Statistical Modeling of Lower Limb Kinetics During Deep Squat and Forward Lunge.

PURPOSE: Modern statistics and higher computational power have opened novel possibilities to complex data analysis. While gait has been the utmost described motion in quantitative human motion analysis, descriptions of more challenging movements like the squat or lunge are currently lacking in the literature. The hip and knee joints are exposed to high forces and cause high morbidity and costs. Pre-surgical kinetic data acquisition on a patient-specific anatomy is also scarce in the literature. Studying the normal inter-patient kinetic variability may lead to other comparable studies to initiate more personalized therapies within the orthopedics. METHODS: Trials are performed by 50 healthy young males who were not overweight and approximately of the same age and activity level. Spatial marker trajectories and ground reaction force registrations are imported into the Anybody Modeling System based on subject-specific geometry and the state-of-the-art TLEM 2.0 dataset. Hip and knee joint reaction forces were obtained by a simulation with an inverse dynamics approach. With these forces, a statistical model that accounts for inter-subject variability was created. For this, we applied a principal component analysis in order to enable variance decomposition. This way, noise can be rejected and we still contemplate all waveform data, instead of using deduced spatiotemporal parameters like peak flexion or stride length as done in many gait analyses. In addition, this current paper is, to the authors' knowledge, the first to investigate the generalization of a kinetic model data toward the population. RESULTS: Average knee reaction forces range up to 7.16 times body weight for the forwarded leg during lunge. Conversely, during squat, the load is evenly distributed. For both motions, a reliable and compact statistical model was created. In the lunge model, the first 12 modes accounts for 95.26% of inter-individual population variance. For the maximal-depth squat, this was 95.69% for the first 14 modes. Model accuracies will increase when including more principal components. CONCLUSION: Our model design was proved to be compact, accurate, and reliable. For models aimed at populations covering descriptive studies, the sample size must be at least 50.

Coexisting driver mutations in MPN: clinical and molecular characteristics of a series of 11 patients.

OBJECTIVES: CML, PV, ET and PMF are so called classical MPN with distinct clinical phenotypes. The discovery of the BCR-ABL1 translocation and mutations in driver genes JAK2, MPL and CALR has provided novel insights in their pathogenesis. While these mutations are thought to be mutually exclusive, rare cases of MPN with coexisting driver mutations have been reported. However, little is known about the clinical, biological and molecular characteristics of these patients and the interaction of the neoplastic clones. METHODS: We retrospectively studied 11 MPN patients with coexisting driver mutations (JAK2 V617F + BCR-ABL1: n = 8; CALR type 2 + BCR-ABL1: n = 1; JAK2 V617F + MPL W515: n = 1; JAK2 V617F + CALR type 1: n = 1). To assess possible associated molecular aberrations, we analysed DNA of six patients using NGS. RESULTS: In four CML patients, decreasing BCR-ABL1 transcript levels with increasing JAK2 V617F allele burden under TKI were observed. This strongly suggests that the coexistence of driver mutations originates from two different clones growing independently. Additional somatic mutations were detected in 5 out of 6 (83%) patients affecting 4 different genes, confirming the heterogeneity of this study cohort. Suboptimal response to TKI was observed with a higher frequency (4/8 patients) than reported in conventional series of CML and the overall tolerance of treatment with hydroxyurea and/or imatinib in our series was poor. CONCLUSION: Given the emergence of NGS in clinical practice, more similar cases will be identified in the coming years. The optimal treatment strategy for this rare group of patients is uncertain and toxicity of combination treatment may have to be considered.

Retrograde access of the left atrium for pulmonary vein isolation using magnetic navigation after closure of an atrial septum defect.

Transseptal puncture is the most commonly used technique to perform electrophysiological procedures in the left atrium. This case report describes a pulmonary vein isolation in a patient with a paroxysmal atrial fibrillation, complicated by the presence of an oversized Amplatzer device (AGA Medical Corp., Golden Valley, MN). A retrograde approach using the magnetic navigation system (Niobe, Stereotaxis Inc., St Louis, USA) was performed, and showed to provide a feasible, safe and successful alternative for catheter ablation of cardiac arrhythmias in patients in whom the classic transseptal approach is impossible.