Endothelin-1 receptor blockade as new possible therapeutic approach in multiple myeloma.

New effective treatments are needed to improve outcomes for multiple myeloma (MM) patients. Receptors with restricted expression on plasmacells (PCs) represent attractive new therapeutic targets. The endothelin-1(EDN1) axis, consisting of EDN1 acting through EDN-receptor A(EDNRA) and B (EDNRB), was previously shown to be overexpressed inseveral tumours, including MM. However, there is incomplete understand-ing of how EDN1 axis regulates MM growth and response to therapy.Besides EDNRA, the majority of MM cell lines and primary malignant PCsexpress high levels of EDNRB and release EDN1. Similarly, bone-marrowmicroenvironment cells also secrete EDN1. Investigating the extent of epi-genetic dysregulation of EDNRB gene in MM, we found that hypermethyla-tion of EDNRB promoter and subsequent down-regulation of EDNRB genewas observed in PCs or B lymphocytes from healthy donors compared toEDNRB-expressing malignant PCs. Pharm acological blockade with the dualEDN1 receptor antagonist bosentan decreased cell viability and MAPK acti-vation of U266 and RPMI-8226 cells. Interestingly, the combination ofbosentan and the proteasome inhibitor bortezomib, currently approved forMM treatment, resulted in synergistic cytotoxic effects. Overall, our datahas uncovered EDN1-mediated autocrine and paracrine mechanisms thatregulate malignant PCs growth and drug response, and support EDN1receptors as new therapeutic targets in MM

A case of warm autoimmune hemolytic anemia with a direct antiglobulin test positive for C3 in rheumatoid arthritis patient successfully treated with low-dose rituximab

A Case of Warm Autoimmune Hemolytic Anemia With a Direct Antiglobulin Test Positive for C3 in Rheumatoid Arthritis Patient Successfully Treated With Low-Dose Rituximab

Alveolar Bone Remodeling with or without Collagen Filling of the Extraction Socket: A High-Resolution X-ray Tomography Animal Study

The healing process of the tooth extraction socket often leads to significant resorption of the alveolar bone, eventually causing clinical difficulties for future implant-supported rehabilitations. The aim of the present animal study was to evaluate alveolar bone remodeling after tooth extraction in a rabbit model, either with or without the use of a plain collagen plug inside the socket, by means of micro-computed tomography. The study included the micro-tomography analysis of 36 rabbits’ incisor extraction sockets, either left empty or filled with a collagen plug. All animals were euthanized in a staggered manner, in order to address molecular, histologic, and radiographic analyses at different time-points, up to 90 days after surgery. The three-dimensional evaluation was carried out using micro-computed tomography technology on excised bone blocks including the alveolus and the contralateral bone. Both linear and volumetric measures were recorded: the percentage of bone volume change (ΔBV) within the region of interest was considered the primary endpoint of the study. The micro-CT analysis revealed mean volumetric changes of −58.1% ± from baseline to 3 months for the control group, and almost no bone loss for the test group, −4.6%. The sockets treated with the collagen plug showed significantly less dimensional resorption, while the natural-healing group showed an evident collapse of the alveolar bone three months after extraction surgery

Evaluation of body fluid mode of Sysmex XN-9000 for white blood cell counts in cerebrospinal fluid

Background: This study was planned to evaluate the analytical performance of the novel and fully automated Sysmex XN-9000 analyzer for rapid analysis of cerebrospinal fluid (CSF) samples. Methods: Forty-four CSF samples were used for method comparison studies between Sysmex XN-9000 body fluid mode and conventional optical microscopy. The bias between data obtained with the two methods was estimated with Bland-Altman plot analysis. The analytical evaluation also included the assessment of imprecision, linearity and carry-over. Results: A good agreement was found between results obtained with Sysmex XN-9000 body fluid mode and optical microscopy. The mean bias was 1.6 7106 cells/L for total white blood cells (95% CI: 1221.8 7106 to 25.1 7106 cells/L), 1.3 7106 cells/L for polymorphonuclear cells (95% CI: 1213.9 7106 to 16.5 7106 cells/L) and 120.6 7106 cells/L for mononuclear cells (95% CI: 1221.5 7106 to 20.3 7106 cells/L). The carryover was found to be lower than 0.01% and the imprecision was lower than 5%. The XN-9000 body fluid mode was also characterized by excellent linearity in the range of values comprised between 85 7106\u20133,197 7106 cells/L, with correlation coefficients (r) always equal to 1.00 (P<0.001). Conclusions: The Sysmex XN-9000 body fluid mode displays excellent analytical performance in terms of imprecision, linearity, carry-over and comparability with conventional optical microscopy, so that it may be used as a first-line, screening technique for rapid analysis of CSF samples referred for both routine and, especially, for urgent testing

Validity and reliability of serologic immunophenotyping of multiple blood group systems by ORTHO Sera with fully automated procedure

The increase of immunization against blood group antigens has reinforced the need for automated extensive blood typing. The aim of this study was to assess both the validity and reliability of red blood cell (RBC) automated agglutination technology in testing for antigens of Kidd (Jk), Duffy (Fy), and MNS (Ss) blood systems. ORTHO Sera (Ortho Clinical Diagnostics, Raritan, NJ) anti-Jka, anti-Jkb, Anti-Fya, anti-Fyb, anti-S, and anti-s reagents were each tested on RBC samples previously typed. Replicates were performed on three separate testing sessions with three consecutive repetitions within each session, thus obtaining 486 test results. Accuracy was assessed by aggregate analysis of sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). Reliability was estimated by a cross-classified mixed-effect logistic model. All reagents tested yielded optimal accuracy (100% for sensitivity and specificity, and 1.00 for AUC), except for anti-S, for which performance was slightly lower (98%, 100%, and 0.99, respectively), owing to misclassification of one sample in a single replicate. Anomalous automated measurements were recorded in 38 of 486 tests (7.8%), which then needed additional manual interpretation. Different sessions and samples were the major contributors to measurement failures (38% and 18%, separately). Order of repetitions and antigen specificity across replicates did not contribute to the risk of failures, although weak evidence of enhanced risk was observed with Jk testing. Automated RBC typing with ORTHO Sera reagents against antigens in the Kidd, Duffy, and MNS blood group systems displayed nearly 100 percent accuracy. However, a sizable number of replicates needed additional ad hoc interpretation, thus suggesting that the reliability could still be improved. Automated agglutination technology represents a viable option for phenotyping large volumes of samples