Muscle activity and rehabilitation in spinal stenosis (MARSS) after conservative therapy and surgical decompression with or without fusion: Protocol for a partially randomized patient preference trial on rehabilitation timing.

Background: Patients affected by lumbar spinal stenosis (LSS) suffer from a multifactorial degeneration of the lumbar spine resulting in narrowing of the neuroforamina and spinal canal, leading to various functional limitations. It remains unclear whether LSS patients after surgery would benefit from early post-operative rehabilitation, or if a delayed rehabilitation would be more advantageous. The purpose of this partially randomized patient preference trial is to evaluate the impact of post-operative rehabilitation timing as well as surgical intervention type on psychometric properties and functional outcomes in patients with LSS. Methods: Data for this patient preference trial are collected before and after surgical (decompression only or decompression and fusion) and rehabilitative interventions as well as six, 12 and 24 months after completing rehabilitation. The study participants are patients diagnosed with LSS who are at least 18 years old. After a medical check-up, participants will complete patient-reported outcome measures (PAREMO-20, SIBAR, FREM-8, SF-12, SFI, ODI) and different functional assessments (functional reach test, loaded reach test, handgrip strength, standing balance control, 6-min walk test). Ethics and dissemination: The results of this study will be published through peer-reviewed publications and scientific contributions at national and international conferences. This research has been approved by the Institutional Review Board of Martin Luther University Halle-Wittenberg (reference number: 2022-128).

Analysis of Complications in Multilevel Anterior Cervical Discectomy and Fusion Using Osteobiologics Other than Bone Morphogenetic Protein: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The aim of this study is to analyze the complications related to multilevel anterior cervical discectomy and fusion (ACDF) using osteobiologics other than bone morphogenetic protein (BMP). METHODS: A systematic review of the literature was conducted using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search to identify studies reporting complications in multilevel ACDF surgery using osteobiologics other than bone morphogenetic protein was performed in August 2020. The study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: A total of 584 articles were found after searching the databases and removing duplicates. Next, screening was performed in a double reviewer process, and 153 eligible articles-with 4 retrospective studies-in full-text were selected; these met all inclusion criteria. A total of 197 patients received 3-level ACDF, while 72 patients received 4-level ACDF. Osteobiologics were used in all selected articles, allograft was used in 4 studies, autologous bone graft was utilized in 3 articles, and hydroxyapatite was used in 1 article. The main complications reported were dysphagia, adjacent segment disease, and pseudarthrosis. CONCLUSIONS: Given the limited evidence, no conclusions on complications in multilevel ACDF using osteobiologics other than BMP could be made. However, descriptively, the most common complications found were dysphagia, adjacent segment disease, and pseudoarthrosis. Further prospective studies separately analyzing complications in multilevel ACDF by osteobiologics and a number of treated levels are needed.

Complications of the Use Allograft in 1- or 2-Level Anterior Cervical Discectomy and Fusion: A Systematic Review.

Study Design: Systematic literature reviewObjective: To critically analyze the literature and describe the complications associated with the use of allograft in 1- or 2- level anterior cervical discectomy and fusion (ACDF)Methods: A systematic search of PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov databases was conducted for literature published between January 2000 and August 2020 reporting complications associated with the use of allograft in 1- or 2- level ACDF.Results: From 584 potentially relevant citations, 21 met the inclusion criteria (4 randomized controlled trials (RCT), 4 prospective, and 13 retrospective studies). The patient number varied between 26 and 463 in comparative studies (RCT and non-RCT) and between 29 and 345 in non-comparative studies. Fusion rate was reported in 14 studies and ranged between 68.5-100%. The most frequently reported complication was post-operative dysphagia or dysphonia, with incidences ranging between .5% and 14.4%. Revision surgery was the second most reported complication (14 studies) and ranged between 0% and 10.3%. Wound-related complications were reported in 6 studies and ranged between 0% and 22.8%.Conclusion: The overall reporting of complications was low with very few comparative studies. Reported complications with allografts are within the range of other osteobiologics and autografts and in most cases may not attributable to the use of osteobiologics and may be complications of the procedure itself. Comparative studies with a more robust methodology analyzing complications with allograft and other osteobiologics are needed to inform current practice with strong recommendations.

Development of an International AO Spine Guideline for the Use of Osteobiologics in Anterior Cervical Fusion and Decompression (AO-GO).

STUDY DESIGN: Methodological study for guideline development. OBJECTIVE: AO Spine Guideline for Using Osteobiologics (AO-GO) project for spine degenerative pathologies was an international, multidisciplinary collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in Anterior Cervical Fusion and Decompression (ACDF). The aim was to formulate precisely defined, clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics, considering regional preferences and cost-effectiveness. METHODS: Guideline was completed in two phases: Phase 1- evidence synthesis; Phase 2- recommendation development based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In Phase 1, key questions identified by a panel of experts were addressed in a series of systematic reviews of randomized and non-randomized studies. In Phase 2, the GRADE approach was used to formulate a series of recommendations, including expert panel discussions via web calls and face-to-face meetings. DISCUSSION: AO-GO aims to bridge an important gap between evidence and use of osteobiologics in spine fusion surgeries. Owing to differences in osteobiologics preparation and functional characteristics, regulatory requirements for approval may vary, therefore it is highly likely that these products enter market without quality clinical trials. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making processes in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries. In Phase 3, the guideline will be disseminated and validated using prospectively collected clinical data in a separate effort of the AO Spine Knowledge Forum Degenerative in a global multicenter clinical study.

The Evidence for the Use of Osteobiologics in Hybrid Constructs (Anterior Cervical Discectomy and Fusion and Total Disc Replacement) in Multilevel Cervical Degenerative Disc Disease: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVE: Examine the clinical evidence for the use of osteobiologics in hybrid surgery (combined anterior cervical discectomy and fusion (ACDF) and total disc replacement (TDR)) in patients with multilevel cervical degenerative disc disease (DDD). METHODS: PubMed and Embase were searched between January 2000 and August 2020. Clinical studies investigating 18-80 year old patients with multilevel cervical DDD who underwent hybrid surgery with or without the use of osteobiologics were considered eligible. Two reviewers independently screened and assessed the identified articles. The methodological index for non-randomized studies (MINORS) tool and the risk of bias (RoB 2.0) assessment tool were used to assess risk of bias. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to evaluate quality of evidence across studies per outcome. RESULTS: Eleven studies were included. A decrease in cervical range of motion was observed in most studies for both the hybrid surgery and the control groups consisting of stand-alone ACDF or TDR. Fusion rates of 70-100% were reported in both the hybrid surgery and control groups consisting of stand-alone ACDF. The hybrid surgery group performed better or comparable to the control group in terms of adjacent segment degeneration. Studies reported an improvement in visual analogue scale for pain and neck disability index values after surgery compared to preoperative scores for both treatment groups. The included studies had moderate methodological quality. CONCLUSIONS: There is insufficient evidence for assessing the use of osteobiologics in multilevel hybrid surgery and additional high quality and controlled research is deemed essential.

The Role of Osteobiologics in Augmenting Spine Fusion in Unplated Anterior Cervical Discectomy and Fusion Compared to Plated Constructs: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare clinical and radiographic outcomes as well as complications of unplated vs plated anterior cervical discectomy and fusion (ACDF) surgery considering the role of osteobiologics in single- and multi-level procedures. METHODS: A systematic search of PubMed/MEDLINE, Scopus, CINAHL, EMBASE, CENTRAL, Cochrane and ClinicalTrials.gov databases was performed. Briefly, we sought to identify studies comparing unplated vs. plated ACDF for cervical degenerative disc disease reporting the use of osteobiologics in terms of clinical outcomes, radiographic fusion, and complications. Data on study population, follow-up time, type of cage and plate used, type of osteobiologic employed, number of levels treated, patient-reported outcomes (PROs), radiographic outcomes and complications were collected and compared. Relevant information was pooled for meta-analyses. RESULTS: Thirty-eight studies met the inclusion criteria. No significant difference was found in terms of clinical outcomes between groups. Unplated ACDF was characterized by reduced blood loss, operation time and length of hospital stay. Fusion was achieved by the majority of patients in both groups, with no evidence of any specific contribution depending on the osteobiologics used. Dysphagia was more commonly associated with anterior plating, while cage subsidence prevailed in the unplated group. CONCLUSION: Unplated and plated ACDF seem to provide similar outcomes irrespective of the osteobiologic used, with minor differences with doubtful clinical significance. However, the heterogeneity and high risk of bias affecting included studies markedly prevent significant conclusions.

What Is the Evidence Supporting Osteobiologic Use in Revision Anterior Cervical Discectomy and Fusion?

STUDY DESIGN: Systematic literature review. OBJECTIVE: To analyze the literature and describe the evidence supporting osteobiologic use in revision anterior cervical discectomy and fusion (ACDF) surgery. METHODS: A systematic search of PubMed/MEDLINE, EMBASE, Cochrane library, and ClinicalTrials.gov databases was conducted for literature reporting the use of osteobiologics in revision ACDF. We searched for studies reporting outcomes of using any osteobiologic use in revision ACDF surgeries (independently of the number of levels) in the above databases. RESULTS: There are currently no studies in the literature describing the outcome and comparative efficacy of diverse osteobiologic agents in the context of revision ACDF surgery. A majority of the current evidence is based only upon studies involving primary ACDF surgery. CONCLUSION: The current study highlights the paucity of literature evidence on the role of diverse osteobiologics in revision ACDF, and foregrounds the need for high-quality evidence on this subject.

AO Spine Guideline for the Use of Osteobiologics (AOGO) in Anterior Cervical Discectomy and Fusion for Spinal Degenerative Cases.

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

Comparative Complications Associated With BMP Use In Patients Undergoing ACDF for Degenerative Spinal Conditions: Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic Review and Meta-Analysis. OBJECTIVES: To compare complication incidence in patients with or without the use of recombinant human Bone Morphogenic Protein-2 (BMP2) undergoing anterior cervical discectomy and fusion (ACDF) for degenerative conditions. METHODS: A systematic search of eight online databases was conducted using PRISMA guidelines. Inclusion criteria included English language studies with a minimum of 10 adult patients undergoing instrumented ACDF surgery for a degenerative spinal condition in which BMP2 was used in all patients or one of the treatment arms. Studies with patients undergoing circumferential fusions, with non-degenerative indications, or which did not report post-operative complication data were excluded. Patients with and without BMP2 were compared in terms of the incidence of dysphagia/dysphonia, anterior soft tissue complications (hematoma, seroma, infection, dysphagia/dysphonia), nonunion, medical complications, and new neurologic deficits. RESULTS: Of 1832 preliminary search results, 27 manuscripts were included. Meta-analysis revealed the relative risk of dysphagia or dysphonia (RR = 1.39, CI 95% 1.18 - 1.64, P = <.001), anterior soft tissue complications (RR = 1.43, CI 95% 1.25-1.64, P = <.001), and medical complications (RR = 1.32, CI 95% 1.06-1.66, P = .013) were statistically significant in the BMP2 group while the relative risk of non-union (RR = .5, CI 95% .23 - 1.13, P = .09) trended lower in the BMP2 group. Neurological deficit (RR = 1.06, CI 95% .82-1.37, P = .66), and additional medical complications (RR = 1.53, CI 95% .98-2.38, P = .06) were not found to be statistically different between the groups. CONCLUSIONS: This meta-analysis identified a high rate of arthrodesis when BMP2 was used in ACDF, but confirmed increased rates of dysphagia and anterior soft tissue complications. Surgeons may consider reserving BMP2 implementation for cases with a high risk of non-union, and should be aware of the risk of airway compromise.

Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (Polyether ether ketone, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? A Systematic Review.

STUDY DESIGN: Systematic Review of the Literature. OBJECTIVE: The purpose of this study was to perform a systematic review describing fusion rates for anterior cervical discectomy and fusion (ACDF) using autograft vs various interbody devices augmented with different osteobiologic materials. METHODS: A systematic review limited to the English language was performed in Medline, Embase and Cochrane library using Medical Subject Heading (MeSH) terms. Studies that evaluated fusion after ACDF using autografts and osteobiologics combined with PEEK, carbon fibre, or metal cages were searched for. Articles in full text that met the criteria were included in the review. The main outcomes evaluated were the time taken to merge, the definition of the fusion assessment, and the modality of the fusion assessment. The risk of bias of each article was assessed by the MINORS score or ROB 2.0 depending on the randomisation process. RESULTS: The total number of references reviewed was six hundred and eighty-two. After applying the inclusion criteria, 54 were selected for the retrieval of the full text. Eight studies were selected and included for final analysis in this study. Fusion rates were reported between 83.3% and 100% for autograft groups compared to 46.5% and 100% for various interbody device/osteobiological combinations. The overall quality of the evidence in all radiographic fusion studies was considered insufficient due to a serious risk of bias. CONCLUSION: Mechanical interbody devices augmented with osteobiologics performed similarly to autografts in terms of reliability and efficacy. Their time to fusion and fusion rate were comparable to autografts at the end of the final follow-up.

Complications With Demineralized Bone Matrix, Hydroxyapatite and Beta-Tricalcium Phosphate in Single and Two-Level Anterior Cervical Discectomy and Fusion Surgery.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To analyze the evidence available reporting complications in single or two-level anterior cervical discectomy and fusion (ACDF) using a demineralized bone matrix (DBM), hydroxyapatite (HA), or beta-tricalcium phosphate (ß-TCP). METHODS: A systematic review of the literature using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases was performed in August 2020 to identify studies reporting complications in one or two-level ACDF surgery using DBM, HA, or ß-TCP. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 1857 patients were included, 981 male and 876 female, across 17 articles; 5 prospective, and 12 retrospectives. We noted heterogeneity among the included studies concerning the study design and combination of graft materials utilized in them. However, we noted a higher incidence of adjacent segment disease (17.7%) and pseudoarthrosis (9.3%) in fusion constructs using DBM. Studies using ß-TCP reported a higher incidence of pseudoarthrosis (28.2%) and implant failures (17.9%). CONCLUSIONS: Degenerative cervical conditions treated with one or two-level ACDF surgery using DBM, HA, or ß-TCP with or without cervical plating are associated with complications such as adjacent segment disease, dysphagia, and pseudarthrosis. However, consequent to the study designs and clinical heterogeneity of the studies, it is not possible to correlate these complications accurately with any specific graft material employed. Further well-designed prospective studies are needed to correctly know the related morbidity of each graft used for achieving fusion in ACDF.

Structural Allograft Versus Mechanical Interbody Devices Augmented With Osteobiologics in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic Literature Review. OBJECTIVE: Perform a systematic review evaluating postoperative fusion rates for anterior cervical discectomy and fusion (ACDF) using structural allograft vs various interbody devices augmented with different osteobiologic materials. METHODS: Comprehensive literature search using PubMed, Embase, The Cochrane Library, and Web of Science was performed. Included studies were those that reported results of 1-4 levels ACDF using pure structural allograft compared with a mechanical interbody device augmented with an osteobiologic. Excluded studies were those that reported on ACDF with cervical corpectomy; anterior and posterior cervical fusions; circumferential (360° or 540°) fusion or revision ACDF for nonunion or other conditions. Risk of bias was determined using the Cochrane review guidelines. RESULTS: 8 articles reporting fusion rates of structural allograft and an interbody device/osteobiologic pair were included. All included studies compared fusion rates following ACDF among structural allograft vs non-allograft interbody device/osteobiologic pairs. Fusion rates were reported between 84% and 100% for structural allograft, while fusion rates for various interbody device/osteobiologic combinations ranged from 26% to 100%. Among non-allograft cage groups fusion rates varied from 73-100%. One study found PEEK cages filled with combinations of autograft, allograft, and demineralized bone matrix (DBM) to have an overall fusion rate of 26%. In one study comparing plate and zero-profile constructs, there was no difference in fusion rates for two-level fusions. CONCLUSION: There was limited data comparing fusion outcomes of patients undergoing ACDF using structural allograft vs interbody devices augmented with osteobiologic materials to support superiority of one method.

Comparison of Different Osteobiologics in Terms of Imaging Modalities and Time Frames for Fusion Assessment in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The study's primary objective was to determine how osteobiologic choice affects fusion rates in patients undergoing anterior cervical discectomy and fusion (ACDF). The study's secondary objectives were to 1) determine the optimal timing of fusion assessment following ACDF and 2) determine if osteobiologic type affects the timing and optimal modality of fusion assessment. METHODS: A systematic search of PubMed/MEDLINE was conducted for literature published from 2000 through October 2020 comparing anterior fusion in the cervical spine with various osteobiologics. Both comparative studies and case series of ≥10 patients were included. RESULTS: A total of 74 studies met the inclusion criteria. Seventeen studies evaluated the efficacy of autograft on fusion outcomes, and 23 studies assessed the efficacy of allograft on fusion outcomes. 3 studies evaluated the efficacy of demineralized bone matrix, and seven assessed the efficacy of rhBMP-2 on fusion outcomes. Other limited studies evaluated the efficacy of ceramics and bioactive glasses on fusion outcomes, and 4 assessed the efficacy of stem cell products. Most studies utilized dynamic radiographs for the assessment of fusion. Overall, there was a general lack of supportive data to determine the optimal timing of fusion assessment meaningfully or if osteobiologic type influenced fusion timing. CONCLUSIONS: Achieving fusion following ACDF appears to remain an intricate interplay between host biology and various surgical factors, including the selection of osteobiologics. While alternative osteobiologics to autograft exist and may produce acceptable fusion rates, limitations in study methodology prevent any definitive conclusions from existing literature.

The Use of Osteobiologics in Single versus Multi-Level Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic literature review. OBJECTIVES: In this study we assessed evidence for the use of osteobiologics in single vs multi-level anterior cervical discectomy and fusion (ACDF) in patients with cervical spine degeneration. The primary objective was to compare fusion rates after single and multi-level surgery with different osteobiologics. Secondary objectives were to compare differences in patient reported outcome measures (PROMs) and complications. METHODS: After a global team of reviewers was selected, a systematic review using different repositories was performed, confirming to PRISMA and GRADE guidelines. In total 1206 articles were identified and after applying inclusion and exclusion criteria, 11 articles were eligible for analysis. Extracted data included fusion rates, definition of fusion, patient reported outcome measures, types of osteobiologics used, complications, adverse events and revisions. RESULTS: Fusion rates ranged from 87.7% to 100% for bone morphogenetic protein 2 (BMP-2) and 88.6% to 94.7% for demineralized bone matrix, while fusion rates reported for other osteobiologics were lower. All included studies showed PROMs improved significantly for each osteobiologic. However, no differences were reported when comparing osteobiologics, or when comparing single vs multi-level surgery specifically. CONCLUSION: The highest fusion rates after 2-level ACDF for cervical spine degeneration were reported when BMP-2 was used. However, PROMs did not differ between the different osteobiologics. Further blinded randomized trials should be performed to compare the use of BMP-2 in single vs multi-level ACDF specifically.

Dosing Strategy for Osteobiologics Used in ACDF Surgery: Influence on Fusion Rates and Associated Complications. A Systematic Literature Review.

STUDY DESIGN: Systematic review. OBJECTIVE: To assess the available evidence related to dose-dependent effectiveness (i.e., bone fusion) and morbidity of osteobiologics used in anterior cervical discectomy and fusion (ACDF). METHODS: Studies with more than 9 adult patients with degenerated/herniated cervical discs operated for one-to four-levels ACDF reporting used osteobiologics doses, fusion rates at six months or later, and related comorbidities were included. PubMed, EMBASE, ClinicalTrials, and Cochrane were searched through September 2021. Data extracted in spread sheet and risk of bias assessed using MINORS and Rob-2. RESULTS: Sixteen studies were selected and sub-grouped into BMP and non-BMP osteobiologics. For the 10 BMP studies, doses varied from 0.26 to 2.1 mg in 649 patients with fusion rates of 95.3 to 100% at 12 months. For other osteobiologics, each of six studies reported one type of osteobiologic in certain dose/concentration/volume in a total of 580 patients with fusion rates of 6.8 to 96.9% at 12 months. Risk of bias was low in three of the 13 non-randomized (18.75%) and in all the three randomized studies (100%). CONCLUSIONS: Taking into account the inconsistent reporting within available literature, for BMP usage in ACDF, doses lower than 0.7 mg per level can achieve equal successful fusion rates as higher doses, and there is no complication-free dose proved yet. It seems that the lower the dose the lower the incidence of serious complications. As for non-BMP osteobiologics the studies are very limited for each osteobiologic and thus conclusions must be drawn individually and with caution.

What Is the Evidence Surrounding the Cost-Effectiveness of Osteobiologic Use in ACDF Surgery? A Systematic Review of the Literature.

STUDY DESIGN: This study constitutes a systematic review of the literature. OBJECTIVE: The aim of this study was to identify and present all available studies that report on the costs of osteobiologics used in anterior cervical discectomy and fusion (ACDF). METHODS: The literature was systematically reviewed to identify studies with specific inclusion criteria: (1) randomized controlled trials and observational studies, (2) in adult patients, (3) with herniated disc(s) or degenerative cervical spine disease, (4) reporting on either direct or indirect costs of using specific osteobiologics in an ACDF operation. (5) Only studies in English were included. The quality of the included studies was assessed using the MINORS and RoB 2.0 tools. RESULTS: Overall, 14 articles were included; one randomized controlled trial and 13 observational studies. The most commonly used osteobiologics other than autograft/iliac crest bone graft (ICBG) were allograft and bone morphogenetic protein (BMP). None of the studies was reported to be industry-supported. There was considerable heterogeneity on the reported costs. Overall, most studies reported on surgery-related costs, such as anesthesia, operating room, surgical materials and surgeon's fee. Only two studies, both using allograft, reported the exact cost of the osteobiologic used (450 GBP, $700). Some of the studies reported on the cost of care during hospitalization for the surgical operation, such as radiology studies, emergency room costs, cardiologic evaluation, laboratory studies, pharmacy costs, and room costs. Only a few studies reported on the cost of follow-up, reoperation, and physical therapy and rehabilitation. CONCLUSION: Based on the data of this current systematic review, no recommendations can be made regarding the cost-effectiveness of using osteobiologics in ACDF. Given the high costs of osteobiologics, this remains a topic of importance. The design of future studies on the subject should include cost effectiveness.

Do the Choice of Fusion Construct With and Without Autograft Influence the Fusion and Complication Rates in Patients Undergoing 1 or 2-Level Anterior Cervical Discectomy and Fusion Surgery? A PRISMA-Compliant Network Meta-Analysis.

STUDY DESIGN: Network meta-analysis. OBJECTIVES: To compare the fusion outcome and complications of different 1 or 2-level anterior cervical decompression and fusion (ACDF) constructs performed with and without the application of autografts. METHODS: We performed an independent and duplicate search in electronic databases including PubMed, Embase, Web of Science, Cochrane, and Scopus for relevant articles published between 2000 and 2020. We included comparative studies reporting fusion rate and complications with and without the use of autografts in ACDF across 5 different fusion constructs. A network meta-analysis was performed in Stata, categorized based on the type of fusion constructs utilized. Fusion constructs were ranked based on p-score approach and surface under cumulative ranking curve (SUCRA) scores. The confidence of results from the analysis was appraised with Cochrane's CINeMA approach. RESULTS: A total of 2216 patients from 22-studies including 6 Randomized Controlled Trials (RCTs) and 16 non-RCTs were included in network analysis. The mean age of included patients was 49.3 (±3.62) years. Based on our meta-analysis, we could conclude that use of autograft in 1- or 2-level ACDF did not affect the fusion and mechanical implant-related complications. The final fusion and mechanical complication rates were also not significantly different across the different fusion constructs. The use of plated constructs was associated with a significant increase in post-ACDF dysphagia rates [OR 3.42; 95%CI (.01,2.45)], as compared to stand-alone constructs analysed. CONCLUSION: The choice of fusion constructs and use of autografts does not significantly affect the fusion and overall complication rates following 1 or 2-level ACDF surgery.

Does the choice of chemoprophylaxis affect the prevention of deep vein thrombosis in lumbar fusion surgery? A systematic review of the literature.

Introduction: To date, the available guidance on venous thromboembolism (VTE) prevention in elective lumbar fusion surgery is largely open to surgeon interpretation and preference without any specific suggested chemoprophylactic regimen. Research question: This study aimed to comparatively analyze the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) with the use of commonly employed chemoprophylactic agents such as unfractionated heparin (UH) and low molecular weight heparin (LMWH) in lumbar fusion surgery. Material and methods: An independent systematic review of four scientific databases (PubMed, Scopus, clinicaltrials.gov, Web of Science) was performed to identify relevant articles as per the preferred reporting in systematic reviews and meta-analysis (PRISMA) guidelines. Studies reporting on DVT/PE outcomes of lumbar fusion surgery in adult patients with UH or LMWH chemoprophylaxis were included for analysis. Analysis was performed using the Stata software. Results: Twelve studies with 8495 patients were included in the analysis. A single-arm meta-analysis of the included studies found a DVT incidence of 14% (95%CI [8%-20%]) and 1% (95%CI [-6% - 8%]) with LMWH and UH respectively. Both the chemoprophylaxis agents prevented PE with a noted incidence of 0% (95%CI [0%-0.1%]) and 0% (95%CI [0%-1%]) with LMWH and UH respectively. The risk of bleeding-related complications with the usage of LMWH and UH was 0% (95% CI [0.0%-0.30%]) and 3% (95% CI [0.3%-5%]) respectively. Discussion and conclusion: Both LMWH and UH reduces the overall incidence of DVT/PE, but there is a paucity of evidence analyzing the comparative effectiveness of the chemoprophylaxis regimens in lumbar fusion procedures. The heterogeneity in data prevents any conclusions, as there remains an evidence gap. We recommend future high-quality randomized controlled trials to investigate in this regard to help develop recommendations on thromboprophylaxis usage.

Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.