To estimate life expectancy of people with HIV (PWH) and describe causes of death.
Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019.
We calculated life ...expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models.
Life expectancy increased from 65.8 95% confidence interval (CI) 65.0-66.6 in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men general population comparators (GPC): 79.1 and 81.2 years, respectively and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/μl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/μl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU.
Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.
Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) ...with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.
Tocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. We investigated the ...association between receipt of tocilizumab and mortality in a large cohort of hospitalized patients.
In this cohort study of patients hospitalized with COVID-19 in Spain, the primary outcome was time to death and the secondary outcome time to intensive care unit (ICU) admission or death. We used inverse probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between receipt of tocilizumab and outcome.
Data from 1229 patients were analysed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between receipt of tocilizumab and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16–0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19–0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings.
In this large observational study, tocilizumab was associated with a lower risk of death or ICU admission or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials.
Despite the scientific and human efforts to understand COVID-19, there are questions still unanswered. Variations in the metabolic reaction to SARS-CoV-2 infection could explain the striking ...differences in the susceptibility to infection and the risk of severe disease. Here, we used untargeted metabolomics to examine novel metabolic pathways related to SARS-CoV-2 susceptibility and COVID-19 clinical severity using capillary electrophoresis coupled to a time-of-flight mass spectrometer (CE-TOF-MS) in plasma samples. We included 27 patients with confirmed COVID-19 and 29 healthcare workers heavily exposed to SARS-CoV-2 but with low susceptibility to infection (“nonsusceptible”). We found a total of 42 metabolites of SARS-CoV-2 susceptibility or COVID-19 clinical severity. We report the discovery of new plasma biomarkers for COVID-19 that provide mechanistic explanations for the clinical consequences of SARS-CoV-2, including mitochondrial and liver dysfunction as a consequence of hypoxemia (citrulline, citric acid, and 3-aminoisobutyric acid (BAIBA)), energy production and amino acid catabolism (phenylalanine and histidine), and endothelial dysfunction and thrombosis (citrulline, asymmetric dimethylarginine (ADMA), and 2-aminobutyric acid (2-AB)), and we found interconnections between these pathways. In summary, in this first report several metabolic pathways implicated in SARS-CoV-2 susceptibility and COVID-19 clinical progression were found by CE-MS based metabolomics that could be developed as biomarkers of COVID-19.
Abstract
In the last decade, studies in persons with HIV (PWH) on antiretroviral therapy (ART) have shed light on the significance of persistently high CD8 counts and low CD4/CD8 ratios. A low ...CD4/CD8 ratio reflects increased immune activation and is associated with an increased risk of severe non-AIDS events. As a result, many clinicians now believe that the CD4/CD8 ratio can help in HIV monitoring, and many researchers now report it as an efficacy marker in interventional studies. However, the topic is more complex. Recent studies have not yielded unanimous conclusions on the ability of the CD4/CD8 ratio to predict adverse outcomes, and only some clinical guidelines recommend monitoring it. Knowledge gaps remain on the best cutoff points, associated clinical events, effects of treatments, and how the CD4/CD8 ratio could improve decision making in the clinic. Here, we critically review the literature, identify knowledge gaps, and discuss the role of the CD4/CD8 ratio as a marker for HIV monitoring.
Cumulative evidence has seeded the idea that the CD4/CD8 ratio could help monitor HIV. However, knowledge gaps exist. Here, we critically review the literature and discuss the role of the CD4/CD8 ratio in the follow-up of persons with HIV.
Graphical Abstract
Graphical Abstract
To evaluate Red blood cell distribution width (RDW) as a sepsis prognostic biomarker.
203 septic patients admitted to the ICU. Analysis of RDW dynamics, hospital mortality discrimination ability and ...the added value when incorporated to the SOFA, LODS, SAPS-II and APACHE-II scores using the AUC-ROC.
Non-survivors presented higher RDW values during the first week after ICU admission (p = 0.048). Only SOFA and RDW were independently associated with mortality when adjusted by Charlson, immunosuppression, nosocomial infection, NEWS2, SAPS-II, septic shock and haemoglobin (p < 0.05). After adjustment, AUC-ROC was 0.827, 0.822, 0.824, 0.834 and 0.812 for each model including admission, 24, 48 and 72-h and 7-days RDW, respectively. When added to the scores, 24-h RDW and admission RDW improved their discrimination ability (SOFA AUC-ROC = 0.772 vs 0.812 SOFA + admission RDW, p = 0.041; LODS AUC-ROC = 0.687 vs 0.710, p = 0.002; SAPS-II AUC-ROC = 0.734 vs 0.785, p = 0.021; APACHE-II AUC-ROC = 0.672 vs 0.755, p = 0.003). Admission RDW with SOFA presented the better discrimination ability for mortality.
RDW is an independent prognostic marker of death in septic patients admitted in the ICU that improves SOFA, LODS, APACHE-II and SAPS-II discrimination ability. This parameter could be incorporated to the prognostic scores as a marker of systemic dysfunction and dysregulated inflammatory response.
•During the first week after ICU admission, non-survivors septic patients presented higher RDW.•Along with SOFA, RDW was the only independently factor associated with mortality after adjustment.•When added to the prognostic scores, 24-hoursh RDW and mostly admission RDW improved their discrimination ability.•RDW is an available parameter that reflects the dysregulated inflammatory response and systemic dysfunction.
Modern ART has now achieved the goal of maintaining HIV RNA suppression with minimum drug-related toxicities. Indeed, in high-income settings, the main health issues in adult people living with HIV ...(PLWH) today are diseases not directly associated with HIV. These conditions have become the central topic of discussion in HIV clinical forums. While they are common in the general population and typically associated with the aging process, their burden, diagnosis, clinical course and subsequent therapy alongside treated HIV infection exhibit specific features. Currently, we are confronted with the formidable challenge of normalizing the health of PLWH and creating a more comprehensive HIV management program. Here, we compile the opinions of a joint effort of 30 HIV specialists who reviewed the literature and debated the latest major challenges in the field of HIV-associated comorbidities and delineated future strategies to fully normalize health in HIV. Six key questions are answered and developed, such as the relevance of comorbidities in the management of HIV-infected patients, their drivers, management, prevention strategies, and possible evolution in the future.
The optoelectronic properties of several Ag
2
S/graphene and FeS
2
/graphene nanostructures are examined through density functional theory calculations including dispersion forces. First, we analyzed ...the electronic structure of Ag
2
S and FeS
2
nanocluster models, as prototypes of quantum dots, focusing on the electronic structure and absorption spectra. In the case of FeS
2
nanoparticle, both ferro- and antiferromagnetic arrangements were considered. Then, Ag
2
S and FeS
2
nanoclusters were adsorbed on top of both graphite and graphene slab models to study the stability of the systems as well as the effect of the nanocluster–surface interaction in the electronic structure, including an insight into the electron injection mechanisms in these systems. Finally, interface models, consisting of Ag
2
S or FeS
2
thin films adsorbed on a graphene layer, were built and their optoelectronic properties examined. Overall, the results obtained in this work, support the suitability of these systems for their usage in solar cells.
Graphical abstract
Background
To study the differences between shallow and residual periodontal pockets in patients with periodontitis (Stages III and IV) after non‐surgical periodontal treatment.
Methods
Twenty ...patients diagnosed of periodontitis who were scheduled for periodontal surgery were included. In each patient, a palatal shallow site (≤3 mm) and a residual site (≥5 mm) were selected and GCF samples were processed by Luminex® analysis to determine the concentrations of interleukins (IL‐1β, IL‐6, IL‐10, and IL‐17a). During the periodontal surgery gingival biopsies were collected and processed for histo‐morphometric and immunohistochemical evaluation to determine the extent of connective tissue inflammatory infiltrate (CTII) using the following markers (CD4, CD5, CD8, CD14, CD19, Elastase, and Syndecan). Mean differences between shallow and residual pockets samples, as well as correlations between GCF cytokine concentrations, area of CTII, and cellularity of the CTII were calculated.
Results
A total of 15 patients were finally included, with analysis of 30 histological specimens and 30 GCF samples. Residual pockets presented significantly higher mean GCF volume, higher mean area of CTII and higher concentrations of IL‐1β and IL‐6 in GCF than shallow pockets. A significant correlation was detected between IL‐10 levels and the CTII area, IL‐10 and the percentage of Syndecan, and the area of CTII and the percentages of CD14 and Syndecan.
Conclusions
The concentration of GCF cytokines did not correlate with the area of CTII measured histologically. A residual CTII and elevated concentrations of proinflammatory cytokines and cells were present in all sites 2 months after non‐surgical treatment. The lack of healthy controls does not allow to establish differences between both groups.
Our objective is to assess the characteristics of respiratory syncytial virus (RSV) infection in adult patients and to establish differences with influenza viruses. Fifty‐four patients diagnosed with ...RSV and 198 with influenza were prospectively included. Compared with influenza, empirical antimicrobial therapy was more frequent in patients diagnosed with RSV, whereas antibiotic withdrawal at the time of diagnosis confirmation was lower (OR, 0.12; CI, 95% 0.01‐0.90; P = 0.040). RSV‐positive patients were more likely to need hospital readmission (OR, 3.00; CI, 95% 0.98‐9.09; P = 0.053). The role of RSV infection in adults is often overlooked, leading to inappropriate use of antibiotics and a probable increase in nosocomial RSV transmission.
Highlights
The prevalence of respiratory syncytial virus infection is high during flu season. ‐ Clinical findings are similar between respiratory syncytial virus and influenza. ‐ Antibiotic therapy was withdrawn in only 7% of patients diagnosed with RSV. ‐ Influenza was associated with a higher percentage of antibiotic withdrawal.
PDF
