Tendon Healing in a Mouse Model of Loeys-Dietz Syndrome: Controlled Study Using a Patellar Tendon Transection Model.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant connective tissue disorder caused by genetic mutations in the transforming growth factor-ß (TGFß) signaling pathway. In addition to vascular malformations, patients with LDS commonly present with bone and tendon abnormalities, including joint laxity. While TGFß signaling dysregulation has been implicated in many of these clinical manifestations, the degree to which it influences the tendinopathy and tendon healing issues in LDS has not been determined. METHODS: Wound healing after patellar tendon transection was compared between wild-type (WT) and Tgfbr2-mutant (LDS) mice (7 mice per group). In all mice, the right patellar tendon was transected at midsubstance, while the left was untouched to serve as a control. Mice were euthanized 6 weeks after surgery. Tendon specimens were harvested for histopathologic grading according to a previously validated scoring metric, and gene expression levels of Mmp2, Tgfb2, and other TGFß-signaling genes were assayed. Between-group comparisons were made using 1-way analysis of variance with post hoc Tukey honestly significant difference testing. RESULTS: Expression levels of assayed genes were similar between LDS and WT tendons at baseline; however, at 6 weeks after patellar tendon transection, LDS tendons showed sustained elevations in Mmp2 and Tgfb2 compared with baseline values; these elevations were not seen in normal tendons undergoing the same treatments. Histologically, untreated LDS tendons had significantly greater cellularity and cell rounding compared with untreated WT tendons, and both WT and LDS tendons had significantly worse histologic scores after surgery. CONCLUSION: We present the first mechanistic insight into the effect of LDS on tendons and tendon healing. The morphologic differences between LDS and WT tendons at baseline may help explain the increased risk of tendon/ligament dysfunction in patients with LDS, and the differential healing response to injury in LDS may account for the delayed healing and weaker repair tissue. LEVEL OF EVIDENCE: Level V.

Low-Intensity Pulsed Ultrasound as a Potential Adjuvant Therapy to Promote Spinal Fusion: Systematic Review and Meta-analysis of the Available Data.

Despite extensive research, nonunion continues to affect a nontrivial proportion of patients undergoing spinal fusion. Recently, preclinical studies have suggested that low-intensity pulsed ultrasound (LIPUS) may increase rates of spinal fusion. In this study, we summarized the available in vivo literature evaluating the effect of LIPUS on spinal fusion and performed a meta-analysis of the available data to estimate the degree to which LIPUS may mediate higher fusion rates. Across 13 preclinical studies, LIPUS was associated with a 9-fold increase in the odds of successful spinal fusion. Future studies are necessary to establish the benefit of LIPUS on spinal fusion in clinical populations.

Role of the Pubic Symphysis in Osseous Pelvic Development: A Novel Model of Bladder Exstrophy in Rabbits.

BACKGROUND: It has been posited that the osseous pelvic anomalies seen in patients with classic bladder exstrophy (CBE) result from disruption of the pubic symphysis. This hypothesis, however, has not been tested. In the present animal study, our objective was to determine whether the tension of the pubic symphysis helps maintain the shape of the pelvic ring, or whether the growing bones maintain a ring shape even without the tension of the symphysis. METHODS: In total, 12 neonatal New Zealand White rabbits underwent pubic symphysiotomy (experimental group, n=9) or sham surgery (control group, n=3) on days 3 or 4 of life. Rabbits were scanned with cone-beam computed tomography at 1, 4, 12, and 20 weeks postoperatively to monitor changes in the following pelvic parameters, which are known to be altered in CBE: anterior segment angle, anterior segment length, intertriradiate distance, interpubic distance, and posterior segment angle. Changes within the experimental and control groups were evaluated using repeated-measures analysis of variance and post hoc Tukey honest significant difference testing. Two-tailed t tests were used to compare treatment groups at each time point. RESULTS: Both groups showed increases in anterior segment length and intertriradiate distance during the study period; rabbits in the experimental group also showed a steady increase in interpubic distance (F=43.9; P<0.001). Experimental rabbits had significantly larger mean values for anterior segment angle, intertriradiate distance, interpubic distance, and posterior segment angle than did control rabbits at all time points. We found no difference in mean anterior segment length between control and experimental groups at any time point. The difference in interpubic distance was particularly pronounced by 20 weeks (experimental group, 13±2.7 mm; control group, 1.1±0.1 mm; P<0.001). CONCLUSIONS: The pubic symphysis is essential for normal pelvic development. Its absence led to early pelvic angulation and progressive pubic separation in a rabbit model. However, we found no significant difference in the mean anterior segment length, and it is likely that other factors are also implicated in the growth disturbance seen in CBE. LEVEL OF EVIDENCE: Level V.

The Spatial Order of Physeal Maturation in the Normal Human Knee Using Magnetic Resonance Imaging.

BACKGROUND: The spatial order of physeal maturation around the distal tibia has been shown to place adolescent patients at risk for certain transitional injuries, such as Tillaux or triplane fractures. Less is known about physeal maturation around the knee. The purpose of this study was to establish the spatial order of physeal maturation in the normal human knee using magnetic resonance imaging (MRI). METHODS: We retrospectively collected all knee MRI scans from patients presenting to our institution from January 2004 to January 2014. Patients who were suspected on the basis of clinical or radiographic findings of having abnormal knee physeal development or injury were excluded. We then applied a previously described MRI staging system of knee physeal maturation to the MRI scans of the remaining patients at 8 defined knee locations. Associations between the stage of maturation and mean chronological age were then evaluated across the 8 knee locations. Interrater and intrarater reliabilities were assessed. RESULTS: A total of 165 knee MRI scans (from 98 boys, 67 girls) met the inclusion criteria. Significant differences were found between each stage of physeal maturation and the mean chronological ages at all 8 knee locations for both boys and girls (each, P<0.001). Interestingly, within each stage of physeal maturation, no significant difference was found in the mean chronological ages at any of the 8 knee locations, suggesting that physeal development occurs uniformly in the normal human knee for both boys and girls. Interrater and intrarater reliability were nearly perfect at all locations. CONCLUSIONS: The spatial order of physeal maturation in the normal human knee was uniform across 8 knee locations for both boys and girls. This uniformity may help to explain why transitional injuries do not follow a recognizable pattern in the knee. Furthermore, the uniformity aids with surgical decision making, because minimal growth modulation or disturbance is likely when early physeal closure is present in a portion of the physis. LEVEL OF EVIDENCE: Level III.

Gene Therapy and Spinal Fusion: Systematic Review and Meta-Analysis of the Available Data.

OBJECTIVE: To analyze the extant literature describing the application of gene therapy to spinal fusion. METHODS: A systematic review of the English-language literature was performed. The search query was designed to include all published studies examining gene therapy approaches to promote spinal fusion. Approaches were classified as ex vivo (delivery of genetically modified cells) or in vivo (delivery of growth factors via vectors). The primary endpoint was fusion rate. Random effects meta-analyses were performed to calculate the overall odds ratio (OR) of fusion using a gene therapy approach and overall fusion rate. Subgroup analyses of fusion rate were also performed for each gene therapy approach. RESULTS: Of 1179 results, 35 articles met criteria for inclusion (all preclinical), of which 26 utilized ex vivo approaches and 9 utilized in vivo approaches. Twenty-seven articles (431 animals) were included in the meta-analysis. Gene therapy use was associated with significantly higher fusion rates (OR 77; 95% confidence interval {CI}: [31, 192]; P < 0.001); ex vivo strategies had a greater effect (OR 136) relative to in vivo strategies (OR 18) (P = 0.017). The overall fusion rate using a gene therapy approach was 80% (95% CI: [62%, 93%]; P < 0.001); overall fusion rates were significantly higher in subjects treated with ex vivo compared to in vivo strategies (90% vs. 42%; P = 0.011). For both ex vivo and in vivo approaches, the effect of gene therapy on fusion was independent of animal model. CONCLUSIONS: Gene therapy may augment spinal fusion; however, future investigation in clinical populations is necessary.

Synthesis and evaluation of a novel vancomycin-infused, biomimetic bone graft using a rat model of spinal implant-associated infection.

Background: Postoperative infection is a complication of spinal fusion surgery resulting in increased patient morbidity. Strategies including intraoperative application of powdered vancomycin have been proposed to reduce the incidence of infection; however, such antimicrobial effects are short-lived. Methods: Instrumentation of the L4-L5 vertebrae was performed mimicking pedicle screw and rod fixation in 30 rats. Titanium instrumentation inoculated with either PBS or 1×105 CFU bioluminescent MRSA, along with biomimetic bone grafts infused with varying concentrations of vancomycin and 125 µg of rhBMP-2 (BioMim-rhBMP-2-VCM) were implanted prior to closure. Infection was quantified during the six-week postoperative period using bioluminescent imaging. Arthrodesis was evaluated using micro-CT. Results: Infected animals receiving a bone graft infused with low-dose (0.18 mg/g) or high-dose vancomycin (0.89 mg/g) both exhibited significantly lower bioluminescent signal over the six-week postoperative period than control animals inoculated with MRSA and implanted with bone grafts lacking vancomycin (p=.019 and p=.007, respectively). Both low and high-dose vancomycin-infused grafts also resulted in a statistically significant reduction in average bioluminescence when compared to control animals (p=.027 and p=.047, respectively), independent of time. MicroCT analysis of animals from each group revealed pseudoarthrosis only in the control group, suggesting a correlation between infection and pseudoarthrosis. MRSA-inoculated control animals also had significantly less bone volume formation on micro-CT than the PBS-inoculated control cohort (p<.001), the MRSA+low-dose vancomycin-infused bone graft cohort (p<.001), and the MRSA+high-dose vancomycin-infused bone graft cohort (p<.001). Conclusion: BioMim-rhBMP-2-VCM presents a novel tissue engineering approach to simultaneously promoting arthrodesis and antimicrobial prophylaxis in spinal fusion. Despite mixed evidence of potential osteotoxicity of vancomycin reported in literature, BioMim-rhBMP-2-VCM preserved arthrodesis and osteogenesis with increasing vancomycin loading doses due to the graft's osteoinductive composition.

In-Human Report of S2 Alar-Iliac Screw Placement Using Augmented Reality Assistance.

BACKGROUND: S2 alar-iliac (S2AI) screws provide spinopelvic fixation with the advantages of minimized dissection, easier rod contouring, and decreased symptomatic screw-head prominence. However, placement of S2AI screws may be challenging because of the anatomy of the lumbosacral junction. Augmented reality is a nascent technology that may enhance placement of S2AI screws. OBJECTIVE: To report the first in-human placement of augmented reality (AR)-assisted S2 alar-iliac screws and evaluate the accuracy of screw placement. METHODS: A retrospective review was performed of patients who underwent AR-assisted S2AI screw placement. All surgeries were performed by 2 neurosurgeons using an AR head-mounted display (Xvision, Augmedics). Screw accuracy was analyzed in a blinded fashion by an independent neuroradiologist using the cortical breach grading scale. RESULTS: Twelve patients underwent AR-assisted S2AI screw placement for a total of 23 screws. Indications for surgery included deformity, degenerative disease, and tumor. Twenty-two screws (95.6%) were accurate-defined as grade 0 or grade 1. Twenty-one screws (91.3%) were classified as grade 0, 1 screw (4.3%) was grade 1, and 1 screw (4.3%) was grade 3. All breaches were asymptomatic. CONCLUSION: AR-assisted S2AI screw placement had an overall accuracy rate of 95.6% (grade 0 and grade 1 screws) in a cohort of 12 patients and 23 screws. This compares favorably with freehand and robotic placement. 1,2 AR enables spine surgeons to both better visualize anatomy and accurately place spinal instrumentation. Future studies are warranted to research the learning curve and cost analysis of AR-assisted spine surgery.

Creation and preclinical evaluation of a novel mussel-inspired, biomimetic, bioactive bone graft scaffold: direct comparison with Infuse bone graft using a rat model of spinal fusion.

OBJECTIVE: Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS: The authors created a polydopamine (PDA)-infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 µg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4-5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS: The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS: Implantation of rhBMP-2-adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.

Comparing the efficacy of adipose-derived and bone marrow-derived cells in a rat model of posterolateral lumbar fusion.

Although bone marrow-derived mesenchymal stem cells (BMCs) have been widely used in spinal fusion procedures, adipose-derived stem cells (ASCs) offer a number of advantages as an alternative clinical cell source. This study directly compares the efficacy of ASCs and BMCs from the same donor animals to achieve successful fusion when combined with a clinical-grade bone graft substitute in a rat lumbar fusion model. ASCs and BMCs were isolated from the same Lewis donor rats and grown to passage 2 (P2). Single-level bilateral posterolateral intertransverse process lumbar fusion surgery was performed on syngeneic rats divided into three experimental groups: clinical-grade bone graft substitute alone (CBGS); CBGS+ rat ASCs (rASC); and, CBGS+ rat BMCs (rBMC). Eight weeks postoperatively, fusion was evaluated via micro-CT, manual palpation and histology. In vitro analysis of the osteogenic capacity of rBMCs and rASCs was also performed. Results indicated that the average fusion volume in the rASC group was the largest and was significantly larger than the CBGS group. Although the rASC group displayed the highest fusion rates via micro-CT and manual palpation, this difference was not statistically significant. Cell-seeded grafts showed more histological bone formation than cell-free grafts. P2 rASCs and rBMCs displayed similar in vitro osteogenic differentiation capacities. Overall, this study showed that, when combined with a clinical-grade bone graft substitute in a rat model, rASCs cells yielded the largest fusion masses and comparable fusion results to rBMCs. These results add to growing evidence that ASCs provide an attractive alternative to BMCs for spinal fusion procedures.

Clinical accuracy and initial experience with augmented reality-assisted pedicle screw placement: the first 205 screws.

OBJECTIVE: Augmented reality (AR) is a novel technology which, when applied to spine surgery, offers the potential for efficient, safe, and accurate placement of spinal instrumentation. The authors report the accuracy of the first 205 pedicle screws consecutively placed at their institution by using AR assistance with a unique head-mounted display (HMD) navigation system. METHODS: A retrospective review was performed of the first 28 consecutive patients who underwent AR-assisted pedicle screw placement in the thoracic, lumbar, and/or sacral spine at the authors' institution. Clinical accuracy for each pedicle screw was graded using the Gertzbein-Robbins scale by an independent neuroradiologist working in a blinded fashion. RESULTS: Twenty-eight consecutive patients underwent thoracic, lumbar, or sacral pedicle screw placement with AR assistance. The median age at the time of surgery was 62.5 (IQR 13.8) years and the median body mass index was 31 (IQR 8.6) kg/m2. Indications for surgery included degenerative disease (n = 12, 43%); deformity correction (n = 12, 43%); tumor (n = 3, 11%); and trauma (n = 1, 4%). The majority of patients (n = 26, 93%) presented with low-back pain, 19 (68%) patients presented with radicular leg pain, and 10 (36%) patients had documented lower extremity weakness. A total of 205 screws were consecutively placed, with 112 (55%) placed in the lumbar spine, 67 (33%) in the thoracic spine, and 26 (13%) at S1. Screw placement accuracy was 98.5% for thoracic screws, 97.8% for lumbar/S1 screws, and 98.0% overall. CONCLUSIONS: AR depicted through a unique HMD is a novel and clinically accurate technology for the navigated insertion of pedicle screws. The authors describe the first 205 AR-assisted thoracic, lumbar, and sacral pedicle screws consecutively placed at their institution with an accuracy of 98.0% as determined by a Gertzbein-Robbins grade of A or B.

Neuroprotective Role of Acidosis in Ischemia: Review of the Preclinical Evidence.

Efforts to develop effective neuroprotective therapies for ischemic stroke have had little success to date. One promising approach to neuroprotection is ischemic postconditioning, which utilizes brief bouts of ischemia after acute ischemic stroke to elicit neuroprotection, although the mechanism is largely unknown. As the primary components of transient ischemia are local hypoxia and acidosis, and hypoxic postconditioning has had little success, it is possible that the acidosis component may be the primary driver. To address the evidence behind this, we performed a systematic review of preclinical studies focused on the neuroprotective role of transient acidosis after ischemia. Animal studies demonstrated that mild-to-moderate acidosis after ischemic events led to better functional neurologic outcomes with reduced infarct volumes, while severe acidosis often led to cerebral edema and worse functional outcomes. In vitro studies demonstrated that mild-to-moderate acidosis improves neuronal survival largely through two means: (1) inhibition of harmful superoxide formation in the excitotoxic pathway and (2) remodeling neuronal mitochondria to allow for efficient ATP production (i.e., oxidative phosphorylation), even in the absence of oxygen. Similar to the animal studies, acidotic postconditioning in humans would entail short cycles of carbon dioxide inhalation, which has already been demonstrated to be safe as part of a hypercapnic challenge when measuring cerebrovascular reactivity. Due to the preclinical efficacy of acidotic postconditioning, its relatively straightforward translation into humans, and the growing need for neuroprotective therapies, future preclinical studies should focus on filling the current knowledge gaps that are currently restricting the development of phase I/II clinical trials.

Removal of instrumentation for postoperative spine infection: systematic review.

OBJECTIVE: Currently, no consensus exists as to whether patients who develop infection of the surgical site after undergoing instrumented fusion should have their implants removed at the time of wound debridement. Instrumentation removal may eliminate a potential infection nidus, but removal may also destabilize the patient's spine. The authors sought to summarize the existing evidence by systematically reviewing published studies that compare outcomes between patients undergoing wound washout and instrumentation removal with outcomes of patients undergoing wound washout alone. The primary objectives were to determine 1) whether instrumentation removal from an infected wound facilitates infection clearance and lowers morbidity, and 2) whether the chronicity of the underlying infection affects the decision to remove instrumentation. METHODS: PRISMA guidelines were used to review the PubMed/MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov databases to identify studies that compared patients with implants removed and patients with implants retained. Outcomes of interest included mortality, rate of repeat wound washout, and loss of correction. RESULTS: Fifteen articles were included. Of 878 patients examined in these studies, 292 (33%) had instrumentation removed. Patient populations were highly heterogeneous, and outcome data were limited. Available data suggested that rates of reoperation, pseudarthrosis, and death were higher in patients who underwent instrumentation removal at the time of initial washout. Three studies recommended that instrumentation be uniformly removed at the time of wound washout. Five studies favored retaining the original instrumentation. Six studies favored retention in early infections but removal in late infections. CONCLUSIONS: The data on this topic remain heterogeneous and low in quality. Retention may be preferred in the setting of early infection, when the risk of underlying spine instability is still high and the risk of mature biofilm formation on the implants is low. However, late infections likely favor instrumentation removal. Higher-quality evidence from large, multicenter, prospective studies is needed to reach generalizable conclusions capable of guiding clinical practice.

Assessing underlying bone quality in spine surgery patients: a narrative review of dual-energy X-ray absorptiometry (DXA) and alternatives.

Poor bone quality and low bone mineral density (BMD) have been previously tied to higher rates of postoperative mechanical complications in patients undergoing spinal fusion. These include higher rates of proximal junctional kyphosis, screw pullout, pseudoarthrosis, and interbody subsidence. For these reasons, accurate preoperative assessment of a patient's underlying bone quality is paramount for all elective procedures. Dual-energy X-ray absorptiometry (DXA) is currently considered to be the gold standard for assessing BMD. However, a growing body of research has suggested that in vivo assessments of BMD using DXA are inaccurate and have, at best, moderate correlations to postoperative mechanical complications. Consequently, there have been investigations into using alternative methods for assessing in vivo bone quality, including using computed tomography (CT) and magnetic resonance imaging (MRI) volumes that are commonly obtained as part of surgical evaluation. Here we review the data regarding the accuracy of DXA for the evaluation of spine bone quality and describe the alternative imaging modalities currently under investigation.

Vertebral bone quality score predicts fragility fractures independently of bone mineral density.

BACKGROUND: Current evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases. PURPOSE: To evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture. STUDY DESIGN/SETTING: Retrospective single-center cohort. PATIENT SAMPLE: Patients followed at a metabolic bone clinic for osteopenia and/or osteoporosis. OUTCOME MEASURES: Radiographically-documented new-onset fragility fracture. METHODS: Patients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults. RESULTS: Seventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48-19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30-4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01-1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03-8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081). CONCLUSIONS: Here we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.

Comparison of Freshly Isolated Adipose Tissue-derived Stromal Vascular Fraction and Bone Marrow Cells in a Posterolateral Lumbar Spinal Fusion Model.

STUDY DESIGN: Rat posterolateral lumbar fusion model. OBJECTIVE: The aim of this study was to compare the efficacy of freshly isolated adipose tissue-derived stromal vascular fraction (A-SVF) and bone marrow cells (BMCs) cells in achieving spinal fusion in a rat model. SUMMARY OF BACKGROUND DATA: Adipose tissue-derived stromal cells (ASCs) offer advantages as a clinical cell source compared to bone marrow-derived stromal cells (BMSCs), including larger available tissue volumes and reduced donor site morbidity. While pre-clinical studies have shown that ex vivo expanded ASCs can be successfully used in spinal fusion, the use of A-SVF cells better allows for clinical translation. METHODS: A-SVF cells were isolated from the inguinal fat pads, whereas BMCs were isolated from the long bones of syngeneic 6- to 8-week-old Lewis rats and combined with Vitoss (Stryker) bone graft substitute for subsequent transplantation. Posterolateral spinal fusion surgery at L4-L5 was performed on 36 female Lewis rats divided into three experimental groups: Vitoss bone graft substitute only (VO group); Vitoss + 2.5 × 106 A-SVF cells/side; and, Vitoss + 2.5 × 106 BMCs/side. Fusion was assessed 8 weeks post-surgery via manual palpation, micro-computed tomography (µCT) imaging, and histology. RESULTS: µCT imaging analyses revealed that fusion volumes and µCT fusion scores in the A-SVF group were significantly higher than in the VO group; however, they were not significantly different between the A-SVF group and the BMC group. The average manual palpation score was highest in the A-SVF group compared with the BMC and VO groups. Fusion masses arising from cell-seeded implants yielded better bone quality than nonseeded bone graft substitute. CONCLUSION: In a rat model, A-SVF cells yielded a comparable fusion mass volume and radiographic rate of fusion to BMCs when combined with a clinical-grade bone graft substitute. These results suggest the feasibility of using freshly isolated A-SVF cells in spinal fusion procedures.Level of Evidence: N/A.

First Report of Pharmacogenomic Profiling in an Outpatient Spine Setting: Preliminary Results from a Pilot Study.

OBJECTIVE: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management. METHODS: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis. RESULTS: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups. CONCLUSIONS: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens.

Impact of Multidisciplinary Intraoperative Teams on Thirty-Day Complications After Sacral Tumor Resection.

OBJECTIVE: To evaluate the impact of multidisciplinary intraoperative teams on surgical complications in patients undergoing sacral tumor resection. METHODS: We reviewed all patients with primary or metastatic sacral tumors managed at a single comprehensive cancer center over a 7-year period. Perioperative complication rates were compared between those treated by an unassisted spinal oncologist and those treated with the assistance of at least 1 other surgical specialty. Statistical analysis involved univariable and stepwise multivariable logistic regression models to identify predictors of multidisciplinary management and 30-day complications. RESULTS: A total of 107 patients underwent 132 operations for sacral tumors; 92 operations involved multidisciplinary teams, including 54% of metastatic tumor operations and 74% of primary tumor operations. Patients receiving multidisciplinary management had higher body mass indexes (29.8 vs. 26.3 kg/m2; P = 0.008), larger tumors (258 vs. 55 cm³; P < 0.001), and higher American Society of Anesthesiologists scores (3 vs. 2; P = 0.049). Only larger tumor volume (odds ratio [OR], 1.007 per cm³; P < 0.001) and undergoing treatment for a malignant primary versus a metastatic tumor (OR, 23.4; P < 0.001) or benign primary tumor (OR, 29.3; P < 0.001) were predictive of multidisciplinary management. Although operations involving multidisciplinary teams were longer (467 vs. 231 minutes; P < 0.001) and had higher blood loss (1698 vs. 774 mL; P = 0.004), 30-day complication rates were similar (37 vs. 27%; P = 0.39). On multivariable analysis, only larger tumor volume (OR, 1.004 per cm³; P = 0.005) and longer surgical duration (OR, 1.002 per minute; P = 0.03) independently predicted higher 30-day complications. CONCLUSIONS: Although patients managed with multidisciplinary teams had larger tumors and worse baseline health, 30-day complications were similar. This finding suggests that the use of multidisciplinary teams may help to mitigate surgical morbidity in those with high baseline risk.

Surgical Decompression for Cervical Spondylotic Myelopathy in Patients with Associated Hypertension: A Single-Center Retrospective Cohort and Systematic Review of the Literature.

OBJECTIVE: To explore the relationship between spinal cord compression and hypertension through analysis of blood pressure (BP) variations in a cervical spondylotic myelopathy (CSM) cohort after surgical decompression, along with a review of the literature. METHODS: A single-institution retrospective review of patients with CSM who underwent cervical decompression between 2016 and 2017 was conducted. Baseline clinical and imaging characteristics, preoperative and postoperative BP readings, heart rate, functional status, and pain scores were collected. In addition, a PRISMA guidelines-based systematic review was performed. RESULTS: We identified 264 patients with CSM treated surgically; 149 (56.4%) of these had hypertension. The degree of spinal canal compromise and spinal cord compression, preoperative neurologic examination, and the presence of T2-signal hyperintensity on magnetic resonance imaging were associated with hypertension. Overall mean arterial pressure (MAP) decreased significantly at 1 and 12 months after surgery. Patients without T2-signal hyperintensity on imaging showed a MAP reduction at 12 months postoperatively, whereas those with T2-signal hyperintensity showed a transient MAP reduction at 1 month postoperatively before returning to preoperative values. At 12 months after surgery, 24 of 97 patients (24.7%) with initially uncontrolled hypertension had controlled BP values with significant reduction of MAP, systolic BP, and diastolic BP. Including the present study, 5 articles were eligible for systematic review, with all reporting a BP decrease in patients with CSM after decompression. CONCLUSIONS: Analysis of our retrospective cohort and a systematic review suggest that cervical surgical decompression reduces BP in some patients with CSM. However, this improvement is less apparent in patients with preoperative spinal cord T2-signal hyperintensity.

A Web-Based Calculator for Predicting the Occurrence of Wound Complications, Wound Infection, and Unplanned Reoperation for Wound Complications in Patients Undergoing Surgery for Spinal Metastases.

BACKGROUND: In the present study, we identified the risk factors for wound complications, wound infection, and reoperation for wound complications after spine metastasis surgery and deployed the resultant model as a web-based calculator. METHODS: Patients treated at a single comprehensive cancer center during a 7-year period were included. The demographics, pathology, comorbidities, laboratory values, and operative details were collected. Factors with P < 0.15 on univariable regression were entered into multivariable logistic regression to generate predictive models internally validated using 1000 bootstrapped samples. RESULTS: Of the 330 patients included, 29 (7.6%) had experienced a surgical site infection. The independent predictive factors for wound-related complications were a higher Charlson comorbidity index (CCI; odds ratio [OR], 1.41 per point; P < 0.01), Karnofsky performance scale score ≤70 (OR, 2.14; P = 0.04), lower platelet count (OR, 0.49 per 105/µL; P < 0.01), revision versus index surgery (OR, 3.10; P = 0.02), and increased incision length (OR, 1.21 per level; P = 0.02). Wound infection was associated with a higher CCI (OR, 1.60 per point; P < 0.01), a lower platelet count (OR, 0.35 per 105/µL; P < 0.01), revision surgery (OR, 4.63; P = 0.01), and a longer incision length (OR, 1.25 per level; P = 0.03). Unplanned reoperation for wound complications was predicted by a higher CCI (OR, 1.39 per point; P = 0.003), prior irradiation (OR, 2.52; P = 0.04), a lower platelet count (OR, 0.57 per 105/µL; P = 0.02), and revision surgery (OR, 3.34; P = 0.03), The optimism-corrected areas under the curve were 0.75, 0.81, and 0.72 for the wound complication, infection, and reoperation models, respectively. CONCLUSIONS: Low platelet counts, poorer health status, more invasive surgery, and revision surgery all independently predicted the risk of wound complications, including infection and unplanned reoperation for infection. Validation of the calculators in a prospective study is merited.