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Abstract Community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) often result in sudden and persistent reduction in health-related quality of life (HRQoL), which may be alleviated with palliative care. Among individuals with COPD, we aimed to investigate potential associations between HRQoL at admission with CAP and the risk of re-hospitalization and mortality and potential associations between specific HRQoL domains and CAP treatment outcomes. HRQoL was assessed at admission and the participants were grouped into tertiles based on the HRQoL utility index and specific domains. The results revealed that participants in the middle and highest tertiles of HRQoL had a lower 90-day re-hospitalization risk compared to those in the lowest tertile, whereas no differences in re-hospitalization risk were observed 30 and 180 days after discharge. Almost one in four had severe pain or discomfort at admission and the domain pain or discomfort emerged as a predictor of re-hospitalization. In addition, participants in the middle and highest tertiles had lower risk of 180-day mortality compared to those in the lowest, while no differences were observed in 30-day or 90-day mortality risk. An increased focus on in-hospital palliative care could alleviate the pain and discomfort reported by many participants with potential to reduce re-hospitalization rates.

Abstract Bacterial colonization is mediated by fimbriae, which are thin hair-like appendages dispersed from the bacterial surface. The aggregative adherence fimbriae from enteroaggregative E. coli are secreted through the outer membrane and consist of polymerized minor and major pilin subunits. Currently, the understanding of the structural morphology and the role of the minor pilin subunit in the polymerized fimbriae are limited. In this study we use small-angle X-ray scattering to reveal the structural morphology of purified fimbriae in solution. We show that the aggregative fimbriae are compact arrangements of subunit proteins Agg5A + Agg3B which are assembled pairwise on a flexible string rather than extended in relatively straight filaments. Absence of the minor subunit leads to less compact fimbriae, but did not affect the length. The study provides novel insights into the structural morphology and assembly of the aggregative adherence fimbriae. Our study suggests that the minor subunit is not located at the tip of the fimbriae as previously speculated but has a higher importance for the assembled fimbriae by affecting the global structure.

IntroductionDiabetes is associated with dysregulated immune function and impaired cytokine release, while transient acute hyperglycaemia has been shown to enhance inflammatory cytokine release in preclinical studies. Although diabetes and acute hyperglycaemia are common among patients with community-acquired pneumonia (CAP), the impact of chronic, acute, and acute-on-chronic hyperglycaemia on the host response within this population remains poorly understood. This study investigated whether chronic, acute, and acute-on- chronic hyperglycaemia are associated with distinct mediators of inflammatory, endothelial, and angiogenic host response pathways in patients with CAP.MethodsIn a cross-sectional study of 555 patients with CAP, HbA1c, admission plasma (p)-glucose, and the glycaemic gap (admission p-glucose minus HbA1c- derived average p-glucose) were employed as measures of chronic, acute, and acute-on-chronic hyperglycaemia, respectively. Linear regression was used to model the associations between the hyperglycaemia measures and 47 proteins involved in inflammation, endothelial activation, and angiogenesis measured at admission. The models were adjusted for age, sex, CAP severity, pathogen, immunosuppression, comorbidity, and body mass index. Adjustments for multiple testing were performed with a false discovery rate threshold of less than 0.05.ResultsThe analyses showed that HbA1c levels were positively associated with IL-8, IL-15, IL-17A/F, IL-1RA, sFlt-1, and VEGF-C. Admission plasma glucose was also positively associated with these proteins and GM-CSF. The glycaemic gap was positively associated with IL-8, IL-15, IL-17A/F, IL-2, and VEGF-C.ConclusionIn conclusion, chronic, acute, and acute-on-chronic hyperglycaemia were positively associated with similar host response mediators. Furthermore, acute and acute-on-chronic hyperglycaemia had unique associations with the inflammatory pathways involving GM-CSF and IL-2, respectively.

BackgroundAdiponectin is secreted by adipocytes and is inversely associated with obesity. Given the association between low body mass index (BMI) and higher mortality risk after community-acquired pneumonia (CAP), we hypothesized that high adiponectin levels are associated with a higher risk of adverse clinical outcomes in patients with CAP.MethodsIn a prospective cohort study of 502 patients hospitalized with CAP, adiponectin was measured in serum at admission. The associations between adiponectin and clinical outcomes were estimated with logistic regression analyses adjusted for age, sex, and measures of obesity (BMI, waist circumference or body fat percentage).ResultsAdiponectin was associated with higher 90-day mortality for each 1 μg/mL increase [OR 1.02, 95% CI (1.00, 1.04), p = 0.048] independent of age and sex. Likewise, adiponectin was associated with a higher risk of 90-day readmission for each 1 μg/mL increase [OR 1.02, 95% CI (1.01, 1.04), p = 0.007] independent of age and sex. The association between adiponectin and 90-day mortality disappeared, while the association with 90-day readmission remained after adjusting for adiposity.ConclusionAdiponectin was positively associated with mortality and readmission. The association with mortality depended on low body fat, whereas the association with readmission risk was independent of obesity.

Abstract Introduction Despite improvements in medical science and public health, mortality of community-acquired pneumonia (CAP) has barely changed throughout the last 15 years. The current SARS-CoV-2 pandemic has once again highlighted the central importance of acute respiratory infections to human health. The “network of excellence on Community Acquired Pneumonia” (CAPNETZ) hosts the most comprehensive CAP database worldwide including more than 12,000 patients. CAPNETZ connects physicians, microbiologists, virologists, epidemiologists, and computer scientists throughout Europe. Our aim was to summarize the current situation in CAP research and identify the most pressing unmet needs in CAP research. Methods To identify areas of future CAP research, CAPNETZ followed a multiple-step procedure. First, research members of CAPNETZ were individually asked to identify unmet needs. Second, the top 100 experts in the field of CAP research were asked for their insights about the unmet needs in CAP (Delphi approach). Third, internal and external experts discussed unmet needs in CAP at a scientific retreat. Results Eleven topics for future CAP research were identified: detection of causative pathogens, next generation sequencing for antimicrobial treatment guidance, imaging diagnostics, biomarkers, risk stratification, antiviral and antibiotic treatment, adjunctive therapy, vaccines and prevention, systemic and local immune response, comorbidities, and long-term cardio-vascular complications. Conclusion Pneumonia is a complex disease where the interplay between pathogens, immune system and comorbidities not only impose an immediate risk of mortality but also affect the patients’ risk of developing comorbidities as well as mortality for up to a decade after pneumonia has resolved. Our review of unmet needs in CAP research has shown that there are still major shortcomings in our knowledge of CAP.

Background: A basic paradigm of human infection is that acute bacterial disease is caused by fast growing planktonic bacteria while chronic infections are caused by slow-growing, aggregated bacteria, a phenomenon known as a biofilm. For lung infections, this paradigm has been thought to be supported by observations of how bacteria proliferate in well-established growth media in the laboratory-the gold standard of microbiology.Objective: To investigate the bacterial architecture in sputum from patients with acute and chronic lung infections.Methods: Advanced imaging technology was used for quantification and direct comparison of infection types on fresh sputum samples, thereby directly testing the acute versus chronic paradigm.Results: In this study, we compared the bacterial lifestyle (planktonic or biofilm), growth rate and inflammatory response of bacteria in freshly collected sputum (n=43) from patient groups presenting with acute or chronic lung infections. We found that both acute and chronic lung infections are dominated by biofilms (aggregates of bacteria within an extracellular matrix), although planktonic cells were observed in both sample types. Bacteria grew faster in sputum from acute infections, but these fast-growing bacteria were enriched in biofilms similar to the architecture thought to be reserved for chronic infections. Cellular inflammation in the lungs was also similar across patient groups, but systemic inflammatory markers were only elevated in acute infections.Conclusions: Our findings indicate that the current paradigm of equating planktonic with acute and biofilm with chronic infection needs to be revisited as the difference lies primarily in metabolic rates, not bacterial architecture. [ABSTRACT FROM AUTHOR]