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Biomedical subjects

Ben B Pradhan

Publications and source records attributed to Ben B Pradhan.

11 recordsLinked to original sources

Controlling bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth using fibrin glue.

STUDY DESIGN: An in vitro and in vivo study. OBJECTIVE: To evaluate the ability of fibrin glue to limit diffusion of recombinant human bone morphogenetic protein (rhBMP)-2 and its ability to protect spinal nerves from rhBMP-2 stimulated bone growth. SUMMARY OF BACKGROUND DATA: Studies have shown bone morphogenetic protein (rhBMP-2) stimulated bone growth can encroach on the spinal canal and nerves, causing neural compression. More recently, rhBMP-2 use in the cervical spine has been associated with life-threatening swelling. Fibrin glue has been used as a biologic carrier but has not been evaluated for its ability to limit rhBMP-2. METHODS: In phase 1 of the study, rhBMP-2 soaked absorbable collagen sponges (ACS) were encapsulated in fibrin glue and immediately incubated in physiologic lactated ringers solution at 38 degrees C. Samples of solution were tested for rhBMP-2 concentration. In phase 2 of the study, rats were surgically treated with laminectomy and placement of rhBMP-2/ACS versus laminectomy and placement of fibrin glue before placement of rhBMP-2/ACS. After 8 weeks, animals were euthanized and imaged using micro-computerized tomography. RESULTS: The diffusion study showed a significant limitation in rhBMP-2 diffusion when encapsulated in fibrin glue. The laminectomy study revealed blockage of bone formation by fibrin glue and protection of the spinal canal. CONCLUSIONS: Fibrin glue can limit the diffusion of rhBMP-2, and, thus, it can be used to help protect the spinal canal and nerve roots from rhBMP-2 stimulated bone growth.

Animals↗

Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2.

STUDY DESIGN: This is a prospective cohort study examining the results and radiographic characteristics of anterior lumbar interbody fusion (ALIF) using femoral ring allografts (FRAs) and recombinant human bone morphogenetic protein-2 (rhBMP-2). This was compared to a historical control ALIF using FRAs with autologous iliac crest bone graft (ICBG). OBJECTIVE: To determine whether the use of rhBMP-2 can enhance fusion ALIF with stand-alone FRAs. SUMMARY OF BACKGROUND DATA: ALIF is a well-accepted procedure in reconstructive spine surgery. Advances in spinal surgery have produced a multitude of anterior interbody implants. The rhBMP-2 has promoted fusion in patients undergoing ALIF with cages and threaded allograft dowels. The FRA still remains a traditional alternative for anterior support. However, as a stand-alone device, the FRA has fallen into disfavor because of high rates of pseudarthrosis. With the advent of rhBMP-2, the FRA may be more attractive because of its simplicity and remodeling potential. It is important to understand the implications when rhBMP-2 is used with such structural allografts. METHODS: A total of 36 consecutive patients who underwent ALIF with stand-alone FRAs by a single surgeon (E.G.D.) at 1 institute were included. A cohort of 9 consecutive patients who received FRAs filled with rhBMP-2 was followed prospectively. After noticing suboptimal results, the senior author terminated this method of lumbar fusion. A total of 27 prior consecutive patients who received FRAs filled with autogenous ICBG were used for comparison. Analyzing sequential radiographs, flexion-extension radiographs, and computerized tomography with multiplanar reconstructions determined nonunions. Minimum follow-up was 24 months. RESULTS: Pseudarthrosis was identified in 10 of 27 (36%) patients who underwent stand-alone ALIF with FRAs and ICBG. Nonunion rate was higher among patients who received FRAs with rhBMP-2 (i.e., 5 of 9 [56%]). Statistical significance was not established because of the early termination of the treatment group (P > 0.3). Of interest, radiographs and computerized tomography revealed early and aggressive resorption of the FRAs when used with rhBMP-2. This preceded graft fracture and even disintegration, resulting in instability and eventual nonunion. CONCLUSION: The use of rhBMP-2 did not enhance the fusion rate in stand-alone ALIF with FRAs. In fact, the trend was toward a higher nonunion rate with rhBMP-2, although this was not significant with the numbers available. This result appears to be caused by the aggressive resorptive phase of allograft incorporation, which occurs before the osteoinduction phase.

Adult↗

Computed tomography assessment of the accuracy of in vivo placement of artificial discs in the lumbar spine including radiographic and clinical consequences.

STUDY DESIGN: Prospective cohort study of 52 patients who had undergone artificial lumbar disc replacement. OBJECTIVES: To evaluate the implantation accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis migration, and the clinical consequences of implant position. SUMMARY OF BACKGROUND DATA: Accuracy of spinal prosthesis implantation has not been evaluated rigorously, especially with a mini-incision approach. It is unknown if the inexact placement of a mobile device in the spine has any biomechanical, radiographic, or clinical repercussions. METHODS: A total of 52 consecutive patients were treated using standard methods of disc implantation with an intervertebral prosthesis. Computed tomography scans were performed within 3 days and again at 6 to 24 months. An independent radiologist analyzed the images for prosthesis position, rotation, migration, and facet changes. Results were compared with clinical outcome, measured by the Visual Analog Scale and Oswestry Disability Index. RESULTS: Deviation of the prosthesis from the center position was under 1.2 mm, and rotation off of midline was under 12 degrees. Follow-up CT scans showed no migration or facet changes. Regression analysis showed no correlation of prosthesis position with clinical outcome. CONCLUSIONS: Current prosthetic disc implantation methods, with minimally invasive access techniques, are relatively accurate. Although there can be deviation of the prosthesis from ideal placement, no repercussions were attributable.

Adult↗

Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment.

STUDY DESIGN: A retrospective study of patients who underwent 1-3-level kyphoplasty procedures at a single institute. OBJECTIVE: To examine and compare the effects of single and multilevel kyphoplasty procedures on local versus overall sagittal alignment of the spine. SUMMARY OF BACKGROUND DATA: Cement augmentation has been a safe and effective method in the treatment of symptomatic vertebral compression fractures (VCFs). In addition to providing rapid pain relief, balloon tamp kyphoplasty has reduced acute fractures, allowed controlled cement placement under lower pressure, and resulted in improvement of deformity. The restoration of normal overall spinal sagittal alignment in the elderly patient with a VCF and kyphotic deformity has obvious benefits. Although significant correction of local kyphosis (fractured vertebra) has been reported in the literature, to our knowledge, there have been no reports on whether this leads to an improved overall sagittal alignment. METHODS: A total of 65 consecutive patients with symptomatic VCFs who underwent 1-3-level kyphoplasty procedures were included in the study. Preoperative and postoperative radiographs were analyzed to quantify local and overall spinal sagittal alignment correction. Preoperative and postoperative vertebral heights at the fractured levels were also measured and categorized into anterior, middle, or posterior vertebral heights. RESULTS: Measurements revealed that kyphoplasty reduced local kyphotic deformity at the fractured vertebra by an average of 7.3 degrees (63% of preoperative kyphosis). This result did not translate to similar correction in overall sagittal alignment. In fact, angular correction decreased to 2.4 degrees (20% of preoperative kyphosis at fractured level) when measured 1 level above and below. The angular correction further decreased to 1.5 degrees and 1.0 degrees (13% and 8% of preoperative kyphosis at fractured level), respectively, at spans of 2 and 3 levels above and below. Average height gain was highest in the middle of the vertebral body (39% increase) compared to the anterior or posterior edges (19% and 3% increases, respectively). With multilevel kyphoplasty procedures, higher angular gains were seen over more vertebrae compared to the 7.3 degrees for a single-level kyphoplasty: 7.8 degrees over 2 levels and 7.7 degrees over 3 levels for 2 and 3-level kyphoplasty procedures, respectively. Kyphoplasty was able to achieve higher angular reduction in thoracic versus lumbar fractures (8.5 vs. 6.4 degrees, P < 0.01). The angular correction was also better maintained over adjacent segments in the thoracic spine. CONCLUSION: The majority of kyphosis correction by kyphoplasty is limited to the vertebral body treated. The majority of height gained after kyphoplasty occurs in the midbody. Higher correction over longer spans of the spine can be achieved with multilevel kyphoplasty procedures, in proportion to the number of levels addressed. Notwithstanding its well-published clinical efficacy, it is unrealistic to expect a 1 or 2-level kyphoplasty to improve significantly the overall sagittal alignment after VCFs.

Aged↗

Clinical results of ProDisc-II lumbar total disc replacement: report from the United States clinical trial.

The much-awaited clinical use of lumbar artificial discs has begun in the United States. The United States Investigational Device Exemption (US IDE) clinical trial of the ProDisc-II prosthetic disc (Synthes, Paoli, PA) was recently completed, with all indications that it meets or surpasses the test of equivalence against fusion controls. This is a review of the clinical performance of the ProDisc-II artificial disc and includes an interim report from the US IDE trial at one site.

Adult↗

A metatarsal equivalent to the metacarpal index in Marfan syndrome.

BACKGROUND: Foot problems are common in patients with Marfan syndrome because of the ligamentous laxity that affects the weightbearing joints most. Such patients frequently are seen by their general practitioners or podiatrists. Educating primary health care providers about a metatarsal index, if it is sufficiently sensitive and specific, may help patients get early and appropriate workup for connective tissue disorders. METHODS: A metatarsal equivalent to the metacarpal index (MCI) in the hand was evaluated as a diagnostic tool for Marfan syndrome (and possibly other connective tissue disorders). Fifty-six patients were studied. Sixteen had a genetic diagnosis of Marfan syndrome. There were 20 controls each for the MCI and the metatarsal index (MTI). Hand and foot radiographs were reviewed. RESULTS: The average MCI in patients with Marfan syndrome was 9.8 compared to 7.6 in the control group (p < 0.0005). The average MTI was 12.7 and 9.8, respectively (p < 0.0005). An MCI value of 8.5 and an MTI value of 10.5 had the best statistical profiles (combination of sensitivity and specificity) in diagnosing Marfan syndrome in our study population. CONCLUSION: The MTI as a screening tool for Marfan syndrome is as effective as, if not more than, the well-recognized MCI.

Adolescent↗

Misrepresentation of research publications among orthopedic surgery fellowship applicants: a comparison with documented misrepresentations in other fields.

STUDY DESIGN: A retrospective study was used to review fellowship applications over 3 years. OBJECTIVES: To assess the prevalence of research misrepresentation in orthopedic fellowship applications, and to compare such activity between subspecialties (e.g., spine, sports, hand). SUMMARY OF BACKGROUND DATA: Competition for orthopedic surgery fellowships is intense. The applicant pool includes orthopedic, plastic, and general surgeons, as well as neurosurgeons. Residency and fellowship training programs in other disciplines have documented shocking levels of misrepresentation in the curriculum vitae of prospective applicants. However, no study has looked at orthopedic residents applying for subspecialty fellowship programs. METHODS: A retrospective analysis investigated 280 applications for fellowship positions in the department of orthopedic surgery at the authors' academic institution from 1996 to 1998 inclusively. To allow for press and publication delays, a minimum 24-month follow-up period was instituted. The listings of applicants' research publications were analyzed for evidence of misrepresentation through an exhaustive literature search. Only the most obvious confirmable discrepancies were labeled as misrepresentations. The results then were compared with those found in studies conducted in other fields: gastroenterology fellowship, emergency medicine residency, pediatric residency, dermatology residency, orthopedic residency, and medical faculty applications. RESULTS: Among 280 (54%) applicants for orthopedic surgery fellowships, 151 claimed journal publications. It was found that 16 (10.6%) of these 151 applicants had misrepresented their citations. This rate was highest in spine fellowship applicants (20%). However, considering the numbers available, this was not significantly different among the various subspecialty fellowship applicants (P > 0.1). In addition, various demographic data did not correlate with the rate of misrepresentation (P > 0.1). These results are comparable with those reported in other medical fields (P > 0.1). CONCLUSIONS: Misrepresentation occurs in orthopedic fellowship applications at a rate comparable with that observed in other fields. This rate is not different among the various subspecialties in orthopedics. Policies that may lessen the incidence of falsification on curriculum vitae should be instituted in an attempt to curb such activity.

Fellowships and Scholarships↗

Misrepresentation of research publications among orthopedic surgery fellowship applicants: a comparison with documented misrepresentations in other fields.

Study Design. A retrospective study was used to review fellowship applications over 3 years. Objectives. To assess the prevalence of research misrepresentation in orthopedic fellowship applications, and to compare such activity between subspecialties (e.g. spine, sports, hand). Summary of Background Data. Competition for orthopedic surgery fellowships is intense. The applicant pool includes orthopedic, plastic, and general surgeons, as well as neurosurgeons. Residency and fellowship training programs in other disciplines have documented shocking levels of misrepresentation in the curriculum vitae of prospective applicants. However, no study has looked at orthopedic residents applying for subspecialty fellowship programs. Methods. A retrospective analysis investigated 280 applications for fellowship positions in the department of orthopedic surgery at the authors' academic institution from 1996 to 1998 inclusively. To allow for press and publication delays, a minimum 24-month follow-up period was instituted. The listings of applicants' research publications were analyzed for evidence of misrepresentation through an exhaustive literature search. Only the most obvious confirmable discrepancies were labeled as misrepresentations. The results then were compared with those found in studies conducted in other fields: gastroenterology fellowship, emergency medicine residency, pediatric residency, dermatology residency, orthopedic residency, and medical faculty applications. Results. Among 280 (54%) applicants for orthopedic surgery candidates, 151 claimed journal publications. It was found that 16 (10.6%) of these 151 applicants had misrepresented their citations. This rate was highest in spine fellowship applicants (20%). However, considering the numbers available, this was not significantly different among the various subspecialty fellowship applicants (P>0.1). In addition, various demographic data did not correlate with the rate of misrepresentation (P>0.1). These results are comparable with those reported in other medical fields (P>0.1). Conclusions. Misrepresentation occurs in orthopedic fellowship applications at a rate comparable with that observed in other fields. This rate is not different among the various subspecialties in orthopedics. Policies that may lessen the incidence of falsification on curriculum vitae should be instituted in an attempt to curb such activity.

Fellowships and Scholarships↗

Single-level lumbar spine fusion: a comparison of anterior and posterior approaches.

This study is a retrospective review of 122 patients who underwent single-level lumbar spine fusion. The objectives were to directly compare perioperative morbidity and early results of single-level anterior interbody posterolateral intertransverse process lumbar spine fusion and to provide objective findings that may be useful in selecting surgical method. Lumbar spinal fusion is a well-recognized surgical treatment of intractable low back pain resulting from DDD or spondylolisthesis. Assessments of techniques, results, and outcomes have been published, but detailed head-to-head comparisons of anterior posterior approaches with objective operative and postoperative data are not available in the literature. A retrospective review of 122 patients who underwent either an anterior interbody or posterolateral intertransverse process (average follow-up 22 and 26 months, respectively) single-level instrumented lumbar spinal fusion was performed. Surgical, perioperative, and follow-up data were obtained directly from medical records. The findings compared included estimated blood loss, need for blood transfusion, number of units transfused, operative time, number of days in hospital, need for transitional facility care, complications, need for further surgery, radiographic fusion, and clinical results. There was significantly less blood loss, need for transfusion, amount of blood transfused, operative time, and hospital stay for patients with anterior fusion procedures (p < 0.01). There was no significant difference in need for transitional facility care, complication rates, and given follow-up period in radiographic fusion rate and clinical outcome. Clinical results were significantly worse for those undergoing revision primary fusion (p < 0.01). The anterior approach to single-level lumbar fusion is associated with less morbidity than the posterolateral approach. This may in turn affect surgical outcome and hospital cost. However, both approaches to single-level lumbar fusion produce similar early fusion rates and clinical results. Revision fusions had poor early results regardless of approach.

Adult↗

An in vitro and in vivo analysis of fibrin glue use to control bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has become popular for augmenting spine fusion in the lumbar and cervical spine. Concerns exist, however, over bone morphogenetic protein (BMP)-stimulated soft-tissue swelling and bone growth stimulation in areas where bone is not desired, especially as the material "leaks" into such spaces. The most detrimental effects of such leakage might be airway compromise, while heterotopic bone formation into the spinal canal has been reported in animal and human studies. Fibrin glue has been used as a carrier of many osteoinductive materials; however, its efficacy at modulating the clinical effects of BMP are not known. The amorphous nature of fibrin glue makes it a candidate to control diffusion of BMP and possibly limit bone formation by limiting BMP diffusion to areas where such bone is not desired. PURPOSE: To evaluate the use of fibrin glue to limit BMP diffusion and BMP-stimulated bone growth. STUDY DESIGN/SETTING: This is an in vitro basic science study and an in vivo prospective randomized animal study. STUDY SAMPLE: Eighteen Lewis rats. OUTCOME MEASURES: In vitro study: Enzyme-linked immunosorbent assay measurement of rh-BMP2 concentration in saline. In vivo study: At day 60, rats were evaluated for neurologic deficits before sacrifice. Spines were harvested, and the following studies were performed: 1) manual testing for fusion and bone growth; 2) X-ray evaluation; 3) Micro-computed tomography (micro-CT) scans. METHODS: In vitro study: Collagen sponges soaked with BMP at two different concentrations were incubated in saline solution with and without encapsulation by fibrin glue. Saline BMP concentrations were measured at consecutive time points. In vivo study: A rat fusion model using rh-BMP2 for fusion has been developed and tested with resultant100% fusion in over 100 rats. Lewis rats were divided into two groups and treated as follows: I: Exposure of L4-L5 transverse processes, decortication, and placement of BMP sponge in the lateral intertransverse space. II: Exposure and decortication as above and placement of fibrin glue before BMP sponge placement. RESULTS: In vitro study: Peak rh-BMP2 concentrations in saline were 20% and 45% of the maximum possible for fibrin glue encapsulated sponges and controls, respectively, with a more gradual increase to peak concentration in samples encapsulated in fibrin glue. In vivo study: No rats exhibited any neurologic deficits. X-rays revealed at least partial bone formation in all rats. Manual testing of intertransverse fusion spines revealed 100% fusion in rats treated with BMP only, whereas rats treated with fibrin glue before placement of BMP sponges revealed only one possible fusion. Posterior-lateral bone formation was present on X-ray in both groups, and micro-CT imaging revealed bridging bone from transverse processes to the BMP-stimulated bone in the control groups. In spines treated with fibrin glue before rh-BMP2 placement, bone formation could still be seen within the soft tissues; however, bridging bone connecting to the transverse processes was either significantly decreased or not present. CONCLUSIONS: Fibrin glue can limit rh-BMP2 diffusion. Also, because it limited bone formation at the transverse processes, it can be inferred that fibrin glue can limit bone formation when used to separate areas of desired bone formation from areas where bone formation is not desired.

Animals↗