Sports-related brain injuries: connecting pathology to diagnosis.

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

Minimally invasive spine surgery for adult degenerative lumbar scoliosis.

OBJECT: Historically, adult degenerative lumbar scoliosis (DLS) has been treated with multilevel decompression and instrumented fusion to reduce neural compression and stabilize the spinal column. However, due to the profound morbidity associated with complex multilevel surgery, particularly in elderly patients and those with multiple medical comorbidities, minimally invasive surgical approaches have been proposed. The goal of this meta-analysis was to review the differences in patient selection for minimally invasive surgical versus open surgical procedures for adult DLS, and to compare the postoperative outcomes following minimally invasive surgery (MIS) and open surgery. METHODS: In this meta-analysis the authors analyzed the complication rates and the clinical outcomes for patients with adult DLS undergoing complex decompressive procedures with fusion versus minimally invasive surgical approaches. Minimally invasive surgical approaches included decompressive laminectomy, microscopic decompression, lateral and extreme lateral interbody fusion (XLIF), and percutaneous pedicle screw placement for fusion. Mean patient age, complication rates, reoperation rates, Cobb angle, and measures of sagittal balance were investigated and compared between groups. RESULTS: Twelve studies were identified for comparison in the MIS group, with 8 studies describing the lateral interbody fusion or XLIF and 4 studies describing decompression without fusion. In the decompression MIS group, the mean preoperative Cobb angle was 16.7° and mean postoperative Cobb angle was 18°. In the XLIF group, mean pre- and postoperative Cobb angles were 22.3° and 9.2°, respectively. The difference in postoperative Cobb angle was statistically significant between groups on 1-way ANOVA (p = 0.014). Mean preoperative Cobb angle, mean patient age, and complication rate did not differ between the XLIF and decompression groups. Thirty-five studies were identified for inclusion in the open surgery group, with 18 studies describing patients with open fusion without osteotomy and 17 papers detailing outcomes after open fusion with osteotomy. Mean preoperative curve in the open fusion without osteotomy and with osteotomy groups was 41.3° and 32°, respectively. Mean reoperation rate was significantly higher in the osteotomy group (p = 0.008). On 1-way ANOVA comparing all groups, there was a statistically significant difference in mean age (p = 0.004) and mean preoperative curve (p = 0.002). There was no statistically significant difference in complication rates between groups (p = 0.28). CONCLUSIONS: The results of this study suggest that surgeons are offering patients open surgery or MIS depending on their age and the severity of their deformity. Greater sagittal and coronal correction was noted in the XLIF versus decompression only MIS groups. Larger Cobb angles, greater sagittal imbalance, and higher reoperation rates were found in studies reporting the use of open fusion with osteotomy. Although complication rates did not significantly differ between groups, these data are difficult to interpret given the heterogeneity in reporting complications between studies.

Exploiting tumor-intrinsic signals to induce mesenchymal stem cell-mediated suicide gene therapy to fight malignant glioma.

BACKGROUND: Human mesenchymal stem cell (MSC)-based tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene delivery is regarded as an effective treatment for glioblastoma (GBM). However, adverse-free target site homing of the delivery vehicles to the tumor microsatellite nests is challenging, leading to erroneously sustained released of this suicide protein into the normal brain parenchyma; therefore, limiting off-target cytotoxicity and controlled expression of the suicide inductor is a prerequisite for the safe use of therapeutic stem cells. METHODS: Utilizing the intrinsic expression profile of GBM and its elevated expression of TGF-ß relative to normal brain tissue, we sought to engineer human adipose-derived MSCs (hAMSC-SBE4-TRAIL) which augment the expression of TRAIL under the trigger of TGF-ß signaling. We validated our therapeutic technology in a series of functional in vitro and in vivo assays using primary patient-derived GBM models. RESULTS: Our current findings show that these biologic delivery vehicles have high tumor tropism efficacy and expression TRAIL gene under the trigger of TGF-ß-secreting GBMs, as well as avoid unspecific TRAIL secretion into normal brain tissue. hAMSC-SBE4-TRAIL inhibited the proliferation and induced apoptosis in experimental GBMs both in vitro and in vivo. In addition, our improved platform of engineered MSCs significantly decreased the tumor volume and prolonged survival time in a murine model of GBM. CONCLUSIONS: Our results on the controlled release of suicide inductor TRAIL by exploiting an endogenous tumor signaling pathway demonstrate a significant improvement for the clinical utility of stem cell-mediated gene delivery to treat brain cancers. Harvesting immune-compatible MSCs from patients' fat by minimally invasive procedures further highlights the clinical potential of this approach in the vision of applicability in a personalized manner. The hAMSC-SBE4-TRAIL exhibit great curative efficacy and are a promising cell-based treatment option for GBM to be validated in clinical exploration.

Transforming Growth Factor-ß Promotes Homing and Therapeutic Efficacy of Human Mesenchymal Stem Cells to Glioblastoma.

Human mesenchymal stem cell-based tumor therapeutic gene delivery is regarded as a promising strategy for the treatment of glioblastoma (GBM). However, the efficiency of these stem cells to home to the target sites limits their potential curative effect and clinical application. In this work, we provide a novel pretreatment approach for enhancing the homing capacity of human adipose-derived mesenchymal stem cells (hAMSCs) for stem cell-based tumor gene delivery for GBM therapy. Pre-exposure of these stem cells to TGF-ß resulted in enhanced homing ability to GBM through increasing CXC chemokine receptor 4 (CXCR4) expression, as evidenced by a diminishing homing capacity when inhibition of the TGF-ß receptor II and CXCR4 was applied. In addition, by pretreating hAMSCs expression of tumor necrosis factor-related apoptosis-inducing ligand with TGF-ß, we achieved significant enhancements in the therapeutic efficacy as demonstrated by an increased number of migrated hAMSCs to target sites, decreased tumor volume, and prolonged survival time in a murine model of GBM. These findings highlight a straightforward method in which cell preconditioning methodology is utilized to promote therapeutic efficacy of a biological treatment for GBM.

Meniscal Transplants and Scaffolds: A Systematic Review of the Literature.

The reported incidence of meniscal tears is approximately 61 per 100,000. In instances where preservation of the native meniscus is no longer a feasible option, meniscal allograft transplantation (MAT) and implants or scaffolds may be considered. The goal of this review was to compare the success and failure rates of two techniques, MAT and meniscal scaffolds, and make an inference which treatment is more preferable at the present time and future. Studies that met inclusion criteria were assessed for technique used, type of transplant used, number of procedures included in the study, mean age of patients, mean follow-up time, number of failures, failure rate, and reported reoperation rate. Fifteen studies for the MAT group and 7 studies for the meniscal scaffold group were identified. In this selection of studies, the average failure rate in the MAT group was 18.7% and average reoperation rate was 31.3%. The average failure rate in the meniscal scaffold group was 5.6%, and average reoperation rate was 6.9%. It appears that although MAT is associated with high reoperation and failure rates, the limited number of studies on both MAT and scaffolds and mainly short-term results of scaffold studies make it difficult to make an objective comparison.

Disparities in Total Hip Arthroplasty Versus Hemiarthroplasty in the Management of Geriatric Femoral Neck Fractures.

INTRODUCTION: Recent clinical evidence suggests that total hip arthroplasty (THA) provides improved clinical outcomes as compared to hemiarthroplasty (HA) for displaced femoral neck fractures in elderly individuals. However, THA is still utilized relatively infrequently. Few studies have evaluated the factors affecting utilization and the role socioeconomics plays in THA versus HA. METHODS: In the United States, the National Inpatient Sample (NIS) database was used to identify patients treated surgically for femoral neck fracture, between 2009 and 2010. Patients were identified using International Classification of Diseases, Ninth Revision, codes for closed, transcervical femoral neck fractures and closed fractures at unspecified parts of the femoral neck. All candidate predictors of THA versus HA were entered into a multilevel mixed-effect regression model. RESULTS: Older patient age, being Asian or Pacific Islander, and having Medicaid payer status were all associated with lower odds of receiving THA. Patients with private insurance including Health Maintenance organization (HMO) had higher odds of THA as did patients with other insurance. Odds of THA were significantly lower among patients in teaching hospitals and higher at hospitals with greater THA volume. DISCUSSION: Ethnicity, payer status, hospital size, and institutional THA volume were all associated with the utilization of THA versus HA in the treatment of geriatric femoral neck fractures. LEVEL OF EVIDENCE: Level III Retrospective Cohort study.

Bilateral Sacral Ala Fractures Are Strongly Associated With Lumbopelvic Instability.

OBJECTIVES: To quantify the incidence of lumbopelvic instability in the setting of unilateral and bilateral sacral fractures and assess whether the presence of bilateral sacral fractures on axial imaging is a useful screening test for lumbopelvic instability. DESIGN: Retrospective case series. SETTING: Level I trauma center at an academic medical center. PATIENTS/PARTICIPANTS: A hospital database was used to identify patients diagnosed with a sacral fracture by The International Classification of Diseases, Ninth Revision (ICD-9) code from 2000 to 2014. INTERVENTION: Axial cross-sectional imaging was reviewed to confirm the presence of unilateral or bilateral sacral ala fractures. Sagittal reconstructions were scrutinized for a transverse fracture line separating the lumbar spine from the pelvis, which was used to define lumbopelvic instability. MAIN OUTCOME MEASUREMENTS: The Roy-Camille classification system was applied to all identified cases of lumbopelvic instability. RESULTS: One thousand five hundred twenty-six patients were diagnosed with sacral fractures by the ICD-9 code. Four hundred ninety had adequate axial and sagittal cross-sectional imaging. Four hundred forty-three of these patients had unilateral sacral ala fractures, and none of these were associated with lumbopelvic instability. Forty-seven patients had bilateral sacral ala fractures, and 41 of these (87%) had a transverse component indicating some degree of lumbopelvic instability. The presence of bilateral sacral fractures was 100% sensitive and 99% specific for lumbopelvic instability. Among fractures with lumbopelvic instability, 27 (66%) were Roy-Camille type 1, 11 (27%) were type 2, and 3 (7%) were type 3. CONCLUSIONS: Bilateral sacral ala fractures are strongly associated with lumbopelvic instability and can be used as a very sensitive and specific screening tool. All patients with bilateral sacral fractures on axial computed tomography or magnetic resonance imaging should have close assessment of the sagittal plane images to evaluate for this pathology. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1.

Mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) have been regarded for their clinical therapeutic potential for central nervous system (CNS) pathologies. Their potential utility is a result of their intrinsic ability to repair damaged tissues, deliver therapeutic proteins, and migrate to sites of pathology within the brain. However, it remains unclear whether the CNS promotes any changes in these potential therapeutic cells, which would be critical to understand before clinical application. A major component of the CNS is cerebrospinal fluid (CSF). Therefore, the aim of this study was to evaluate the influence that human CSF has on the function of human adipose-derived MSCs (hAMSCs) and human fetal-derived NPCs (hfNPCs) in regard to cell proliferation, survival, and migration. This study demonstrated that human noncancerous CSF promoted proliferation and inhibited apoptosis of hAMSCs and hfNPCs. Preculturing these stem cells in human CSF also increased their migratory speed and distance traveled. Furthermore, insulin-like growth factor-1 (IGF-1) in human CSF enhanced the migration capacity and increased the expression of C-X-C chemokine receptor type 4 (CXCR4) in both stem cell types. These current findings highlight a simple and natural way in which human CSF can enhance the proliferation, migration, and viability of human exogenous primary hAMSCs and hfNPCs. This study may provide insight into improving the clinical efficacy of stem cells for the treatment of CNS pathologies.

Factors associated with survival and recurrence for patients undergoing surgery of cerebellar metastases.

OBJECTIVE: Patients with cerebellar and non-cerebellar metastases are often included in the same study population, even though posterior fossa lesions typically have different presenting symptoms, clinical outcomes, and complications. This is because the outcomes for patients with cerebellar metastases are unclear. METHODS: Adult patients who underwent surgery for an intracranial metastasis (single or multiple) between 2007 and 2011 were retrospectively reviewed. Stepwise multivariate proportional hazards regression analysis was used to identify an association between cerebellar location with survival and recurrence. RESULTS: Of the 708 patients who underwent intracranial metastatic surgery, 140 (19.8%) had surgery for cerebellar metastasis. A cerebellar location was associated with poorer survival [RR (95% CI); 1.231 (1.016-1.523), P  =  0.04] and increased spinal recurrence [RR (95% CI); 2.895 (1.491-5.409), P  =  0.002], but not local (P  =  0.61) or distal recurrence (P  =  0.88). The factors independently associated with prolonged survival for patients with cerebellar metastases were: decreasing number of intracranial metastases (P  =  0.0002), decreasing tumor size (P  =  0.002), and radiation (P  =  0.0006). The factors associated with prolonged local progression free survival were: decreasing tumor size (P  =  0.0009), non small cell lung cancer (NSCLC) (P  =  0.006), non-bladder cancer (P  =  0.0005), and post-operative radiation therapy (P  =  0.02). The factors independently associated with prolonged distal progression free survival were: age > 40 years (P  =  0.02), surgical resection (P  =  0.01), and whole brain radiation (WBRT) therapy (P  =  0.02). DISCUSSION: Patients with cerebellar metastases have more distinct clinical presentations and outcomes than patients with non-cerebellar lesions. The findings of this study may help risk stratify and guide treatment regimens aimed at maximizing outcomes for patients with cerebellar metastases.