5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were <5% in most subgroups, except for fosfomycin and three French regions. Overall and across most subgroups, the correlation between Xponent and SNDS monthly aggregated estimates was almost perfect (r ≥ 0.992 for all subgroups, except for one region). ARIMA modelling showed high consistency between Xponent’s and SDNS’s DrID time series, but detected timepoints where the series significantly diverged.

IQVIA’s Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.

IQVIA’s Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.

Differential responsiveness to interleukin (IL)-2 between effector CD4¬+ T cells (Teff) and regulatory T cells (Treg) is a fundamental mechanism of immunoregulation. The single nucleotide polymorphism rs61839660, located within IL2RA (CD25), has been associated with the development of Crohn’s disease. We sought to identify the T cell immune phenotype of IBD patients who carry this SNP.

Teff and Treg were isolated from individuals homozygous (TT), heterozygous (CT) or wild type (CC) for the minor allele at rs61839660, and used for phenotyping (flow cytometry, Cytometry Time Of Flight) functional assays or T cell receptor (TCR) sequencing. Phosphorylation of signal transducer and activator of transcription 5 (STAT5) was assessed in response to IL-2, IL-7 and in the presence of basiliximab, a monoclonal antibody directed against CD25. Teff proinflammatory cytokine expression levels were assessed by reverse transcription quantitative polymerase chain reaction after IL-2 and/or TCR stimulation.

Presence of the minor T allele enhances CD25 expression leading to increased STAT5 phosphorylation and proinflammatory cytokine transcript expression by Teff in response to IL-2 stimulation in vitro. check details Teff from TT individuals demonstrate a more activated gut homing phenotype. TCR sequencing analysis suggests that TT patients may have a reduced clonal capacity to mount an optimal regulatory T cell response.

rs61839660 regulates the responsiveness of T cells to IL-2 signaling by modulating CD25 expression. As low dose IL-2 is being trialed as a selective Treg modulator in CD, these findings highlight the potential for adverse effects in patients with this genotype.

rs61839660 regulates the responsiveness of T cells to IL-2 signaling by modulating CD25 expression. As low dose IL-2 is being trialed as a selective Treg modulator in CD, these findings highlight the potential for adverse effects in patients with this genotype.

Switching from boosted PIs to dolutegravir in people living with HIV (PLWH) with high cardiovascular risk improved plasma lipids at 48 weeks in the NEAT022 trial. Whether this strategy may have an impact on cardiovascular biomarkers is unknown.

We assessed 48 week changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury, and glomerular and tubular kidney injury.

Of 415 PLWH randomized in the NEAT022 study, 313 (75.4%) remained on allocated therapy and had paired samples available. Soluble CD14 (-11%, P < 0.001) and adiponectin (-11%, P < 0.001) significantly declined and high-sensitive C-reactive protein (-13%, P = 0.069) and oxidized LDL (-13%, P = 0.084) tended to decrease with dolutegravir. Switching to dolutegravir remained significantly associated with soluble CD14 and adiponectin reductions after adjustment for baseline variables. There were inverse correlations between soluble CD14 and CD4 count changes (P = 0.05), and between adiponectin and BMI changes (P < 0.001).

Switching from boosted PIs to dolutegravir in PLWH with high cardiovascular risk led to soluble CD14 and adiponectin reductions at 48 weeks. While decreasing soluble CD14 may entail favourable health effects in PLWH, adiponectin reduction may reflect less insulin sensitivity associated with weight gain.

Switching from boosted PIs to dolutegravir in PLWH with high cardiovascular risk led to soluble CD14 and adiponectin reductions at 48 weeks. While decreasing soluble CD14 may entail favourable health effects in PLWH, adiponectin reduction may reflect less insulin sensitivity associated with weight gain.

The aim of this study was to derive and validate the SCORE2-Older Persons (SCORE2-OP) risk model to estimate 5- and 10-year risk of cardiovascular disease (CVD) in individuals aged over 70 years in four geographical risk regions.

Sex-specific competing risk-adjusted models for estimating CVD risk (CVD mortality, myocardial infarction, or stroke) were derived in individuals aged over 65 without pre-existing atherosclerotic CVD from the Cohort of Norway (28 503 individuals, 10 089 CVD events). Models included age, smoking status, diabetes, systolic blood pressure, and total- and high-density lipoprotein cholesterol. Four geographical risk regions were defined based on country-specific CVD mortality rates. Models were recalibrated to each region using region-specific estimated CVD incidence rates and risk factor distributions. For external validation, we analysed data from 6 additional study populations 338 615 individuals, 33 219 CVD validation cohorts, C-indices ranged between 0.63 [95% confidence intervasion-making between clinicians and patients in CVD risk management in older persons.

Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis.

In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed.

Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.