Citations

Abstract IntroductionRadiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newerfocused radiotherapy strategies with enhanced conformalitycould offer improved fusion rates for these patients, but this has not been confirmed.MethodsWe performed a retrospective analysis of patients at three tertiary care academic institutions withprimary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used theLenke fusion score to grade fusion status at6 and 12-months after surgery. Secondary outcomes includedclinical pseudoarthrosis, wound complications, and the effect of radiation timing, radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location,and use of autograft on fusion outcomes.ResultsAfter reviewof 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy,20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such assmoking status,obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p=0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p=0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohortcompared to patients in the focused radiotherapy cohort (19.1% versus 0%,p=0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use ofintra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p=0.043). ConclusionFocused radiotherapy may be associated withan improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategiesin patients with spinal tumors.Use of autograft at the time of surgery may be associated with improved 12-month fusion rates.Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Background: Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes. Methods: A systematic review was performed by querying PubMed, Ovid MEDLINE, EMBASE, and Cumulative Index to Nursing and Allied Health Literature databases with the MeSH terms: “adipose-derived stem cells,” “cranial bone defect,” “stromal vascular factor,” “fat grafting,” as well as synonyms in combinations determined by our search strategy. We included human models that used hADSCs as primary therapy. We excluded studies in languages other than English. Results: One hundred ninety-four studies were identified after removal of duplicates. Four articles that used hADSCs as the main therapy to treat calvarial defects in humans were included. One article applied the cell therapy alone, and 3 used β-tricalcium phosphate granules as a scaffold to seed the hADSCs. Conclusions: Bone regeneration was reached in a short and intermediate period using autologous hADSCs in humans with no major adverse effects in all 4 articles included. A long-term follow-up study (6 years) exhibited late infections and reabsorption of the β-tricalcium phosphate scaffold seeded with hADSCs.

Abstract BACKGROUND Brain mapping is the most reliable intraoperative tool for identifying surrounding functional cortical and subcortical brain parenchyma. Brain mapping procedures are nuanced and require a multidisciplinary team and a well-trained neurosurgeon. Current training methodology involves real-time observation and operation, without widely available surgical simulation. OBJECTIVE To develop a patient-specific, anatomically accurate, and electrically responsive biomimetic 3D-printed model for simulating brain mapping. METHODS Imaging data were converted into a 2-piece inverse 3D-rendered polyvinyl acetate shell forming an anatomically accurate brain mold. Functional and diffusion tensor imaging data were used to guide wire placement to approximate the projection fibers from the arm and leg areas in the motor homunculus. Electrical parameters were generated, and data were collected and processed to differentiate between the 2 tracts. For validation, the relationship between the electrical signal and the distance between the probe and the tract was quantified. Neurosurgeons and trainees were interviewed to assess the validity of the model. RESULTS Material testing of the brain component showed an elasticity modulus of 55 kPa (compared to 140 kPa of cadaveric brain), closely resembling the tactile feedback a live brain. The simulator's electrical properties approximated that of a live brain with a voltage-to-distance correlation coefficient of r 2 = 0.86. Following 32 neurosurgeon interviews, ∼96% considered the model to be useful for training. CONCLUSION The realistic neural properties of the simulator greatly improve representation of a live surgical environment. This proof-of-concept model can be further developed to contain more complicated tractography, blood and cerebrospinal fluid circulation, and more in-depth feedback mechanisms.

The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study’s goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.

OBJECTIVE High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. METHODS The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). RESULTS Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19–76) years were included in the analysis. Eighteen patients had H3 K27M mutation–positive tumors, and 12 had H3 K27M mutation–negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation–positive tumors (p = 0.017). CONCLUSIONS Although H3 K27M mutant–positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant–positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant–negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.

Abstract Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.

Abstract Introduction/Purpose: There is a general lack of consensus onboth the anatomic definition and function of Broca’s area. Given the belief that this region plays a critical role in expressive language, resective surgery is often avoided topreserve function. However, the putative role of Broca’s area in speech production has been recently challenged.The current study aims to investigatethe feasibilityof glioma resection and neurological outcomes in “Broca’s area” in 15 patients.Methods: We report a feasibility study describing the resection of gliomas within the IFG. Awake brain surgery for resection with mapping and intraoperative neuropsychological evaluation was carried out in all individuals. Results: All included patientshad tumors located in traditional “Broca’s area” and eight patients (53.33%) had tumors that additionally extendedinto the insula and subinsular regions. During stimulation, positive speech-language sites within the IFG were identified in ten patients. Two patients (13.33%) experienced a declinein naming during intraoperative cognitive monitoring and thirteen (86.66%) had a stable performance throughout surgery. With all patients had recovery of language functions at a two-week follow up. Extent of resection was stratified in anatomical regions within the IFG, being the pOr the area with the greatest EOR (97.4%), followed by the pT (84.1%), pOp (83.8%), and vPMC (80%).Conclusion: The belief that Broca’s area is not safe to resect is challenged. Adequate mapping and careful patient selection allow maximum safe resection of tumors located in thetraditional “Broca’s area”,with low risk of postoperative morbidity.

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I 2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I 2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I 2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.

Objective Observational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming. Methods A prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn–Tolosa–Marín tremor rating score compared to the preoperative baseline. Results Among the six patients, tremor rating scores differed significantly among the three experimental conditions ( P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R 2 =0.24; P=0.04). No significant adverse events were encountered. Conclusions Using a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.