Comprehensive multidisciplinary patient assessment and selection before TAVI procedure.

Aortic stenosis is a common disorder that affects nearly 5% of persons >75 years of age. Aortic valve replacement is indicated for symptomatic patients with severe aortic stenosis, as the prognosis of untreated patients is poor. Nevertheless, many patients with symptomatic severe aortic stenosis do not undergo surgical valve replacement, which has been attributed to comorbidities.

Schwann cell autophagy counteracts the onset and chronification of neuropathic pain.

Axonal degeneration in peripheral nerves after injury is accompanied by myelin degradation initiated by Schwann cells (SCs). These cells activate autophagy, a ubiquitous cytoprotective process essential for degradation and recycling of cellular constituents. Concomitantly to nerve insult and axonal degeneration, neuropathic pain (NeP) arises.

Estimating incidence of organ cancer related to PCI radiation exposure in patients treated for acute and chronic total occlusions.

Background: Minimal data exist on the number of additional cancer cases related to radiation exposure following percutaneous coronary intervention (PCI). The aim of this study is to estimate the lifetime attributable risk (LAR) of cancer incidence for individual organs following radiation exposure during PCI in the context of two opposite sides of the angiographic spectrum of coronary occlusive disease: ST-elevation myocardial infarction (STEMI) and chronic coronary total occlusion (CTO).

Methods And Results: We identified all consecutive patients treated with PCI for STEMI (n = 555) and for CTO (n = 543) in a tertiary care center in 6 years.

PlaCor PRT measurement of shear-activated platelet aggregate formation in stable patients treated with single and dual antiplatelet therapy.

Shear forces play a key role in thrombus formation and shear-based tests may better reflect physiological conditions in vivo compared with agonist-based tests. We evaluated the PlaCor PRT®, a novel platelet reactivity test based on shear-induced platelet aggregation, in patients with stable coronary artery disease (CAD) treated with single (SAPT) and dual antiplatelet therapy (DAPT). We examined 100 patients with multiple risk factors for CAD and/or documented stable CAD: 38 treated with SAPT, aspirin 100 mg qd, 62 treated with DAPT, aspirin 100 mg + clopidogrel 75 mg qd, compared with age- and sex-matched healthy volunteers without antiplatelet therapy (HV, n = 35).

Management of large coronary dissection after STAR.

The guided-STAR technique is an alternative anterograde approach for treatment of coronary chronic total occlusion (CTO) and it is usually followed by implantation of multiple stents. We describe a case of residual long coronary dissection left unstented after guided-STAR, with good results at 2months follow-up. This case emphasizes the fact that sometimes even the longest coronary dissections can be left unstented especially in the contest of a CTO.

Long-term results after transcatheter aortic valve implantation: positive and side effects.

The scientific and technological progress in the field of medicine has allowed to treat patients with severe aortic valve stenosis and with a high perioperative risk. Before the introduction of transcatheter aortic valve implantation (TAVI), patients considered at high risk for surgical treatment were managed with medical therapy or with balloon aortic valvuloplasty. With more than 50000 transcatheter aortic valves implanted in patients around the world, TAVI has demonstrated to be a valid alternative to surgical aortic valve replacement in inoperable and high-risk patients.

Fibroblast autophagy in fibrotic disorders.

Fibrotic disorders are multistage progressive processes that often arise from different causes and are commonly associated with chronic inflammation. Excessive deposition of extracellular matrix is the hallmark of many fibrotic diseases. This may be due to an excess of fibroblast recruitment and activation, as well as to their differentiation in myofibroblasts.

L1CAM and its cell-surface mutants: new mechanisms and effects relevant to the physiology and pathology of neural cells.

The L1 syndrome, a genetic disease that affects 1/30 000 newborn males, is sustained by numerous missense mutations of L1 cell adhesion molecule (L1CAM), an adhesion surface protein active also in transmembrane signaling, essential for the development and function of neurons. To investigate the cell biology of L1CAM, we employed a high RE1-silencing transcription (factor) clone of the pheochromocytoma PC12 line, defective in L1CAM expression and neurite outgrowth. The clone was transfected with wild-type L1CAM and four missense, disease-inducing point mutants encoding proteins distributed to the cell surface.

Cell surface estrogen receptor alpha is upregulated during subchronic metabolic stress and inhibits neuronal cell degeneration.

In addition to the classical nuclear estrogen receptor, the expression of non-nuclear estrogen receptors localized to the cell surface membrane (mER) has recently been demonstrated. Estrogen and its receptors have been implicated in the development or progression of numerous neurodegenerative disorders. Furthermore, the pathogenesis of these diseases has been associated with disturbances of two key cellular programs: apoptosis and autophagy.

miR-511-3p modulates genetic programs of tumor-associated macrophages.

Expression of the mannose receptor (MRC1/CD206) identifies macrophage subtypes, such as alternatively activated macrophages (AAMs) and M2-polarized tumor-associated macrophages (TAMs), which are endowed with tissue-remodeling, proangiogenic, and protumoral activity. However, the significance of MRC1 expression for TAM's protumoral activity is unclear. Here, we describe and characterize miR-511-3p, an intronic microRNA (miRNA) encoded by both mouse and human MRC1 genes.

Takayasu arteritis: intravascular contrast medium for MR angiography in the evaluation of disease activity.

Objective: Takayasu arteritis is difficult to diagnose, and the evaluation of disease activity is even more challenging. Laboratory, clinical, and radiologic criteria are limited indicators of disease activity. Gadofosveset trisodium is a recently introduced intravascular contrast agent.

Manipulating Immune Tolerance with Micro-RNA Regulated Gene Therapy.

The success of in vivo gene therapy greatly depends on the ability to control the immune response toward the therapeutic transgene. Over the last decade several vector-based and pharmacological approaches have been explored to control the immune-mediated clearance of transgene-expressing cells after viral delivery. One important outcome from these studies is the concept that expression of a transgene in tolerance-promoting organs, such as the liver and tolerogenic antigen-presenting cells, can help safeguard transgene-expressing cells from immune-mediated clearance.

Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus.

Objective: Estrogens influence many physiologic processes and are also implicated in the development or progression of numerous diseases, including autoimmune disorders. Aberrations of lymphocyte homeostasis that lead to the production of multiple pathogenic autoantibodies, including autoantibodies specific to estrogen receptor (ER), have been detected in the peripheral blood of patients with systemic lupus erythematosus (SLE). This study was undertaken to assess the presence of both anti-ERα and anti-ERβ antibodies in sera from patients with SLE, to analyze the effect of these antibodies on peripheral blood T lymphocyte homeostasis, and to evaluate their role as determinants of disease pathogenesis and progression.

Site-specific integration and tailoring of cassette design for sustainable gene transfer.

Integrative gene transfer methods are limited by variable transgene expression and by the consequences of random insertional mutagenesis that confound interpretation in gene-function studies and may cause adverse events in gene therapy. Site-specific integration may overcome these hurdles. Toward this goal, we studied the transcriptional and epigenetic impact of different transgene expression cassettes, targeted by engineered zinc-finger nucleases to the CCR5 and AAVS1 genomic loci of human cells.

Coronary chronic total occlusions: mid-term comparison of clinical outcome following the use of the guided-STAR technique and conventional anterograde approaches.

Aim: There are limited data on the mid-term safety following the use of the guided-subintimal tracking and re-entry (guided-STAR) technique for the treatment of chronic total occlusions (CTO) and concerns have arisen about a potential increased risk of stent thrombosis (ST).

Objectives: The aim of this study was to evaluate the mid-term safety in terms of cardiac death and ST after recanalization using the contrast guided-STAR technique when compared to conventional anterograde CTO recanalization (CA-CTO).

Methods And Results: This retrospective study analyzed 355 consecutive patients with successful angiographic recanalization (residual stenosis <20% and TIMI flow grade ≥2) of CTO lesion.

In vivo fate analysis reveals the multipotent and self-renewal features of embryonic AspM expressing cells.

Radial Glia (RG) cells constitute the major population of neural progenitors of the mouse developing brain. These cells are located in the ventricular zone (VZ) of the cerebral cortex and during neurogenesis they support the generation of cortical neurons. Later on, during brain maturation, RG cells give raise to glial cells and supply the adult mouse brain of Neural Stem Cells (NSC).

Celiac plexus block for pancreatic cancer pain in adults.

Background: Pancreatic cancer causes severe pain in 50 to 70% of patients and is often difficult to treat. Celiac plexus block (CPB) is thought to be a safe and effective technique for reducing the severity of pain.

Objectives: To determine the efficacy and safety of celiac plexus neurolysis in reducing pancreatic cancer pain, and to identify adverse effects and differences in efficacy between the different techniques.

Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial.

Background: Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial.

Methods: The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer.

Outgrowth of neurites is a dual process.

In neurons and neurosecretory (nerve) cells, neurite outgrowth requires the enlargement of the plasma membrane sustained by the exocytosis of specific vesicles. The well known, slow canonical form of outgrowth induced in pheochromocytoma PC12 cells by NGF, as well as the outgrowth taking place in neurons, involve vesicles positive for the vSNARE Ti-VAMP. Working in defective PC12 clones expressing high levels of the transcriptional repressor REST, we have identified now a new, rapid form of outgrowth, triggered by activation of a small GTPase, Rac1.

Outcomes after transcatheter aortic valve implantation with both Edwards-SAPIEN and CoreValve devices in a single center: the Milan experience.

Objectives: Our aim was to assess clinical outcome after transcatheter aortic valve implantation (TAVI) performed with the 2 commercially available valves with 3 delivery approaches selected in a stepwise fashion.

Background: Limited data exist on the results of a comprehensive TAVI program using different valves with transfemoral, transapical, and transaxillary approaches for treatment of severe aortic stenosis.

Methods: We report 30-day and 6-month outcomes of high-risk patients consecutively treated in a single center with either the Medtronic-CoreValve (MCV) (Medtronic, Minneapolis, Minnesota) or Edwards-SAPIEN valve (ESV) (Edwards Lifesciences, Irvine, California) delivered via the transfemoral or transaxillary approaches and ESV via the transapical approach.

Coronary left main and non-left main bifurcation angles: how are the angles modified by different bifurcation stenting techniques?

Background: Investigation of the correlation between bifurcation angles and outcomes is limited with discordant results. The aim of this study is to investigate left main (LM) and non-left main (N-LM) bifurcation angles and their modification after percutaneous coronary intervention (PCI). Measurement of all three angles adds to our understanding of bifurcation anatomy and the resultant effect of different stenting techniques.