 to <22 weeks., Interpretation: BNT162b2 XBB.1.5-adapted vaccine provided protection against JN.1-related hospitalization, regardless of prior vaccination history, with no evidence of waning through five months. These data support yearly vaccination against COVID-19 to prevent severe illness during the respiratory virus season., Funding: Pfizer., Competing Interests: All authors have completed the ICMJE disclosure form and declare: Pfizer Inc. funded this study. C Marques, HRV, JLN, JMML, JY, MMu, LJ, and SV are employees of Pfizer Inc. HRV, JLN, JMML, JY, MMu, LJ, and SV hold stocks or stock options in Pfizer Inc. EC-S, KB, LD, LdM, MMi, and TMPT are employees of P95 Epidemiology & Pharmacovigilance, a company providing scientific services in the field of vaccines. KB and TMPT declare stock or stock options in P95. KB has received consulting fees from Pfizer Inc. for conducting this study, royalties for the book ‘Vaccination Programmes: epidemiology, monitoring, evaluation’ by Hahné, Bollaerts, Farrington, and consulting fees from AstraZeneca, Bavarian Nordic, CureVac, Janssen, GSK, Pfizer, Novavax, Valneva, and the World Health Organization. AOS reports that Pfizer partially funded the hospital network for the collection of data via id.DRIVE. IC reports support from Pfizer for congress attendance. AM-I reports being a co-principal investigator from VAHNSI (Fisabio). Fisabio received funding from P95 via id.DRIVE to conduct the study. BG and GI declare payment from the id.DRIVE Consortium to their institutions for conducting the study. BG further declares that data collaboration between P95 and Pfizer is reported. GI has received grants or contracts, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, support for attending meetings and/or travel, and declares participation on a Data Safety Monitoring Board (DSMB) or Advisory Board from GSK, MSD, Sanofi, Pfizer, Seqirus, Moderna, AstraZeneca, Viatris, and Novavax. GR declares payments to his institution by the CAPNETZ foundation, of whose executive board he is the chairman. Furthermore, GR reports personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, and Pfizer for consultancy during advisory board meetings and personal fees from AstraZeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer, and Vertex for lectures. SO-R declares payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK and Sanofi. AÁ, C Martin, EC-S, GLtK, LdM, LD and MMI declare no conflicts of interest., (© 2024 The Authors.)

Background: Community-acquired pneumonia (CAP) remains a leading cause of infectious disease mortality globally, necessitating intensive care unit (ICU) admission for ∼10% of hospitalised patients. Accurate prediction of disease severity facilitates timely therapeutic interventions., Methods: Our study aimed to enhance the predictive capacity of the clinical CRB-65 score by evaluating eight candidate biomarkers: troponin T high-sensitive (TnT-hs), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide, angiopoietin-2, copeptin, endothelin-1, lipocalin-2 and mid-regional pro-adrenomedullin. We utilised a machine-learning approach on 800 samples from the German CAPNETZ network (competence network for CAP) to refine risk prediction models combining these biomarkers with the CRB-65 score regarding our defined end-point: death or ICU admission during the current CAP episode within 28 days after study inclusion., Results: Elevated levels of biomarkers were associated with the end-point. TnT-hs exhibited the highest predictive performance among individual features (area under the receiver operating characteristic curve, AUC=0.74), followed closely by PCT (AUC=0.73). Combining biomarkers with the CRB-65 score significantly improved prediction accuracy. The combined model of CRB-65, TnT-hs and PCT demonstrated the best balance between high predictive value and parsimony, with an AUC of 0.77 (95% CI: 0.72-0.82), while CRB-65 alone achieved an AUC of 0.67 (95% CI: 0.64-0.73)., Conclusion: Our findings suggest that augmenting the CRB-65 score with TnT-hs and PCT enhances the prediction of death or ICU admission in hospitalised CAP patients. Validation of this improved risk score in additional CAP cohorts and prospective clinical studies is warranted to assess its broad clinical utility., Competing Interests: Conflict of interest: M. Scholz received funding from Pfizer Inc. for epidemiological modelling of pneumococcal serotypes and vaccinations, and has an ongoing cooperation with Owkin for a project not related to this research. M. Witzenrath received funding from Aptarion, Biotest and Pantherna for research outside the current study. The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: B. C. W. reports one unpaid participation in an Advisory Board with AstraZeneca. A. L. J. reports research grants from the Behring Röntgen Foundation. G. R. reports personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, and Pfizer for consultancy during advisory board meetings and personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer, and Vertex for lectures including service on speakers’ bureaus. F. T. reports consulting fees from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Fisher & Paykel, GlaxoSmithKline, Janssen-Cilag, Novartis, Omron, OM-Pharma, Roche, Sanofi-Aventis, and support for attending meetings or travel from AstraZeneca, Actelion, Bayer, Berlin Chemie, Boehringer Ingelheim, Chiesi, Mundipharma, Novartis, Pfizer, TEVA. T. G. reports Grant from Grifols to institution for AATD laboratory, consulting fees from AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma, Novartis, Takeda, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma, Takeda, support for attending meetings or travel from AstraZeneca, Berlin-Chemie, Chiesi, CSL-Behring, Grifols, GSK, Novartis, participation on a Data Safety Monitoring Board or Advisory Board with AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, Grifols, GSK, Mundipharma, Novartis, Takeda, leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid as scientific Advisor for Alpha-1-Deutschland. C. F. V. reports grants or contracts from German Ministery of Education and Science (BMBF), AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols, Novartis, consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis, Nuvaira, Sanofi, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Aerogen, AstraZeneca, Boehringer Ingelheim, CSL Behring, Chiesi, GlaxoSmithKline, Insmed, Menarini, Novartis, Roche, Sanofi. Bernd Schmeck reports Grants or contracts from CSL-Behring. None declared (H. P., A. R., N. J., K. K., S. R., C. S., I. S., H. R., S. Fähndrich., W. B., A. M., D. Z., S. Finotto., S. S., S. A. S., B. S.).

Purpose: MET amplification is a common resistance mechanism to EGFR inhibition in EGFR-mutant non-small cell lung cancer (NSCLC). Several trials showed encouraging results with combined EGFR and MET inhibition (EGFRi/METi). However, MET amplification has been inconsistently defined and frequently included both polysomy and true amplification., Methods: This is a multicenter, real-world analysis in patients with disease progression on EGFR inhibition and MET copy number gain (CNG), defined as either true amplification (MET to centromere of chromosome 7 ratio [MET-CEP7] ≥ 2) or polysomy (gene copy number ≥ 5, MET-CEP7 < 2)., Results: A total of 43 patients with MET CNG were included, 42 of whom were detected by FISH. Twenty-three, 7, and 14 received EGFRi/METi, METi, and SoC, respectively. Patients in the EGFRi/METi cohort exhibited a superior real-world clinical benefit rate, defined as stable disease or better, of 82% (95% confidence interval [CI], 60-95) compared to METi (29%, 4-71) and SoC (50%, 23-77). Median real-world progression-free survival was longer with EGFRi/METi with 9.8 vs. 4.3 months with METi (hazard ratio [HR], 0.19, 95% CI, 0.06-0.57) and 3.7 months with SoC (0.41, 0.18-0.91), respectively. Overall survival was numerically improved. Interaction analysis with treatment and type of CNG (amplification vs. polysomy) suggests that differences were exclusively driven by MET-amplified patients receiving EGFRi/METi (HR for OS, 0.09, 0.01-0.54)., Conclusion: In this real-world study, EGFRi/METi showed clinical benefit over METi and SoC. Future studies should focus on the differential impact of the type of MET CNG with a focus on true MET amplification as predictor of response., Competing Interests: Disclosure F. A. received support for attending meetings and speaker's honoraria from AstraZeneca, and consultant fees from IQVIA. P. C. received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Merck, Novartis, Roche, and Takeda, speaker's honoraria from AstraZeneca, Gilead, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, and Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Janssen, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. H.-D. H. received personal fees for participating to advisory boards from Amgen, speaker's honoraria from Amgen, Boehringer Ingelheim, and Bristol-Myers Squibb. C. F. W. received personal fees for participating to advisory boards from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Lilly, Merck, MSD, Novartis, Pfizer, Roche, and Takeda, consultancy fees from Mylan/Viatris, Alvotech, Roche, support for attending meetings from Amgen, Bristol-Myers Squibb, Janssen, Lilly. A. Ri. received speaker's honoraria and consulting fees from Abbvie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Lilly, GSK, MSD, Novartis, Pfizer, Roche/Genentech. H. Z. received support for attending meetings from Janssen, speaker's honoraria from Pierre Fabre, and Roche. A. L. received support for attending meetings from Abbvie. D. K.-G. received consultant fees from AstraZeneca, Boehringer Ingelheim, Roche, MSD, Pfizer, Bristol-Myers Squibb, GSK, Novartis, Takeda, Sanofi, and Janssen, support for attending meetings from Takeda, Boehringer-Ingelheim, Janssen. R. B. received honoraries for lectures and advisory boards for AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Illumina, Janssen, Lilly, Merck-Serono, MSD, Novartis, Qiagen, Pfizer, Roche, Targos MP Inc. R.B. is a Co-Founder and Co-Owner of Targos Inc / Kassel (previous); Gnothis Inc / Stockholm (current); Timer Therapeutics Inc / Fulda & Freiburg (current). M. D. received personal fees for participating in advisory boards from AstraZeneca, Bayer, Diaceutics, Biocartis, Sophia Genetics, and ThermoFisher. F. C. A. has received research grants from Novartis, support for attending meetings and/or travel from Amgen, and consultant fees from IQVIA. S. H. has received research grants from Novartis and travel support from BeiGene. J. A. S. received personal fees from Boehringer Ingelheim, AstraZeneca, Roche, Bristol-Myers Squibb, Amgen, LEO pharma, Novartis, and Takeda. J. W. received speaker's honoraria and personal fees for participating in advisory boards from Amgen, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, Merck, Mirati, MSD, Novartis, Nuvalent, Pfizer, Roche, Seattle Genetics, Takeda, and Turning Point and received institutional research grants from Bristol-Myers Squibb, Janssen, Novartis, Pfizer, and AstraZeneca. M. S. received research grants from AstraZeneca, consulting fees from AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Lilly, Roche, Boehringer Ingelheim, Amgen, Takeda, Johnson, Merck-Serono, and GSK, and speaker's honoraria from AstraZeneca, Bristol-Myers Squibb, MSD, Novartis, Lilly, Roche, Boehringer Ingelheim, Amgen, Takeda, Johnson, CureVac, BioNTech, Merck-Serono, GSK, Daiichi, and Pfizer. S. M. has received research grants from Novartis and Pfizer, personal fees from Eli Lilly, Janssen, and Astra Zeneca as well as support for attending meetings and/or travel from Eli Lilly, and Janssen. A. S. has received speaker's honoraria from Agilent, Aignostics, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, Roche, Seagen, Servier, Takeda, and Thermo Fisher, and institutional research grants from Bayer, BMS, Chugai, and Incyte. All other authors declared no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management., Methods: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment., Results: Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70])., Conclusion: Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens., Competing Interests: Declarations. Conflict of interest: H.-J. M. reports a personal fee from Astra Zeneca for a lecture. G. R. reports personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis, and Pfizer for consultancy during advisory board meetings and personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer, and Vertex for lectures. M. W. received funding for research, lectures, or advisory from Alexion, Aptarion, Astra Zeneca, Bayer Health Care, Biotest, Boehringer Ingelheim, Chiesi, Glaxo Smith Kline, Insmed, Novartis, Pantherna, Pfizer, Teva, and Vaxxilon. T. Z. received funding for research from Bundesministerium für Bildung und Forschung, Else Kröner Fresenius Stiftung and Gesellschaft für Internationale Zusammenarbeit., (© 2024. The Author(s).)

Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo). In addition, DLL3 expression was explored as potential novel therapeutic target., Methods: We conducted a retrospective study on patients with EGFR+ NSCLC and SCT treated at 19 centers in Europe and the United States. A total of 47 patients were included of whom 17 received chemo, 20 ICI+chemo, and 10 EGFRi+chemo. We analyzed DLL3 expression by immunohistochemistry., Results: In the entire cohort, median overall survival (OS) from start of first SCT therapy was 11 months (95 % confidence interval [95 %CI] 9.1-12.9) and median progression-free survival (PFS) was 5 months (95 %CI 4.2-5.8). Median PFS was similar in all three groups (chemo and ICI+chemo 4 months, EGFRi+chemo 6 months), and 12-months PFS was 12 % (95 %CI 2 %-31 %), 13 % (95 %CI 0 %-43 %), and 0 % for ICI+chemo, EGFRi+chemo, and chemo, respectively. Median OS in the ICI+chemo group was 13 months (95 %CI 5.5-20.5) compared to 10 months (95 %CI 7.6-12.4) with chemo and EGFRi+chemo (95 %CI 8.1-11.9), respectively. Before and after SCT, 0 % and 93 % of tumors were DLL3-positive., Conclusions: Our results suggest that ICI+chemo and DLL3-targeting agents are worth further exploration in EGFR+ NSCLC undergoing SCT., Presented Elsewhere: Part of this work has been presented at ESMO annual meeting in Madrid, Spain in October 2023 (Poster 1336 P)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Allgäuer, M received speaker fees from Boehringer Ingelheim. Alt, J received speaker fees and/or honoraria for advisory boards by Astra Zeneca, Pfizer, Daichii Sankyo, Roche, Amgen, MSD, Novartis, Janssen, Boehringer Ingelheim, Merck, BMS. Aust, DEA received honoraria from Roche, Astra Zeneca, MSD, Pfizer, Novartis. Christopoulos. P received research funding from Roche, Amgen, Boehringer Ingelheim, Takeda, Merck, AstraZeneca, and Novartis, honoraria from Roche, Takeda, Gilead, AstraZeneca, Merck, Thermo Fisher, Janssen, Pfizer, and Novartis, travel support from AstraZeneca, Pfizer, Janssen, Merck, Gilead, Daiichi Sankyo, Takeda, Novartis, Eli Lilly and compensation for advisory roles for Pfizer, Chugai, Boehringer Ingelheim, Takeda, Janssen, Novartis, astraZeneca, MSD, Roche. Griesinger, F received speaker fees and/or honoraria for advisory boards from AstraZeneca, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Tesaro/GSK, Siemens, Tesaro, Amgen, Sanofi, Daiichi-Sankyo, Beigene. Grohé, C received honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche, and has had consulting or advisory roles with Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Hochmair, M received honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche, and has had consulting or advisory roles with Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Illini, O received speaker fees and/or honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Menarini, Merck Sharp & Dohme, Pfizer, and Roche and received research grants from Amgen and AstraZeneca outside of the submitted study. Jöhrens, K received compensation for advisory roles for BMS, GSK, Merck Sharp & Dohme, honoraria from AstraZeneca, Agilent, Boehringer Ingelheim, and DSO, and serves as medical advisor for QuIP. Kauffmann-Guerrero received speaker fees and/or honoraria for advisory boards from AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. Kirfel, J received speaker fees and/or honoraria for advisory boards, from AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer and Roche. König, D received a personal grant from Geistlich-Stucki-Stiftung, consulting fees from AstraZeneca, Merck, MSD, Novartis, PharmaMar, honoraria for presentations from Amgen, BMS, Mirati, Sanofi, Swiss Oncology in Motion, support for attending meetings from Amgen, Roche, Sanofi, honoraria for advisory boards from AstraZeneca, BMS, Merck, MSD, PharmaMar, Roche. Michels, S received research grants from Novartis and Pfizer, personal fees from Eli Lilly, Janssen, and Astra Zeneca as well as support for attending meetings and/or travel from Eli Lilly, and Janssen. Overbeck, T received speaker fees and/or honoraria for advisory boards by AstraZeneca, BMS, Boehringer-Ingelheim, Eli Lilly, Janssen-Cilag, Merck, MSD, Novartis, Roche, Takeda, Tesaro/GSK, Lilly, Roche, travel reimbursement by AstraZeneca, Boehringer-Ingelheim, Janssen-Cilag, Lilly, and Roche. Rohde, G received personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis and Pfizer for consultancy during advisory board meetings and personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures. Rothschild, S received honoraria (institutional) from, Roche, AstraZeneca, BMS, Boheringer Ingelheim, MSD Oncology, Novartis, Amgen, Lilly, Eisai, Merck serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, and Sanofi, compensation for advisory roles for AstraZeneca, Boerhinger Ingelheim, BMS, Pfizer, Eisai, Eli Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Amgen, Otsuka, PharmaMar, serves for the speakers bureau of Roche Pharma AG, Sanodi/Aventis, Amgen, AstraZeneca, Takeda, received research funding from Abbvie, BMS, AstraZeneca, Boerhinger Ingelheim, Merck Serono, Roche Pharma AG, and travel support, accomodation, expenses from Sanofi, Roche Pharma AG, BMS, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen. He serves at the Federal Drug Comission of the Federal Office of Public Health and the Swiss Group for Clinical Cancer Research (SAKK). Saalfeld, F received research funding from Roche, consultancy fees from Boehringer Ingelheim, honoraria for lectures from AstraZeneca, Janssen, Takeda, Pfizer, Novartis, Thieme, and GWT-TUD, travel support from Janssen and Eli Lilly, and compensation for advisory meetings with BMS, Pfizer, AstraZeneca, Janssen, MSD, and Roche. Stenzinger, A received research grants from Bayer, BMS, Chugai, Incyte, and MSD, and compensation for advisory boards/speaker’s bureau: Agilent, Aignostics, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, QuiP, Roche, Sanofi, Seagen, Servier, Takeda, Thermo Fisher. Syrigos, K received honoraria for advisory boards from Merck Sharp & Dohme, AstraZeneca, BMS Amgen. Thomas, M received research funding (institution) from AstraZeneca, BMS, Merck, Roche, Takeda, speaker fees and/or honoraria for advisory boards by Amgen, AstraZeneca, Beigene, BMS, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, Merck, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Takeda. Veluswamy, R served on advisory boards for Bristol-Myers Squibb, Astrazeneca, Merck, Boehringer Ingelheim, Merus, Novocure, Regeneron, BerGenBio, and Serna Bio, on unbranded speaker’s bureau of Astrazeneca and EMD Serono, received consulting honorarium from Beigene, received research funding from Bristol-Myers Squibb, Onconova, Astrazeneca, Boehringer Ingelheim, Lung Cancer Research Foundation, Stand Up 2 Cancer. Wenzel, C received speaker fees from Astra Zeneca. Wermke, M received honorary from Lilly, Boehringer-Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer, BMS and has/had paid consulting or advisory positions for BMS, Novartis, Lilly, Boehringer-Ingelheim, ISA Pharmaceuticals, Amgen, Immatics, Bayer, ImCheck, AstraZeneca, Tacalyx, Regeneron, Daiichi, Zymeworks, PharmaMar. He receive research funding (instution) from Roche and travel support from Pfizer, BMS, AstraZeneca, Amgen, Gemoab, Sanofi-Aventis, Merck Serono, Immatics, Janssen, Iovance, Daiichi-Sankyo. Wesseler, C received speaker fees and/or honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, MSD, Novartis, Takeda, AstraZeneca, Chugai, BMS. Wiesweg, M received honoraria and Advisory Role: Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Takeda, and travel costs from Amgen, Janssen, Daiichi Sankyo, and research funding from Bristol-Myers Squibb, Takeda. Klimova, A, Kulhvay, J, Möller, J, Pelusi, N, Rasokat, A, Schubart, C, Schütz, M, Wang, A, and Vathiotis, J have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia., Methods: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation., Results: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). 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. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. 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: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany., Competing Interests: Declarations. Conflict of interest: JR received research support from Bundesministerium für Bildung und Forschung (BMBF), Bundesministerium für Gesundheit (BMG) Infectopharm; lecture fees from AstraZeneca, GSK, Chiesi, Esanum, Novartis, ThermoFisher, Berlin-Chemie, MSD, Boehringer, Pfizer, Shionogi; Consultant fees from Shionogi, GSK, Advanz, Gilead, MSD BG received lecture fees from Biotest, Gilead, Infectopharm, MIP, MSD, Pfizer and Shionogi; consultant fees from MSD, Pfizer, Gilead und Mundipharma. SG received speaker fees from Becton Dickinson, bioMérieux and Bio-Rad. SH received research support from Bundesministerium für Bildung und Forschung (BMBF); lecture fees from Pfizer, MSD, Infectopharm, Philips, Advanz, Beckman Coulter, Thermofisher, Shionogi, Tillots; Consultant fees from Advanz, Shionogi, Pfizer CPH received personal fees from Schering-Plough; grants and personal fees from Pfizer, Boehringer Ingelheim, Siemens; personal fees from Basilea, Novartis, Roche, Astellas, Gilead, MSD, Lilly, Intermune, Fresenius, Essex, AstraZeneca, Bracco, MEDA Pharma, Chiesi, Covidien, Pierre Fabre, Grifols, Bayer; and grants from MeVis, German Center for Lung Research. SK received research support from Cytosorbents and Daiichi Sankyo; lecture fees from ADVITOS, Biotest, Daiichi Sankyo, Fresenius Medical Care, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Shionogi and Zoll; consultant fees from ADVITOS, Fresenius, Gilead, MSD and Pfizer. MK received research support from Pfizer; lecture fees from Astra-Zeneca, Berlin-Chemie, Böhringer-Ingelheim, Gilead, GSK, Insmed, Pfizer; consultant fees from AstraZeneca, Sanofi, GSK, Insmed MP received lecture fees from Siemens Healthineers, Roche, Janssen-Cilag, Diasorin; consultant fees from Sanofi, GR received support for research from BMBF, GSK, and honoraria from AstraZeneca, Boehringer, Bayer, Berlin-Chemie, Grifols, Insmed, MSD, Novartis, Pfizer, GSK, Roche. H.J.F. Salzer received honoraria for lectures or consulting fees from Insmed, GlaxoSmithKline, AstraZeneca, Advanz Pharma, MSD and Chiesi, MAW reports personal fees from MSD, Gilead, Pfizer, Shionogi, Mundipharma, Eumedica, Coulter, Biotest, Sedana, SOBI, and Böhringer; and patent EPA17198330 “Delta- Like Ligand 1 for diagnosing severe infections”. TW received support for research from DFG, BMBF, GSK, and honoraria for lectures/ad board from AstraZeneca, GSK, Jansen, Moderna, MSD, Pfizer, Sanofi-Aventis. TW provides unpaid advice to Leopoldina, EMA, CDC and is honorary Chairman of the Board of Trustees of CAPNETZ Foundation, MWP received support for research from DFG, BMBF, EKFS, Manchot Foundation, Sonnenfeld Foundation, Aptarion, Biotest, Pantherna, Vaxxilon, and honoraria from Aptarion, AstraZeneca, Biotest, Chiesi, Gilead, Insmed, Pantherna, Vaxxilon. All other authors declare no competing interests., (© 2024. The Author(s).)

Background: In organ donation from deceased donors, the interaction between the donor's relatives and intensive care personnel is an important factor. The organ donation (OD) process is complex, and patients' relatives play a vital role. Intensive care professionals need knowledge about how relatives perceive and experience the process to create a caring environment and support them throughout. Therefore, this collaborative project aims to explore both relatives' and intensive care personnel's perspectives of care in deceased organ donation in Scandinavia., Objective: This study aims to (1) investigate donor relatives' satisfaction and ICU personnel's perception of their own professional competence and (2) explore donor relatives' and ICU personnel's experiences in the OD process to design for care and support in OD., Methods: This protocol outlines a Scandinavian (Norway, Sweden, and Denmark) project, including 4 work packages. Work package 1 started in 2023 with the translation and validation of the Family Satisfaction in the Intensive Care Unit questionnaire into a Danish version and the translation of the Professional Competence in Organ Donation Questionnaire into a Swedish and Danish version. A cross-sectional survey measuring Scandinavian relatives' perception of support in and satisfaction with the organ donation process and a cross-sectional survey measuring Scandinavian intensive care personnel's competence in organ donation are the foundation for work package 2 (2024). The data from both surveys will be analyzed using descriptive and comparative analysis. The results will inform the interview guides in qualitative studies (work packages 3 and 4). Participants in the quantitative study will be invited to participate in in-depth interviews. In work package 3, in-depth interviews will be conducted to illuminate relatives' experiences in the organ donation process. The interviews will be analyzed using thematic analysis, according to Braun and Clarke. In work package 4 (2025-2026), 1 qualitative design study will be conducted to illuminate ICU personnel's experiences. Furthermore, the results from work packages 2 and 3 will inform the development of specific programs for care, support, and communication in the organ donation process., Results: The project was funded by the Norwegian Organ Donor Foundation in 2022 and Scandiatransplant in 2023. The Norwegian Nurses Organisation supports the project by funding a PhD student. The PhD student was employed by the University in Agder in May 2024., Conclusions: This project will provide new knowledge that will assist us in designing and establishing programs for care, support, and donor relatives' involvement in OD processes., International Registered Report Identifier (irrid): PRR1-10.2196/55643., (©Kathe B Meyer, Gudrun Rohde, Gro Frivold. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.11.2024.)

Purpose: This study aimed to develop utility weights for the European Organization for Research and Treatment of Cancer (EORTC) QLU-C10D, a cancer-specific utility instrument, tailored to the Norwegian and Swedish populations. The utility weights are intended for use in the specific welfare contexts of Norway and Sweden to support more precise healthcare decision-making in cancer treatment and care., Methods: This cross-sectional study included 1019 Norwegian and 1048 Swedish participants representative in age and gender of the two general populations. Participants completed a discrete choice experiment involving 960 choice sets, each consisting of two EORTC QLU-C10D health states described by the instrument's domains and the duration of each state. Utility weights were calculated using generalized estimation equation models, and non-monotonic levels were merged to ensure consistent valuation., Results: In the Norwegian participants, the largest utility decrements were seen for the domain of physical functioning (decrement of - 0.263 for highest level "very much"), followed by pain (decrement - 0.205 for level "very much") and role functioning (- 0.139). Among the cancer-specific domains, nausea had the largest utility decrement (- 0.124). In the Swedish participants, the largest utility decrements were also observed for physical functioning (- 0.207 for the response "very much"), followed by pain (- 0.139), role functioning (- 0.133), and nausea (- 0.119). Emotional functioning also exhibited a sizable utility decrement (- 0.115)., Conclusion: This study provides the first set of utility weights for the EORTC QLU-C10D specific to Norway and Sweden, reflecting the unique health preferences of these populations. The generated utility decrements can inform cost-utility analyses and optimize resource allocation in cancer care within the Norwegian and Swedish healthcare systems., (© 2024. The Author(s).)

Background: Cardiac symptoms due to postacute inflammatory cardiac involvement affect a broad segment of previously well people with only mild acute coronavirus disease 2019 (COVID-19) illness and without overt structural heart disease. Cardiovascular magnetic resonance (CMR) imaging can identify the underlying subclinical disease process, which is associated with chronic cardiac symptoms. Specific therapy directed at reducing postacute cardiac inflammatory involvement before development of myocardial injury and impairment is missing., Methods: Prospective multicenter randomized placebo-controlled study of myocardial protection therapy (combined immunosuppressive/antiremodeling) of low-dose prednisolone and losartan. Consecutive symptomatic individuals with a prior COVID-19 infection, no pre-existing significant comorbidities or structural heart disease, undergo standardized assessments with questionnaires, CMR imaging, and cardiopulmonary exercise testing (CPET). Eligible participants fulfilling the criteria of subclinical post-COVID inflammatory heart involvement on baseline CMR examination are randomized to treatment with either verum or placebo for a total of 16 weeks (W16). Participants and investigators remain blinded to the group allocation throughout the study duration. The primary efficacy endpoint is the absolute change of left ventricular ejection fraction to baseline at W16, measured by CMR, between the verum treatment and placebo group by absolute difference, using unpaired t-test confirmatively at a significance level of 0.05 significance level. Secondary endpoints include assessment of changes of symptoms, CMR parameters, and CPET after W16, and frequency of major adverse cardiac events after 1 year. Safety data will be analyzed for frequency, severity, and types of adverse events (AEs) for all treatment groups. The proportion of AEs related to the contrast agent gadobutrol will also be analyzed. A calculated sample size is a total of 280 participants (accounting for 22 subjects (8%) drop out), randomized in 1:1 fashion to 140 in the verum and 140 placebo groups., Conclusion: Myoflame-19 study will examine the efficacy of a myocardial protection therapy in symptomatic participants with post-COVID inflammatory cardiac involvement determined by CMR. The aim of the intervention is to reduce the symptoms and inflammatory myocardial injury, improve exercise tolerance, and preclude the development of cardiac impairment., Competing Interests: Declaration of competing interests The authors declare that they have no competing interests. No generative AI tools were used in preparation of this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The role of qualitative research in response-shift research has not been well characterized. This scoping review summarizes the status of qualitative studies on response shift., Methods: A scoping review of the medical literature was done using the keywords "response shift" and "qualitative" or "interview." After excluding ineligible works, each retained article was rated by two independent raters according to the modified Critical Appraisal Skill Program (CASP) criteria. A synthesis of adjudicated review results further characterized the articles., Results: The search yielded 50 unique articles published from 1991 to 2023, 39 of which were retained after applying exclusion criteria. Most (69%) had the highest possible CASP score. Studies involved a broad range of patients by diagnosis or therapeutic context, caregivers, and healthcare professionals. While studies were often purely descriptive, many addressed components of response-shift theory or assumptions of response-shift methods. Study goals varied by design, time-focus (i.e., retrospective, present-focus or prospective), and by whether response-shift hypotheses were planned or post-hoc. The theoretical value added by the qualitative process involved examining the cognitive/emotional processes underlying quality-of-life ratings and response shifts. The methodological value added by the qualitative process facilitates understanding measurement error and non-responsiveness, and whether the methods used reflect the researchers' presumptions., Conclusion: The use of qualitative methods in response-shift research yields a nuanced understanding of what response-shift "looks like" in different patient populations, thereby helping to translate results more directly to clinical experience. Studies contributed to response-shift theory or methods in ways not easily captured by purely quantitative research., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction : Approximately 20% of Norwegian adolescents are frequently using Over-the-Counter Analgesics (OTCAs). The WHO emphasizes the need for research to identify the key determinants of health problems in adolescence. Thus, our aim was to describe and explore pain, stress, and Health-Related Quality of Life (HRQOL) in Norwegian adolescents and investigate possible associations upon high/low usage of OTCAs. Methods : This cross-sectional study included 315 adolescents (92 boys, 223 girls) with an average age of 14.1 years (13-15 years). All participants reported using OTCAs. Weekly usage was categorized as high and less than weekly as low. Using a validated questionnaire, we explored the following variables: pain, as measured using the Brief Pain Inventory, stress (Perceived Stress Questionnaire), and HRQOL (KIDSSCREEN-27). Binary logistic regression models were conducted using IBM SPSS Statistics (version 27). Results : Our descriptive findings reveal that high users of OTCAs reported higher pain intensity of 3.4 (SD = 1.9) and perceived stress of 0.38 (SD = 0.18) compared to low users, who reported 2.5 (SD = 1.9) and 0.32 (SD = 0.16), respectively. High OTCA users reported lower average scores than low users across all HRQOL subscales. Binary logistic regression revealed 30% higher odds for higher levels of pain intensity and 14 times higher odds of perceived stress associated with being a high user of OTCAs compared to a low user. Conclusions : Our study shows significantly higher odds for experiencing pain and stress among adolescents using OTCAs daily-to-weekly, compared to those seldom using such medicines. Health professionals should be aware of young people who have a high consumption of OTCAs and investigate whether the use is related to pain or stress. This might be important in designing a personalized and appropriate intervention. Parents and caregivers have an important responsibility in supporting adolescents' appropriate pain management. Longitudinal studies are needed to better explore predictive factors of OTCA use in adolescents, particularly in relation to psychological variables such as stress and quality of life.

Purpose: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score., Methods: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L)., Results: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001)., Conclusion: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities., Trail Registration Number: The cohort is registered at www., Clinicaltrials: gov under NCT04768998., (© 2024. The Author(s).)

Background: Identifying patients at risk of nontuberculous mycobacterial pulmonary disease (NTM-PD) is challenging. Delays in NTM-PD identification and management are associated with declining lung function and increased morbidity and mortality., Study Design and Methods: European NTM-PD experts (n=12) participated in a three-round modified Delphi process to score symptoms and comorbidities potentially associated with NTM-PD as reasons to test for nontuberculous mycobacteria., Results: Experts reached a consensus on the symptoms and comorbidities that should and should not prompt testing for nontuberculous mycobacteria. Requirements for testing were scored as high (mean ≥7), medium (mean ≥4-<7) or low (mean <4). Nontuberculous mycobacteria testing should be undertaken when multiple suggestive symptoms are present simultaneously in all patients except those with cancer (7.3-8.8), or when radiology is indicative of NTM-PD (≥8.9). Symptoms of persistent sputum production, recurrent respiratory infection and haemoptysis should prompt testing for nontuberculous mycobacteria, particularly in those with underlying respiratory diseases. Symptomatic patients with bronchiectasis or previous tuberculosis/NTM-PD or those being prescribed or undergoing long-term macrolide therapy for a respiratory condition should also be tested. Testing is not warranted in patients without an underlying respiratory disorder or in those without a history of respiratory disorders unless presenting with multiple symptoms., Conclusions: Assessing patients' risk of NTM-PD is challenging. This Delphi consensus process provides insight into symptoms and clinical characteristics that should prompt NTM-PD assessment. Timely testing and diagnosis would enable initiation of appropriate management., Competing Interests: Conflict of interest: M.R. Loebinger reports consultancy work and/or educational talks for 30 Technology, Armata, AN2 Therapeutics, AstraZeneca, Chiesi, Electromed, Insmed B.V., Parion, Recode, Savara and Zambon. Conflict of interest: S. Aliberti has received honoraria for speaker and consultancy services for GSK, INSMED Inc., Insmed Italy, Insmed Ireland Ltd, Zambon, AstraZeneca, CSL Behring GmbH, Menarini, MSD Italy S.r.l. and Thermofisher Scientific. Conflict of interest: C. Haworth reports consultancy work and/or educational talks for 30 Technology, Aradigm, CSL Behring, Chiesi, Gilead, Grifols, GSK, Insmed B.V., Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shionogi, Teva, Vertex and Zambon. Conflict of interest: M. Jankovic Makek has received honoraria for speaker and consultancy services from Insmed B.V., Biomerieux, MSD and Boeringher Ingelheim, and speaker services from Teva, Alkaloid, AstraZeneca and GSK. Conflict of interest: C. Lange has received honoraria for speaking at events supported by Insmed B.V., Gilead and Janssen. He has been a member of a scientific advisory board of Insmed B.V. and received honorarium for this function. Conflict of interest: N. Lorent has received speaker and consultancy services from Insmed B.V., GSK and AstraZeneca. She has been the coordinator of the Belgian NTM faculty meetings and a member of the scientific advisory board, both for Insmed. For these services, fees were paid to her institution (Katholieke Universiteit Leuven/University Hospitals Leuven). Conflict of interest: E. Polverino has received speaker and consultancy services from Insmed B.V., Chiesi, Grifols, GSK, Teva, Electromed, Pfizer, Moderna and Zambon. Conflict of interest: G. Rohde performed speaker and/or consultancy services for Insmed B.V. and Becton Dickinson, and received support for congress attendance from Otsuka. Conflict of interest: N. Veziris performed speaker and/or consultancy services for Insmed B.V. and Becton Dickinson, and is involved in an IMI-AMR project led by Janssen. Conflict of interest: D. Wagner participated in clinical trials supported by Insmed Inc. but otherwise has no conflict of interests to declare. Conflict of interest: J. van Ingen reports honoraria for speaking or advisory boards from Janssen Pharmaceuticals, Insmed B.V, Spero Therapeutics and Paratek., (Copyright ©The authors 2024.)

Background: The incidence of adverse events during endobronchial ultrasound is low. Nevertheless, it is unclear, whether patients with impaired pulmonary function have an increased risk of respiratory events during the intervention., Methods: A monocentric prospective observational study was performed at the Department of Respiratory Medicine, University Hospital Frankfurt/Main, Germany. Adult patients undergoing an endobronchial ultrasound examination with propofol-sedation were included. Pre-interventional screening included pulmonary function testing, laboratory tests and electrocardiogram. The occurrence of hypercapnia >55 mmHg or reduced oxygen saturation <85% was defined as a respiratory event was recorded and compared between patients with normal and impaired pulmonary function tests., Results: In total, 126 patients were included. Pulmonary function testing revealed a median FEV1 of 2.2 l (range 0.4-6.04l) and a predicted FEV1 of 79.5% (range 20-127.8%) respectively. The median FVC was 3.0 l (range 0.87-7.28l), the median predicted FVC was 82% (range 31.4-128.4%). In 72 examinations (60%) pCO 2 levels >55 mmHg were measured. Transient oxygen desaturation <85% occurred in 31 cases (25.8%). The Mann Whitney U-test showed a significantly lower FEV1 (% predicted value) in patients with respiratory events ( p = 0.007). ROC analysis identified a predicted FEV1 of 78.5% as the optimal cut-off with a sensitivity of 58% and a specificity of 71%. Using Z-score instead of predicted values, there was no significant association between a lower Z- score of FEV or FVC and hypercapnic or hypoxic events. However, both a lower absolute value of FEV1/FVC and a lower Z-score of the FEV1/FVC index were associated with the occurrence of respiratory events. In binary logistic regression analysis, we could not demonstrate any association with other relevant parameters (age, BMI, sedation dosage, sedation duration, or ASA-score)., Conclusions: An impaired forced expiratory volume is associated with the frequency of respiratory events during endobronchial ultrasound examination under propofol-sedation., Competing Interests: AG reports personal fees from Boehringer Ingelheim for lectures and GSK for advisory boards. GR reports personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Solvay, Takeda, Novartis, Pfizer, and Vertex for consultancy during advisory board meetings, from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Solvay, Takeda, Novartis, Pfizer, and Vertex for lectures including service on speakers' bureaus., (Copyright © 2024 Grünewaldt and Rohde.)

Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes. These molecular responses to dexamethasone were detected in circulating and pulmonary monocytes, and they were directly linked to survival. Monocyte single-cell RNA sequencing (scRNA-seq)-derived signatures were enriched in whole blood transcriptomes of patients with fatal outcome in two independent cohorts, highlighting the potential for identifying non-responders refractory to dexamethasone. Our findings link the effects of dexamethasone to specific immunomodulation and reversal of monocyte dysregulation, and they highlight the potential of single-cell omics for monitoring in vivo target engagement of immunomodulatory drugs and for patient stratification for precision medicine approaches., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While high-flow nasal cannulas (HFNCs) represent the standard of care in the intensive care unit for patients with severe hypoxemia, its use in homecare settings is uncommon despite its potential. The potential benefits and challenges of the high-flow nasal cannula (HFNC) in homecare settings compared to standard long-term oxygen via nasal low-flow therapy are unclear. Methods: We conducted a prospective monocentric feasibility study at the Department of Respiratory Medicine, University Hospital, Goethe University Frankfurt, Germany. Patients with interstitial lung disease or severe bronchiectasis (including cystic fibrosis) were enrolled into the study. The HFNC was introduced during hospitalization. The patients' compliance with home use advice and arterial blood gas results were evaluated at a 4-6-week follow-up. Results: A total of 12 patients were analyzed. HFNC initiation did not result in a significant improvement of the pO 2 /fiO 2 (p/f) ratio. Only 8 out of 12 (66.6%) patients used the HFNC at home after the initial in-hospital initiation. Only 7 of the total 12 patients were using the therapy at a follow-up 3-6 weeks after HFNC onset. Two patients died during the observation, resulting in a surveillance mortality rate of 16.7%. Conclusions: The feasibility data showed low adherence to the HFNC at home. The lack of any positive effect on the p/f ratio may be due to low airflow rates and overall mild hypoxemia compared to patients with severe respiratory failure in the ICU.

Background: Community-acquired pneumonia (CAP) is a major global cause of death and hospitalization. Bacteria or community-acquired viruses (CARVs) cause CAP. COVID-19 associated restrictions effectively reduced the circulation of CARVs., Objectives: The aim of this study was to analyze the proportion of CARVs in adult patients with CAP from mid-2020 to mid-2023. Specifically, we aimed to compare the rate of influenza virus, SARS-CoV-2, and RSV detections in patients aged 18-59 years and ≥60 years., Study Design: We analyze the proportion of 21 community-acquired respiratory viruses (CARVs) and three atypical bacteria (Bordetella pertussis, Legionella pneumophila, and Mycoplasma pneumoniae) in nasopharyngeal swab samples using molecular multiplex methods within the prospective, multicentre, multinational study of the German study Group CAPNETZ. We used stringent inclusion criteria throughout the study., Results: We identified CARVs in 364/1,388 (26.2 %) patients. In detail, we detected SARS-CoV-2 in 210/1,388 (15.1 %), rhino-/enterovirus in 64/1,388 (4.6 %), influenza virus in 23/1,388 (1.6 %) and RSV in 17/1,388 (1.2 %) of all patients. We detected RSV and influenza more frequently in patients ≥60 years, especially in 22/23 compared to the previous season. None of the atypical bacteria were detected., Conclusions: Beginning in 2023, we demonstrate a re-emergence of CARVs in CAP patients. Effective vaccines or specific antiviral therapies for more than two thirds of the detected viral infections are currently available. High detection rates of vaccine-preventable viruses in older age groups support targeted vaccination campaigns., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: This study assessed the frequency, clinical significance, and risk factors for Herpes simplex virus (HSV) reactivation in immunocompetent patients with community-acquired pneumonia (CAP)., Methods: The study included adult CAP-patients who were enrolled in the CAPNETZ study between 2007 and 2017 and had a residual sputum sample available for analysis. In addition to routine diagnostics, sputum and blood samples were tested for HSV-1/2 using PCR. Demographics, comorbidities, and CRB-65 score were compared between HSV-positive and negative patients using Fisher exact or Mann Whitney test. Logistic regression analyses investigated the influence of HSV reactivation on a modified hospital recovery scale (HRS) until day 7, divided into 3 categories (no oxygen therapy, oxygen therapy, ICU admission or death)., Results: Among 245 patients, HSV-1 and HSV-2 were detected in 30 patients (12.2%, 95%CI 8.7-16.9) and 0 patients, respectively. All HSV-positive patients were hospitalized, had a CRB-65 severity score of 0-2 and survived the first 28 day. In the HSV-positive group, patients had a non-significantly higher median age (70.5 versus 66 years) and a higher rate of oncological comorbidities (16.7% versus 8.8%) compared to the HSV-negative group. Distribution of co-pathogens and outcome parameters did not significantly differ between both groups. In a multivariate logistic regression model, age (AOR 1.029, p = 0.012) and CRB-65 score (AOR 1.709, p = 0.048), but not HSV-1 as single or co-pathogen were independently associated with higher HRS., Conclusion: Our study suggests that HSV-1 reactivation is common in CAP but might not be associated with specific risk factors or a complicated disease course., (© 2024. The Author(s).)

Purpose: The present study examines how the coronavirus disease 2019 (COVID-19) experience affected values and priorities., Methods: This cross-sectional study collected data between January and April 2023, from 1,197 individuals who are chronically ill or part of a general population sample. Using open-ended prompts and closed-ended questions, we investigated individuals' perceptions about COVID-19-induced changes in what quality of life means to them, what and who are important, life focus, and changes in norms and stressors. Data analyses included content and psychometric analysis, leading to latent profile analysis (LPA) to characterize distinct groups, and analysis of variance and chi-squared to compare profile groups' demographic characteristics., Results: About 75% of the study sample noted changes in values and/or priorities, particularly in the greater prominence of family and friends. LPA yielded a four-profile model that fit the data well. Profile 1 (Index group; 64% of the sample) had relatively average scores on all indicators. Profile 2 (COVID-Specific Health & Resignation to Isolation Attributable to COVID-19; 5%) represented COVID-19-specific preventive health behaviors along with noting the requisite isolation and disengagement entailed in the social distancing necessary for COVID-19 prevention. Profile 3 (High Stress, Low Trust; 25%) represented high multi-domain stress, with the most elevated scores both on focusing on being true to themselves and perceiving people to be increasingly uncivil. Profile 4 (Active in the World, Low Trust; 6%) was focused on returning to work and finding greater meaning in their activities. These groups differed on race, marital status, difficulty paying bills, employment status, number of times they reported having had COVID-19, number of COVID-19 boosters received, whether they had Long COVID, age, BMI, and number of comorbidities., Conclusion: Three years after the beginning of the worldwide COVID-19 pandemic, its subjective impact is notable on most study participants' conceptualization of quality of life, priorities, perspectives on social norms, and perceived stressors. The four profile groups reflected distinct ways of dealing with the long-term effects of COVID-19., Competing Interests: CE, KB, AW were employed by DeltaQuest Foundation, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schwartz, Borowiec, Waldman, Sutherland, Contreras, Abatan, Huang, Rohde, Rapkin and Skolasky.)

Background: Stress impacts healthy behaviours and may influence life and health-related quality of life (HRQOL). A stressful event occurred when the COVID-19 pandemic hit in March 2020. The present study aims to explore possible gender differences in stress, psychosocial factors (self-efficacy, self-esteem, loneliness), pain, HL, and HRQOL in parents of adolescents one year into the COVID-19 pandemic, and to explore possible associations between gender, demographic and psychosocial factors, pain, HL, and HRQOL., Methods: Parents of adolescents aged 16-17 took part in the study from January to February 2021, when the COVID-19 pandemic was ongoing. Data on socio-demographics, stress, self-efficacy, self-esteem, pain, HL, loneliness, and HRQOL were collected. HRQOL was assessed using RAND-36., Results: Among the 320 parents from the general population, the mean age was 47.6 (standard deviation (SD) = 4.6) years, 81% were mothers, 79% were married or cohabiting, 81% had a university degree, and the majority worked full time (78%) or part time (13%). The average pain score was low, 0.48 (95% CI [0.43-0.54]). However, 50% of the parents reported persistent pain and more mothers reported persistent pain compared to fathers (53% vs. 37%). The parents' mean (SD) score for RAND-36 was 52.1 (95% CI [51.2-53.0]) for the physical component summary (PCS) score and 51.0 (95% CI [50.0-52.1]) for the mental component summary (MCS) score. Mothers reported significantly lower scores for all the eight RAND-36 domains and the PCS and MCS scores. Adjusting for gender, age, living condition, education, pain, HL, self-efficacy and loneliness, we revealed no associations between stress and RAND-36-PCS. University education of four years or more was positively associated (B = 3.29, 95% CI: [0.78-5.80]) with RAND-36-PCS, while persistent pain was negatively associated (B = -7.13, CI: [-9.20- -5.06]). We identified a strong negative association between RAND-36-MCS and stress (B = -43.11, CI: [-48.83- -37.38]) and a positive association with older age (B = 0.21, CI: [ 0.04, 0.39)]., Conclusion: One year into the COVID-19 pandemic, we identified a strong negative association between stress and mental HRQOL, while pain was strongly negatively associated with physical HRQOL., (© 2024. The Author(s).)

Introduction: Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany., Methods: Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2 years and adults ≥ 60 years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities)., Results: Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60 years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44 year old persons (five to sixfold higher) than in ≥ 75 year old persons (two to threefold higher)., Conclusions: This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60 years and among adults with underlying risk factors., (© 2024. Pfizer.)