Leukocyte and platelet activation in patients with giant cell arteritis and polymyalgia rheumatica: A clue to thromboembolic risks?

Ischemia is a leading causes of morbidity in giant cell arteritis (GCA). We studied circulating platelets and leukocytes in patients with GCA and with polymyalgia rheumatica. Normal healthy donors (>60 a) served as controls. Patients had a significantly greater fraction of platelets expressing P-selectin, of platelet–Nph and platelet–Mo aggregates, and of Nph and Mo expressing tissue factor. These differences were correlated with the percentage of platelets expressing P-selectin and were not influenced by clinical features or by systemic inflammation. Activated circulating leukocytes and platelets could contribute to indolent vessel inflammation and possibly to thromboembolic events in patients with systemic large vessel vasculitis.     

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.     

Cicatricial iatrogenic lower eyelid malposition in skin cancer surgery: results of a combined approach

PurposeMalposition of the lower lid, including rounding of the lateral canthal angle, lower eyelid retraction with inferior scleral show, and ectropion, is a relatively frequent complication in the surgical treatment of skin cancer of the cheek and zygomatic areas. The tarsal strip technique, in association with a vertical vector cheek lift, is a reliable method for correcting lower lid malposition.Materials and patientsFrom January 2008 to January 2010, we treated 19 patients with lower eyelid malposition after skin cancer surgery of the cheek and zygomatic areas. To correct lower eyelid malposition, we used the tarsal strip technique and a vertical vector cheek lift in all patients.ResultsEleven patients had scleral show and eight patients had ectropion. Sixteen patients obtained satisfactory correction of the eyelid malposition in a single surgical procedure, while three patients required a second surgical step to correct the remaining scleral show. Good esthetic and functional results were achieved in all cases.ConclusionsThe surgical treatment of skin cancer of the cheek and zygomatic areas has the potential for postoperative sequelae. The tarsal strip technique, in association with a vertical vector cheek lift, is a relatively simple technique for correcting scleral show and ectropion.     

Pure Erythroid Leukemia Mimicking Ewing Sarcoma/Primitive Neuroectodermal Tumor in an Infant

Pure erythroid leukemia (PEL) is a rare type of acute myeloid leukemia (AML) with a very aggressive clinical course. Presentation as a myeloid/erythroid sarcoma is exceedingly rare. We describe an infantile PEL presenting as a multifocal myeloid sarcoma, clinically and pathologically mimicking Ewing sarcoma/PNET family of tumors. The patient died 8 weeks after the initial presentation due to widespread disease. Our case shows that PEL needs to be considered in the differential diagnosis of small round blue cell tumors in infancy. A meticulous workup including immunohistochemistry, flow cytometry, molecular, and cytogenetic studies was required to reach the diagnosis.     

Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux

The multidrug resistance protein 1 (MRP1) is involved in multidrug resistance of cancer cells by mediating drug efflux out of cells, often in co-transport with glutathione (GSH). GSH efflux mediated by MRP1 can be stimulated by verapamil. In cells overexpressing MRP1, we have previously shown that verapamil induced a huge intracellular GSH depletion which triggered apoptosis of the cells. That phenomenon takes place in the more global anticancer strategy called “collateral sensitivity” and could be exploited to eradicate some chemoresistant cancer cells. Seeking alternative compounds to verapamil, we screened a library of natural flavonoids and synthetic derivatives. A large number of these compounds stimulate MRP1-mediated GSH efflux and the most active ones have been evaluated for their cytotoxic effect on MRP1-overexpressing cells versus parental cells. Interestingly, some are highly and selectively cytotoxic for MRP1-cells, leading them to apoptosis. However, some others do not exhibit any cytotoxicity while promoting a strong GSH efflux, indicating that GSH efflux is necessary but not sufficient for MRP1-cells apoptosis. In support to this hypothesis, structure activity relationships show that the absence of a hydroxyl group at position 3 of the flavonoid C ring is an absolute requirement for induction of MRP1-cells death, but is not for GSH efflux stimulation. Chrysin (compound 8) and its derivatives, compounds 11 and 22, exhibit a high selectivity toward MRP1-cells with a IC₅₀ value of 4.1 μM for compound 11 and 4.9 μM for chrysin and compound 22, making them among the best described selective killer compounds of multidrug ABC transporter-overexpressing cells.     

Association between nocturnal blood pressure dipping and insulin resistance in children affected by NAFLD

The aim of this study was to analyse the relationship between insulin–glucose metabolism, nocturnal blood pressure dipping and nonalcoholic fatty liver disease (NAFLD) in obese adolescents without diabetes. One hundred one consecutive children, with biopsy-proven NAFLD, were included in this study. Blood samples were drawn for the analyses of liver function tests, insulin–glucose metabolism and lipid profile appraisal. An ambulatory blood pressure measurement (ABPM) was performed. Seventy-six children (75.3 %) were systolic nondippers, and 23 of them were diastolic nondippers (30.3 %). No differences were found in the anthropometric parameters between the two groups. When compared to the systolic dippers, the systolic nondippers had higher medians of mean nocturnal blood pressure, glucose at 0, 60 and 120 min in the oral glucose tolerance test (OGTT), OGTT insulin at all time points and insulin-resistance values. No correlation of histopathological features with dipping/nondipping statuses was found. Conclusions: We found an association between a nocturnal blood pressure fall and measures of insulin levels, independent of obesity, or daytime blood pressure levels, among the obese patients with NAFLD. Although no association between nondipping profiles and NAFLD was observed in our study, further studies with a longer term follow-up are needed, to better elucidate the complex link between these particular entities.     

The Osteoprint: A bioinspired two-photon polymerized 3-D structure for the enhancement of bone-like cell differentiation

The need for a better understanding of cell behavior and for exploiting cell functions in various healthcare applications has driven biomedical research to develop increasingly complex fabrication strategies to reproduce the natural biological microenvironment in vitro. Different approaches have led to the development of refined examples of 2- and 3-D structures able to sustain cellular proliferation, differentiation and functionality very similar to those normally occurring in living organisms. One such approach is two-photon polymerization. In this paper, we present a trabecula-like structure (which we have named “Osteoprint”) that resembles to the typical microenvironment of trabecular bone cells. Starting from microtomography images of the trabecular bone, we prepared several Osteoprints through two-photon polymerization and tested the behavior of SaOS-2 bone-like cells cultured on our structures. Interestingly, we found that Osteoprints deeply affect cellular behavior, determining an exit from the cell cycle and an enhancement of osteogenic differentiation. Indeed, we found an up-regulation of the genes involved in SaOS-2 cell maturation and an increase in hydroxyapatite production and accumulation upon SaOS-2 culture on the Osteoprints. The findings we obtained are extremely interesting, and open up new perspectives in “bioinspired” approaches for tissue engineering and regenerative medicine.