Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients.

We have chosen to test the safety of human intracerebroventricular (ICV) brain injections of autologous non-genetically-modified adipose-derived stromal vascular fraction (ADSVF). In this IRB-approved trial, 24 patients received ICV ADSVF via an implanted reservoir between 5/22/14 and 5/22/17. Seven others were injected via their ventriculo-peritoneal shunts. Ten patients had Alzheimer's disease (AD), 6 had amyotrophic lateral sclerosis (ALS), 6 had progressive multiple sclerosis (MS-P), 6 had Parkinson's "Plus" (PD+), 1 had spinal cord injury, 1 had traumatic brain injury, and 1 had stroke. Median age was 74 (range 41-83). Injections were planned every 2-3 months. Thirty-one patients had 113 injections. Patients received SVF injection volumes of 3.5-20 cc (median:4 cc) containing 4.05 × 105 to 6.2 × 107 cells/cc, which contained an average of 8% hematopoietic and 7.5% adipose stem cells. Follow-up ranged from 0 to 36 months (median: 9.2 months). MRIs post injection(s) were unchanged, except for one AD patient whose hippocampal volume increased from < 5th percentile to 48th percentile (NeuroQuant® volumetric MRI). Of the 10 AD patients, 8 were stable or improved in tests of cognition. Two showed improvement in P-tau and ß-amyloid levels. Of the 6 MS-P patients all are stable or improved. Four of 6 ALS patients died of disease progression. Twelve of 111 injections (11%) led to 1-4 days of transient meningismus, and mild temperature elevation, which resolved with acetaminophen and/or dexamethasone. Two (1.8% of injections) required hospitalization for these symptoms. One patient (0.9% of injections) had his reservoir removed and later replaced for presumed infection. In this Phase 1 safety trial, ADSVF was safely injected into the human brain ventricular system in patients with no other treatment options. Secondary endpoints of clinical improvement or stability were particularly promising in the AD and MS-P groups. These results will be submitted for a Phase 2 FDA-approved trial.

Effective Treatment of Traumatic Brain Injury in Rowett Nude Rats with Stromal Vascular Fraction Transplantation.

Traumatic brain injury (TBI) affects 1.9 million Americans, including blast TBI that is the signature injury of the Iraq and Afghanistan wars. Our project investigated whether stromal vascular fraction (SVF) can assist in post-TBI recovery. We utilized strong acoustic waves (5.0 bar) to induce TBI in the cortex of adult Rowett Nude (RNU) rats. One hour post-TBI, harvested human SVF (500,000 cells suspended in 0.5 mL lactated Ringers) was incubated with Q-Tracker cell label and administered into tail veins of RNU rats. For comparison, we utilized rats that received SVF 72 h post-TBI, and a control group that received lactated Ringers solution. Rotarod and water maze assays were used to monitor motor coordination and spatial memories. Rats treated immediately after TBI showed no signs of motor skills and memory regression. SVF treatment 72 h post-TBI enabled the rats maintain their motor skills, while controls treated with lactated Ringers were 25% worse statistically in both assays. Histological analysis showed the presence of Q-dot labeled human cells near the infarct in both SVF treatment groups; however, labeled cells were twice as numerous in the one hour group. Our study suggests that immediate treatment with SVF would serve as potential therapeutic agents in TBI.

Role of Swallowing Function of Tracheotomised Patients in Major Head and Neck Cancer Surgery.

INTRODUCTION: Tracheotomy is a frequent procedure in extended head and neck cancer surgery and known to be a risk factor for prolonged hospitalization. The authors hypothesized that the clinical course and delayed decannulation of patients are not only influenced by airway narrowing, but also by a compromised postoperative swallowing function. MATERIAL AND METHODS: The investigators implemented a retrospective cohort study. The sample was composed of a tertiary care center patients who underwent major head and neck cancer surgery, each receiving a tracheostomy. Data collected include general clinical data as well as endoscopical evaluation of swallowing function and aspiration rate. Descriptive and bivariate statistics were computed and the P value was set at.05. RESULTS: The sample was composed of 96 patients with an average age of 64.2 and sex ratio of 1.4:1 (m:f). There was a strong statistically significant relation between swallowing function and timing of decannulation (P < 0.001) and duration of hospitalization (P < 0.001). Age (P = 0.55), sex (P = 0.54), tumor size (P = 0.12), general diseases (P = 0.24), distant metastases (P = 0.15), or extent of neck dissection (P = 0.15) were not significantly associated to swallowing function. Permanent cannulation was significantly correlated to a primary cancer of the soft palate or base of the tonge (P < 0.001). CONCLUSION: The results of this study confirm the importance of the evaluation of swallowing function before the removal of the tracheotomy cannula in head and neck cancer patients.

Validation of Acoustic Wave Induced Traumatic Brain Injury in Rats.

BACKGROUND: This study looked to validate the acoustic wave technology of the Storz-D-Actor that inflicted a consistent closed-head, traumatic brain injury (TBI) in rats. We studied a range of single pulse pressures administered to the rats and observed the resulting decline in motor skills and memory. Histology was observed to measure and confirm the injury insult. METHODS: Four different acoustic wave pressures were studied using a single pulse: 0, 3.4, 4.2 and 5.0 bar (n = 10 rats per treatment group). The pulse was administered to the left frontal cortex. Rotarod tests were used to monitor the rats' motor skills while the water maze test was used to monitor memory deficits. The rats were then sacrificed ten days post-treatment for histological analysis of TBI infarct size. RESULTS: The behavioral tests showed that acoustic wave technology administered an effective insult causing significant decreases in motor abilities and memory. Histology showed dose-dependent damage to the cortex infarct areas only. CONCLUSIONS: This study illustrates that the Storz D-Actor effectively induces a repeatable TBI infarct, avoiding the invasive procedure of a craniotomy often used in TBI research.

A comparison of functional mobility in standard vs. ultralight wheelchairs as measured by performance on a community obstacle course.

PURPOSE: Appropriate wheelchair prescription requires maximizing user function while justifying cost. The purpose of this study was to investigate differences in a user's performance of mobility skills (on a community obstacle course) between an ultralight (UWC) and standard wheelchair (SWC). SUBJECTS: Sixty healthy adults (mean = 28.3 years) without wheelchair experience performed one course trial. METHODS: Participants were randomly assigned to an UWC or a SWC. Researchers recorded time for completion, Rating of Perceived Exertion (RPE), and number, location, and types of errors committed. Errors included contact of WC and any obstacle, front casters leaving the ground, or loss of directional control (veering). RESULTS: A MANOVA of the data (p < 0.05) showed a significant difference in numbers of contact errors (higher in the SWC) and castor errors (higher in the UWC) between the two wheelchairs. Number of veering errors, time to complete, and RPE were not significantly different. CONCLUSIONS: Differences in wheelchair design can lead to differences in a user's performance of functional mobility skills. Choice of wheelchair may affect a user's ability to be independent in a community setting.