Publications by authors named "Elisa Rossi"

105 Publications

Serum Inflamma-miR Signature: A Biomarker of Myelodysplastic Syndrome?

Front Oncol 2020 20;10:595838. Epub 2020 Nov 20.

Hematology Clinic, Department of Clinical and Molecular Sciences, DISCLIMO, AOU Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.595838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713643PMC
November 2020

Interleukin-8 Receptors CXCR1 and CXCR2 Are Not Expressed by Endothelial Colony-forming Cells.

Stem Cell Rev Rep 2020 Nov 13. Epub 2020 Nov 13.

Innovative Therapies in Haemostasis, INSERM, Université de Paris, F-75006 , Paris, France.

Endothelial colony-forming cells (ECFCs) are human vasculogenic cells described as potential cell therapy product and good candidates for being a vascular liquid biopsy. Since interleukin-8 (IL-8) is a main actor in senescence, its ability to interact with ECFCs has been explored. However, expression of CXCR1 and CXCR2, the two cellular receptors for IL-8, by ECFCs remain controversial as several teams published contradictory reports. Using complementary technical approaches, we have investigated the presence of these receptors on ECFCs isolated from cord blood. First, CXCR1 and CXCR2 were not detected on several clones of cord blood- endothelial colony-forming cell using different antibodies available, in contrast to well-known positive cells. We then compared the RT-PCR primers used in different papers to search for the presence of CXCR1 and CXCR2 mRNA and found that several primer pairs used could lead to non-specific DNA amplification. Last, we confirmed those results by RNA sequencing. CXCR1 and CXCR2 were not detected in ECFCs in contrary to human-induced pluripotent stem cell-derived endothelial cells (h-iECs). In conclusion, using three different approaches, we confirmed that CXCR1 and CXCR2 were not expressed at mRNA or protein level by ECFCs. Thus, IL-8 secretion by ECFCs, its effects in angiogenesis and their involvement in senescent process need to be reanalyzed according to this absence of CXCR-1 and - 2 in ECFCs.Graphical Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-020-10081-yDOI Listing
November 2020

Human Aortic Valve Interstitial Cells Display Proangiogenic Properties During Calcific Aortic Valve Disease.

Arterioscler Thromb Vasc Biol 2021 01 5;41(1):415-429. Epub 2020 Nov 5.

Université de Paris, Innovative Therapies in Haemostasis, INSERM, France (N.G., A.B., E.R., S.I., S.L., A. Cras, N.N., J.R., P.G., D.M.S.).

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC) mesenchymal-like phenotype was confirmed by CD90/CD73/CD44 expression and multipotent-like differentiation ability. When VIC were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC-conditioned media and confirmed at the mRNA level in VIC compared with control VIC. Conditioned media from VIC induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC involvement in angiogenesis by a VEGF-A dependent mechanism.

Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/ATVBAHA.120.314287DOI Listing
January 2021

The exosomal surface phenotype and inflamma-miR cargo correlate with MDS diagnosis.

Br J Haematol 2021 Jan 23;192(1):e4-e7. Epub 2020 Oct 23.

Hematology, Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17113DOI Listing
January 2021

Terminal deoxynucleotidyl transferase (TdT) expression is associated with FLT3-ITD mutations in Acute Myeloid Leukemia.

Leuk Res 2020 12 15;99:106462. Epub 2020 Oct 15.

Department of Biomedicine and Prevention, University of Tor Vergata, Rome, Italy; Santa Lucia Foundation, I.R.C.C.S., Neuro-Oncohematology, Rome, Italy. Electronic address:

The terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in acute myeloid leukemias (AMLs), where it may be involved in the generation of NPM1 and FLT3-ITD mutations. We studied the correlations between TdT expression and FLT3-ITD or NPM1 mutations in primary AML samples, and the impact on patients' survival. TdT expression was analyzed in 143 adult AML patients by flow cytometry as percentage of positivity and mean fluorescence intensity (MFI) on blasts. TdT was positive in 49 samples (34.2%), with a median of 48% TdT-positivity (range 7-98) and a median MFI of 2.70 (range 1.23-30.54). FLT3-ITD and NPM1 mutations were present in 24 (16.7%) and 34 (23.7%) cases, respectively. Median TdT expression on blasts was significantly higher in FLT3-ITD+, as compared with FLT3-ITD- AMLs (median 8% vs 0% respectively, p = 0.035). NPM1 mutational status, FLT3-ITD allelic ratio, karyotype, and ELN risk groups, did not correlate with TdT expression or MFI on blasts. TdT + patients had poorer survival as compared to TdT-, but this result was not confirmed by the multivariable analysis, where ELN risk stratification as well as age and type of treatment remained independent prognostic factors for OS. In summary, our results support the possible implication of TdT enzyme in the generation of FLT3-ITD mutations in AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.leukres.2020.106462DOI Listing
December 2020

A view on the quality of diabetes care in Italy and the role of Diabetes Clinics from the 2018 ARNO Diabetes Observatory.

Nutr Metab Cardiovasc Dis 2020 10 22;30(11):1945-1953. Epub 2020 Aug 22.

CINECA - Interuniversity Consortium, Bologna, Italy.

Backgrounds And Aims: To investigate relevant indicators of quality of care in a large population-based sample of people with diabetes representative of clinical practice in Italy in 2018.

Methods And Results: We analyzed data from 11,300,750 subjects. All administrative healthcare claims collected in 2018 were scrutinized to identify subjects with diabetes and investigate several indicators of quality of care. Subjects with diabetes were identified by anti-hyperglycemic drug prescriptions, disease-specific co-payment exemption and hospital discharge codes. Indicators of quality of care pertained to monitoring (HbA1c, creatinine, lipid profile, microalbuminuria, eye examination, ECG, ultrasonography of carotid and lower limb arteries) and diabetes treatment (anti-hyperglycemic agents in subjects with cardiovascular disease, CVD). Subjects attending and nonattending Diabetes Clinics were compared. We identified 697,208 individuals with diabetes. HbA1c was assessed at least once in the year in 62.7%, creatinine in 62.3%, total cholesterol in 59.6%, microalbuminuria in 34.3%. Frequency of eye examination was 8.2%, ECG 23.5%, carotid ultrasonography 14.3%, lower limb ultrasonography 7.6%. Among anti-hyperglycemic drugs, SGLT-2 inhibitors were prescribed to ~5% and GLP-1 receptor agonists to ~5% although the proportion of subjects with CVD was ~45%. Subjects attending Diabetes Clinics had higher figures for all these monitoring and treatment indicators.

Conclusions: The implementation of national and international guidelines regarding disease monitoring and treatment is far from being satisfactory, especially among subjects nonattending Diabetes Clinics. Further efforts and investments are needed for better disseminating guidelines, more efficaciously engaging healthcare professionals and more strongly empowering the healthcare system to improve diabetes care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.08.018DOI Listing
October 2020

COPD is deleterious for pericytes: implications during training-induced angiogenesis in skeletal muscle.

Am J Physiol Heart Circ Physiol 2020 11 28;319(5):H1142-H1151. Epub 2020 Sep 28.

PhyMedExp, INSERM-CNRS-Montpellier University, CHU Montpellier, Montpellier, France.

Improvements in skeletal muscle endurance and oxygen uptake are blunted in patients with chronic obstructive pulmonary disease (COPD), possibly because of a limitation in the muscle capillary oxygen supply. Pericytes are critical for capillary blood flow adaptation during angiogenesis but may be impaired by COPD systemic effects, which are mediated by circulating factors. This study compared the pericyte coverage of muscle capillaries in response to 10 wk of exercise training in patients with COPD and sedentary healthy subjects (SHS). Fourteen patients with COPD were compared with seven matched SHS. SHS trained at moderate intensity corresponding to an individualized moderate-intensity patient with COPD trained at the same relative (%V̇o: COPD-RI) or absolute (mL·min·kg: COPD-AI) intensity as SHS. Capillary-to-fiber ratio (C/F) and NG2 pericyte coverage were assessed from muscle biopsies, before and after 5 and 10 wk of training. We also tested in vitro the effect of COPD and SHS serum on pericyte morphology and mesenchymal stem cell (MSC) differentiation into pericytes. SHS showed greater improvement in aerobic capacity (V̇o) than both patients with COPD-RI and patients with COPD-AI (Group × Time: = 0.004). Despite a preserved increase in the C/F ratio, NG2 pericyte coverage did not increase in patients with COPD in response to training, contrary to SHS (Group × Time: = 0.011). Conversely to SHS serum, COPD serum altered pericyte morphology ( < 0.001) and drastically reduced MSC differentiation into pericytes ( < 0.001). Both functional capacities and pericyte coverage responses to exercise training are blunted in patients with COPD. We also provide direct evidence of the deleterious effect of COPD circulating factors on pericyte morphology and differentiation. This work confirms the previously reported impairment in the functional response to exercise training of patients with COPD compared with SHS. Moreover, it shows for the first time that pericyte coverage of the skeletal capillaries is drastically reduced in patients with COPD compared with SHS during training-induced angiogenesis. Finally, it provides experimental evidence that circulating factors are involved in the impaired pericyte coverage of patients with COPD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.00306.2020DOI Listing
November 2020

Clinical burden of diabetes in Italy in 2018: a look at a systemic disease from the ARNO Diabetes Observatory.

BMJ Open Diabetes Res Care 2020 07;8(1)

CINECA, Casalecchio di Reno, Italy.

Introduction: Diabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.

Research Design And Methods: We investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.

Results: We identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p<0.001). Age was 69±15 (mean±SD). As compared with non-diabetic subjects, patients with diabetes received more prescriptions of any drugs (+30%, p<0.001), laboratory tests, radiologic exams and outpatient specialist consultations (+20%, p<0.001) and were hospitalized more frequently (+86%, p<0.001), with a longer stay (+1.4 days, p<0.001). Although cardiovascular diseases accounted for many hospital discharge diagnoses, virtually all diseases contributed to the higher rate of hospital admissions in diabetic subjects (235 vs 99 per 1000 person-years, p<0.001). Healthcare costs were >2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.

Conclusions: The burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjdrc-2020-001191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383948PMC
July 2020

Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation.

Thromb Haemost 2020 Sep 20;120(9):1313-1322. Epub 2020 Jul 20.

Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3-6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values ( = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found ( = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0040-1713751DOI Listing
September 2020

The Social Construction of Gender in Medical Interactions: A Case for the Perpetuation of Stereotypes?

Authors:
Elisa Rossi

Health Commun 2020 Mar 16:1-11. Epub 2020 Mar 16.

Department of Studies on Language and Culture, University of Modena and Reggio Emilia.

This paper focuses on the ways in which gender, conceived as the product of an ongoing social and cultural construction in and through communication processes, is accomplished during medical encounters and through the narratives produced within these interactions. The main objective is to examine: (1) when and by what devices gender becomes interactionally relevant; (2) the participants' narratives on 'gender issues'; (3) the interplay between the narratives produced and the forms of communication created, also considering which form may be more effective in challenging gender stereotypes and bias. Data are drawn from a corpus of self-administered audio-recorded interactions between a female gynecologist/midwife and pregnant patients. The consultations (half of them mediated, half not) took place in a city of North Italy; the patients (sometimes accompanied by the husband) are migrant women from North and West Africa. The main results show that: (1) at each stage of the examinations, an orientation to gender emerges, mainly through questions that display categorizations, category-bound activities, and cultural assumptions about gender: when referred to the patient, these devices often reproduce the traditional cultural model of femininity and, connected to this, the 'normal' (heterosexual and stable) intimate relationship as socially expected; (2) medical dialogue as patient-centered approach is the most recurrent form of interaction and often leads to a co-construction of narratives in which personal uniqueness is more relevant than gender roles, expectations, and stereotyped representations; when husbands are involved, however, the interactions seem to shift toward doctor-centered forms of communication, and this usually leads to asymmetrical and directive constructions of narratives about differentiated and traditional gender roles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10410236.2020.1735698DOI Listing
March 2020

Spin-orbit coupling is the key to unraveling intriguing features of the halogen bond involving astatine.

Phys Chem Chem Phys 2020 Jan 8;22(4):1897-1910. Epub 2020 Jan 8.

Department of Chemistry, Biology and Biotechnology, University of Perugia, via Elce di Sotto 8, 06123 Perugia, Italy. and CNR Institute of Chemical Science and Technologies "Giulio Natta" (CNR-SCITEC), via Elce di Sotto 8, 06123 Perugia, Italy. and Consortium for Computational Molecular and Materials Sciences (CMS)2, via Elce di Sotto 8, 06123 Perugia, Italy.

The effect of spin-orbit coupling (SOC) on the halogen bond involving astatine has been investigated using state-of-the-art two- and four-component relativistic calculations. Adducts between Cl-X (X = Cl, Br, I and At) and ammonia have been selected to establish a trend on going down the periodic table. The SOC influence has been explored not only on the geometric and energetic features that can be used to characterize the halogen bond strength but also on the three main contributions to it that are the charge transfer, the "σ-hole" (i.e. the localized region with a net positive electrostatic potential at the halogen site) and the "polar flattening" (which is related to the effective shape of the halogen site). A surprisingly large increase of the Cl-At dipole moment, due to the inclusion of SOC, has been worked out using four-component CCSD(T) reference calculations, indicating that this bond is significantly more ionic than one may predict. Due to the SOC effect, which induces a peculiar charge accumulation on the At side in the Cl-At dimer, a weakening of the astatine-mediated halogen bond occurs arising from the (i) reduced amount of charge transfer, (ii) decrease of the polar flattening and (iii) lowering of the short-range Coulomb potential. The analysis of the electronic structure of the Cl-At moiety allows for a rationalization of the SOC effects on all the considered features of the halogen bond, including an unprecedented unsymmetrical charge back-donation from Cl-At to ammonia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cp06293aDOI Listing
January 2020

Human Endothelial Colony Forming Cells Express Intracellular CD133 that Modulates their Vasculogenic Properties.

Stem Cell Rev Rep 2019 08;15(4):590-600

Sorbonne Paris Cité, Université Paris Descartes, Paris, France.

Stem cells at the origin of endothelial progenitor cells and in particular endothelial colony forming cells (ECFCs) subtype have been largely supposed to be positive for the CD133 antigen, even though no clear correlation has been established between its expression and function in ECFCs. We postulated that CD133 in ECFCs might be expressed intracellularly, and could participate to vasculogenic properties. ECFCs extracted from cord blood were used either fresh (n = 4) or frozen (n = 4), at culture days <30, to investigate the intracellular presence of CD133 by flow cytometry and confocal analysis. Comparison with HUVEC and HAEC mature endothelial cells was carried out. Then, CD133 was silenced in ECFCs using specific siRNA (siCD133-ECFCs) or scramble siRNA (siCtrl-ECFCs). siCD133-ECFCs (n = 12), siCtrl-ECFCs (n = 12) or PBS (n = 12) were injected in a hind-limb ischemia nude mouse model and vascularization was quantified at day 14 with H&E staining and immunohistochemistry for CD31. Results of flow cytometry and confocal microscopy evidenced the positivity of CD133 in ECFCs after permeabilization compared with not permeabilized ECFCs (p < 0.001) and mature endothelial cells (p < 0.03). In the model of mouse hind-limb ischemia, silencing of CD133 in ECFCs significantly abolished post-ischemic revascularization induced by siCtrl-ECFCs; indeed, a significant reduction in cutaneous blood flows (p = 0.03), capillary density (CD31) (p = 0.01) and myofiber regeneration (p = 0.04) was observed. Also, a significant necrosis (p = 0.02) was observed in mice receiving siCD133-ECFCs compared to those treated with siCtrl-ECFCs. In conclusion, our work describes for the first time the intracellular expression of the stemness marker CD133 in ECFCs. This feature could resume the discrepancies found in the literature concerning CD133 positivity and ontogeny in endothelial progenitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-019-09881-8DOI Listing
August 2019

Endoglin as an Adhesion Molecule in Mature and Progenitor Endothelial Cells: A Function Beyond TGF-β.

Front Med (Lausanne) 2019 30;6:10. Epub 2019 Jan 30.

Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Endoglin (ENG) is a transmembrane glycoprotein expressed on endothelial cells that functions as a co-receptor for several ligands of the transforming growth factor beta (TGF-β) family. ENG is also a recognized marker of angiogenesis and mutations in the endoglin gene are responsible for Hereditary Hemorrhagic Telangiectasia (HHT) type 1, a vascular disease characterized by defective angiogenesis, arteriovenous malformations, telangiectasia, and epistaxis. In addition to its involvement in the TGF-β family signaling pathways, several lines of evidence suggest that the extracellular domain of ENG has a role in integrin-mediated cell adhesion via its RGD motif. Indeed, we have described a role for endothelial ENG in leukocyte trafficking and extravasation its binding to leukocyte integrins. We have also found that ENG is involved in vasculogenic properties of endothelial progenitor cells known as endothelial colony forming cells (ECFCs). Moreover, the binding of endothelial ENG to platelet integrins regulate the resistance to shear during platelet-endothelium interactions under inflammatory conditions. Because of the need for more effective treatments in HHT and the involvement of ENG in angiogenesis, current studies are aimed at identifying novel biological functions of ENG which could serve as a therapeutic target. This review focuses on the interaction between ENG and integrins with the aim to better understand the role of this protein in blood vessel formation driven by progenitor and mature endothelial cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2019.00010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363663PMC
January 2019

Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation.

Mol Pharm 2019 03 5;16(3):1312-1326. Epub 2019 Feb 5.

Inserm , U1144 , Paris F-75006 , France.

The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood-brain barrier (BBB). TRPV2 expression and its role on Ca cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Intracellular Ca levels were increased by heat and CBD and blocked by the nonspecific TRP antagonist ruthenium red (RR) and the selective TRPV2 inhibitor tranilast (TNL) or by silencing cells with TRPV2 siRNA. CBD dose-dependently induced the hCMEC/D3 cell number (EC 0.3 ± 0.1 μM), and this effect was fully abolished by TNL or TRPV2 siRNA. A wound healing assay showed that CBD induced cell migration, which was also inhibited by TNL or TRPV2 siRNA. Tubulogenesis of hCMEC/D3 cells in 3D matrigel cultures was significantly increased by 41 and 73% after a 7 or 24 h CBD treatment, respectively, and abolished by TNL. CBD also increased the TEER of hPBMEC monolayers cultured in transwell, and this was blocked by TNL. Our results show that CBD, at extracellular concentrations close to those observed in plasma of patients treated by CBD, induces proliferation, migration, tubulogenesis, and TEER increase in human brain endothelial cells, suggesting CBD might be a potent target for modulating the human BBB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.molpharmaceut.8b01252DOI Listing
March 2019

Interleukin-8 release by endothelial colony-forming cells isolated from idiopathic pulmonary fibrosis patients might contribute to their pathogenicity.

Angiogenesis 2019 05 3;22(2):325-339. Epub 2019 Jan 3.

Hematology Department, AP-HP, European Georges Pompidou Hospital, 20 rue Leblanc, 75015, Paris, France.

Introduction: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties.

Methods And Results: ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis.

Conclusion: To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10456-018-09659-5DOI Listing
May 2019

Teaching NeuroImages: Melkersson-Rosenthal syndrome with permanent bilateral facial weakness.

Neurology 2019 01;92(1):e81

From the Clinical Neurophysiology Laboratory (F.R.), Comprehensive Headaches Center (N.T.), Department of Neurology (N.T., E.M.R.), and Behavioral and Cognitive Center (M.H.), Orlando VA Medical Center; and Department of Neurology (F.R., M.H.), UCF Medical School, Orlando, FL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000006683DOI Listing
January 2019

Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC).

Oncotarget 2018 Apr 3;9(25):17554-17563. Epub 2018 Apr 3.

Department of Oncology and Hematology, AUSL della Romagna, Ravenna, Italy.

Background: This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients' clinical responses and survival outcome.

Methods: Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher's test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and -value.

Results: Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort ( = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months ( = 0.062) and 8.8 vs 9.3 months ( = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant ( = 0.063).

Conclusions: This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.24785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915137PMC
April 2018

Exploding Head Syndrome as Aura of Migraine with Brainstem Aura: A Case Report.

J Oral Facial Pain Headache 2018 Spring;32(2):e34-e36

This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion in the head, visual flashing, vertigo, hearing loss, tinnitus, confusion, ataxia, dysarthria, and bilateral visual impairment followed by migraine headache. The condition was diagnosed as MBA. Explosive head sensation, sensory phenomena, and headaches improved over time with nortriptyline. This case shows that EHS can present as a primary aura symptom in patients with MBA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11607/ofph.1950DOI Listing
September 2018

Healthcare resources utilisation in primary progressive multiple sclerosis.

Neurol Sci 2018 Jul 10;39(7):1169-1174. Epub 2018 Apr 10.

CORE srl-Collaborative Outcome Research, Via Magnanelli 2, 40033 Casalecchio di Reno, Bologna, Italy.

Epidemiological data on primary progressive multiple sclerosis (PPMS) are scarce. This study was aimed to evaluate the burden of PPMS in Italy with healthcare resources utilisation and costs for Italian National Health System (INHS). A 2-year cross-sectional analysis of real-world data collected in the ARCO database, covering > 10 million Italian inhabitants, was performed. From a cohort of patients affected by MS in 2014, those supposedly affected by PPMS were defined by the concurrent matching of absence of disease-modifying treatments and use of rehabilitation services. Any other drug prescriptions, outpatient services and hospitalisations were analysed in 2015 for each subject. The average annual cost per patient was provided both for each expenditure item and by integrating these. Of 13,253,591 inhabitants, 18,453 resulted affected by MS (prevalence 139 × 100,000). Of these, 1849 agreed with additional criteria to identify PPMS (10% of MS population). The 26.8% of these experienced at least one admission in 1 year, 97.3% used at least one outpatient service and 94.3% received at least one reimbursed drug. In the perspective of INHS, PPMS generated an average annual cost of € 3783 per person: 49% for hospitalisations, 28% for outpatient services and 23% for drugs. This study provides a reliable estimation of the PPMS burden in Italy, in terms of healthcare utilisation and direct costs. These findings could be useful to estimate the changes in health expenditure following the incoming of new drugs to treat PPMS with increase of pharmaceutical cost and potential decrease of rehabilitation and hospitalisation costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10072-018-3404-4DOI Listing
July 2018

Endothelial Microparticles are Associated to Pathogenesis of Idiopathic Pulmonary Fibrosis.

Stem Cell Rev Rep 2018 Apr;14(2):223-235

Inserm UMR-S1140, Paris, France.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms remain unclear but involve a concomitant accumulation of scar tissue together with myofibroblasts activation. Microparticles (MPs) have been investigated in several human lung diseases as possible pathogenic elements, prognosis markers and therapeutic targets. We postulated that levels and cellular origins of circulating MPs might serve as biomarkers in IPF patients and/or as active players of fibrogenesis. Flow cytometry analysis showed a higher level of Annexin-V positive endothelial and platelet MPs in 41 IPF patients compared to 22 healthy volunteers. Moreover, in IPF patients with a low diffusing capacity of the lung for carbon monoxide (DL<40%), endothelial MPs (EMPs) were found significantly higher compared to those with DL>40% (p = 0.02). We then used EMPs isolated from endothelial progenitor cells (ECFCs) extracted from IPF patients or controls to modulate normal human lung fibroblast (NHLF) properties. We showed that EMPs did not modify proliferation, collagen deposition and myofibroblast transdifferentiation. However, EMPs from IPF patients stimulated migration capacity of NHLF. We hypothesized that this effect could result from EMPs fibrinolytic properties and found indeed higher plasminogen activation potential in total circulating MPs and ECFCs derived MPs issued from IPF patients compared to those isolated from healthy controls MPs. Our study showed that IPF is associated with an increased level of EMPs in the most severe patients, highlighting an active process of endothelial activation in the latter. Endothelial microparticles might contribute to the lung fibroblast invasion mediated, at least in part, by a fibrinolytic activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-017-9778-5DOI Listing
April 2018

Human endoglin as a potential new partner involved in platelet-endothelium interactions.

Cell Mol Life Sci 2018 04 28;75(7):1269-1284. Epub 2017 Oct 28.

Centro de Investigaciones Biologicas, Consejo Superior de Investigaciones Científicas (CSIC), Ramiro de Maeztu, 9, 28040, Madrid, Spain.

Complex interactions between platelets and activated endothelium occur during the thrombo-inflammatory reaction at sites of vascular injuries and during vascular hemostasis. The endothelial receptor endoglin is involved in inflammation through integrin-mediated leukocyte adhesion and transmigration; and heterozygous mutations in the endoglin gene cause hereditary hemorrhagic telangiectasia type 1. This vascular disease is characterized by a bleeding tendency that is postulated to be a consequence of telangiectasia fragility rather than a platelet defect, since platelets display normal functions in vitro in this condition. Here, we hypothesize that endoglin may act as an adhesion molecule involved in the interaction between endothelial cells and platelets through integrin recognition. We find that the extracellular domain of human endoglin promotes specific platelet adhesion under static conditions and confers resistance of adherent platelets to detachment upon exposure to flow. Also, platelets adhere to confluent endothelial cells in an endoglin-mediated process. Remarkably, Chinese hamster ovary cells ectopically expressing the human αIIbβ3 integrin acquire the capacity to adhere to myoblast transfectants expressing human endoglin, whereas platelets from Glanzmann's thrombasthenia patients lacking the αIIbβ3 integrin are defective for endoglin-dependent adhesion to endothelial cells. Furthermore, the bleeding time, but not the prothrombin time, is significantly prolonged in endoglin-haplodeficient (Eng ) mice compared to Eng animals. These results suggest a new role for endoglin in αIIbβ3 integrin-mediated adhesion of platelets to the endothelium, and may provide a better understanding on the basic cellular mechanisms involved in hemostasis and thrombo-inflammatory events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-017-2694-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843676PMC
April 2018

Egfl7 Represses the Vasculogenic Potential of Human Endothelial Progenitor Cells.

Stem Cell Rev Rep 2018 Feb;14(1):82-91

Sorbonne Paris Cité, Université Paris Descartes, Paris, France.

Egfl7 (VE-statin) is a secreted protein mostly specific to the endothelial lineage during development and in the adult and which expression is enhanced during angiogenesis. Egfl7 involvement in human postnatal vasculogenesis remains unresolved yet. Our aim was to assess Egfl7 expression in several angiogenic cell types originating from human bone marrow, peripheral blood, or cord blood. We found that only endothelial colony forming cells (ECFC), which are currently considered as the genuine endothelial precursor cells, expressed large amounts of Egfl7. In order to assess its potential roles in ECFC, Egfl7 was repressed in ECFC by RNA interference and ECFC angiogenic capacities were tested in vitro and in vivo. Cell proliferation, differentiation, and migration were significantly improved when Egfl7 was repressed in ECFC in vitro, whereas miR-126-3p levels remained unchanged. In vivo, repression of Egfl7 in ECFC significantly improved post-ischemic revascularization in a model of mouse hind-limb ischemia. In conclusion, ECFC are the sole postnatal angiogenic cells which express large amounts of Egfl7 and whose angiogenic properties are repressed by this factor. Thus, Egfl7 inhibition may be considered as a therapeutic option to improve ECFC-mediated postnatal vasculogenesis and to optimize in vitro ECFC expansion in order to develop an optimized cell therapy approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-017-9775-8DOI Listing
February 2018

Endoglin and alk1 as therapeutic targets for hereditary hemorrhagic telangiectasia.

Expert Opin Ther Targets 2017 10 20;21(10):933-947. Epub 2017 Aug 20.

a Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) , Madrid , Spain.

Introduction: Hereditary Haemorrhagic Telangiectasia (HHT) is as an autosomal dominant trait characterized by frequent nose bleeds, mucocutaneous telangiectases, arteriovenous malformations (AVMs) of the lung, liver and brain, and gastrointestinal bleedings due to telangiectases. HHT is originated by mutations in genes whose encoded proteins are involved in the transforming growth factor β (TGF-β) family signalling of vascular endothelial cells. In spite of the great advances in the diagnosis as well as in the molecular, cellular and animal models of HHT, the current treatments remain just at the palliative level. Areas covered: Pathogenic mutations in genes coding for the TGF-β receptors endoglin (ENG) (HHT1) or the activin receptor-like kinase-1 (ACVRL1 or ALK1) (HHT2), are responsible for more than 80% of patients with HHT. Therefore, ENG and ALK1 are the main potential therapeutic targets for HHT and the focus of this review. The current status of the preclinical and clinical studies, including the anti-angiogenic strategy, have been addressed. Expert opinion: Endoglin and ALK1 are attractive therapeutic targets in HHT. Because haploinsufficiency is the pathogenic mechanism in HHT, several therapeutic approaches able to enhance protein expression and/or function of endoglin and ALK1 are keys to find novel and efficient treatments for the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14728222.2017.1365839DOI Listing
October 2017

Co-injection of mesenchymal stem cells with endothelial progenitor cells accelerates muscle recovery in hind limb ischemia through an endoglin-dependent mechanism.

Thromb Haemost 2017 10 3;117(10):1908-1918. Epub 2017 Aug 3.

Prof. David Smadja, European Hospital Georges Pompidou, Hematology Department and UMR-S1140, 20 rue Leblanc, 75015 Paris, France, Tel.: +31 56093933, Fax: +31 56093393, E-mail:

Endothelial colony-forming cells (ECFCs) are progenitor cells committed to endothelial lineages and have robust vasculogenic properties. Mesenchymal stem cells (MSCs) have been described to support ECFC-mediated angiogenic processes in various matrices. However, MSC-ECFC interactions in hind limb ischemia (HLI) are largely unknown. Here we examined whether co-administration of ECFCs and MSCs bolsters vasculogenic activity in nude mice with HLI. In addition, as we have previously shown that endoglin is a key adhesion molecule, we evaluated its involvement in ECFC/MSC interaction. Foot perfusion increased on day 7 after ECFC injection and was even better at 14 days. Co-administration of MSCs significantly increased vessel density and foot perfusion on day 7 but the differences were no longer significant at day 14. Analysis of mouse and human CD31, and in situ hybridization of the human ALU sequence, showed enhanced capillary density in ECFC+MSC mice. When ECFCs were silenced for endoglin, coinjection with MSCs led to lower vessel density and foot perfusion at both 7 and 14 days (p<0.001). Endoglin silencing in ECFCs did not affect MSC differentiation into perivascular cells or other mesenchymal lineages. Endoglin silencing markedly inhibited ECFC adhesion to MSCs. Thus, MSCs, when combined with ECFCs, accelerate muscle recovery in a mouse model of hind limb ischemia, through an endoglin-dependent mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH17-01-0007DOI Listing
October 2017

Subclinical hypothyroidism in paediatric population treated with levothyroxine: a real-world study on 2001-2014 Italian administrative data.

Endocr Connect 2017 Aug 14;6(6):367-374. Epub 2017 Jun 14.

CORE srl - Collaborative Outcome ResearchBologna, Italy

Objective: To estimate the prevalence of subclinical hypothyroidism (SH) among children, by using levothyroxine low dosage as disease proxy, and to describe prescription pattern.

Design: An historical cohort study was performed through administrative databases of 12 Italian Local Health Units covering 3,079,141 inhabitants. A cohort of children (aged 0-13 years) was selected in the period 2001-2014. A subgroup of new users (aged 0-9 years) was identified and followed up for 5 years.

Methods: The prevalence was provided as mean value of the whole period, as annual trend, by patient gender and age. Demographic details, information on levothyroxine dosage, comorbidities and co-medications were provided. Therapy duration and medication persistence were evaluated among new users.

Results: 644 children treated with levothyroxine low dosage was selected, with a mean annual prevalence of 0.20 per 1000 children. The temporal trend of prevalence was stable, with a slight reduction in the 2005-2008. Prevalence by age showed an increase after 10 years. Patients were treated with an average annual dose of 4290 µg/year and 66.9% of children were affected by comorbidities. Among 197 new users, 62.9% received therapy only for one year, whereas out of those treated two or more years, 89.0% resulted persistent to the therapy.

Conclusions: This study provides real-world epidemiology of SH among children, and it depicts the clinical and therapeutic characteristics of these subjects. Its findings showed that the SH treatment of this disorder was widely variable, also due to lack of evidence concerning paediatric population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-17-0066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527356PMC
August 2017

Permanent Cerebellar Degeneration After Acute Hyperthermia with Non-toxic Lithium Levels: a Case Report and Review of Literature.

Cerebellum 2017 Dec;16(5-6):973-978

Department of Neurology, Veteran Health Care System, St Louis, MO, 63104, USA.

This was a study of a 33-year-old man with bipolar disorder treated with lithium who developed cerebellar atrophy after an event of extreme hyperthermia. Unlike previously reported cases of acute cerebellar atrophy after heat stroke, neuroleptic syndrome or lithium toxicity, this case was characterized by a chronic cerebellar atrophy that developed after sepsis-induced hyperthermia in the setting of non-toxic lithium levels. Unique to this case also was the early finding of cerebellar atrophy on MRI 2 weeks after the episode of hyperthermia, long-term neurotoxicity after the novo lithium therapy, and longest follow-up case of chronic cerebellar syndrome after hyperthermia with non-toxic lithium levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-017-0868-3DOI Listing
December 2017

Human very Small Embryonic-like Cells Support Vascular Maturation and Therapeutic Revascularization Induced by Endothelial Progenitor Cells.

Stem Cell Rev Rep 2017 Aug;13(4):552-560

Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Very small embryonic-like stem cells (VSELs) are major pluripotent stem cells defined as cells of small size being Lineage- negative, CD133-positive, and CD45-negative. We previously described that human bone marrow VSELs were able to differentiate into endothelial cells and promoted post-ischemic revascularization in mice with surgically induced critical limb ischemia. In the present work, we isolated bone marrow VSELs from patients with critical limb ischemia and studied their ability to support endothelial progenitor cells therapeutic capacity and revascularization potential. Sorted bone marrow VSELs cultured in angiogenic media were co-injected with endothelial progenitor cells and have been show to trigger post-ischemic revascularization in immunodeficient mice, and support vessel formation in vivo in Matrigel implants better than human bone marrow mesenchymal stem cells. In conclusion, VSELs are a potential new source of therapeutic cells that may give rise to cells of the endothelial and perivascular lineage in humans. VSELs are the first real vasculogenic stem cells able to differentiate in endothelial and perivascular lineage in human adult described from now. Thus, because VSELs presence have been proposed in adult tissues, we think that VSELs are CD45 negative stem cells able to give rise to vascular regeneration in human tissues and vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-017-9731-7DOI Listing
August 2017

Use of lipid lowering drugs in patients at very high risk of cardiovascular events: An analysis on nearly 3,000,000 Italian subjects of the ARNO Observatory.

Int J Cardiol 2017 Nov 28;246:62-67. Epub 2017 Feb 28.

Drug & Health, Rome, Italy.

Aim: To assess clinical characteristics, use of resources and costs of patients at very high risk (VHR) of cardiovascular (CV) events. Further, to assess how VHR patients are treated with statins (rate of prescription, dosages, adherence).

Methods And Results: A record linkage analysis was carried out of patient demographics, drug prescriptions, hospital discharge, specialty procedures from the ARNO Observatory, including 2,989,512 subjects of Local Health Units well representing the whole Italian country. Accrual lasted from January 1 to December 31, 2011. Among these subjects, 17,126 (0.56%) experienced a CV event, representing the cohort at VHR. Between VHR patients, 4810 (28.1%) individuals represent the diabetic cohort. Mean age of VHR patients was 77±13, females were 43.8%. Statins and/or ezetimibe were prescribed in 59.9% and 68.5% during the first year of follow respectively in VHR and VHR-diabetics. Prescription continuity at 1year was 64.7% in patients at VHR, and 63.4% in VHR diabetics. At 1year, at least one re-hospitalization occurred in 55.0% of patients for a total of 17,631 re-hospitalizations. In VHR diabetics, at least one readmission occurred in 59.6% of patients. Average annual cost for a single VHR patient was €11,644 (drugs: €1007; hospitalizations: €10,097; specialty procedures: €540); the corresponding cost for diabetics was €13,199 (drugs: €1394; hospitalizations: €11,032, specialty procedures €773).

Conclusions: Atherothrombotic events are a relevant cause of hospitalization in the community setting. Prescription rate and continuity of treatment with statins seem to be at least suboptimal. NHS costs are high, with re-hospitalizations being the main cost-driver.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2017.02.108DOI Listing
November 2017

Late presentation increases risk and costs of non-infectious comorbidities in people with HIV: an Italian cost impact study.

AIDS Res Ther 2017 Feb 16;14(1). Epub 2017 Feb 16.

Department of Medical and Surgical Sciences for Adults and Children, Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Emilia-Romagna, Modena, Italy.

Background: Late presentation (LP) at the time of HIV diagnosis is defined as presentation with AIDS whatever the CD4 cell count or with CD4 <350 cells/mm. The objective of our study was to assess the prevalence of non-infectious comorbidities (NICM) and multimorbidity among HIV-positive individuals with and without a history of LP (HIV + LP and HIV + EP, respectively), and compare them to matched HIV-negative control participants from a community-based cohort. The secondary objective was to provide estimates and determinants of direct cost of medical care in HIV patients.

Methods: We performed a matched cohort study including HIV + LP and HIV + EP among people attending the Modena HIV Metabolic Clinic (MHMC) in 2014. HIV-positive participants were matched in a 1:3 ratio with HIV-negative participants from the CINECA ARNO database. Multimorbidity was defined as the concurrent presence of ≥2 NICM. Logistic regression models were constructed to evaluate associated predictors of NICM and multimorbidity.

Results: We analyzed 452 HIV + LP and 73 HIV + EP participants in comparison to 1575 HIV-negative controls. The mean age was 46 ± 9 years, 27.5% were women. Prevalence of NICM and multimorbidity were fourfold higher in the HIV + LP compared to the general population (p < 0.001), while HIV + EP present an intermediate risk. LP was associated with increased total costs in all age strata, but appear particularly relevant in patients above 50 years of age, after adjusting for age, multimorbidity, and antiretroviral costs.

Conclusions: LP with HIV infection is still very frequent in Italy, is associated with higher prevalence of NICM and multimorbidity, and contributes to higher total care costs. Encouraging early testing and access to care is still urgently needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12981-016-0129-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311843PMC
February 2017

Relevance of pre-analytical blood management on the emerging cardiovascular protein biomarkers TWEAK and HMGB1 and on miRNA serum and plasma profiling.

Clin Biochem 2017 Mar 12;50(4-5):186-193. Epub 2016 Nov 12.

Department of Medicine - DIMED, University of Padova, Italy.

Background: Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers.

Methods: An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0.5, 3, 6 and 9h) and centrifugation (one or two-step). Aliquots of all processed samples were immediately frozen (-80°C) before analysis. Proteins were assayed by ELISAs, miRNA expression profile by microarray and peptidome profiling by MALDI-TOF/MS.

Results: Temperature, time and centrifugation had no impact on TWEAK and HMGB1 results, which were significantly influenced by matrix type, TWEAK levels being significantly higher (F=194.7, p<0.0001), and HMGB1 levels significantly lower (F=36.32, p<0.0001) in serum than in any other plasma type. Unsuitable miRNA results were obtained using Heparin-plasma. Serum miRNA expression profiles depended mainly on temperature, while EDTA-plasma miRNA expression profiles were strongly affected by the centrifugation method used. MALDI-TOF/MS allowed the identification of seven features as indices of pre-analytical serum (m/z at 1206, 1350, 1865 and 2021) or EDTA-plasma (m/z 1897, 2740 and 2917) degradation.

Conclusions: Serum and EDTA-plasma allow the analysis of both proteins and miRNA emerging biomarkers of heart diseases. Refrigerated storage prevents an altered miRNA expression profile also in cases of a prolonged time-interval between blood drawing and processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2016.11.005DOI Listing
March 2017