Lumbar Facet Arthroplasty Versus Fusion for Grade-I Degenerative Spondylolisthesis with Stenosis: A Prospective Randomized Controlled Trial.

BACKGROUND: The comparative effectiveness of decompression plus lumbar facet arthroplasty versus decompression plus instrumented lumbar spinal fusion in patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis is unknown. METHODS: In this randomized, controlled, Food and Drug Administration Investigational Device Exemption trial, we assigned patients who had single-level lumbar spinal stenosis and grade-I degenerative spondylolisthesis to undergo decompression plus lumbar facet arthroplasty (arthroplasty group) or decompression plus fusion (fusion group). The primary outcome was a predetermined composite clinical success score. Secondary outcomes included the Oswestry Disability Index (ODI), visual analog scale (VAS) back and leg pain, Zurich Claudication Questionnaire (ZCQ), Short Form (SF)-12, radiographic parameters, surgical variables, and complications. RESULTS: A total of 321 adult patients were randomized in a 2:1 fashion, with 219 patients assigned to undergo facet arthroplasty and 102 patients assigned to undergo fusion. Of these, 113 patients (51.6%) in the arthroplasty group and 47 (46.1%) in the fusion group who had either reached 24 months of postoperative follow-up or were deemed early clinical failures were included in the primary outcome analysis. The arthroplasty group had a higher proportion of patients who achieved composite clinical success than did the fusion group (73.5% versus 25.5%; p < 0.001), equating to a between-group difference of 47.9% (95% confidence interval, 33.0% to 62.8%). The arthroplasty group outperformed the fusion group in most patient-reported outcome measures (including the ODI, VAS back pain, and all ZCQ component scores) at 24 months postoperatively. There were no significant differences between groups in surgical variables or complications, except that the fusion group had a higher rate of developing symptomatic adjacent segment degeneration. CONCLUSIONS: Among patients with lumbar spinal stenosis and grade-I degenerative spondylolisthesis, lumbar facet arthroplasty was associated with a higher rate of composite clinical success than fusion was at 24 months postoperatively. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Bridging the literacy gap for surgical consents: an AI-human expert collaborative approach.

Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.

Demographic Representation in 3 Leading Artificial Intelligence Text-to-Image Generators.

Importance: The progression of artificial intelligence (AI) text-to-image generators raises concerns of perpetuating societal biases, including profession-based stereotypes. Objective: To gauge the demographic accuracy of surgeon representation by 3 prominent AI text-to-image models compared to real-world attending surgeons and trainees. Design, Setting, and Participants: The study used a cross-sectional design, assessing the latest release of 3 leading publicly available AI text-to-image generators. Seven independent reviewers categorized AI-produced images. A total of 2400 images were analyzed, generated across 8 surgical specialties within each model. An additional 1200 images were evaluated based on geographic prompts for 3 countries. The study was conducted in May 2023. The 3 AI text-to-image generators were chosen due to their popularity at the time of this study. The measure of demographic characteristics was provided by the Association of American Medical Colleges subspecialty report, which references the American Medical Association master file for physician demographic characteristics across 50 states. Given changing demographic characteristics in trainees compared to attending surgeons, the decision was made to look into both groups separately. Race (non-White, defined as any race other than non-Hispanic White, and White) and gender (female and male) were assessed to evaluate known societal biases. Exposures: Images were generated using a prompt template, "a photo of the face of a [blank]", with the blank replaced by a surgical specialty. Geographic-based prompting was evaluated by specifying the most populous countries on 3 continents (the US, Nigeria, and China). Main Outcomes and Measures: The study compared representation of female and non-White surgeons in each model with real demographic data using χ2, Fisher exact, and proportion tests. Results: There was a significantly higher mean representation of female (35.8% vs 14.7%; P < .001) and non-White (37.4% vs 22.8%; P < .001) surgeons among trainees than attending surgeons. DALL-E 2 reflected attending surgeons' true demographic data for female surgeons (15.9% vs 14.7%; P = .39) and non-White surgeons (22.6% vs 22.8%; P = .92) but underestimated trainees' representation for both female (15.9% vs 35.8%; P < .001) and non-White (22.6% vs 37.4%; P < .001) surgeons. In contrast, Midjourney and Stable Diffusion had significantly lower representation of images of female (0% and 1.8%, respectively; P < .001) and non-White (0.5% and 0.6%, respectively; P < .001) surgeons than DALL-E 2 or true demographic data. Geographic-based prompting increased non-White surgeon representation but did not alter female representation for all models in prompts specifying Nigeria and China. Conclusion and Relevance: In this study, 2 leading publicly available text-to-image generators amplified societal biases, depicting over 98% surgeons as White and male. While 1 of the models depicted comparable demographic characteristics to real attending surgeons, all 3 models underestimated trainee representation. The study suggests the need for guardrails and robust feedback systems to minimize AI text-to-image generators magnifying stereotypes in professions such as surgery.

Geriatric Surgery Produces a Hypoactive Molecular Phenotype in the Monocyte Immune Gene Transcriptome.

Surgery is a major challenge for the immune system, but little is known about the immune response of geriatric patients to surgery. We therefore investigated the impact of surgery on the molecular signature of circulating CD14+ monocytes, cells implicated in clinical recovery from surgery, in older patients. We enrolled older patients having elective joint replacement (N = 19) or spine (N = 16) surgery and investigated pre- to postoperative expression changes in 784 immune-related genes in monocytes. Joint replacement altered the expression of 489 genes (adjusted p < 0.05), of which 38 had a |logFC| > 1. Spine surgery changed the expression of 209 genes (adjusted p < 0.05), of which 27 had a |logFC| > 1. In both, the majority of genes with a |logFC| > 1 change were downregulated. In the combined group (N = 35), 471 transcripts were differentially expressed (adjusted p < 0.05) after surgery; 29 had a |logFC| > 1 and 72% of these were downregulated. Notably, 21 transcripts were common across procedures. Thus, elective surgery in older patients produces myriad changes in the immune gene transcriptome of monocytes, with many suggesting development of an immunocompromised/hypoactive phenotype. Because monocytes are strongly implicated in the quality of surgical recovery, this signature provides insight into the cellular and molecular mechanisms of the immune response to surgery and warrants further study as a potential biomarker for predicting poor outcomes in older surgical patients.

Clinical and Radiographic Outcomes for Patients with Cervical Adjacent Segment Disease Treated with Anterior Cervical Discectomy and Fusion with Integrated Interbody Spacers.

INTRODUCTION: Anterior cervical discectomy and fusion (ACDF) is among the most common spine procedures. Adjacent segment disease (ASD), characterized by degenerative disease at an adjacent spinal level to a prior fusion, is a well-recognized and significant sequela following ACDF. Adjacent segment ACDF may be considered after the failure of non-surgical options for patients with symptomatic ASD. This study aimed to assess the incidence of dysphagia and other complications as well as radiographic outcomes in adult patients who have undergone ACDF with an integrated interbody spacer device for symptomatic ASD. METHODS: This was a retrospective review of patients who underwent ACDF for symptomatic ASD with commercially available integrated interbody spacers by three spine surgeons at an academic institution from March 2018 to April 2022. Demographic, radiographic, and postoperative data were collected, including dysphagia, device-related complications, and the need for revision surgery. RESULTS: There were 48 patients (26 male, 22 female) who met inclusion criteria (mean age 59.7 years, mean body mass index 19.5 kg/m2) who underwent ACDF for symptomatic ASD (1one-level, n = 44; 2-level, n = 4). Overall, 12 patients (25%) experienced dysphagia postoperatively before the first follow-up appointment. Nine of 44 (20.4%) of 1-level ACDF patients experienced dysphagia, and 3 of 4 (75%) of 2-level ACDF patients experienced dysphagia. Three patients had severe dysphagia which prompted an otolaryngology referral. Two of those patients remained symptomatic at 6 weeks postoperatively. Of 43 patients with prior plate cage systems, none required hardware removal at the time of surgery. Preoperative global and segmental lordosis were 9.07° ± 8.36° (P = 0.22) and 3.58° ± 4.57° (P = 0.14), respectively. At 6 weeks postoperatively, global and segmental lordosis were 11.44° ± 9.06° (P = 0.54) and 5.11° ± 4.44° (P = 0.44), respectively. This constitutes a change of +2.37° and +1.53° in global and segmental lordosis, respectively. The mean anterior disc height change between preoperative and immediate postoperative time points was 6.3 ± 3.1 mm. Between the immediate postoperative and 6-week postoperative time points, the mean anterior disc height change was -1.5 ± 2.7 mm. Between the immediate postoperative and 3-month postoperative time points, the mean anterior disc height change was -3.7 ± 5.0 mm. The posterior disc height changes at the same time points were 2.5 ± 1.7 mm, -0.4 ± 1.8. and -0.5 ± 1.4 mm, respectively. This fusion rate was 50% and 70% at 6 months and 1 year post-surgery, respectively. CONCLUSIONS: ACDF with integrated spacer is a viable alternative to traditional plate-cage systems for symptomatic ASD. An advantage over traditional plate-cage systems is that the removal of prior instrumentation is not needed in order to place implants. Based on a review of the literature, these standalone systems allowed for a shorter operative time and had less incidence of dysphagia than plate-cage systems for ASD after ACDF. The different standalone and plate-cage systems used in treating ASD after ACDF surgeries should be compared in prospective studies.

Gross total resection of spinal chondrosarcoma is associated with improved locoregional relapse-free survival and overall survival.

BACKGROUND: Spinal chondrosarcomas are rare malignant osseous tumors. The low incidence of spinal chondrosarcomas and the complexity of spine anatomy have led to heterogeneous treatment strategies with varying curative and survival rates. The goal of this study is to investigate prognostic factors for locoregional recurrence-free survival (LRFS) and overall survival (OS) comparing en bloc vs. piecemeal resection for the management of spinal chondrosarcoma. METHODS: We retrospectively identified patients who underwent curative-intent resection of primary and metastatic spinal chondrosarcoma over a 25-year period. Univariate and multivariate survival analyses were conducted with LRFS as primary endpoint and OS as secondary endpoint. LRFS and OS were modeled using the Kaplan-Meier method and assessed using Cox regression analysis. RESULTS: For 72 patients who underwent first resection, the median follow-up time was 5.1 years (95% CI 2.2-7.0). Thirty-three patients (45.8%) had en bloc resection, and 39 (54.2%) had piecemeal resection. Of the 68 patients for whom extent of resection was known, 44 patients had gross total resection (GTR) and 24 patients had subtotal resection. In survival analyses, both LRFS and OS showed statistically significant difference based on the extent of resection (p = 0.001; p = 0.04, respectively). However, only LRFS showed statistically significant difference when assessing the type of resection (p = 0.02). In addition, higher tumor grade and more invasive disease were associated with worse LRFS and OS rates. CONCLUSION: Although in our study en bloc and GTR were associated with improved survival, heterogenous and complex spinal presentations may limit total resection. Therefore, the surgical management should be tailored individually to ensure the best local control and maximum preservation of function.

Evaluation of interdisciplinary care pathway implementation in older elective surgery patients.

BACKGROUND: The American College of Surgeons Geriatric Surgery Verification Program outlines best practices for surgical care in older adults. These recommendations have guided institutions to create workflows to better support needs specific to older surgical patients. This qualitative study explored clinician experiences to understand influences on implementation of frailty screening and an interdisciplinary care pathway in older elective colorectal surgery and neurosurgery patients. STUDY DESIGN: Semi-structured in-person and video-based interviews were conducted from July 2021 to March 2022 with clinicians caring for patients ≥70 years on the colorectal surgery and neurosurgery services. Interviews addressed familiarity with and beliefs about the intervention, intervention alignment with routine workflow and workflow adaptations, and barriers and facilitators to performing the intervention. Interviews were analyzed using the consolidated framework for implementation research (CFIR) to find themes related to ongoing implementation. RESULTS: Thirty-two clinicians participated (56.3% female, 58.8% White). Fifteen relevant CFIR constructs were identified. Key themes to implementation success included strong participant belief in effectiveness of the intervention and its advantage over standard care; the importance of training, reference materials, and champions; and the need for institution-level investment in resources to amplify the impact of the intervention on patients and expand the capacity to address their needs. CONCLUSION: Systematic evaluation found implementation of frailty screening and an interdisciplinary care pathway in elective colorectal surgery and neurosurgery patients to be supported by participating clinicians, yet sustainability of the intervention and further adoption across surgical services to better meet the needs of older patients would necessitate organizational resource allocation.

Impact of Neurosurgery Research and Education Foundation awards on subsequent grant funding and career outcomes of neurosurgeon-scientists.

OBJECTIVE: The Neurosurgery Research and Education Foundation (NREF) provides diverse funding opportunities for in-training and early-career neurosurgeon-scientists. The authors analyzed the impact of NREF funding on the subsequent career success of neurosurgeons in obtaining research funding and academic achievements. METHODS: The NREF database was queried to identify NREF winners from 2000 to 2015. The award recipients were surveyed to obtain information about their demographic characteristics, academic career, and research funding. Only subsequent research support with an annual funding amount of $50,000 or greater was included. The primary outcome was the NREF impact ratio, defined as the ratio between NREF award research dollars and subsequent grant funding dollars. The secondary outcomes were time to subsequent grant funding as principal investigator (PI), clinical practice settings, and final academic position achieved. RESULTS: From 2000 to 2015, 158 neurosurgeons received 164 NREF awards totaling $8.3 million (M), with $1.7 M awarded to 46 Young Clinician Investigators (YCIs), $1.5 M to 18 Van Wagenen Fellows (VWFs), and $5.1 M to 100 resident Research Fellowship Grant (RFG) awardees. Of all awardees, 73% have current academic appointments, and the mean ± SD number of publications and H-index were 71 ± 82 and 20 ± 15, respectively. The overall response rate to our survey was 70%, and these respondents became the cohort for our analysis. In total, respondents cumulatively obtained $776 M in post-NREF award grant funding, with the most common sources of funding including the National Institutes of Health ($327 M) and foundational awards ($306 M). The NREF impact ratios for awardees were $1:$381 for YCI, $1:$113 for VWF, and $1:$41 for resident RFG. Awardees with NREF projects in functional neurosurgery, pediatric neurosurgery, and neuro-oncology had the highest NREF impact ratios of $1:$194, $1:$185, and $1:$162, respectively. Of respondents, 9% became department chairs, 26% became full professors, 82% received at least 1 subsequent research grant, and 66% served as PI on a subsequent research grant after receiving their NREF awards. CONCLUSIONS: In-training and early-career neurosurgeons who were awarded NREF funding had significant success in acquiring subsequent grant support, research productivity, and achievements of academic rank. NREF grants provide a tremendous return on investment across various career stages and subspecialities. They also appeared to have a broader impact on trajectory of research and innovation within the field of neurosurgery.

Anxiety, depression, and sleep-related outcomes of glaucoma patients: systematic review and meta-analysis.

OBJECTIVE: This study aims to synthesize data quantifying the prevalence and severity of common psychological conditions in patients with glaucoma. DESIGN: Systematic review and meta-analysis. METHODS: Databases including Ovid MEDLINE, CINAHL, EMBASE, PsycINFO, Cochrane Library, Web of Science, Open Grey, and ProQuest Theses and dissertations were searched. Two reviewers independently assessed and screened all studies, followed by quality assessment of included studies using the modified Downs and Black checklist. Data were pooled using fixed-effect and random-effects models. RESULTS: Of 2067 studies identified by the search strategy, 57 passed full-text screening, and 45 studies (4 995 538 subjects) were eligible for analysis. Overall, the prevalence of depression (effect size [ES] = 0.19, 95% CI 0.16-0.23; n = 31), anxiety (ES = 0.25, 95% CI 0.21-0.30; n = 18), and sleep disorders (ES = 0.47, 95% CI 0.26-0.68; n = 7) were high in patients with glaucoma. Similarly, symptomatic measurements of depression (standardized mean difference [SMD] = 0.46, 95% CI 0.19-0.73), anxiety (SMD = 0.44, 95% CI 0.08-0.81), and sleep quality (SMD = 0.72, 95% CI 0.22-1.21) were significant in glaucoma patients. CONCLUSIONS: A higher prevalence and severity of depression, anxiety, and sleep disorders was experienced in patients with glaucoma compared with patients without glaucoma. Caregivers as well as health care providers may need to be aware of unique psychological and social stressors placed on glaucoma patients.

The New England Neurosurgical Society: growth and evolution over 70 years.

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.

Prospective, randomized controlled multicenter study of posterior lumbar facet arthroplasty for the treatment of spondylolisthesis.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of a posterior facet replacement device, the Total Posterior Spine (TOPS) System, for the treatment of one-level symptomatic lumbar stenosis with grade I degenerative spondylolisthesis. Posterior lumbar arthroplasty with facet replacement is a motion-preserving alternative to lumbar decompression and fusion. The authors report the preliminary results from the TOPS FDA investigational device exemption (IDE) trial. METHODS: The study was a prospective, randomized controlled FDA IDE trial comparing the investigational TOPS device with transforaminal lumbar interbody fusion (TLIF) and pedicle screw fixation. The minimum follow-up duration was 24 months. Validated patient-reported outcome measures included the Oswestry Disability Index (ODI) and visual analog scale (VAS) for back and leg pain. The primary outcome was a composite measure of clinical success: 1) no reoperations, 2) no device breakage, 3) ODI reduction of ≥ 15 points, and 4) no new or worsening neurological deficit. Patients were considered a clinical success only if they met all four measures. Radiographic assessments were made by an independent core laboratory. RESULTS: A total of 249 patients were evaluated (n = 170 in the TOPS group and n = 79 in the TLIF group). There were no statistically significant differences between implanted levels (L4-5: TOPS, 95% and TLIF, 95%) or blood loss. The overall composite measure for clinical success was statistically significantly higher in the TOPS group (85%) compared with the TLIF group (64%) (p = 0.0138). The percentage of patients reporting a minimum 15-point improvement in ODI showed a statistically significant difference (p = 0.037) favoring TOPS (93%) over TLIF (81%). There was no statistically significant difference between groups in the percentage of patients reporting a minimum 20-point improvement on VAS back pain (TOPS, 87%; TLIF, 64%) and leg pain (TOPS, 90%; TLIF, 88%) scores. The rate of surgical reintervention for facet replacement in the TOPS group (5.9%) was lower than the TLIF group (8.8%). The TOPS cohort demonstrated maintenance of flexion/extension range of motion from preoperatively (3.85°) to 24 months (3.86°). CONCLUSIONS: This study demonstrates that posterior lumbar decompression and dynamic stabilization with the TOPS device is safe and efficacious in the treatment of lumbar stenosis with degenerative spondylolisthesis. Additionally, decompression and dynamic stabilization with the TOPS device maintains segmental motion.

A Prospective Study of Lumbar Facet Arthroplasty in the Treatment of Degenerative Spondylolisthesis and Stenosis: Results from the Total Posterior Spine System (TOPS) IDE Study.

STUDY DESIGN: Prospective randomized Food and Drug Administration investigational device exemption clinical trial. OBJECTIVE: The purpose of the present study is to report the 1-year clinical and radiographic outcomes and safety profile of patients who underwent lumbar facet arthroplasty through implantation of the Total Posterior Spine System (TOPS) device. SUMMARY OF BACKGROUND DATA: Lumbar facet arthroplasty is one proposed method of dynamic stabilization to treat grade-1 spondylolisthesis with stenosis; however, there are currently no Food and Drug Administration-approved devices for facet arthroplasty. METHODS: Standard demographic information was collected for each patient. Radiographic parameters and patient-reported outcome measures were assessed preoperatively and at regular postoperative intervals. Complication and reoperation data were also collected for each patient. RESULTS: At the time of this study, 153 patients had undergone implantation of the TOPS device. The mean surgical time was 187.8 minutes and the mean estimated blood loss was 205.7cc. The mean length of hospital stay was 3.0 days. Mean Oswestry Disability Index, Visual Analog Score leg and back, and Zurich Claudication Questionnaire scores improved significantly at all postoperative time points ( P >0.001). There were no clinically significant changes in radiographic parameters, and all operative segments remained mobile at 1-year follow-up. Postoperative complications occurred in 11 patients out of the 153 patients (7.2%) who underwent implantation of the TOPS device. Nine patients (5.9%) underwent a total of 13 reoperations, 1 (0.6%) of which was for device-related failure owing to bilateral L5 pedicle screw loosening. CONCLUSIONS: Lumbar facet arthroplasty with the TOPS device demonstrated a statistically significant improvement in all patient-reported outcome measures and the ability to maintain motion at the index level while limiting sagittal translation with a low complication rate.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Background: Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. Objective: To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Design: Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Setting: Five Ontario pediatric oncology centers. Patients: The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Measurements: Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Methods: Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Limitations: Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Conclusions: Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Evaluation of Load-To-Strength Ratios in Metastatic Vertebrae and Comparison With Age- and Sex-Matched Healthy Individuals.

Vertebrae containing osteolytic and osteosclerotic bone metastases undergo pathologic vertebral fracture (PVF) when the lesioned vertebrae fail to carry daily loads. We hypothesize that task-specific spinal loading patterns amplify the risk of PVF, with a higher degree of risk in osteolytic than in osteosclerotic vertebrae. To test this hypothesis, we obtained clinical CT images of 11 cadaveric spines with bone metastases, estimated the individual vertebral strength from the CT data, and created spine-specific musculoskeletal models from the CT data. We established a musculoskeletal model for each spine to compute vertebral loading for natural standing, natural standing + weights, forward flexion + weights, and lateral bending + weights and derived the individual vertebral load-to-strength ratio (LSR). For each activity, we compared the metastatic spines' predicted LSRs with the normative LSRs generated from a population-based sample of 250 men and women of comparable ages. Bone metastases classification significantly affected the CT-estimated vertebral strength (Kruskal-Wallis, p < 0.0001). Post-test analysis showed that the estimated vertebral strength of osteosclerotic and mixed metastases vertebrae was significantly higher than that of osteolytic vertebrae (p = 0.0016 and p = 0.0003) or vertebrae without radiographic evidence of bone metastasis (p = 0.0010 and p = 0.0003). Compared with the median (50%) LSRs of the normative dataset, osteolytic vertebrae had higher median (50%) LSRs under natural standing (p = 0.0375), natural standing + weights (p = 0.0118), and lateral bending + weights (p = 0.0111). Surprisingly, vertebrae showing minimal radiographic evidence of bone metastasis presented significantly higher median (50%) LSRs under natural standing (p < 0.0001) and lateral bending + weights (p = 0.0009) than the normative dataset. Osteosclerotic vertebrae had lower median (50%) LSRs under natural standing (p < 0.0001), natural standing + weights (p = 0.0005), forward flexion + weights (p < 0.0001), and lateral bending + weights (p = 0.0002), a trend shared by vertebrae with mixed lesions. This study is the first to apply musculoskeletal modeling to estimate individual vertebral loading in pathologic spines and highlights the role of task-specific loading in augmenting PVF risk associated with specific bone metastatic types. Our finding of high LSRs in vertebrae without radiologically observed bone metastasis highlights that patients with metastatic spine disease could be at an increased risk of vertebral fractures even at levels where lesions have not been identified radiologically.

Effectiveness of crizotinib versus entrectinib in ROS1-positive non-small-cell lung cancer using clinical and real-world data.

Aims: To compare clinical trial results for crizotinib and entrectinib in ROS1-positive non-small-cell lung cancer and compare clinical trial data and real-world outcomes for crizotinib. Patients & methods: We analyzed four phase I-II studies using a simulated treatment comparison (STC). A STC of clinical trial versus real-world evidence compared crizotinib clinical data to real-world outcomes. Results: Adjusted STC found nonsignificant trends favoring crizotinib over entrectinib: objective response rate, risk ratio = 1.04 (95% CI: 0.85-1.28); median duration of response, mean difference = 16.11 months (95% CI: -1.57- 33.69); median progression-free survival, mean difference = 3.99 months (95% CI: -6.27-14.25); 12-month overall survival, risk ratio = 1.01 (95% CI: 0.90-1.12). Nonsignificant differences were observed between the trial end point values and the real-world evidence for crizotinib. Conclusions: Crizotinib and entrectinib have comparable efficacy in ROS1-positive non-small-cell lung cancer.

Neurosurgery Research and Education Foundation funding conversion to National Institutes of Health funding.

OBJECTIVE: The Neurosurgery Research and Education Foundation (NREF) provides research support for in-training and early career neurosurgeon-scientists. To define the impact of this funding, the authors assessed the success of NREF awardees in obtaining subsequent National Institutes of Health (NIH) funding. METHODS: NREF in-training (Research Fellowship [RF] for residents) and early career awards/awardees (Van Wagenen Fellowship [VW] and Young Clinician Investigator [YCI] award for neurosurgery faculty) were analyzed. NIH funding was defined by individual awardees using the NIH Research Portfolio Online Reporting tool (1985-2014). RESULTS: Between 1985 and 2014, 207 unique awardees were supported by 218 NREF awards ($9.84 million [M] in funding), including 117 RF ($6.02 M), 32 VW ($1.68 M), and 69 YCI ($2.65 M) awards. Subspecialty funding included neuro-oncology (79 awards; 36% of RF, VW, and YCI awards), functional (53 awards; 24%), vascular (37 awards; 17%), spine (22 awards; 10%), pediatrics (18 awards; 8%), trauma/critical care (5 awards; 2%), and peripheral nerve (4 awards; 2%). These awardees went on to receive $353.90 M in NIH funding that resulted in an overall NREF/NIH funding ratio of 36.0:1 (in dollars). YCI awardees most frequently obtained later NIH funding (65%; $287.27 M), followed by VW (56%; $41.10 M) and RF (31%; $106.59 M) awardees. YCI awardees had the highest NREF/NIH funding ratio (108.6:1), followed by VW (24.4:1) and RF (17.7:1) awardees. Subspecialty awardees who went on to obtain NIH funding included vascular (19 awardees; 51% of vascular NREF awards), neuro-oncology (40 awardees; 51%), pediatrics (9 awardees; 50%), functional (25 awardees; 47%), peripheral nerve (1 awardees; 25%), trauma/critical care (2 awardees; 20%), and spine (2 awardees; 9%) awardees. Subspecialty NREF/NIH funding ratios were 56.2:1 for vascular, 53.0:1 for neuro-oncology, 47.6:1 for pediatrics, 34.1:1 for functional, 22.2:1 for trauma/critical care, 9.5:1 for peripheral nerve, and 0.4:1 for spine. Individuals with 2 NREF awards achieved a higher NREF/NIH funding ratio (83.3:1) compared to those with 1 award (29.1:1). CONCLUSIONS: In-training and early career NREF grant awardees are an excellent investment, as a significant portion of these awardees go on to obtain NIH funding. Moreover, there is a potent multiplicative impact of NREF funding converted to NIH funding that is related to award type and subspecialty.

Predictors of thoracic and lumbar spine injuries in patients with TBI: A nationwide analysis.

OBJECTIVE: Cervical spine injury screening is common practice for traumatic brain injury (TBI) patients. However, risk factors for concomitant thoracolumbar trauma remain unknown. We characterized epidemiology and clinical risk for concomitant thoracolumbar trauma in TBI. METHODS: We conducted a multi-center, retrospective cohort analysis of TBI patients in the National Trauma Data Bank from 2011-2014 using multivariable logistic regression. RESULTS: Out of 768,718 TBIs, 46,654 (6.1%) and 42,810 (5.6%) patients were diagnosed with thoracic and lumbar spine fractures, respectively. Only 11% of thoracic and 7% of lumbar spine fracture patients had an accompanying spinal cord injury at any level. The most common mechanism of injury was motor vehicle accident (67% of thoracic and 71% and lumbar fractures). Predictors for both thoracic and lumbar fractures included moderate (thoracic: OR 1.26, 95%CI 1.21-1.31; lumbar: OR 1.13, 95%CI 1.08-1.18) and severe Glasgow Coma Scale (GCS) score (OR 1.71, 95%CI 1.67-1.75; OR 1.17, 95%CI 1.13-1.20) compared to mild; epidural hematoma (OR 1.36, 95%CI 1.28-1.44; OR 1.1, 95%CI 1.04-1.19); lower extremity injury (OR 1.38, 95%CI 1.35-1.41; OR 2.50, 95%CI 2.45-2.55); upper extremity injury (OR 2.19, 95%CI 2.14-2.23; OR 1.15, 95%CI 1.13-1.18); smoking (OR 1.09, 95%CI 1.06-1.12; OR 1.12, 95%CI 1.09-1.15); and obesity (OR 1.39, 95%CI 1.34-1.45; OR 1.29, 95%CI 1.24-1.35). Thoracic injuries (OR 4.45; 95% CI 4.35-4.55) predicted lumbar fractures, while abdominal injuries (OR 2.02; 95% CI 1.97-2.07) predicted thoracic fractures. CONCLUSIONS: We identified GCS, smoking, upper and lower extremity injuries, and obesity as common risk factors for thoracic and lumbar spinal fractures in TBI.

Late Kidney Effects of Nephron-Sparing vs Radical Nephrectomy for Wilms Tumor: A Systematic Review and Meta-Analysis.

PURPOSE: We compare differences in long-term kidney function between patients undergoing either radical nephrectomy (RN) or nephron-sparing surgery (NSS) in unilateral and bilateral Wilms tumor (WT), respectively. MATERIALS AND METHODS: A systematic search was performed in September 2020. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed long-term (>1-year postoperative) outcomes included chronic kidney disease, hypertension and glomerular filtration rate, among others. Odds ratio and mean difference with 95% confidence interval were extrapolated from available data for quantitative synthesis. Random-effects meta-analysis and meta-regression were performed according to study design and techniques. The systematic review was prospectively registered on PROSPERO (CRD42020205378). RESULTS: A total of 23 studies describing 293 cases of unilateral WT and 386 cases of bilateral WT were included in the qualitative synthesis. Overall effect estimates demonstrate that patients undergoing RN have significantly increased odds of developing abnormal kidney function (OR 4.29, 95% CI 1.02, 18.00) and lower estimated glomerular filtration rate at long-term followup (mean difference -8.99, 95% CI -16.40, -1.58) compared to those undergoing NSS. In bilateral WT, patients undergoing RN with contralateral NSS have higher odds of developing abnormal kidney function (OR 3.82, 95% CI 1.76, 8.33) and hypertension (OR 5.81, 95% CI 1.31, 25.68) compared to bilateral NSS. CONCLUSIONS: Current evidence is low quality but suggests that NSS for unilateral and bilateral WT may be associated with better kidney function or blood pressure at late followup. Further research to investigate sources of heterogeneity is recommended.

Improved estimates of strength and stiffness in pathologic vertebrae with bone metastases using CT-derived bone density compared with radiographic bone lesion quality classification.

OBJECTIVE: The aim of this study was to compare the ability of 1) CT-derived bone lesion quality (classification of vertebral bone metastases [BM]) and 2) computed CT-measured volumetric bone mineral density (vBMD) for evaluating the strength and stiffness of cadaver vertebrae from donors with metastatic spinal disease. METHODS: Forty-five thoracic and lumbar vertebrae were obtained from cadaver spines of 11 donors with breast, esophageal, kidney, lung, or prostate cancer. Each vertebra was imaged using microCT (21.4 µm), vBMD, and bone volume to total volume were computed, and compressive strength and stiffness experimentally measured. The microCT images were reconstructed at 1-mm voxel size to simulate axial and sagittal clinical CT images. Five expert clinicians blindly classified the images according to bone lesion quality (osteolytic, osteoblastic, mixed, or healthy). Fleiss' kappa test was used to test agreement among 5 clinical raters for classifying bone lesion quality. Kruskal-Wallis ANOVA was used to test the difference in vertebral strength and stiffness based on bone lesion quality. Multivariable regression analysis was used to test the independent contribution of bone lesion quality, computed vBMD, age, gender, and race for predicting vertebral strength and stiffness. RESULTS: A low interrater agreement was found for bone lesion quality (κ = 0.19). Although the osteoblastic vertebrae showed significantly higher strength than osteolytic vertebrae (p = 0.0148), the multivariable analysis showed that bone lesion quality explained 19% of the variability in vertebral strength and 13% in vertebral stiffness. The computed vBMD explained 75% of vertebral strength (p < 0.0001) and 48% of stiffness (p < 0.0001) variability. The type of BM affected vBMD-based estimates of vertebral strength, explaining 75% of strength variability in osteoblastic vertebrae (R2 = 0.75, p < 0.0001) but only 41% in vertebrae with mixed bone metastasis (R2 = 0.41, p = 0.0168), and 39% in osteolytic vertebrae (R2 = 0.39, p = 0.0381). For vertebral stiffness, vBMD was only associated with that of osteoblastic vertebrae (R2 = 0.44, p = 0.0024). Age and race inconsistently affected the model's strength and stiffness predictions. CONCLUSIONS: Pathologic vertebral fracture occurs when the metastatic lesion degrades vertebral strength, rendering it unable to carry daily loads. This study demonstrated the limitation of qualitative clinical classification of bone lesion quality for predicting pathologic vertebral strength and stiffness. Computed CT-derived vBMD more reliably estimated vertebral strength and stiffness. Replacing the qualitative clinical classification with computed vBMD estimates may improve the prediction of vertebral fracture risk.