Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized,Double-Blind,Placebo-Controlled Study

In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial ({"type":"clinical-trial","attrs":{"text":"NCT02207946","term_id":"NCT02207946"}}NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn–Tolosa–Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, n = 19; placebo, n = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 (p = 0.003) and Week 8 (p = 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 (p < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 (p = 0.004) and Week 8 (p < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.     

Schmerztherapeutische Möglichkeiten in der Unfallchirurgie

Sufficient acute pain therapy has been scientifically proven to be one of the therapeutic pillars for rapid patient convalescence, a low rate of pain chronification, and a high grade of patient satisfaction. This includes not only systemic pharmacological pain therapy, but also nonpharmaceutical measures, e.g., physical, psychological, locoregional, and adequate patient information. This requires a specific infrastructure, exact clinical control mechanisms, and fundamental knowledge about pain avoidance. The surgeon can responsibly contribute to this. The goal of the following article is to demonstrate and deepen this knowledge and to describe the newest scientific developments.     

Next‐generation sequencing for the diagnosis of MYH9‐RD: Predicting pathogenic variants

The heterogeneous manifestations of MYH9‐related disorder (MYH9‐RD), characterized by macrothrombocytopenia, Döhle‐like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE‐BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9‐RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9‐RD should always be considered. A HTS‐based strategy is a reliable method to reach a conclusive diagnosis of MYH9‐RD in clinical practice.     

Mutant Cu,Zn superoxide dismutase in motor neuron disease

Cu,Zn superoxide dismutase (Cu,Zn SOD) is one of several anti-oxidant enzymes which defend the cell against damage by oxygen free radicals. Mutations of the SOD1 gene encoding Cu,Zn SOD are found familial amyotrophic lateral sclerosis, a progressive and fatal paralytic disease which is caused by the death of motor neurons in cortex, brainstem and spinal cord. The disease can be reproduced in transgenic mice by expression of mutant human Cu,Zn SOD. Recent studies both in vitro and in vivo suggest that the effect of mutation is to enhance the generation of oxygen radicals by the mutant enzyme. Thus, mutation converts a protective, antioxidant enzyme into a destructive pro-oxidant form which catalyzes free radical damage to which motor neurons are uniquely vulnerable.     

Absetzen der Sekund?rprophylaxe bei Aids-Patienten mit inaktiver CMV-Retinitis unter HAART

Hintergrund.“Highly active antiretroviral therapy” (HAART) führt bei Patienten mit der Immunschw?che Aids zu einer teilweisen Rekonstitution ihrer Immunkompetenz. Ein Anstieg der CD₄-Zellen und ein Absinken der Viruslast sind dafür die wichtigsten Verlaufsparameter. Durch diese verbesserte Immunlage sinkt das Risiko für opportunistische Infektionen. Eine dieser Infektionen ist die Zytomegalievirus- (CMV-)Retinitis, die vor der Verfügbarkeit der HAART nach narbiger Abheilung unter Anti-CMV-Therapie mit einer lebenslangen Sekund?rprophylaxe behandelt werden musste. Es stellt sich nun die Frage, ob bei wiedererlangter Immunkompetenz unter HAART eine vernarbte CMV-Retinitis weiterhin eine Sekund?rprophylaxe erfordert.     

Poly ADP-ribosylation in two L5178Y murine lymphoma sublines differentially sensitive to DNA-damaging agents

Purpose : To characterize the response to X-irradiation of the poly ADP-ribosylation system in two closely related murine lymphoma sublines, L5178Y-R (LY-R) and L5178Y-S (LY-S), with differential sensitivity to various DNA damaging agents (UV-C and ionizing radiation, hydrogen peroxide). Materials and methods : LY cells were X-irradiated (2 Gy). NAD + was determined in cell extracts by high-pressure liquid chromatography. ADP-ribose polymers were purified and analysed by densitometry after polyacrylamide gel electrophoresis. Nuclear matrix proteins were separated by SDS-polyacrylamide gel electrophoresis and processed for ADP-ribose polymer blots to estimate their ability to bind poly(ADP-ribose). Results : In the radiosensitive LY-S cells, the constitutive levels of ADP-ribose polymers were twofold higher than in radioresistant LY-R cells, but unresponsive to a challenge with 2 Gy X-rays. The concentrations of NAD + - the substrate for poly(ADP-ribose) synthesis - were identical in the two cell lines. X-rays (2 Gy) depleted NAD + only in LY-S cells. These cells also produced shorter poly(ADP-ribose) molecules as compared with LY-R cells. Nuclear matrix preparations of LY-S cells exhibited lower poly(ADP-ribose)-binding capacity than those of LY-R cells. Conclusion : The results demonstrate disturbances in the poly ADP-ribosylation response of the radiosensitive LY-S cells and reduced poly(ADP-ribose)-binding affinity of the nuclear matrix of these cells.