Surgical correction of lumbar kyphotic deformity: posterior reduction eggshell osteotomy

Transcription

1 J Neurosurg (Spine 1) 92:50 56, 2000 Surgical correction of lumbar kyphotic deformity: posterior reduction eggshell osteotomy OLUMIDE A. DANISA, M.D., DENNIS TURNER, M.D., M.A., AND WILLIAM J. RICHARDSON, M.D. Departments of Surgery (Divisions of Neurosurgery and Orthopaedics) and Neurobiology, Duke University Medical Center, and Durham Veterans Administration Medical Center, Durham, North Carolina Object. Progressive kyphotic deformity of the lumbar or thoracolumbar spine may lead to back pain, cosmetic deformity, and risk of neurological compromise. The authors describe a series of patients in whom they performed a singlestage, posterior reduction ( eggshell ) osteotomy procedure to improve sagittal contour by creating lordosis within a single vertebral body. Methods. From 1995 to 1997 the authors performed 12 osteotomy procedures in 11 patients with thoracolumbar or lumbar kyphosis. Seven patients presented with iatrogenic deformity, three with deformity secondary to traumatic injury, and one patient with ankylosing spondylitis. Their mean age at time of surgery was 46.6 years (range years). All patients suffered from back pain and were unable to stand upright, but in only one patient were neurological findings demonstrated. The mean preoperative deformity was 26 (range 90 to 0 ). At 6-month follow-up examination the mean sagittal contour measured 17.5 (range 17 to 44 ), indicating that the mean surgical correction was 40.1 (range 25 to 58 ). All patients reported decreased back pain at follow up, and none required narcotic analgesic medication. Complications included a dense paresis that developed immediately postoperatively in a patient who was found to have residual dural compression, which was corrected by emergency decompressive surgery. One elderly patient suffered a perioperative cerebrovascular accident, and three patients suffered neurapraxia with transient muscle weakness of the quadriceps. There was one case of a dural tear. There were no deaths, and prolonged intensive care stays were not required. Conclusions. Single-level posterior reduction osteotomy provides excellent sagittal correction of kyphotic deformity in the lumbar region, with a risk of cauda equina and root and plexus compromise due to the extensive neural exposure. KEY WORDS flat-back syndrome lumbar fracture wedge osteotomy lumbar instrumentation K YPHOTIC deformity in the lumbar or thoracolumbar spine is a well-documented complication of the surgical treatment of scoliosis, spinal trauma (such as burst fractures), and extensive laminectomy. 2,3,5,10,17 22,25 In several reports the authors have cited the loss of normal sagittal contour as an untoward sequela of posterior distraction instrumentation in the correction of scoliosis. 2,3,5,20,21 There are also reports of patients who develop progressive lumbar kyphosis along fusion segments after fusion and placement of anterior instrumentation in the treatment of scoliotic deformity. 14,24,28 The term iatrogenic flat-back syndrome is now commonly applied to postsurgical patients in whom clinical loss of lumbar lordosis is demonstrated and who are unable to stand erect without concomitant knee and hip flexion and who experience increasing fatigue and pain as the day progresses. 16,19,21 50 Abnormal spinal kyphosis, regardless of cause, poses a therapeutic challenge when considering pain, progressive cosmetic and biomechanical deformity, and even late neurological deficit. Nonoperative modalities primarily ameliorate pain. Surgical intervention consists of performing either a single-level or multilevel vertebral osteotomy to obtain sagittal plane correction. In 1945 Smith-Petersen, et al., 27 were the first to treat gibbus secondary to ankylosing spondylitis by performing a multilevel extension osteotomy procedure. Several modifications of this posterior extension osteotomy procedure have since evolved. 1,4,13,23,26 The success of such osteotomy procedures, as demonstrated radiographically, however, has been tempered by the relatively high complication rate. 1,3,31 33 For example, in the correction of kyphosis secondary to ankylosing spondylitis, mortality rates have been reported to be as high as 10% in

2 Lumbar posterior reduction osteotomy for kyphosis patients who underwent the Smith-Petersen type procedure. In the treatment of patients with iatrogenic flat-back syndrome, Kostuik and colleagues 16,19 have performed a single-stage anterior opening wedge osteotomy combined with a Smith-Petersen posterior extension osteotomy. They reported an average angular correction of 29 and pain relief was achieved in 90% of cases. There were, however, five major arterial injuries, one leading to death by exsanguination. Heinig and Boyd in the 1970s and Thomasen in 1985 were the first surgeons to propose a dorsal decancellation or reduction osteotomy, an eggshell procedure, to correct kyphosis in patients with ankylosing spondylitis. 31 The technique consists of removing a posteriorly based wedge of bone from the vertebral body, which subsequently produces lordotic correction as the spine is hyperextended. Several authors have also reported excellent correction and relatively few complications when performing the decancellation osteotomy in cases of ankylosing spondylitics. 15,30,32 In a limited series Gertzbein and Harris 10 also successfully performed the decancellation eggshell procedure in three patients with posttraumatic kyphosis. We report here the technique and results of performing the posterior decancellation ( eggshell or reduction) osteotomy in 11 patients who presented with debilitating lumbar kyphosis secondary to ankylosing spondylitis, trauma, or previous operative procedures. FIG. 1. Diagrams depicting the steps of the reduction osteotomy procedure. A: The posterior elements are removed initially (shaded area), including the spinous process of the critical level and also part of the spinous processes above and below. The facets and pedicles are then removed, although the transverse processes are left embedded (but disconnected) in the paraspinal muscle for a grafting bed. B: A side view after removal of the posterior elements and the pedicle. The last stage is removal of a wedge of bone of the body, first inside the body (leaving an eggshell behind) and then removing a wedge of the outer cortex until the body can be collapsed. C: The final, closed wedge, with the created lordotic correction allowing the posterior elements nearly to coapt. Clinical Material and Methods From March 1995 to December 1997 lumbar spine reduction eggshell osteotomy procedures to correct kyphotic deformity were performed in 11 patients. We retrospectively assessed the results obtained in this group for sagittal plane correction, pain relief, and blood loss. Charts were reviewed, patients were examined at follow up at 3, 6, and 12 months postoperatively, and follow-up radiographs were acquired to measure correction. The group included eight men and three women whose mean age at the time of operation was 46.6 years (range years). In three patients lumbar or thoracolumbar kyphosis secondary to traumatic injury was demonstrated; in one patient ankylosing spondylitis was revealed; the remaining seven patients were classified as having iatrogenic kyphotic deformity. Of these seven patients, four had undergone either previous placement of distraction instrumentation or anterior surgery, two had undergone multiple previous destabilizing laminectomy procedures, and one had developed postirradiation kyphosis. All patients in our study group complained of back pain and experienced tenderness at the apex of the deformity; in four, pain was reported as severe, necessitating chronic intake of narcotic medication to obtain pain relief. All patients also had difficulty maintaining erect posture while ambulating. No patient was found to have fixed flexion contractures of the hips or knees. Only one patient sustained a neurological deficit Grade 4/5 motor strength in the lower extremities prior to surgery. Lumbar kyphosis was measured by using the method of Cobb on plain lateral radiographs obtained preoperatively and at 6 months postoperatively. Further diagnostic imaging included magnetic resonance imaging or contrast-enhanced computerized tomography scanning to delineate concomitant spinal stenosis, neural foraminal stenosis with nerve root entrapment, and the level of the conus medullaris. Surgical Technique The patient is placed prone on the operating table with adequate padding over bony prominences; chest and abdomen pads are also used to minimize compression of the abdomen. Care is taken to position the level of the planned osteotomy, usually L-2 or L-3, over the break in the operating room table. If the osteotomy is planned for L-1, somatosensory evoked potentials are monitored. Cell-saver autotransfusion is also routinely used. A midline skin incision is made and the spine is exposed by subperiosteal dissection of the paraspinal muscles, thereby allowing visualization of laminae, facet joint capsules, and as far laterally as the transverse processes. Radiographic confirmation of the osteotomy level is made. Prior to performing the osteotomy, pedicle screws are inserted at two levels, above and below the osteotomy site. When the bone is osteopenic and a longer fusion is desired, a hybrid construct, such as pedicle screws in caudal vertebrae with pedicle or laminar hooks in the cephalad vertebrae, is used. Figures 1 to 4 illustrate the overall sequence of the procedure. The shaded area indicates the portion of bone removed from the posterior aspect of the spine (Fig. 1A) and from the lateral aspect (Fig. 1B). Figure 1C (lateral view) shows the completed wedge reduction after cracking the thinned eggshell vertebra. The posterior column, which is composed of the spinous process, laminae, facets, and pedicles, is first removed from the vertebral body at the focal point of the osteotomy (Fig. 2A). In addition, a decompressive laminectomy and partial resection of the spinous processes of the adjacent vertebrae are performed to 51

3 O. A. Danisa, D. Turner, and W. J. Richardson FIG. 2. Diagrams. A: The posterior elements are removed and the pedicles drilled as the entry into the vertebral body. B: The pedicles have been hollowed, in addition to the interior of the vertebral body, leaving in effect an eggshell. The posterior cortical rim of the body is then cracked into the defect, under the dural sac. FIG. 4. Diagram showing that the posterior elements above and below the wedge osteotomy level are now apposed, following the careful closure of the wedge. Care must be taken during this process so as not to pinch the main dural sac or the individual exiting nerve roots. The transpedicular instrumentation is also shown, anchoring the now closed wedge. FIG. 3. Diagram depicting the next stage of the procedure, after the posterior elements have been removed and the body has been thinned into a cortical eggshell. The posterior cortical margin beneath the dura has been removed, and the lateral cortical margin has also been thinned and removed. At this stage there is a hollow, wedge-shaped opening in the interior of the previous vertebral body, and the two pairs of nerve roots (NR) and dura have been widely exposed. allow adequate room for the redundant dura once the osteotomy is closed. This decompression extends from the pedicle above the wedge osteotomy level to the pedicle below. The dura is exposed after the ligamentum flavum is carefully excised and the adjacent pair of exiting nerve roots are mobilized and freed. A high-speed drill is used to core a path from both pedicles into the vertebral body (Fig. 2B). The transverse processes on each side are disconnected (but remain as a fusion nidus laterally). The cancellous bone is then removed bilaterally from the interior of the vertebral body by using angled curettes to form an apex anterior wedge, and the integrity of both superior and inferior endplates is maintained. At this intermediate stage only, a thin rim of cortical bone remains laterally and posteriorly hence, the term eggshell. Once the ventral surface of the dura is freed, the osteotomy wedge is completed by removing the posterior vertebral cortex (Fig. 2B). Figure 3 shows the posterior perspective at the next stage, following removal of the posterior vertebral cortex from beneath the dura and excision of the thinned, lateral cortical margins, just immediately prior to closure of the wedge. The osteotomy is closed by gradual hyperextension of the operating table together with applied pressure, which causes the spinous processes of the adjacent vertebrae to touch (Fig. 1C, lateral perspective). During the closure procedure, the dura and nerve roots are carefully elevated to prevent entrapment in the wedge or posterior elements. Lordotic correction is maintained after 52

4 Lumbar posterior reduction osteotomy for kyphosis FIG. 5. Representative radiographs demonstrating a classic example of flat-back syndrome. Left: Preoperative thoracolumbar radiograph demonstrating the instrumentation and the significant upper lumbar and lower thoracic kyphosis. Right: Postoperative radiograph obtained after the L-1 osteotomy revealing significant correction of the kyphosis, including both a mild lumbar lordosis and a lower thoracic residual kyphosis. The new instrumentation includes lower pedicle screws and upper laminar hooks. the closure by the addition of rods to the existing pedicle screw construct, as shown (Fig. 4, posterior perspective). At this stage two nerve roots exit through a single foramen on each side (not explicitly shown in Fig. 4), and the transverse processes above and below are brought closer together. Autogenous bone graft is then laid laterally along decorticated transverse processes of the remaining vertebrae, and a transverse connector is placed. A drain is placed, and the wound is closed in several layers. Postoperatively the patient is fitted with a custom-molded orthosis, and ambulation with a physical therapist is begun on Day 2. Correction of Kyphosis Results In our patient group, a total of 12 eggshell procedures were performed: four L-1 osteotomy procedures; five L-2; two L-3; and one L-4 procedure. One patient with a severe kyphotic deformity, ( 90 ), underwent two eggshell procedures: one at L-1 and one at L-3. The radiographs in Fig. 5 demonstrate a case of flat-back syndrome, following an earlier procedure in which instrumentation was placed preoperatively (Fig. 5 left) and after correction for kyphosis (Fig. 5 right). A typical case of posttraumatic kyphosis is shown in Fig. 6 left. The osteotomy was performed at L-4, with pedicle screws placed in both L-3 and the sacrum. Postoperatively, excellent correction of a lumbar lordosis was achieved (Fig. 6 center) with excellent bone healing with the lateral fusion (Fig. 6 right). The mean preoperative sagittal deformity measured in our patient group was 26 (range 0 to 90 ). At the most recent follow-up examination (all at least 6 months postoperatively), the sagittal contour over the same vertebral segments measured a mean of 17.5 (range 17 to 44 ). As a result, the eggshell procedure led to a mean correction of 40.1 (range 25 to 58 ). In all patients clinical improvement of their lumbar lordosis was shown, and they were able to maintain erect posture. All patients reported marked reduction of their back pain, and none required narcotic analgesic medication after the immediate postoperative period. The one patient in whom preoperative Grade 4/5 motor weakness in the proximal lower extremities and a 90 deformity were demonstrated regained full lower-extremity strength 6 weeks after surgery. The mean operative blood loss for the eggshell procedure was 2436 ml (range ml). 53

5 O. A. Danisa, D. Turner, and W. J. Richardson FIG. 6. Radiographic studies demonstrating an example of posttraumatic kyphosis that resulted from a burst fracture at L4 5. Left: Preoperative lateral lumbar radiograph demonstrating the kyphosis that resulted from the burst fracture and telescoping of L-4 into the superior aspect of L-5. Center: Postoperative lateral lumbar radiograph obtained after an L-4 osteotomy, demonstrating excellent correction of the kyphotic deformity into a lordosis. The pedicle screws are located in L-3 and the sacrum. Right: Anteroposterior radiograph of the lumbar spine obtained at 6 months postoperatively, revealing an extensive lateral fusion mass. Procedure-Related Complications Five patients developed new neurological deficits postoperatively. In three, there was transient Grade 4/5 motor weakness of the quadriceps muscle, which was thought to be secondary to mobilization of the nerve roots and plexus; all patients completely recovered by 6 months postoperatively. One patient, in whom surgery was performed early in this study, was found, in the recovery room, to have dense paresis. An emergency computerized tomography scan revealed an infolded ligamentum flavum and remnants of pedicle impinging on the dural sac. He underwent decompressive surgery and regained full motor strength by the time of discharge. One elderly patient, who was noted preoperatively to have a significant premorbid medical history, suffered a right-sided cerebrovascular accident in the perioperative period. He eventually was discharged to a rehabilitation facility and underwent intensive physical therapy for ambulation, slowly recovering over a 6-month period. One patient sustained a dural tear that was repaired primarily without sequelae. There were no deaths in our study group, and all patients stayed in the intensive care unit less than 48 hours. Discussion Traumatic injury, ankylosing spondylitis, and prior surgical treatment are all capable of producing spinal kyphosis. 2,3 5,10,13,15,17 21,23,25 27,29,30 32 The growing concern over flat-back syndrome stems from the widespread use of Harrington instrumentation, up to the middle of the 1980s, to treat scoliotic deformity and vertebral fractures. 5 9,12,15, 19 21,34 Those patients who had previously undergone placement of distraction instrumentation are subsequently at risk for developing iatrogenic flat back. The goals of performing either an osteotomy or a vertebrectomy are to restore spinal biomechanics and cosmesis by placing the head over the hips in the sagittal contour. Decompressive procedures can also be performed as an adjunct to relieve dural or nerve root compression, particularly in cases of posttraumatic kyphotic deformity. Thus, both neurological decompression and spinal reconstruction to obtain a more normal sagittal contour can be achieved. The Smith-Petersen extension osteotomy procedure, dating back to 1945, has been the gold standard in the restoration of sagittal balance. Despite successful angular correction, which averages 20 to 40, the procedure does have its pitfalls. In the literature that addresses ankylosing spondylitis, mortality rates have approached 10%, whereas neurological complications, including paraplegia, have been as high as 30%. 1,3,31,33 More recent studies by Cammargo, et al., 4 and McMaster 23 have shown decreased morbidity rates following the procedure when using intraoperative spinal monitoring and careful wedge closure. Despite these encouraging reports, potential complications include the following: aortic or other major vascular rupture, thrombosis of mesenteric vessels, epidural or subdural hemorrhage, cauda equina syndrome due to elongation of the spinal canal, acute gastric dilation, paralytic ileus, and even superior mesenteric artery syndrome. 3,31 In patients who present with a greater magnitude of sagittal deformity, the Smith-Petersen procedure, by necessity, must be more extensive. An osteotomy must be performed at multiple levels, which increases the risk of the 54

6 Lumbar posterior reduction osteotomy for kyphosis aforementioned complications and also increases the rate of pseudarthrosis. The rationale for combined anterior posterior procedures is to provide and maintain greater angular correction, minimize the number of vertebral levels requiring osteotomy, and to reduce the rate of pseudarthrosis. In the treatment of patients with iatrogenic flat back, Kostuik, et al., 19 have performed a single-stage anterior opening wedge osteotomy combined with a single-level Smith- Petersen posterior osteotomy. They reported an average angular correction of 29 along with 90% pain relief in their series of 54 patients. Postoperatively, in all cases bone union was demonstrated. There were, however, five major arterial injuries, one leading to death by exsanguination, and one patient who developed permanent cauda equina syndrome. The transpedicular decancellation or reduction procedure performed at a single level is capable of providing angular correction comparable with that obtained using the Smith- Petersen osteotomy. Our reported mean correction of 40 is in accordance with such data. 31 Lordosis is created through removal of the posterior aspect of a single vertebral body; the hinge is located at the anterior column. Once closed, there is bone contact in all three columns, and the spinal canal is, in effect, reduced or shortened. The Smith-Petersen multilevel procedure, in contrast, has its fulcrum located in the middle column. If incorrectly performed, the hinges will be at the anterior aspect of the spinal canal. 3 Once closed, this osteotomy can actually lengthen the anterior column, potentially resulting in intraabdominal complications caused by excessive distraction of the abdominal cavity and vessels. In light of this risk, we performed a two-level eggshell procedure in one patient because his preoperative kyphosis ( 90 ) was thought to be too severe to be corrected by a single-level procedure. Thus, the posterior reduction osteotomy can provide excellent sagittal correction while allowing neural decompression, forming a highly stable construct. Conclusions Sagittal imbalance poses a difficult problem, and in some instances the late occurrence of this complication can be prevented. Distraction instrumentation that lengthens the posterior column, anterior column shortening procedures, and spinal destabilizing procedures should all be avoided. Vertebral osteotomy, although successful in restoring balance, should be viewed as a salvage procedure, because of the high blood loss and risk of neural injury. However, the eggshell osteotomy has a lower reported complication rate than the Smith-Petersen procedure. With greater experience we hope to decrease the associated complication rate, and with longer follow-up periods we will be able to study the extent to which correction is maintained as well as any attendant symptoms. References 1. Adams JC: Technique, dangers, and safeguards in osteotomy of the spine. J Bone Joint Surg (Br) 34: , Balderston RA, Winter RB, Moe JH, et al: Fusion to the sacrum for nonparalytic scoliosis in the adult. Spine 11: , Bradford DS, Tribus CB: Current concepts and management of patients with fixed decompensated spinal deformity. Clin Orthop 306:64 72, Camargo FP, Cordeiro EN, Napoli MM: Corrective osteotomy of the spine in ankylosing spondylitis. Experience with 66 cases. Clin Orthop 208: , Cochran T, Irstam L, Nachemson A: Long-term anatomic and functional changes in patients with adolescent idiopathic scoliosis treated by Harrington rod fusion. Spine 8: , Cotler JM, Vernace JV, Michalski JA: The use of Harrington rods in thoracolumbar fractures. Orthop Clin North Am 17: , Dickson JH, Harrington PR, Erwin WD: Results of reduction and stabilization of the severely fractured thoracic and lumbar spine. J Bone Joint Surg (Am) 60: , Farcy JP, Schwab FJ: Management of flatback and related kyphotic decompensation syndromes. Spine 22: , Flesch JR, Leider LL, Erickson DL, et al: Harrington instrumentation and spine fusion for unstable fractures and fracturedislocations of the thoracic and lumbar spine. J Bone Joint Surg (Am) 59: , Gertzbein SD, Harris MB: Wedge osteotomy for the correction of post-traumatic kyphosis. A new technique and a report of three cases. Spine 17: , Haher TR, Merola AA, Caruso SA, et al: Post-traumatic spinal deformity. Curr Opin Orthop 9:16 24, Harrington PR, Dickson JH: An eleven year clinical investigation of Harrington instrumentation: a preliminary report on 578 cases. Clin Orthop 93: , Hehne HJ, Zielke K, Bohm H: Polysegmental lumbar osteotomies and transpedicled fixation for correction of longcurved kyphotic deformities in ankylosing spondylitis. Report on 177 cases. Clin Orthop 258:49 55, Horton WC, Holt RT, Johnson JR, et al: Zielke instrumentation in idiopathic scoliosis: late effects and minimizing complications. Spine 13: , Jaffray D, Becker V, Eisenstein S: Closing wedge osteotomy with transpedicular fixation in ankylosing spondylitis. Clin Orthop 279: , Kostuik JP: Flat back deformity with loss of lumbar lordosis. Curr Opin Orthop 9:25 38, Kostuik JP, Hall BB: Spinal fusions to the sacrum in adults with scoliosis. Spine 8: , Kostuik JP, Matsusaki H: Anterior stabilization, instrumentation, and decompression for post-traumatic kyphosis. Spine 14: , Kostuik JP, Maurais GR, Richardson WJ, et al: Combined single-stage anterior and posterior osteotomy for correction of iatrogenic lumbar kyphosis. Spine 13: , Lagrone MO: Loss of lumbar lordosis: a complication of spinal fusion for scoliosis. Orthop Clin North Am 19: , Lagrone MO, Bradford DS, Moe JH, et al: Treatment of symptomatic flatback after spinal fusion. J Bone Joint Surg (Am) 70: , Lazennec JY, Saillant G, Saidi K, et al: Surgery of the deformities in ankylosing spondylitis: our experience of lumbar osteotomies in 31 patients. Eur Spine J 6: , McMaster MJ: A technique for lumbar spinal osteotomy in ankylosing spondylitis. J Bone Joint Surg (Br) 67: , Ogilvie JW: Anterior spine fusion with Zielke instrumentation for idiopathic scoliosis in adolescents. Orthop Clin North Am 19: , Roberson JR, Whitesides TE Jr: Surgical reconstruction of late post-traumatic thoracolumbar kyphosis. Spine 10: , Simmons EH: Kyphotic deformity of the spine in ankylosing spondylitis. Clin Orthop 128:65 77,

7 O. A. Danisa, D. Turner, and W. J. Richardson 27. Smith-Petersen MN, Larson CB, Aufranc OE: Osteotomy of the spine for correction of flexion deformity in rheumatoid arthritis. J Bone Joint Surg (Br) 27:1 11, Suk SI, Lee CK, Chung SS. Comparison of Zielke ventral derotation system and Cotrel-Dubousset instrumentation in the treatment of idiopathic lumbar and thoracolumbar scoliosis. Spine 19: , Swank S, Lonstein JE, Moe JH, et al: Surgical treatment of adult scoliosis. A review of two hundred and twenty two cases. J Bone Joint Surg (Am) 63: , Thiranont N, Netrawichien P: Transpedicular decancellation closed wedge vertebral osteotomy for treatment of fixed flexion deformity of spine in ankylosing spondylitis. Spine 18: , Thomasen E: Vertebral osteotomy for correction of kyphosis in ankylosing spondylitis. Clin Orthop 194: , Van Royen BJ and Slot GH: Closing-wedge posterior osteotomy for ankylosing spondylitis. Partial corporectomy and transpedicular fixation in 22 cases. J Bone Joint Surg (Br) 77: , Weatherley C, Jaffray D, Terry A: Vascular complications associated with osteotomy in ankylosing spondylitis: a report of two cases. Spine 13:43 46, Winter RB: Posterior spinal fusion in scoliosis: indications, techniques, and results. Orthop Clin North Am 10: , 1979 Manuscript received July 2, Accepted in final form October 6, This work was supported by grants from Sofamor-Danek (to O.A.D.), the National Institute of Aging Grant No. AG13165 (to D.A.T.), and the Veterans Affairs Merit Review (to D.A.T.). Current address for Dr. Danisa: The Hughston Clinic, 1590 Adamson Parkway, Suite 140, Morrow, Georgia Address reprint requests to: William J. Richardson, M.D., Division of Orthopaedics, Box 3077, Duke University Medical Center, Durham, North Carolina Richa015@mc.duke.edu. 56