Spinal cord injury - assessing tolerability and use of combined rehabilitation and NeuroAiD (SATURN) study - primary results of an exploratory study.

OBJECTIVE: MLC601/MLC901 has demonstrated neuroprotective and neuroregenerative properties that enhance neurological recovery in stroke and traumatic brain injury. We aimed to evaluate its safety and potential efficacy in patients with severe spinal cord injury. METHODS: Patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B were included in an open-label cohort study. Each received a course of MLC601/MLC901 for 6 months in addition to standard care and rehabilitation. Key endpoints were safety, AIS grade and motor scores at month 6 (M6). RESULTS: Among 30 patients included (mean age 42.2 ± 17.6 years, 24 men), 20 patients had AIS A while 10 patients had AIS B at baseline. Ten patients experienced 14 adverse events including one serious adverse event and six deaths, none were considered treatment-related. AIS improved in 25% of AIS A and 50% of AIS B. Improvement in ASIA motor score was seen most with cervical injury (median change from baseline 26.5, IQR: 6-55). These findings appear to be better than reported rates of spontaneous recovery for SCI AIS A and B. CONCLUSION: MLC601/MLC901 is safe and may have a role in the treatment of patients with SCI. A controlled trial is justified.

Prospect of Metal Ceramic (Titanium-Wollastonite) Composite as Permanent Bone Implants: A Narrative Review.

This literature review discusses the influence of titanium ceramic composites as a biomaterial towards the fabrication of implants for orthopedic applications. The concept of applying metal-ceramic composites enable many novel combinations in the design and fabrication of complex materials which enhances functionality to improve cell and tissue matrix interactions particularly in the formation of bone. Specific focus is placed on its plethora of materials selected from the metals and ceramic group and identifying the optimal combination that matches them. The prospect of wollastonite as the ceramic counterpart is also highlighted. In this review, we have highlighted the different fabrication methods for such metal-ceramic materials as well as the role that these hybrids play in an in vitro and in vivo environment. Its economic potential as a bone implant material is also discussed.

Early Experience, Setup, Learning Curve, Benefits, and Complications Associated with Exoscope and Three-Dimensional 4K Hybrid Digital Visualizations in Minimally Invasive Spine Surgery.

STUDY DESIGN: Prospective observational study (n=74). PURPOSE: To evaluate the learning curve for exoscope and three-dimensional (3D) 4K hybrid visualization in terms of operating time, advantages, disadvantages, and surgical complications in tubular-access minimally invasive spine surgery (MISS) and to assess surgeon satisfaction with image quality, ergonomics, and ability to perform target site treatment. OVERVIEW OF LITERATURE: Working through tubular retractors poses a challenge. The extreme angulations during microsurgical decompression, especially contralateral decompression, require surgeons to work non-ergonomically. An exoscope allows surgeons to work ergonomically and independently of the microscope oculars as visualizations are now provided by large 3D 4K monitors. However, the value and efficacy of solely depending on an exoscope and 3D 4K monitors during microsurgical work are still unknown. METHODS: Seventy-four patients (99 levels) underwent trans-tubular MISS between March 2018 and January 2019. Five patients were excluded: one had pyogenic discitis, two had revisions, and two were trans-tubular transoral. In total, we analyzed 69 for operating time, blood loss, and complications. The learning curve graph was plotted using the surgical time for each procedure. Surgeons were asked to rate their satisfaction with image quality, ability to maintain ergonomic posture, and efficient target site treatment. RESULTS: For tubular microdiscectomy, the operating time plateaued after six cases, and for tubular decompression and minimally invasive transforaminal lumbar interbody fusion, the operating time plateaued after nine cases. Mean operating time was significantly reduced after the plateau. Complications included four cases of dural tear. All patients improved symptomatically, and there were no postoperative neurological deficits. CONCLUSIONS: Use of the exoscope has a short learning curve. Surgeons benefit from improved ergonomic posture during surgery, and resident teaching appears to be good. The only drawback is the need to rearrange the operating table setup. Complications were comparable to those when using the surgical microscope. An exoscope with hybrid digital visualization provides excellent visualization, depth perception, clarity, and precision target site treatment.

Efficacy of Human Cell-Seeded Muscle-Stuffed Vein Conduit in Rat Sciatic Nerve Repair.

We investigated the efficacy of a muscle-stuffed vein (MSV) seeded with neural-transdifferentiated human mesenchymal stem cells as an alternative nerve conduit to repair a 15-mm sciatic nerve defect in athymic rats. Other rats received MSV conduit alone, commercial polyglycolic acid conduit (Neurotube®), reverse autograft, or were left untreated. Motor and sensory functions as well as nerve conductivity were evaluated for 12 weeks, after which the grafts were harvested for histological analyses. All rats in the treatment groups demonstrated a progressive increase in the mean Sciatic Functional Index (motor function) and nerve conduction amplitude (electrophysiological function) and showed positive withdrawal reflex (sensory function) by the 10th week of postimplantation. Autotomy, which is associated with neuropathic pain, was severe in rats treated with conduit without cells; there was mild or no autotomy in the rats of other groups. Histologically, harvested grafts from all except the untreated groups exhibited axonal regeneration with the presence of mature myelinated axons. In conclusion, treatment with MSV conduit is comparable to that of other treatment groups in supporting functional recovery following sciatic nerve injury; and the addition of cells in the conduit alleviates neuropathic pain. Impact Statement It is shown that pretreated muscle-stuffed vein conduit is comparable to that of commercial nerve conduit and autograft in supporting functional recovery following peripheral nerve injury. The addition of neural-differentiated mesenchymal stem cells in the conduit is shown to alleviate neuropathic pain.

Spinal Cord Injury-Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN Study): Protocol of An Exploratory Study In Assessing the Safety and Efficacy of NeuroAiD Amongst People Who Sustain Severe Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) is a devastating condition with limited therapeutic options despite decades of research. Current treatment options include use of steroids, surgery, and rehabilitation. Nevertheless, many patients with SCI remain disabled. MLC601 (NeuroAiD), a combination of natural products, has been shown to be safe and to aid neurological recovery after brain injuries and may have a potential role in improving recovery after SCI. OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of NeuroAiD amongst people who sustain SCI in the study setting. METHODS: Spinal Cord Injury-Assessing Tolerability and Use of Combined Rehabilitation and NeuroAiD (SATURN) is a prospective cohort study of patients with moderately severe to severe SCI, defined as American Spinal Injury Association (ASIA) Impairment Scale (AIS) A and B. These patients will be treated with open-label NeuroAiD for 6 months in addition to standard care and followed for 24 months. Anonymized data will be prospectively collected at baseline and months 1, 3, 6, 12, 18, and 24 and will include information on demographics; main diagnostics; and neurological and functional state assessed by the Spinal Cord Independence Measure, ASIA-International Standard for Neurological Classification Spinal Cord Injury, and Short Form (SF-8) Health Survey. In addition, NeuroAiD treatment, compliance, concomitant therapies, and side effects, if any, will be collected. Investigators will use a secured online system for data entry. The study is approved by the ethics committee of Hospital University Kebangsaan Malaysia. RESULTS: The coprimary endpoints are safety, AIS grade, and improvement in ASIA motor score at 6 months. Secondary endpoints are AIS grade, ASIA motor scores and sensory scores, Spinal Cord Independence Measure (SCIM), SF-8 Health Survey, and compliance at other time points. CONCLUSIONS: SATURN investigates the promising role of NeuroAiD in SCI especially given its excellent safety profile. We described here the protocol and online data collection tool we will use for this prospective cohort study. The selection of moderately severe to severe SCI provides an opportunity to investigate the role of NeuroAiD in addition to standard rehabilitation in patients with poor prognosis. The results will provide important information on the feasibility of conducting larger controlled trials to improve long-term outcome of patients with SCI. TRIAL REGISTRATION: Clinicaltrials.gov NCT02537899; https://clinicaltrials.gov/ct2/show/NCT02537899 (Archived by WebCite at http://www.webcitation.org/6m2pncVTG).

Modified hybrid fixator for high-energy Schatzker V and VI tibial plateau fractures.

High-energy tibial plateau fractures associated with severe soft tissue injury are difficult to manage. The risk of wound complications following open reduction and internal fixation is notably high owing to extensive soft tissue dissection. Alternatively, application of hybrid external fixator minimizes soft tissue dissection and provides adequate fracture stabilization to allow early range of motion and correction of any mal-alignment. With this technique, soft tissue complications particularly surgical site infections are expected to be significantly reduced. This prospective study aims to determine the effectiveness of a modified hybrid external fixator in the management of high-energy tibial plateau fractures. Thirty-three patients with high-energy Schatzker V and VI tibial plateau fracture with severe soft tissue injury precluding formal open reduction were enrolled into the study. The fixator was a construct combining the Ilizarov ring with a monolateral external fixator. The results-bony union, range of motion, and associated complications of the treatment-were assessed. All fractures united within an average time of 14 weeks. Neither loss of reduction nor surgical site wound breakdown/osteomyelitis was noted. Eight patients developed superficial pin track infection and one septic arthritis of the knee joint. Hybrid external fixation is a safe option for complex high-energy tibial plateau fractures by simultaneously providing adequate fracture stabilization and protection of soft tissue healing to achieve bony union. The complication is mainly related to pin tract infection.