Radiologic Assessment of Interbody Fusion: A Systematic Review on the Use, Reliability, and Accuracy of Current Fusion Criteria.

BACKGROUND: Lumbar interbody fusion (IF) is a common procedure to fuse the anterior spine. However, a lack of consensus on image-based fusion assessment limits the validity and comparison of IF studies. This systematic review aims to (1) report on IF assessment strategies and definitions and (2) summarize available literature on the diagnostic reliability and accuracy of these assessments. METHODS: Two searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Search 1 identified studies on adult lumbar IF that provided a detailed description of image-based fusion assessment. Search 2 analyzed studies on the reliability of specific fusion criteria/classifications and the accuracy assessed with surgical exploration. RESULTS: A total of 442 studies were included for search 1 and 8 studies for search 2. Fusion assessment throughout the literature was highly variable. Eighteen definitions and more than 250 unique fusion assessment methods were identified. The criteria that showed most consistent use were continuity of bony bridging, radiolucency around the cage, and angular motion <5°. However, reliability and accuracy studies were scarce. CONCLUSION: This review highlights the challenges in reaching consensus on IF assessment. The variability in IF assessment is very high, which limits the translatability of studies. Accuracy studies are needed to guide innovations of assessment. Future IF assessment strategies should focus on the standardization of computed tomography-based continuity of bony bridging. Knowledge from preclinical and imaging studies can add valuable information to this ongoing discussion. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Bone Regeneration in a Large Animal Model Featuring a Modular Off-the-Shelf Soft Callus Mimetic.

Implantation of engineered cartilage with soft callus features triggers remodeling to bone tissue via endochondral bone regeneration (EBR). Thus far, EBR has not progressed to the level of large animals on the axis of clinical translation. Herein, the feasibility of EBR is aimed for a critical-sized defect in a large animal model. Chondrogenesis is first induced in goat-derived multipotent mesenchymal stromal cells (MSCs) by fine-tuning the cellular differentiation process. Through a unique devitalization process, two off-the-shelf constructs aimed to recapitulate the different stages of the transient cartilaginous soft callus template in EBR are generated. To evaluate bone regeneration, the materials are implanted in an adapted bilateral iliac crest defect model in goats, featuring a novel titanium star-shaped spacer. After 3 months, the group at the more advanced differentiation stage shows remarkable regenerative capacity, with comparable amounts of bone regeneration as the autograft group. In contrast, while the biomaterial mimicking the earlier stages of chondrogenesis shows improved regeneration compared to the negative controls, this is subpar compared to the more advanced material. Concluding, EBR is attainable in large animals with a soft callus mimetic material that leads to fast conversion into centimeter-scale bone, which prospects successful implementation in the human clinics.

Preclinical model for lumbar interbody fusion in small ruminants: Rationale and guideline.

Lumbar interbody fusion (IF) is a common procedure to obtain fusion of the spine by replacement of the intervertebral disc with a cage. Optimization of spinal cages is ongoing to reduce complications such as a pseudoarthrosis and subsidence of the cage. IF animal models (primate, dog, pig, goat and sheep) remain important to assess implant effectivity. But currently the available literature is dispersed and not IF model specific. Therefore unwanted inconsistencies between studies occur that limit generalizability. Based on our experience, anatomical preparation and literature research, we present a rationale for species selection and a practical guide for the surgical procedure in the goat animal model. The translational Potential of this Article: Rigorous methodologic design is an important means to improve translational value and generalizability of large animal IF efficacy studies. This paper provides a rationale and practical guide for animal selection and surgical decision making that can help reduce unnecessary variation between models and improve methodologic rigor and documentation for future experiments.

Assessment of Posterolateral Lumbar Fusion: A Systematic Review of Imaging-Based Fusion Criteria.

BACKGROUND: Noninvasive assessment of osseous fusion after spinal fusion surgery is essential for timely diagnosis of patients with symptomatic pseudarthrosis and for evaluation of the performance of spinal fusion procedures. There is, however, no consensus on the definition and assessment of successful posterolateral fusion (PLF) of the lumbar spine. This systematic review aimed to (1) summarize the criteria used for imaging-based fusion assessment after instrumented PLF and (2) evaluate their diagnostic accuracy and reliability. METHODS: First, a search of the literature was conducted in November 2018 to identify reproducible criteria for imaging-based fusion assessment after primary instrumented PLF between T10 and S1 in adult patients, and to determine their frequency of use. A second search in July 2021 was directed at primary studies on the diagnostic accuracy (with surgical exploration as the reference) and/or reliability (interobserver and intraobserver agreement) of these criteria. Article selection and data extraction were performed by at least 2 reviewers independently. The methodological quality of validation studies was assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and QAREL (Quality Appraisal of Reliability Studies). RESULTS: Of the 187 articles included from the first search, 47% used a classification system and 63% used ≥1 descriptive criterion related to osseous bridging (104 articles), absence of motion (78 articles), and/or absence of static signs of nonunion (39 articles). A great variation in terminology, cutoff values, and assessed anatomical locations was observed. While the use of computed tomography (CT) increased over time, radiographs remained predominant. The second search yielded 11 articles with considerable variation in outcomes and quality concerns. Agreement between imaging-based assessment and surgical exploration with regard to demonstration of fusion ranged between 55% and 80%, while reliability ranged from poor to excellent. CONCLUSIONS: None of the available criteria for noninvasive assessment of fusion status after instrumented PLF were demonstrated to have both sufficient accuracy and reliability. Further elaboration and validation of a well-defined systematic CT-based assessment method that allows grading of the intertransverse and interfacet fusion mass at each side of each fusion level and includes signs of nonunion is recommended. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Joint arthropathy at the cranio-vertebral junction. Scintigraphic patterns on bone SPECT/CT.

Osteoarthritic degeneration at the cranio-vertebral junction (CVJ) is an underrecognized source of suboccipital and neck pain, limited range of motion and cervicogenic headaches. Correlation of radiographic findings with clinical symptoms is often difficult. Limited evidence currently exists to support the use of bone single-photon emission computed tomography/computed tomography (SPECT/CT) in this subgroup of patients. The aim of this study was to describe the scintigraphic patterns of joint arthropathy at the CVJ on bone SPECT/CT in patients with suboccipital/neck pain and cervicogenic headache. Patients with more than 3 months of suboccipital/neck pain/cervicogenic headache and abnormal SPECT/CT findings at the CVJ were included. Patients with known/suspected malignancy, trauma, infectious processes and previous surgery at the CVJ were excluded. Neck disability index (NDI), visual analogue scale (VAS) and treatment were recorded for each patient. Patterns of osteoblastic activity at the CVJ on bone SPECT/CT were described and correlated with arthritic changes on conventional scans. Eighteen patients were included (10 females, mean age 68). Mean NDI score was 22. Mean VAS was 7.5. On bone SPECT/CT, it was found that 13 patients had high osteoblastic activity unilaterally at the atlanto-axial joint (AAJ); two patients at the atlanto-dental joint (ADJ), one at the occipito-atlantal joint (OAJ), one at both OAJ and ADJ and one at the level of C2 pars/pedicle unilaterally. Metabolic activity on SPECT/CT was associated with severe degenerative changes on CT scans. The ability of hybrid bone SPECT/CT to precisely localize osteoblastic activity at the CVJ may provide significant improvement in the diagnosis and treatment of patients with suboccipital/neck pain and joint arthropathy at the CVJ. Further clinical studies are needed to establish the real clinical impact of bone SPECT/CT in the treatment of patients with suboccipital neck pain.

Serum leptin is not altered nor related to cognitive decline in Alzheimer's disease.

BACKGROUND: Low plasma leptin levels can be a risk factor for Alzheimer's disease (AD) but the relation of leptin with disease progression in clinical AD is unknown. OBJECTIVE: The aim of this study was to investigate the relation between serum leptin concentrations and cognitive decline in clinical AD. METHODS: Serum leptin levels were analyzed in 295 non-obese subjects including healthy controls (n = 65), patients with subjective memory complaints (n = 99), patients with AD (n = 100), and patients with vascular dementia (n = 31). Leptin levels were related to hippocampal atrophy, baseline Mini-Mental State Examination (MMSE) scores and annual decline in MMSE measured over 2 years (range 0.4-4.5 years). RESULTS: Serum leptin levels were similar in AD patients compared to healthy controls and patients with subjective memory complaints. No correlation was observed between leptin concentrations and MMSE, annual change in MMSE during follow-up or atrophy. CONCLUSION: Serum leptin levels are not altered in this population of relatively young AD or vascular dementia patients (mean 60) compared to healthy and clinical control groups and were not related to cognitive decline. These results suggest that peripheral leptin levels do not play a role in evolution of AD pathology.