Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome

Atypical hemolytic uremic syndrome (aHUS) is caused by alternative complement pathway dysregulation, leading to systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Based on 2 prospective studies in mostly adults and retrospective data in children, eculizumab, a terminal complement inhibitor, is approved for aHUS treatment. Here we prospectively evaluated efficacy and safety of weight-based dosing of eculizumab in eligible pediatric patients with aHUS in an open-label phase II study. The primary end point was complete TMA response by 26 weeks. Twenty-two patients (aged 5 months-17 years) were treated; 16 were newly diagnosed, 12 had no prior plasma exchange/infusion during current TMA symptomatology, 11 received baseline dialysis, and 2 had prior renal transplants. By week 26, 14 achieved a complete TMA response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. Plasma exchange/infusion was discontinued in all, and 9 of the 11 patients who required dialysis at baseline discontinued, whereas none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. Bone marrow failure, wrist fracture, and acute respiratory failure were reported as unrelated severe adverse events. Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children

Coulomb excitation of 68^{68}Ni at safe energies

The $B(E2;0^+\to2^+)$ value in $^{68}$Ni has been measured using Coulomb excitation at safe energies. The $^{68}$Ni radioactive beam was post-accelerated at the ISOLDE facility (CERN) to 2.9 MeV/u. The emitted $\gamma$ rays were detected by the MINIBALL detector array. A kinematic particle reconstruction was performed in order to increase the measured c.m. angular range of the excitation cross section. The obtained value of 2.8$^{+1.2}_{-1.0}$ 10$^2$ e$^2$fm$^4$ is in good agreement with the value measured at intermediate energy Coulomb excitation, confirming the low $0^+\to2^+$ transition probability.Comment: 4 pages, 5 figure

A multi-modal network approach to model public transport accessibility impacts of bicycle-train integration policies

In the Netherlands, the bicycle plays an important in station access and, to a lesser extent, in station egress. There is however fairly little knowledge in the potential effects of bicycle-train integration policies. The aim of this paper is to examine the impacts of bicycle-train integration policies on train ridership and job accessibility for public transport users.MethodsWe extended the Dutch National Transport Model (NVM) by implementing a detailed bicycle network linked to the public transport network, access/egress mode combinations and station specific access and egress penalties by mode and station type derived from a stated choice survey. Furthermore, the effects of several bicycletrain integration policy scenarios were examined for a case study for Randstad South, in the Netherlands, comprising a dense train network with 54 train stations.ConclusionsOur analysis shows that improving the quality of bicycle routes and parking can substantially increase train ridership and potential job accessibility for train users. Large and medium stations are more sensitive to improvements in bicycle-train integration policies, while small stations are more sensitive to improvements in the train level of service

Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications

Sodium retention and edema are common features of nephrotic syndrome that are classically attributed to hypovolemia and activation of the renin–angiotensin–aldosterone system. However, numbers of clinical and experimental findings argue against this underfill theory. In this review we analyze data from the literature in both nephrotic patients and experimental models of nephrotic syndrome that converge to demonstrate that sodium retention is not related to the renin–angiotensin–aldosterone status and that fluid leakage from capillary to the interstitium does not result from an imbalance of Starling forces, but from changes of the intrinsic properties of the capillary endothelial filtration barrier. We also discuss how most recent findings on the cellular and molecular mechanisms of sodium retention has allowed the development of an efficient treatment of edema in nephrotic patients

Clinical practice recommendations for native vitamin D therapy in children with chronic kidney disease Stages 2-5 and on dialysis

Vitamin D deficiency is widely prevalent and often severe in children and adults with chronic kidney disease (CKD). Although native vitamin D {25-hydroxyvitamin D [25(OH)D]} is thought to have pleiotropic effects on many organ systems, its skeletal effects have been most widely studied. The 25(OH)D deficiency is causally linked with rickets and fractures in healthy children and those with CKD, contributing to the CKD–mineral and bone disorder (MBD) complex. There are few studies to provide evidence for vitamin D therapy or guidelines for its use in CKD. A core working group (WG) of the European Society for Paediatric Nephrology (ESPN) CKD–MBD and Dialysis WGs have developed recommendations for the evaluation, treatment and prevention of vitamin D deficiency in children with CKD. We present clinical practice recommendations for the use of ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) in children with CKD Stages 2–5 and on dialysis. A parallel document addresses treatment recommendations for active vitamin D analogue therapy. The WG has performed an extensive literature review to include meta-analyses and randomized controlled trials in healthy children as well as children and adults with CKD, and prospective observational studies in children with CKD. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system has been used to develop and grade the recommendations. In the absence of applicable study data, the opinion of experts from the ESPN CKD–MBD and Dialysis WGs is provided, but clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to individual patient needs as appropriate