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Biomedical subjects

John P Kostuik

Publications and source records attributed to John P Kostuik.

At least 19 recordsLinked to original sources

Small intestinal submucosa as a potential bioscaffold for intervertebral disc regeneration.

STUDY DESIGN: To evaluate the capacity of porcine small intestine submucosa to support the in vitro proliferation of human disc cells and the synthesis of extracellular matrix that could restore the biochemical properties of the disc. OBJECTIVE: To evaluate if porcine small intestine submucosa is a potential bioactive scaffold for rescuing degenerative disc cells. SUMMARY OF BACKGROUND DATA: Discogenic back pain is associated with alterations of the disc and abnormal turnover of the disc extracellular matrix. We hypothesize that a biodegradable and biocompatible acellular scaffold such as small intestine submucosa, which contains entrapped growth factors, may stimulate disc cells to synthesize extracellular matrix, thereby arresting the degeneration, or even promoting the regeneration, of the disc. METHODS: Human degenerative anulus and nucleus cells were seeded onto small intestine submucosa scaffolds, and evaluated over a 3-month period for cell growth (proliferation assay, deoxyribonucleic acid content) and matrix composition (glycosaminoglycan and collagen contents). RESULTS: As hematoxylin and eosin staining revealed, more than 70% of seeded cells attached to the small intestine submucosa surface and invaded throughout the scaffold. The macroscopic appearance of cell-seeded scaffolds was dramatically modified over time. Cell metabolic activity was confirmed for up to 3 months. Seeded scaffolds showed a higher glycosaminoglycan content as compared to control scaffolds. Toluidine blue staining detected large areas of proteoglycans. Positive gene expression for collagens I, II, and X, aggrecan, and Sox-9 confirmed deposition of new extracellular matrix components. CONCLUSIONS: This pilot study shows that small intestine submucosa is a promising bioactive material that could potentially serve as a temporary scaffold for intervertebral disc regeneration.

Animals↗

In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion.

STUDY DESIGN: A posterolateral lumbar interbody arthrodesis animal model was selected to evaluate the percutaneous delivery of OP-1 plasmid DNA. OBJECTIVE.: To evaluate the feasibility of achieving ectopic bone formation using nonviral gene delivery with a minimally invasive technique, by coinjecting plasmid DNA encoding OP-1 with collagen into the paraspinal muscle. SUMMARY OF BACKGROUND DATA: Osteoinductive proteins show great promise for achieving spine fusion but suffer from poor bioavailability. Viral gene transfer can produce therapeutic and sustained levels of osteoinductive proteins to achieve osteogenesis in a variety of animal models. Toxicity and immunogenicity concerns, however, limit the appeal of viral gene therapy for spine fusion. METHODS: Single-level posterior lumbar arthrodesis was attempted at L5-L6 in 64 adult Sprague-Dawley rats bilaterally. OP-1 plasmid DNA was injected with and without collagen carrier above the L5 transverse process either percutaneously or after open surgery. Bone formation was evaluated at 2 and 4 weeks by manual palpation, posterolateral radiographs, and nondecalcified histology. Control animals received the rhOP-1 protein. RESULTS: Bone formation was detected histologically after the percutaneous and open surgical delivery of 25 microg or 500 microg, respectively, of OP-1 plasmid DNA (pVR1055-OP1) and collagen (bone formation = 75% and 50%), but was weaker than that observed after injection of 30 microg of rhOP-1 protein and collagen (bone formation = 100%). Single-level spine fusion was only achieved in groups receiving percutaneous OP-1 protein and collagen (30 microg protein, fusion rate = 100%) or high concentrations of OP-1 protein alone (40 microg protein, 100%), as confirmed through manual palpation, histology, and radiography. CONCLUSIONS.: These data confirm that OP-1 plasmid DNA can successfully generate bone formation in vivo.

Animals↗

Interaction of human mesenchymal stem cells with disc cells: changes in extracellular matrix biosynthesis.

STUDY DESIGN: To evaluate the in vitro interactions between human mesenchymal stem cells (MSCs) and degenerative disc cells. OBJECTIVES: To demonstrate the potential of MSCs in regulating the extracellular matrix synthesis of degenerative disc cells. SUMMARY OF BACKGROUND DATA: Culture of degenerative disc cells followed by their reinsertion into a disc can retard the degeneration process in an animal model. However, harvesting cells without accelerating degeneration is problematic. Autologous MSCs can be safely harvested from the bone marrow and transplanted into degenerative discs. METHODS: Human degenerative nucleus pulposus (NP), anulus fibrosus (AF) cells, and MSCs were cultured as pellets, and coculture pellets were formed by addition of MSCs to disc cells (50:50 ratio). Glycosaminoglycan (GAG) and DNA content were measured. Proteoglycan synthesis was analyzed by RT-PCR and western blot. Type II collagen expression was assessed by immunohistochemistry. RESULTS: Coculture pellets formed by the addition of MSCs to AF cells were superior in size to all other pellets. AF/MSC pellets showed higher experimental GAG content than the predicted values represented by the sum of individual control pellets, with 10.2 versus 5.6 microg/pellet at week 3, respectively. The effect was not observed in the NP/MSC coculture, or when chondrogenic medium was used. Close contact between cells was necessary to obtain this enhancement of GAG content. Proteoglycan and collagen expression in both individual and coculture pellets was confirmed by PCR analysis and western blot. CONCLUSION: Addition of MSCs to AF cells resulted in an up-regulation of the proteoglycans synthesis. This study provides the rationale for further investigation of the potential of MSC therapy in treating intervertebral disc degeneration.

Adult↗

Spinal fusion after revision surgery for pseudarthrosis in adult scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE.: To decipher the incidence, characteristics, functional outcomes, and complications of spinal fusion after revision surgery for recurrent pseudarthrosis in adult patients with scoliosis. SUMMARY OF BACKGROUND DATA: While the rate of spinal fusion has been examined in the past, there have been no studies that have examined the incidence, characteristics, functional outcomes, and complications of spinal fusion after pseudarthrosis repair in adult patients with scoliosis. MATERIALS AND METHODS: A total of 132 patients with failed spinal fusion surgery for adult scoliosis and painful pseudarthroses were studied. Each patient had an average of 3.7 spinal surgeries before undergoing revision at our institution. In addition to clinical assessment and imaging studies, pseudarthrosis was confirmed intraoperatively in all patients. All patients underwent reinstrumentation and fusion along with adjunctive procedures as needed. Spinal fusion was assessed clinically and radiographically after surgery for a minimum of 40 months. Subjective functional outcomes and complications associated with the procedures were also studied. RESULTS: The overall incidence of spinal fusion after revision surgery for pseudarthrosis in adult scoliosis was 90%. There was a propensity for pseudarthrosis to recur at the thoracolumbar and lumbosacral junctions. Increasing thoracolumbar kyphosis and loss of sagittal balance were significant risk factors for recurrent pseudarthrosis after revision surgery (mean thoracolumbar kyphosis of 23 degrees and mean sagittal balance of 7.9 cm anteriorly associated with persistent pseudarthrosis). Additionally, patients with multiple preoperative sites of pseudarthroses were at a higher risk for continued pseudarthrosis after surgery. Cigarette smoking, age, and surgical approach did not have any significant correlation with pseudarthrosis. Seventy-two percent of patients were satisfied with the outcome and 80% would have chosen to undergo surgery again if necessary. Thirty-three percent of patients who underwent surgery had some complication related to the surgery. CONCLUSION: Revision surgery for pseudarthrosis repair in adult scoliosis is most successful at attaining fusion when thoracolumbar and overall sagittal alignment are restored as much as possible.

Adult↗

Temperature-responsive hydroxybutyl chitosan for the culture of mesenchymal stem cells and intervertebral disk cells.

Temperature-responsive polymers are attractive candidates for applications related to injectable delivery of biologically active therapeutics, such as stem cells. In this study, we evaluate the potential of thermosensitive hydroxybutyl chitosan (HBC) as a biomaterial for the culture of human mesenchymal stem cells (hMSC) and cells derived from the intervertebral disk, with the eventual goal of using the HBC polymer as an injectable matrix/cell therapeutic. Conjugation of hydroxybutyl groups to chitosan renders the polymer water soluble and thermally responsive. Below its lower critical solution temperature, a solution of HBC can be maintained indefinitely in its solvated state. Upon exposure to a 37 degrees C environment, within 60 s, a 3.8 wt% HBC solution rapidly forms a gel that can be maneuvered with forceps. Upon cooling, the gel once again is able to revert to its solvated state. The gel exhibits a dramatic increase in both G' and G'' with increasing temperature, signifying a temperature-dependent enhancement of gel mechanical properties. Although a solid structure upon gelation, due to its physical nature of polymer interaction and gel formation, the gel exhibits a fluid-like viscoelastic behavior when exposed to shear stresses of up to 10% strain, with both G' and G'' approaching zero with increasing shear stress. Formulations of HBC gels presented in this study have gelation temperatures ranging from 13.0 to 34.6 degrees C and water contents of 67-95%. Minimal cytotoxicity in MSC and disk cell cultures was observed with these polymers up to a concentration of 5 wt%. Detection of metabolic activity, genetic analysis of synthesized mRNA, and histological staining of MSC and disk cell cultures in these gels collectively indicate cell proliferation without a loss in metabolic activity and extracellular matrix production. This study suggests the potential of HBC gel as an injectable carrier for future applications of delivering therapeutics to encourage a biologically relevant reconstruction of the degenerated disk.

Aggrecans↗

Lumbar nerve root palsy after adult spinal deformity surgery.

STUDY DESIGN: A retrospective study was conducted to investigate the incidence and prognosis of postoperative lumbar nerve root palsy after surgical treatment for adult spinal deformity. OBJECTIVE: To decipher the incidence of postoperative lumbar nerve root palsy and recovery in 361 adult spinal deformity patients who underwent 407 spinal fusion surgeries. SUMMARY OF BACKGROUND DATA: Although lumbar nerve root palsy is a known complication of spinal surgery, there are no large studies that have examined its incidence or prognosis. METHODS: Three hundred and sixty-one consecutive patients who underwent 407 procedures for adult deformity spinal surgery were reviewed. Patients in this study did not have spinal cord injury or nerve root compression on the postoperative imaging study (obtained for change in neurologic examination). The incidence of nerve root palsy was based on postoperative muscle strength, which was followed for a minimum of 3 and an average of 7 years. RESULTS: The overall incidence of lumbar nerve root palsy was 2.9% with a 1.4% incidence in primary and 3.8% incidence in revision surgery. The incidence was 0.9, 1.5, and 7.4% for fusion of <5 levels, 5 to 10 levels, and >10 levels, respectively. The incidence of nerve root palsy for posterior only, same day anterior-posterior, and staged posterior was 1.3, 3, and 7.2%, respectively. While L5 was the most commonly injured nerve root, all other lumbar nerve roots were also involved. There were no S1 injuries. Although there was some recovery in most injuries, Grade IV injuries had the best recovery at 1-year follow-up. CONCLUSION: Patients with increasingly complex spinal deformities are at a higher risk for postoperative lumbar nerve root palsy. These injuries can be treated nonoperatively when there is no identifiable cause on postoperative imaging studies.

Adult↗

Central cord syndrome after total hip arthroplasty: a patient report.

STUDY DESIGN: Case report. OBJECTIVE: To present a patient with central cord syndrome injury after total hip arthroplasty performed under general endotracheal anesthesia. SUMMARY OF BACKGROUND DATA: Central cord syndrome, a common injury usually sustained as a result of an extension injury to the cervical spine, often occurs in geriatric patients with underlying spondylotic changes. The injury results in weakness and sensory changes, which are more pronounced in the upper than in the lower extremities. Patients with this syndrome experience variable return of function, but some degree of residual deficit and spasticity is likely. METHODS: The medical record, including the intraoperative anesthesia records, operative notes, progress notes, discharge summary, clinic notes, and radiology studies and reports, was reviewed. RESULTS: The patient developed signs of central cord syndrome after total hip arthroplasty. Despite nonoperative intervention, including physiotherapy, the patient's upper and lower extremity weakness continued. Magnetic resonance imaging revealed evidence of cervical cord compression, and the patient underwent a cervical laminectomy, which produced mild improvement in his symptoms. CONCLUSIONS: To avoid life-altering complications, it is important to evaluate the cervical spine (especially in the elderly), avoid neck extension during intubation, and use careful airway management in patients with suspected stenosis/spondylosis.

Aged↗

Sacral insufficiency fracture surgically treated by fibular allograft.

Sacral insufficiency fractures have been known to occur distally after long instrumentation to the sacrum. Most such fractures are treated nonoperatively, but surgery is indicated for patients who have nonunions, persistent pain, neurologic deficits, or gross displacement. The current report elucidates the potential complication of sacral fracture after long lumbar arthrodesis, reviews the pertinent literature, presents three patients with sacral fractures after long instrumented lumbar spinal arthrodesis to the sacrum, and describes a new surgical technique for stabilizing such fractures. One patient was treated nonoperatively, and two patients were treated with arthrodesis from a posterior approach and augmentation with a strut fibular allograft. All three patients were followed to radiographic and clinical union. The authors conclude that sacral fracture is a potential complication after a long lumbar arthrodesis. Nonoperative techniques are often successful, but when they are not, a new technique using fibular allografts can be successful.

Aged↗

Evaluation of registration methods used in frameless stereotactic surgery for the lumbar and cervical regions of the spine.

Computer-assisted pedicle screw insertion is feasible but has proved to be problematic. The purpose of this study was to detail the accuracy of registration techniques and pedicle screw insertion using a frameless stereotactic system. Two registration techniques were evaluated on a model spine. The frameless stereotactic system was then used to insert 26 pedicle and 8 lateral mass screws in human cadavers. For posterior vertebral elements, trajectory accuracy was 2.5 +/- 1.0 mm between T12 and L5 and 2.2 +/- 0.9 mm between C2 and T1. Registration of the anterior elements, however, was less accurate. Despite this flaw, all screws were inserted without penetrating the cortex. Screw trajectory was accurate to 2 degrees. The main limitation of frameless stereotactic surgery in the spine stems from the fact that only the posterior vertebral elements are used during registration. Despite this flaw, the system placed all screws correctly. Given these limitations, we believe that this system is most useful for locating the screw insertion point and providing a trajectory in the pedicle.

Bone Screws↗

Functional outcome and radiographic correction after spinal osteotomy.

STUDY DESIGN: A prospective clinical trial to study the radiographic parameters and functional outcome in patients undergoing spinal osteotomy. OBJECTIVES: To determine whether correction of specific radiographic parameters is associated with improved functional outcome. SUMMARY OF BACKGROUND DATA: Although vertebral osteotomies have been shown to improve functional outcome in patients with spinal deformity, no prospective reports have studied whether correction of specific radiographic parameters is associated with improvement in functional outcome. METHODS: Eighty-three patients with fixed sagittal and/or coronal deformity were followed over a 7-year period. Patients were evaluated clinically and radiographically and completed a SF-36 Health Survey and American Academy of Orthopedic Surgeons Modems Instrument questionnaire. Spearman correlation analysis was used to determine the association between correction of radiographic parameters and functional outcome. RESULTS: Mean preoperative lumbar lordosis measured -14.2 degrees (i.e., kyphosis) with an average postoperative correction of 27.9 degrees. Mean preoperative lumbar scoliosis measured 40.1 degrees with an average postoperative correction of 15.1 degrees. Mean preoperative plumb sagittal and coronal plane alignment was 8.37 cm and 4.22 cm, respectively; after surgery they improved to 3.33 cm and 2.31 cm, respectively. A significant association was found between sagittal angular correction and physical function (P = 0.034) and role-physical (P = 0.01) when postoperative lumbar lordosis was >25 degrees. A significant association was also found between plumb coronal correction and physical function (P = 0.041), vitality (P = 0.05), and social function (P = 0.047) when postoperative plumb coronal alignment was <2.5 cm. CONCLUSIONS: Correction of sagittal and coronal deformity is important in the treatment of spinal deformity. A significant association was found between outcomes and radiographic correction of coronal and/or sagittal deformity if postoperative sagittal lordosis was >25 degrees and if postoperative plumb coronal alignment was <2.5 cm. Therefore, these radiographic parameters should be the goal of a spinal osteotomy. The surgery has a relatively high complication rate.

Adult↗

The etiology of adolescent idiopathic scoliosis.

The etiology of adolescent idiopathic scoliosis (AIS), the most common form of scoliosis, is unclear. Researchers with divergent perspectives have tried to better define this etiology. Genetics, growth hormone secretion, connective tissue structure, muscle structure, vestibular dysfunction, melatonin secretion, and platelet microstructure are major areas of focus. In this article, we review the literature in these areas and present the consensus on proposed hypotheses. Studies that simplify the etiology to a single factor have been inconclusive or unsuccessful. Most likely, the etiology is multifactorial, and reported associations are links in pathogenesis rather than etiologic factors. Research is needed to better define the role of all factors in AIS development.

Adolescent↗

Role of femoral ring allograft in anterior interbody fusion of the spine.

A review was carried out on 59 patients (10 males and 49 females) who had anterior interbody fusion performed with femoral ring allograft packed with autograft bone chips with a minimum follow up of 2 years. The average age at the time of surgery was 49.1 year old (26 to 75). The total number of levels grafted was 141. The diagnosis consisted of multiple degenerative disease in 6, degenerative change below the long segment of fusion for scoliosis in 9, osteoporosis with collapsed fracture in 3, pseudarthrosis after posterior laminectomy and fusion in 35, congenital scoliosis in 3, scoliosis in 2 and paralytic scoliosis due to multiple sclerosis in one. The distribution of levels fused was T12-L1 in 6, L1-2 in 12, L2-3 in 17, L3-4 in 22, L4-5 in 35 and L5-S1 in 39. The remaining 10 levels were in the lower thoracic areas (T7-T12). The operations were performed as anterior fusion alone in 13 patients, one-stage anterior and posterior fusion in 26 patients and two-stage surgery in 20 patients. Anterior instrumentation was used in all 141 levels. At average follow-up (33.7 months) there was no significant change in allograft angles (average = 1.6 degrees ). Fusion of the allograft was classified by Bridwell's grading system. At 24 months of the follow up, 97 % of the allografts were in grade I (fully incorporated) and 3% were in grade II (partially incorporated). Compared to 12 months follow-up only 76.2% of the grafts were in grade I, 28 % were in grade II and 0.8% were in grade III. Two patients had deep posterior infections which required further surgery (without resorption of the allograft anteriorly). One patient had a screw migration anteriorly which required removal. Three patients had persistence of radiolucent line at one of the vertebral end plates - graft interfaces but no subsidence of the graft or pain. In conclusion, the femoral ring allograft appeared to benefit the anterior interbody fusion in complex spinal surgery.

Journal Article↗