A 3-Year Study Investigating the Utility of Patient-Reported Outcomes Measurement Information System-29 for Long-Term Follow-Up in Adult Spinal Deformity.

BACKGROUND: Adult spinal deformity (ASD) significantly impacts the quality of life due to three-dimensional spinal abnormalities. Patient-reported outcome measures, such as the Patient-Reported Outcomes Measurement Information System (PROMIS-29), play a crucial role in assessing postoperative outcomes. This study aims to investigate trends in PROMIS-29 scores over 36 months in patients undergoing long-segment thoracolumbar fusion for ASD and provide insights into its long-term utility. METHODS: A retrospective study including 163 ASD patients undergoing long-segment thoracolumbar fusion was conducted. PROMIS-29 scores were collected at baseline and at postoperative (0-), 3-, 6-, 12-, 18-, 24-, 30-, and 36-month follow-ups. Statistical analyses was performed to assess significant score changes from baseline and in consecutive recordings. RESULTS: Significant improvements in all PROMIS-29 categories were observed at 36 months, with the greatest changes in pain intensity (-35.19%, P < 0.001), physical function (+29.13%, P < 0.001), and pain interference (-28.8%, P < 0.001). Between the 0 and 3 month mark, the greatest significant changes were recorded in pain intensity (-26.5%, P < 0.001), physical function (+24.3%, P < 0.001), and anxiety (-16.9%, P < 0.018). However, scores plateaued after the 3-month mark, with zero categories showing significant changes with subsequent consecutive recordings. CONCLUSIONS: PROMIS-29 scores demonstrated notable improvements in ASD patients particularly in pain intensity, pain interference, and physical function. However, scores plateaued beyond the 3-month mark, suggesting PROMIS-29's limited sensitivity to nuanced changes in long-term patient recovery. Future investigations exploring optimal combinations of patient reported outcome measures for comprehensive short- and long-term outcome assessments in ASD surgery would be beneficial.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy.

Purpose: Despite significant advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors and are grown without artificial extracellular scaffolding. We aimed to develop the first matched patient-derived SXO and cell line models of MBM to investigate responses to targeted therapy. Methods: MBM SXOs were created by a novel protocol incorporating techniques for establishing glioma and cutaneous melanoma organoids. A BRAFV600K-mutant and BRAF-wildtype MBM sample were collected directly from the operating room for downstream experiments. Organoids were cultured in an optimized culture medium without an artificial extracellular scaffold. Concurrently, matched patient-derived cell lines were created. Drug screens were conducted to assess treatment response in SXOs and cell lines. Results: Organoid growth was observed within 3-4 weeks, and MBM SXOs retained histological features of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, and strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF and MEK inhibitors. Conclusion: Here, we describe the creation of a scaffold-free organoid model of MBM. Further study using SXOs may improve the translational relevance of preclinical studies and enable the study of the metastatic melanoma tumor microenvironment.

Trends of the Oswestry Disability Index in Adult Spinal Deformity Patients: A 3-Year Study.

BACKGROUND: Patients with adult spinal deformity (ASD) undergoing operative treatment may have varying degrees of improvement in patient-reported outcomes. The Oswestry Disability Index (ODI) assesses improvement in quality of life. We aim to measure longitudinal outcomes of ODI scores over 3 years to determine if early ODI scores predict late ODI scores and to analyze longitudinal changes in ODI scores. METHODS: Two hundred thirty-five patients above the age of 18 who underwent surgical correction of ASD at a single institution from 2016 to 2021 and completed ODI questionnaires at follow-up appointments met inclusion criteria. ODI scores were included from follow-up visits at 0 months (immediately postoperative) and within ±1 month of 3, 6, 12, 18, 24, 30, and 36 months. Percent change in ODI from 0 months was calculated, and unpaired t tests were conducted. RESULTS: ODI scores increased by 8.8% immediately postoperatively, and the percent change from preoperative ODI scores at each subsequent visit were as follows: -11.1% at 3 months, -21.4% at 6 months, -25.4% at 12 months, -28% at 18 months, -31.3% at 24 months, -25.7% at 30 months, and -36.5% at 36 months. ODI scores at each follow-up visit showed significant improvement from baseline (P < 0.001). There was an improvement in scores from 3 to 6 months (P = 0.04), but no significant difference in 6-month interval visits following 6 months. CONCLUSIONS: Our results demonstrate a significant and sustained improvement in ODI scores over 3 years following surgical correction of ASD. ODI scores were stable after 6 months, indicating that ODI scores at 6 months may be predictive of scores out to 3 years postoperatively. Examining individual components of ODI sub-scores and comparing ODI results to other PROMs are critical to better assess long-term outcomes in ASD.

Identifying Correlation Among Patient-Reported Outcome Measures: A Study of PROMIS-29, ODI, and VAS in Adult Spinal Deformity Patients.

BACKGROUND: Adult spinal deformity (ASD) is becoming increasingly common in aging populations. Patient-reported outcome measures (PROMs) are self-reported patient surveys administered pre- and postoperatively that provide insight into patient improvement. We aim to compare 3 of the most utilized PROMs: PROMIS-29, Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS), to investigate whether they provide unique and independent assessments of patient outcomes when assessed longitudinally. METHODS: We retrospectively reviewed a database of ASD at UT Southwestern Medical Center between 2016 and 2021. Adult patients (>18 years old) were included if they underwent long-segment (>4 levels) thoracolumbar fusion. PROMIS-29, ODI, and VAS scores were collected preoperatively and at 3-, 6-, 12-, 18-, 24-, 30-, and 36-month follow-ups. Scores were recorded ±1 month of the time points. Pearson correlation coefficients for each PROM were then calculated in a pairwise fashion. RESULTS: A total of 163 patients were included in our analysis. ODI and VAS showed significant covariance, with VAS Neck and VAS Back having Pearson coefficients of 0.95 and 0.94, respectively. ODI and PROMIS-29 also showed significant covariance, with Physical Function and ODI showing a Pearson coefficient of 0.95. PROMIS-29 and VAS demonstrated less correlation regarding Pain and Physical Function; however, they showed a significantly high Pearson coefficient when comparing VAS Back with PROMIS-29 Sleep and Pain Intensity (r = 0.97 and r = 0.96, respectively). CONCLUSIONS: All 3 PROMs demonstrated significant correlation over 36 months, indicating that simultaneous administration of each during follow-up is redundant. The measure that provided the least unique information was ODI, as both VAS and PROMIS-29 demonstrated similar progression and assessed additional metrics. PROMIS-29 provided the same information as VAS and ODI, with extra facets of patient-reported outcomes, indicating that it may be a more comprehensive measure of longitudinal patient improvement.

Retropharyngeal Blastomycosis Abscess Causing Osteomyelitis, Discitis, Cervical Deformity, and Cervical Epidural Abscess: A Case Report.

Blastomycosis infection is caused by the inhalation of the spores of the dimorphic Blastomyces sp.fungus. While more commonly a self-limited infection of the lungs, extrapulmonary manifestations arise from hematogenous or contiguous spread. Disseminated infection most often includes skin lesions and osteomyelitis; however, central nervous system (CNS) involvement is infrequently reported in the literature. Herein, we present a case of a retropharyngeal blastomycosis abscess leading to cervical spine osteonecrosis with retropulsion, deformity, and a spinal epidural abscess, and we discuss the relevant literature. The patient was successfully treated with cervical traction, followed by a combined anterior-posterior cervical approach, including abscess drainage, corpectomies, and instrumented fixation. Postoperatively, the patient completed 12 months of voriconazole and had near resolution of preoperative symptoms. Expediting neurosurgical intervention, such as the utilization of decompression, the clearance of infectious burden, and the correction of alignment, is critical for preventing downstream complications. Retropharyngeal blastomycosis abscesses are rare, and we report one of the rare instances of dissemination to and the degeneration of the cervical spine.

Human plasma-like medium facilitates metabolic tracing and enables upregulation of immune signaling pathways in glioblastoma explants.

Purpose: Metabolism within the tumor microenvironment (TME) represents an increasing area of interest to understand glioma initiation and progression. Stable isotope tracing is a technique critical to the study of tumor metabolism. Cell culture models of this disease are not routinely cultured under physiologically relevant nutrient conditions and do not retain cellular heterogeneity present in the parental TME. Moreover, in vivo, stable isotope tracing in intracranial glioma xenografts, the gold standard for metabolic investigation, is time consuming and technically challenging. To provide insights into glioma metabolism in the presence of an intact TME, we performed stable isotope tracing analysis of patient-derived, heterocellular Surgically eXplanted Organoid (SXO) glioma models in human plasma-like medium (HPLM). Methods: Glioma SXOs were established and cultured in conventional media or transitioned to HPLM. We evaluated SXO cytoarchitecture and histology, then performed spatial transcriptomic profiling to identify cellular populations and differential gene expression patterns. We performed stable isotope tracing with 15N2-glutamine to evaluate intracellular metabolite labeling patterns. Results: Glioma SXOs cultured in HPLM retain cytoarchitecture and cellular constituents. Immune cells in HPLM-cultured SXOs demonstrated increased transcription of immune-related signatures, including innate immune, adaptive immune, and cytokine signaling programs. 15N isotope enrichment from glutamine was observed in metabolites from diverse pathways, and labeling patterns were stable over time. Conclusion: To enable ex vivo, tractable investigations of whole tumor metabolism, we developed an approach to conduct stable isotope tracing in glioma SXOs cultured under physiologically relevant nutrient conditions. Under these conditions, SXOs maintained viability, composition, and metabolic activity while exhibiting increased immune-related transcriptional programs.

Evaluating risk of recurrence in patients with meningioma.

OBJECTIVE: Meningioma prognostication and treatment continues to evolve with an increasing understanding of tumor biology. In this study, the authors aimed to test conventional predictors of meningioma recurrence, histopathology variables for which there exists some controversy (brain invasion), as well as a novel molecular-based location paradigm. METHODS: This is a retrospective study of a consecutive series of patients with WHO grade I-III meningioma resected at The University of Texas Southwestern Medical Center between 1994 and 2015. Time to meningioma recurrence (i.e., recurrence-free survival [RFS]) was the primary endpoint measured. Kaplan-Meier curves were constructed and compared using log-rank tests. Cox univariate and multivariate analyses were performed to identify predictors of RFS. RESULTS: A total of 703 consecutive patients with meningioma underwent resection at The University of Texas Southwestern Medical Center between the years 1994 and 2015. A total of 158 patients were excluded for insufficient follow-up (< 3 months). The median age of the cohort was 55 years (range 16-88 years) and 69.5% (n = 379) were female. The median follow-up was 48 months (range 3-289 months). There was not a significantly increased risk of recurrence in patients with evidence of brain invasion, in patients with otherwise WHO grade I meningioma (Cox univariate HR 0.92, 95% CI 0.44-1.91, p = 0.82, power 4.4%). Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence (n = 52, Cox univariate HR 0.21, 95% CI 0.03-1.61, p = 0.13, power 71.6%). Location (midline skull base, lateral skull base, and paravenous) was significantly associated with RFS (p < 0.01, log-rank test). In patients with high-grade meningiomas (WHO grade II or III), location was predictive of RFS (p = 0.03, log-rank test), with paravenous meningiomas exhibiting the highest rates of recurrence. Location was not significant on multivariate analysis. CONCLUSIONS: The data suggest that brain invasion does not increase the risk of recurrence in otherwise WHO grade I meningioma. Adjuvant radiosurgery to subtotally resected WHO grade I meningiomas did not prolong the time to recurrence. Location categorized by distinct molecular signatures did not predict RFS in a multivariate model. Larger studies are needed to confirm these findings.

Psoas Muscle Index as a Predictor of Perioperative Outcomes in Geriatric Patients Undergoing Spine Surgery.

STUDY DESIGN: Single-center retrospective study. OBJECTIVE: The objective of this study was to evaluate the association of psoas muscle mass defined sarcopenia with perioperative outcomes in geriatric patients undergoing elective spine surgery. METHODS: We included geriatric patients undergoing thoracolumbar spinal surgery. Total psoas surface area (TPA) was measured on preoperative axial computerized tomography or magnetic resonance imaging at the L3 vertebra and normalized to the L3 vertebral body area. Patients were divided into quartiles by normalized TPA, and the fourth quartile (Q4) was compared to quartiles 1-3 (Q1-3). Outcomes included perioperative transfusions, length of stay (LOS), delirium, pseudoarthrosis, readmission, discharge disposition, revision surgery, and mortality. RESULTS: Of the patients who met inclusion criteria (n = 196), the average age was 73.4 y, with 48 patients in Q4 and 148 patients in Q1-3. Q4 normalized TPA cut-off was <1.05. Differences in Q4 preoperative characteristics included significantly lower body mass index, baseline creatinine, and a greater proportion of females (Table 1). Q4 patients received significantly more postoperative red blood cell and platelet transfusions and had longer ICU LOS (P < .05; Table 2). There was no difference in intraoperative transfusion volumes, delirium, initiation of walking, discharge disposition, readmission, pseudoarthrosis, or revision surgery (Tables 2 and 3). Mortality during follow-up was higher in Q4 but was not statistically significant (P = .075). CONCLUSION: Preoperative TPA in geriatric patients undergoing elective spine surgery is associated with increased need for intensive care and postoperative blood transfusion. Preoperative normalized TPA is a convenient measurement and could be included in geriatric preoperative risk assessment algorithms.

A Comparative Analysis of Frailty, Disability, and Sarcopenia With Patient Characteristics and Outcomes in Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective case series study. OBJECTIVES: This study aims to compare preoperative indices, including the modified frailty index-11 (mFI-11), modified frailty index-5 (mFI-5), Oswestry Disability Index (ODI), and psoas muscle index (PMI), as they relate to outcomes in adult spinal deformity (ASD) surgery. METHODS: We identified 235 patients who underwent thoracolumbar ASD surgery (≥4 levels). The mFI-11, mFI-5, ODI, and PMI were determined from preoperative visits and correlated to outcome measures, including perioperative transfusion, duration of anesthesia, hospital and ICU length of stay (LOS), discharge disposition, readmission, change in ODI at last follow-up, revision surgery, and mortality. RESULTS: Our cohort had a mean age of 69.6 years and a male:female ratio of 1:2 with 177 undergoing an index surgery and 58 patients presenting after a failed multilevel fusion. The average number of levels fused was 9.3. The mFI-11 and mFI-5 were similar in predicting the need for intraoperative and postoperative transfusion. However, the mFI-11 was able to predict longer ICU and hospital LOS and mortality. The average preoperative ODI was 44.9% with an average decrease of 10.1% at the last follow-up. Preoperative ODI was the most significant predictor of postoperative change of ODI. Sarcopenia, defined as the lowest quartile of PMI values measured at L3 and L4, was not associated with any meaningful outcomes. CONCLUSION: The mFI-11 better correlated with outcomes, indicating its increased prognostic value compared to other preoperative indices in ASD surgery. Preoperative ODI remains a significant predictor of postoperative change in ODI when evaluating ASD patients.

Semi-Automated Computational Assessment of Cancer Organoid Viability Using Rapid Live-Cell Microscopy.

The creation of patient-derived cancer organoids represents a key advance in preclinical modeling and has recently been applied to a variety of human solid tumor types. However, conventional methods used to assess in vivo tumor tissue treatment response are poorly suited for the evaluation of cancer organoids because they are time-intensive and involve tissue destruction. To address this issue, we established a suite of 3-dimensional patient-derived glioma organoids, treated them with chemoradiotherapy, stained organoids with non-toxic cell dyes, and imaged them using a rapid laser scanning confocal microscopy method termed "Apex Imaging." We then developed and tested a fragmentation algorithm to quantify heterogeneity in the topography of the organoids as a potential surrogate marker of viability. This algorithm, SSDquant, provides a 3-dimensional visual representation of the organoid surface and a numerical measurement of the sum-squared distance (SSD) from the derived mass center of the organoid. We tested whether SSD scores correlate with traditional immunohistochemistry-derived cell viability markers (cellularity and cleaved caspase 3 expression) and observed statistically significant associations between them using linear regression analysis. Our work describes a quantitative, non-invasive approach for the serial measurement of patient-derived cancer organoid viability, thus opening new avenues for the application of these models to studies of cancer biology and therapy.

Transfusion Guidelines in Brain Tumor Surgery: A Systematic Review and Critical Summary of Currently Available Evidence.

OBJECTIVE: Red blood cell (RBC) transfusion is commonly indicated in brain tumor surgery due to risk of blood loss. Current transfusion guidelines are based on evidence derived from critically ill patients and may not be optimal for brain tumor surgeries. Our study is the first to synthesize available evidence to suggest RBC transfusion thresholds in brain tumor patients undergoing surgery. METHODS: A systematic review was conducted using PubMed, EMBASE, and Google Scholar databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to critically assess RBC transfusion thresholds in adult patients with brain tumors and complications secondary to transfusion following blood loss in the operating room or perioperative period. RESULTS: Seven articles meeting our search criteria were reviewed. Brain tumor patients who received blood transfusions were older, had greater rates of American Society of Anesthesiologists class 3 or 4, and presented with increased number of comorbidities including diabetes, hypertension, and cardiovascular diseases. In addition, transfused patients had a prolonged surgical time. Transfusions were associated with multiple postoperative major and minor complications, including longer hospital length of stay, increased return to the operating room, and elevated 30-day mortality. Analysis of transfusion thresholds showed that a restrictive hemoglobin threshold of 8 g/dL is safe in patients, as evidenced by a reduction in length of stay, mortality, and complications (level C class IIa). CONCLUSIONS: A restrictive Hb threshold of 8 g/dL appears to be safe and minimizes potential complications of transfusion in brain tumor patients.

Neurological outcomes following awake and asleep craniotomies with motor mapping for eloquent tumor resection.

OBJECTIVE: Cortical mapping has been used as a tool to ensure maximal safe resection of intracranial tumors for several decades. Post-surgical motor and language deficits, including seizures, weakness, aphasia, and dysarthria have been well-documented in patients undergoing these operations, particularly on eloquent cortical regions. However, it is not known whether awake versus asleep cortical mapping contributes to differences in postoperative neurological deficits. METHODS: A comprehensive review of the literature utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was completed for articles describing cortical mapping for tumor resection. We critically assessed all articles published in the last 20 years describing complications of patients who had undergone either awake or asleep motor mapping for eloquent brain tumor resection. Studies were analyzed for number of patients, follow-up duration, rates of transient and permanent motor and sensory deficits in the perioperative period, and outcomes at one-month follow-up. RESULTS: Thirty-one studies met inclusion criteria, 24 of which reported long-term post-operative follow-up data. Follow-up among selected studies ranged from one month to four years. Nine of the 31 studies directly compared the postoperative outcomes of awake versus asleep mapping. The rate of transient deficits among patients who underwent awake and asleep mapping was 31.6% and 32.7%, respectively. The rate of permanent deficits was 10.8% in awake mapping patients and 12.7% in asleep mapping patients. Qualitative analysis showed that motor and sensory complications occurred at similar rates. CONCLUSIONS: Review of the current evidence suggests that the rates of transient and permanent postoperative neurologic deficits among awake versus asleep cortical mapping groups are similar. Thus, use of both techniques is reasonable to minimize perioperative morbidity.

Postoperative Transfusion Guidelines in Aneurysmal Cerebral Subarachnoid Hemorrhage: A Systematic Review and Critical Summary of Available Evidence.

OBJECTIVE: Surgical management of aneurysmal subarachnoid hemorrhage (SAH) often involves red blood cell (RBC) transfusion, which increases the risk of postoperative complications. RBC transfusion guidelines report on chronically critically ill patients and may not apply to patients with SAH. Our study aims to synthesize the evidence to recommend RBC transfusion thresholds among adult patients with SAH undergoing surgery. METHODS: A systematic review was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to critically assess primary articles discussing RBC transfusion thresholds and describe complications secondary to RBC transfusion in adult patients with SAH in the perioperative period. RESULTS: Sixteen articles meeting our search strategy were reviewed. Patients with SAH who received blood transfusion were older, female, had World Federation of Neurosurgical Societies grade IV-V and modified Fisher grade 3-4 scores, and presented with more comorbidities such as hypertension, diabetes, and cardiovascular and pulmonary diseases. In addition, transfusion was associated with multiple postoperative complications, including higher rates of vasospasms, surgical site infections, cardiovascular and respiratory complications, increased postoperative length of stay, and 30-day mortality. Analysis of transfused patients showed that a higher hemoglobin (>10 g/dL) goal after SAH was safe and that patients may benefit from a higher whole hospital stay hemoglobin nadir, as shown by a reduction in risk of cerebral vasospasm and improvement in clinical outcomes (level B class II). CONCLUSIONS: Among patients with SAH, the benefits of reducing cerebral ischemia and anemia are shown to outweigh the risks of transfusion-related complications.

Contiguous Meningioma and B-Cell Lymphoma: A Scoping Review and Case Illustration.

BACKGROUND: The diagnosis of a contiguous, synchronous meningioma and central nervous system B-cell lymphoma is rare and associated with paradoxical treatment paradigms. We performed a scoping review of contiguous meningioma and B-cell lymphoma and included an additional illustrative case. METHODS: The OVID Medline and PubMed databases were systematically searched using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis guidelines. Only human clinical reports of contiguous, synchronous meningioma and B-cell lymphoma were included. We concurrently detailed a representative case from our institution. RESULTS: Nine case reports met our criteria, including the present case. The average age at diagnosis was 67.4 years. Patients showed a female-to-male predominance of 7:2. The diagnosis of synchronous intracranial tumors was not suspected or discovered until after surgical resection in 100% of cases. All meningiomas were grade I on histopathologic diagnosis, while lymphomas were distributed between diffuse large B-cell lymphoma (56%), metastatic lymphoma (22%), Burkitt lymphoma (11%), and follicular lymphoma (11%). All patients underwent surgical resection. Patients (n = 5) treated with adjuvant chemotherapy had evidence of longer progression-free survival (median 12 months; range, 3-18 months) than patients without adjuvant chemotherapy (n = 2; median 2 months; range, 1-3 months). CONCLUSIONS: Contiguous, synchronous meningioma/B-cell lymphoma is a rare diagnosis that may appear as an inconspicuous solitary intracranial neoplasm on imaging. Based on the limited cases and current treatment of lymphoma, progression-free survival may be contingent on the prompt initiation of chemotherapy targeting the lymphoma rather than surgical resection of the meningeal mass. Providers should prioritize prompt medical management.

Establishment of patient-derived organoid models of lower-grade glioma.

BACKGROUND: Historically, creating patient-derived models of lower-grade glioma (LGG) has been challenging, contributing to few experimental platforms that support laboratory-based investigations of this disease. Although organoid modeling approaches have recently been employed to create in vitro models of high-grade glioma (HGG), it is unknown whether this approach can be successfully applied to LGG. METHODS: In this study, we developed an optimized protocol for the establishment of organoids from LGG primary tissue samples by utilizing physiologic (5%) oxygenation conditions and employed it to produce the first known suite of these models. To assess their fidelity, we surveyed key biological features of patient-derived organoids using metabolic, genomic, histologic, and lineage marker gene expression assays. RESULTS: Organoid models were created with a success rate of 91% (n = 20/22) from primary tumor samples across glioma histological subtypes and tumor grades (WHO Grades 1-4), and a success rate of 87% (13/15) for WHO Grade 1-3 tumors. Patient-derived organoids recapitulated stemness, proliferative, and tumor-stromal composition profiles of their respective parental tumor specimens. Cytoarchitectural, mutational, and metabolic traits of parental tumors were also conserved. Importantly, LGG organoids were maintained in vitro for weeks to months and reanimated after biobanking without loss of integrity. CONCLUSIONS: We report an efficient method for producing faithful in vitro models of LGG. New experimental platforms generated through this approach are well positioned to support preclinical studies of this disease, particularly those related to tumor immunology, tumor-stroma interactions, identification of novel drug targets, and personalized assessments of treatment response profiles.

Transfusion Guidelines in Traumatic Brain Injury: A Systematic Review and Meta-Analysis of the Currently Available Evidence.

Our study aims to provide a synthesis of the best available evidence on the hemoglobin (hgb) red blood cell (RBC) transfusion thresholds in adult traumatic brain injury (TBI) patients, as well as describing the risk factors and outcomes associated with RBC transfusion in this population. A systematic review and meta-analysis was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to assess articles discussing RBC transfusion thresholds and describe complications secondary to transfusion in adult TBI patients in the perioperative period. Fifteen articles met search criteria and were reviewed for analysis. Compared to non-transfused, TBI patients who received transfusion tended to be primarily male patients with worse Injury Severity Score (ISS) and Glasgow Coma Scale. Further, the meta-analysis corroborated that transfused TBI patients are older (p = 0.04), have worse ISS scores (p = 0.001), receive more units of RBCs (p = 0.02), and have both higher mortality (p < 0.001) and complication rates (p < 0.0001). There were no differences identified in rates of hypertension, diabetes mellitus, and Abbreviated Injury Scale scores. Additionally, whereas many studies support restrictive (hgb <7 g/dL) transfusion thresholds over liberal (hgb <10 g/dL), our meta-analysis revealed no significant difference in mortality between those thresholds (p = 0.79). Current Class B/C level III evidence predominantly recommends against a liberal transfusion threshold of 10 g/dL for TBI patients (Class B/C level III), but our meta-analysis found no difference in survival between groups. There is evidence suggesting that an intermediate threshold between 7 and 9 g/dL, reflecting the physiological oxygen needs of cerebral tissue, may be worth exploring.

Large Animal Models of Glioma: Current Status and Future Prospects.

Enhanced understanding of the molecular features of glioma has led to an expansion of murine glioma models and successful preclinical studies. However, clinical trials continue to have a high cost, extended production time, and low proportion of success. Studies in large-animal models of various cancer types have emerged to bridge the translational gap between in vitro and in vivo animal studies and human clinical trials. The anatomy and physiology of large animals are of more direct relevance to human disease, allowing for more rigorous testing of treatments such as surgical resection and adjuvant therapy in glioma. The recent generation of multiple porcine glioma models supports their use in high-throughput preclinical studies. The demonstration of spontaneous glioblastoma formation in canines further provides a unique avenue for the study of de novo glioma. The aim of this review was to outline the current status of large animal models of glioma and their value as a transitional step between rodent models and human clinical trials.

Economic implications of the modern treatment paradigm of glioblastoma: an analysis of global cost estimates and their utility for cost assessment.

INTRODUCTION: Glioblastoma is the most common primary brain tumor in adults. Standard of care includes maximal surgical resection of the tumor followed by concurrent chemotherapy and radiation. The treatment of glioblastoma must account for an increased disease severity and treatment intensity compared to other cancers which place a significant cost burden on the patient and health system. Cost assessments of glioblastoma treatment have been sparse in comparison to other solid cancer subtypes. This study evaluates all currently available cost literature with an emphasis on the modern treatment paradigm to properly assess the economic implications of this disease. METHODS: A critical review of 21 studies from 13 different countries measuring direct costs related to glioblastoma management was performed. Evaluated data included itemized costs, total costs of treatment regimens from diagnosis until death, the cost of second-line care after recurrence, and the incremental costs and cost-effectiveness of emerging therapies. RESULTS: The average cost of a craniotomy was $10,042 across studies. Imaging for the duration of glioblastoma care had a mean cost of $2,788 ± 3,719. Studies examined different combinations of treatment modalities. Utilization of the modern treatment paradigm led to survival of 16.3 months across studies and had a mean cost of $62,602. Surgery for the recurrent disease had an average cost of $27,442 ± 18,992. LIMITATIONS AND CONCLUSIONS: Direct cost estimates for glioblastoma varied substantially between institutions and countries and often failed to uniformly describe direct cost estimates associated with care for glioblastoma. The limitations of these studies make a true economic assessment of standards of care, costs of recurrence, and incremental costs associated with adjunctive therapy uncertain.

Contemporary Mouse Models in Glioma Research.

Despite advances in understanding of the molecular pathogenesis of glioma, outcomes remain dismal. Developing successful treatments for glioma requires faithful in vivo disease modeling and rigorous preclinical testing. Murine models, including xenograft, syngeneic, and genetically engineered models, are used to study glioma-genesis, identify methods of tumor progression, and test novel treatment strategies. Since the discovery of highly recurrent isocitrate dehydrogenase (IDH) mutations in lower-grade gliomas, there is increasing emphasis on effective modeling of IDH mutant brain tumors. Improvements in preclinical models that capture the phenotypic and molecular heterogeneity of gliomas are critical for the development of effective new therapies. Herein, we explore the current status, advancements, and challenges with contemporary murine glioma models.