NGS-Panel Diagnosis Developed for the Differential Diagnosis of Idiopathic Toe Walking and Its Application for the Investigation of Possible Genetic Causes for the Gait Anomaly.

Idiopathic toe walking (ITW) describes a condition affecting approximately 4.5% of children. Toe walking is an accompanying symptom for many hereditary disorders. This retrospective study uses next-generation sequencing-panel-diagnosis to investigate the feasibility of genetic testing to research the possible genetic causes of ITW and for differential diagnosis. Data were taken from our inhouse database, the minimum age for participants was 3 years. Underlying neurological or orthopaedic conditions were tested for and ruled out prior to diagnosing ITW. Patients, who experienced complications before, during or immediately after birth, children with autism, and patients toe walking less than 50% of the time were excluded. Eighty-nine patients were included in the study, in which 66 (74.2%) patients were boys and 23 (25.8%) girls. Mean age at testing was 7.7 years (range: 3-17 years). Fifteen of the 89 patients included in the study (16.9%) had a genetic variant identified as likely pathogenic or pathogenic by the genetics laboratory. Additionally, we found 129 variants of uncertain significance. About 65.2% of patients showed a pes cavus foot deformity, 27% of patients reportedly had at least one relative who also displayed the gait anomaly, and 37.1% had problems with their speech development. Despite the limitations of the sample size and the scope of our genetic testing targets, our results indicate that research into the genetic causes of ITW could better our understanding of the causes of ITW in otherwise healthy children, to help develop novel methods to detect serious conditions early. ITW could be an early onset symptom for further hereditary conditions.

Improving antithrombotic management in patients with atrial fibrillation: current status and perspectives.

Despite overwhelming evidence of the benefits of risk-adjusted oral anticoagulation on stroke reduction in patients with atrial fibrillation (AF), there is still considerable undertreatment. A multidisciplinary expert group was formed to discuss issues surrounding anticoagulant treatment of patients with AF to try and achieve consensus on various aspects of the implementation of guidelines on oral anticoagulation therapy in AF. Panel members were cardiologists, hematologists, and laboratory and primary care physicians with specific expertise from Europe and the United States. One of the most important conclusions of the meeting was to enhance guideline adherence by better communication of the data showing that the benefits of stroke reduction outweigh the risk of bleeding associated with treatment with vitamin K antagonists. Management of oral anticoagulation therapy by dedicated centers, such as anticoagulation clinics, or by patient self-management may improve the quality of anticoagulation and facilitate the management of these patients and thereby further facilitate optimal antithrombotic management in patients with AF.

Evaluation of two Mg2+-selective electrodes by means of a flow-through device.

Monitoring the ionized magnesium (Mg2+) concentration in critically ill patients can prevent development of serious and potentially fatal complications. The analyzers KONE Microlyte 6 (KONE Instruments, Espoo, Finland) and NOVA CRT (NOVA Biomedical, Waltham, MA, USA) provide the discontinuous measurement of Mg2+ and were evaluated in several studies. It was our objective to integrate the Mg2+-selective electrodes into a device for continuous on-line measurements. This device is suitable not only for research but also for a specific evaluation of electrode characteristics. It allowed us to compare the genuine electrodes and reference systems independently of their specific analyzers. Precision, accuracy, response time, limit of detection, drift and interferences were assessed by continuous flow-through measurements and discussed in comparison to the results of previous studies. The NOVA electrode proved to be superior regarding accuracy, sensitivity and selectivity, especially with respect to calcium. It was demonstrated that current commercial serum-like control materials were not appropriate for quality control of the assessed Mg2+-electrodes. However, despite the fact that the electrodes are commercially used for discontinuous measurements, both sensor types can be used for continuous on-line measurements in an extracorporeal circulation in a rat model. The NOVA electrode showed superior characteristics with this application as well. This study should also be understood as a contribution to the development of devices for online analyzers used in point-of-care-testing.