Gerard P. Slobogean

Cerebrospinal Fluid Inflammatory Cytokines and Biomarkers of Injury Severity in Acute Human Spinal Cord Injury

There is an urgent need for both the scientific development and clinical validation of novel therapies for acute spinal cord injury (SCI). The scientific development of novel therapies would be facilitated by a better understanding of the acute pathophysiology of human SCI. Clinical validation of such therapies would be facilitated by the availability of biomarkers with which to stratify injury severity and predict neurological recovery. Cerebrospinal fluid (CSF) samples were obtained over a period of 72 h in 27 patients with complete SCI (ASIA A) or incomplete SCI (ASIA B or C). Cytokines were measured in CSF and serum samples using a multiplex cytokine array system and standard enzyme-linked immunosorbent assay (ELISA) techniques. Neurological recovery was monitored, and patient-reported neuropathic pain was documented. IL-6, IL-8, MCP-1, tau, S100beta, and glial fibrillary acidic protein (GFAP) were elevated in a severity-dependent fashion. A biochemical model was established using S100beta, GFAP, and IL-8 to predict injury severity (ASIA A, B, or C). Using these protein concentrations at 24-h post injury, the model accurately predicted the observed ASIA grade in 89% of patients. Furthermore, segmental motor recovery at 6 months post injury was better predicted by these CSF proteins than with the patients baseline ASIA grade. The pattern of expression over the first 3 to 4 days post injury of a number of inflammatory cytokines such as IL-6, IL-8, and MCP-1 provides invaluable information about the pathophysiology of human SCI. A prediction model that could use such biological data to stratify injury severity and predict neurological outcome may be extremely useful for facilitating the clinical validation of novel treatments in acute human SCI.

Patient-Reported Outcome Instruments for Femoroacetabular Impingement and Hip Labral Pathology: A Systematic Review of the Clinimetric Evidence

PURPOSEnThe purpose of this study is to systematically review the content and clinimetric evidence (rigor of rating scales and indexes for the description of clinical phenomena) of published patient-reported outcome (PRO) instruments used to assess femoroacetabular impingement (FAI) and labral hip pathology.nnnMETHODSnWe used Medical Subject Heading terms related to FAI and labrum/labral tears to search the Medline, Embase, and Cochrane databases for studies of FAI and labral hip pathology. Studies with hip-related PRO instruments, with any operative intervention except total hip arthroplasty, were included. We excluded studies with a skeletally immature population, revision surgeries in more than 10% of cases, or a primary diagnosis of hip osteoarthritis. We conducted a second review using the same databases for studies reporting clinimetric properties of at least 1 of the PRO instruments identified previously. Articles were selected in an independent, stepwise manner by 2 reviewers. Selected articles were evaluated to determine the presence and quality of measurement properties of the outcome instruments.nnnRESULTSnWe found 5 articles assessing 3 PRO instruments: the Hip Outcome Score (HOS), the Non-Arthritic Hip Score, and the 12-item modified Western Ontario and McMaster Universities Osteoarthritis Index. The HOS had the highest positive rating for internal consistency, construct validity, agreement, responsiveness, lack of floor/ceiling effect, and interpretability. The Non-Arthritic Hip Score showed evidence for validity and lack of floor/ceiling effect. The modified Western Ontario and McMaster Universities Osteoarthritis Index was only strong for internal consistency and was indeterminate for construct validity.nnnCONCLUSIONSnOnly 3 PRO instruments have shown clinimetric evidence to support their use to measure outcomes in FAI and labral pathology patients. The HOS has the greatest amount of clinimetric evidence and is the most proven instrument for use in this population. This review shows that further clinimetric evaluation of commonly used PRO instruments for nonarthritic hip pathology is warranted.

Surgical Fixation vs Nonoperative Management of Flail Chest: A Meta-Analysis

BACKGROUNDnFlail chest is a life-threatening injury typically treated with supportive ventilation and analgesia. Several small studies have suggested large improvements in critical care outcomes after surgical fixation of multiple rib fractures. The purpose of this study was to compare the results of surgical fixation and nonoperative management for flail chest injuries.nnnSTUDY DESIGNnA systematic review of previously published comparative studies using operative and nonoperative management of flail chest was performed. Medline, Embase, and the Cochrane databases were searched for relevant studies with no language or date restrictions. Quantitative pooling was performed using a random effects model for relevant critical care outcomes. Sensitivity analysis was performed for all outcomes.nnnRESULTSnEleven manuscripts with 753 patients met inclusion criteria. Only 2 studies were randomized controlled designs. Surgical fixation resulted in better outcomes for all pooled analyses including substantial decreases in ventilator days (mean 8 days, 95% CI 5 to 10 days) and the odds of developing pneumonia (odds ratio [OR] 0.2, 95% CI 0.11 to 0.32). Additional benefits included decreased ICU days (mean 5 days, 95% CI 2 to 8 days), mortality (OR 0.31, 95% CI 0.20 to 0.48), septicemia (OR 0.36, 95% CI 0.19 to 0.71), tracheostomy (OR 0.06, 95% CI 0.02 to 0.20), and chest deformity (OR 0.11, 95% CI 0.02 to 0.60). All results were stable to basic sensitivity analysis.nnnCONCLUSIONSnThe results of this meta-analysis suggest surgical fixation of flail chest injuries may have substantial critical care benefits; however, the analyses are based on the pooling of primarily small retrospective studies. Additional prospective randomized trials are still necessary.

Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial

OBJECTnIschemia is an important factor in the pathophysiology of secondary damage after traumatic spinal cord injury (SCI) and, in the setting of thoracoabdominal aortic aneurysm repair, can be the primary cause of paralysis. Lowering the intrathecal pressure (ITP) by draining CSF is routinely done in thoracoabdominal aortic aneurysm surgery but has not been evaluated in the setting of acute traumatic SCI. Additionally, while much attention is directed toward maintaining an adequate mean arterial blood pressure (MABP) in the acute postinjury phase, little is known about what is happening to the ITP during this period when spinal cord perfusion pressure (MABP - ITP) is important. The objectives of this study were to: 1) evaluate the safety and feasibility of draining CSF to lower ITP after acute traumatic SCI; 2) evaluate changes in ITP before and after surgical decompression; and 3) measure neurological recovery in relation to the drainage of CSF.nnnMETHODSnTwenty-two patients seen within 48 hours of injury were prospectively randomized to a drainage or no-drainage treatment group. In all cases a lumbar intrathecal catheter was inserted for 72 hours. Acute complications of headache/nausea/vomiting, meningitis, or neurological deterioration were carefully monitored. Acute Spinal Cord Injury motor scores were documented at baseline and at 6 months postinjury.nnnRESULTSnOn insertion of the catheter, mean ITP was 13.8 +/- 1.3 mm Hg (+/- SD), and it increased to a mean peak of 21.7 +/- 1.5 mm Hg intraoperatively. The difference between the starting ITP on catheter insertion and the observed peak intrathecal pressure after decompression was, on average, an increase of 7.9 +/- 1.6 mm Hg (p < 0.0001, paired t-test). During the postoperative period, the peak recorded ITP in the patients randomized to the no-drainage group was 30.6 +/- 2.3 mm Hg, which was significantly higher than the peak intraoperative ITP (p = 0.0098). During the same period, the peak recorded ITP in patients randomized to receive drainage was 28.1 +/- 2.8 mm Hg, which was not statistically higher than the peak intraoperative ITP (p = 0.15).nnnCONCLUSIONSnThe insertion of lumbar intrathecal catheters and the drainage of CSF were not associated with significant adverse events, although the cohort was small and only a limited amount of CSF was drained. Intraoperative decompression of the spinal cord results in an increase in the ITP measured caudal to the injury site. Increases in intrathecal pressure are additionally observed in the postoperative period. These increases in intrathecal pressure result in reduced spinal cord perfusion that will otherwise go undetected when measuring only the MABP. Characteristic changes in the observed intrathecal pressure waveform occur after surgical decompression, reflecting the restoration of CSF flow across the SCI site. As such, the waveform pattern may be used intraoperatively to determine if adequate decompression of the thecal sac has been accomplished.

The reliability and validity of the Disabilities of Arm, Shoulder, and Hand, EuroQol-5D, Health Utilities Index, and Short Form-6D outcome instruments in patients with proximal humeral fractures

HYPOTHESISnThe Disabilities of Arm, Shoulder, Hand (DASH), EuroQol-5D (EQ-5D), Health Utilities Index Mark 3 (HUI3), and Short Form (SF)-6D questionnaires are reliable and valid measures of functional outcome and health state values in patients with proximal humeral fractures.nnnMATERIALS AND METHODSnPatients aged 55 and older treated for a proximal humeral fracture during a 5-year period completed the DASH, EQ-5D, HUI3, and SF-12 questionnaires. Test-retest reliability was quantified using intraclass correlation (ICC 2,1) and Bland-Altman agreement statistics during a second administration of the questionnaires. Correlations between the 4 study instruments, the SF-12, and a subjective global assessment of shoulder function were used to test construct validity. Ceiling/floor effects were quantified for each questionnaire.nnnRESULTSnSixty-one individuals (mean age, 69+/-10 years) participated. ICC showed the reliability (95% confidence interval) was 0.926 (0.860-0.963) for the DASH, 0.783 (0.604-0.875) for the EQ-5D, 0.794 (0.634-0.889) for the SF-6D, and 0.469 (0.184-0.686) for the HUI3. The Bland-Altman limits of agreement, however, highlighted limitations for repeated measurements with all 4 instruments at the individual patient level. Moderate construct validity was confirmed for all instruments. A significant ceiling effect was observed with the EQ-5D: 30% of participants reported perfect health, compared with less than 7% with DASH, HUI3, or SF-6D questionnaires.nnnDISCUSSIONnThe DASH and SF-6D questionnaires demonstrated the best psychometric properties among the study instruments. These results support their use as appropriate measures of functional outcome and health state values in patients with proximal humeral fractures.

Single- versus multiple-dose antibiotic prophylaxis in the surgical treatment of closed fractures: a meta-analysis.

Objectives: The use of prophylactic antibiotics in the surgical treatment of closed long bone fractures is well established. The duration and dosage of prophylaxis, however, vary significantly among surgeons. A systematic review and meta-analysis were performed to determine if multiple-dose perioperative antibiotic prophylaxis is more effective than a single preoperative dose in the prevention of surgical wound infections during the treatment of closed long bone fractures. Data Sources: Articles were identified by searching the following medical databases: Medline, Medline In Process & Other Non-indexed Citations, Embase, CENTRAL, and the Cochrane Database of Systematic Reviews. Relevant conference proceedings and the reference section of selected manuscripts were also searched for additional studies. Study Selection: Studies were included if they were prospective randomized controlled trials of patients with closed fractures treated with surgical fixation or arthroplasty. The interventions must have directly compared a single preoperative prophylactic dose to a multiple-dose perioperative strategy. Studies were excluded if they involved open fractures. Data Extraction: The demographic information, prophylaxis strategy, wound infection rate, and risk ratio were extracted from each article. Data Synthesis: Seven trials and 3,808 patients were pooled using a random effects model. When compared to a regimen of multiple doses of prophylactic antibiotics, administration of a single preoperative dose has a risk ratio of 1.24 (95% CI 0.60-2.60). The pooled risk difference between the 2 strategies is 0.005 (95% CI −0.011-0.021). Neither result is significant. Conclusions: In the setting of closed long bone fractures, the pooled results failed to demonstrate superiority of multiple-dose prophylaxis over a single-dose strategy. The pooled estimates suggest that surgical wound infections are relatively rare events and that any potential difference in infection rates between prophylaxis strategies is likely quite small. However, because the confidence interval surrounding the pooled risk ratio spans 1.0 by such a large amount, we are unable to definitively recommend a preferred dosing regimen to prevent surgical wound infections. Although future research is required to ensure our prophylaxis decisions continue to be evidence based and cost-effective, it is unlikely that a single clinical trial will be able to provide the answer. The use of other quantitative methods, such as cost-effectiveness analysis, may be helpful in modeling an optimal prophylaxis strategy.

Prevalence of shoulder pain in adult- versus childhood-onset wheelchair users: A pilot study

Shoulder pain is a common overuse problem in long-term adult wheelchair users. The current study examined whether the prevalence of shoulder pain in adult wheelchair users who began using their wheelchairs during childhood (childhood-onset [CH-O] group) is similar to those who began using their wheelchairs as adults (adult-onset [AD-O] group). We compared 31 CH-O and 22 AD-O wheelchair users using the Wheelchair Users Shoulder Pain Index (WUSPI), an overall pain score (Brief Pain Inventory), and a lifestyle questionnaire to determine frequency and duration of physical activity. Shoulder pain (WUSPI) was greater in the AD-O wheelchair users compared with the CH-O group (p < 0.008), even though their general lifestyles were not different. The immature skeleton can possibly respond to the repetitive forces of wheeling better than that of those who begin using a wheelchair once their skeletal structure is completely developed.

MEDLINE, EMBASE, and Cochrane index most primary studies but not abstracts included in orthopedic meta-analyses

OBJECTIVEnTo test the hypothesis that all primary studies used in orthopedic meta-analyses are indexed in MEDLINE or EMBASE.nnnSTUDY DESIGN AND SETTINGnUsing MEDLINE from 1995 to 2005, we retrieved all published meta-analyses of orthopedic surgical interventions. The primary studies in each meta-analysis were defined as the gold standard set. MEDLINE and EMBASE were searched for each primary study, and a recall rate was calculated. Secondary searches were performed using Web of Science (WoS), the Cochrane databases, and CINAHL.nnnRESULTSnHigh recall rates were achieved searching MEDLINE (90%) and EMBASE (81%) for the gold standard set, and the combined search retrieved 91%. Titles not indexed by MEDLINE or EMBASE included 45 abstracts, eight journal articles, and three unpublished studies. Searching the Cochrane databases yielded 36 titles not in MEDLINE or EMBASE. Using all three databases produced 97% recall of the primary studies; WoS and CINAHL did not increase the recall rate.nnnCONCLUSIONSnThese results suggest that a very high percentage of primary research in orthopedics can be found using the major databases. Additional database searches are unlikely to increase the yield of published manuscripts; however, conference proceedings and journal supplements should still be searched to ensure that relevant remaining reports are identified.

Measuring shoulder injury function: Common scales and checklists

The increasing shift towards patient-centred healthcare has lead to an emergence of patient-reported outcome instruments to quantify functional outcomes in orthopaedic patients. Unfortunately, selecting an instrument for use in a shoulder trauma population is often problematic because most shoulder instruments were initially designed for use with chronic shoulder pathology patients. To ensure an instrument is valid, reliable, and sensitive to clinical changes, it is important to obtain psychometric evidence of its use in the target population. Four commonly used shoulder outcome instruments are reviewed in this paper: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES); Constant-Murley shoulder score (CMS); Disabilities of Arm, Shoulder, and Hand (DASH); Oxford Shoulder Score (OSS). Each instrument was reviewed for floor or ceiling effects, validity, reliability, responsiveness, and interpretability. Additionally, evidence of each instruments psychometric properties was sought in shoulder fracture populations. Based on the current literature, each instrument has limited amounts of evidence to support their use in shoulder trauma populations. Overall, psychometric evaluations in isolated shoulder fracture populations remain scarce, and clinicians must remember that an instruments properties are defined for the population tested and not the instrument. Therefore, caution must always be exercised when using an instrument that has not been fully evaluated in trauma populations.

Complications following young femoral neck fractures

BACKGROUNDnFemoral neck fractures in patients 60 years of age or younger are challenging injuries to treat because of the high-energy trauma mechanisms and the displaced fracture patterns typically found in this patient population. Understanding the burden of disease is an important first step in addressing treatment controversies in this population. The purpose of the current study is to quantitatively pool the incidence of patient important complications following internal fixation of young femoral neck fractures.nnnMETHODSnA comprehensive search of the Medline, Embase, CINAHL, Cochrane Database of Systematic Reviews, and Central databases was completed under the direction of a biomedical librarian. Multiple outcomes of interest (complications) were collected and included: reoperation, femoral head avascular necrosis, fracture non-union, infection, implant failure, and malunion.nnnRESULTSn1558 fractures from 41 studies were included in the meta-analysis. An18.0% pooled reoperation incidence was observed for isolated femoral neck fractures. The total pooled incidence of avascular necrosis (AVN) was 14.3%, and the total incidence of nonunion was 9.3%. When stratified for fracture displacement displaced fractures were more likely to undergo reoperation and to result in AVN or non-union. The total incidence of malunion was 7.1%, implant failure was 9.7%, and surgical site infection was 5.1%. Complications associated with a femoral neck fracture treated in conjunction with an ipsilateral femoral shaft fracture were lower overall than the pooled estimates for isolated neck fractures.nnnCONCLUSIONSnThe results of our analysis demonstrate that the incidence of complications experienced by young femoral neck fracture patients is relatively high. Reoperation following internal fixation of isolated femoral neck fractures occurred in nearly 20% of cases, and AVN and nonunion were the most common complications that likely contributed to repeat surgeries. These results highlight the importance of further efforts to improve the clinical outcomes in this population.