Search

Numerous studies have shown that the aetiology of community-acquired pneumonia (CAP) varies considerably among different healthcare settings. Because empiric therapies for CAP should cover the major pathogens, reports examining CAP aetiology are considered crucial, particularly in Nordic countries that still rely on penicillin G or V treatments for most patients with CAP. The primary objective of our study was to report CAP aetiology. Secondary objectives included the estimation of positivity rates for different tests and the odds of a positive test for various subgroups. In this cohort study, microbiological data were analysed for an overall cohort (variable degree of microbiological testing) and for a subgroup that was tested for both, bacteria, viruses and fungi, using routine methods (defined as extensive testing). The overall cohort comprised 2,264 patients, including 315 who were extensively tested. Bacterial and viral monoinfections were the most commonly identified infections. The dominant pathogen identified among extensively tested patients was Haemophilus influenzae (23.7%), followed by Streptococcus pneumoniae (20.6%). The tests with the highest positivity rates were sputum cultures (34.7%) and viral polymerase chain reaction (PCR, 24.4%). The odds of achieving a microbiological diagnosis increased significantly when extensive testing was performed compared with selective testing (OR 2.86, 95% CI 2.24–3.64). Our study indicated that H. influenzae is the dominant responsible pathogen for bacterial CAP in Denmark. Thus, we believe that the current treatment recommendations that encourage the use of penicillin G or V for the majority of patients with CAP need to be revised. [ABSTRACT FROM AUTHOR]

This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3+CD4+CD25+CD127low), naive Tregs (CD3+CD4+CD25+CD45RA+) and activation markers (CD38+human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4+ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART ( P < 0·001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV-infected patients ( P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4+ cells ( P = 0·038). In summary, Treg levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV-infection. [ABSTRACT FROM AUTHOR]

This study determines levels of regulatory T cells (Tregs), naive Tregs, immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive Tregs may represent recent thymic emigrant Tregs. HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of Tregs (CD3+CD4+CD25+CD127low), naive Tregs (CD3+CD4+CD25+CD45RA+) and activation markers (CD38+human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (TREC) content in CD4+ cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of Tregs were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART ( P < 0·001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive Tregs were elevated significantly in HIV-infected patients ( P < 0·001) and were associated with thymic output measured as the TREC frequency in CD4+ cells ( P = 0·038). In summary, Treg levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive Tregs may contribute to higher Treg levels in HIV-infection. [ABSTRACT FROM AUTHOR]

Introduction: Halm's clinical stability criteria have long guided antibiotic treatment and hospital discharge decisions for patients hospitalised with community-acquired pneumonia (CAP). Originally introduced in 1998, these criteria were established based on a relatively small and select patient population. Consequently, our study aims to reassess their applicability in management of CAP in a contemporary real-world setting., Methods: This cohort study included 2918 immunocompetent patients hospitalised with CAP from three hospitals in Denmark between 2017-2020. The primary outcome was time to achieve clinical stability as defined by Halm's criteria. Additionally, we examined recurrence of clinical instability and severe complications. Cumulative incidence function or Kaplan-Meier survival curves were used to analyse these outcomes, considering competing risks., Findings: The study population primarily comprised elderly individuals (median age: 75 years) with significant comorbidities. The median time to clinical stability according to Halm's criteria was 4 days, with one-fifth experiencing recurrence of instability after early clinical response (stability within 3 days). Severe complications within 30 days mainly comprised mortality, with rates of 5.1% (64/1257) overall in those with early clinical response, 1.7% (18/1045) in the subgroup without do-not-resuscitate orders, and 17.3% (276/1595) among the rest., Interpretation: Halm's clinical stability criteria effectively classify CAP patients with different disease courses, yet achieving stability required more time in this aging population with substantial comorbidities and more severe disease. Early clinical response indicates reduced risk of complications, especially in those without do-not-resuscitate orders., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: We aimed to evaluate post-COVID-19 fatigue, change in functional capacity and health-related quality of life (HRQoL) eight months after discharge from hospital due to COVID-19., Methods: A total of 83 patients (35 women) admitted to the Copenhagen University Hospital - North Zealand Hospital, Denmark, for COVID-19 during the period from March to June 2020 were evaluated eight months after discharge using validated questionnaires quantifying fatigue, HRQoL and post-COVID-19 functional status. Follow-up data were correlated with measures of pre-COVID-19 status (anthropometrics, comorbidities) and measures of severity of the acute infection., Results: A total of 22 (65%) women and 12 (26%) men reported excessive fatigue. In all, 20 women (67%) and 17 men (37%) reported decreased physical function. Female sex was associated with fatigue. Loss of physical function was associated with pre-COVID-19 presence of heart disease and absence of lung disease. Severity of the acute COVID-19 infection was not associated with fatigue or change in functional status. Fatigue and functional status were correlated with both generic HRQoL and lung disease-specific HRQoL., Conclusions: Female sex was associated with a higher risk of fatigue eight months after hospitalisation with COVID-19 infection. Regarding loss of functional capacity after COVID-19, we found an apparently protective effect of pre-COVID-19 lung disease. Our findings underscore the urgent need for further research and the importance of evaluating those recovering from COVID-19 for symptoms of excessive fatigue and change in functional capacity irrespective of the severity of the initial infection., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

This thesis is based on seven previously published articles. The work was performed during my employment at The Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, as a scholarship student from 2000-2001 and as a research assistant in the period 2004-2010. HIV-infection is characterized by CD4+ cell depletion. The differences between patients in the degree of CD4+ cell recovery upon treatment with highly active antiretroviral therapy (HAART) may in part be due to differences in the supply of naïve CD4+ cells from the thymus. The thymus atrophies with increasing age for which reason the adult thymus was previously assumed to be without function. The aim of these investigations was to examine the role of the thymus in different aspects of HIV-infection: In adult HIV-infected patients, during HIV-positive pregnancy, and in HIV-exposed uninfected (HIV-EU) children born to HIV-infected mothers. Thymic size and output were determined in 25 adult HIV-infected patients receiving HAART and in 10 controls. Larger thymic size was associated with higher CD4 counts and higher thymic output. Furthermore, patients with abundant thymic tissue seemed to have broader immunological repertoires, compared with patients with minimal thymic tissue. The study supports the mounting evidence of a contribution by the adult thymus to immune reconstitution in HIV-infection. In a follow-up study conducted till 5 years of HAART, the importance of the thymus to the rate of cellular restoration was found to primarily lie within the first two years of HAART. The effect of recombinant human growth hormone (rhGH) was then investigated in a randomized, double-blinded placebo controlled trial in 46 adult HIV-infected patients on HAART. Daily treatment with a low dose of rhGH of 0.7mg for 40 weeks stimulated thymopoiesis as expressed by thymic size, density, and output strongly supporting the assumption that rhGH possesses the potential to stimulate the ageing thymus, holding promise as a future means to complete CD4 restoration and renew the TCR repertoire in patients who respond insufficiently to HAART. Apart from naïve T cells, regulatory T cells (Tregs) are developed in the thymus. Tregs play a critical role in peripheral tolerance and suppress inappropriate immune activation such as induced by HIV. We studied levels of Tregs in adult HIV-infected patients with known thymic output. Our studies demonstrate increased levels of Tregs in HIV-infected patients despite long-term treatment with HAART, suppressed viral loads, and normalized CD4 counts and immune activation suggesting that Tregs expand irreversibly in HIV-infection independently of viral load, CD4 depletion or level of immune activation. Our data further suggest that elevated levels of Tregs in HIV-infected adults may in part be due to increased thymic production of naive Tregs. During pregnancy, establishing fetal-maternal tolerance is essential to pregnancy success. In a prospective study on HIV-positive and HIV-negative pregnant women we found alterations in thymic output and Treg levels in HIV-negative pregnant women compatible with such an establishment. HIV-infected women, however, displayed different immunological profiles from HIV-negative women, and this immune unbalance may interfere with the prevention of fetal rejection and may partly explain the increased risk of abortion in HIV-infected women. We finally examined thymic function in 20 HIV-EU children at 15 months of age. The thymus was reduced in size in HIV-EU children compared with children born to HIV-negative mothers, but no evidence of impaired thymic function, immune regulation, or antibody vaccination response was detected, suggesting that no qualitative immune deficits persist in HIV-EU children beyond infancy. In conclusion, the thymus is functional in adults, and it contributes to immunological recovery in HIV-infected patients primarily during the first two years of HAART. Treg levels are increased in HIV-infected patients independent of viral load, CD4 cell depletion or level of immune activation, and this may be due to increased thymic production of naïve Tregs. Alteration of thymic function in adults is possible, both by stimulation of thymopoiesis with rhGH therapy and as a result of pregnancy. Finally, immunological abnormalities detected in HIV-EU infants are recovered at 15 months of age, and even if diminished in size, thymic function is normalized at this age.