371 publications from this institution
Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.
Idiopathic pulmonary fibrosis (IPF) is associated with a vascular remodeling process. Fibrocytes are a distinct population of blood-borne cells that coexpress hematopoietic cell antigens and fibroblast products, which have been shown to contribute to organ fibrosis. The purpose of this study was to test the hypothesis that fibrocytes may cooperate with endothelial progenitors to induce angiogenesis. We successfully isolated fibrocytes from blood of IPF patients. The characterization of fibrocytes used flow cytometry, real time q-PCR and confocal analysis. We investigated the interaction between fibrocytes and cord blood derived endothelial colony forming cells (ECFC) angiogenic potential in vitro and in vivo in a preclinical model of vascularization. We show for the first time the formation of functional microvascular beds in immunodeficient mice when human ECFC and fibrocytes isolated from IPF patients were co-implanted in matrigel plugs. Evaluation of implants after 2 weeks revealed an extensive network of blood vessels containing erythrocytes. Secreted media from fibrocytes enhances SDF-1/CXCR4 pathway in ECFC in vitro. Blocking CXCR4 in vivo in implants significantly inhibited blood vessel formation. Finally, we confirmed the relevance of these data by showing that vessels close to fibrotic areas in biopsy specimens from IPF patients expressed high levels of CXCR4, in contrast to control lungs. Circulating fibrocytes might be involved in vascular remodeling process observed in patients with fibrotic disease and should represent a useful biomarker for fibrosis progression.
The endothelium and its integrity are in the center of numerous cardiovascular, pulmonary and tumoral diseases. Several studies identified different circulating cellular sub-populations, which allow a noninvasive exploration of endothelial dysfunction. Furthermore, angiogenesis plays a major role in the biology of benign and malignant hematologic diseases. Among these biomarkers, circulating endothelial cells could be considered as a marker of endothelial injury and/or endothelial activation as well as vascular remodeling, whereas circulating endothelial progenitor cells would be only involved in the vascular regeneration. In the future, the quantification of circulating endothelial cells in many diseases could be a noninvasive biomarker used in diagnosis, prognostic and therapeutic follow-up of lung vasculopathy and/or residual disease of hematological malignancies.
We investigated whether baseline levels of biomarkers related to endotheliopathy, thromboinflammation, and fibrosis were associated with clinical outcomes in hospitalized COVID-19 patients. We analyzed the associations between baseline levels of 21 biomarkers and time to hospital discharge and change in NEWS-2 score in patients from DisCoVeRy trial. We fitted multivariate models adjusted for baseline ISARIC 4C score, disease severity, D-dimer values, and treatment regimen. Between March 22 and June 29, 2020, 603 participants were randomized; 454 had a sample collected at baseline and analyzed. The backward selection of multivariate models showed that higher baseline levels of soluble suppressor of tumorigenicity 2 (sST2) and nucleosomes were statistically associated with a lower chance of hospital discharge before day 29 (sST2: aHR 0.24, 95% CI [0.15-0.38], p < 10<sup>-9</sup>; nucleosomes: aHR 0.62, 95% CI [0.48-0.81], p < 10<sup>-3</sup>). Likewise, higher levels of baseline sST2 were statistically associated with lower changes in the NEWS-2 score between baseline and day 15 (adjusted beta 4.47, 95% CI [2.65-6.28], p < 10<sup>-5</sup>). Moreover, we evaluated sST2 involvement in a confirmation cohort (SARCODO study, 103 patients) and found that elevated baseline sST2 levels were significantly associated with lower rates of hospital discharge before day 29 and a higher model performance (AUC at day 29 of 92%) compared to models without sST2. sST2 emerged as an independent predictor of clinical outcomes in two large cohort of hospitalized COVID-19 patients, warranting further investigation to elucidate its role in disease progression and potential as a therapeutic target.
Background The decision for withholding and withdrawing of life-sustaining treatments (LSTs) in COVID-19 patients is currently based on a collegial and mainly clinical assessment. In the context of a global pandemic and overwhelmed health system, the question of LST decision support for COVID-19 patients using prognostic biomarkers arises. Methods In a multicenter study in 24 French hospitals, 2878 COVID-19 patients hospitalized in medical departments from 26 February to 20 April 2020 were included. In a propensity-matched population, we compared the clinical, biological, and management characteristics and survival of patients with and without LST decision using Student's t -test, the chi-square test, and the Cox model, respectively. Results An LST was decided for 591 COVID-19 patients (20.5%). These 591 patients with LST decision were secondarily matched (1:1) based on age, sex, body mass index, and cancer history with 591 COVID-19 patients with no LST decision. The patients with LST decision had significantly more cardiovascular diseases, such as high blood pressure (72.9 vs. 66.7%, p = 0.02), stroke (19.3 vs. 11.1%, p &lt; 0.001), renal failure (30.4 vs. 17.4%, p &lt; 0.001), and heart disease (22.5 vs. 14.9%, p &lt; 0.001). Upon admission, LST patients were more severely attested by a qSOFA score ≥2 (66.5 vs. 58.8%, p = 0.03). Biologically, LST patients had significantly higher values of D-dimer, markers of heart failure (BNP and NT-pro-BNP), and renal damage (creatinine) ( p &lt; 0.001). Their evolutions were more often unfavorable (in-hospital mortality) than patients with no LST decision (41.5 vs. 10.3%, p &lt; 0.001). By combining the three biomarkers (D-dimer, BNP and/or NT-proBNP, and creatinine), the proportion of LST increased significantly with the number of abnormally high biomarkers (24, 41.3, 48.3, and 60%, respectively, for none, one, two, and three high values of biomarkers, trend p &lt; 0.01). Conclusion The concomitant increase in D-dimer, BNP/NT-proBNP, and creatinine during the admission of a COVID-19 patient could represent a reliable and helpful tool for LST decision. Circulating biomarker might potentially provide additional information for LST decision in COVID-19.
This study observed an imbalance between venous and arterial thrombotic events in mRNA vaccines while with AZ1222 they are evenly shared. Our analysis highlights cerebral vein thrombosis with the three vaccines. https://bit.ly/3mZqguE
