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Background and Objectives: Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis., Methods: We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths., Results: Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths., Conclusion: The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Image recognition is a pervasive task in many information-processing environments. We present a solution to a difficult pattern recognition problem that lies at the heart of experimental particle physics. Future experiments with very high-intensity beams will produce a spray of thousands of particles in each beam-target or beam-beam collision. Recognizing the trajectories of these particles as they traverse layers of electronic sensors is a massive image recognition task that has never been accomplished in real time. We present a real-time processing solution that is implemented in a commercial field-programmable gate array using high-level synthesis. It is an unsupervised learning algorithm that uses techniques of graph computing. A prime application is the low-latency analysis of dark-matter signatures involving metastable charged particles that manifest as disappearing tracks., (© 2024. The Author(s).)

Objective: Metastatic spinal tumors represent a rare but concerning complication of primary thyroid carcinoma. We identified demographics, metastatic features, outcomes, and treatment strategies for these tumors in our institutional cohort., Materials and Methods: We retrospectively reviewed patients surgically treated for spinal metastases of primary thyroid carcinoma. Demographics, tumor characteristics, and treatment modalities were collected. The functional outcomes were quantified using Nurik, Modified Rankin, and Karnofsky Scores., Results: Twelve patients were identified who underwent 17 surgeries for resection of spinal metastases. The primary thyroid tumor pathologies included papillary (4/12), follicular (6/12), and Hurthle cell (2/12) subtypes. The average number of spinal metastases was 2.5. Of the primary tumor subtypes, follicular tumors averaged 2.8 metastases at the highest and Hurthle cell tumors averaged 2.0 spinal metastases at the lowest. Five patients (41.7%) underwent preoperative embolization for their spinal metastases. Seven patients (58.3%) received postoperative radiation. There was no significant difference in progression-free survival between patients receiving surgery with adjuvant radiation and surgery alone ( P = 0.0773). Five patients (41.7%) experienced postoperative complications. Two patients (16.7%) succumbed to disease progression and two patients (16.7%) experienced tumor recurrence following resection. Postsurgical mean Nurik scores decreased 0.54 points, mean Modified Rankin scores decreased 0.48 points, and mean Karnofsky scores increased 4.8 points., Conclusion: Surgery presents as an important treatment modality in the management of spinal metastases from thyroid cancer. Further work is needed to understand the predictive factors for survival and outcomes following treatment., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Craniovertebral Junction and Spine.)

Objective: The aim of this study was to obtain aggregated baseline pediatric neurosurgery well-being data at a tertiary care institution., Methods: An institutional grant funded the completion of the Maslach Burnout Inventory (MBI) by 100% (n = 13) of the trainees during a 1-year period, including 1 pediatric neurosurgery fellow and 12 residents from 4 regional neurosurgery training programs. Aggregated and anonymized group results included frequency scores ranging from 0 (never) to 6 (every day). The mean ± SD group scores were compared to the general population of > 11,000 people in the human services professions. Burnout profiles were calculated on the basis of MBI scale scores by using established comparisons to standardized normal values. Burnout profile types include engaged, ineffective, overextended, disengaged, and burnout., Results: The mean ± SD score for emotional exhaustion was 2.6 ± 1.1 for trainees compared with 2.3 ± 1.2 in the comparison population. The mean ± SD score for depersonalization was 1.6 ± 1 compared with 1.7 ± 1.2 in the comparison population. The mean ± SD score for personal accomplishment was 4.9 ± 0.7 compared with 4.3 ± 0.9 in the comparison population. Profiles were classified as engaged (n = 6), ineffective (n = 3), overextended (n = 3), and burnout (n = 1)., Conclusions: Problematic profiles were present for more than half (7 [53.8%]) of pediatric neurosurgery trainees who cited higher emotional exhaustion than the general population of healthcare providers. Trainees scored lower in depersonalization and higher in personal accomplishment compared with the general population, which are both protective against burnout. Targeting factors that contribute to emotional exhaustion may have an impact on improving the overall well-being of pediatric neurosurgery trainees.

Objective This study examined the interaction between adolescent idiopathic scoliosis (AIS) and pregnancy, focusing on pregnancy outcomes, changes in back pain, and anesthesia use. Methods A retrospective analysis was conducted on adult patients with AIS who gave birth at our institution between 2006 and 2022. Results A total of 163 AIS patients with 263 pregnancies were included. The median age at delivery was 33 (range 18 to 50) years. Among 157 patients with information on prior scoliosis treatment, 66.9% had not received treatment, 20.4% had undergone spinal fusion, and 12.7% had received bracing. Of the 260 pregnancies with available data, 90.4% were delivered at term and 8.5% were preterm. Of the 257 pregnancies with information on anesthesia type, 35.0% received epidural anesthesia, 17.9% received spinal anesthesia, 37.7% received combined spinal and epidural anesthesia, 8.2% received no anesthesia, and 1.2% received intravenous or general anesthesia. Difficulty administering neuraxial anesthesia was reported in 6.1% of cases, and these patients were less likely to receive combined spinal and epidural anesthesia (6.3% versus 39.8%, p = 0.0123). Among 116 cases with recorded back pain during pregnancy, 67.2% reported increased pain, 31.9% reported similar pain, and one patient reported decreased pain. Of the 16 patients with pre and postpartum radiographs, eight showed a Cobb angle increase ≥ 3°, with five patients having an increase ≥ 5°. Conclusions Pregnancy can exacerbate back pain and pose challenges for neuraxial anesthesia in some AIS patients. Further large-scale, multi-institutional studies with standardized data collection are needed to fully understand the impact of pregnancy on AIS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nandoliya et al.)

Objective: Frailty is a measure of physiologic vulnerability conceptualized as the accumulation of deficits with aging, and may be useful for predicting risk of adverse events following posterior spinal fusion. Our objective was to investigate the utility of the Canadian Study on Health and Aging (CHSA) Modified Frailty Index (mFI) in patients undergoing posterior spinal fusion (PSF) as a predictor of several surgical quality metrics including readmission, reoperation, and surgical site infection., Methods: We examined 3965 consecutive PSF patients treated at our institution between 2000 and 2015, and collected demographic, clinical, and frailty and comorbid disease burden measures using the mFI and Charlson Comorbidity Index (CCI). We examined trends and changes in these clinical and demographic characteristics over the course of the study period. We performed multivariable regression to identify independent predictors of readmission, reoperation, and surgical site infection., Results: Over the course of the study period, the mean patient age increased linearly year-over-year (ß=0.60 [0.48, 0.72], p < 0.0001, R=0.94), while the SSI rate decreased linearly (ß=-0.14 [-0.27, -0.02], p = 0.0249, R=0.56), and frailty scores did not change significantly (p = 0.8124, R=0.065). Among all patients undergoing PSF, postoperative wound infection was independently associated with number of levels fused (OR=1.104 p < 0.001), frailty as measured by mFI (OR=1.150 p = 0.006), and BMI (OR=1.041 p = 0.008). Frailty was also independently associated with postoperative ICU admission (OR=1.1080 p = 0.005), 30-day readmission (OR=1.181 p < 0.001), and 30-day reoperation (OR=1.128 p < 0.001). Among all patients, rate of postoperative wound infection increased with increasing frailty (p = 0.0002) and increasing comorbid disease burden (chi-square p = 0.0012)., Conclusion: The mFI predicts adverse events among patients undergoing PSF, including readmission, reoperation, and surgical site infection. When controlling for frailty, age was not an independent predictor of adverse events., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The goal of this study was to analyze the visibility of women within organized neurosurgery, including leadership positions, lectureships, and honored guest/award recipients at neurosurgical conferences., Methods: A cross-sectional study was used to analyze the gender demographics within the five major national neurosurgical societies (Congress of Neurological Surgeons [CNS], American Association of Neurological Surgeons [AANS], Society of Neurological Surgeons [SNS], American Board of Neurological Surgery [ABNS], and Council of State Neurosurgical Societies [CSNS]) from 2000 to 2020. Data for top leadership positions, keynote speakers, honored guests, and invited lectureships at these neurosurgical societies were reviewed. Additionally, national neurosurgical residency match data from 2018 to 2020 were collected. For each aforementioned data point, gender was determined and confirmed via publicly available data. Data from the US News and World Report best hospitals publication for 2020 were applied for analyzing gender trends within neurosurgical residencies specifically., Results: In the past 2 decades (2000-2020), top leadership positions across the neurosurgical organizations were held by 45 individuals, of whom 5 (11.1%) were women. Spanning from 2000 to 2018, just 8.1% (50 of 618) of guests/honored speakers on the national neurosurgical stage of the CNS, AANS, SNS, and CSNS meetings have been female. Excluding the Louise Eisenhardt Lecture (honoring women), the percentage of female guests/honored speakers at the AANS meeting was just 5% (17 of 367). For the CNS annual meetings, 13.4% (20 of 149) of the speakers were women from 2000 to 2018, whereas the CSNS annual meeting data from 2001 to 2018 found that 11.9% (7 of 59) of speakers were women. From 1952 to the present, there have been no female honored guests at the CNS annual meeting. Across the residency match cycles from 2018 to 2020, the percentages of matched applicants identifying as female have been 22.7%, 28.1%, and, most recently, 25.3%. The percentage of female residents is 28.5% (top 20 program) versus 24.3% (non-top 20 program) (p = 0.267)., Conclusions: This study found that for all the data points surveyed, including leadership positions, invited lectureships at national neurosurgical meetings, and successful neurosurgical residency applicants, disproportionate female underrepresentation was evident. Consistent lack of visibility leads to a negative impact on progress in the recruitment and retention of women in neurosurgery. Visibility, mentorship, role models, and sponsorship are highly interrelated processes and are essential for meaningful progress.

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., (© 2018 International Neuromodulation Society.)

Background: Laser ablation (LA) is used as an upfront treatment in patients with deep seated newly diagnosed Glioblastoma (nGBM)., Objective: To evaluate the outcomes of LA in patients with nGBM and compare them with a matched biopsy-only cohort., Methods: Twenty-four nGBM patients underwent upfront LA at Cleveland clinic, Washington University in St. Louis, and Yale University (6/2011-12/2014) followed by chemo/radiotherapy. Also, 24 out of 171 nGBM patients with biopsy followed by chemo/radiotherapy were matched based on age (< 70 vs ≥ 70), gender, tumor location (deep vs lobar), and volume (<11 cc vs ≥11 cc). Progression-free survival (PFS), overall survival (OS), and disease-specific PFS and OS were outcome measures. Three prognostic groups were identified based on extent of tumor ablation by thermal-damage-threshold (TDT)-lines., Results: The median tumor volume in LA (n = 24) and biopsy only (n = 24) groups was 9.3 cm3 and 8.2 cm3 respectively. Overall, median estimate of OS and PFS in LA cohort was 14.4 and 4.3 mo compared to 15.8 mo and 5.9 mo for biopsy only cohort. On multivariate analysis, favorable TDT-line prognostic groups were associated with lower incidence of disease specific death (P = .03) and progression (P = .05) compared to other groups including biopsy only cohort. Only age (<70 yr, P = .02) and tumor volume (<11 cc, P = .03) were favorable prognostic factors for OS., Conclusion: The maximum tumor coverage by LA followed by radiation/chemotherapy is an effective treatment modality in patients with nGBM, compared to biopsy only cohort. The TDT-line prognostic groups were independent predictor of disease specific death and progression after LA., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: Unplanned hospital readmissions contribute significantly to soaring national healthcare expenditures. To alleviate this burden, Centers for Medicare and Medicaid Services implemented initiatives to penalize hospitals for unplanned 30-d hospital readmissions. There is a paucity of data identifying patient risk factors independently associated with 30- and 90-d readmissions., Objective: To investigate similarities in patient risk factors associated with 30- and 90-d unplanned readmissions following elective lumbar spine surgery., Methods: The National Readmission Database (NRD) was queried to identify patients undergoing elective lumbar spine surgery between 2013 and 2014. Patients were grouped by no readmission (Non-R), unplanned readmission within 30 days (30-R), and unplanned readmission within 31 to 90 days (90-R). Multivariate analysis determined factors associated with 30- and 90-d readmissions., Results: We identified 144 123 patients with 10 592 (7.3%) patients experiencing an unplanned readmission (30-R: n = 7228 [5.0%]; 90-R: n = 3364 [2.3%]; Non-R: n = 133 531). The most common inpatient complication observed in those patients readmitted was dural tear (30-R: 7.7%, 90-R: 4.6%, Non-R: 4.3%). The most prevalent 30- and 90-d complication seen among the readmitted cohort was infection (30-R: 18.5%, 90-R: 7.4%). In multivariate regression analysis, age, insurance status, chronic obstructive pulmonary disorder (COPD), depression, hypertension, diabetes, deficiency anemia, and obesity were independently associated with 30-d readmission; however, age and obesity were not independently associated with 90-d readmission., Conclusion: Our study demonstrated national unplanned readmission rates after elective spinal surgery to be 7.3%. With age, insurance status, COPD, depression, hypertension, diabetes, deficiency anemia, obesity, and depression all independently associated with unplanned hospital readmission. Future solutions that focus on reducing preventable readmissions may improve patient outcomes and reduce healthcare costs., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Background: Premature fusion of the cranial sutures can lead to significant neurocognitive, developmental, and esthetic consequences, especially if not corrected within the first year of life. This study aimed to identify the drivers of delayed cranial vault reconstruction (CVR) and its impact on complication and 30-day readmission rates among craniosynostosis patients., Methods: The medical records of all children who underwent CVR for craniosynostosis between 2005 and 2017 at an academic institution were retrospectively reviewed. A delay in operation was defined by surgery performed >12 months of age. Patient demographics, comorbidities, perioperative complication rates, and 30-day readmission rates were collected., Results: A total of 96 patients underwent primary CVR, with 79 (82.3%) patients undergoing nondelayed surgery and 17 (17.7%) patients undergoing surgery >12 months of age. Children undergoing delayed surgery were significantly more likely to be non-White (P < 0.0001), have Medicaid insurance (P = 0.023), and have a non-English primary language (P < 0.005). There was increased incidence of developmental disability identified at first consult (no-delay: 3.9% vs delay: 41.2%, P < 0.0001) and increased intracranial pressure (no-delay: 6.3% vs delay: 29.4%, P < 0.005) among children undergoing delayed surgery. The delayed cohort had a significantly higher unplanned 30-day readmission rate (no-delay: 0.0% vs delay: 5.9%, P = 0.03)., Conclusion: Our study suggests that craniosynostosis patients who are non-White, have a non-English primary language, and have Medicaid insurance are at risk for delayed primary surgery, which may lead to increased 30-day readmission. Interventions are necessary to reduce craniosynostosis patients' barriers to care to minimize the sequelae associated with delayed surgery.

Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amid immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide , exhaustion among T cells infiltrating human and murine GBM. Experimental Design: Tumor-infiltrating and peripheral blood lymphocytes (TILs and PBLs) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and poststimulation levels of the cytokines IFNγ, TNFα, and IL2 were assessed by flow cytometry. T-cell receptor Vβ chain expansion was also assessed in TILs and PBLs. Similar analysis was extended to TILs isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers. Results: Our data reveal that GBM elicits a particularly severe T-cell exhaustion signature among infiltrating T cells characterized by: (1) prominent upregulation of multiple immune checkpoints; (2) stereotyped T-cell transcriptional programs matching classical virus-induced exhaustion; and (3) notable T-cell hyporesponsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations. Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Clin Cancer Res; 24(17); 4175-86. ©2018 AACR See related commentary by Jackson and Lim, p. 4059 ., (©2018 American Association for Cancer Research.)

Objective: To investigate the impact that chronic obstructive pulmonary disease (COPD) has on postoperative complication rates, ambulation, and hospital length of stay for elderly spinal deformity patients after elective spinal fusion (≥3 levels)., Methods: The medical records of 559 elderly (≥60 years old) spine deformity patients undergoing elective spinal fusion (≥3 levels) at a major academic institution from 2005 to 2015 were reviewed. We identified 60 patients with COPD (10.7%) and 499 patients without COPD (89.3%). Patient demographics, comorbidities, postoperative complications, ambulatory status, and readmission rates were collected. The primary outcomes investigated in this study were complication rates and length of hospital stay., Results: Demographics and comorbidities were similar between groups, with a difference in proportion of smokers (COPD group: 25.0% vs. no COPD group: 9.6%, P = 0.0004). The median number of fusion levels (P = 0.840), operative time (P = 0.842), estimated blood loss (P = 0.336), and incidences of durotomy (P = 0.258) was similar between both cohorts. The COPD cohort experienced a higher rate of postoperative fever (10.0% vs. 3.0%, P = 0.007) and pneumonia (5.0% vs. 0.4%, P = 0.0004), respectively. There was a significant difference in the number of feet walked on the first day of ambulation after surgery (COPD group: 58.6 ± 78.4 vs. no COPD group: 84.0 ± 102.8, P = 0.040). Length of hospital stay was significantly longer in the COPD cohort than the no COPD cohort (7.7 ± 6.4 vs. 6.0 ± 4.0 days, respectively; P = 0.0498)., Conclusions: Our study demonstrates that elderly patients with COPD have increased lengths of stay and higher rates of postoperative pneumonia after spinal fusion. This determination identifies a potentially modifiable risk factor for increased utilization of health care resources., (Copyright © 2018 Elsevier Inc. All rights reserved.)

OBJECTIVE In spine surgery, racial disparities have been shown to impact various aspects of surgical care. Previous studies have associated racial disparities with inferior surgical outcomes, including increased complication and 30-day readmission rates after spine surgery. Recently, patient-reported outcomes (PROs) and satisfaction measures have been proxies for overall quality of care and hospital reimbursements. However, the influence that racial disparities have on short- and long-term PROs and patient satisfaction after spine surgery is relatively unknown. The aim of this study was to investigate the impact of racial disparities on 3- and 12-month PROs and patient satisfaction after elective lumbar spine surgery. METHODS This study was designed as a retrospective analysis of a prospectively maintained database. The medical records of adult (age ≥ 18 years) patients who had undergone elective lumbar spine surgery for spondylolisthesis (grade 1), disc herniation, or stenosis at a major academic institution were included in this study. Patient demographics, comorbidities, postoperative complications, and 30-day readmission rates were collected. Patients had prospectively collected outcome and satisfaction measures. Patient-reported outcome instruments-Oswestry Disability Index (ODI), visual analog scale for back pain (VAS-BP), and VAS for leg pain (VAS-LP)-were completed before surgery and at 3 and 12 months after surgery, as were patient satisfaction measures. RESULTS The authors identified 345 medical records for 53 (15.4%) African American (AA) patients and 292 (84.6%) white patients. Baseline patient demographics and comorbidities were similar between the two cohorts, with AA patients having a greater body mass index (33.1 ± 6.6 vs 30.2 ± 6.4 kg/m 2 , p = 0.005) and a higher prevalence of diabetes (35.9% vs 16.1%, p = 0.0008). Surgical indications, operative variables, and postoperative variables were similar between the cohorts. Baseline and follow-up PRO measures were worse in the AA cohort, with patients having a greater baseline ODI (p < 0.0001), VAS-BP score (p = 0.0002), and VAS-LP score (p = 0.0007). However, mean changes from baseline to 3- and 12-month PROs were similar between the cohorts for all measures except the 3-month VAS-BP score (p = 0.046). Patient-reported satisfaction measures at 3 and 12 months demonstrated a significantly lower proportion of AA patients stating that surgery met their expectations (3 months: 47.2% vs 65.5%, p = 0.01; 12 months: 35.7% vs 62.7%, p = 0.007). CONCLUSIONS The study data suggest that there is a significant difference in the perception of health, pain, and disability between AA and white patients at baseline and short- and long-term follow-ups, which may influence overall patient satisfaction. Further research is necessary to identify patient-specific factors associated with racial disparities that may be influencing outcomes to adequately measure and assess overall PROs and satisfaction after elective lumbar spine surgery.

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., (© 2017 International Neuromodulation Society.)

While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction. We screened commercially available nanoliposomal preparations and identified the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as an efficient mRNA courier to antigen-presenting cells (APCs). When administered intravenously, RNA-NPs mediate systemic activation of APCs in reticuloendothelial organs such as the spleen, liver, and bone marrow. RNA-NPs increase percent expression of MHC class I/II, B7 co-stimulatory molecules, and maturation markers on APCs (all vital for T-cell activation). RNA-NPs also increase activation markers on tumor APCs and elicit potent expansion of antigen-specific T-cells superior to peptide vaccines formulated in complete Freund's adjuvant. We demonstrate that both model antigen-encoding and physiologically-relevant tumor-derived RNA-NPs expand potent antitumor T-cell immunity. RNA-NPs were shown to induce antitumor efficacy in a vaccine model and functioned as a suitable alternative to DCs in a stringent cellular immunotherapy model for a radiation/temozolomide resistant invasive murine high-grade glioma. Although cancer vaccines have suffered from weak immunogenicity, we have advanced a RNA-NP formulation that systemically activates host APCs precipitating activated T-cell frequencies necessary to engender antitumor efficacy. RNA-NPs can thus be harnessed as a more feasible and effective immunotherapy to re-program host-immunity.

Adoptive cellular therapy (ACT) after lymphodepletive conditioning can induce dramatic clinical responses, but this approach has been largely limited to melanoma due to a lack of reliable methods for expanding tumor-specific lymphocytes from the majority of other solid cancers. We have employed tumor RNA-pulsed dendritic cells (DCs) to reliably expand CD4 + and CD8 + tumor-reactive T lymphocytes for curative ACT in a highly-invasive, chemotherapy- and radiation-resistant malignant glioma model. Curative treatment of established intracranial tumors involved a synergistic interaction between myeloablative (MA) conditioning, adoptively transferred tumor-specific T cells, and tumor RNA-pulsed DC vaccines. Hematopoietic stem cells (HSCs), administered for salvage from MA conditioning, rapidly migrated to areas of intracranial tumor growth and facilitated the recruitment of tumor-specific lymphocytes through HSC-elaborated chemokines and enhanced immunologic rejection of intracranial tumors during ACT. Furthermore, HSC transplant under non-myeloablative (NMA) conditions also enhanced immunologic tumor rejection, indicating a novel role for the use of HSCs in the immunologic treatment of malignant gliomas and possibly other solid tumors.