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Background: Increased cancer risk has been reported in patients with acute coronary syndrome (ACS)., Objectives: To investigate geographic differences in risk malignancy long after ACS., Methods: We enrolled 586 ACS patients admitted to hospitals in three provinces in the Veneto region of Italy in this prospective study. Patient's residency was classified into three urban and three nearby rural areas., Results: All (except for 3) patients completed the follow-up (22 years or death) and 54 % were living in rural areas. Sixteen patients had pre-existing malignancy, and 106 developed the disease during follow-up. Cancer prevalence was 17 % and 24 % (p = 0.05) and incidence of malignancy was 16 and 21/1000 person-years for urban and rural areas, respectively. In unadjusted logistic regression analysis, cancer risk increased from urban to rural areas (odds ratio [OR] 3.4;95 % confidence interval [CI] 1.7-7.1; p = 0.001), with little change from north to south provinces (OR 1.5;95 % CI 1.0-2.2; p = 0.06). Yet, we found a strong positive interaction between urban-rural areas and provinces (OR 2.1;95 % CI 1.2-3.5; p = 0.003). These results kept true in the fully adjusted model. Unadjusted Cox regression analysis revealed increasing hazards ratios (HRs) for malignancy onset from urban to rural areas (HR 3.0;95 % CI 1.5-6.2; p = 0.02), but not among provinces (HR 1.3;95 % CI 1.0-2.0; p = 0.14). Also, we found a strong positive interaction between geographic areas (HR 2.1;95 % CI 1.3-3.5; p = 0.002), even with a fully adjusted model., Conclusions: The results in unselected real-world patients demonstrate a significant geographic difference in malignancy risk in ACS patients, with the highest risk in the north-rural area.

Granulomatosis polyangiitis (GPA) is an ANCA-related vasculitis (AAV) whose clinical manifestations mainly concern the respiratory tract (upper and lower) and the kidney. The treatment of GPA (as well as other AAV) includes the use of immunosuppressive drugs with numerous side effects; the most frequent complications are infectious and neoplastic. GPA frequently relapses. Epstein Barr Virus (EBV) is a ubiquitous virus; it is estimated that about 90% of the world’s population has BEEN EXPOSED TO with this pathogen and has subsequently developed a latent infection. Under certain conditions including immunosuppression EBV may reactivate. We report the clinical case of a 67-year-old woman who presented with GPA involving the upper respiratory tract and renal failure with the need for hemodialysis treatment. The fourth month of induction therapy with cyclophosphamide and methylprednisone she presented with dyspnea and respiratory failure. After excluding pulmonary embolism and heart failure, a series of investigations including high resolution tomography and fibroscopy with broncoalveolar lavage (BAL) were performed which excluded recurrence of pulmonary vasculitis including alveolar haemorrhage A BAL demonstrated EBV-DNA. On this basis EBV pneumonia was diagnosed, and antiviral therapy with acyclovir was begun, followed by clinical and radiological improvement. In patients with GPA treated with immunosuppressive drugs pulmonary involvement may not only be due to the underlying vasculitis, but also to opportunistic agents, which must always be considered., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Angiogenesis, the process by which new vessels form from existing ones, plays an important role in many developmental processes and pathological conditions. We study angiogenesis in the context of a highly controllable experimental environment: the cornea micropocket assay. Using a multidisciplinary approach that combines experiments, image processing and analysis, and mathematical modelling, we aim to provide mechanistic insight into the action of two angiogenic factors, vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF). We use image analysis techniques to extract quantitative data, which are both spatially and temporally resolved, from experimental images, and we develop a mathematical model, in which the corneal vasculature evolves in response to both VEGF-A and bFGF. The experimental data are used for model parametrization, while the mathematical model is used to assess the utility of the cornea micropocket assay and to characterize proposed synergies between VEGF-A and bFGF., (© 2015 The Author(s).)

First clinical report of Harlequin color change (HCC) phenomenon came in 1952 from Neligan and Strang. Since then, HCC has been described in a fairly broad number of clinical reports involving neonates, infants, children, and adult patients. We here present a small case series of HCC occurring in neonates, pointing out three of the different possible presentations (hemifacial, patchy scattered across the whole body, and hemiscrotal) of this phenomenon. A brief discussion and literature review encompassing epidemiology, clinical features, physiopathology, associated conditions, and differential diagnoses of HCC is then presented. In most cases, HCC represents a benign, idiopathic, and rapidly autoresolutive phenomenon, with no need for treatment. Some drugs (especially anesthetics and prostaglandin E) are thought to enhance HCC expression through their influence on the capillary tone in the peripheral vascular bed; this effect is anyway promptly reversible with drug withdrawal. Only in rare circumstances, HCC may act as a clue for serious central nervous system disorders (e.g., meningitis; hypothalamic, brain stem, or sympathetic nervous system lesions); anyway, in these rare occurrences HCC always represents an epiphenomenon of the disease, never acting as the sole sign of the underlying disorder.

Laryngeal Mask Airway (LMA) has been indicated as an effective device for airway management when face-mask ventilation and intubation have both failed in infants weighing >2000 g or delivered ≥34 weeks of gestation. All previous studies used a classic LMA. The current report describes the first case of a very low birthweight infant (1470 g, <3rd centile; 36(+3)gestational weeks) with micrognathia and palate cleft with Cornelia De Lange syndrome, resuscitated at birth with a new supraglottic airway device, i-gel size-1, positioned by a trainee paediatrician at first attempt. The procedure allowed reaching prompt effective ventilation and oxygenation of the patient, who was stabilised and intubated through i-gel., (2015 BMJ Publishing Group Ltd.)

Purpose: VEGF-A blockade has been clinically validated as a treatment for human cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key regulator of tumor angiogenesis and metastasis., Experimental Design: We have applied the recently developed CrossMab technology for the generation of a bispecific antibody recognizing VEGF-A with one arm based on bevacizumab (Avastin), and the other arm recognizing Ang-2 based on LC06, an Ang-2 selective human IgG1 antibody. The potency of Ang-2-VEGF CrossMab was evaluated alone and in combination with chemotherapy using orthotopic and subcutaneous xenotransplantations, along with metastasis analysis by quantitative real-time Alu-PCR and ex vivo evaluation of vessels, hypoxia, proliferation, and apoptosis. The mechanism of action was further elucidated using Western blotting and ELISA assays., Results: Ang-2-VEGF-A CrossMab showed potent tumor growth inhibition in a panel of orthotopic and subcutaneous syngeneic mouse tumors and patient or cell line-derived human tumor xenografts, especially at later stages of tumor development. Ang-2-VEGF-A CrossMab treatment led to a strong inhibition of angiogenesis and an enhanced vessel maturation phenotype. Neoadjuvant combination with chemotherapy resulted in complete tumor regression in primary tumor-bearing Ang-2-VEGF-A CrossMab-treated mice. In contrast to Ang-1 inhibition, anti-Ang-2-VEGF-A treatment did not aggravate the adverse effect of anti-VEGF treatment on physiologic vessels. Moreover, treatment with Ang-2-VEGF-A CrossMab resulted in inhibition of hematogenous spread of tumor cells to other organs and reduced micrometastatic growth in the adjuvant setting., Conclusion: These data establish Ang-2-VEGF-A CrossMab as a promising antitumor, antiangiogenic, and antimetastatic agent for the treatment of cancer., (©2013 AACR.)

Even after a successful renal transplantation, the renal transplant recipients (RTRs) keeps on suffering the consequences of the uremic sickness. Cardiovascular risk, work capacity, and quality of life do not improve according to expectations since biological and psychological problems are not completely solved by pharmacological treatment. Furthermore, post-transplant treatment, per se, induces additional problems (i.e., side effects of drugs). It becomes, indeed, very important to insert "non-pharmacological" therapies able to reverse this trend. Exercise may represent an important contribution in the solution of this problem. In fact, many studies have demonstrated, in the last two decades, that physical training is able both, to improve graft function, work capacity and quality of life, and to reduce cardiovascular risk. In conclusion, if the analysis of the available data suggests that an appropriate dose of physical training represent a useful, safe and non-pharmacologic contribution to RTR treatment, it becomes a kidney transplantologist responsibility to introduce exercise in the current therapy of RTRs.

We have recently reported that elastin microfibril interface located protein 2 (EMILIN2), an extracellular matrix (ECM) glycoprotein, triggers cell death through a direct binding to death receptors. EMILIN2 thus influences cell viability through a mechanism that is unique for an ECM molecule. In the present work, we report an additional function for this molecule. First, we identify the region responsible for the proapoptotic effects, a 90-amino acid residue-long coiled-coil fragment toward the N-terminus of the molecule. The fragment recapitulates EMILIN2 proapoptotic mechanisms. In addition, using either the full molecule or the active fragment, for the first time, we demonstrate a significant antitumoral effect in vivo, likely due to a decrease in tumor cell viability. Unexpectedly, tumors treated with EMILIN2 or the deletion mutant display a significant increase of tumor angiogenesis. In view of this novel finding, the cotreatment of the growing tumors with an antiangiogenic drug led, in most cases, to a complete regression of tumor growth. These results grant further support to recent findings that pinpoint the microenvironment as an important regulator of cell fate under both physiological and pathological conditions and disclose the possibility of using EMILIN2 fragments as potent antineoplastic tools for cancer treatment.

Elastin microfibril interface-located proteins (EMILINs) constitute a family of extracellular matrix (ECM) glycoproteins characterized by the presence of an EMI domain at the N terminus and a gC1q domain at the C terminus. EMILIN1, the archetype molecule of the family, is involved in elastogenesis and hypertension etiology, whereas the function of EMILIN2 has not been resolved. Here, we provide evidence that the expression of EMILIN2 triggers the apoptosis of different cell lines. Cell death depends on the activation of the extrinsic apoptotic pathway following EMILIN2 binding to the TRAIL receptors DR4 and, to a lesser extent, DR5. Binding is followed by receptor clustering, colocalization with lipid rafts, death-inducing signaling complex assembly, and caspase activation. The direct activation of death receptors by an ECM molecule that mimics the activity of the known death receptor ligands is novel. The knockdown of EMILIN2 increases transformed cell survival, and overexpression impairs clonogenicity in soft agar and three-dimensional growth in natural matrices due to massive apoptosis. These data demonstrate an unexpected direct and functional interaction of an ECM constituent with death receptors and discloses an additional mechanism by which ECM cues can negatively affect cell survival.