Berg RM, Plovsing RR, Ronit A, Bailey DM, Holstein-Rathlou NH, Møller K. Disassociation of static and dynamic cerebral autoregulatory performance in healthy volunteers after lipopolysaccharide infusion and in patients with sepsis.

Abdominal obesity was associated with proaterogenic metabolic factors including elevated LDL-C, hypertension, and hypertriglyceridemia and remains a distinct HIV-related phenotype, particularly among older PLWH. Effective interventions to reduce the apparent detrimental impact on cardiovascular risk from this phenotype are needed.

Background Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. Objective Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). Methods We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. Results Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and T H 17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. Conclusion COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.

BackgroundModern combination antiretroviral therapy (cART) has improved survival for people living with HIV (PLWHIV). Non-AIDS comorbidities have replaced opportunistic infections as leading causes of mortality and morbidity, and are becoming a key health concern as this population continues to age. The aim of this study is to estimate the prevalence and incidence of non-AIDS comorbidity among PLWHIV in Denmark in the cART era and to determine risk factors contributing to the pathogenesis. The study primarily targets cardiovascular, respiratory, and hepatic non-AIDS comorbidity.Methods/designThe Copenhagen comorbidity in HIV-infection (COCOMO) study is an observational, longitudinal cohort study. The study was initiated in 2015 and recruitment is ongoing with the aim of including 1500 PLWHIV from the Copenhagen area. Follow-up examinations after 2 and 10 years are planned. Uninfected controls are derived from the Copenhagen General Population Study (CGPS), a cohort study including 100,000 uninfected participants from the same geographical region. Physiological and biological measures including blood pressure, ankle-brachial index, electrocardiogram, spirometry, exhaled nitric oxide, transient elastography of the liver, computed tomography (CT) angiography of the heart, unenhanced CT of the chest and upper abdomen, and a number of routine biochemical analysis are uniformly collected in participants from the COCOMO study and the CGPS. Plasma, serum, buffy coat, peripheral blood mononuclear cells (PBMC), urine, and stool samples are collected in a biobank for future studies. Data will be updated through periodical linking to national databases.DiscussionAs life expectancy for PLWHIV improves, it is essential to study long-term impact of HIV and cART. We anticipate that findings from this cohort study will increase knowledge on non-AIDS comorbidity in PLWHIV and identify targets for future interventional trials. Recognizing the demographic, clinical and pathophysiological characteristics of comorbidity in PLWHIV may help inform development of new guidelines and enable us to move forward to a more personalized HIV care.Trial registrationClinicalTrials.gov: NCT02382822.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-2026-9) contains supplementary material, which is available to authorized users.

NCT02382822.

Objective: We studied the association of plasma albumin with cardiovascular disease (CVD) and explored potential mechanisms behind the association in the CGPS (Copenhagen General Population Study). We also performed a meta-analysis to summarize the association between plasma albumin and CVD in individuals without preexisting CVD. Approach and Results: We included 100 520 individuals without prior CVD with 8247 incident CVD events developed during a median follow-up of 8.5 years. Rates of CVD outcomes were calculated using Cox regression and Fine and Gray competing-risks regression. The association of plasma albumin and CVD was approximately linear and confounder adjustment had little influence on the effect estimates, except for some attenuation after CRP (C-reactive protein) adjustment. In analyses according to subtypes of CVD events, the hazard ratios for each 10 g/L lower plasma albumin were 1.17 (95% CI, 1.08–1.28) for ischemic heart disease, 1.25 (95% CI, 1.09–1.43) for myocardial infarction, 1.37 (95% CI, 1.21–1.54) for any stroke, and 1.46 (95% CI, 1.28–1.68) for ischemic stroke. In the meta-analysis, we combined estimates from prospective and nested case-control studies investigating the association of plasma albumin with CVD. The meta-analysis included 14 studies with 150 652 individuals (12 studies reported events totaling 11 872). The risk ratio for a CVD event per 10 g/L lower plasma albumin was 1.96 (95% CI, 1.43–2.68) in previous studies and 1.85 (95% CI, 1.39–2.47) including our study with 57% weight in the meta-analysis. Exploratory analyses of the mechanism of the association indicated that it was probably not due to fatty acid binding but may be due to the regulation of plasma albumin by inflammation. Conclusions: There is a robust, independent association of low plasma albumin with CVD, partly explained by plasma albumin as a negative acute-phase reactant. Clinical Trial Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=95796 . Unique identifier: CRD42018095796

The aim of this study was to examine regulatory T cells (Tregs) in peripheral blood and liver tissue in patients with chronic hepatitis C virus (HCV) mono‐infection and in patients with HIV/HCV co‐infection. In a cross‐sectional study were included 51 patients with chronic HCV infection, 24 patients with HIV/HCV co‐infection and 24 healthy individuals. CD4+ and CD8+ Tregs were determined using flow cytometry. Fibrosis was examined by transient elastography. Inflammation, fibrosis and Tregs were determined in liver biopsies from 12 patients. Increased frequency of CD4+ and CD8+ Tregs was found in HIV/HCV co‐infected patients [median: 6.4% (IQR: 5.7–6.9) and 1.0% (0.7–1.2), respectively] compared to HCV mono‐infected patients [5.6% (4.2–6.3), P = 0.01 and 0.5% (0.3–0.7), P < 0.001, respectively]. Furthermore, HCV mono‐infected patients had increased frequencies of Tregs compared with healthy controls (P < 0.05). However, no associations between the frequency of Tregs and fibrosis were found. Furthermore, characterization of CD4+ Tregs using CD45RA demonstrated a higher frequency of activated Tregs in both HCV mono‐infected and HIV/HCV co‐infected patients compared with healthy controls. Finally, number of intrahepatic Tregs was associated with both peripheral CD8+ Tregs and intrahepatic inflammation. In conclusion, HCV mono‐infected patients and particularly HIV/HCV co‐infected patients have increased the frequency of CD4+ and CD8+ Tregs compared with healthy controls. Furthermore, CD4+ Tregs in infected patients displayed an active phenotype. Tregs were not associated with fibrosis, but a positive correlation between intrahepatic Tregs and inflammation was found. Taken together, these results suggest a role for Tregs in the pathogenesis of chronic HCV infection.

HIV-infected patients on cART with undetectable viral load had an increased level of inflammation and immune activation. However, intact cognitive function was found, and only weak correlations were found between cognitive function and markers of inflammation and immune activation, indicating that peripheral inflammation and immune activation are not major drivers of cognitive decay in HIV-infected patients.