Systematic Review and Meta-Analysis of the Effect of Osteoporosis on Fusion Rates and Complications Following Surgery for Degenerative Cervical Spine Pathology.

BACKGROUND: As the elderly population grows, the increasing prevalence of osteoporosis presents a unique challenge for surgeons. Decreased bone strength and quality are associated with hardware failure and impaired bone healing, which may increase the rate of revision surgery and the development of complications. The purpose of this review is to determine the impact of osteoporosis on postoperative outcomes for patients with cervical degenerative disease or deformity. METHODS: A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Medical Subject Headings terms involving spine surgery for cervical degenerative disease and osteoporosis were performed. This review focused on radiographic outcomes, as well as surgical and medical complications. RESULTS: There were 16 studies included in the degenerative group and 9 in the deformity group. Across degenerative studies, lower bone mineral density was associated with increased rates of cage subsidence in osteoporotic patients undergoing operative treatment for cervical degenerative disease. Most studies reported varied results on the relationship between osteoporosis and other outcomes such as revision and readmission rates, costs, and perioperative complications. Our meta-analysis suggests that osteoporotic patients carry a greater risk of reduced fusion rates at 6 months and 1 year postoperatively. With respect to cervical deformity correction, although individual complication rates were unchanged with osteoporosis, the collective risk of incurring any complication may be increased in patients with poor bone stock. CONCLUSIONS: Overall, the literature suggests that outcomes for osteoporotic patients after cervical spine surgery are multifactorial. Osteoporosis seems to be a significant risk factor for developing cage subsidence and pseudarthrosis postoperatively, whereas reports on medical and hospital-related metrics were inconclusive. Our findings highlight the challenges of caring for osteoporotic patients and underline the need for adequately powered studies to understand how osteoporosis changes the risk index of patients undergoing cervical spine surgery. CLINICAL RELEVANCE: In patients undergoing cervical spine surgery for degenerative disease, osteoporosis is a significant risk factor for long-term postoperative complications-notably cage subsidence and pseudarthrosis. Given the elective nature of these procedures, interdisciplinary collaboration between providers should be routinely implemented to enable medical optimization of patients prior to cervical spine surgery.

Systematic Review and Meta-Analysis of the Effect of Osteoporosis on Reoperation Rates and Complications after Surgical Management of Lumbar Degenerative Disease.

BACKGROUND: There is considerable heterogeneity in findings and a lack of consensus regarding the interplay between osteoporosis and outcomes in patients with lumbar degenerative spine disease. Therefore, the purpose of this systematic review and meta-analysis was to gather and analyze existing data on the effect of osteoporosis on radiographic, surgical, and clinical outcomes following surgery for lumbar degenerative spinal disease. METHODS: A systematic review was performed to determine the effect of osteoporosis on the incidence of adverse outcomes after surgical intervention for lumbar degenerative spinal diseases. The approach focused on the radiographic outcomes, reoperation rates, and other medical and surgical complications. Subsequently, a meta-analysis was performed on the eligible studies. RESULTS: The results of the meta-analysis suggested that osteoporotic patients experienced increased rates of adjacent segment disease (ASD; p=0.015) and cage subsidence (p=0.001) while demonstrating lower reoperation rates than non-osteoporotic patients (7.4% vs. 13.1%; p=0.038). The systematic review also indicated that the length of stay, overall costs, rates of screw loosening, and rates of wound and other medical complications may increase in patients with a lower bone mineral density. Fusion rates, as well as patient-reported and clinical outcomes, did not differ significantly between osteoporotic and non-osteoporotic patients. CONCLUSIONS: Osteoporosis was associated with an increased risk of ASD, cage migration, and possibly postoperative screw loosening, as well as longer hospital stays, incurring higher costs and an increased likelihood of postoperative complications. However, a link was not established between osteoporosis and poor clinical outcomes.

The Effect of Osteoporosis on Complications and Reoperation Rates After Surgical Management of Adult Thoracolumbar Spinal Deformity: A Systematic Review and Meta Analysis.

STUDY DESIGN: Systematic Review. OBJECTIVES: While substantial research has explored the impact of osteoporosis on patients undergoing adult spinal deformity (ASD) correction, the literature remains inconclusive. As such, the purpose of this study is to synthesize and analyze existing studies pertaining to osteoporosis as a predictor of postoperative outcomes in ASD surgery. METHODS: We performed a systematic review and meta-analysis to determine the effect that a diagnosis of osteoporosis, based on ICD-10 coding, dual-energy X-ray absorptiometry (DEXA) or computed tomography, has on the incidence of adverse outcomes following surgical correction of ASD. Statistical analysis was performed using Comprehensive Meta-Analysis (Version 2) using a random effects model to account for heterogeneity between studies. RESULTS: After application of inclusion and exclusion criteria, 36 and 28 articles were included in the systematic review and meta-analysis, respectively. The meta-analysis identified greater rates of screw loosening amongst osteoporotic patients (70.5% vs 31.9%, P = .009), and decreased bone mineral density in patients who developed proximal junctional kyphosis (PJK) (.69 vs .79 g/cm2, P = .001). The systematic review demonstrated significantly increased risk of any complication, reoperation, and proximal junctional failure (PJF) associated with reduced bone density. No statistical difference was observed between groups regarding fusion rates, readmission rates, and patient-reported and/or functional outcome scores. CONCLUSION: This study demonstrates a higher incidence of screw loosening, PJK, and revision surgery amongst osteoporotic ASD patients. Future investigations should explore outcomes at various follow-up intervals in order to better characterize how risk changes with time and to tailor preoperative planning based on patient-specific characteristics.

Development and characterization of an automated active mixing platform for hydrogel bioink preparation.

Bioink preparation is an important yet challenging step for bioprinting with hydrogels, as it involves fast and homogeneous mixing of various viscous components. In this study, we have developed an automated active mixing platform (AAMP), which allows for high-quality preparation of hydrogel bioinks. The design of AAMP, adapted from syringe pumps, provides many advantages, including low cost, automated control, high precision, customizability, and great cytocompatibility, as well as the potential to intelligently detect the homogeneity. To demonstrate the capability of AAMP, mixing of different hydrogel components, including alginate and xanthan gum with and without Ca2+, alginate and Laponite, PEGDMA and xanthan gum, was performed to investigate an alginate hydrogel preparation process. Colorimetric analyses were carried out to evaluate the mixing outcome with AAMP. Result showed that AAMP can prepare homogeneous hydrogel mixing in a fast and automated fashion. A multiphysics COMSOL simulation is carried out to further validate the results. Moreover, cell viability and proliferation study were performed in a cell encapsulation mixing experiment to validate the cytocompatibility of the AAMP. The AAMP has demonstrated great capability in hydrogel bioink preparation and could therefore holds great promise and wide applications in bioprinting and tissue engineering.

Somatic Lineage Reprogramming.

Embryonic development and cell specification have been viewed as an epigenetically rigid process. Through accumulation of irreversible epigenetic marks, the differentiation process has been considered unidirectional, and once completed cell specification would be permanent and stable. However, somatic cell nuclear transfer that involved the implantation of a somatic nucleus into a previously enucleated oocyte accomplished in amphibians in the 1950s and in mammals in the late 1990s-resulting in the birth of "Dolly the sheep"-clearly showed that "terminal" differentiation is reversible. In parallel, work on lineage-determining factors like MyoD revealed surprising potential to modulate lineage identity in somatic cells. This work culminated in the discovery that a set of four defined factors can reprogram fibroblasts into induced pluripotent stem (iPS) cells, which were shown to be molecularly and functionally equivalent to blastocyst-derived embryonic stem (ES) cells, thus essentially showing that defined factors can induce authentic reprogramming without the need of oocytes. This concept was further extended when it was shown that fibroblasts can be directly converted into neurons, showing induced lineage conversion is possible even between cells representing two different germ layers. These findings suggest that "everything is possible" (i.e., once key lineage reprogramming factors are identified, cells should be able to convert into any desired lineage).

Neuroligin-4 Regulates Excitatory Synaptic Transmission in Human Neurons.

The autism-associated synaptic-adhesion gene Neuroligin-4 (NLGN4) is poorly conserved evolutionarily, limiting conclusions from Nlgn4 mouse models for human cells. Here, we show that the cellular and subcellular expression of human and murine Neuroligin-4 differ, with human Neuroligin-4 primarily expressed in cerebral cortex and localized to excitatory synapses. Overexpression of NLGN4 in human embryonic stem cell-derived neurons resulted in an increase in excitatory synapse numbers but a remarkable decrease in synaptic strength. Human neurons carrying the syndromic autism mutation NLGN4-R704C also formed more excitatory synapses but with increased functional synaptic transmission due to a postsynaptic mechanism, while genetic loss of NLGN4 did not significantly affect synapses in the human neurons analyzed. Thus, the NLGN4-R704C mutation represents a change-of-function mutation. Our work reveals contrasting roles of NLGN4 in human and mouse neurons, suggesting that human evolution has impacted even fundamental cell biological processes generally assumed to be highly conserved.