Cerebrospinal fluid leaks following cervical spine surgery.

BACKGROUND: A cerebrospinal fluid leak during cervical spine surgery is a feared complication. However, little is known about the prevalence, management, and long-term course of these events. METHODS: The medical records of 1994 patients who had elective cervical spine surgery during an eleven-year period (1994 through 2005) were reviewed. Patients with cervical cerebrospinal fluid leaks identified at the time of surgery were followed both clinically and radiographically for an average of 5.4 years postoperatively. The prevalence, etiology, management, and outcome of all of the cervical cerebrospinal fluid leaks were analyzed. RESULTS: The overall prevalence of cerebrospinal fluid leaks was 1%. The prevalence of cerebrospinal fluid leaks was higher in patients with a diagnosis of ossification of the posterior longitudinal ligament (12.5%), patients having a revision anterior procedure (1.92%), men (1.56%), and patients undergoing an anterior cervical corpectomy and arthrodesis (1.77%). CONCLUSIONS: Many cervical dural tears can be managed by observation alone or by placement of a lumbar cerebrospinal fluid shunt either during the index procedure or in the postoperative period. At an average follow-up of 5.4 years, there were no long-term sequelae of the cervical dural tears in our series.

Utilization of predonated autologous blood in anterior cervical corpectomy and fusion surgery.

OBJECTIVE: To determine the utilization of predonated autologous blood in patients treated with anterior cervical corpectomy and fusion (ACCF). METHODS: Retrospective chart review of 154 patients who underwent 1, 2, or 3-level ACCF over a 6-year period was performed. Variables collected included patterns of autologous and allogenic blood use, blood loss, and hematocrit at admission and discharge from the hospital. RESULTS: For 1-level ACCF, only 16.7% of the predonated autologous blood was used. As expected, use of predonated autologous blood increased with the number of corpectomy levels: Patients with 2 and 3-level ACCF used 29.0% and 53.4% of the predonated blood, respectively. The use of autologous blood significantly reduced the need for allogenic blood transfusion for 2 and 3-level ACCF. CONCLUSIONS: Autologous blood was used efficiently in 3-level ACCF, and predonation is associated with decreased allogeneic blood transfusion requirement in 2 and 3-level ACCF.

Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model.

BACKGROUND: The heterotopic ossification of muscles, tendons, and ligaments is a common problem faced by orthopaedic surgeons. We investigated the ability of Noggin (a BMP [bone morphogenetic protein] antagonist) to inhibit heterotopic ossification. METHODS: Part 1: A retroviral vector carrying the gene encoding human Noggin was developed and used to transduce muscle-derived stem cells. Part 2: Cells transduced with BMP-4 were implanted into both hind limbs of mice along with either an equal number, twice the number, or three times the number of Noggin-expressing muscle-derived stem cells (treated limb) or with nontransduced muscle-derived stem cells (control limb). At four weeks, the mice were killed and radiographs were made to look for evidence of heterotopic ossification. Part 3: Eighty milligrams of human demineralized bone matrix was implanted into the hind limbs of SCID (severe combined immunodeficiency strain) mice along with 100,000, 500,000, or 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At eight weeks, the mice were killed and radiographs were made. Part 4: Immunocompetent mice underwent bilateral Achilles tenotomy along with the implantation of 1,000,000 Noggin-expressing muscle-derived stem cells (treated limbs) or nontransduced muscle-derived stem cells (control limbs). At ten weeks, the mice were killed and radiographs were made. RESULTS: Part 1: An in vitro BMP inhibition assay demonstrated that Noggin was expressed by muscle-derived stem cells at a level of 280 ng per million cells per twenty-four hours. Part 2: Three varying doses of Noggin-expressing muscle-derived stem cells inhibited the heterotopic ossification elicited by BMP-4-expressing muscle-derived stem cells. Heterotopic ossification was reduced in a dose-dependent manner by 53%, 74%, and 99%, respectively (p < 0.05). Part 3: Each of three varying doses of Noggin-expressing muscle-derived stem cells significantly inhibited the heterotopic ossification elicited by demineralized bone matrix. Heterotopic ossification was reduced by 91%, 99%, and 99%, respectively (p < 0.05). Part 4: All eleven animals that underwent Achilles tenotomy developed heterotopic ossification at the site of the injury in the control limbs. In contrast, the limbs treated with the Noggin-expressing muscle-derived stem cells had a reduction in the formation of heterotopic ossification of 83% and eight of the eleven animals had no radiographic evidence of heterotopic ossification (p < 0.05). CONCLUSIONS: The delivery of Noggin mediated by muscle-derived stem cells can inhibit heterotopic ossification caused by BMP-4, demineralized bone matrix, and trauma in an animal model. CLINICAL RELEVANCE: Gene therapy to deliver Noggin may become a powerful method to inhibit heterotopic ossification in targeted areas of the body.

Gene therapy in orthopaedic surgery.

Gene therapy has the potential to revolutionize the treatment of a variety of musculoskeletal disorders. In the past decade, more than 4,000 patients have been enrolled in clinical trials involving gene therapy. Gene therapy is becoming increasingly important in modern orthopaedic clinical practice. It is important to discuss the issues that physicians and scientists face when designing an experiment or clinical trial involving gene therapy, along with the potential clinical applications for gene therapy in the treatment of patients with musculoskeletal problems.