Clinical gait analysis using video-based pose estimation: Multiple perspectives, clinical populations, and measuring change.

Gait dysfunction is common in many clinical populations and often has a profound and deleterious impact on independence and quality of life. Gait analysis is a foundational component of rehabilitation because it is critical to identify and understand the specific deficits that should be targeted prior to the initiation of treatment. Unfortunately, current state-of-the-art approaches to gait analysis (e.g., marker-based motion capture systems, instrumented gait mats) are largely inaccessible due to prohibitive costs of time, money, and effort required to perform the assessments. Here, we demonstrate the ability to perform quantitative gait analyses in multiple clinical populations using only simple videos recorded using low-cost devices (tablets). We report four primary advances: 1) a novel, versatile workflow that leverages an open-source human pose estimation algorithm (OpenPose) to perform gait analyses using videos recorded from multiple different perspectives (e.g., frontal, sagittal), 2) validation of this workflow in three different populations of participants (adults without gait impairment, persons post-stroke, and persons with Parkinson's disease) via comparison to ground-truth three-dimensional motion capture, 3) demonstration of the ability to capture clinically relevant, condition-specific gait parameters, and 4) tracking of within-participant changes in gait, as is required to measure progress in rehabilitation and recovery. Importantly, our workflow has been made freely available and does not require prior gait analysis expertise. The ability to perform quantitative gait analyses in nearly any setting using only low-cost devices and computer vision offers significant potential for dramatic improvement in the accessibility of clinical gait analysis across different patient populations.

MiSDEED: a synthetic data engine for microbiome study power analysis and study design.

Summary: MiSDEED (Microbial Synthetic Data Engine for Experimental Design) is a command-line tool for generating synthetic longitudinal multinode data from simulated microbial environments. It generates relative-abundance timecourses under perturbations for an arbitrary number of time points, samples, locations and data types. All simulation parameters are exposed to the user to facilitate rapid power analysis and aid in study design. Users who want additional flexibility may also use MiSDEED as a Python package. Availability and implementation: MiSDEED is written in Python and is freely available at https://github.com/pchlenski/misdeed.

Evidence for increased neuromuscular drive following spinal manipulation in individuals with subacromial pain syndrome.

BACKGROUND: Thoracic spinal manipulation can improve pain and function in individuals with shoulder pain; however, the mechanisms underlying these benefits remain unclear. Here, we evaluated the effects of thoracic spinal manipulation on muscle activity, as alteration in muscle activity is a key impairment for those with shoulder pain. We also evaluated the relationship between changes in muscle activity and clinical outcomes, to characterize the meaningful context of a change in neuromuscular drive. METHODS: Participants with shoulder pain related to subacromial pain syndrome (n = 28) received thoracic manipulation of low amplitude high velocity thrusts to the lower, middle and upper thoracic spine. Electromyographic muscle activity (trapezius-upper, middle, lower; serratus anterior; deltoid; infraspinatus) and shoulder pain (11-point scale) was collected pre and post-manipulation during arm elevation, and normalized to a reference contraction. Clinical benefits were assessed using the Pennsylvania Shoulder Score (Penn) at baseline and 2-3 days post-intervention. FINDINGS: A significant increase in muscle activity was observed during arm ascent (p = 0.002). Using backward stepwise regression analysis, a specific increase in the serratus anterior muscle activity during arm elevation explained improved Penn scores following post-manipulation (p < 0.05). INTERPRETATION: Thoracic spinal manipulation immediately increases neuromuscular drive. In addition, increased serratus anterior muscle activity, a key muscle for scapular motion, is associated with short-term improvements in shoulder clinical outcomes.

Classifying vertebral artery anatomy abnormality in children with skeletal dysplasia.

PURPOSE: Skeletal dysplasia (SKD) have predictably abnormal occipitocervical skeletal anatomy, but a similar understanding of their vertebral artery anatomy is not known. Knowledge and classification of vertebral artery anatomy in SKD patients is important for safe surgical planning. We aimed to determine if predictably abnormal vertebral artery anatomy exists in pediatric SKD. METHODS: We performed a retrospective review of CTAs of the neck for pediatric patients at a single institution from 2006 to 2018. CTAs in SKD and controls were reviewed independently in blinded fashion by two radiologists who classified dominance, vessel curvature at C2, direction at C3, and presence of fenestration and intersegmental artery. RESULTS: 14 skeletal dysplasia patients were compared to 32 controls. The path of the vertebral artery at C2 foramen was no different between the cohorts or by side, right (p = 0.43) or left (p = 0.13), nor for medial or lateral exiting direction from C3 foramen on right (p = 0.82) or left (p = 0.60). Dominance was most commonly neutral in both groups (71% in SKD and 63% in controls). There were no fenestrated nor first intersegmental arteries in our cohort. CONCLUSION: No systematic differences were detected between SKD and control patients with respect to vertebral artery anatomy. Nonetheless, surgically relevant variability was observed in both groups. Paying particular attention to the direction of exit at C3 and curvature at C2 with respect to the foramen and vessel dominance are important and easily classifiable abnormalities that both surgeons and radiologists can use to communicate and employ in pre-operative planning. LEVEL OF EVIDENCE: III.

Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation.

PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.Experimental Design: In this study, we examined the immune landscape and function of PD-1 expression by T cells from tumor and peripheral blood in patients with malignant glioma. RESULTS: We found several differences between PD-1+ tumor-infiltrating lymphocytes (TIL) and patient-matched PD-1+ peripheral blood T lymphocytes. Phenotypically, PD-1+ TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1+ T cells, which instead had increased markers of memory. A comparison of the T-cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1+ T cells had a significantly increased proliferative capacity upon activation compared with PD-1- T cells. CONCLUSIONS: Our evidence suggests that PD-1 expression in patients with glioma reflects chronically activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomic location. The decreased diversity in PD-1+ T cells suggests that the PD-1-expressing population has a narrower range of cognate antigen targets compared with the PD-1 nonexpression population. This information can be used to inform how we interpret immune responses to PD-1-blocking therapies or other immunotherapies.

TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination.

Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.

Radiofrequency ablation of advanced head and neck cancer.

OBJECTIVE: To determine if the application of radiofrequency ablation to advanced head and neck cancer (HNC) would result in local control of the tumor. DESIGN: Radiofrequency ablation was applied to advanced head and neck malignant tumors in the participants of this nonrandomized controlled trial. SETTING: Academic tertiary care medical center. PARTICIPANTS: Twenty-one participants with recurrent and/or unresectable HNC who failed treatment with surgery, radiation, and/or chemotherapy were selected for the trial. Patients deemed appropriate for curative standard radiation or surgery were not accepted as participants. INTERVENTION: Radiofrequency ablation was applied to head and neck tumors under general anesthesia and computed tomographic scan guidance. MAIN OUTCOME MEASURES: The primary end point was local control. Computed tomographic scan tumor measurements were used to assess response by standard response evaluation criteria in solid tumors (RECIST) guidelines. Secondary outcome measures included survival and quality of life. RESULTS: Eight of 13 participants had stable disease after intervention. Median survival was 127 days, and an improvement in University of Washington quality-of-life scores was noted. Adverse outcomes included 1 death due to carotid hemorrhage and 2 strokes. CONCLUSION: Radiofrequency ablation is a palliative treatment alternative that shows promise in addressing the challenges of local control and quality of life in patients with incurable HNC who have failed standard curative treatment.