Fabio Mazza

Immunoadsorption apheresis and immunosuppressive drug therapy in the treatment of complicated HCV‐related cryoglobulinemia

The immunosuppressive drug therapy (IDT) is not always effective to avoid the development of complications in hepatitis C virus‐related cryoglobulinemia (HCV‐Cr). Removal of cryoglobulins by therapeutic plasmapheresis is currently accepted. In this randomized, parallel group study, 17 male and female patients aged 43–79 years, with complicated HCV‐Cr, were submitted for 12 weeks (initial immunosuppressive therapy) to IDT (α‐interferon, pegylated‐interferon α‐2a, cyclophosphamide, methylprednisolone, prednisone, cyclosporine, ribavirin, and melphalan). Then, they were randomly assigned to two parallel groups: A # 9 patients treated by immunoadsorption apheresis (Selesorb®) (IA) plus IDT, and B # 8 patients submitted to IDT only, for further 12 weeks. # 187 IA aphereses were performed. No adverse reactions or complications were observed. A Clinical Score (CS) was adapted from a pre‐existing scoring model to evaluate signs and symptoms inherent to the underlying immunologic disorder. The CS was calculated at baseline (CS0), after the initial immunosuppressive therapy (CS1 = 12 weeks) when patients were treated only with IDT, and at the end of the study (24 weeks) in the group A (CSA; IA plus IDT) and B (CSB; IDT only). The score did not change significantly from CS0 to CS1. However, statistically significant differences were observed between CS1 and CSA (P < 0.001), and CSA versus CSB (P = 0.03), respectively. The changes observed were favorable to the patients assigned to the IA plus IDT group (A): in most case relief of symptoms and complications have been obtained. J. Clin. Apheresis, 2009.

Effects of Low-Dose Atorvastatin and Rosuvastatin on Plasma Lipid Profiles A Long-Term, Randomized, Open-Label Study in Patients with Primary Hypercholesterolemia

Background and objectiveDespite the favorable effects of reduction of low-density lipoprotein-cholesterol (LDL-C) levels in decreasing the risk of coronary heart disease, many patients treated with lipid-lowering HMG-CoA reductase inhibitors (statins) do not achieve goal LDL-C levels. This may be due to high doses of statins prescribed that could potentially induce adverse effects and compromise patient safety and compliance with considerable expense in the long-term. We compared the actions of rosuvastatin and atorvastatin, administered at the low dosages of 10 and 20 mg/day, respectively, in reducing plasma LDL-C levels and their effects on other components of the atherogenic lipid profile in patients with primary hypercholesterolemia.MethodsIn this randomized, parallel group, open-label clinical study, 106 patients with LDL-C >200 mg/dL were treated with rosuvastatin 10 mg/day (group A; n = 52), or atorvastatin 20 mg/day (group B; n = 54) for 48 weeks.ResultsAt 48 weeks, rosuvastatin 10 mg/day was associated with a significantly greater reduction in plasma LDL-C levels compared with atorvastatin 20 mg/day (−44.32% vs −30%; p < 0.005). Compared with atorvastatin, rosuvastatin also produced a greater reduction in plasma total cholesterol, triglycerides, and non-high-density lipoprotein-cholesterol (non-HDL-C) levels (p < 0.005). Plasma HDL-C levels were not affected significantly, independent of the drug used.ConclusionIn high-risk patients with primary hypercholesterolemia, rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels, enabling goal LDL-C levels to be achieved and improving other lipid parameters. Both treatments were well tolerated over 48 weeks.

Multiple Lipid-lowering Treatment in Pediatric Patients with Hyperlipidemia

UNLABELLED 256 pediatric patients with primary hyperlipidemia aged 14.2 ± 8.5 years (females: 155; males:101) seen in our lipid clinic were evaluated retrospectively to assess the effect of multiple lipid-lowering treatment (diet only, diet+glucomannan 1.000 mg/day (G), diet+ezetimibe (E) 10 mg/day and diet+atorvastatin (A) 10 mg/day). The patients were assigned to four groups according to their type of treatment: A-Diet (#82; age 12.7 ± 8 years; females 52, males:30); B-Diet+G (#78; age 13.3 ± 9 years; females 61, males 17); C-Diet+E 10 mg/day (#50; age 14.5 ± 7 years; females 31, males 19); D-Diet+A 10 mg/day (#46; age 16.4 ± 10 years; males 35, females 11). The follow-up visits were at 3, 6 and 9 months, respectively. The time period considered was of 9 months. The results obtained in the four groups after 9 months of treatment are given below: GROUP A Total Cholesterol (TC) (-20%), LDL-Cholesterol (LDLC) (-26%), triglycerides (TG) (-25%), nonHDL-Cholesterol (nonHDLC) (-26%) levels, and TC/HDLC ratio (-21%) were statistically significant reduced (all: P < 0001). HDLC was not significantly increased (+2%). The body weight (BW) mean change in the group was statistically significant (-22%; P≤0.001). GROUP B TC (-24%), LDLC (-32%), TG (-29%), nonHDLC (-32%) levels and TC/HDLC (-26%) were significantly decreased (all: P≤0.001). HDLC showed a -2.3% not significant decrease. The BW mean change was not statistically significant (-18%). GROUP C: TC (-36%), LDLC (-51%), nonHDLC (-45%) levels and TC/HDLC (-38%) were significantly decreased (all: P≤0.001). HDLC (+4%) was only slightly increased, and TG (-16%) decreased, but the changes were not statistically significant. The BW mean change was not statistically significant (-15%). GROUP D: TC (-47%), LDLC (-63%), TG (-23%) and nonHDLC (-58%) levels and TC/HDLC (-50%) showed a statistically significant reduction (all: P≤0001). HDLC concentration in plasma showed only a slight not significant reduction (-4%). The BW mean change was statistically significant (-20%; P≤0.001). Hyperlipidemia in children can be successfully treated without side effects. The most severe hyperlipidemia is, the most appropriate treatment (diet only,or diet+G, or diet+drugs) is to be given. The reduction of TC/HDLC ratio in childhood prevents future increase of cardiovascular risk in adulthood.

Relationship between Sustained Reductions in Plasma Lipid and Lipoprotein Concentrations with Apheresis and Plasma Levels and mRNA Expression of PTX3 and Plasma Levels of hsCRP in Patients with HyperLp(a)lipoproteinemia.

The effect of lipoprotein apheresis (Direct Adsorption of Lipids, DALI) (LA) on plasma levels of pentraxin 3 (PTX3), an inflammatory marker that reflects coronary plaque vulnerability, and expression of PTX3 mRNA was evaluated in patients with hyperLp(a)lipoproteinemia and angiographically defined atherosclerosis/coronary artery disease. Eleven patients, aged 55 ± 9.3 years (mean ± SD), were enrolled in the study. PTX3 soluble protein levels in plasma were unchanged by 2 sessions of LA; however, a downregulation of mRNA expression for PTX3 was observed, starting with the first session of LA (p < 0.001). The observed reduction was progressively increased in the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session. A statistically significantly greater treatment-effect correlation was observed in patients undergoing weekly treatments, compared with those undergoing treatment every 15 days. A progressive reduction in plasma levels of C-reactive protein was also seen from the first session of LA, with a statistically significant linear correlation for treatment-effect in the change in plasma levels of this established inflammatory marker (R 2 = 0.99; p < 0.001). Our findings suggest that LA has anti-inflammatory and endothelium protective effects beyond its well-established efficacy in lowering apoB100-containing lipoproteins.

Hot Structural Sandwich Panel for Reusable Launch Vehicles

To protect reentry systems, as reusable launch vehicles (RLV), from the exposed extreme environment, the external surfaces are usually covered with Carbon Matrix Composite (CMC) in particular Reinforced Carbon-Carbon (RCC). Although these materials are strong and capable of withstanding extreme temperatures, they are thermally conductive. This brings a need to extensively use insulating blankets and tiles behind the RCC panels to protect the structure and attach fittings from heat radiated from the backside. This sandwich panel concept considerably insulates the internal structure from over heating and also provides partial structural function. The panel is composed of a three-layer sandwich structure which can be adapted to a specific mission profile. The core of the sandwich is a high-temperature-resistant carbon vitreous foam functioning as heat capacitor for the system while the face sheets are Carbon-Carbon (C/C) laminate composite. This layering approach allows one to design the hot structure with just the strictly necessary thickness of the foam core and face sheet material. To prevent oxidation of the exposed skin surface, a thin SiC coating is deposited using CVD technique. The sandwich mechanical and bonding properties are characterized through mechanical testing. Once the graphite adhesive deposition and surface treatment have been optimized the panel assembly is achieved through vacuum bag curing. The main advantages of this concept are a potential mass saving, its adaptability to particular mission requirements (varying the foam and face sheet thicknesses), an increased failure tolerance due to the high temperature capacity and low insulation protection on attach fittings.