Cyclosporine‐impregnated allograft bone sterilized with low‐temperature plasma

Deep‐freezing, freeze‐drying and gamma (γ)‐irradiation have deleterious effects on bone healing and mechanical properties of allograft bones. We tried preparing bone allografts using cyclosporine plus low‐temperature‐plasma sterilization. To explore the feasibility of this method of preparation, segmental defects in the right radii of rabbits were repaired with cyclosporine‐impregnated allograft bones (CABs) sterilized with low‐temperature‐plasma (in the study group) and deep‐frozen/freeze‐dried irradiated allograft bones (D/FIABs) (in the control group). X‐ray and quantitative histological analysis, peripheral blood T lymphocyte subset analysis and CD₂₅ molecule immunohistochemistry stain, the four‐point bending test and safety evaluations were respectively conducted to compare bone‐healing, immunosuppression, mechanical properties and safety between the two groups. X‐ray scores were higher in the study group than those in the control (p = 0.032). There were significant differences in new bone areas at most repairs in both groups (p < 0.05). There were no significant differences in the percentages of CD₄⁺ T, CD₈⁺ T, ratios of CD₄⁺ T:CD₈⁺ T or serum concentrations of GPT/Cr in both groups (p > 0.05). At 16 weeks postoperatively, the density of CD₂₅ molecules in the control group was higher than that in the study group. The ultimate loading in the study group was significantly higher than that in the control (p = 0.048). Bone marrow stromal cells (BMSCs) grew thickly around and on the surface of a cyclosporine‐impregnated allograft. Livers and kidneys in the study and control groups remained histologically normal at 7 days postoperatively. These results indicate that the CAB might be a better material than the D/FIAB in terms of bone healing, preservation of mechanical properties and immunosuppression without severe side‐effects. Copyright © 2010 John Wiley & Sons, Ltd.     

Heparin‐induced non‐necrotizing skin lesions: rarely associated with heparin‐induced thrombocytopenia

See also Warkentin TE, Linkins L‐A. Non‐necrotizing heparin‐induced skin lesions and the 4T’s score. This issue, pp 1483–. Summary. Background: Recently, there has been an increasing number of reports regarding adverse skin reactions to subcutaneous heparin administration. Case series have implied that heparin‐induced skin lesions are predominantly associated with life‐threatening heparin‐induced thrombocytopenia (HIT) in at least 22% of patients. Skin lesions, therefore, have been included in clinical scores for HIT. Objectives: To determine the association of heparin‐induced skin lesions with HIT. This would have a pivotal impact on further anticoagulatory management in patients with heparin‐induced skin lesions. Patients/Methods: In our observational cohort study, 87 consecutive patients with heparin‐induced skin lesions (85 occurring during low‐molecular‐weight heparin administration) were evaluated using a standardized internal protocol, including HIT diagnostics (heparin‐platelet factor 4‐ELISA, heparin‐induced platelet activation assay), platelet count monitoring, clinical/sonographical screening for thrombosis, skin allergy testing and, if necessary, histology. Results: None of the observed heparin‐induced skin lesions was due to HIT; all lesions were caused by delayed‐type IV‐hypersensitivity reactions (DTH) instead. Even the cutaneous reaction in one patient with concomitant HIT could be classified histologically as DTH reaction, amounting to an association of heparin‐induced skin lesions and HIT in 1.2% (1/87; 95% confidence interval, 0.00–0.06). Conclusion: Heparin‐induced skin lesions associated with use of low‐molecular‐weight heparins do not seem to be strongly associated with a systemic immunologic reaction in terms of HIT and might rather be due to DTH reactions than due to microvascular thrombosis. Hence, we propose refining existing pretest probability scores for HIT, unless underlying causes have been clarified.     

Erythrocyte‐exchange with the OPTIA™ cell separator in patients with sickle‐cell disease

Erythrocyte–exchange (EEX) has proven to be a very useful tool in sickle‐cell disease (SCD) patients either during acute painful crisis unresponsive to hydration and/or analgesia or as a prophylactic treatment in high risk patients in those who do not tolerate hydroxyurea (HU), with the aim of lowering HbS levels. EEX may be performed either by using continuous‐ or discontinuous flow devices, the former being of choice in children or in low‐weight patients. Thus, a low extracorporeal blood volume (EBV) could allow for a better and safer procedure management. In this study we compared EEX procedure performed with the recently released OPTIA device with EEX procedures performed using the COBE Spectra device (EBV 185 vs 270 mL, respectively). Twenty‐one EEX (4 as emergency treatment) were performed in 12 patients with the Spectra device and 25 (9 as emergency treatment) in 15 patients with the OPTIA device. All the procedures were well tolerated and uneventful. We did not observe significant differences between the two devices as to pre‐ and post‐EEX parameters, namely in target hematocrit and in HbS reduction. Noteworthy, due to the lowest EBV allowed by the OPTIA device, an EEX procedure performed in a 13 Kg‐ child did not require a preliminary priming of the circuit. In conclusion, the OPTIA device proved to be as effective as the Spectra device in treating SCD patients either during sickling crisis or as prophylactic therapy. The OPTIA device can be safely used in the pediatric setting since it allows a lower EBV. J. Clin. Apheresis, 28:411–415, 2013. © 2013 Wiley Periodicals, Inc.     

Imaging integrin alpha‐v‐beta‐3 expression in tumors with an 18F‐labeled dimeric RGD peptide

Integrin α_vβ₃ receptors are expressed on activated endothelial cells during neovascularization to maintain tumor growth. Many radiolabeled probes utilize the tight and specific association between the arginine–glycine–aspartatic acid (RGD) peptide and integrin α_vβ₃, but one main obstacle for any clinical application of these probes is the laborious multistep radiosynthesis of ¹⁸F. In this study, the dimeric RGD peptide, E‐[c(RGDfK)]₂, was conjugated with NODAGA and radiolabeled with ¹⁸F in a simple one‐pot process with a radiolabeling yield of 20%, the whole process lasting only 45 min. NODAGA‐E‐[c(RGDfK)]₂ labeled with ¹⁸F at a specific activity of 1.8 MBq nmol^?1 and a radiochemical purity of 100% could be achieved. The logP value of ¹⁸F‐labeled NODAGA‐E‐[c(RGDfK)]₂ was ?4.26 ± 0.02. In biodistribution studies, ¹⁸F‐NODAGA‐E‐[c(RGDfK)]₂ cleared rapidly from the blood with 0.03 ± 0.01 percentage injected dose per gram (%ID g^?1) in the blood at 2 h p.i., mainly via the kidneys, and showed good in vivo stability. Tumor uptake of ¹⁸F‐NODAGA‐E‐[c(RGDfK)]₂ (3.44 ± 0.20 %ID g^?1, 2 h p.i.) was significantly lower than that of reference compounds ⁶⁸Ga‐labeled NODAGA‐E‐[c(RGDfK)]₂ (6.26 ± 0.76 %ID g^?1; p <0.001) and ¹¹¹In‐labeled NODAGA‐E‐[c(RGDfK)]₂ (4.99 ± 0.64 %ID g^?1; p < 0.01). Co‐injection of an excess of unlabeled NODAGA‐E‐[c(RGDfK)]₂ along with ¹⁸F‐NODAGA‐E‐[c(RGDfK)]₂ resulted in significantly reduced radioactivity concentrations in the tumor (0.85 ± 0.13 %ID g^?1). The α_vβ₃ integrin‐expressing SK‐RC‐52 tumor could be successfully visualized by microPET with ¹⁸F‐labeled NODAGA‐E‐[c(RGDfK)]₂. In conclusion, NODAGA‐E‐[c(RGDfK)]₂ could be labeled rapidly with ¹⁸F using a direct aqueous, one‐pot method and it accumulated specifically in α_vβ₃ integrin‐expressing SK‐RC‐52 tumors, allowing for visualization by microPET. Copyright © 2013 John Wiley & Sons, Ltd.     

Out‐of‐home Placement of School‐age Children with Disabilities and High Support Needs

Background This study explored the relationship between family life variables and out‐of‐home placement tendency for families of school‐age children with disabilities and high support needs. Method This study was a prospective cohort study of 81 families with children with disabilities and high support needs aged between 6 and 13 years. There were two waves of data collection 12–18 months apart involving in‐depth interviews with the primary carer. Results Out‐of‐home placement tendency was associated with three interrelated family life variables: (i) difficulty balancing the demands of caring and the needs of other family members; (ii) sharing workload and responsibility; and (iii) integrating the child into the everyday world. Conclusion Family capacity to continue balancing the demands of caring and the needs of other family members is central to maintaining family‐based placement.     

Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT

Summary. Background: Early‐onset hypertensive disorders (HD) of pregnancy and small‐for‐gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding low‐molecular‐weight heparin (LMWH) to aspirin at < 12 weeks gestation reduces the recurrence of HD in women with previous early‐onset HD (pre‐eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies. Patients/methods: In a multicenter randomized control trial (RCT), 139 women included were < 12 weeks gestation. Inclusion criteria: previous delivery < 34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected. Intervention: either daily LMWH (dalteparin, 5000 IU weight‐adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone. Main outcome measures: Primary outcomes: recurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age. Secondary outcomes: recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention‐to‐treat. Results: Low‐molecular‐weight heparin with aspirin reduced recurrent HD onset < 34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9–15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects. Trial Registration: http://www.isrctn.org ) (isrctn87325378). Conclusions: Adding LMWH to aspirin at < 12 weeks gestation reduces recurrent HD onset < 34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.