Longitudinal growth on an everolimus‐ versus an MMF‐based steroid‐free immunosuppressive regimen in paediatric renal transplant recipients

Concerns have been raised that mammalian target of rapamycin inhibitors in pediatric transplant recipients might interfere with longitudinal bone growth by inhibition of growth factor signaling and growth plate chondrocyte proliferation. We therefore undertook a prospective nested, case‐control study on longitudinal growth over 2 years in steroid‐free pediatric renal transplant recipients. Fourteen patients on a steroid‐free maintenance immunosuppressive regimen consisting of low‐dose everolimus (EVR) in conjunction with low‐dose cyclosporine (CsA) were compared to a matched cohort of 14 steroid‐free patients on a standard dose mycophenolate mofetil (MMF) regimen in conjunction with a standard dose calcineurin inhibitor (CNI). The mean change in height standard deviation (SD) score in the first study year was 0.31 ± 0.71 SD score in the EVR group compared to 0.31 ± 0.64 SD score in the MMF group (P = 0.20). For the entire study period of 2 years, the change in height SD score in the EVR group was 0.43 ± 0.81 SDS compared to 0.75 ± 0.85 SDS in the MMF group (P = 0.32). The percentage of prepubertal patients experiencing catch‐up growth, defined as an increase in height SD score ≥0.5 in 2 years, was similar in the EVR group (5/8, 65%) and the MMF group (6/8, 75%; P = 1.00). Longitudinal growth over 2 years in steroid‐free pediatric patients on low‐dose EVR and CsA is not different to that of a matched steroid‐free control group on an immunosuppressive regimen with standard‐dose CNI and MMF. Hence, low‐dose EVR does not appear to negatively impact short‐term growth in pediatric renal transplant recipients.     

Subarachnoid blood infusion versus raised intracranial pressure: Effects on the amino acid pattern in the extracellular fluid of the rabbit hippocampus

Abstract

In order to evaluate the role of a hemorrhage versus that of a transient increase in intracranial pressure in subarachnoid hemorrhage, the two components were induced separately in rabbits. Extracellular glutamate, sampled from the hippocampus with microdialysis, was used to evaluate the degree of CNS tissue damage. In four rabbits, autologous arterial blood was infused in the cisterna magna in a volume that would not affect the intracranial pressure. The other group of animals was infused with saline to elevate the intracranial pressure from 10 to > 100 mmHg. The increase of intracranial pressure per se did not induce significant changes in extracellular glutamate. However, 20-60 min after infusion of blood, a significant glutamate increase was recorded. Furthermore, aspartate, alanine, glycine and serine were also raised. The results indicate that blood in the subarachnoid space damages the brain primarily by inducing ischemia. Furthermore, the parameters employed gave no indication that an increase in intracranial pressure had a deleterious effect on CNS tissue. [Neurol Res 1999; 21: 404-408]     

Bone formation after sinus augmentation with engineered bone

Objectives: The aim of the following investigation was to quantify the resorption rate of tissue-engineered bone grafts in the maxillary sinus using volume measurements. MATERIAL AND METHODS: Sinus floor augmentation using autologous bone grafts from the iliac crest (n=17, group 1) was compared with commercially produced transplants of human cells seeded on polyglycolid-polylactid (PLGA) scaffolds (Oral Bone) (n=14, group 2). RESULTS: The total resorption rate for autologous transplants 3 months post operation was 29%, while the tissue-engineered bone showed a resorption rate of 90%. The autologous bone had a bone density of up to 266-551 Hounsfield units (HU), while sufficient mineralization of tissue-engineered bone was found in only one case (152 HU). CONCLUSION: In this clinical study, the use of autologous cancellous bone grafts in sinus augmentation was more reliable than scaffolds containing cultured osteoblasts. Further tissue-engineered bone transplants should be examined to draw general conclusions about the use of tissue-engineered grafts compared with autologous bone grafts for maxillary sinus augmentation.     

The new regulation to investigate potentially beneficial diagnostic and therapeutic methods in Germany: Up to international standard?

Funding of diagnostic and therapeutic methods in Germany's statutory health insurance (SHI) follows a dichotomy: in outpatient care, only methods with proven benefit are reimbursed while in inpatient care, all methods may be provided unless they are excluded due to proven harm or lack of benefit. In January 2012, a new section 137e was added to the Social Code Book V (SGB V), allowing for the inclusion of innovative and potentially beneficial diagnostic or therapeutic methods in the SHI benefit basket, while additional evidence regarding their effectiveness and safety must be gathered. In 2013, the Federal Joint Committee (G-BA) has specified the details of this new approach, which can be considered a variety of “Coverage with Evidence Development” (CED). Our comparison with CED schemes in selected countries reveals a dependence of the CED implementation on the encompassing healthcare system. However, we identify a clear legislative foundation, a definitive decision-making body, the possibility to obtain public funding, and the preference for high quality study designs as constituting factors of an emerging international standard for CED. In addition, it is necessary to ensure the suitability of circumstances and technologies for the successful application of CED in a clear and transparent way.