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Biomedical subjects

Francis H Shen

Publications and source records attributed to Francis H Shen.

30 records · Page 2Linked to original sources

Systemically administered mesenchymal stromal cells transduced with insulin-like growth factor-I localize to a fracture site and potentiate healing.

OBJECTIVE: To determine to the ability of systemically administered pluripotential mesenchymal stromal cells to localize to a fracture site and whether transduction with a therapeutic gene, insulin-like growth factor-I (D1-IGF-I), could potentiate healing. DESIGN: Murine model, basic science study. SETTING: Laboratory. SPECIMENS: Closed, transverse, mid-shaft femur fractures were produced in 108 Balb/c mice after intramedullary stabilization. INTERVENTIONS: A cloned, pluripotential, mesenchymal cell line, termed D1, was stably transfected with either the gene beta-galactosidase (D1-BAG) as a histologic marker or with the gene IGF-I (D1-IGF-I) growth factor. Mice received systemic injections of either D1-BAG cells for in vivo localization or D1-IGF-I for therapeutic intervention. A third group received lactated Ringer's solution and served as control. MAIN OUTCOME MEASUREMENTS: Sections obtained from the fracture site and contralateral femurs were examined histologically and by deoxyribonucleic acid-polymerase chain reaction (DNA-PCR) to detect the presence of transplanted cells at 2, 4, and 6 weeks after fracture. Matrix mineralization and callus maturation were evaluated by histology. RESULTS: At all time points, using histologic staining with X-gal and deoxyribonucleic acid-polymerase chain reaction for marker genes, there was a statistically greater number of transplanted cells ( p< 0.001) and significantly higher DNA-PCR for marker genes ( p< 0.001) in the fractured femurs than in the nonfractured femurs. Mice receiving D1-IGF-I cells demonstrated a greater percent of mineralized callus than controls at two weeks (p < 0.05). At 4 and 6 weeks, treated mice demonstrated on average greater mineralized matrix and accelerated progression to an osseous callus as compared with the control group. CONCLUSIONS: Cell-based gene therapy has the potential to deliver higher therapeutic levels of growth factors specifically at the site of cell localization while minimizing wider systemic side effects. This study demonstrates that systemically injected IGF-I transduced, mesenchymal cells are able to return to and repopulate the bone marrow. More importantly, these cells localize preferentially to a fracture site and accelerated fracture healing.

Animals↗

The fate of stable femoral components retained during isolated acetabular revision: a six-to-twelve-year follow-up study.

BACKGROUND: The decision as to whether to revise a well-fixed femoral component in hips requiring isolated acetabular revision is challenging. The purpose of the present study was to determine the long-term results of, and the complications associated with, retention of a stable and well-fixed femoral component during isolated acetabular revision. METHODS: We retrospectively reviewed the clinical and radiographic results for thirty-one patients (thirty-two hips) who underwent isolated revision acetabuloplasty without removal of a well-fixed femoral component. The reason for acetabular revision was aseptic loosening in thirty-one hips and malposition in one hip. Of the thirty-two femoral components, twenty-one were cemented and eleven were cementless. The average duration of follow-up from the time of the index revision was 8.1 years (range, 6.4 to 12.5 years), and the average duration of total service of the femoral component was seventeen years (range, seven to twenty-five years) from time of the initial implantation. The average age of the patients at the time of the index revision was sixty-six years (range, twenty-nine to eighty-seven years). RESULTS: Thirty-one (97%) of the primary femoral components were judged to be stable and well fixed at the latest follow-up evaluation. One femoral component (3%) was revised because of aseptic loosening, eight years after the index acetabular revision and seventeen years after the initial total hip arthroplasty. Radiographic evaluation of the thirty-one femoral components that were not revised demonstrated no evidence of loosening or subsidence. There were no dislocations, nerve palsies, or intraoperative fractures associated with retention of the femoral component. Twenty-seven (84%) of the acetabular components were judged to be stable at the latest follow-up evaluation. CONCLUSION: In hips treated with isolated acetabular revision, a well-fixed femoral component can be retained successfully without adversely affecting the acetabular exposure; the placement, position, or stability of the acetabular component; or the ability to restore bone stock. The data from the present study support the decision to retain a well-fixed femoral component when the acetabular component needs to be revised.

Acetabulum↗

Comparison of clinical and radiographic outcome in instrumented anterior cervical discectomy and fusion with or without direct uncovertebral joint decompression.

BACKGROUND CONTEXT: Anterior cervical discectomy and fusion (ACDF) is an established procedure for the operative treatment of cervical disc disease in patients with radiculopathy resulting from impingement from uncovertebral joint osteophytes. Studies demonstrate that direct decompression of the lesion provides good result. However, known complications include vertebral artery injury, dural tears, nerve root injury, loss of biomechanical stability and increased operative time. Other studies suggest that disc space distraction may play an important role by indirectly decompressing neural elements. Therefore, if equivalent functional outcomes can be achieved without sacrificing the uncovertebral joint, then potential morbidity and mortality could be decreased. PURPOSE: To assess and compare clinical and radiographic outcomes of patients with neck pain and cervical radiculopathy who underwent instrumented ACDF with or without direct uncovertebral joint decompression. STUDY DESIGN/SETTING: Retrospective clinical chart and radiographic review to assess clinical outcome and graft fusion in 109 patients who underwent one- or two-level ACDF with rigid anterior plate fixation. PATIENT SAMPLE: Radiographs and clinical charts for 109 patients (mean, 46 years; range, 27 to 83) who underwent ACDF with rigid anterior plate fixation were retrospectively reviewed at a single institution. Patients with radiculopathy resulting from herniated disc, spondylosis or a combination of both refractory to conservative treatment underwent surgery using a standard Smith-Robinson left-sided approach. Seventy-one patients who received direct uncovertebral joint decompression (Group 1) were compared with 38 patients without direct decompression but indirect decompression by disc space distraction (Group 2). In Group 1, 37 one-level and 34 two-level ACDFs were performed. In Group 2, 11 and 27 were one-level and two-level ACDFs, respectively. Smoking and work-related injuries involved 26.7% and 38.0% of Group 1 and 28.9% and 28.9% of Group 2, respectively. Autologous iliac crest grafts were used in 51 patients, whereas 58 patients received allograft. OUTCOME MEASURES: Independent blinded analyses of plain lateral neutral, flexion and extension radiographs were conducted to assess fusion, evaluate graft and plate and screw integrity (mean, 12 months). Clinical outcomes were reported as excellent, good, fair or poor (mean, 23 months) based on Odom's criteria. METHODS: Postoperative clinical outcome and radiographic studies of graft and instrument integrity were assessed in 71 patients undergoing ACDF with uncovertebral joint decompression and 38 patients without uncovertebral joint decompression, but with indirect decompression through disc space distraction. RESULTS: Fusion occurred in 95.8% of Group 1 and 100% of Group 2. In Group 1, 26.8% of the patients reported excellent results, 57.7% reported good results, 12.7% reported fair results and 2.8% reported poor results. In Group 2, 23.7% of the patients reported excellent results, 60.5% reported good results and 15.8% reported fair results. All nonunions reported good outcomes. Postoperative respiratory distress developed in one patient and dysphagia developed in another both from Group 1. No other complications were noted. The presence or absence of direct uncovertebral joint decompression and clinical outcome was not statistically significant (p>.05). The use of graft-type, operative level, presence of smoking and work-related injury in relation to clinical outcome was not found to be significant (p>.05). CONCLUSION: Good to excellent results were obtained in 84.5% and 84.2% of patients for Groups 1 and 2, respectively. Indirect foraminal decompression through distraction remains somewhat controversial during ACDF. However, sacrificing the uncovertebral joint can increase operative time and potentially increase complication rates. This study demonstrates that ACDF with or without direct uncovertebral joint decompression can provide good clinical results for neck pain with cervical radiculopathy. Therefore, routine direct uncovertebral joint decompression should not be undertaken during ACDF.

Cervical Vertebrae↗

Does rigid instrumentation increase the fusion rate in one-level anterior cervical discectomy and fusion?

BACKGROUND CONTEXT: Although plate fixation enhances the fusion rate in multilevel anterior cervical discectomy and fusion (ACDF), debate exists regarding the efficacy of nonplating to rigid plate fixation in one-level ACDF. PURPOSE: To determine the efficacy of nonplating to rigid plate fixation in regards to fusion rate and clinical outcome in patients undergoing one-level ACDF with autograft. STUDY DESIGN: A review of 69 consecutive patients who underwent one-level ACDF with autograft and with or without rigid anterior cervical plate fixation. PATIENT SAMPLE: Sixty-nine patients who underwent one-level ACDF (mean age, 45 years) were evaluated for radiographic evidence of fusion (mean, 14 months) and for clinical outcome. All patients received tricortical iliac crest autografts. Disc space distraction was 2 mm, the grafts were inserted with the cortical surface positioned anteriorly, and each graft was countersunk 2 mm from the anterior vertebral border. Thirty-eight patients underwent nonplated ACDF and 31 patients underwent plated ACDF. Eighteen Orion (Sofamor-Danek, Memphis, TN), eight Atlantis (Sofamor-Danek) and five PEAK polyaxial (Depuy-Acromed, Rayham, MA) anterior cervical plating systems were used. Rigid plate fixation was used in all patients with instrumentation. Postoperatively, hard collars were worn 6 to 8 weeks in nonplated patients and soft collars were worn for 3 to 4 weeks in plated patients. Twenty-four patients were smokers (54.2% nonplating; 45.8% plating) and work-related injuries entailed 23 patients (47.8% nonplating; 52.2% plating). OUTCOME MEASURES: Fusion was assessed based on last follow-up of lateral neutral, flexion and extension radiographs. Radiographs were evaluated blindly to assess fusion and instrumentation integrity between nonplated and plated patients. Clinical outcomes were assessed with the Cervical Spine Outcomes Questionnaire and also assessed on last follow-up as excellent, good, fair or poor based on Odom's criteria. METHODS: Fusion rate and postoperative clinical outcome were assessed in 69 patients who underwent one-level ACDF with autograft and with or without rigid anterior plate fixation. Additional risk factors were also analyzed. Statistical significance was established at p<.05. RESULTS: Sixty-six patients (95.7%) achieved a solid fusion (100% nonplated; 90.3% plated). Nonunions occurred in three patients (1 smoker; 2 nonsmokers) with Orion instrumentation. Slight screw penetration into the involved and uninvolved interbody spaces occurred in one patient who was a nonsmoker and did not achieve fusion. One superficial cervical wound infection was noted in a nonplated patient. No other intraoperative or postoperative complications were noted. No statistically significant difference was noted between nonplating to rigid plating upon fusion rate (p>.05). All nonunions occurred at the C5-C6 level. Mean estimated intraoperative blood loss was significantly greater in plated patients (p=.043). Revision surgery involved 9.7% of the plated patients, whereas none of the nonplated patients required reoperation. Postoperative clinical outcome was assessed in all patients (mean, 21 months). Excellent results were noted in 18.8%, good results in 72.5% and fair results in 8.7% of the patients. Nonunion patients reported satisfactory clinical outcome. No statistical significance was noted between clinical outcome of fused and nonfused patients, the presence of a work-related injury and the use of plating (p>.05). Demographics and history of smoking were not factors influencing fusion or clinical outcome in this series (p>.05). The effect on fusion by various plate types could not be discerned from this study. CONCLUSION: A 100% and 90.3% fusion rate was obtained for one-level nonplated and plated ACDF procedures with autograft, respectively. The effects of smoking or level of fusion could not be discerned from these one-level cases. Excellent and good clinical outcome results were obtained for 91.3%. Nonplating or rigid plate fixation for ACDF in properly selected patients to treat radiculopathy with or without myelopathy has a high fusion rate and yields a satisfactory clinical outcome. Although controversy exists as to the efficacy of rigid plate fixation in one-level ACDF, solid bone fusion can be adequately obtained without plate fixation and instrumentation-related complications can be avoided. In line with the literature, plate fixation should be reserved for patients unwilling or unable to wear a hard orthosis postoperatively for an extended period of time or for those patients who seek a quicker return to normal activities. Proper patient selection, meticulous operative technique and postoperative care is essential to promote optimal graft-host incorporation.

Adult↗

Rheumatoid arthritis: evaluation and surgical management of the cervical spine.

BACKGROUND CONTEXT: Rheumatoid arthritis is a debilitating polyarthropathic degenerative condition. Eighty-six percent of patients with rheumatoid arthritis have cervical spine involvement. Often these lesions are clinically asymptomatic or symptoms are erroneously attributed to peripheral manifestation of the patient's rheumatoid disease. Because these lesions are common and missed diagnosis can result in death, early recognition is vital. PURPOSE: The purpose of this literature review is to identify common lesions present in the rheumatoid neck and review diagnostic methods as well as treatment options for those requiring surgical intervention. STUDY DESIGN: A review of the English medical literature with focus on more recent studies on the presentation, diagnosis, management, surgical treatment and clinical outcomes of rheumatoid arthritis of the cervical spine. METHODS: A comprehensive literature review of the English medical literature obtained through Medline up to November 2003 was performed identifying relevant and more recent articles that addressed the presentation, evaluation, surgical management and outcomes of rheumatoid patients with cervical spine involvement. RESULTS: If left untreated, a large percentage of rheumatoid patients with cervical spine involvement progress toward complex instability patterns resulting in significant morbidity and mortality. Once myelopathy occurs, prognosis for neurologic recovery and long-term survival is poor. In properly selected patients, anterior and/or posterior cervical procedures can prevent neurologic injuries and preserve remaining function. CONCLUSION: Cervical spine involvement in the rheumatoid patient is common and progressive. Early diagnosis and treatment is imperative; however, surgical intervention should be considered carefully because associated morbidity and mortality is high.

Arthritis, Rheumatoid↗

Cell technologies for spinal fusion.

For a successful spinal fusion to occur, several vital elements are necessary. They consist of the presence of the bone-forming cell (osteoblast) or its precursor, the appropriate biological signals directing bone synthesis, and a biocompatible scaffold on which the process can occur. The most critical of these components is the osteoblast or its precursor, the mesenchymal stem cell (MSC), both of which possess the ability to form bone. As a result, many current techniques attempt to maximize the benefits derived from harvesting the ready source of MSCs from bone marrow, while minimizing the associated complications. These cellular technologies seek to improve on the harvest and concentration of the MSCs or enhance their delivery and action. This review focuses on the terminology, historical underpinnings, and current research rationale and techniques and discusses the possible future of these technologies.

Animals↗

Comparison of allograft to autograft in multilevel anterior cervical discectomy and fusion with rigid plate fixation.

BACKGROUND CONTEXT: A relatively high pseudarthrosis rate is associated with multilevel anterior cervical discectomy and fusion (ACDF). Anterior plate fixation increases fusion rate in multilevel ACDF. A debate still exists between the effectiveness of allograft versus autograft in plated multilevel ACDF. PURPOSE: To determine the efficacy of allograft versus autograft in fusion rate and clinical outcome in patients undergoing two- and three-level ACDFs with rigid anterior plate fixation. STUDY DESIGN: A retrospective radiographic and clinical review to assess fusion, risk factors and clinical outcome of 80 consecutive patients who underwent ACDF with rigid anterior plate fixation involving two and three levels with either allograft or autograft. PATIENT SAMPLE: There were 45 patients (56%) who had autogenous iliac crest tricortical grafts and 35 patients (44%) who received tricortical allograft with an average age of 49 years who were treated by multilevel ACDF with rigid anterior plate fixation at a single institution. Thirty-three Peak polyaxial (Depuy-Acromed, Rayham, MA), 26 Orion (Sofamor-Danek, Memphis, TN), 16 Atlantis (Sofamor-Danek, Memphis, TN) and 5 Synthes (Paoli, PA) anterior cervical plating systems were used. All patients underwent ACDF (61 two-level, 19 three-level) by a Smith Robinson technique. All patients had burring of the end plates, 2-mm distraction of the motion segment and graft countersunk 2 mm from the anterior vertebral border. Anterior cervical plate with unicortical screw purchase was used in all cases. Segmental screw fixation was performed in 46 patients. Soft collars were worn postoperatively for 3 to 4 weeks. OUTCOME MEASURES: Follow-up lateral neutral, flexion and extension radiographs were used to assess fusion. The radiographs were reviewed by an independent blinded observer in assessing fusion grades between autograft versus allograft. Clinical outcomes were rated excellent, good, fair and poor based on Odom's criteria. METHODS: Fusion rate and postoperative clinical outcome were assessed in 80 patients who underwent two- or three-level ACDF with rigid anterior plate fixation. Additional risk factors were also analyzed. RESULTS: Radiographic fusion was assessed in all patients (mean, 16 months). Seventy-eight patients (97.5%) achieved solid arthrodesis. Pseudarthrosis occurred in two patients who had allograft for two-level and three-level fusions. Nonsegmental screws were used in the two-level nonunion case. Postoperative dysphagia developed in one two-level nonunion patient, and revision surgery was performed in the other nonunion three-level patient. Twenty-three patients were smokers, and 26 patients had work-related injuries. Clinical outcome (mean, 20 months) was excellent in 23, good in 48 and fair in 9 patients. No statistical significance was noted between demographics, history of tobacco use, graft-type, end plate preparation technique, intermediate segmental screws, plate-type, clinical outcome of fused and nonfused patients and presence of work-related injuries (p>.05). CONCLUSIONS: A high fusion rate of 97.5% was obtained for multilevel ACDF with rigid plating with either autograft or allograft. In this study, nonunion occurred in patients with allograft but this difference was not statistically significant. Fusion was obtained in 97.8% of patients with segmental screw fixation and 97.1% with nonsegmental screw fixation. Nonsegmental screw fixation may contribute to less than adequate stability and contribute to a higher rate of nonunion, but such effects could not be discerned from this study. Excellent and good clinical outcome was noted in 88.8% of the patients. Proper patient selection and meticulous operative technique is essential to obtain high fusion rates and optimal clinical outcome, which is more important than graft type.

Adult↗