Autologous incubated macrophage therapy in acute, complete spinal cord injury: results of the phase 2 randomized controlled multicenter trial.

STUDY DESIGN: Randomized controlled trial with single-blinded primary outcome assessment. OBJECTIVES: To determine the efficacy and safety of autologous incubated macrophage treatment for improving neurological outcome in patients with acute, complete spinal cord injury (SCI). SETTING: Six SCI treatment centers in the United States and Israel. METHODS: Participants with traumatic complete SCI between C5 motor and T11 neurological levels who could receive macrophage therapy within 14 days of injury were randomly assigned in a 2:1 ratio to the treatment (autologous incubated macrophages) or control (standard of care) groups. Treatment group participants underwent macrophage injection into the caudal boundary of the SCI. The primary outcome measure was American Spinal Injury Association (ASIA) Impairment Scale (AIS) A-B or better at ≥6 months. Safety was assessed by analysis of adverse events (AEs). RESULTS: Of 43 participants (26 treatment, 17 control) having sufficient data for efficacy analysis, AIS A to B or better conversion was experienced by 7 treatment and 10 control participants; AIS A to C conversion was experienced by 2 treatment and 2 control participants. The primary outcome analysis for subjects with at least 6 months follow-up showed a trend favoring the control group that did not achieve statistical significance (P=0.053). The mean number of AEs reported per participant was not significantly different between the groups (P=0.942). CONCLUSION: The analysis failed to show a significant difference in primary outcome between the two groups. The study results do not support treatment of acute complete SCI with autologous incubated macrophage therapy as specified in this protocol.

A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics.

STUDY DESIGN: Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (SCI). OBJECTIVES: Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics. SETTING: Subjects were recruited to one of six international study centers. METHODS: Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized. RESULTS: Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment. CONCLUSION: The 'funnel effect' (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.

MRI of the athletic knee. Findings in asymptomatic professional basketball and collegiate football players.

For the dedicated athlete in whom minor injuries are frequent and major injuries relatively common, a noninvasive knee assessment could either obviate the need for arthroscopy or focus its direction. The opportunity to study asymptomatic athletes was not feasible before the advent of magnetic resonance imaging (MRI). In this preliminary work, we examined 40 knees in 20 asymptomatic volunteer athletes, including five professional basketball players and 15 collegiate football players. Images were obtained at 0.5 T or 1.5 T. Spin echo sequences were used to obtain 5.0 mm thick coronal and sagittal sections. Fifty percent of asymptomatic athletes (10/20) had significant baseline MRI abnormalities that could have adversely affected scan interpretation in the context of an acute injury. Half of these athletes with MRI abnormalities, or 25% of the total (5/20), had no previous surgery and were unaware of significant injury.

Phenotypic adaptations in human muscle fibers 6 and 24 wk after spinal cord injury.

The effects of spinal cord injury (SCI) on the profile of sarco(endo) plasmic reticulum calcium-ATPase (SERCA) and myosin heavy chain (MHC) isoforms in individual vastus lateralis (VL) muscle fibers were determined. Biopsies from the VL were obtained from SCI subjects 6 and 24 wk postinjury (n = 6). Biopsies from nondisabled (ND) subjects were obtained at two time points 18 wk apart (n = 4). In ND subjects, the proportions of VL fibers containing MHC I, MHC IIa, and MHC IIx were 46 +/- 3, 53 +/- 3, and 1 +/- 1%, respectively. Most MHC I fibers contained SERCA2. Most MHC IIa fibers contained SERCA1. All MHC IIx fibers contained SERCA1 exclusively. SCI resulted in significant increases in fibers with MHC IIx (14 +/- 4% at 6 wk and 16 +/- 2% at 24 wk). In addition, SCI resulted in high proportions of MHC I and MHC IIa fibers with both SERCA isoforms (29% at 6 wk and 54% at 24 wk for MHC I fibers and 16% at 6 wk and 38% at 24 wk for MHC IIa fibers). Thus high proportions of VL fibers were mismatched for SERCA and MHC isoforms after SCI (19 +/- 3% at 6 wk and 36 +/- 9% at 24 wk) compared with only ~5% in ND subjects. These data suggest that, in the early time period following SCI, fast fiber isoforms of both SERCA and MHC are elevated disproportionately, resulting in fibers that are mismatched for SERCA and MHC isoforms. Thus the adaptations in SERCA and MHC isoforms appear to occur independently.

Influence of complete spinal cord injury on skeletal muscle within 6 mo of injury.

This study examined the influence of spinal cord injury (SCI) on affected skeletal muscle. The right vastus lateralis muscle was biopsied in 12 patients as soon as they were clinically stable (average 6 wk after SCI), and 11 and 24 wk after injury. Samples were also taken from nine able-bodied controls at two time points 18 wk apart. Surface electrical stimulation (ES) was applied to the left quadriceps femoris muscle to assess fatigue at these same time intervals. Biopsies were analyzed for fiber type percent and cross-sectional area (CSA), fiber type-specific succinic dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (GPDH) activities, and myosin heavy chain percent. Controls showed no change in any variable over time. Patients showed 27-56% atrophy (P = 0.000) of type I, IIa, and IIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSA approximately one-third that of controls. Their fiber type specific SDH and GPDH activities increased (P

Esophageal and hypopharyngeal injuries in patients with cervical spine trauma.

The authors review their recent experience with four patients referred to the Shepherd Spinal Center, Atlanta, with cervical spine fracture dislocation and quadriplegia. The patients were subsequently found to have tears of the hypopharynx or the esophagus as a complication of their injury. Unexplained fever, swelling of the neck, dysphagia or leukocytosis in the patient with acute cervical spine injury suggest, the authors urge, the possibility of esophageal or hypopharyngeal perforation. The authors review the kinematics and pathophysiology of cervical fractures and provide clues to early detection and management of perforation of the hypopharynx or esophagus, including the use of radiographic study and endoscopy.

Spinal cord injury in youth.

To identify special characteristics of the pediatric spinal cord-injured (SCI) population, we analyzed a database of 1,770 traumatic SCI patients; 88 (5%) fell into the two pediatric subgroups: 0-12 years (n = 26) and 13-15 years (n = 62) at time of injury. Differences between age groups were identified with regard to demographics, neurologic characteristics, associated injuries and complications, and management. Mode level of bony injury was C2 in preteens, C4 in teens, and C4-C5 in adults. Scoliosis developed far more frequently in children, particularly preteens (23%), than in adults (5%). Violent etiologies, predominantly gunshots, accounted for a disproportionate share of injuries to preteens (19%) and African-Americans (28%), as compared with adults (12%) and Caucasians (7%). This last finding underscores the urgent need to mount a response to the nationwide proliferation of gunshot-related SCI in children and minorities.

Adolescent runners.

The inherent flexibility of young and adolescent runners does not protect them from injury. An understanding of the similarities to and differences from adult problems will help the physician to not only treat appropriately but also give meaningful advice to parents and coaches.

End stage running problems.

What is the problem of a runner who is not recovering? It may be that the diagnosis is incorrect or that the treatment is improper. This article reviews uncommon problems of the lower extremities that may provide the answer.

Spinal cord injury occurring in patients with ankylosing spondylitis: a multicenter study.

Treatment of spinal fractures causing paralysis in patients with ankylosing spondylitis is difficult. A multicenter concurrent study evaluated 59 patients--22 managed operatively and 37 nonoperatively. The two groups were compared for neurologic outcome, complications, mortality, and length of stay. The results indicated that patients in the nonoperative group had a significantly shorter length of stay and, therefore, a significantly lower cost of care. No other differences between operative and nonoperative groups were identified in regard to other outcome variables. Results of descriptive analyses of patient characteristics and treatment choices have significant implications for practitioners.

Basketball Injuries: An Overview.

In brief: Why have basketball injuries escalated? The author points out that before 1960 basketball was largely a no-contact sport. Since then the amount of body contact allowed has increased, players are larger, and more athletes are playing basketball. In addition to these and other possible reasons for the increase in injuries, the author describes common basketball injuries-contusions, sprains, strains, inflammatory conditions, and stress fractures. He also outlines steps for diagnosis and treatment and makes recommendations.

Sportsmedicine forum.

A Forum For Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondance to Sports medicine Forum, THE PHYSIC/AN AND SPORTSMEDICINE, 4530 W 77th St, Minneapolis, MN 55435.

sportsmedicine forum.

A Forum For Our Readers Sportsmedicine Forum is intended to provide a sounding board for our readers. Perhaps you have a special way to treat a common medical problem, or you may want to air your views on a controversial topic. You may object to an article that we have published, or you may want to support one. You may have a new trend to report, identified through an interesting case or a series of patients. Whatever your ideas, we invite you to send them to us. Illustrative figures are welcomed. Address correspondence to Sportsmedicine Forum, The Physician And Sportsmedicine, 4530 W 77th St, Minneapolis. MN 55435.

Hysterical spinal paralysis.

Seventeen patients were diagnosed as having hysterical paralysis. Although a variety of patterns of motor and sensory loss were seen, 15 out of 17 patients had normal reflexes, and all the patients had bowel and bladder control, an important diagnostic point. All but 1 were improved after an average 3.8 days hospital stay with 13 being fully recovered. When a patient is encountered with paralysis, normal reflexes and bowel and bladder control, the only initial diagnostic study indicated is routine X-rays.

Knee pain in runners.

Of 149 runners seen with knee pain, 60 had common orthopedic problems as the cause. Eighty-nine had recurring pain but few or no classic findings. These runners were divided into four groups depending on localization of the pain. Gait mechanical problems were identified and treatment regimens developed. Questionnaires were returned by 40 runners who fit into these four pain groups. Treatment by injections, anti-inflammatory agents, and advice to rest or stop running had produced only temporary results. Correction of biomechanical problems related to running relieved or improved the pain in 37 of 40 patients.

Ipsilateral fractures of the elbow and forearm.

One hundred and fifty-one patients with distal humeral fractures admitted to three major hospitals in Atlanta were studied retrospectively. Of these, 15 (10%) also had a fracture of the ipsilateral forearm. These appeared to be more severe injuries with a history of greater trauma and more displacement in the elbow fractures. The incidence of complications was the same in both groups with the exception of a higher incidence of cubitus varus among patients with combined fractures.