Background:The main histopathological features of abdominal aortic aneurysm (AAA) are tissue proteolysis mediated by matrix metalloproteinases (MMPs) and inflammation. This study aimed at verifying ...the presence and contribution of mesenchymal stromal cells (MSCs) to aneurysmal tissue remodeling.Methods and Results:MSCs were successfully isolated from the AAA wall of 12 male patients and were found to express mesenchymal and stemness markers. MMP-2/-9 are involved in AAA progression and their mRNA levels in AAA-MSCs resulted higher than healthy MSCs (cMSCs), especially MMP-9 (400-fold increased). Moreover, MMP-9 protein and activity were pronounced in AAA-MSCs. Immunomodulation was tested in AAA-MSCs after co-culture with activated peripheral blood mononuclear cells (PBMCs) and revealed a weak immunosuppressive action on PBMC proliferation (bromodeoxyuridine incorporation, flow cytometry assay), together with a reduced expression of anti-inflammatory molecules (HLA-G, IL-10) by AAA-MSCs compared to cMSCs. MMP-9 expression in AAA-MSCs was shown to be negatively modulated under the influence of cMSCs and exogenous IL-10.Conclusions:MSCs with stemness properties are niched in human AAA tissues and display a dysregulation of functional activities; that is, upregulation of MMP-9 and ineffective immunomodulatory capacity, which are crucial in the AAA progression; the possibility to modulate the increased MMP-9 expression by healthy MSCs and IL-10 suggests that novel therapeutic strategies are possible for slowing down AAA progression. (Circ J 2015; 79: 1460–1469)
Anemia is the most common hematological abnormality in human immunodeficiency virus (HIV)-infected patients. Besides chronic disease, opportunistic infections, nutritional deficiencies and ...antiretroviral drug toxicity, the direct role of HIV in the development of anemia has not yet been fully investigated. To explore the HIV-related mechanisms involved in the genesis of anemia, we used two experimental designs. In the first, HPCs purified from cord blood were challenged with HIV-1IIIb or recombinant gp120 (rgp120) and then committed to erythrocyte differentiation (EPO-post-treated HPCs). In the second, HPCs were first committed to differentiate towards the erythroid lineage and only afterwards challenged with HIV-1IIIb or rgp120 (EPO-pre-treated HPCs). Our results showed that HPCs and EPO-induced HPCs were not susceptible to HIV-1 infection. In addition, the two experimental designs (EPO post or pre-treated HPCs) independently showed that HIV-1IIIb or rgp120 were able to induce the impairment of survival, proliferation, and differentiation albeit differing in kinetics and extent. Interestingly, the gp120 interaction with CD4 and CXCR4 played a pivotal role in the impairment of erythrocyte differentiation by inducing TGF-b1 expression. These observations reveal an important additional mechanism involved in the genesis of anemia suggesting a complex competition between EPO-positive regulation and HIV-negative priming regarding erythrocyte survival, proliferation and maturation.
This study was aimed at assessing the anti-HBs persistence and immune memory 18-19 y after vaccination against hepatitis B in healthy individuals primed as infants or adolescents. We enrolled 405 ...teenagers (Group A) vaccinated as infants, and 409 young adults (Group B) vaccinated as adolescents. All vaccinees were tested for anti-HBs and anti-HBc antibodies; those found anti-HBc positive were further tested for HBsAg and HBV DNA. Eight individuals belonging to Group B were positive for anti-HBc alone, and were excluded from analysis. Individuals with anti-HBs concentration ≥ 10 mIU/ml were considered protected while those with anti-HBs concentration <10 mIU/ml were offered a booster dose and re-tested 2 weeks later. Overall, 67.9% individuals showed anti-HBs concentrations ≥ 10 mIU/ml (48.9% in Group A vs 87.0% in Group B, p < 0.001). The antibody geometric mean concentration (GMC) was higher in Group B than in Group A (102.5 mIU/ml vs 6.9 mIU/ml; p < 0.001). When boosted, 94.2% of vaccinees with anti-HBs <10 mIU/ml belonging to Group A and 94.7% to Group B showed an anamnestic response. Post-booster GMCs were similar in both groups (477.9 mIU/ml for Group A vs 710.0 mIU/ml for Group B, p = n.s.). Strong immunological memory persists for at least 18-19 y after immunization of infants or adolescents with a primary course of vaccination. Thus, booster doses are not needed at this time, but additional follow up is required to assess the long-life longevity of protection.
To investigate the morphological changes of corneal epithelium and subbasal nerves by in vivo confocal microscopy in patients with ocular surface disease (OSD) treated with cord blood serum (CBS) eye ...drops.
Twenty patients with OSD (mean age 61.1 ± 12.6 years) were included in this prospective 1-arm study and treated with CBS eye drops for 2 months. Corneal sensitivity, Schirmer test score, breakup time, subjective symptoms Ocular Surface Disease Index (OSDI) and Visual Analogue Scale (VAS), and corneal staining were evaluated before (T0) and after (T1) treatment. In vivo confocal microscopy analyzed giant epithelial cells, subbasal nerve number and tortuosity, neuromas, beading, and dendritic cells (DCs) in the central cornea.
OSDI, Visual Analogue Scale, and Oxford grading values significantly decreased at T1 versus T0 (respectively, 44.1 ± 18.9 vs. 74.2 ± 13.9; 3.7 ± 1.5 vs. 8.9 ± 0.9; and 2.4 ± 1.1 vs. 3.3 ± 1.3; P < 0.0001), whereas corneal sensitivity, Schirmer test score, and breakup time significantly increased (respectively, 49.5 ± 2.6 vs. 47.9 ± 2.9; 3.2 ± 2.0 vs. 2.4 ± 2.2; 4.6 ± 3.1 vs. 3.8 ± 2.1; P < 0.0001). Corneal nerve morphology improved at T1 versus T0 with a higher total nerve number (3.4 ± 1.6 vs. 2.5 ± 1.6 per frame) and lower tortuosity (3.0 ± 0.7 vs. 3.5 ± 0.6) (P < 0.01). The number of patients presenting with giant epithelial cells, beading, and neuromas decreased at T1. DC density did not change after treatment. The detection of neuromas and higher DC density at T0 were associated with greater OSDI reduction at T1 (P < 0.001).
CBS eye drops significantly improved corneal nerve morphology and subjective symptoms in patients with severe OSD. The presence of neuromas and higher dendritic cell density at baseline were associated with greater reduction of discomfort symptoms after treatment.
Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs.
To develop a set of evidence-based recommendations for patient blood ...management (PBM) and for research.
The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018.
From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization.
The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.
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