Michele Centra

Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients.

ABO-mismatch adult living donor liver transplantation using antigen-specific immunoadsorption and quadruple immunosuppression without splenectomy.

ABO‐incompatible (ABO‐I) liver transplantation is a controversial issue because of the generally less favorable outcome as compared to compatible transplants. Encouraging results have been shown by the introduction of new strategies to reduce posttransplant‐specific hemagglutinin (HA) titers with plasmapheresis, reinforced immunosuppression (IS), and the use of splenectomy. We describe a new protocol consisting of daclizumab (DAC) induction, mycophenolate mofetil (MMF)/tacrolimus (TAC)/steroids without splenectomy. Five recipients (mean age of 47 ± 14 yr) undergoing ABO‐I living donor liver transplantation (LDLT) were included in this protocol. Immunoadsorbent columns (Glycosorb ABO) were used for antigen‐specific immunoadsorption (ASI). The median follow‐up was 18.5 ± 10.5 months. ASI was very efficient in lowering HA titers (mean log2 immunoglobulin [Ig] M [IgM] and IgG values before and after ASI were 5.9 ± 2.8 and 1.2 ± 1.4 [P= 0.0038] and 6.5 ± 2.3 and 1.1± 1.9, respectively [P= 0.0001]). Persisting low HA titers were observed over time. No sepsis nor cytomegalovirus infection episodes were recorded. Acute cellular rejection (ACR) occurred in 1 recipient responding to steroid pulse therapy. Two grafts were lost in 2 patients due to technical failure during the first postoperative month. We conclude that ASI using Glycosorb ABO, quadruple immunosuppression including DAC and MMF provide high efficiency to lower HA titers over time, avoiding the need for splenectomy. ABO‐I LDLT can be performed with this adapted IS protocol. Liver Transpl 12:1412‐1417, 2006.

Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia

PURPOSE To build and evaluate a national network able to improve the care of thalassemia, a genetic disorder in haemoglobin synthesis often associated with iron accumulation in a variety of organs, due to the continuous blood transfusions. METHODS The MIOT (Myocardial Iron Overload in Thalassemia) network is constituted by thalassemia and magnetic resonance imaging (MRI) centers. Thalassemia centers are responsible for patient recruitment and collection of anamnestic and clinical data. MRI centers have been equipped with a standardized acquisition technique and an affordable workstation for image analysis. They are able to perform feasible and reproducible heart and liver iron overload assessments for a consistent number of thalassemia patients in a robust manner. All centers are linked by a web-based network, configured to collect and share patient data. RESULTS On 30th March 2008, 695 thalassemia patients were involved in the network. The completion percentage of the patient records in the database was 85+/-6.5%. Six hundred and thirteen patients (88%) successfully underwent MRI examination. Each MRI center had a specific absorption capacity that remained constant over time, but the network was capable of sustaining an increasing number of patients due to continuous enrollment of new centers. The patients comfort, assessed as the mean distance from the patient home locations to the MRI centers, significantly increased during the networks evolution. CONCLUSION The MIOT network seems to be a robust and scalable system in which T2* MRI-based cardiac and liver iron overload assessment is available, accessible and reachable for a significant and increasing number of thalassemia patients in Italy (about 420 per year), reducing the mean distance from the patient locations to the MRI sites from 951km to 387km. A solid, wide and homogeneous database will constitute an important scientific resource, shortening the time scale for diagnostic, prognostic and therapeutical evidence-based research on the management of thalassemia disease.

Myocardial fibrosis by late gadolinium enhancement cardiac magnetic resonance and hepatitis C virus infection in thalassemia major patients.

Aims Our aim was to evaluate the correlation between myocardial fibrosis detected using the late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) technique and chronic hepatitis C (CHC) in a large, retrospective, multicentre cohort of thalassemia major patients. Methods LGE images were acquired in 434 thalassemia major patients (233 men, 31 ± 9 years) enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) study. Hepatitis C virus (HCV)-RNA tests were sensitive to detect more than 50 copies/ml. Results No patient manifested moderate/severe adverse events associated with the use of Gadobutrol. Myocardial fibrosis was detected in 90 (21%) patients. Among the 312 patients tested for HCV-RNA, there was a significant correlation between the presence of myocardial fibrosis and CHC (P = 0.011). Among the 62 patients with myocardial fibrosis tested for HCV-RNA, we found a significantly higher prevalence of diabetes mellitus in CHC patients versus the no-CHC patients (P = 0.049). Conclusion Our findings support the use of the LGE CMR approach well tolerated in the thalassemia major patients with CHC. HCV infection can be involved in the pathogenesis of myocardial fibrosis through both myocarditis directly and the pancreas and liver damage with the development of diabetes indirectly. These patients could therefore benefit from cardioactive drugs and therapeutic interventions directed towards the eradication of virus.

Prospective comparison on cardiac iron by MR in thalassemia major patients treated with combination deferipron-desferrioxamine versus deferipron and desferrioxamine in monoterapy

Background Combination therapy with deferipron and desferrioxamine (DFP+DFO) seems more effective than DFP and DFO in monotherapy in removing myocardial iron. However, no data are available in literature about prospective comparisons on cardiac iron and function in TM patients treated with DFP+DFO versus DFP and DFO in monotherapy. Aim: The aim of this multi-centre study was to assess prospectively in a large clinical setting the efficacy of the DFP+DFO versus DFP and DFO in TM patients by quantitative MR. Methods

Effectiveness of universal precautions in limiting nosocomial transmission of hepatitis C virus in haemodialysis units.

In spite of the high prevalence of anti-HCV positive patients in haemodialysis units (1), there are conflicting results regarding the incidence rate and, consequently, the preventive strategies. Here we report our experience with a three-year follow-up: 88 patients on ROT for at least 6 months were enrolled in three dialysis units. Mean duration of follow-up was 37.2 months. All patients enrolled were tested every 4 months with a 2nd generation antiHCV test (Elisa, Ortho); confirmation of positive samples was performed with Riba test (Ortho), RT-nested PCR was used to detect HCV RNA sequence in serum. The prevention of nosocomial transmission was set up as follows. No segregation of anti-HCV positive patients was set up, no dedicated machines were used, and no dialyzer was reused. Utmost attention was paid in applying universal precautions for prevention of community acquired infection as in Center For Disease Control Recommendation (2). The disinfection protocol for dialysis monitors included a chemical disinfection with peracetic acid or hypoclorite solution after the last dialysis session of the day, while only a washing cycle was applied between dialysis sessions. Anti-HCV antibodies were initially detected in 32 subjects (35.2%); 56 patients were seronegative (Tab. I). The prevalence of anti-HCV positive patients ranged from 18.18% to 41.37%. During the follow-up five seroconversions were observed: 1 in the first, 2 in the second, 2 in the third year (3 in the hospital center, 1 for each outside centers). Thus, mean incidence of seroconversion was 2.79% / year. All seroconverted patients but one were PCR positive and all but one had a positive Riba 2° test (one was indeterminate); two patients received blood transfusion. None of the seroconverted subjects were dialyzing on single pass monitors; three were dialyzed on the same machines of an anti-HCV positive patients: one of these was also transfused 19 months before SC; one was dialyzed next to an anti-HCV positive patient, and the last had none of these risk conditions, but was transfused 15 months before SC (Tab. II). Up to now there is no agreement on applying a segregation protocol for anti-HCV positive and negative patients as has been done for hepatitis B. However, some authors have advocated the segregation of anti-HCV positive patients (3, 4). Should an isolation protocol be accepted, there will be many clinical and organizing problems: the delay between HCV infection and detection of anti-HCV antibodies; the great variability of HCV genomes (5); when isolation was performed SC rate decreased but did not disappear (6); on the other hand, there are organizing problems: we will need up to four different facilities to dialyze patients with or without HBV and HCV infection or coinfec-