Nonlethal transfusion associated graft-versus-host disease in a severe combined immunodeficient patient

An X-linked severe combined immunodeficient (SCID) patient received a nonirradiated erythrocyte transfusion and developed transfusion-associated graft-versus-host disease (TAGVHD), which was controllable with high-dose corticosteroids. Haplo-identical SCT was performed, after a myeloablative conditioning regimen. At day +26, he developed GVHD. Chimerism studies revealed DNA of the erythrocyte transfusion donor (ETD) and recipient only. Because of early nonengraftment and the presence of alloreactive T cells of ETD origin, the patient was treated with an immunosuppressive conditioning regimen followed by a second SCT from the same donor. While tapering immunosuppression, he again developed mild GVHD, and DNA of ETD and bone marrow donor origin were both present. On cyclosporin, the ETD-DNA signal finally disappeared. High-resolution HLA typing revealed haplo-identity between BMD, ETD and the patient, which might have contributed to the relative mild course of the TAGVHD.     

Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin

Background

Weekly maternal intravenous immunoglobulin (IVIG) is the cornerstone of antenatal treatment of foetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to describe the neonatal outcome and management in neonates with FNAIT treated antenatally with IVIG.

Materials and methods

All neonates treated antenatally and delivered at our centre between 2006 and 2012 were included in the study. We assessed the neonatal outcome and management, including the occurrence of intracranial haemorrhage, platelet count at birth and need for postnatal platelet transfusions or postnatal IVIG treatment.

Results

A total of 22 neonates were included of whom 12 (55%) had severe thrombocytopenia at birth (platelet count ≤50×10⁹/L). Most neonates (67%, 8/12) with severe thrombocytopenia received a platelet transfusion after birth. None of the neonates required postnatal treatment with IVIG. Three neonates had petechiae and haematomas, without clinical consequences. One foetus suffered from intracranial haemorrhage, which was detected just before the planned start of antenatal IVIG at 28 weeks’ gestation.

Discussion

Our results suggest that antenatal maternal IVIG and, if necessary, postnatal matched platelet transfusions, are effective and safe for the treatment of FNAIT.     

Dutch Cycling: Quantifying the Health and Related Economic Benefits

The Netherlands is well known for their high bicycle use. We used the Health Economic Assessment Tool and life table calculations to quantify the population-level health benefits from Dutch cycling levels. Cycling prevents about 6500 deaths each year, and Dutch people have half-a-year-longer life expectancy because of cycling. These health benefits correspond to more than 3% of the Dutch gross domestic product. Our study confirmed that investments in bicycle-promoting policies (e.g., improved bicycle infrastructure and facilities) will likely yield a high cost–benefit ratio in the long term.The Netherlands is well known for their high cycling levels.1,2 Currently, about 27% of all trips in the Netherlands are made by bicycle.3 Investments in bicycle paths, bicycle parking, traffic calming, and other policies contribute to these high cycling levels; therefore, the Dutch approach is internationally recognized as an example for other countries.1,2 Although the health benefits of cycling as a means to reduce the risk of sedentary lifestyle diseases and all-cause mortality are well known,4–6 no previous study has actually quantified the health benefits and related economic benefits at a population level in the Netherlands, which has the highest level of bicycle use in the world.1 Quantifying and monetizing these benefits are important to inform policymakers in the field of transport.7 Therefore, we examined the health benefits and health-related economic benefits of population cycling levels in the Netherlands.     

Docosahexaenoic acid reduces amyloid-β(1-42) secretion in human AβPP-transfected CHO-cells by mechanisms other than inflammation related to PGE₂

The effect of supplementation with the omega 3 polyunsaturated fatty acid (n3 PUFA) docosahexaenoic acid (DHA) on membrane composition and amyloid-β???? (Aβ??) secretion was studied in human amyloid-β protein precursor-transfected Chinese Hamster Ovary (CHO) cells. Twenty-four hour incubation with a range of DHA concentrations resulted in a dose-dependent increase in membrane DHA and eicosapentaenoic acid content and a decrease in arachidonic acid content. In addition, DHA supplementation caused a dose-dependent reduction in the secreted Aβ?? levels and resulted in a 4-8 fold decrease in extracellular prostaglandin E? (PGE?) levels. Tocopherol, which was added to DHA to prevent oxidation, may have contributed to the effect of DHA, since it slightly decreased extracellular Aβ?? and PGE? levels when given alone. The addition of selective COX2 inhibitors Celebrex and curcumin to the culture medium resulted in a significant and comparable inhibition of PGE? release, but did not inhibit Aβ?? secretion, and even significantly increased Aβ?? production in this cell system. Together, the present data show that, whereas both DHA and COX2 inhibitors may reduce PGE? production, only DHA in the presence of tocopherol significantly reduced Aβ?? production and concurrently changed membrane lipid composition in CHO cells. It is concluded that in this in vitro setting DHA reduced Aβ?? secretion through membrane-related, but not PGE?-related mechanisms.     

Efficacy of a medical food in mild Alzheimer's disease: A randomized,controlled trial

ObjectiveTo investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD).MethodsA total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale–revised, and the 13-item modified Alzheimer's Disease Assessment Scale–cognitive subscale at week 12.ResultsAt 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale–cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study–Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated.ConclusionsSupplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials.     

Flexible and elastic porous poly(trimethylene carbonate) structures for use in vascular tissue engineering

Biocompatible and elastic porous tubular structures based on poly(1,3-trimethylene carbonate), PTMC, were developed as scaffolds for tissue engineering of small-diameter blood vessels. High-molecular-weight PTMC (M_n = 4.37 × 10⁵) was cross-linked by gamma-irradiation in an inert nitrogen atmosphere. The resulting networks (50–70% gel content) were elastic and creep resistant. The PTMC materials were highly biocompatible as determined by cell adhesion and proliferation studies using various relevant cell types (human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs) and mesenchymal stem cells (MSCs)). Dimensionally stable tubular scaffolds with an interconnected pore network were prepared by particulate leaching. Different cross-linked porous PTMC specimens with average pore sizes ranging between 55 and 116 μm, and porosities ranging from 59% to 83% were prepared. These scaffolds were highly compliant and flexible, with high elongations at break. Furthermore, their resistance to creep was excellent and under cyclic loading conditions (20 deformation cycles to 30% elongation) no permanent deformation occurred. Seeding of SMCs into the wall of the tubular structures was done by carefully perfusing cell suspensions with syringes from the lumen through the wall. The cells were then cultured for 7 days. Upon proliferation of the SMCs, the formed blood vessel constructs had excellent mechanical properties. Their radial tensile strengths had increased from 0.23 to 0.78 MPa, which is close to those of natural blood vessels.