Impact of IFN lambda 3/4 single nucleotide polymorphisms on the cytomegalovirus reactivation in autologous stem cell transplant patients

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation

Fibrin glue for endoscopic gastrointestinal bleeding in patients with impaired haemostasis.

No abstract availabl

Use of autologous bone marrow cells concentrate enriched with platelet-rich fibrin on corticocancellous bone allograft for posterolateral multilevel cervical fusion

The outcomes of posterolateral multilevel spine fusion in difficult clinical settings, such as in an aged multi-diseased osteoporotic patient, remain unpredictable. The osteoprogenitor cells in bone marrow decrease with ageing without losing their osteogeneic potential. Autologous bone marrow cells (BMCs) from iliac crest aspirate can be concentrated in the operating room and platelet-rich fibrin (PRF) can be obtained from a peripheral blood as a source of autologous osteoprogenitor cells and growth factors, respectively. We present the case of an 88 year-old multi-diseased osteoporotic patient affected by cervical stenosis and subjected to C3--C7 posterior decompression, instrumentation and posterolateral fusion, using an intraoperative 'tissue-engineered' composite made of corticocancellous bone allograft augmented with autologous BMCs concentrate from iliac crest aspirate enriched with PRF from peripheral blood. Lateral dynamic X-rays and CT scan showed consolidation signs at 3 months follow-up, with solid C3--C7 fusion at 6 months follow-up. This paper describes a simple and effective method for potentially improving the fusion rate in aged osteoporotic patients by using corticocancellous bone allograft augmented with autologous BMCs concentrate from the iliac crest, enriched with PRF from peripheral blood, rapidly obtained before the surgical procedure

Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders.

Data from the Italian Hemophilia Centres were collected to perform a retrospective survey of joint arthroplasty in patients with severe hemophilia. Twenty-nine of 49 hemophilia centers reported that 328 of the 347 operations were carried out in 253 patients with severe hemophilia A (HA) and 19 in 15 patients with severe hemophilia B (HB). When results were normalized to the whole Italian hemophilia population (1770 severe HA and 319 severe HB), patients with HA had a 3-fold higher risk of undergoing joint arthroplasty (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.97-5.77; P < .001). These results were confirmed after adjustment for age, HIV, hepatitis C virus (HCV), and inhibitor in a Cox regression model (HR, 2.65; 95% CI, 1.62-4.33; P < .001). The survival analysis of time to joint arthroplasty in the subset of patients with severe HA was not affected by the severity of factor VIII (FVIII) gene mutations. A systematic review of literature articles reporting joint arthroplasties in HA and HB showed that the proportion of HA patients who had undergone arthroplasties was higher than that of HB patients, in agreement with the findings in our Italian cohort. These data suggest that the 2 inherited coagulation disorders have a different severity of clinical phenotype

Treatment of 72 newly diagnosed Waldenstrom macroglobulinemia cases with oral melphalan, cyclophosphamide, and prednisone.

BACKGROUND: Current treatment regimens for Waldenstrom macroglobulinemia (WM) are based on the use of oral alkylating agents. Recently, however, other more costly agents have been proposed for the treatment of WM. In the current study, the authors report on results obtained using oral melphalan, cyclophosphamide, and prednisone (MCP) to treat 72 patients with WM, and they compare these results (and the associated costs) with those observed using more aggressive protocols. METHODS: Between July 1973 and April 2002, the authors documented overexpression of the immunoglobulin M paraprotein in 317 consecutive patients. Of these, 100 had newly diagnosed WM, and the 72 who were symptomatic were treated using the MCP protocol. Response rate, overall survival (OS), response duration, freedom from progression (FFP), event-free survival (EFS) duration, toxicity, and cost per course in Euro and U.S. dollars were evaluated for patients receiving this regimen. RESULTS: Seventy-one of 72 patients (99%) were evaluable. Of these patients, 55 (77%) achieved a response; 7 others (10%) experienced disease stabilization, and the remaining 9 (13%) experienced disease progression. After a median follow-up of 72 months (range, 3-195 months), the median durations of EFS, FFP, response, and OS were 47, 55, 64, and 66 months, respectively. No World Health Organization Grade III or IV toxicities were observed, and side effects were limited to transient nausea, emesis, and mild neutropenia. The cost per course of the MCP regimen was $16, similar to that of standard protocols involving chlorambucil and much less than that of more aggressive protocols (price range,$91-11091) proposed for the treatment of WM. CONCLUSIONS: Like chlorambucil-based protocols, the MCP regimen is a cost-effective and safe option for the treatment of patients with WM. Furthermore, the results obtained do not appear to be inferior to those yielded by more expensive, aggressive, and toxic intravenous protocols

Zoledronic acid induces significant and long-lasting modifications of circulating angiogenic factors in cancer patients

Purpose: The commercial availability of zoledronic acid, a third generation bisphosphonate, prompted us to evaluate the modifications in angiogenic cytokines levels after a single i.v. infusion of this drug. Experimental Design: Thirty consecutive cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg of zoledronic acid before any chemotherapy. The patients were prospectively evaluated for circulating levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion. Results: Basal serum VEGF median levels were significantly decreased at days 2 (-23%), 7 (-28%), and 21 (-34%) after zoledronic acid infusion (P = 0.0498, 0.0090, and 0.0011, respectively). Serum PDGF levels were significantly decreased by 25% 1 day after zoledronic acid infusion (P = 0.0032). This effect on circulating PDGF levels persisted for 2 days after bisphosphonate infusion (P = 0.0050). PDGF levels had returned to values similar to the median basal value at 7 and 21 days. Moreover, a linear regression model with variance analysis showed a significant positive correlation between basal VEGF and PDGF values but not at the following time points. No significant differences were recorded in platelet levels, WBC count, or hemoglobin concentration before and after zoledronic acid single infusion. Conclusions: This study confirms that zoledronic acid could have an in vivo antiangiogenic property through a significant and long-lasting reduction in serum VEGF levels