Ankle-foot orthoses for improving walking in adults with calf muscle weakness due to neuromuscular disorders.

Background: Calf muscle weakness is a common symptom in slowly progressive neuromuscular disorders that lead to walking problems like instability and increased walking effort. The mainstay of treatment to improve walking in this population is the provision of ankle-foot-orthoses (AFOs). Since we are not aware of an up-to-date and complete overview of the effects of AFOs used for calf muscle weakness in slowly progressive neuromuscular disorders, we reviewed the evidence for the effectiveness of AFOs to improve walking in this patient group, in order to support clinical decision-making.

Adaptation of functional gait parameters to a newly provided stiffness-optimized ankle-foot orthosis.

Background: Clinical decisions regarding ankle-foot-orthosis stiffness in people with calf muscle weakness are based on immediate evaluations, not taking gait adaptation into account. This study examined adaptation of step length, walking speed and energy cost of walking in the 3-months post-provision and whether individuals with higher gait variability adapt more compared to individuals with lower gait variability.

Methods: We conducted a post-hoc analysis in eighteen stiffness-optimized ankle-foot-orthosis users with bilateral calf muscle weakness.

Determination of the clinical relevance of donor epitope-specific HLA-antibodies in kidney transplantation.

In kidney transplantation, survival rates are still partly impaired due to the deleterious effects of donor specific HLA antibodies (DSA). However, not all luminex-defined DSA appear to be clinically relevant. Further analysis of DSA recognizing polymorphic amino acid configurations, called eplets or functional epitopes, might improve the discrimination between clinically relevant vs.

Gait stability and the relationship with energy cost of walking in polio survivors with unilateral plantarflexor weakness.

Background: Polio survivors often exhibit plantarflexor weakness, which impairs gait stability, and increases energy cost of walking. Quantifying gait stability could provide insights in the control mechanisms polio survivors use to maintain gait stability and in whether impaired gait stability is related to the increased energy cost of walking.

Research Question: Is gait stability impaired in polio survivors with plantarflexor weakness compared to able-bodied individuals, and does gait stability relate to energy cost of walking?

Methods: We retrospectively analyzed barefoot biomechanical gait data of 31 polio survivors with unilateral plantarflexor weakness and of 24 able-bodied individuals.

Effects of specialist care lower limb orthoses on personal goal attainment and walking ability in adults with neuromuscular disorders.

Background: Lower limb orthoses intend to improve walking in adults with neuromuscular disorders (NMD). Yet, reported group effects of lower limb orthoses on treatment outcomes have generally been small and heterogeneous. We propose that guideline-based orthotic care within a multidisciplinary expert setting may improve treatment outcomes.

T-Cell Epitopes Shared Between Immunizing HLA and Donor HLA Associate With Graft Failure After Kidney Transplantation.

CD4 T-helper cells play an important role in alloimmune reactions following transplantation by stimulating humoral as well as cellular responses, which might lead to failure of the allograft. CD4 memory T-helper cells from a previous immunizing event can potentially be reactivated by exposure to HLA mismatches that share T-cell epitopes with the initial immunizing HLA. Consequently, reactivity of CD4 memory T-helper cells toward T-cell epitopes that are shared between immunizing HLA and donor HLA could increase the risk of alloimmunity following transplantation, thus affecting transplant outcome.

Specialised orthotic care to improve functioning in adults with neuromuscular disorders: protocol of a prospective randomised open-label blinded end-point study.

Introduction: People suffering from leg muscle weakness caused by neuromuscular disorders (NMDs) are often provided with leg orthoses to reduce walking problems such as increased walking effort, diminished walking speed, reduced balance and falls. However, evidence for the effectiveness of leg orthoses to improve walking in this patient group is limited and there is an absence of standardised practice in orthotic prescription. In 2012 a Dutch multidisciplinary guideline was developed aimed to standardise the orthotic treatment process in NMD.

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients.

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation.

Development and Validation of a Multiplex Non-HLA Antibody Assay for the Screening of Kidney Transplant Recipients.

The best treatment for patients with end-stage renal disease is kidney transplantation. Although graft survival rates have improved in the last decades, patients still may lose their grafts partly due to the detrimental effects of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) and to a lesser extent also by antibodies directed against non-HLA antigens expressed on the donor endothelium. Assays to detect anti-HLA antibodies are already in use for many years and have been proven useful for transplant risk stratification.

Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients.

Background: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients.

Psychosocial consequences of living kidney donation: a prospective multicentre study on health-related quality of life, donor-recipient relationships and regret.

Background: Previous studies have indicated decreased health-related quality of life (HRQoL) shortly after kidney donation, returning to baseline in the longer term. However, a subgroup of donors experiences persistent HRQoL problems. To identify which HRQoL aspects are impacted most by the donation and to identify at-risk donors, more specific insight into psychosocial donation consequences is needed.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.

Background: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.

Methods: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples.

Toward a Sensible Single-antigen Bead Cutoff Based on Kidney Graft Survival.

Background: There is no consensus in the literature on the interpretation of single-antigen bead positive for a specific HLA antibody.

Methods: To inform the debate, we studied the relationship between various single-antigen bead positivity algorithms and the impact of resulting donor-specific HLA antibody (DSA) positivity on long-term kidney graft survival in 3237 deceased-donor transplants.

Results: First, we showed that the interassay variability can be greatly reduced when working with signal-to-background ratios instead of absolute median fluorescence intensities (MFIs).

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.

Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.

PIRCHE-II Is Related to Graft Failure after Kidney Transplantation.

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in donor-specific HLA antibodies formation after kidney transplantation.

Differential effects of donor-specific HLA antibodies in living versus deceased donor transplant.

The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch.

Female urothelial cell carcinoma in a failed kidney graft of a male recipient.

We present a case of a male kidney transplant patient harbouring two kidney grafts of which one is functional. In the failed graft, he developed urothelial cell carcinoma with cells containing XX-chromosome, and female tumour cells were also found in the bladder. The patient underwent donor nephrectomy, was treated with epirubicin bladder instillations, and immunosuppression was tapered.

How can we reduce costs of solid-phase multiplex-bead assays used to determine anti-HLA antibodies?

Solid-phase multiplex-bead assays are widely used in transplantation to detect anti-human leukocyte antigen (HLA) antibodies. These assays enable high resolution detection of low levels of HLA antibodies. However, multiplex-bead assays are costly and yield variable measurements that limit the comparison of results between laboratories.

The PROCARE consortium: toward an improved allocation strategy for kidney allografts.

Kidney transplantation is the best treatment option for patients with end-stage renal failure. At present, approximately 800 Dutch patients are registered on the active waiting list of Eurotransplant. The waiting time in the Netherlands for a kidney from a deceased donor is on average between 3 and 4 years.

The Maastricht Transplant Center: clinical setting and epitope searches in HLA class II molecules: does the structural localization of a polymorphic site contribute to its immunogenicity?

Our understanding of the immunological processes influencing the clinical outcome after kidney transplantation has advanced majorly over the last few decades. However, many factors still restrict graft and patient survival. Within the Maastricht transplant center we have successfully implemented an alternative immunosuppressive regimen involving Tacrolimus monotherapy in order to minimize the adverse effects associated with long-term use of immunosuppressive drugs.

Harmonization of description and classification of fetal observations: achievements and problems still unresolved: report of the 7th Workshop on the Terminology in Developmental Toxicology Berlin, 4-6 May 2011.

This article summarizes the 7th Workshop on the Terminology in Developmental Toxicology held in Berlin, May 4-6, 2011. The series of Berlin Workshops has been mainly concerned with the harmonization of terminology and classification of fetal anomalies in developmental toxicity studies. The main topics of the 7th Workshop were knowledge on the fate of anomalies after birth, use of Version 2 terminology for maternal-fetal observations and non-routinely used species, reclassification of "grey zone" anomalies and categorization of fetal observations for human health risk assessment.

Preservation of renal function and cardiovascular risk factors.

An update is given about some factors leading to loss of renal allograft, especially in relation to the use of tacrolimus and cyclosporine. We discuss both immunological, such as suboptimal immunosuppression, acute rejection, and noncompliance, as well as nonimmunological factor's such as hypertension, hyperlipidemia, chronic toxic effects of immunosuppressants, older donors, and delayed graft function.