bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Endovascular and Surgical Treatment of Type I Spinal Dural Arteriovenous Fistulas
Authors: Vukic Miroslav , Ozretic David , Rados Marko , Marasanov Sergej , Rozankovic Marjan , Lupret Velimir , Nemir Jakob , Duric Kresimir Sasa 
Published: May 2015

Introduction Spinal dural arteriovenous fistulas (SDAVFs) are rare but most common form of spinal vascular malformations, accounting for approximately 70% of all such lesions. They are low-flow vascular shunts fed by radicular arteries. Patients most often present with myelopathy. The presumed pathophysiological mechanism is venous hypertension and congestion of the cord with edema. We present our experiences and results in combined endovascular and surgical treatment of type I SDAVFs. Patients and Methods We conducted a retrospective review of prospectively collected data from patients with a diagnosis of SDAVFs who underwent treatment at University Hospital Centre Rebro Zagreb between January 2012 and June 2014. The complication and recurrence rates from clinical and imaging follow-up in these patients are analyzed. Results A total of 14 patients with a diagnosis of SDAVFs were treated in our institution during the analyzed period. Of these, 12 patients underwent endovascular embolization as first-line therapy. Onyx was used in 1 patient and NBCA in 11 patients. Two patients underwent surgical ligation as the initial therapeutic procedure. Patients in both groups showed significant improvement in clinical status after treatment on the Aminoff-Logue Scale. One patient in the endovascular group developed spinal infarction because of the accidental embolization of posterior spinal artery. Six patients in embolization group had recurrence of the fistula during the course of follow-up requiring surgical ligation. Two patients in the surgical group had recurrence of fistula during the course of follow-up and were reoperated. Conclusion Although most type I SDAFs are amenable to endovascular embolization, microsurgical obliteration as first option is indicated in specific anatomic situations and usually the only solution for recurrent cases. The combined endovascular and microsurgical approach offers best results after careful selection of patients based on imaging.
Does Intrawound Application of Vancomycin Influence Bone Healing in Spinal Surgery?
Authors: Eder Claudia , Schenk Stefan , Trifinopoulos Jana , Kuelekci Buesra , Kienzl Melanie , Schildboeck Sabrina , Ogon Michael 
Published: May 2015

Introduction Surgical site infections represent a major complication of spinal surgery. The application of lyophilized vancomycin into the wound is reported to significantly decrease infection rates. As concentrations applied locally can exceed the minimal bacterial inhibitory concentration for more than a 1000-fold, toxic side effects on local tissue may be possible. Materials and Methods Primary osteoblast cell cultures were generated from bone tissue samples of 10 patients. Samples were incubated in absence or presence of 3, 6, or 12 mg/cm2 vancomycin according to a planned phase I clinical trial protocol. Changes in pH, osteoblast migration, proliferation, and viability were analyzed. Alkaline phosphatase and mineralization patterns were studied. Results The application of more than 3 mg/cm2 vancomycin induced a decline of pH toward the acidic range. The migration potential of osteoblasts was decreased from 100% (control samples) to zero (12 mg/cm2 vancomycin) in a dose-dependent manner. Cell proliferation was significantly inhibited at dosages above 3 mg/cm2. Significant cell death was observed if the dosage applied exceeded 6 mg/cm2. The synthesis of alkaline phosphatase was markedly reduced in all dosages applied and calcium deposition was significantly decreased in dosages above 3 mg/cm2. Conclusion As bone remodeling requires the immigration, proliferation, and differentiation of osteoblasts at the fusion site, high dosages of intrawound vancomycin might interfere with regenerative processes and increase the risk of nonunion. To allow an appropriate balance of infection risk and the risk of nonunion, the minimal local concentration required should be determined by controlled in vivo studies.
Mesenchymal Stem Cells Derived from Vertebrae Show Best Biological Properties
Authors: Brodano Giovanni Barbanti , Maroni Giorgia , Trombi Luisa , Valtieri Mauro , Griffoni Cristiana , Boriani Stefano , Magli Maria Cristina 
Published: May 2015

Introduction Due to their properties and characteristics, human mesenchymal stem cells (MSCs) appear to have great therapeutic potential, because they can contribute to the tissue regeneration. Many different populations of MSCs that differ for the embryonic origin and the anatomical localization have been described and to understand whether they have equivalent biological properties is a critical issue for their therapeutic application. Spine fusion is frequently used to treat traumatic, degenerative, and oncological spine diseases. Autologous bone graft has been considered the gold standard for spine fusion procedures because of its osteogenic, osteoinductive, and osteoconductive ability. However, its use is associated with significant disadvantages, including donor site pain, increased operative time, insufficient availability, and nonunion postlumbar fusion. Various bone substitutes have been developed to promote spinal fusion. Also, MSCs have been successfully tested for spinal fusion in several small and large animal models. Material and Methods To define the properties of MSCs for the use in clinical applications, we proposed to analyze the cellular and molecular characteristics of human adult MSCs derived from different body locations, such as bone marrow from the iliac crest (Ic-MSCs), sternum (St-MSCs), and vertebrae (vMSCs), as well as colon (Co-MSCs) and dental pulp (DPSCs), to identify the cell population showing better biological properties for spine fusion clinical application. Results MSCs from different sources presented very different growth kinetics. While iliac crest and sternum-derived MSCs could be maintained in culture for about 3 months, undergoing a limited expansion, mesenchymal cultures derived from dental pulp and colon grew much more rapidly, but could not be maintained longer. Strikingly, vMSCs continued to propagate at high rate even after 3.5 months ex vivo. MSCs from different sources were also induced to osteogenic, adipogenic, and chondrogenic differentiation following exposure to specific inducing agents. We observed that vMSCs generate mature cells of all mesenchymal lineages with greater efficiency, resulting into the best population both in terms of expansion and differentiation. Conclusion This finding could be very interesting and open new perspectives for the improvement of spine fusion, which is a mandatory step for the success of spinal surgical procedures. In the course of a surgical procedure for spinal fusion, vertebral bone marrow can be harvested simultaneously with the preparation of the site for pedicle screw insertion. Then multipotent MSCs can be isolated from vertebral bone marrow during the progress of the surgical procedure and reintroduced in the fusion site (using homologous or autologous bone tissue or biomaterials as scaffold), without any additional surgical time or any other donor site involvement.
Developing a Mouse Model to Study Mesenchymal Stem Cell Survival, Proliferation, and Migration in Lumbar Posterolateral Spinal Fusion
Authors: Lina Ioan , Holmes Christina , Liauw Jason , Lo Sheng-Fu Larry , Elder Benjamin , Theodros Debebe , Witham Timothy 
Published: May 2015

Introduction While spinal fusion surgery has advanced over the past decade, a great deal is unknown regarding the underlying mechanisms that contribute to spinal fusion failure or pseudoarthrosis. Clinically, bone marrow aspirate has been successfully used alongside a variety of grafting materials to augment fusion (Neen et al. Spine (Phila Pa 1976). 2006;31(18):E636; Carter et al. Spine J. 2009;9(6):434). To date, studies evaluating these procedures have focused on radiographic monitoring and endpoint analysis. Little is known about the survival and proliferation of these transplanted mesenchymal cells or how much they contribute to bone formation compared with host cells from adjacent decorticated bone. Insights into these cell dynamics will give us a deeper understanding of the biological processes underlying spinal fusion and allow for evaluation and development of fusion therapies that reduce rates of pseudoarthrosis. Material and Methods A total of 40 FVB/NJ mice underwent posterolateral lumbar spinal fusion surgery and were divided into four groups based upon the fusion graft employed: syngeneic iliac crest bone graft ( n = 10), Vitoss bone-matrix alone ( n = 10), Vitoss bone-matrix with syngeneic bone marrow cells (2.5 × 106 cell/side) ( n = 10), and Vitoss bone-matrix with transgenic luciferase-expressing syngeneic bone marrow cells (2.5 × 106 cell/side) ( n = 10). Bone marrow cells were isolated from the long bones of either syngeneic FVB/NJ mice or syngeneic FVB mice which constitutively express the luciferase gene (FVB-Tg (CAG-luc,-GFP) L2G85Chco/J mice). The in vivo survival, distribution, and proliferation of the luciferase-expressing bone marrow-derived cells were monitored via bioluminescence imaging over a period of 8 weeks. Spinal fusion was assessed 4, 6, and 8 weeks postsurgery via micro-CT imaging, as well as via manual palpation at 8 weeks. Immunohistochemistry was performed to assess fusion bone growth as well as determine the number of donor versus host cells within the fusion mass. Results Bioluminescent imaging data demonstrated quantifiable cellular viability within the fusion mass as early as 24 hours following surgery, with increasing bioluminescent signal over the first 2 weeks postsurgery, thus indicating cellular proliferation. Bioluminescence decreased between weeks 4 and 8 suggesting a loss of transplanted mesenchymal progenitor cells within the fusion mass at later time points. Correlations with histology and micro-CT imaging of the developing fusion mass are currently under analysis. Conclusions We have demonstrated a novel murine model which enables noninvasive in vivo monitoring of implanted transgenic luciferase-expressing bone marrow cells following spinal fusion surgery. Future applications of this model will include the assessment of additional therapeutics for improving spinal fusion in translational research studies.
Investigating Human VANGL1, as a Candidate Gene for Adolescent Idiopathic Scoliosis
Authors: Simony Ane , Andersen Malene Rask , Larsen Lars Allan , Andersen Mikkel O. 
Published: May 2015

Introduction The human VANGL1 genes has been predicted to be associated with idiopathic scoliosis, as a mutation (c.676C > T, L226F) was identified in a family with dominant inheritance of the disease. A previous investigation of the gene revealed the candidate to segregate, with all but one family member (Sharma, et al. ASHG 2012 Annual Meeting Program Guide. 2012). Adolescent idiopathic scoliosis (AIS) is generally considered multigenetic, but the determining genes remain yet to be characterized. In this study, we have examined VANGL1 as a contributor to the phenotype of AIS. Materials and Methods We have conducted automated Sanger sequencing of the seven coding exons of VANGL1 gene in a disease cohort of 170 AIS patients ( n = 340) and 177 controls ( n = 354). Localization of mutated VANGL1 proteins was investigated in cell systems using immunofluorescence microscopy. Results Two novel mutations, each in separate individuals within the considered disease cohort, were identified. One mutation is situated in the third coding exon, which encodes the transmembrane parts of the VANGL1 protein. This mutation is a c.407T > A (I136N) conversion, for which the patient is heterozygotes. Furthermore, this mutation was also identified in the dizygotic unaffected twin of the patient. The second mutation was found in the seventh coding exon, which encodes the C-terminal of the VANGL1 protein. This mutation is a c.1318T > G (F440V) conversion, for which the patient is also heterozygotes. Neither of the identified mutations was present in the sequenced controls or in 2000 Danish exomes (Lohmueller et al. Am J Hum Genet 2013;93:1072–1086). The F440V mutation results in altered localization of the VANGL1 protein, from very clear membrane association to a cytoplasmic distribution, with possible retainment in endoplasmic reticulum and the Golgi apparatus, near the cell nucleus. Conclusion Our results show that mutations in the VANGL1 gene can cause AIS and suggest that defects in planar cell polarity may be an underlying cause of AIS. Examination of the expression of VANGL1 in juvenile or adult stages of life is wanted, as well as examinations of effects on downstream targets of mutated VANGL1 and polarity in affected cells.
Lidocaine and Bupivacaine Toxicity on Human Intervertebral Disc Cells in Vitro
Authors: Velnar Tomaz , Gradisnik Lidija , Bunc Gorazd 
Published: May 2015

Introduction The treatment and diagnostics of discogenic low back pain often employ local anesthetic agents. Lidocaine and bupivacaine are most commonly used for controlling and relieving the pain in interventional spine procedures. It is known that these local anesthetics may be cytotoxic to the intervertebral disc cells following the intradiscal injections and that they may provoke or accelerate the intervertebral disc degeneration. However, the potential effects of these agents still remain unclear, as many studies so far have been accomplished on animal cells. The purpose of the study was to evaluate the effect of various local anesthetics on human intervertebral disc cells in vitro and to compare the cytotoxicity of lidocaine, bupivacaine, and its mixture to saline control solution. Materials and Methods Annulus fibrosus and nucleus pulposus cells were isolated from human lumbar intervertebral disc fragments following discectomies. They were cultured in the microtiter plates and exposed to various concentrations of lidocaine, bupivacaine, as well as their mixture. The saline solution was used for control. Three different dilutions (undiluted, 1:2, and 1:4) of anesthetic agents were tested. The cells were treated for 6, 24, and 48 hours. They were then examined with the crystal violet cell staining. The percentage of live cells after treatment was determined. Results Human intervertebral disc cells demonstrated a time- and dose-dependent response to lidocaine and bupivacaine. Nucleus pulposus cells were more susceptible than annulus fibrosus cells to the toxic effects of both anesthetic agents. Lidocaine was the most toxic in all three tested concentrations (undiluted, 1:2, and 1:4) with the cell survival of 0, 10, and 20%, respectively. Bupivacaine presented less cytotoxicity than lidocaine with the survival rates of 10, 60, and 80%, respectively. Lidocaine–bupivacaine mixture showed an intermediate toxicological effect. The cell death was mainly caused by necrosis rather than apoptosis. Conclusions When incubating the human intervertebral disc cells in vitro with a combination of anesthetic agents commonly used for discography, the cytotoxic effects were observed in a dose- and time-dependent manner. According to our study, lidocaine and its mixtures should be avoided due to their high toxicity to the intervertebral disc cells. Bupivacaine was the least toxic, especially when used in 1:4 dilutions and may be thus recommended for the intradiscal diagnostics. It is assumed that the genesis of disc degeneration might be contributed also by the toxic effects of the anesthetics used, culminating to progressive tissue damage after the diagnostic measures.
Hyaluronate, Collagen, and Ionic Distribution: A Relation Study with Annulus Fibrosus Cells (Fibroblast-Like Cells)
Authors: Martins Delio , Medeiros Valquiria , Demerov Gabriela , Accardo Camila , Paredes-Gamero Edgar , Wajchenberg Marcelo , Reginato Rejane , Nader Helena , Puertas Eduardo , Faloppa Flavio 
Published: May 2015

Introduction Degenerative disc disease has been associated with low back pain and many therapies have been proposed for its treatment. The correlation between disc degeneration and back pain is still to be determined, however, studies tend to analyze potential therapies including gene applications and molecular biology to deal with this complex public health problem. Precise methods to quantify disc components are mandatory for any type of proposed therapy. The aim of this study was to correlate glycosaminoglycan amounts with the quantitation of cellular ions and collagen fiber distributions in different intervertebral disc sections. Materials and Methods In total, 14 intervertebral discs were used from 14 tails of 24 to 30-month old cattle. All of the discs were dehydrated, separated in seven sections and digested in sodium-free papain buffer. Sulfated glycosaminoglycan measurements were performed in the samples according to DMMB and agarose electrophoresis methods; hyaluronate was determined by an ELISA-like fluorimetric method, total cells were measured using the PicoGreen technique, ions were quantified by an automated procedure, and collagen fiber birefringence was analyzed with polarized light microscopy. Results Significant differences were observed between electrophoresis and DMMB ( p < 0.01); GAGs were up to six times higher when using electrophoresis in annulus (mean/SD = 3.82/1.96) and were almost two times higher in the nucleus (mean/SD = 1.63/0.21). The correlation between HA and GAG ( p < 0.001), cell number, sodium ( p = 0.007), and hyaluronate ( p = 0.034) were significant. Thin collagen fibers were largest in the nucleus ( p < 0.001). Fibroblast-like cells were negatively correlated with hyaluronate and sodium concentrations. Collagen thin fibers (collagen II) were more related to hyaluronate. Conclusion In summary, this report demonstrated a positive correlation between hyaluronate and glycosaminoglycan; and a negative correlation between hyaluronate and cell number, suggesting that fibroblast-like cells are also sensitive to changes in hyaluronate and ionic concentrations. Hyaluronate could be closely related to thin collagen fibers (collagen type II). Acknowledgments This work was supported by INFAR/UNIFESP Confocal and Flow Cytometry Facility and by grants from the “Fundacao de Amparo à Pesquisa do Estado de São Paulo” (FAPESP: Grant number: 2009/54793–6). D.E.M. was supported by a PhD's fellowship grant from CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nível Superior).
Sagittal Deformity Correction during the Lateral Transpsoas Approach with Hyperlordotic Interbody Grafting, Adjunctive ALL Release, and Subsequent Smith–Peterson Osteotomy
Authors: Staub Blake , Holman Paul , Hanson Darrell , Huang Meng 
Published: May 2015

Introduction Traditionally, surgical intervention for patients with thoracolumbar sagittal imbalance relied on posterior column shortening techniques such as the Smith–Peterson osteotomy (SPO) and pedicle subtraction osteotomy (PSO). The lateral retroperitoneal, transpsoas approach has been proven to afford significant coronal deformity correction; however, the evidence for its use in the sagittal deformity correction is less robust. Recently, the use of hyperlordotic grafts has provided all the benefits of the transpsoas approach while also allowing for sagittal deformity correction. Hyperlordotic interbody grafts and a subsequent SPO can theoretically provide a similar sagittal correction as provided by a PSO or multiple SPOs while minimizing the associated morbidities. Materials and Methods This is a retrospective review examining the preoperative and postoperative segmental lordosis after placement of a hyperlordotic cage and subsequent SPO. A total of 22 patient charts were reviewed. The mean patient age was 58.6. There were 8 males and 14 females. A 20-degree hyperlordotic cage was utilized at four intervertebral levels. The 30-degree cage was used at 19 levels. The surgical procedure involved the release of the anterior longitudinal ligament and placement of a hyperlordotic graft (NuVasive CoRoent XL-Hyperlordotic) via the lateral, retroperitoneal, transpsoas approach followed by posterior instrumentation and SPO at that level. In each instance, the hyperlordotic graft and subsequent SPO were part of a large, multilevel deformity correction and were not simply performed as a standalone procedure. Results Hyperlordotic cages were placed from T12–L1 to L4–L5 in this series. A total of 10 cages were placed at the L3–L4 interspace. The mean preoperative lordosis was 0.4 and 4.2 degrees in the 20 and 30-degree cohorts, respectively. The mean postoperative, segmental lordosis was 23.0 and 28.2 degrees in the two groups, yielding a mean correction of 22.6 degrees with the 20-degree cage and 24.0 degrees with the 30-degree cage. The 30-degree cage yielded a sagittal correction of 8.5 to 54.0 degrees. A correction of greater than 30 degrees was achieved in five cases. The single case with less than 10 degrees of lordosis restoration resulted from graft subsidence. The greatest increase in lordosis occurred in patients with the most significant preoperative segmental kyphosis. Conclusion Segmental lordosis increase of approximately 20 to 25 degrees can be expected with the placement of either a 20- or 30-degree hyperlordotic cage via the transpsoas approach with subsequent SPO at that level. This hybrid approach provides a degree of correction similar to a PSO without the associated morbidity.
Classification of Sagittal Imbalance Based on Spinal Alignment and Compensatory Mechanisms
Authors: Lamartina Claudio , Cecchinato Riccardo , Ismael Maryem , Damilano Marco , Berjano Pedro 
Published: May 2015

Introduction Sagittal balance is an independent predictor of clinical outcomes in spinal care. Surgical treatment is challenging and jeopardized by frequent complications. Guidelines for surgical treatment are currently not based on a classification of the disease. A comprehensive classification of sagittal balance, based on regional deformities and compensatory mechanisms combined with deformity patterns is proposed. Though the sagittal shape of the spine can change due to degeneration or trauma, correlations between sagittal shape parameters and pelvic incidence (PI) have been described. Pelvic incidence is not changed by degeneration, thus representing a permanent source of information on the original sagittal shape of the spine. Material and Methods A total of 128 full-spine lateral standing radiographs of patients with different spinal conditions were evaluated and classified by one rater. One random subseries of 35 patients was evaluated by two raters for calculation of interrater agreement. Spinopelvic parameters were measured in all the radiographs. The internal validity of the classification system was evaluated comparing the values of regional sagittal parameters that distinguish one category from the others. Results Eight different patterns were identified regarding the site of the deformity and the presence of compensatory mechanisms: cervical, thoracic, thoracolumbar junction, lumbar, lower lumbar, global and pelvic kyphosis, and normal sagittal alignment. Interrater agreement was almost perfect (j = 0.963). Statistically significant differences were found comparing the means of selected sagittal spinopelvic parameters that conceptually divide pairs or groups of categories: C2-C7 SVA for cervical kyphosis versus all other patients, TK-PI mismatch for thoracic kyphosis versus all other patients, T11-L2 kyphosis for thoracolumbar kyphosis versus all other patients, global alignment (LL? TK-PI) and SVA for lumbar kyphosis versus global kyphosis, and pelvic tilt for pelvic kyphosis versus lumbar, lower lumbar, and global kyphosis. Conclusion A comprehensive classification of sagittal imbalance is presented. This classification permits a better interpretation of the deformity and muscle forces acting on the spine, and helps surgical planning. Preliminary validation has been provided.