Bruce Simon

Treatment of nonunions with electric and electromagnetic fields.

Electric and electromagnetic fields are, collectively, one form of biophysical technique which regulate extracellular matrix (ECM) synthesis and may be useful in clinically stimulating repair of fractures and nonunions. Preclinical studies have shown that electric and electromagnetic fields regulate proteoglycan (PG) and collagen synthesis in models of endochondral ossification, and increase bone formation in vivo and in vitro. A substantial number of clinical studies have been done that suggest acceleration of bone formation and healing, particularly osteotomies and spine fusions, by electric and electromagnetic fields. Many of these studies have used randomized, placebo controlled designs. In osteotomy trials, greater bone density, trabecular maturation, and radiographic healing were observed in actively treated, compared with placebo-treated patients. In spine fusions, average union rates of 80% to 90% were observed in actively treated patients across numerous studies compared with 65% to 75% in placebo-treated patients. Uncontrolled, longitudinal cohort studies of delayed and nonunions report mean union rates of approximately 75% to 85% in fractures previously refractory to healing. The few randomized controlled studies in delayed and nonunions suggest improved results with electric and electromagnetic fields compared with placebo treatment, and equivalent to bone grafts.

Stimulation of growth factor synthesis by electric and electromagnetic fields.

Biophysical input, including electric and electromagnetic fields, regulate the expression of genes in connective tissue cells for structural extracellular matrix (ECM) proteins resulting in an increase in cartilage and bone production. In in vivo models and clinical situations, this can be manifested as enhanced repair and a gain in mechanical properties of the repairing tissues. The mechanisms by which cell functions are regulated by biophysical input is the subject of this review. Biophysical interactions of electric and electromagnetic fields at the cell membrane are not well understood and require considerable additional study. We review information on transmembrane signaling, channel activation and receptor stimulation or blockade. Understanding physical interactions and transmembrane signaling will most likely be necessary to establish dosing paradigms and improve therapeutic efficacy. Considerable information has been generated on an intermediary mechanism of activity - growth factor stimulation. Electric and electromagnetic fields increase gene expression for, and synthesis of, growth factors and this may function to amplify field effects through autocrine and paracrine signaling. Electric and electromagnetic fields can produce a sustained upregulation of growth factors, which enhance, but do not disorganize endochondral bone formation. Progress in the areas of signal transduction and growth factor synthesis is very rapid and future directions are suggested.

Modification of osteoarthritis by pulsed electromagnetic field--a morphological study.

OBJECTIVE Hartley guinea pigs spontaneously develop arthritis that bears morphological, biochemical, and immunohistochemical similarities to human osteoarthritis. It is characterized by the appearance of superficial fibrillation by 12 months of age and severe cartilage lesions and eburnation by 18 months of age. This study examines the effect of treatment with a pulsed electromagnetic field (PEMF) upon the morphological progression of osteoarthritis in this animal model. DESIGN Hartley guinea pigs were exposed to a specific PEMF for 1h/day for 6 months, beginning at 12 months of age. Control animals were treated identically, but without PEMF exposure. Tibial articular cartilage was examined with histological/histochemical grading of the severity of arthritis, by immunohistochemistry for cartilage neoepitopes, 3B3(-) and BC-13, reflecting enzymatic cleavage of aggrecan, and by immunoreactivity to collagenase (MMP-13) and stromelysin (MMP-3). Immunoreactivity to TGFbeta, interleukin (IL)-1beta, and IL receptor antagonist protein (IRAP) antibodies was examined to suggest possible mechanisms of PEMF activity. RESULTS PEMF treatment preserves the morphology of articular cartilage and retards the development of osteoarthritic lesions. This observation is supported by a reduction in the cartilage neoepitopes, 3B3(-) and BC-13, and suppression of the matrix-degrading enzymes, collagenase and stromelysin. Cells immunopositive to IL-1 are decreased in number, while IRAP-positive cells are increased in response to treatment. PEMF treatment markedly increases the number of cells immunopositive to TGFbeta. CONCLUSIONS Treatment with PEMF appears to be disease-modifying in this model of osteoarthritis. Since TGFbeta is believed to upregulate gene expression for aggrecan, downregulate matrix metalloprotease and IL-1 activity, and upregulate inhibitors of matrix metalloprotease, the stimulation of TGFbeta may be a mechanism through which PEMF favorably affects cartilage homeostasis.

Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release.

Background: Chronic wounds, particularly in diabetics, result in significant morbidity and mortality and have a profound economic impact. The authors demonstrate that pulsed electromagnetic fields significantly improve both diabetic and normal wound healing in 66 mice through up-regulation of fibroblast growth factor (FGF)-2 and are able to prevent tissue necrosis in diabetic tissue after an ischemic insult. Methods: Db/db and C57BL6 mice were wounded and exposed to pulsed electromagnetic fields. Gross closure, cell proliferation, and vascularity were assessed. Cultured medium from human umbilical vein endothelial cells exposed to pulsed electromagnetic fields was analyzed for FGF-2 and applied topically to wounds. Skin flaps were created on streptozocin-induced diabetic mice and exposed to pulsed electromagnetic fields. Percentage necrosis, oxygen tension, and vascularity were determined. Results: Pulsed electromagnetic fields accelerated wound closure in diabetic and normal mice. Cell proliferation and CD31 density were significantly increased in pulsed electromagnetic field–treated groups. Cultured medium from human umbilical vein endothelial cells in pulsed electromagnetic fields exhibited a three-fold increase in FGF-2, which facilitated healing when applied to wounds. Skin on diabetic mice exposed to pulsed electromagnetic fields did not exhibit tissue necrosis and demonstrated oxygen tensions and vascularity comparable to those in normal animals. Conclusions: This study demonstrates that pulsed electromagnetic fields are able to accelerate wound healing under diabetic and normal conditions by up-regulation of FGF-2–mediated angiogenesis. They also prevented tissue necrosis in response to a standardized ischemic insult, suggesting that noninvasive angiogenic stimulation by pulsed electromagnetic fields may be useful to prevent ulcer formation, necrosis, and amputation in diabetic patients.

Pediatric minor head trauma: indications for computed tomographic scanning revisited.

BACKGROUND Although the use of computed tomographic (CT) scanning in severe head trauma is an accepted practice, the indications for its use in minor injury remain ill defined and subjective. We sought to define the incidence and identify risk factors for intracranial injury (ICI) after minor head trauma in children who did not have suspicious neurologic symptoms in the field or on presentation. METHODS From January 1, 1992, until April 1, 2000, 569 blunt trauma patients (age < 16 years) with a Glasgow Coma Scale score of 14 or 15 triaged by American College of Surgeons Pediatric Mechanism Criteria at a Level I trauma center received head CT scan. Loss of consciousness (LOC) status was known for 429. This subgroup was retrospectively reviewed for mechanism, age, Injury Severity Score, LOC status, GCS score, associated injuries, and CT scan findings (normal, fracture only, or intracranial injury). Relative risk values for intracranial injury were generated and statistical significance was assessed. RESULTS Fourteen percent (62 of 429) of study patients (GCS score of 14 and 15) had ICI. Sixteen percent of patients (35 of 215) with GCS score of 15 and (-)LOC (negative for LOC) had intracranial injury manifesting as subdural hematoma, epidural hematoma, subarachnoid hemorrhage, or brain contusion. Three required surgery for intracranial mass lesions. One patient deteriorated and required intubation and intensive care unit management. Neither (+)LOC (positive for LOC) nor GCS score of 14 increased the likelihood of intracranial injury over those patients without loss of consciousness or with GCS score of 15. Distant injury was also not an independent predictor of ICI for those with GCS scores of 14 or 15, as 84% of the ICI group had head injury only. Skull fracture was a risk factor for ICI but had poor negative predictive value, as 45% of patients with ICI did not have fractures. Similarly, minor craniofacial soft tissue trauma was a significant risk factor (relative risk, 11) that had marginal negative predictive value (0.95), as 14% (9 of 62) of ICI patients did not have superficial craniofacial injury. CONCLUSION A normal neurologic exam and maintenance of consciousness does not preclude significant rates of intracranial injury in pediatric trauma patients. Contrary to convention, neither LOC nor mild altered mentation is a sensitive indicator with which to select patients for CT scanning. Skull fractures and superficial craniofacial injury are similarly unreliable. Identification of these patients is important for the occasional case requiring intervention and for the tracking of complications. A liberal policy of CT scanning is warranted for pediatric patients with a high-risk mechanism of injury despite maintenance of normal neurologic status in the field and at hospital screening.

Use of Physical Forces in Bone Healing

Abstract During the past two decades, a number of physical modalities have been approved for the management of nonunions and delayed unions. Implantable direct current stimulation is effective in managing established nonunions of the extremities and as an adjuvant in achieving spinal fusion. Pulsed electromagnetic fields and capacitive coupling induce fields through the soft tissue, resulting in low‐magnitude voltage and currents at the fracture site. Pulsed electromagnetic fields may be as effective as surgery in managing extremity nonunions. Capacitive coupling appears to be effective both in extremity nonunions and lumbar fusions. Low‐intensity ultrasound has been used to speed normal fracture healing and manage delayed unions. It has recently been approved for the management of nonunions. Despite the different mechanisms for stimulating bone healing, all signals result in increased intracellular calcium, thereby leading to bone formation.

Long-term functional status and mortality of elderly patients with severe closed head injuries.

OBJECTIVE To evaluate long-term clinical outcome of elderly patients with severe closed head injuries. DESIGN Retrospective study. PATIENTS AND METHODS All patients older than 65 years of age admitted to a regional trauma center with a diagnosis of closed head injury and an admission Glasgow Coma Scale (GCS) score of 8 or less. Using chi 2 analysis, Students t test, and multiple logistic regression, we correlated age, sex, mechanism of injury, pupillary reactivity, alcohol and drug use, admission GCS score, Injury Severity Score, Revised Trauma Score, heart rate, and blood pressure to the main outcome measures, i.e. long-term functional outcome and mortality. RESULTS Among 40 elderly patients who met the criteria, 27% were still alive at the end of 38 +/- 3 month follow-up. Eighty-five percent of patients who were discharged from the hospital were still alive long-term, but did not show significant neurologic improvement. In a univariate analysis, GCS and pupillary reactivity were predictive for long-term functional outcome and mortality. In a multivariate analysis, GCS and heart rate were predictive. All patients with an admission GCS score of 3 died in-hospital. All patients with an admission GCS score of 3 to 7 were either deceased or lived in persistent vegetative or dependent functional states. CONCLUSIONS Elderly patients with severe closed head injuries have high in-hospital mortality. Those who survived the hospital stay had high long-term survival, but did not show significant functional improvement. Prediction of long-term functional status is vital to the trauma care of elderly patients with severe closed head injuries.

Effects of pulsed electromagnetic fields on bone healing in a rabbit tibial osteotomy model.

OBJECTIVE The purpose of this study was to determine the effect of pulsed electromagnetic field (PEMF) exposure on healing tibial osteotomies in New Zealand White rabbits. DESIGN One-millimeter Gigli saw osteotomies were stabilized by external fixation. One day after surgery, rabbits were randomly assigned to receive either no exposure (sham control) or thirty minutes or sixty minutes per day of low-frequency, low-amplitude PEMF. Radiographs were obtained weekly throughout the study. Rabbits were euthanized at fourteen, twenty-one, or twenty-eight days, and tibiae underwent either destructive torsional testing or histologic analysis. To determine the baseline torsional strength and stiffness of rabbit tibiae, eleven normal intact tibiae were tested to failure. RESULTS Sixty-minute PEMF-treated osteotomies had significantly higher torsional strength than did sham controls at fourteen and twenty-one days postoperatively. Thirty-minute PEMF-treated osteotomies were significantly stronger than sham controls only after twenty-one days. Normal intact torsional strength was achieved by fourteen days in the sixty-minute PEMF group, by twenty-one days in the thirty-minute PEMF group, and by twenty-eight days in the sham controls. Maximum fracture callus area correlated with the time to reach normal torsional strength. CONCLUSION In this animal model, low-frequency, low-amplitude PEMF significantly accelerated callus formation and osteotomy healing in a dose-dependent manner.

Management of pulmonary contusion and flail chest: An Eastern Association for the Surgery of Trauma practice management guideline

Background Despite the prevalence and recognized association of pulmonary contusion and flail chest (PC-FC) as a combined, complex injury pattern with interrelated pathophysiology, the mortality and morbidity of this entity have not improved during the last three decades. The purpose of this updated EAST practice management guideline was to present evidence-based recommendations for the treatment of PC-FC. Methods A query was conducted of MEDLINE, Embase, PubMed and Cochrane databases for the period from January 1966 through June 30, 2011. All evidence was reviewed and graded by two members of the guideline committee. Guideline formulation was performed by committee consensus. Results Of the 215 articles identified in the search, 129 were deemed appropriate for review, grading, and inclusion in the guideline. This practice management guideline has a total of six Level 2 and eight Level 3 recommendations. Conclusion Patients with PC-FC should not be excessively fluid restricted but should be resuscitated to maintain signs of adequate tissue perfusion. Obligatory mechanical ventilation in the absence of respiratory failure should be avoided. The use of optimal analgesia and aggressive chest physiotherapy should be applied to minimize the likelihood of respiratory failure. Epidural catheter is the preferred mode of analgesia delivery in severe flail chest injury. Paravertebral analgesia may be equivalent to epidural analgesia and may be appropriate in certain situations when epidural is contraindicated. A trial of mask continuous positive airway pressure should be considered in alert patients with marginal respiratory status. Patients requiring mechanical ventilation should be supported in a manner based on institutional and physician preference and separated from the ventilator at the earliest possible time. Positive end-expiratory pressure or continuous positive airway pressure should be provided. High-frequency oscillatory ventilation should be considered for patients failing conventional ventilatory modes. Independent lung ventilation may also be considered in severe unilateral pulmonary contusion when shunt cannot be otherwise corrected. Surgical fixation of flail chest may be considered in cases of severe flail chest failing to wean from the ventilator or when thoracotomy is required for other reasons. Self-activating multidisciplinary protocols for the treatment of chest wall injuries may improve outcome and should be considered where feasible. Steroids should not be used in the therapy of pulmonary contusion. Diuretics may be used in the setting of hydrostatic fluid overload in hemodynamically stable patients or in the setting of known concurrent congestive heart failure.

In vivo evaluation of coralline hydroxyapatite and direct current electrical stimulation in lumbar spinal fusion

STUDY DESIGN An animal model of posterolateral intertransverse process lumbar spinal fusion using autologous bone, coralline hydroxyapatite, and/or direct current electrical stimulation. OBJECTIVES To evaluate the effect of an osteoconductive bone graft substitute and direct-current electrical stimulation on the rate of pseudarthrosis in a rabbit spinal fusion model. SUMMARY OF BACKGROUND DATA Conventional techniques for the surgical treatment of degenerative conditions in the lumbar spine have a substantial failure rate and associated morbidity. Bone graft substitutes and electrical stimulation are alternative techniques to enhance fusion rates and limit the morbidity associated with posterolateral intertransverse process fusion using autologous iliac crest bone graft. METHODS Fifty-three adult female New Zealand White rabbits underwent single-level lumbar posterolateral intertransverse process fusion. Animals were assigned to one of four groups using either autologous bone (Group I), coralline hydroxyapatite with autologous bone marrow aspirate (Group II), coralline hydroxyapatite with a 40-microA implantable direct current electrical stimulator and bone marrow aspirate (Group III), or coralline hydroxyapatite with a 100-microA implantable direct current electrical stimulator and bone marrow aspirate (Group IV). Animals were killed at 8 weeks, and fused motion segments were subjected to manual palpation, mechanical testing, and radiographic and histologic analysis to assess the fusion mass. RESULTS Successful fusion was achieved in 57% (8/14) of animals in Group I, 25% (3/12) in Group II, 50% (6/12) in Group III, and 87% (13/15) in Group IV. Mean stiffness and ultimate load to failure were significantly higher in Group IV than in all other groups (P < 0.05). Histologic analysis demonstrated a qualitative increase in fusion mass in Group IV versus all other groups. CONCLUSIONS Direct-current electrical stimulation increased fusion rates in a dose-dependent manner in a rabbit spinal fusion model. Coralline hydroxyapatite is an osteoconductive bone graft substitute, and thus requires an osteoinductive stimulus to ensure reliable fusion rates. Furthermore, coralline hydroxyapatite and direct current electrical stimulation can be used together to increase fusion rates in a rabbit spinal fusion model while avoiding the morbidity associated with harvesting iliac crest bone.