A Single-Center Retrospective Analysis of Intracranial and Spinal Solitary Fibrous Tumor/Hemangiopericytoma Clinical Outcomes: Sex Association With Aggressiveness.

BACKGROUND: Solitary fibrous tumor/hemangiopericytoma (SFT/HPCT) is a rare tumor characterized by high recurrence rate and metastatic potential, even after surgical resection. We report on the clinical outcomes and risk factors for metastasis and progression-free survival (PFS) of patients diagnosed with SFT/HPCT. METHODS: We retrospectively identified patients with intracranial or spinal SFT/HPCT who underwent surgical resection and/or radiation therapy at our institution between 1995 and 2021. Baseline demographics, tumor characteristics, and outcome data were collected, and factors associated with PFS and metastasis were analyzed. RESULTS: Thirty-four subjects (mean age, 46.4 years; 44% female) with a histopathologically proven diagnosis of SFT/HPCT were included; the median follow-up was 89.7 months. Twenty-two tumors were supratentorial (67%), 6 (18%) were infratentorial, and 5 (15%) were spinal. Eleven patients had documented occurrence of metastasis (32%). Detailed preoperative and postoperative data were available for 25 patients (74%) who received treatment at our institution after their initial diagnosis. Of those, 20 (80%) underwent gross total resection (GTR), and 12 (48%) received either adjuvant or salvage radiotherapy. Univariate analyses revealed that males had a shorter mean PFS compared with females (25 months vs. 78 months; P = 0.01), and that patients who underwent GTR had a longer mean PFS compared with those who underwent subtotal resection (54 months vs. 23 months; P = 0.02). Male sex was the sole risk factor for metastasis (odds ratio, 6.75; 95% confidence interval, 1.19-38.02). CONCLUSIONS: Our data demonstrate a strong association between male sex and the outcomes of shorter PFS and higher risk for metastases. Further research is warranted to understand the clinical characteristics and outcomes of this rare tumor.

Osteobiologics.

BACKGROUND: Osteobiologics are engineered materials that facilitate bone healing and have been increasingly used in spine surgery. Autologous iliac crest bone grafts have been used historically, but morbidity associated with graft harvesting has led surgeons to seek alternative solutions. Allograft bone, biomaterial scaffolds, growth factors, and stem cells have been explored as bone graft substitutes and supplements. OBJECTIVE: To review current and emerging osteobiologic technologies. METHODS: A literature review of English-language studies was performed in PubMed. Search terms included combinations of "spine," "fusion," "osteobiologics," "autologous," "allogen(e)ic," "graft," "scaffold," "bone morphogenic protein," and "stem cells." RESULTS: Evidence supports allograft bone as an autologous bone supplement or replacement in scenarios where minimal autologous bone is available. There are promising data on ceramics and P-15; however, comparative human trials remain scarce. Growth factors, including recombinant human bone morphogenic proteins (rhBMPs) 2 and 7, have been explored in humans after successful animal trials. Evidence continues to support the use of rhBMP-2 in lumbar fusion in patient populations with poor bone quality or revision surgery, while there is limited evidence for rhBMP-7. Stem cells have been incredibly promising in promoting fusion in animal models, but human trials to this point have only involved products with questionable stem cell content, thereby limiting possible conclusions. CONCLUSION: Engineered stem cells that overexpress osteoinductive factors are likely the future of spine fusion, but issues with applying viral vector-transduced stem cells in humans have limited progress.

Evaluation of neurapheresis therapy in vitro: a novel approach for the treatment of leptomeningeal metastases.

BACKGROUND: Leptomeningeal metastases (LM), late-stage cancer when malignant cells migrate to the subarachnoid space (SAS), have an extremely poor prognosis. Current treatment regimens fall short in effectively reducing SAS tumor burden. Neurapheresis therapy is a novel approach employing filtration and enhanced circulation of the cerebrospinal fluid (CSF). Here, we examine the in vitro use of neurapheresis therapy as a novel, adjunctive treatment option for LM by filtering cells and augmenting the distribution of drugs that may have the potential to enhance the current clinical approach. METHODS: Clinically relevant concentrations of VX2 carcinoma cells were suspended in artificial CSF. The neurapheresis system's ability to clear VX2 carcinoma cells was tested with and without the chemotherapeutic presence (methotrexate [MTX]). The VX2 cell concentration following each filtration cycle and the number of cycles required to reach the limit of detection were calculated. The ability of neurapheresis therapy to circulate, distribute, and maintain therapeutic levels of MTX was assessed using a cranial-spinal model of the SAS. The distribution of a 6 mg dose was monitored for 48 h. An MTX-specific ELISA measured drug concentration at ventricular, cervical, and lumbar sites in the model over time. RESULTS: In vitro filtration of VX2 cancer cells with neurapheresis therapy alone resulted in a 2.3-log reduction in cancer cell concentration in 7.5 h and a 2.4-log reduction in live-cancer cell concentration in 7.5 h when used with MTX. Cranial-spinal model experiments demonstrated the ability of neurapheresis therapy to enhance the circulation of MTX in CSF along the neuraxis. CONCLUSION: Neurapheresis has the potential to act as an adjunct therapy for LM patients and significantly improve the standard of care.

Association of Race with Survival in Intracranial World Health Organization Grade II and III Meningioma in the United States: Systematic Literature Review.

BACKGROUND: Recent literature has shown significant differences in meningioma incidence among different races, but minimal conclusive data exist on the role of race and ethnicity in overall survival for patients with high-grade intracranial meningioma. We conducted a systematic review to investigate the impact of race and ethnicity on survival in patients with high-grade intracranial meningioma. METHODS: A systematic literature review was conducted for studies using Ovid, PubMed, Cochrane, Embase, and Scopus databases. Databases were queried for the following: Meningioma AND [Ethnic OR Demography, OR African American OR Arab OR Hispanic OR Asian, OR White OR race OR racial] AND [survival OR survival analysis OR survival rate OR treatment outcome OR Survivor OR Outcome]. RESULTS: A literature search yielded a total of 412 abstracts, which were screened according to criteria that were determined a priori, and a total of 129 full-text articles were reviewed. Four articles were included in the final analysis, reporting on a total of 13,424 patients. Three studies saw an overall survival benefit in White non-Hispanics compared with Black non-Hispanics, and 1 reported a survival benefit in White non-Hispanics and Black non-Hispanics among patients who received gross total resection. One study additionally reported an increased likelihood of White patients receiving gross total resection when compared with non-White patients. CONCLUSIONS: The limited data available suggest that White patients have improved measures of survival compared with nonw-White patients, for reasons that are likely complex and multifactorial. Further studies are needed to explore these survival differences seen.

Prevalence and Cost Analysis of Chronic Pain After Hernia Repair: A Potential Alternative Approach With Neurostimulation.

OBJECTIVES: Chronic pain (CP) affects a significant number of patients following hernia repair, ranging from 11 to 54% in the literature. The aim of this study was to assess the prevalence, overall costs, and health care utilization associated with CP after hernia repair. MATERIALS AND METHODS: A retrospective longitudinal study was performed using the Truven MarketScan® data base to identify patients who develop chronic neuropathic posthernia repair pain from 2001 to 2012. Patients were grouped into CP and No Chronic Pain (No CP) cohorts. Patients were excluded if they 1) were under 18 years of age; 2) had a previous pain diagnosis; 3) had CP diagnosed <90 days after the index hernia repair; 4) had less than one year of follow-up; or 5) had less than one-year baseline record before hernia repair. Patients were grouped into the CP cohort if their CP diagnosis was made within the two years following index hernia repair. Total, outpatient, and pain prescription costs were collected in the period of five years prehernia to nine years posthernia repair. A longitudinal multivariate analysis was used to model the effects of chronic neuropathic posthernia repair pain on total inpatient/outpatient and pain prescription costs. RESULTS: We identified 76,173 patients who underwent hernia repair and met inclusion criteria (CP: n = 14,919, No CP: n = 61,254). There was a trend for increased total inpatient/outpatient and pain prescription costs one-year posthernia repair, when compared to baseline costs for both cohorts. In both cohorts, total inpatient/outpatient costs remained elevated from baseline through nine years posthernia repair, with the CP cohort experiencing significantly higher cumulative median costs (CP: $51,334, No CP: $37,388). The CP diagnosis year was associated with a 1.75-fold increase (p < 0.001) in total inpatient/outpatient costs and a 2.26-fold increase (p < 0.001) in pain prescription costs versus all other years. In the longitudinal analysis, the CP cohort had a 1.14-fold increase (p < 0.001) in total inpatient/outpatient costs and 2.00-fold increase (p < 0.001) in pain prescription costs. CONCLUSIONS: Our study demonstrates the prevalence of CP after hernia surgery to be nearly 20%, with significantly increased costs and healthcare resource utilization. While current treatment paradigms are effective for many, there remains a large number of patients that could benefit from an overall approach that includes nonopioid treatments, such as potentially incorporating neurostimulation, for CP that presents posthernia repair.

Novel Treatment of Cryptococcal Meningitis via Neurapheresis Therapy.

Cryptococcal meningitis (CM) has emerged as the most common life-threatening fungal meningitis worldwide. Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared with uniform mortality without treatment, this drug paradigm has not led to a consistent cure. Neurapheresis therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a 5-log reduction in concentration of the yeast and a 1-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM.

Prevalence and Cost Analysis of Complex Regional Pain Syndrome (CRPS): A Role for Neuromodulation.

OBJECTIVE: The diagnosis and treatment of complex regional pain syndrome (CRPS) is challenging and there is a paucity of data describing its overall cost burden and quantifying its impact on the US healthcare system. The aim of this study was to assess the prevalence and healthcare utilization costs associated with CRPS. MATERIALS AND METHODS: A retrospective longitudinal study was performed using the Truven MarketScan® database to identify patients with a new indexed diagnosis of CRPS (Type I, II, or both) from 2001 to 2012. We collected total, outpatient, and pain prescription costs three years prior to CRPS diagnosis (baseline), at year of CRPS diagnosis, and eight-year post-CRPS diagnosis. A longitudinal multivariate analysis was used to model the estimated total and pain prescription cost ratios comparing patients diagnosed before and after CRPS. RESULTS: We included 35,316 patients with a newly indexed diagnosis of CRPS (Type I: n = 18,703, Type II: n = 14,599, Unspecified: n = 2014). Baseline characteristics were similar between the CRPS cohorts. Compared to two- and three-year baseline costs, one-year prior to diagnosis for all CRPS patients yielded the highest interquartile median [IQR] costs: total costs $7904[$3469, $16,084]; outpatient costs $6706[$3119, $12,715]; and pain prescription costs $1862[$147, $7649]. At the year of CRPS diagnosis, the median [IQR] costs were significantly higher than baseline costs: total costs $8508[$3943, $16,666]; outpatient costs $7251[$3527, $13,568]; and pain prescription costs $2077[$140, $8856]. Over the eight-year period after CRPS diagnosis, costs between all the years were similar, ranging from the highest (one-year) to lowest (seven-years), $4845 to $3888. The median total cumulative cost 8-years after CRPS diagnosis was $43,026 and $12,037 for pain prescription costs. [Correction added on 06 November 2017 after first online publication: the preceding sentence has been updated to demonstrate the median cumulative cost in replacement of the additive cumulative mean costs.]. During the CRPS diagnosis period, patients are expected to have a total cost 2.17-fold and prescription cost 2.56-fold of their baseline cost annually. CONCLUSIONS: Our study demonstrates that there is a significant increase in cost and healthcare resource utilization one-year prior to and around the time of CRPS diagnosis. Furthermore, there is an increased annual cost post-diagnosis compared to baseline costs prior to CRPS diagnosis.

Drivers and Risk Factors of Unplanned 30-Day Readmission Following Spinal Cord Stimulator Implantation.

OBJECTIVES: Unplanned 30-day readmission rates contribute significantly to growing national healthcare expenditures. Drivers of unplanned 30-day readmission after spinal cord stimulator (SCS) implantation are relatively unknown. The aim of this study was to determine drivers of 30-day unplanned readmission following SCS implantation. METHODS: The National Readmission Database was queried to identify all patients who underwent SCS implantation for the 2013 calendar year. Patients were grouped by readmission status, "No Readmission" and "Unplanned 30-day Readmission." Patient demographics and comorbidities were collected for each patient. The primary outcome of interest was the rate of unplanned 30-day readmissions and associated driving factors. A multivariate analysis was used to determine independent predictors of unplanned 30-day readmission after SCS implantation. RESULTS: We identified 1521 patients who underwent SCS implantation, with 113 (7.4%) experiencing an unplanned readmission within 30 days. Baseline patient demographics, comorbidities, and hospital characteristics were similar between both cohorts. The three main drivers for 30-day readmission after SCS implantation include: 1) infection (not related to SCS device), 2) infection due to device (limited to only hardware infection), and 3) mechanical complication of SCS device. Furthermore, obesity was found to be an independent predictor of 30-day readmission (OR: 1.86, p = 0.008). CONCLUSION: Our study suggests that infectious and mechanical complications are the primary drivers of unplanned 30-day readmission after SCS implantation, with obesity as an independent predictor of unplanned readmission. Given the technological advancements in SCS, repeated studies are necessary to identify factors associated with unplanned 30-day readmission rates after SCS implantation to improve patient outcomes and reduce associated costs.

Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis.

Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.

Leptomeningeal disease: current diagnostic and therapeutic strategies.

Leptomeningeal disease has become increasingly prevalent as novel therapeutic interventions extend the survival of cancer patients. Although a majority of leptomeningeal spread occurs secondary to breast cancer, lung cancer, and melanoma, a wide variety of malignancies have been reported as primary sources. Symptoms on presentation are equally diverse, often involving a combination of neurological deficits with the possibility of obstructive hydrocephalus. Diagnosis is definitively made via cerebrospinal fluid cytology for malignant cells, but neuro-imaging with high quality T1-weighted magnetic resonance imaging can aid diagnosis and localization. While leptomeningeal disease is still a terminal, late-stage complication, a variety of treatment modalities, such as intrathecal chemotherapeutics and radiation therapy, have improved median survival from 4-6 weeks to 3-6 months. Positive prognosticative factors for survival include younger age, high performance scores, and controlled systemic disease. In looking to the future, diagnostics that improve early detection and chemotherapeutics tailored to the primary malignancy will likely be the most significant advances in improving survival.