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Abstract: Objective: : To investigate possible associations of TNF-α and TNF-RII gene polymorphisms with diffuse or limited skin involvement phenotype in a cohort of Systemic Sclerosis (SSc) patients. Methods: : One-hundred and fourteen consecutive SSc patients attending the referral centres of three academic hospitals in Italy (University of Naples, Pavia and Udine), 56 with the diffuse (dcSSc) and 58 with limited (lcSSc) skin involvement subsets, and 170 healthy blood donors (HBDs) were included in the study. The extracted DNA was genotyped for the following polymorphisms: TNF-α (-238, +489) and TNF-RII (+196), using the polymerase chain reaction (PCR) and the restriction enzymes BamHI, HpyCH4 IV and NlaIII, respectively. Results: : The AG/AA (presence of allele A) genotypes in position -238 and the AG genotype in position +489 of the TNF-α gene were found significantly increased in SSc, as a whole, when compared with healthy blood donors (, p=0.03 for -238 and , p=0.02 for +489, respectively). The rare GG genotype in exon 6 (codon 196) of the TNF-RII gene was also found increased in SSc compared to HBDs, even though the difference did not show statistical significance (, p=0.17). The strength of the association was mainly due to the dcSSc phenotype (Fisher test, p=0.04 for -238, , p<0.01 for +489 and , p=0.04 for the +196 TNF-RII, respectively). Conclusions: : TNF-α and TNF-RII gene polymorphisms seem to contribute to the development of SSc and in particular to the diffuse phenotype. [Copyright &y& Elsevier]

Background: Allogeneic stem cell transplantation is a potentially curative treatment for myelofibrosis, although its use is limited by a high rate of transplant-related mortality. In this study, we evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors., Design and Methods: One hundred patients were transplanted in 26 Italian centers between 1986 and 2006. We analyzed the influence of the patients' characteristics and the clinical features of their disease before stem cell transplantation and of transplant procedures on transplant-related mortality, overall survival, and relapse-free survival by means of univariate and multivariate analyses., Results: The median age of the patients at the time of stem cell transplantation was 49 years (range, 21-68) and 90% of them had an intermediate or high Dupriez score. Forty-eight percent received a myeloablative conditioning regimen and 78% received stem cells from matched sibling donors. The cumulative incidence of engraftment at day 90 after transplant was 87% (95% CI, 0.87-0.97). The cumulative 1-year and 3-year incidences of transplant-related mortality were 35% and 43%, respectively. The estimated 3-year overall and relapse-free survival rates after stem cell transplantation were 42% and 35%, respectively. In multivariate analysis, negative predictors of transplant-related mortality were year of stem cell transplantation before 1995, unrelated donor, and a long interval between diagnosis and transplantation. There was a trend towards longer overall and relapse-free survival in patients receiving peripheral blood stem cells rather than bone marrow as the source of their graft (p=0.070 and p=0.077, respectively). The intensity of the conditioning regimen (myeloablative versus reduced intensity regimens) did not significantly influence the outcome., Conclusions: We conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. We observed that a reduction in transplant-related mortality was associated with the choice of a matched sibling donor, whereas longer overall survival was associated with the use of peripheral blood as the source of stem cells.

Rituximab 375 mg/m(2) weekly for four weeks has significant activity in patients with immune thrombocytopenia. We evaluated the activity of lower dose rituximab (100 mg iv weekly for 4 weeks) in 28 adults with idiopathic thrombocytopenic purpura. Overall (platelet count > 50 x 10(9)/L) and complete responses (platelet count > 100 x 10(9)/L) were achieved in 21/28 (75%) and 12/28 (43%) patients respectively. The median time to response and time to complete response were 31 and 44 days respectively. After a median follow-up of 11 months (range 3-18), 7/21 (33%) patients relapsed and 3 needed further treatments. In patients with idiopathic thrombocytopenic purpura, lower dose rituximab seems to show similar activity to standard dose.

Objective: The objective of our study was to test dynamic MRI in evaluating mammographically detected suspicious microcalcifications., Materials and Methods: One hundred twelve patients with mammographically detected microcalcifications with BI-RADS category 5 (n = 78) or 4 (n = 34) lesions were studied at 17 centers a using 3D gradient-echo dynamic coronal technique (< or = 3 mm thickness) and 0.1 mmol/kg of gadoteridol. A pathologic sample was obtained in all cases. Agreement between the major diameter measured on mammography, MRI, or both and the major diameter measured at pathologic examination was calculated in 62 cases., Results: Of the 112 lesions, pathologic examination revealed 37 benign lesions, 33 ductal carcinoma in situ (DCIS), and 42 invasive carcinomas. The specificity of MRI for benign lesions was 68%. Considering the subgroups of calcifications alone and calcifications associated with masses, the specificity values became 79% and 33%, respectively. The sensitivity of MRI for DCIS was 79%. Analysis of the two subgroups showed sensitivity values of 68% for calcifications alone and of 1% for calcifications associated with masses. The sensitivity for invasive carcinomas was 93%. Analysis of the two subgroups showed sensitivity values to be 92% for calcifications alone and 94% for calcifications associated with masses. Considering the overall results, the sensitivity of MRI was 87%; specificity, 68%; positive predictive value, 84%; negative predictive value, 71%; and accuracy, 80%. Considering the subgroups of calcifications alone and calcifications associated with masses, the sensitivity values became 80% and 97%; the positive predictive values, 86% and 82%; the negative predictive values, 71% and 75% (95% confidence interval [CI], 0.19-0.99); and the accuracy values, 80% and 82% (95% CI, 0.66-0.92), respectively. An odds ratio (OR) of 13.54 (95% CI, 5.20-35.28) showed a raised risk of malignant breast tumor in subjects with positive MR examination of mammographically detected suspicious clusters of microcalcifications. The statistical analysis on each subgroup showed an OR of 15.07 (95% CI, 4.73-48.08) for calcifications alone and an OR of 14.00 (95% CI, 1.23-158.84) for calcifications associated with masses. Any significant improvement in the predictive ability of dynamic MRI depending on the extent of calcifications on mammography was not proved. Considering the 62 cases of proved malignancy with measured maximal diameter at pathologic examination, both mammography and MR examination seem to overestimate tumor extent., Conclusion: The not-perfect sensitivity of MRI (87%), when applying our interpretation criteria and imaging sequences, is a crucial point that prevents us from clinical use of MRI in the diagnosis of mammographically detected microcalcifications.

In this paper preliminary results are presented of a prospective study designed to examine the effect of maxillary fixation methods on postoperative stability. The purpose of this study was to evaluate the stability of Le Fort I osteotomy stabilized with semirigid fixation of the maxilla (SRMF) or rigid fixation of the maxilla (RMF). All patients had skeletal Class III malocclusion and underwent bimaxillary surgery (Le Fort I maxillary advancement with or without superior repositioning and bilateral sagittal split osteotomies of the mandible). Standardized cephalometric analysis was performed on serial radiographs of 42 patients immediately before surgery, 1 week after surgery, after release of fixation, and 1 year postoperatively. The patients were randomized into 2 treatment groups: 23 patients received RMF (group A), and 19 patients received SRMF (group B). Within the groups, patients showed good stability with regard to their baseline characteristics. To show the therapeutic equivalence of the 2 treatments, analysis of the recorded data followed the approach for an equivalence trial. The mean surgical advancement was 5.34 +/- 1.50 mm for group A and 4.51 +/- 1.37 mm for group B. The mean amount of postsurgical relapse was 0.98 +/- 1.27 mm for group A and 0.30 +/- 1.04 mm for group B. Group A patients experienced 93% of their relapse (0.92 mm) during fixation, while group B patients experienced 96% of their relapse (0.29 mm) after release of fixation. RMF provided better stability than SRMF for all maxillary landmarks in the vertical plane. All considered points both in horizontal and vertical plane exhibited full equivalence for 95% confidence intervals, which seems to indicate equivalent stability between the surgical procedures.