Adipose-derived Human Perivascular Stem Cells May Improve Achilles Tendon Healing in Rats.

BACKGROUND: Achilles tendon rupture is a common injury and the best treatment option remains uncertain between surgical and nonoperative methods. Biologic approaches using multipotent stem cells such as perivascular stem cells pose a possible treatment option, although there is currently a paucity of evidence regarding their clinical therapeutic use. QUESTIONS/PURPOSES: The purpose of this study was to determine whether injected perivascular stem cells (PSCs) would (1) improve histologic signs of tendon healing (such as percent area of collagen); and (2) improve biomechanical properties (peak load or stiffness) in a rat model of Achilles tendon transection. METHODS: Two subtypes of PSCs were derived from human adipose tissue: pericytes (CD146CD34CD45CD31) and adventitial cells (CD146CD34CD45CD31). Thirty-two athymic rats underwent right Achilles transection and were randomized to receive injection with saline (eight tendons), hydrogel (four tendons), pericytes in hydrogel (four tendons), or adventitial cells in hydrogel (eight tendons) 3 days postoperatively with the left serving as an uninjured control. Additionally, a subset of pericytes was labeled with CM-diI to track cell viability and localization. At 3 weeks, the rats were euthanized, and investigators blinded to treatment group allocation evaluated tendon healing by peak load and stiffness using biomechanical testing and percent area of collagen using histologic analysis with picrosirius red staining. RESULTS: Histologic analysis showed a higher mean percent area collagen for pericytes (30%) and adventitial cells (28%) than hydrogel (21%) or saline (26%). However, a nonparametric statistical analysis yielded no statistical difference. Mechanical testing demonstrated that the pericyte group had a higher peak load than the saline group (41 ± 7 N versus 26 ± 9 N; mean difference 15 N; 95% confidence interval [CI], 4-27 N; p = 0.003) and a higher peak load than the hydrogel group (41 ± 7 N versus 25 ± 3 N; mean difference 16; 95% CI, 8-24 N; p = 0.001). The pericyte group demonstrated higher stiffness than the hydrogel group (36 ± 12 N/mm versus 17 ± 6 N/mm; mean difference 19 N/mm; 95% CI, 5-34 N/mm; p = 0.005). CONCLUSIONS: Our results suggest that injection of PSCs improves mechanical but not the histologic properties of early Achilles tendon healing. CLINICAL RELEVANCE: This is a preliminary study that provides more insight into the use of adipose-derived PSCs as a percutaneous therapy in the setting of Achilles tendon rupture. Further experiments to characterize the function of these cells may serve as a pathway to development of minimally invasive intervention aimed at improving nonoperative management while avoiding the complications associated with surgical treatment down the line.

Epidural Hematoma Following Cervical Spine Surgery.

STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. METHODS: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. CONCLUSION: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements.

Intraoperative Death During Cervical Spinal Surgery: A Retrospective Multicenter Study.

STUDY DESIGN: A retrospective multicenter study. OBJECTIVE: Routine cervical spine surgeries are typically associated with low complication rates, but serious complications can occur. Intraoperative death is a very rare complication and there is no literature on its incidence. The purpose of this study was to determine the intraoperative mortality rates and associated risk factors in patients undergoing cervical spine surgery. METHODS: Twenty-one surgical centers from the AOSpine North America Clinical Research Network participated in the study. Medical records of patients who received cervical spine surgery from January 1, 2005, to December 31, 2011, were reviewed to identify occurrence of intraoperative death. RESULTS: A total of 258 patients across 21 centers met the inclusion criteria. Most of the surgeries were done using the anterior approach (53.9%), followed by posterior (39.1%) and circumferential (7%). Average patient age was 57.1 ± 13.2 years, and there were more male patients (54.7% male and 45.3% female). There was no case of intraoperative death. CONCLUSIONS: Death during cervical spine surgery is a very rare complication. In our multicenter study, there was a 0% mortality rate. Using an adequate surgical approach for patient diagnosis and comorbidities may be the reason how the occurrence of this catastrophic adverse event was prevented in our patient population.

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ2 tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.

Perivascular Stem Cells Diminish Muscle Atrophy Following Massive Rotator Cuff Tears in a Small Animal Model.

BACKGROUND: Rotator cuff tears are a common cause of shoulder pain and often necessitate operative repair. Muscle atrophy, fibrosis, and fatty infiltration can develop after rotator cuff tears, which may compromise surgical outcomes. This study investigated the regenerative potential of 2 human adipose-derived progenitor cell lineages in a murine model of massive rotator cuff tears. METHODS: Ninety immunodeficient mice were used (15 groups of 6 mice). Mice were assigned to 1 of 3 surgical procedures: sham, supraspinatus and infraspinatus tendon transection (TT), or TT and denervation via suprascapular nerve transection (TT + DN). Perivascular stem cells (PSCs) were harvested from human lipoaspirate and sorted using fluorescence-activated cell sorting into pericytes (CD146 CD34 CD45 CD31) and adventitial cells (CD146 CD34 CD45 CD31). Mice received no injection, injection with saline solution, or injection with pericytes or adventitial cells either at the time of the index procedure ("prophylactic") or at 2 weeks following the index surgery ("therapeutic"). Muscles were harvested 6 weeks following the index procedure. Wet muscle weight, muscle fiber cross-sectional area, fibrosis, and fatty infiltration were analyzed. RESULTS: PSC treatment after TT (prophylactic or therapeutic injections) and after TT + DN (therapeutic injections) resulted in less muscle weight loss and greater muscle fiber cross-sectional area than was demonstrated for controls (p < 0.05). The TT + DN groups treated with pericytes at either time point or with adventitial cells at 2 weeks postoperatively had less fibrosis than the TT + DN controls. There was less fatty infiltration in the TT groups treated with pericytes at either time point or with adventitial cells at the time of surgery compared with controls. CONCLUSIONS: Our findings demonstrated significantly less muscle atrophy in the groups treated with PSCs compared with controls. This suggests that the use of PSCs may have a role in the prevention of muscle atrophy without leading to increased fibrosis or fatty infiltration. CLINICAL RELEVANCE: Improved muscle quality in the setting of rotator cuff tears may increase the success rates of surgical repair and lead to superior clinical outcomes.