The TGFß pathway is a key player for the endothelial-to-hematopoietic transition in the embryonic aorta.

The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor ß (TGFß) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGFß signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGFß pathway is preferentially balanced with a prominent role of Alk1/TgfßR2/Smad1 and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acvrl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGFß through the Alk1/TgfßR2 receptor axis is acting on endothelial cells to produce hematopoiesis.

Application and results of the AO internal fixation system in nontraumatic indications.

The AO internal skeletal fixation system (ISFS) permits posterior spine fixation to be restricted to the vertebrae immediately adjacent to the lesion and allows manipulation of each instrumented vertebra in three planes. In a prospective study to assess the value of this fixation for adult spinal disorders, 68 patients were reviewed. The device was used in spondylolisthesis, postlaminectomy instability, post-traumatic kyphosis, degenerative scoliosis, spinal stenosis, tumors, and infections. A total of 322 transpedicular screws have been inserted without neurologic complication. Satisfactory results were achieved in 88% of the patients, and only four pseudarthroses (6%) occurred. The ISFS provides rigid stabilization to enhance bone graft consolidation and to allow rapid postoperative mobilization in a light external orthosis.

The case for pedicle fixation of the lumbar spine.

STUDY DESIGN: This was a retrospective review of one surgeon's results using three different lumbosacral arthrodesis techniques: Group 1, no instrumentation; Group 2, Luque Rod and sublaminar wire technique; and Group 3, AO intrapedicular screw and plate technique. OBJECTIVE: To determine whether the use of metal implants results in a higher fusion rate. Once a solid arthrodesis is achieved, is this correlated with a good clinical result? SUMMARY OF BACKGROUND DATA: Controversy persists regarding the value of the use of intrapedicular fixation to augment arthrodesis of the lumbosacral junction. Controversy also exists regarding the correlation of solid arthrodesis with relief of preoperative symptoms. METHODS: Three serial sequential populations (50 subjects each) undergoing varied primary multiple-level lumbosacral arthrodesis procedures were studied retrospectively. The ultimate clinical results of these three different surgical populations were studied after prolonged follow-up. RESULTS: Group one had a 14% fusion rate and a 4% complication rate. Group two had a 36% fusion rate and an 8% complication rate. Group three had a 64% fusion rate and an 18% complication rate. Complications were intraoperative dural tears and nerve root injuries. Patient satisfaction with each operative procedure to relieve preoperative low back pain was statistically correlated with whether a solid arthrodesis was obtained. CONCLUSION: Intrapedicular fixation technique is the most reliable method for obtaining a solid multiple-level lumbosacral arthrodesis. Solid arthrodesis is correlated with a successful clinical result. Complications associated with the use of intrapedicular fixation were frequent but their occurrence demonstrated a "learning curve pattern."

Stabilization of the lower thoracic and lumbar spine with the internal spinal skeletal fixation system. Indications, techniques, and first results of treatment.

Since 1984, 30 patients with burst fractures of the lower thoracic and lumbar spine were treated with AO internal spinal skeletal fixation system. All patients in this series had a minimum follow-up of 12 months. This new instrumentation is a posterior intrapedicular system developed by Dick in 1982. It allows stable fixation that is limited only to adjacent spinal segments. The internal fixator permits reduction in all three planes. Independently, it is possible to add distraction or compression to the involved segments. It also is able to reduce effectively the "middle column" which is thought to be accomplished by "ligamentotaxis." In this series there were 16 neurologically intact patients and 14 with partial or complete neurologic injury. There were two minor instrumentation loosenings early in the series. Most patients in this series had a near-anatomic reduction of all three columns in the involved segment. It was also possible to re-establish the normal lordosis of the lumbar spine. The device provided sufficient rigid fixation for rapid postoperative mobilization in a light external orthosis.

Anterior interbody fusion of the cervical spine with coralline hydroxyapatite.

STUDY DESIGN: A nonrandomized, retrospective human study of patients requiring anterior discectomy and reconstruction from C3 to T1. The pattern of incorporation, presence or absence of disc space collapse, maintenance of correction, and clinical outcomes were considered. OBJECTIVE: To determine the efficacy of coralline hydroxyapatite as a bone replacement in anterior interbody fusions of the cervical spine used in conjunction with rigid plate fixation. SUMMARY OF THE BACKGROUND DATA: Autograft is the gold standard for anterior interbody fusion of the cervical spine. Reported complication and morbidity rates with the use of autograft are as high as 21%. Using allograft instead of autograft presents numerous problems including lower rates of fusion. Other bone substitutes such as ceramics and polymethylmethacrylate are ineffective for fusion. METHODS: Twenty-six skeletally mature patients underwent anterior decompression, stabilization, microdiscectomy, and reconstruction with Pro Osteon 200 (Interpore Cross International, Irvine, CA) coralline hydroxyapatite and AO anterior cervical locking plates. Iliac crest autograft, local bone, and allograft were not used. RESULTS: The minimum follow-up period was 2 years (average, 30 months). There was no evidence of plate breakage, screw breakage, resorption of the implant, or pseudarthrosis. Two patterns of incorporation were identified. The implant incorporated totally in 100% of the disc spaces. Average hospital stay was 1.6 days. The average decrease in pain was 75.8%. There was no evidence of nonunion. CONCLUSIONS: The use of Pro Osteon 200 with rigid anterior plating seems promising as a bone replacement in the cervical spine. The incorporation rate is exceedingly high, and the complication rate nonexistent.

Reconstruction of the lumbar spine using AO DCP plate internal fixation.

Augmentation of lumbar spine fusion with internal fixation using pedicle screw systems has gained wide currency because it offers rigid stabilization to foster fusion healing. The AO DCP plate has been employed in Europe as a spinal implant with pedicle fixation using 6.5 mm, full-threaded cancellous bone screws with success. This report details the experience of using this device for lumbar spine fusion in a series of 46 North American patients with a mean follow-up of 1.25 years (range 1-2.5 years). Thirty-one patients had had prior lumbar spine surgery with poor outcomes, and 15 had had no prior surgery. All were treated surgically for lumbar degenerative disease with canal decompression, internal fixation with AO plates, and fusion with autologous bone grafting posterolaterally. Complications included two early and one delayed wound infection; five cases of screw loosening; three cases of screw breakage; and three cases of screw impingement upon a nerve. Results of surgery in 17 patients with failed interbody fusion included good to excellent pain relief in 59%, and solid fusion in 76%. In 14 patients with failed posterior surgery the good to excellent pain relief rate was 79%, and the fusion rate was 86%. In 15 patients undergoing primary surgery there was 89% good to excellent pain relief and a solid fusion rate of 87%. The benefits accruing from augmentation of the fusion with internal fixation using AO DCP plates are positive and justify its continued use. Complications encountered in the early experience have been significantly reduced in subsequent series, indicating the existence of a "learning curve" effect which would mandate specific training of spinal surgeons in the technique.

Reconstruction of failed lumbar surgery with narrow AO DCP plates for spinal arthrodesis.

Forty-five patients underwent surgical reconstruction with transpedicular fixation of the lumbar spine with narrow AO DCP plates. Preoperatively, all patients underwent spinal imaging with either magnetic resonance imaging, computed tomography, or myelogram as well as provocative discography to determine the location and the number of symptomatic segments. The minimum follow-up in this series was 2 years. The determination of solid posterior fusion in the presence of plate instrumentation was difficult. The patients in the series were classified as having 1) solid fusion; 2) radiographic flaws within the posterolateral fusion without implant failure; or 3) frank pseudarthrosis with implant failure. Thirty-six (80%) of the patients had a solid fusion, 9 of whom required an additional anterior interbody fusion to obtain symptom control. Twenty percent of the patients in the series had radiographic evidence of reabsorption without implant failure. Four patients in the series (8.8%) had screw breakage, three of which required anterior interbody fusions. The highest rate of reabsorption and pseudarthrosis implant failure was in the 12 patients who had three-level instrumentation; 33% of these patients required anterior interbody fusion to obtain a solid arthrodesis. The average preoperative pain scale was 8.9, and the average postoperative pain scale was a 3.3. Twenty-two patients in the series were cigarette smokers and had a slightly lower fusion rate than non-smokers. They did, however, have a higher use of narcotics after surgery. Forty percent of the patients in this series continued to have radiculopathy after their reconstruction. This study demonstrates the utility of transpedicular fixation in salvage lumbar surgery in obtaining a solid arthrodesis with a beneficial clinical result. Anterior interbody fusions are highly successful in the management of pseudarthrosis and implant failure after transpedicular instrumentation.

Odontoid fractures treated by anterior odontoid screw fixation.

While odontoid fractures are common injuries, disagreement exists regarding treatment. Some authors claim a high rate of pseudoarthrosis and have therefore recommended early posterior fixation and fusion. This, however, results in decreased cervical rotation. Therefore, it has been recommended that a more direct approach to the fracture be taken. Results on anterior screw fixation in 14 patients are reported. The technique was found to be especially useful in multiple trauma patients, patients who refuse halo treatment, and in some nonunions.

Postoperative infections in spinal implants. Classification and analysis--a multicenter study.

A multicenter study was undertaken to analyze postoperative wound infections after posterior spinal instrumentation and fusion. The infection rate of these procedures has been documented in multiple reports. From these results, a classification scheme was developed that can guide therapy and determine the populations at risk. The patients were categorized according to two parameters, the first being the severity or type of infection, and the second being the host response or physiologic classification of the patient. This classification scheme is based on the clinical staging system for adult osteomyelitis developed by Cierny. The severity of infection is divided into three groups. Group 1 is a single-organism infection, either superficial or deep. Group 2 is a multiple-organism, deep infection. Group 3 is multiple organisms with myonecrosis. The host response, likewise, is divided into three classes. Class A is a host with normal systemic defenses, metabolic capabilities, and vascularity. Class B patients demonstrate local or multiple systemic diseases, including cigarette smoking. Class C requires an immunocompromised or severely malnourished host. Our data have demonstrated that single organisms, Group 1, generally can be dealt with by single irrigation and debridement, and closure over suction drainage tubes without the use of an inflow-irrigation system. The Group 2 patients, with multiple organisms and deep infection, required an average of three irrigation debridements. They have a higher percentage of successful closures with closed inflow-outflow suction irrigation systems when compared to simple suction drainage systems without constant inflow irrigation. Multiple-organism infections with myonecrosis, Group 3, are exceedingly difficult to manage, and portend a poor outcome. Patients without normal host defenses, Classes B and C, are at high risk for developing postoperative wound infection. Specifically, this study demonstrated that cigarette smoking may be a significant risk factor.

The contoured anterior spinal plate system (CASP). Indications, techniques, and results.

The contoured anterior spinal plate (CASP) was developed for secure fixation of the anterior thoracolumbar spine. This is a report of 38 patients with various spinal pathologies treated with this system. The results were excellent regarding plate fixation and fusion. Comments on surgical technique and indications are provided.

Management of metastatic tumors to the spine using simple plate fixation.

Frequency of metastasis to the spine in the population of patients suffering from malignant disease is a significant clinical problem, as these patients present with intractable pain and neurologic impairment. The sequelae of metastatic tumors to the spinal column significantly decrease the quality of the patient's life. With the advent of modern chemotherapeutic regimens in metastatic disease, patients with metastatic tumors are living longer and more productive lives. The goal of surgical management of this problem is to increase the quality of the patient's life, and not longevity. The immediate technical goals are resection of the pathological segment, restoration of load bearing capacity for mobilization of the patient, and decompression of compromised neural structures, as well as maintenance of spinal stability to decrease pain and increase the patient's quality of life during the terminal stages. This is a series of 28 patients with metastatic tumors to the spine, with an average age of 61.5 years, ranging from 25-81 years of age. Within this population there were 11 different tumor types. The postoperative survivorship was an average of 6.4 months. Twenty patients in this series had an anterior procedure alone using a combination of Methylmethacrylate and inexpensive plate fixation. Six patients required an anterior/posterior procedure for circumferential spinal compression and instability. These techniques provide immediate spinal stability for rapid mobilization of the patient. Twenty-four patients in the series had significant pain relief, and 17 experienced neurologic improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Instrumented posterolateral lumbar fusion using coralline hydroxyapatite with or without demineralized bone matrix, as an adjunct to autologous bone.

BACKGROUND CONTEXT: Autogenous posterolateral fusion with and without instrumentation has been reported with good results. However, difficult-to-fuse patients, such as smokers, elderly patients with poor bone quality and/or quantity, or patients with prior posterior surgeries, may have somewhat lower fusion rates. PURPOSE: To determine the efficacy of coralline hydroxyapatite with or without demineralized bone matrix as a bone graft extender in a human clinical model with long-term follow-up. STUDY DESIGN/SETTING: A retrospective series of 40 patients undergoing instrumented autogenous posterolateral lumbar fusion augmented with coralline hydroxyapatite with or without demineralized bone matrix. PATIENT SAMPLE: Long-term clinical and radiographic follow-up were examined for 40 patients who underwent an instrumented posterolateral fusion only. Patients undergoing anterior lumbar interbody fusion (ALIF) procedures were not considered part of the sample. METHODS: All patients underwent successful transpedicular fixation with autogenous posterolateral lumbar fusion. Fifteen cc of Pro Osteon 500 coralline hydroxyapatite (Interpore Cross International, Irvine, CA) was used at each level. An additional 10 cc of Grafton demineralized bone matrix gel (Osteotech, Eatontown, NJ) was used in 70% of these patients. RESULTS: An overall fusion rate of 92.5% was achieved. Pain and function improvement were good but somewhat age dependent and correlated with the number of comorbidities. Patients with Grafton DBM gel had a lower fusion rate of 89.3%. CONCLUSIONS: Based on this small retrospective review, coralline hydroxyapatite is an effective bone graft extender in difficult-to-fuse patients as an adjunct to autologous bone for posterolateral fusion of the lumbar spine when combined with rigid instrumentation.

[A new minimally invasive approach to interior lumbal spine fusion.]. / Nový minimálne ínvazivní prístup k prední intersomatické spondylodéze bederní pátere.

The authors are presenting results on minimally-invasive laparoscopic approach to obtain anterior fusion of the lumbar spine on group of 62 patients. 12 patients had to have a conversion to open procedure. 50 patients were included in the follow up and evaluated in average 22 months after surgery. The advantages of the approach were documented by good overall rating of the procedure by the patients themselves, low blood loss, short hospital stay and high fusion rate. More than 50 % of patients had previously at least one spine surgery. The endoscopic retroperitoneal gasless approach (BERG) is very convenient as it enables surgery without gas insuflation in space large enough to treat as many as 3 spine levels at the same time. Key words: anterior interbody lumbar fusion, laparoscopic, minimally-invasive surgery.

The internal skeletal fixation system. A new treatment of thoracolumbar fractures and other spinal disorders.

A new internal skeletal fixation system (ISFS) for stabilizing thoracolumbar fractures and other spinal disorders was developed by Dick in Switzerland. The ISFS is a modification of the Magerl external skeletal fixation system of the spine. The Dick modification consists of a threaded rod connected by clamps to Schanz screws and is located in the vertebral pedicles on both sides of the spine. Due to a stable angle between the rod and Schanz screw, a one-point fixation above and below the diseased vertebra is sufficient. The ISFS provides a short fixation and promotes fusion. Control of lordosis, kyphosis, and rotation of the spine is possible with threaded rod distraction and compression and through manipulation of the Schanz screws held by movable clamps. The advantage of the ISFS is the ability to achieve reduction and fixation with the same instrumentation. ISFS has been used in more than 90 patients and proven most adequate for thoracolumbar fractures and other localized spinal disorders. The Harrington system and its modifications are no longer in use for these problems.

Adult spondylolisthesis treated with posterolateral lumbar fusion and pedicular instrumentation with AO DC plates.

Attainment of successful lumbar fusion in adults with spondylolisthesis has historically been unpredictable. Recent results and conclusions have been conflicting regarding the role of instrumentation in improving the fusion rate and clinical outcome in this patient population. In a retrospective multicenter clinical study, we assessed the outcome of 42 adults with spondylolisthesis who underwent posterolateral lumbar fusion by using pedicular instrumentation with AO DC plates. No attempt was made to reduce slippage. Follow-up clinical outcome was obtained from a patient questionnaire administered and assessed by an independent reviewer. Fusion status was assessed by anteroposterior, lateral, and oblique radiographs at the most recent follow-up examination. Spondylolisthesis was classified as degenerative in 21 patients and isthmic in 21 patients. Solid fusion was achieved in 32 (76%) patients; pseudoarthrosis occurred in two (5%) patients; the fusion mass was indeterminate in eight (19%) patients. Clinical outcome parameters rated 73% excellent to good and 27% fair to poor. Complications included four infections and two screw breakages. Poor results correlated strongly with cigarette smoking and multiple previous surgeries. In this study, fusion rate and clinical outcome were consistent with previous reports of adult spondylolisthesis. Rates of successful fusion varied according to the type of spondylolisthesis.

Four year experience with the AO Anterior Thoracolumbar Locking Plate.

For decades spinal surgeons have attempted to design simple, single stage anterior internal fixation systems for the thoracic and lumbar spine. Early devices presented both biomechanical and technical problems. The AO Anterior Thoracolumbar Locking Plate (ATLP) was designed to solve some of the problems encountered with early anterior instrumentation. The ATLP system is constructed in Commercially Pure titanium. It is a low profile device indicated for use for unstable burst fractures in the anterior column; metastatic tumor management; and degenerative diseases of the thoracolumbar spine between levels T10 and L5. Implantation of the device involves direct anterior decompression with sagittal reduction and corpectomy. This is followed by grafting reconstruction, and plate fixation. This device has been implanted in 25 patients with an average follow-up of 38 months. There were five (5) broken screws in three (3) patients, and no broken plates. Implant related postoperative complications included two misplaced screws. Preliminary results indicate that the ATLP system seems to be a safe, low profile, MRI/CT compatible device that provides definitive single stage fixation of the anterior spinal column.

Improved outcome with early fixation of skeletally unstable pelvic fractures.

Thirty-seven consecutive patients with unstable pelvic fractures were divided into two groups: Group 1 (July 1981 to December 1984; n = 18), when early fixation was not routinely used, and Group 2 (January 1985 to March 1988; n = 19), when early fixation was performed unless contraindicated. Hospital stay decreased by 37.8% in Group 2 (p = 0.04). Of Group 1 patients, 60% were disabled for at least 6 months versus 15.7% in Group 2 (p = 0.001), and 45% were discharged to a rehabilitation facility versus 26.4% in Group 2. Group 1 had more complications, 1.3 per patient, versus 1.0. Patients in Group 2 (undergoing early fixation) required 27.2% fewer units of blood than those in Group 1 in whom fracture surgery was delayed. Survival was better in Group 2, 100% versus 83.3% (p = 0.06). Early pelvic fracture fixation reduces hospital stay, long-term disability, and may result in fewer complications, decreased blood loss, and better survival.

Gasless endoscopic anterior lumbar interbody fusion utilizing the B. E.R.G. approach.

BACKGROUND: Several authors have reported success using a gas-mediated transperitoneal approach for lumbar interbody fusion. However, this approach has not been shown to reliably and predictably address segments above L4-5. METHODS: The B.E.R.G. approach was attempted in 202 patients who required anterior lumbar interbody fusion (ALIF). Of those, 168 were completed successfully without conversion to an open procedure. The anterior retroperitoneal approach required no gas insufflation. The gasless environment allowed for the use of standard anterior instrumentation and a variety of fusion grafts and devices. RESULTS: Mean hospital stay was 1.95 days, with 73% of patients discharged in <47 h following surgery. Clinical results from the first 50 patients, with a minimum 2-year follow-up, include a 92% fusion rate and 78% of patients reporting significant pain relief of greater than 50%. CONCLUSIONS: The B.E.R.G. approach offers significant technical advantages over the standard gas-mediated transperitoneal approach for ALIF. The clinical results are similar to those reported for open approaches and the gas-mediated transperitoneal approach.

Minimally invasive 360 degrees instrumented lumbar fusion.

A retrospective preliminary study was undertaken of combined minimally invasive instrumented lumbar fusion utilizing the BERG (balloon-assisted endoscopic retroperitoneal gasless) approach anteriorly, and a posterior small-incision approach with translaminar screw fixation and posterolateral fusion. The study aimed to quantify the clinical and radiological results using this combined technique. The traditional minimally invasive approach to the anterior lumbar spine involves gas insufflation and provides reliable access only to L5-S1 and in some cases L4-5. A gas-mediated approach yields many technical drawbacks to performing spinal surgery. A minimally invasive posterior approach involving suprafascial pedicle screw instrumentation has been developed, but without wide-spread use. Translaminar facet fixation may be a viable alternative to transpedicular fixation in a 360 degrees instrumented fusion model. Past studies have shown open 360 degrees instrumented lumbar fusion yields high arthrodesis rates. The study examined the cases of 46 patients who underwent successful 360 degrees instrumented lumbar fusion using a combined minimally invasive approach. Anterior lumbar interbody fusion (ALIF) at one or two levels was performed through the BERG approach; a gasless retroperitoneal approach to the lumbar spine allowing the use of standard anterior instrumentation. Posteriorly, all patients underwent successful decompression, translaminar fixation, and posterolateral fusion at one or two levels through one small (2.5-5.0 cm) incision. Results showed mean hospital stay of 2.02 days; mean combined blood loss was 255 cc; and mean pain relief was 56%, with 75.5% of patients reporting good, excellent, or total pain relief. Forty-two of 46 patients (93.2%) achieved a solid fusion 24 months after surgery. A total of 47% of all patients working prior to surgery returned to work following surgery. The study showed that minimally invasive 360 degrees instrumented lumbar fusion, when performed utilizing these approaches, yields a high rate of solid arthrodesis (93.3%), good pain relief, short hospital stays, low blood losses, accelerated rehabilitation, and a quick return to the workforce. The BERG approach offers technical advantages over the traditional gas-mediated laparoscopic approach to the anterior lumbar spine.