Faculty Bibliography

STUDY DESIGN/METHODS: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.

STUDY DESIGN/METHODS: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/CONCLUSIONS: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.

STUDY DESIGN/METHODS:Systematic Review and Meta-Analysis. OBJECTIVES/OBJECTIVE: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:= .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.

STUDY DESIGN/METHODS: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/CONCLUSIONS: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.

STUDY DESIGN/METHODS:Systematic review. OBJECTIVES/OBJECTIVE: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.

STUDY DESIGN/METHODS:Guideline. OBJECTIVES/OBJECTIVE: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/CONCLUSIONS: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.

STUDY DESIGN/METHODS: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.

STUDY DESIGN/METHODS: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/CONCLUSIONS: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.

PURPOSE/OBJECTIVE:To evaluate the relationship between nerve root retraction time, post-operative radiculitis and patient reported outcomes. METHODS:Patients who underwent single- or multi-level lumbar discectomy between 2020 and 2022 for lumbar disk herniations were prospectively followed with pre-operative, interoperative and post-operative variables including radiculitis and patient reported outcomes including VAS, ODI and CAT domains Pain interference, Pain intensity and Physical function. Intraoperative nerve root retraction time was recorded. Paired sample two-tailed t-test and multivariate regression were utilized with p < 0.05 being significant. RESULTS:A total of 157 patients who underwent single- or multi-level endoscopic lumbar discectomy. Average patient age was 44 years, and 64% were male patients. Nerve retraction time ranged from 4 to 15 min. Eighteen percent reported new radiculitis at 2-weeks post-operatively. In patients with new-onset radiculitis 79.2% reported significantly worse VAS leg at 2 weeks post-operative (4.2 vs. 8.3, p < 0.001) compared to 12.5% who had improved VAS leg (9.3 vs. 7, p = 0.1181). Patients with radiculitis and worse VAS scores had substantially longer nerve retraction time (13.8 ± 7.5 min) than patients with improved VAS leg (6.7 ± 1.2 min). At 6 months, patients with longer nerve retraction time had no significant improvement in the ODI or CAT compared to the baseline. CONCLUSIONS:This is the first study in discectomy literature to show that new onset radiculitis and poorer outcomes in VAS leg correlate with longer nerve retraction time at early and later time points.