Evolution of the AO Spine Sacral and Pelvic Classification System: a systematic review.

OBJECTIVE The purpose of this study was to describe the genesis of the AO Spine Sacral and Pelvic Classification System in the context of historical sacral and pelvic grading systems. METHODS A systematic search of MEDLINE, EMBASE, Google Scholar, and Cochrane databases was performed consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all existing sacral and pelvic fracture classification systems. RESULTS A total of 49 articles were included in this review, comprising 23 pelvic classification systems and 17 sacral grading schemes. The AO Spine Sacral and Pelvic Classification System represents both the evolutionary product of these historical systems and a reinvention of classic concepts in 5 ways. First, the classification introduces fracture types in a graduated order of biomechanical stability while also taking into consideration the neurological status of patients. Second, the traditional belief that Denis central zone III fractures have the highest rate of neurological deficit is not supported because this subgroup often includes a broad spectrum of injuries ranging from a benign sagittally oriented undisplaced fracture to an unstable "U-type" fracture. Third, the 1990 Isler lumbosacral system is adopted in its original format to divide injuries based on their likelihood of affecting posterior pelvic or spinopelvic stability. Fourth, new discrete fracture subtypes are introduced and the importance of bilateral injuries is acknowledged. Last, this is the first integrated sacral and pelvic classification to date. CONCLUSIONS The AO Spine Sacral and Pelvic Classification is a universally applicable system that redefines and reorders historical fracture morphologies into a rational hierarchy. This is the first classification to simultaneously address the biomechanical stability of the posterior pelvic complex and spinopelvic stability, while also taking into consideration neurological status. Further high-quality controlled trials are required prior to the inclusion of this novel classification within a validated scoring system to guide the management of sacral and pelvic injuries

Evolution of the AO Spine Sacral and Pelvic Classification System: A systematic review

OBJECTIVE: The purpose of this study was to describe the genesis of the AO Spine Sacral and Pelvic Classification System in the context of historical sacral and pelvic grading systems. METHODS: A systematic search of MEDLINE, EMBASE, Google Scholar, and Cochrane databases was performed consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify all existing sacral and pelvic fracture classification systems. RESULTS: A total of 49 articles were included in this review, comprising 23 pelvic classification systems and 17 sacral grading schemes. The AO Spine Sacral and Pelvic Classification System represents both the evolutionary product of these historical systems and a reinvention of classic concepts in 5 ways. First, the classification introduces fracture types in a graduated order of biomechanical stability while also taking into consideration the neurological status of patients. Second, the traditional belief that Denis central zone III fractures have the highest rate of neurological deficit is not supported because this subgroup often includes a broad spectrum of injuries ranging from a benign sagittally oriented undisplaced fracture to an unstable U-type fracture. Third, the 1990 Isler lumbosacral system is adopted in its original format to divide injuries based on their likelihood of affecting posterior pelvic or spinopelvic stability. Fourth, new discrete fracture subtypes are introduced and the importance of bilateral injuries is acknowledged. Last, this is the first integrated sacral and pelvic classification to date. CONCLUSIONS: The AO Spine Sacral and Pelvic Classification is a universally applicable system that redefines and reorders historical fracture morphologies into a rational hierarchy. This is the first classification to simultaneously address the biomechanical stability of the posterior pelvic complex and spinopelvic stability, while also taking into consideration neurological status. Further high-quality controlled trials are required prior to the inclusion of this novel classification within a validated scoring system to guide the management of sacral and pelvic injuries

Variations in management of A3 and A4 cervical spine fractures as designated by the AO Spine Subaxial Injury Classification System

Objective: Optimal management of A3 and A4 cervical spine fractures, as defined by the AO Spine Subaxial Injury Classification System, remains controversial. The objectives of this study were to determine whether significant management variations exist with respect to 1) fracture location across the upper, middle, and lower subaxial cervical spine and 2) geographic region, experience, or specialty. Methods: A survey was internationally distributed to 272 AO Spine members across six geographic regions (North America, South America, Europe, Africa, Asia, and the Middle East). Participants\u27 management of A3 and A4 subaxial cervical fractures across cervical regions was assessed in four clinical scenarios. Key characteristics considered in the vignettes included degree of neurological deficit, pain severity, cervical spine stability, presence of comorbidities, and fitness for surgery. Respondents were also directly asked about their preferences for operative management and misalignment acceptance across the subaxial cervical spine. Results: In total, 155 (57.0%) participants completed the survey. Pooled analysis demonstrated that surgeons were more likely to offer operative intervention for both A3 (p \u3c 0.001) and A4 (p \u3c 0.001) fractures located at the cervicothoracic junction compared with fractures at the upper or middle subaxial cervical regions. There were no significant variations in management for junctional incomplete (p = 0.116) or complete (p = 0.342) burst fractures between geographic regions. Surgeons with more than 10 years of experience were more likely to operatively manage A3 (p \u3c 0.001) and A4 (p \u3c 0.001) fractures than their younger counterparts. Neurosurgeons were more likely to offer surgical stabilization of A3 (p \u3c 0.001) and A4 (p \u3c 0.001) fractures than their orthopedic colleagues. Clinicians from both specialties agreed regarding their preference for fixation of lower junctional A3 (p = 0.866) and A4 (p = 0.368) fractures. Overall, surgical fixation was recommended more often for A4 than A3 fractures in all four scenarios (p \u3c 0.001). Conclusions: The subaxial cervical spine should not be considered a single unified entity. Both A3 and A4 fracture subtypes were more likely to be surgically managed at the cervicothoracic junction than the upper or middle subaxial cervical regions. The authors also determined that treatment strategies for A3 and A4 subaxial cervical spine fractures varied significantly, with the latter demonstrating a greater likelihood of operative management. These findings should be reflected in future subaxial cervical spine trauma algorithms

The AO Spine Thoracolumbar Injury Classification System and Treatment Algorithm in Decision Making for Thoracolumbar Burst Fractures Without Neurologic Deficit

STUDY DESIGN: Prospective Observational Study. OBJECTIVE: To determine the alignment of the AO Spine Thoracolumbar Injury Classification system and treatment algorithm with contemporary surgical decision making. METHODS: 183 cases of thoracolumbar burst fractures were reviewed by 22 AO Spine Knowledge Forum Trauma experts. These experienced clinicians classified the fracture morphology, integrity of the posterior ligamentous complex and degree of comminution. Management recommendations were collected. RESULTS: There was a statistically significant stepwise increase in rates of operative management with escalating category of injury (P \u3c .001). An excellent correlation existed between recommended expert management and the actual treatment of each injury category: A0/A1/A2 (OR 1.09, 95% CI 0.70-1.69, P = .71), A3/4 (OR 1.62, 95% CI 0.98-2.66, P = .58) and B1/B2/C (1.00, 95% CI 0.87-1.14, P = .99). Thoracolumbar A4 fractures were more likely to be surgically stabilized than A3 fractures (68.2% vs 30.9%, P \u3c .001). A modifier indicating indeterminate ligamentous injury increased the rate of operative management when comparing type B and C injuries to type A3/A4 injuries (OR 39.19, 95% CI 20.84-73.69, P \u3c .01 vs OR 27.72, 95% CI 14.68-52.33, P \u3c .01). CONCLUSIONS: The AO Spine Thoracolumbar Injury Classification system introduces fracture morphology in a rational and hierarchical manner of escalating severity. Thoracolumbar A4 complete burst fractures were more likely to be operatively managed than A3 fractures. Flexion-distraction type B injuries and translational type C injuries were much more likely to have surgery recommended than type A fractures regardless of the M1 modifier. A suspected posterior ligamentous injury increased the likelihood of surgeons favoring surgical stabilization

Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE null Mice.

Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE null mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE null hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p < 0.05), nitric oxide (p < 0.01), altered lipid profiles (cholesterol, triglycerides, Chylomicrons, VLDL) (p < 0.05) as well as accelerated aortic plaque formation in ApoE null mice (p < 0.05). Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model

Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer. The rationale behind their therapeutic ability is that they can transfer signaling biomolecules, and subsequently induce metabolic and physiological changes in diseased cells and tissues. In addition, exosomes can be used as a drug delivery system and may be very effective at reducing toxicity and increasing bioavailability of therapeutic molecules and drugs. Although exosomes were first believed to be a waste product of the cell, current research has demonstrated that these particles can serve as modulators of the immune system, act as cancer biomarkers, cause re-differentiation of cancer cells, and induce apoptosis in diseased cells. Extensive research has been performed specifically using amniotic fluid-derived extracellular vesicles, named "cytosomes". While the use of cytosomes in clinical application is still in the early stages, researchers have shown great potential for these EVs in regenerative medicine as immune modulators, in controlling microbial infection and by inducing tissue repair through the activation of endogenous, tissue-specific stem cells. This review emphasizes the capabilities of specific subsets of extracellular vesicles that can potentially be used for cancer therapy, principally as a source of bi-informational reprogramming for malignant cells

CRISPR genome editing of murine hematopoietic stem cells to create Npm1-Alk causes ALK+ lymphoma after transplantation

CRISPR/Cas9 genomic editing of wild-type hematopoietic stem cells generates Npm1-Alk , leading to ALK + large-cell lymphomas in recipients. CD30 + postthymic T-cell lymphomas are polyclonal but transplantable to secondary recipients with long latency