Use of high-plex data provides novel insights into the temporal artery processes of giant cell arteritis

ObjectiveTo identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets.MethodsUsing human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < −2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA.ResultsMost of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media.ConclusionThis study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies

L'hypothermie inexpliquée est associée à une infection bactérienne dans les services d'urgence

BackgroundEarly recognition and antibiotic therapy improve the prognosis of bacterial infections. Triage temperature in the Emergency department (ED) constitutes a diagnostic and prognostic marker of infection. The objective of this study was to assess the prevalence of community-acquired bacterial infections and the diagnostic ability of conventional biological markers in patients presenting to the ED with hypothermia.MethodsWe conducted a retrospective single-center study over a 1-year period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with hypothermia (body temperature < 36.0 °C) were eligible. Patients with evident cause of hypothermia and patients with viral infections were excluded. Diagnosis of infection was based on the presence of at least two among the three following pre-defined criteria: (i) the presence of a potential source of infection, (ii) microbiology data, and (iii) patient outcome under antibiotic therapy. The association between traditional biomarkers (white blood cells, lymphocytes, C-reactive protein [CRP], Neutrophil to Lymphocyte Count Ratio [NLCR]) and underlying bacterial infections was evaluated using a univariate and a multivariate (logistic regression) analysis. Receiver operating characteristic curves were built to determine threshold values yielding the best sensitivity and specificity for each biomarker.ResultsOf 490 patients admitted to the ED with hypothermia during the study period, 281 were excluded for circumstantial or viral origin, and 209 were finally studied (108 men; mean age: 73 ± 17 years). A bacterial infection was diagnosed in 59 patients (28%) and was mostly related to Gram-negative microorganisms (68%). The area under the curve (AUC) for the CRP level was 0.82 with a confidence interval (CI) ranging from 0.75 to 0.89. The AUC for the leukocyte, neutrophil and lymphocyte counts were 0.54 (CI: 0.45–0.64), 0.58 (CI: 0.48–0.68) and 0.74 (CI: 0.66–0.82), respectively. The AUC of NLCR and quick Sequential Organ Failure Assessment (qSOFA) reached 0.70 (CI: 0.61–0.79) and 0.61 (CI: 0.52–0.70), respectively. In the multivariate analysis, CRP ≥ 50 mg/L (OR: 9.39; 95% CI: 3.91–24.14; p < 0.01) and a NLCR ≥10 (OR: 2.73; 95% CI: 1.20–6.12; p = 0.02) were identified as independent variables associated with the diagnosis of underlying bacterial infection.ConclusionCommunity-acquired bacterial infections represent one third of diagnoses in an unselected population presenting to the ED with unexplained hypothermia. CRP level and NLCR appear useful for the diagnosis of causative bacterial infection

Concentrations of serum NGF (A), BDNF (B) and NT-3 (C) detected by ELISA in SLE patients (SLE, grey boxes) and healthy controls (Controls, white boxes).

<p>The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent the median. Significant differences were assessed with Mann-Whitney tests.</p

Percentage of B lymphocytes (flow cytometry) expressing NGF (A) and BDNF (B) (SLE, grey boxes) and healthy controls (Controls, white boxes).

<p>The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent median values. Significant differences were assessed with Mann-Whitney tests.</p

Correlations between NT-3 and CH 50 NGF (A) and T regulatory cell counts (flow cytometry) in SLE patients (B).

<p>The linear regression curve and coefficient of determination yielded by the analysis of variance are both represented. Each point represents an individual patient and a healthy control. Γ defines the coefficient of determination yielded by the analysis of the variance table. <i>P</i>-values were determined by Spearman’s rank correlation test.</p

Serum BDNF concentrations in SLE patients before (SLE1, grey box) and after (SLE2, dotted box) treatment of the disease flare compared to healthy controls (Controls, white box).

<p>The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent the median. Significant differences were assessed with Mann-Whitney tests.</p

Diagnostic Value of 18F-FDG PET/CT vs. Chest-Abdomen-Pelvis CT Scan in Management of Patients with Fever of Unknown Origin, Inflammation of Unknown Origin or Episodic Fever of Unknown Origin: A Comparative Multicentre Prospective Study

International audienceFluorodesoxyglucose Positron Emission Tomography (PET/CT) has never been compared to Chest-Abdomen-Pelvis CT (CAPCT) in patients with a fever of unknown origin (FUO), inflammation of unknown origin (IUO) and episodic fever of unknown origin (EFUO) through a prospective and multicentre study. In this study, we investigated the diagnostic value of PET/CT compared to CAPCT in these patients. The trial was performed between 1 May 2008 through 28 February 2013 with 7 French University Hospital centres. Patients who fulfilled the FUO, IUO or EFUO criteria were included. Diagnostic orientation (DO), diagnostic contribution (DC) and time for diagnosis of both imaging resources were evaluated. One hundred and three patients were included with 35 FUO, 35 IUO and 33 EFUO patients. PET/CT showed both a higher DO (28.2% vs. 7.8%, p 30 mg/L (OR 3.70, p = 0.033), and chills (OR 3.06, p = 0.0248) were associated with the achievement of a diagnosis (Se: 89.1%, Sp: 56.8%). PET/CT both orients and contributes to diagnoses at a higher rate than CAPCT, especially in patients with FUO and IUO, and reduces the time for diagnosis

Serum NT-3 concentrations (ELISA) in SLE patient with severe systemic flare (SLEDAI>10, grey box), moderate flare (SLEDAI≤10, dotted box) and healthy controls (Controls, white box).

<p>The boxes represent the 50th percentile, the bars outside the boxes show the 10th and 90th percentiles, and the horizontal black lines represent the median. Significant differences were assessed with Mann-Whitney tests.</p