[The development of a Hub & Spoke network for transcatheter aortic valve replacement procedures: the operational model of the Interventional Cardiology Unit at the IRCCS San Raffaele Hospital (OSR Hub-Spoke)].

Recently, an increase in the number of patients with severe aortic stenosis eligible for transcatheter aortic valve implantation (TAVI) has been observed worldwide. In order to reduce waiting lists, provide to all patients referred to us equal access to care and to further improve the collaboration with spoke centers, we developed a specific Hub & Spoke specific protocol for TAVI. According to our protocol, a clinical selection (with echo and computed tomography scan) is done by Spoke centers, the case is discussed with a multidisciplinary team online and the procedure is planned (access, valve type size).

Meniscal Replacement With a Silk Fibroin Scaffold Reduces Contact Stresses in the Human Knee.

The aim of the current study was to verify if a previously developed silk fibroin scaffold for meniscal replacement is able to restore the physiological distribution of contact pressure (CP) over the articulating surfaces in the human knee joint, thereby reducing peak loads occurring after partial meniscectomy. The pressure distribution on the medial tibial articular surface of seven human cadaveric knee joints was analysed under continuous flexion-extension movements and under physiological loads up to 2,500 N at different flexion angles. Contact area (CA), maximum tibiofemoral CP, maximum pressure under the meniscus and the pressure distribution were analysed for the intact meniscus, after partial meniscectomy as well as after partial medial meniscal replacement using the silk fibroin scaffold.

Articular cartilage and meniscus reveal higher friction in swing phase than in stance phase under dynamic gait conditions.

Most previous studies investigated the remarkably low and complex friction properties of meniscus and cartilage under constant loading and motion conditions. However, both load and relative velocity within the knee joint vary considerably during physiological activities. Hence, the question arises how friction of both tissues is affected by physiological testing conditions occurring during gait.

The challenge of implant integration in partial meniscal replacement: an experimental study on a silk fibroin scaffold in sheep.

Purpose: To restore meniscal function after excessive tissue damage, a silk fibroin implant for partial meniscal replacement was developed and investigated in an earlier sheep model. After 6 months implantation, it showed promising results in terms of chondroprotection and biocompatibility. To improve surgical fixation, the material was subjected to optimisation and a fibre mesh was integrated into the porous matrix.

Tracking in vivo dynamics of NK cells transferred in patients undergoing stem cell transplantation.

Haploidentical stem cell transplantation (haploSCT) offers an alternative treatment option for advanced leukemia patients lacking a HLA-compatible donor. Transfer of NK cells represents a promising therapeutic option in combination with SCT, as NK cells can promote graft versus leukemia with low risk of GVH disease. In this study, we show results from a phase I/II trial in which 24 acute myeloid leukemia patients underwent haploSCT in combination with early transfer of unmodified NK cells and observed a promising 2-year overall survival rate of 37%.

Peptide-directed spatial organization of biomolecules in dynamic gradient scaffolds.

Specific binding peptides are used to spatially organize biomolecule gradients within an electrospun fiber scaffold. Different biomolecule-binding peptide-polymer conjugates are sequentially co-electrospun with a fiber-forming host polymer to generate opposing gradients of peptide functionalization. The binding peptides specifically and non-covalently guide the spatial arrangement of biomolecules into dynamic gradients within the scaffold, mimicking biological gradients found in native tissues.

Treatment of abdominal aortic aneurysm with a new type of polymer-filled low profile device.

Purpose Of The Study: To evaluate the mid-term safety and effectiveness of a novel stent graft for treatment of abdominal aortic aneurysm (AAA).

Methods: Thirty-three patients with AAA (20 males and 13 females; mean age: 71.3 y) were treated with the Ovation™ Abdominal Stent Graft System (TriVascular, Inc.

Responsive poly (γ-glutamic acid) fibres for biomedical applications.

A novel responsive system using a protein-based biopolymer was designed to undergo structural, geometric, and chemical changes upon temperature change or solvent interaction. Poly(γ-glutamic acid) (γ-PGA) is an attractive candidate for various biomedical applications as it is naturally produced, biocompatible and enzymatically degradable. The responsive material was fabricated using an electrospun modified γ-PGA to create a sub-micron fibrous mat.

Functionalized poly(γ-Glutamic Acid) fibrous scaffolds for tissue engineering.

Poly(γ-glutamic acid) (γ-PGA) is a biocompatible, enzymatically-degradable, natural polymer with a higher resistance to hydrolysis than polyesters commonly used for tissue engineering scaffolds such as poly(L-lactide) (PLLA). Notably, γ-PGA's free carboxyl side groups allow for simple chemical functionalization, making it a versatile candidate for producing scaffolds. Here, a series of water-resistant fibrous scaffolds were engineered from ethyl (Et), propyl (Pr) and benzyl (Bn) esterifications of γ-PGA.

Self-organization of mixtures of fluorocarbon and hydrocarbon amphiphilic thiolates on the surface of gold nanoparticles.

Self-assembled monolayers composed of a mixture of thiolate molecules, featuring hydrocarbon or perfluorocarbon chains (H- and F-chains) terminating with a short poly(oxoethylene) (PEG) moiety, are the most extreme example of surfactant immiscibility on gold nanoparticles reported so far. The phase segregation between H-chains and F-chains and the consequent, peculiar folding of PEG chains are responsible for the increased affinity of a selected radical probe for the fluorinated region, which increases as the size of the fluorinated domains decrease, independently of the shape of such domains. This feature has been revealed by ESR measurements and an in silico innovative multiscale molecular simulations approach in explicit water.

Impaired function of dendritic cells deficient in angiotensin II type 1 receptors.

Dendritic cells (DC) are highly specialized antigen-presenting cells with a unique ability to activate resting T lymphocytes and initiate primary immune responses. Angiotensin II (AII) is involved in key events of the inflammatory response. Because our previous work implicated an effect of AII on differentiation and function of murine and human DC, we investigated the impact of AII type 1 receptor (AT(1)) deficiency on the phenotypical and functional properties of mouse DC in vitro and in vivo.

Formation of patches on 3D SAMs driven by thiols with immiscible chains observed by ESR spectroscopy.

Beyond stripes: The extreme lipophobicity of perfluorinated chains attached to amphiphilic thiolates triggers the formation of "stars" (or patches) surrounded by amphiphilic alkylthiolates in three-dimensional self-assembled monolayers. This strategy led to the first example of a water-soluble multicompartment monolayer wrapped around a gold core.

Mesenchymal stem cells remain host-derived independent of the source of the stem-cell graft and conditioning regimen used.

Background: Human bone marrow contains hematopoietic stem cells and stroma cells known as mesenchymal stem cells (MSC). MSC are cells with the morphological features of fibroblasts, which, in addition to their nursing function for hematopoietic stem cells, retain the ability to differentiate into cartilage, bone, fat, muscle, and tendon and have an important immunmodulatory function. To understand in more detail hematopoietic engraftment and immune modulation after hematopoietic cell transplantation, we investigated the ability of donor MSC to engraft after hematopoietic cell transplantation in dependency to the conditioning regimen (myeloablative vs.

Water-soluble gold nanoparticles protected by fluorinated amphiphilic thiolates.

The preparation and the properties of gold nanoparticles (Au NPs) protected by perfluorinated amphiphiles are described. The thiols were devised to form a perfluorinated region close to the gold surface and to have a hydrophilic portion in contact with the bulk solvent to impart solubility in water. The monolayer protected clusters were prepared, in an homogeneous phase using sodium thiolates because of the low nucleophilicity of the alpha-perfluorinated thiols, and fully characterized with (1)H, (19)F NMR spectrometry, IR and UV-vis absorption spectroscopies, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS).

Identification of NM23-H2 as a tumour-associated antigen in chronic myeloid leukaemia.

Therapeutic effects of haematopoietic stem cell transplantation are not limited to maximal chemoradiotherapy and subsequent bone marrow regeneration, but include specific as well as unspecific immune reactions known as graft-versus-leukaemia (GvL) effects. Specific immune reactions are likely to be particularly relevant to the long-term treatment of diseases, such as chronic myeloid leukaemia (CML), in which residual cells may remain quiescent and unresponsive to cytotoxic and molecular therapies for long periods of time. Specific GvL effects result from the expression on leukaemic cells of specific tumour-associated antigens (TAAs) in the context of HLA proteins.

The type of ATG matters -- natural killer cells are influenced differentially by Thymoglobulin, Lymphoglobulin and ATG-Fresenius.

Although ATG is frequently used in hematopoietic stem cell transplantation and solid organ transplantation, little is known on its effects on NK cells, which mediate important functions in post-transplantation immunology. We incubated peripheral blood lymphocytes of healthy donors with Thymoglobulin, Lymphoglobulin or ATG-Fresenius. Cell death and apoptosis of NK cells and T cells were determined by flow cytometry using propidium iodide and Annexin V.

Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell transplantation.

Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay.

A novel method to quantify and characterize leukemia-reactive natural killer cells in patients undergoing allogeneic hematopoietic stem cell transplantation following conventional or reduced-dose conditioning.

The antitumor activity of natural killer (NK) cells has recently been shown to be assessable at a single-cell level via flow cytometric detection of CD107a. We used this novel method to prospectively quantify and characterize tumor-reactive NK cells in patients undergoing myeloablative or nonmyeloablative conditioning and allogeneic hematopoietic stem cell transplantation (HSCT). Degranulation of NK cells in the peripheral blood of 34 patients after HSCT (day +30, day +90) was determined by evaluating CD107a expression after coincubation of the cells with tumor targets.

Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation.

Human cytomegalovirus (CMV) is a major cause of death after transplantation. The frequency of pp65-specific T cells was examined in 38 HLA-A2+ stem cell recipients during the first year after transplantation. Patients were divided into four groups based on donor/recipient serostatus: d+/r+ (n=17), d+/r- (n=7), d-/r+ (n=9) and d-/r- (n=5).

Replacement of calcineurin inhibitors with daclizumab in patients with transplantation-associated microangiopathy or renal insufficiency associated with graft-versus-host disease.

Transplantation-associated microangiopathy (TAM) or renal insufficiency (RI) after allogeneic hematopoietic stem cell transplantation is associated with a high mortality. As calcineurin inhibitors (CI) may contribute to TAM or RI, we evaluated the efficacy of replacing CI by daclizumab in patients with graft-versus-host disease (GVHD). Thirteen patients with GVHD-associated TAM and five patients with RI were treated with daclizumab 1 mg/kg intravenous (i.

Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation.

Allogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation.

The anti-lymphoma effect of antibody-mediated immunotherapy is based on an increased degranulation of peripheral blood natural killer (NK) cells.

Background: In patients treated with rituximab and alemtuzumab for lymphomas or CLL, antibody-dependent cellular cytotoxicity (ADCC) is a major mechanism of action. Therefore, assessment of ADCC is mandatory to understand the complex mechanisms leading to the anti-lymphoma effects of monoclonal antibodies (mAb). Due to methodical difficulties, little is yet known about the relevant cell subpopulations and effector mechanisms leading to tumor lysis in ADCC.

Allogeneic hematopoietic cell transplantation following conditioning with 90Y-ibritumomab-tiuxetan.

Radioimmunotherapy (RIT) of relapsed lymphoma is gaining increasing importance. Especially the commercially available anti-CD20 antibody 90Y-ibritumomab tiuxetan is currently under investigation in various trials including dose escalation and autologous hematopoietic progenitor cell support. It is not clear, however, whether the implementation of this radiolabeled antibody into another treatment option for relapsed or poor risk lymphoma patients-allogeneic hematopoietic cell transplantation-interferes with or delays successful engraftment.

Effect of core size on the partition of organic solutes in the monolayer of water-soluble nanoparticles: an ESR investigation.

ESR spectroscopy has been used to study the interaction of para-pentylbenzyl hydroxyalkyl nitroxide with the monolayer of water-soluble protected gold clusters having a core diameter ranging from 1.6 to 5.3 nm.