Comparing a Portable Motion Analysis System against the Gold Standard for Potential Anterior Cruciate Ligament Injury Prevention and Screening.

Knee kinematics during a drop vertical jump, measured by the Kinect V2 (Microsoft, Redmond, WA, USA), have been shown to be associated with an increased risk of non-contact anterior cruciate ligament injury. The accuracy and reliability of the Microsoft Kinect V2 has yet to be assessed specifically for tracking the coronal and sagittal knee angles of the drop vertical jump. Eleven participants performed three drop vertical jumps that were recorded using both the Kinect V2 and a gold standard motion analysis system (Vicon, Los Angeles, CA, USA). The initial coronal, peak coronal, and peak sagittal angles of the left and right knees were measured by both systems simultaneously. Analysis of the data obtained by the Kinect V2 was performed by our software. The differences in the mean knee angles measured by the Kinect V2 and the Vicon system were non-significant for all parameters except for the peak sagittal angle of the right leg with a difference of 7.74 degrees and a p-value of 0.008. There was excellent agreement between the Kinect V2 and the Vicon system, with intraclass correlation coefficients consistently over 0.75 for all knee angles measured. Visual analysis revealed a moderate frame-to-frame variability for coronal angles measured by the Kinect V2. The Kinect V2 can be used to capture knee coronal and sagittal angles with sufficient accuracy during a drop vertical jump, suggesting that a Kinect-based portable motion analysis system is suitable to screen individuals for the risk of non-contact anterior cruciate ligament injury.

Using an Affordable Motion Capture System to Evaluate the Prognostic Value of Drop Vertical Jump Parameters for Noncontact ACL Injury.

BACKGROUND: Knee kinematic parameters during a drop vertical jump (DVJ) have been demonstrated to be associated with increased risk of noncontact anterior cruciate ligament (ACL) injury. However, standard motion analysis systems are not practical for routine screening. Affordable and practical motion sensor alternatives exist but require further validation in the context of ACL injury risk assessment. PURPOSE/HYPOTHESIS: To prospectively study DVJ parameters as predictors of noncontact ACL injury in collegiate athletes using an affordable motion capture system (Kinect; Microsoft). We hypothesized that athletes who sustained noncontact ACL injury would have larger initial and peak contact coronal abduction angles and smaller peak flexion angles at the knee during a DVJ. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: 102 participants were prospectively recruited from a collegiate varsity sports program. A total of 101 of the 102 athletes (99%) were followed for an entire season for noncontact ACL injury. Each athlete performed 3 DVJs, and the data were recorded using the motion capture system. Initial coronal, peak coronal, and peak sagittal angles of the knee were identified by our software. RESULTS: Five of the 101 athletes sustained a noncontact ACL injury. Peak coronal angles were significantly greater and peak sagittal flexion angles were significantly smaller in ACL-injured athletes (P = .049, P = .049, respectively). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve of 0.88, 0.92, and 0.90 for initial coronal, peak coronal, and peak sagittal angle, respectively. An initial coronal angle cutoff of 2.96° demonstrated 80% sensitivity and 72% specificity, a peak coronal angle cutoff of 6.16° demonstrated 80% sensitivity and 72% specificity, and a peak sagittal flexion cutoff of 93.82° demonstrated 80% sensitivity and 74% specificity on the study cohort. CONCLUSION: Increased peak coronal angle and decreased peak sagittal angle during a DVJ were significantly associated with increased risk for noncontact ACL injury. Based on ROC analysis, initial coronal angle showed good prognostic ability, whereas peak coronal angle and peak sagittal flexion provided excellent prognostic ability. Affordable motion capture systems show promise as cost-effective and practical options for large-scale ACL injury risk screening.

Detection of Pathogenic Isoforms of IKZF1 in Leukemic Cell Lines and Acute Lymphoblastic Leukemia Samples: Identification of a Novel Truncated IKZF1 Transcript in SUP-B15.

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1-, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.

Potent induction of apoptosis by givinostat in BCR-ABL1-positive and BCR-ABL1-negative precursor B-cell acute lymphoblastic leukemia cell lines.

We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052µM and 0.25±0.028µM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1. As in SUP-B15, givinostat induced apoptosis in both cell lines but showed different levels of cleavage of the procaspase proteins Casp-3, Casp-7 and PARP. Levels of cell cycle-DNA repair regulator p21, CHK1 and FANCD2 levels were markedly affected by givinostat treatment. These data further enrich our understanding of the mechanisms of the antineoplastic effects of givinostat in B-ALL and provide a preclinical rationale for the inclusion of givinostat or similar agent in leukemia therapy.