Allogeneic Disc Progenitor Cells Safely Increase Disc Volume and Improve Pain, Disability, and Quality of Life in Patients With Lumbar Disc Degeneration-Results of an FDA-Approved Biologic Therapy Randomized Clinical Trial.

BACKGROUND: Progenitor cells derived from intervertebral disc tissue demonstrated immunomodulatory and regenerative properties in preclinical studies. We report the safety and efficacy results of a US Food and Drug Administration-approved clinical trial of these cells for the treatment of symptomatic degenerative disc disease. METHODS: Sixty patients with symptomatic single-level lumbar degenerative disc disease (mean age 37.9 years, 60% men) were enrolled in a randomized, double-blinded, placebo-controlled Phase I/Phase II study at 13 clinical sites. They were randomized to receive single intradiscal injections of either low-dose cells (N = 20), high-dose cells (N = 20), vehicle alone (N = 10), or placebo (N = 10). The primary endpoint was mean visual analog scale (VAS) pain improvement >30% at 52 weeks. Disc volume was radiologically assessed. Adverse events (AEs), regardless of whether they were related to treatment, were reported. Patients were assessed at baseline and at 4, 12, 26, 52, 78, and 104 weeks posttreatment. RESULTS: At week 52, the high-dose group had a mean VAS percentage decrease from baseline (-62.8%, P = 0.0005), achieving the endpoint of back pain improvement >30%; the mean change was also significantly greater than the minimal clinically important difference of a 20-point decrease (-42.8, P = 0.001). This clinical improvement was maintained at week 104. The vehicle group had a smaller significant decrease in VAS (-52.8%, P = 0.044), while the low-dose and placebo groups showed nonsignificant improvements. Only the high-dose group had a significant change in disc volume, with mean increases of 249.0 mm3 (P = 0.028) at 52 weeks and 402.1 mm3 (P = 0.028) at 104 weeks. A minority of patients (18.3%) reported AEs that were severe. Overall, 6.7% of patients experienced serious AEs, all in the vehicle (n = 1) or placebo (n = 3) groups, none treatment related. CONCLUSIONS: High-dose allogeneic disc progenitor cells produced statistically significant, clinically meaningful improvements in back pain and disc volume at 1 year following a single intradiscal injection and were safe and well tolerated. These improvements were maintained at 2 years post-injection. CLINICAL TRIAL REGISTRATION: NCT03347708-Study to Evaluate the Safety and Preliminary Efficacy of Injectable Disc Cell Therapy, a Treatment for Symptomatic Lumbar Intervertebral Disc Degeneration.

Complications and Avoidance in Adult Spinal Deformity Surgery.

Adult spinal deformity (ASD) is a complex disease that can result in significant disability. Although surgical treatment has been shown to be of benefit, the complication rate in the perioperative and postoperative periods can be as high as 70%. Some of the most common complications of ASD surgery include intraoperative cerebrospinal fluid leak, high blood loss, new neurologic deficit, hardware failure, proximal junctional kyphosis/failure, pseudarthrosis, surgical site infection, and medical complications. For each of these complications, one or more strategies can be utilized to avoid and/or minimize the consequences.

Alternatives to DEXA for the assessment of bone density: a systematic review of the literature and future recommendations.

OBJECTIVE: Osteoporosis has significant implications in spine fusion surgery, for which reduced spinal bone mineral density (BMD) can result in complications and poorer outcomes. Currently, dual-energy x-ray absorptiometry (DEXA) is the gold standard for radiographic diagnosis of osteoporosis, although DEXA accuracy may be limited by the presence of degenerative spinal pathology. In recent years, there has been an evolving interest in using alternative imaging, including CT and MRI, to assess BMD. In this systematic review of the literature, the authors assessed the use and effectiveness of MRI, opportunistic CT (oCT), and quantitative CT (qCT) to measure BMD. METHODS: In accordance with the PRISMA guidelines, the authors conducted a systematic search for articles posted on PubMed between the years 2000 and 2022 by using the keywords "opportunistic CT, quantitative CT, MRI" AND "bone density" AND "spine." Inclusion criteria consisted of articles written in English that reported studies pertaining to human or cadaveric subjects, and studies including a measure of spinal BMD. Articles not related to spinal BMD, osteoporosis, or spinal surgery or reports of studies that did not include the use of spinal MRI or CT were excluded. Key study outcomes were extracted from included articles, and qualitative analysis was subsequently performed. RESULTS: The literature search yielded 302 articles. Forty-two articles reported studies that met the final inclusion criteria. Eighteen studies utilized MRI protocols to correlate spinal BMD with vertebral bone quality scores, M-scores, and quantitative perfusion markers. Eight studies correlated oCT with spinal BMD, and 16 studies correlated qCT with spinal BMD. With oCT and qCT imaging, there was consensus that Hounsfield unit (HU) values > 160 demonstrated significant reduction in risk of osteoporosis, whereas HU values < 110 were significantly correlated with osteoporosis. CONCLUSIONS: Osteoporosis is increasingly recognized as a significant risk factor for complications after spinal fusion surgery. Consequently, preoperative assessment of BMD is a critical factor to consider in planning surgical treatment. Although DEXA has been the gold standard for BMD measurement, other imaging modalities, including MRI, oCT, and qCT, appear to be viable alternatives and may offer cost and time savings.

Complications of surgical intervention in adult lumbar scoliosis.

If nonoperative measures are unsuccessful in managing the pain and disability of adult spinal deformities, surgical correction may provide the potential for significant improvement in a patient's quality of life. However, these procedures have a relatively high risk of complications. Identifying patients that may benefit from surgical intervention requires a thorough understanding of potential complications and managing the risks of any individual patient. Complications do not necessarily result in poor outcomes, and good outcomes are not always complication free. Higher risk patients potentially have more to gain, even if they experience complications. With the rapidly expanding senior population and expanded capabilities to manage high-risk patients, it is helpful to consider the lessons provided by ever expanding databases of outcome measures to refine the surgical decision-making process.

Traumatic Lumbar Subdural Hematoma in the Absence of Intracranial Disease.

BACKGROUND: Traumatic spinal subdural hematoma is an exceedingly rare condition, with those occurring in the absence of intracranial disease being particularly uncommon. Only 13 such cases have been reported. Although theories exist to describe the pathophysiology of traumatic spinal subdural hematoma, the precise mechanism and guidelines for management remain unclear. CASE DESCRIPTION: This report describes a 37-year-old woman who suffered a traumatic assault who developed progressive low back pain with radicular symptoms 2 days after presentation. Magnetic resonance imaging revealed a lumbar subdural hematoma extending from L1 to L5. No intracranial disease was detected on imaging. CONCLUSIONS: Definitive guidelines for management of this condition are uncertain; however, successful use of conservative management, lumbar drainage, and surgical evacuation has been reported. This patient underwent a lumbar laminectomy with evacuation of the hematoma, resulting in immediate pain relief and resolution of symptoms within 1 week of the procedure.

Malignant carotid body tumor presenting with myelopathy: case report.

Malignant carotid body tumors are rare, with spread of the tumor mostly noted in regional lymph nodes. Vertebral metastases are an exceedingly rare presentation, only reported in isolated case reports, and present a diagnostic and management challenge. A case of widespread vertebral metastasis, presenting with myelopathy, from a carotid body tumor is discussed in this paper, along with management strategies.

Glioblastoma: molecular pathways, stem cells and therapeutic targets.

Glioblastoma (GBM), a WHO-defined Grade IV astrocytoma, is the most common and aggressive CNS malignancy. Despite current treatment modalities, the survival time remains dismal. The main cause of mortality in patients with this disease is reoccurrence of the malignancy, which is attributed to treatment-resistant cancer stem cells within and surrounding the primary tumor. Inclusion of novel therapies, such as immuno- and DNA-based therapy, may provide better means of treating GBM. Furthermore, manipulation of recently discovered non-coding microRNAs, some of which regulate tumor growth through the development and maintenance of GBM stem cells, could provide new prospective therapies. Studies conducted by The Cancer Genome Atlas (TCGA) also demonstrate the role of molecular pathways, specifically the activated PI3K/AKT/mTOR pathway, in GBM tumorigenesis. Inhibition of the aforementioned pathway may provide a more direct and targeted method to GBM treatment. The combination of these treatment modalities may provide an innovative therapeutic approach for the management of GBM.

Human mesenchymal stem cells modulate inflammatory cytokines after spinal cord injury in rat.

Transplantation of mesenchymal stem cells (MSC) improves functional recovery in experimental models of spinal cord injury (SCI); however, the mechanisms underlying this effect are not completely understood. We investigated the effect of intrathecal implantation of human MSC on functional recovery, astrogliosis and levels of inflammatory cytokines in rats using balloon-induced spinal cord compression lesions. Transplanted cells did not survive at the lesion site of the spinal cord; however, functional recovery was enhanced in the MSC-treated group as was confirmed by the Basso, Beattie, and Bresnahan (BBB) and the flat beam test. Morphometric analysis showed a significantly higher amount of remaining white matter in the cranial part of the lesioned spinal cords. Immunohistochemical analysis of the lesions indicated the rearrangement of the glial scar in MSC-treated animals. Real-time PCR analysis revealed an increased expression of Irf5, Mrc1, Fgf2, Gap43 and Gfap. Transplantation of MSCs into a lesioned spinal cord reduced TNFα, IL-4, IL-1ß, IL-2, IL-6 and IL-12 and increased the levels of MIP-1α and RANTES when compared to saline-treated controls. Intrathecal implantation of MSCs reduces the inflammatory reaction and apoptosis, improves functional recovery and modulates glial scar formation after SCI, regardless of cell survival. Therefore, repeated applications may prolong the beneficial effects induced by MSC application.

Transcervical drainage of epidural and retropharyngeal abscess.

This report describes treatment of concurrent epidural and retropharyngeal abscesses and presents a novel surgical approach to treating this pathology. The treatment of epidural and retropharyngeal prevertebral abscesses requires surgical drainage in addition to systemic antibiotics. After the patient's airway is secured, urgent otolaryngologic surgery consultation is obtained for transoral drainage of the retropharyngeal abscesses to minimize risk to vascular and nervous structures within the neck. If epidural extension is also present, urgent neurosurgical evaluation and decompression may be necessary. We report a patient with an epidural and prevertebral abscess. A posterior approach was taken for wide decompression of the cervical spine and evacuation of the epidural collection. During this procedure, under fluoroscopic guidance, an 8 Fr soft rubber catheter was slowly advanced ventrally in the epidural space through the C5-6 intervertebral disk into the retropharyngeal abscess with evacuation of this collection as well. Using a single, wide posterior approach, the dorsal epidural, the ventral epidural, and prevertebral abscesses were all successfully evacuated. This report describes a novel approach for evacuation of prevertebral abscess concurrent with multilevel laminectomy for epidural abscess evacuation.