ABSTRACT
Duchenne muscular dystrophy (DMD) is a severe X-linked disorder characterized by dystrophin gene mutations and mitochondrial dysfunction, leading to progressive muscle weakness and premature death of DMD patients. We developed human Dystrophin Expressing Chimeric (DEC) cells, created by the fusion of myoblasts from normal donors and DMD patients, as a foundation for DT-DEC01 therapy for DMD. Our preclinical studies on mdx mouse models of DMD revealed enhanced dystrophin expression and functional improvements in cardiac, respiratory, and skeletal muscles after systemic intraosseous DEC administration. The current study explored the feasibility of mitochondrial transfer and fusion within the created DEC cells, which is crucial for developing new therapeutic strategies for DMD. Following mitochondrial staining with MitoTracker Deep Red and MitoTracker Green dyes, mitochondrial fusion and transfer was assessed by Flow cytometry (FACS) and confocal microscopy. The PEG-mediated fusion of myoblasts from normal healthy donors (MBN/MBN) and normal and DMD-affected donors (MBN/MBDMD), confirmed the feasibility of myoblast and mitochondrial fusion and transfer. The colocalization of the mitochondrial dyes MitoTracker Deep Red and MitoTracker Green confirmed the mitochondrial chimeric state and the creation of chimeric mitochondria, as well as the transfer of healthy donor mitochondria within the created DEC cells. These findings are unique and significant, introducing the potential of DT-DEC01 therapy to restore mitochondrial function in DMD patients and in other diseases where mitochondrial dysfunction plays a critical role.
ABSTRACT
Chimerism-based strategies represent a pioneering concept which has led to groundbreaking advancements in regenerative medicine and transplantation. This new approach offers therapeutic potential for the treatment of various diseases, including inherited disorders. The ongoing studies on chimeric cells prompted the development of Dystrophin-Expressing Chimeric (DEC) cells which were introduced as a potential therapy for Duchenne Muscular Dystrophy (DMD). DMD is a genetic condition that leads to premature death in adolescent boys and remains incurable with current methods. DEC therapy, created via the fusion of human myoblasts derived from normal and DMD-affected donors, has proven to be safe and efficacious when tested in experimental models of DMD after systemic-intraosseous administration. These studies confirmed increased dystrophin expression, which correlated with functional and morphological improvements in DMD-affected muscles, including cardiac, respiratory, and skeletal muscles. Furthermore, the application of DEC therapy in a clinical study confirmed its long-term safety and efficacy in DMD patients. This review summarizes the development of chimeric cell technology tested in preclinical models and clinical studies, highlighting the potential of DEC therapy in muscle regeneration and repair, and introduces chimeric cell-based therapies as a promising, novel approach for muscle regeneration and the treatment of DMD and other neuromuscular disorders.
Subject(s)
Cell- and Tissue-Based Therapy , Dystrophin , Muscle, Skeletal , Muscular Dystrophy, Duchenne , Regeneration , Muscular Dystrophy, Duchenne/therapy , Muscular Dystrophy, Duchenne/genetics , Humans , Animals , Cell- and Tissue-Based Therapy/methods , Dystrophin/genetics , Dystrophin/metabolism , Myoblasts/metabolismABSTRACT
Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutation in the dystrophin gene. Currently there is no cure for DMD. We introduced a novel human Dystrophin Expressing Chimeric (DEC) cell therapy of myoblast origin and confirmed the safety and efficacy of DEC in the mdx mouse models of DMD. In this study, we assessed histological and morphological changes in the cardiac, diaphragm, and gastrocnemius muscles of the mdx/scid mice after the transplantation of human DEC therapy via the systemic-intraosseous route. The efficacy of different DEC doses was evaluated at 90 days (0.5 × 106 and 1 × 106 DEC cells) and 180 days (1 × 106 and 5 × 106 DEC cells) after administration. The evaluation of Hematoxylin & Eosin (H&E)-stained sectional slices of cardiac, diaphragm, and gastrocnemius muscles included assessment of muscle fiber size by minimal Feret's diameter method using ImageJ software. The overall improvement in muscle morphology was observed in DMD-affected target muscles in both studies, as evidenced by a shift in fiber size distribution toward the wild type (WT) phenotype and by an increase in the mean Feret's diameter compared to the vehicle-injected controls. These findings confirm the long-term efficacy of human DEC therapy in the improvement of overall morphological pathology in the muscles affected by DMD and introduce DEC as a novel therapeutic approach for DMD patients.
ABSTRACT
Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6-15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic-intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.
Subject(s)
Muscular Dystrophy, Duchenne , Male , Humans , Child , Adolescent , Muscular Dystrophy, Duchenne/drug therapy , Muscular Dystrophy, Duchenne/genetics , Dystrophin/genetics , Muscle, Skeletal , Biomarkers , Cell- and Tissue-Based TherapyABSTRACT
Duchenne Muscular Dystrophy (DMD) is a progressive and fatal muscle-wasting disease with no known cure. We previously reported the preliminary safety and efficacy up to six months after the administration of DT-DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of myoblasts of DMD patient and the normal donor. In this 12-month follow-up study, we report on the safety and functional outcomes of three DMD patients after the systemic intraosseous administration of DT-DEC01. The safety of DT-DEC01 was confirmed by the absence of Adverse Events (AE) and Severe Adverse Events (SAE) up to 21 months after intraosseous DT-DEC01 administration. The lack of presence of anti-HLA antibodies and Donors Specific Antibodies (DSA) further confirmed DT-DEC01 therapy safety. Functional assessments in ambulatory patients revealed improvements in 6-Minute Walk Test (6MWT) and timed functions of North Star Ambulatory Assessment (NSAA). Additionally, improvements in PUL2.0 test and grip strength correlated with increased Motor Unit Potentials (MUP) duration recorded by Electromyography (EMG) in both ambulatory and non-ambulatory patients. DT-DEC01 systemic effect was confirmed by improved cardiac and pulmonary parameters and daily activity recordings. This follow-up study confirmed the safety and preliminary efficacy of DT-DEC01 therapy in DMD-affected patients up to 12 months after intraosseous administration. DT-DEC01 introduces a novel concept of personalized myoblast-based cellular therapy that is irrespective of the mutation type, does not require immunosuppression or the use of viral vectors, and carries no risk of off target mutations. This establishes DT-DEC01 as a promising and universally effective treatment option for all DMD patients.
Subject(s)
Muscular Dystrophy, Duchenne , Humans , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Follow-Up Studies , Cell- and Tissue-Based Therapy , Heart , Immunosuppression TherapyABSTRACT
Duchenne Muscular Dystrophy (DMD) is a X-linked progressive lethal muscle wasting disease for which there is no cure. We present first-in-human study assessing safety and efficacy of novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of patient myoblasts with myoblasts of normal donor origin. We report here on safety and functional outcomes of the first 3 DMD patients. No study related adverse events (AE) and no serious adverse events (SAE) were observed up to 14 months after systemic-intraosseous administration of DEC01. Ambulatory patients showed improvements in functional tests (6-Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA)) and both, ambulatory and non-ambulatory in PUL, strength and fatigue resistance which correlated with improvement of Electromyography (EMG) parameters. DEC01 therapy does not require immunosuppression, involves no risks of off target mutations, is not dependent upon the causative mutation and is therefore a universal therapy that does not use viral vectors and therefore can be readministered, if needed. This study was approved by the Bioethics Committee (approval No. 46/2019). Mechanism of action of the Dystrophin Expressing Chimeric Cell (DEC) cells created via ex vivo fusion of human myoblast from normal and DMD-affected donors. Following systemic-intraosseous administration, DEC engraft and fuse with the myoblasts of DMD patients, deliver dystrophin and improve muscle strength and function. (Created with BioRender.com).
Subject(s)
Muscular Dystrophy, Duchenne , Humans , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/therapy , Dystrophin/genetics , Follow-Up Studies , Myoblasts , Cell- and Tissue-Based TherapyABSTRACT
Augmented reality (AR) is the superimposition of a virtual environment on the real world. The use of AR in spine surgery continues to grow, with multiple companies and products becoming available. The proposed benefits of AR include decreased attention shift, decreased line-of-site interruption, opportunity for more minimally invasive approaches, decreased radiation exposure to the operative team, and improved pedicle screw accuracy. In this review, we examine our institutional experiences with utilization and implementation of some of the current AR products.
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Introduction: We previously reported that systemic delivery of dystrophin expressing chimeric (DEC) cells of normal (wt) and dystrophin-deficient (mdx) myoblast (MB) or mesenchymal stem cell (MSC) origin restored dystrophin expression and improved cardiac function in the mdx mouse model of Duchenne muscular dystrophy (DMD). Aim: This study evaluated the effect of intraosseous delivery of murine DEC lines of MB (MB wt /MB mdx ) and MSC (MB wt /MSC mdx ) origin on function of gastrocnemius muscle (GM). Material and methods: DEC lines created by ex vivo fusion were tested in the mdx mouse model of DMD: Group 1 - vehicle (control), Group 2 - non-fused 0.25 × 106 MB wt and 0.25 × 106 MSC mdx (control), Group 3 - fused 0.5 × 106 MB wt /MB mdx DEC and Group 4 - fused 0.5 × 106 MB wt /MSCmdx DEC. In situ and in vitro muscle force tests assessed GM function at 90 days post-transplant. Results: Application of MB wt /MSC mdx and MB wt /MB mdx DEC significantly improved the fatigue ratio of GM compared to vehicle-injected controls detected by in vivo muscle force tests (0.567 ±0.116, p = 0.045 and 0.489 ±0.087, p < 0.05, respectively). MB wt /MSCmdx DEC recipients presented enhanced maximum force at tetanus (0.145 ±0.040 g/mg, p < 0.05); furthermore, recipients of MB wt /MBmdx DEC showed a significant increase in the maximum force generation rate compared to vehicle controls (4.447 ±1.090 g/s/mg, p < 0.05). The ex vivo GM force testing in MB wt /MSCmdx DEC recipients detected increased average GM force compared to vehicle and non-fused controls. Conclusions: Systemic-intraosseous administration of MB wt /MBmdx and MB wt /MSCmdx DEC therapy combining the myogenic and immunomodulatory properties of MB and MSC significantly improved skeletal muscle (GM) function of force and resistance to fatigue in an mdx mouse model of DMD.
ABSTRACT
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by mutations in dystrophin gene. Currently, there is no cure for DMD. Cell therapies are challenged by limited engraftment and rejection. Thus, more effective and safer therapeutic approaches are needed for DMD. We previously reported increased dystrophin expression correlating with improved function after transplantation of dystrophin expressing chimeric (DEC) cells of myoblast origin in the mdx mouse models of DMD. This study established new DEC cell line of myoblasts and mesenchymal stem cells (MSC) origin and tested its efficacy and therapeutic potential in mdx/scid mouse model of DMD. Fifteen ex vivo cell fusions of allogenic human myoblast [normal myoblasts (MBN)] and normal human bone marrow-derived MSC (MSCN) from normal donors were performed using polyethylene glycol. Flow cytometry, confocal microscopy, polymerase chain reaction (PCR)-short tandem repeats, polymerase chain reaction-reverse sequence-specific oligonucleotide probe assessed chimeric state of fused MBN/MSCN DEC cells, whereas Comet assay assessed fusion procedure safety testing genotoxicity. Immunofluorescence and real-time PCR assessed dystrophin expression and myogenic differentiation. Mixed lymphocyte reaction (MLR) evaluated DEC's immunogenicity. To test MBN/MSCN DEC efficacy in vivo, gastrocnemius muscle of mdx/scid mice were injected with vehicle (n = 12), nonfused MBN and MSCN (n = 9, 0.25 × 106/each) or MBN/MSCN DEC (n = 9, 0.5 × 106). Animals were evaluated for 90 days using ex vivo and in vivo muscle strength tests. Histology and immunofluorescence staining assessed dystrophin expression, centrally nucleated fibers and scar tissue formation. Post-fusion, MBN/MSCN DEC chimeric state, myogenic differentiation, and dystrophin expression were confirmed. MLR reveled reduced DEC's immune response compared with controls (P < 0.05). At 90 days post-DEC transplant, increase in dystrophin expression (20.26% ± 2.5%, P < 0.05) correlated with improved muscle strength and function in mdx/scid mice. The created human MBN/MSCN DEC cell line introduces novel therapeutic approach combining myogenic and immunomodulatory properties of MB and MSC, and as such may open a universal approach for muscle regeneration in DMD.
Subject(s)
Dystrophin/genetics , Hybrid Cells/transplantation , Mesenchymal Stem Cells/metabolism , Muscular Dystrophy, Duchenne/therapy , Myoblasts/metabolism , Stem Cell Transplantation/methods , Animals , Cell Differentiation/genetics , Cell Fusion , Cells, Cultured , Disease Models, Animal , Dystrophin/metabolism , Gene Expression , Humans , Hybrid Cells/cytology , Hybrid Cells/metabolism , Mesenchymal Stem Cells/cytology , Mice, Inbred C57BL , Mice, Inbred mdx , Mice, SCID , Muscle, Skeletal/cytology , Muscular Dystrophy, Duchenne/genetics , Muscular Dystrophy, Duchenne/physiopathology , Myoblasts/cytology , Transplantation, HeterologousABSTRACT
OBJECTIVE: To identify possible radiographic predictors markers of dynamic instability including disc height (DH), disc degeneration, and spondylosis in the setting of degenerative spondylolisthesis (DS). METHODS: A retrospective review with prospectively collected data was performed on 125 patients with L4-5 DS who underwent decompression and fusion. Patients were divided into groups with dynamic instability and those without. Radiographs of the lumbar spine in neutral, flexion, and extension were used to determine degree of slip, DH, translational motion, angular motion, spondylotic changes, and lumbar lordosis. Magnetic resonance imaging (MRI) scans were reviewed to assess disc degeneration. RESULTS: Thirty-one percent of the patients met criteria for dynamic instability. Significant correlations (p < 0.05) were found between preserved DH and dynamic instability; increased spondylotic changes and decreased translational motion; as well as advanced MRI-based disc degeneration scores with decreased angular motion, respectively. Six radiographic parameters were utilized to create a predictive model for dynamic instability, and a receiver operating characteristic curve was able to validate the predictive model (area = 0.891, standard error = 0.034, p < 0.001). CONCLUSION: In DS patients, preserved DH was significantly related to dynamic instability. This finding may represent a greater potential for slip progression over time in these patients. In contrast, disc degeneration on MRI, and spondylotic changes were inversely related to dynamic instability and may represent restabilization mechanisms that decrease the chance of future slip progression in DS.
ABSTRACT
Duchenne Muscular Dystrophy (DMD) is a progressive and lethal disease caused by mutations of the dystrophin gene. Currently no cure exists. Stem cell therapies targeting DMD are challenged by limited engraftment and rejection despite the use of immunosuppression. There is an urgent need to introduce new stem cell-based therapies that exhibit low allogenic profiles and improved cell engraftment. In this proof-of-concept study, we develop and test a new human stem cell-based approach to increase engraftment, limit rejection, and restore dystrophin expression in the mdx/scid mouse model of DMD. We introduce two Dystrophin Expressing Chimeric (DEC) cell lines created by ex vivo fusion of human myoblasts (MB) derived from two normal donors (MBN1/MBN2), and normal and DMD donors (MBN/MBDMD). The efficacy of fusion was confirmed by flow cytometry and confocal microscopy based on donor cell fluorescent labeling (PKH26/PKH67). In vitro, DEC displayed phenotype and genotype of donor parent cells, expressed dystrophin, and maintained proliferation and myogenic differentiation. In vivo, local delivery of both DEC lines (0.5 × 106) restored dystrophin expression (17.27%±8.05-MBN1/MBN2 and 23.79%±3.82-MBN/MBDMD) which correlated with significant improvement of muscle force, contraction and tolerance to fatigue at 90 days after DEC transplant to the gastrocnemius muscles (GM) of dystrophin-deficient mdx/scid mice. This study establishes DEC as a potential therapy for DMD and other types of muscular dystrophies.
Subject(s)
Dystrophin/metabolism , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/therapy , Animals , Cell Proliferation/genetics , Cell Proliferation/physiology , Cells, Cultured , Flow Cytometry , Fluorescent Antibody Technique , Humans , Mice , Muscle Development/genetics , Muscle Development/physiology , Real-Time Polymerase Chain ReactionABSTRACT
Cervical kyphotic deformity represents a difficult to treat pathology often arising from multiple factors including, but not limited to, traumatic injuries, degenerative changes, and ankylosing spondylitis. Furthermore, treatment of these deformities becomes increasingly difficult with any preexisting instrumentation. Currently, several options exist to treat these severe deformities, with the Smith-Petersen osteotomy and C-7 pedicle subtraction osteotomy being the most frequently used approaches. However, these techniques come with significant risk to the patient including nerve root injury as well as compression of the vertebral arteries. The authors here report on a series of 4 patients with rigid cervical deformity who underwent T-1 pedicle subtraction osteotomy. The authors review the relevant literature and provide a novel, less risky, and potentially more corrective approach for treating cervical deformities.
Subject(s)
Cervical Vertebrae/surgery , Kyphosis/surgery , Osteotomy , Thoracic Vertebrae/surgery , Aged , Cervical Vertebrae/diagnostic imaging , Female , Follow-Up Studies , Humans , Intraoperative Neurophysiological Monitoring , Kyphosis/diagnostic imaging , Middle Aged , Osteotomy/methods , Retrospective Studies , Thoracic Vertebrae/diagnostic imagingABSTRACT
CONTEXT: Cervical spondylotic myelopathy (CSM) is a progressive disease that can result in significant disability. Single-level stenosis can be effectively decompressed through either anterior or posterior techniques. However, multilevel pathology can be challenging, especially in the presence of significant spinal stenosis. Three-level anterior decompression and fusion are associated with higher nonunion rates and prolonged dysphagia. Posterior multilevel laminectomies with foraminotomies jeopardize the bone stock required for stable fixation with lateral mass screws (LMSs). AIMS: This is the first case series of multilevel laminectomy and fusion for CSM instrumented with posterior cervical cages. SETTINGS AND DESIGN: Three patients presented with a history of worsening neck pain, numbness in bilateral upper extremities and gait disturbance, and examination findings consistent with myeloradiculopathy. Cervical magnetic resonance imaging demonstrated multilevel spondylosis resulting in moderate to severe bilateral foraminal stenosis at three cervical levels. MATERIALS AND METHODS: The patients underwent a multilevel posterior cervical laminectomy and instrumented fusion with intervertebral cages placed between bilateral facet joints over three levels. Oswestry disability index and visual analog scores were collected preoperatively and at each follow-up. Pre- and post-operative images were analyzed for changes in cervical alignment and presence of arthrodesis. RESULTS: Postoperatively, all patients showed marked improvement in neurological symptoms and neck pain. They had full resolution of radicular symptoms by 6 weeks postoperatively. At 12-month follow-up, they demonstrated solid arthrodesis on X-rays and computed tomography scan. CONCLUSIONS: Posterior cervical cages may be an alternative option to LMSs in multilevel cervical laminectomy and fusion for cervical spondylotic myeloradiculopathy.
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CONTEXT: Posterior cervical cages have recently become available as an alternative to lateral mass fixation in patients undergoing cervical spine surgery. AIMS: The purpose of this study was to quantify the perioperative complications associated with cervical decompression and fusion in patients treated with a posterior cervical fusion (PCF) and bilateral cages. SETTINGS AND DESIGN: A retrospective, multicenter review of prospectively collected data was performed at 11 US centers. SUBJECTS AND METHODS: The charts of 89 consecutive patients with cervical radiculopathy treated surgically at one level with PCF and cages were reviewed. Three cohorts of patients were included standalone primary PCF with cages, circumferential surgery, and patients with postanterior cervical discectomy and fusion pseudarthrosis. Follow-up evaluation included clinical status and pain scale (visual analog scale). STATISTICAL ANALYSIS USED: The Wilcoxon test was used to test the differences for the data. The P level of 0.05 was considered significant. RESULTS: The mean follow-up interval was 7 months (range: 62 weeks - 2 years). The overall postsurgery complication rate was 4.3%. There were two patients with neurological complications (C5 palsy, spinal cord irritation). Two patients had postoperative complications after discharge including one with atrial fibrillation and one with a parietal stroke. After accounting for relatedness to the PCF, the overall complication rate was 3.4%. The average (median) hospital stay for all three groups was 29 h. CONCLUSIONS: The results of our study show that PCF with cages can be considered a safe alternative for patients undergoing cervical spine surgery. The procedure has a favorable overall complication profile, short length of stay, and negligible blood loss.
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INTRODUCTION: Lateral mass screw (LMS) fixation with plates or rods is the current standard procedure for posterior cervical fusion. Recently, implants placed between the facet joints have become available as an alternative to LMS or transfacet screws for patients with cervical spondylotic radiculopathy. The purpose of this study was to evaluate the biomechanical stability of the DTRAX(®) cervical cage for single- and two-level fusion and compare this to the stability achieved with LMS fixation with rods in a two-level construct. METHODS: Six cadaveric cervical spine (C3-C7) specimens were tested in flexion-extension, lateral bending, and axial rotation to ±1.5 Nm moment without preload (0 N) in the following conditions: 1) intact (C3-C7), 2) LMS and rods at C4-C5 and C5-C6, 3) removal of all rods (LMS retained) and placement of bilateral posterior cages at C5-C6, 4) bilateral posterior cages at C4-C5 and C5-C6 (without LMS and rods), and 5) C4-C5 and C5-C6 bilateral posterior cages at C4-C5 and C5-C6 with rods reinserted. RESULTS: Bilateral posterior cervical cages significantly reduced range of motion in all tested directions in both single- and multilevel constructs (P<0.05). Similar stability was achieved with bilateral posterior cages and LMS in a two-level construct: 0.6°±0.3° vs 1.2°±0.4° in flexion-extension (P=0.001), (5.0°±2.6° vs 3.1°±1.3°) in lateral bending (P=0.053), (1.3°±1.0° vs 2.2°±0.9°) in axial rotation (P=0.091) for posterior cages and LMS, respectively. Posterior cages, when placed as an adjunct to LMS, further reduced range of motion in a multilevel construct (P<0.05). CONCLUSION: Bilateral posterior cages provide similar cervical segmental stability compared with a LMS and rod construct and may be an alternative surgical option for select patients. Furthermore, supplementation of a lateral mass construct with posterior cages increases cervical spine stability in single- and multilevel conditions.
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INTRODUCTION: Supplemental posterior instrumentation has been widely used to enhance stability and improve fusion rates in higher risk patients undergoing anterior cervical discectomy and fusion (ACDF). These typically involve posterior lateral mass or pedicle screw fixation with significant inherent risks and morbidities. More recently, cervical cages placed bilaterally between the facet joints (posterior cervical cages) have been used as a less disruptive alternative for posterior fixation. The purpose of this study was to compare the stability achieved by both posterior cages and ACDF at a single motion segment and determine the stability achieved with posterior cervical cages used as an adjunct to single- and multilevel ACDF. METHODS: Seven cadaveric cervical spine (C2-T1) specimens were tested in the following sequence: intact, C5-C6 bilateral posterior cages, C6-C7 plated ACDF with and without posterior cages, and C3-C5 plated ACDF with and without posterior cages. Range of motion in flexion-extension, lateral bending, and axial rotation was measured for each condition under moment loading up to ±1.5 Nm. RESULTS: All fusion constructs significantly reduced the range of motion compared to intact in flexion-extension, lateral bending, and axial rotation (P<0.05). Similar stability was achieved with bilateral posterior cages and plated ACDF at a single level. Posterior cages, when placed as an adjunct to ACDF, further reduced range of motion in both single- and multilevel constructs (P<0.05). CONCLUSION: The biomechanical effectiveness of bilateral posterior cages in limiting cervical segmental motion is comparable to single-level plated ACDF. Furthermore, supplementation of single- and multilevel ACDF with posterior cervical cages provided a significant increase in stability and therefore may be a potential, minimally disruptive option for supplemental fixation for improving ACDF fusion rates.
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INTRODUCTION: We describe a patient who had cervical spine osteomyelitis caused by Blastomyces dermatitidis that resulted in cord compression and cervical spine instability. CASE PRESENTATION: A 25-year-old Hispanic woman presented with fever, sweats, neck pain, and an enlarging neck mass with purulent discharge after sustaining a C6 vertebral body fracture. Magnetic resonance imaging confirmed C6 vertebral osteomyelitis, demonstrated by vertebral body destruction, cervical spine instability, prevertebral abscess, and spinal cord compression. She underwent C6 anterior cervical corpectomy and fusion, with fungal cultures confirming Blastomyces dermatitidis. CONCLUSIONS: Anterior cervical corpectomy and fusion successful debrided, decompressed, and restored cervical spine stability in a patient with vertebral osteomyelitis caused by Blastomyces dermatitidis. The patient was subsequently treated with a 1-year course of itraconazole and had no recurrence of infection 4 years postoperatively.
Subject(s)
Antifungal Agents/administration & dosage , Blastomycosis/pathology , Cervical Vertebrae/pathology , Itraconazole/administration & dosage , Magnetic Resonance Imaging , Osteomyelitis/pathology , Spinal Cord Compression/pathology , Adult , Blastomycosis/complications , Blastomycosis/drug therapy , Decompression, Surgical , Drainage , Female , Fever/etiology , Humans , Neck Pain/etiology , Osteomyelitis/drug therapy , Osteomyelitis/microbiology , Spinal Cord Compression/etiology , Spinal Cord Compression/microbiology , Spinal Fusion , Treatment OutcomeABSTRACT
BACKGROUND: Pedicle screws are widely used in adolescent idiopathic scoliosis (AIS) surgeries. Pedicle screw malposition may lead to serious vascular and neurologic complications. Knowledge of the morphometric anatomy of the thoracic and lumbar vertebrae is essential for the surgeon while implanting pedicle screws. It has been reported that there is a reduction of pedicle width at the concavity of the curve in AIS patients. However, it is unclear if gender plays a role in this pedicle width pattern. The goal of this study is to assess the vertebrae morphology in a more homogeneous group of AIS patients - female patients with Lenke type 1 curve. METHODS: The thoracic and lumbar vertebra and pedicle morphometry of 17 consecutive Lenke type 1 female AIS patients was analyzed based on 1mm fine cut CT scans. Morphometric anatomy of 539 pedicles from T1 to L5 was studied. Measurements included pedicle length, chord length, transverse pedicle width, transverse pedicle angle and vertebral rotation angle. RESULTS: The mean age of the patients was 14 years old (range 12-18). The mean Cobb angle was 56° (range 43° -88°) and the mean angle of vertebral rotation varied between 4-13.8°. The apical vertebra was between T7 and T11. The transverse pedicle width was significantly smaller (p < 0.05) on the concave side in the apical region of the thoracic spine (T7 and T8), measuring between 2.1-2.2 mm on the concave side and 2.7-3.1 mm on the convex side. Meanwhile, in some upper thoracic vertebrae (T3, T4, T5), the width was significantly bigger (p < 0.05) on the concave side than on the convex side, measuring between 2.8-4 mm on the concave side and 1.8-2.4 mm on the convex side. In the lumbar spine, the width varied between 4.1-9.9 mm without significant differences between the concave and convex sides (p > 0.05). The pedicle length varied between 15.4-28.7 mm and was significantly smaller (p < 0.05) on the concave side at T4, T5 and L2. The chord length was shortest at T1, measuring 32.4 mm and increased gradually to 54.3 mm at L3 but no statistical difference was found between the concave and convex sides. The transverse pedicle angle varied between 11.8° and 35° and was significantly bigger on the concave side at T7 and on the convex side at L1 (p < 0.05). CONCLUSIONS: The vertebrae morphology in Lenke type 1 female AIS patients is substantially different from the vertebrae in normal spines especially at the apex and in the upper thoracic region. This is consistent with some previous reports which did not distinguish between male and female patients. Our findings suggest that gender does not play a major role in the vertebrae morphology pattern of AIS patients. Furthermore, recognizing this pattern is critical in order to optimize pedicle screw instrumentation and may allow for some leeway adjustments in the pedicle screw trajectory regardless of the methods of implantation.
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STUDY DESIGN: A single-center retrospective study. OBJECTIVE: To identify predictors of length of stay (LOS) days in patients undergoing 1 level minimally invasive (MIS) transforaminal lumbar interbody fusions (TLIF). SUMMARY OF BACKGROUND DATA: Recent studies suggest intraoperative fluid administration, and colloid and crystalloid administration among other intraoperative variables may prolong LOS days and increase complications. Therefore, an understanding of which preoperative, intraoperative, and immediate postoperative parameters best predict immediate LOS days will help risk stratify patients and guide decision making. METHODS: We retrospectively reviewed 104 patients undergoing a MIS TLIF at 1 institution between 2008 and 2010. Two groups were selected on the basis of the time of discharge. Group 1 consisted of patients discharged within 24 hours after surgery and group 2 consisted of patients discharged more than 24 hours after surgery. Multiple regression analysis was performed to determine which preoperative, intraoperative, and postoperative variables were independent predictors of LOS days. RESULTS: Seventy-eight patients (75%) with a LOS greater than 24 hours had significantly higher estimated blood loss, received more crystalloids, had higher total fluids, longer surgical time, lower end of case temperature, lower hemoglobin during hospitalization, and a lower preoperative narcotic use. Multiple regression analysis showed that significant predictors of increased LOS were postoperative creatinine, visual analogue scale score, intraoperative colloids, fluids input at the end of surgical case, crystalloid to colloid ratio, fluid balance, oxycodone (Oxycontin) use, mean percentage of fraction of inspired oxygen, and preoperative hemoglobin. CONCLUSION: Patients undergoing 1 level MIS TLIF for degenerative conditions can overall expect a short LOS postoperatively. Multiple preoperative, intraoperative, and immediate postoperative factors can prolong the LOS in this group. This information should help the surgical team in optimizing their intraoperative patient management.
Subject(s)
Length of Stay , Lumbar Vertebrae/surgery , Minimally Invasive Surgical Procedures/instrumentation , Spinal Fusion/instrumentation , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Operative Time , Postoperative Period , Retrospective Studies , Treatment OutcomeABSTRACT
The purpose of this study was to evaluate the effects of intraoperative fluid therapy on length of hospital stay and pulmonary complications in patients undergoing spine surgery. A total of 1307 patients were analyzed. Sixteen pulmonary complications were observed. Patients with a higher volume of administered crystalloids, colloids, and total intravenous fluids were more likely to have postoperative respiratory complications: the odds of postoperative respiratory complications increased by 30% with an increase of 1000 mL of crystalloid administered. The best cutoff point for total fluids was 4165 mL, with a sensitivity of 0.8125 and specificity of 0.7171, for postoperative pulmonary complications. A direct correlation existed between fluids and length of stay: patients who received >4165 mL of total fluids had an average length of stay of 3.88±4.66 days vs 2.3±3.9 days for patients who received <4165 mL of total fluids (P<.0001). This study should be considered as hypothesis-generating to design a prospective trial comparing high vs low intraoperative fluid regiments for patients undergoing spine surgery.