Philip Giordano

Elevated Levels of Serum Glial Fibrillary Acidic Protein Breakdown Products in Mild and Moderate Traumatic Brain Injury Are Associated With Intracranial Lesions and Neurosurgical Intervention

STUDY OBJECTIVE This study examines whether serum levels of glial fibrillary acidic protein breakdown products (GFAP-BDP) are elevated in patients with mild and moderate traumatic brain injury compared with controls and whether they are associated with traumatic intracranial lesions on computed tomography (CT) scan (positive CT result) and with having a neurosurgical intervention. METHODS This prospective cohort study enrolled adult patients presenting to 3 Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score of 9 to 15. Control groups included normal uninjured controls and trauma controls presenting to the emergency department with orthopedic injuries or a motor vehicle crash without traumatic brain injury. Blood samples were obtained in all patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for GFAP-BDP (nanograms/milliliter). RESULTS Of the 307 patients enrolled, 108 were patients with traumatic brain injury (97 with GCS score 13 to 15 and 11 with GCS score 9 to 12) and 199 were controls (176 normal controls and 16 motor vehicle crash controls and 7 orthopedic controls). Receiver operating characteristic curves demonstrated that early GFAP-BDP levels were able to distinguish patients with traumatic brain injury from uninjured controls with an area under the curve of 0.90 (95% confidence interval [CI] 0.86 to 0.94) and differentiated traumatic brain injury with a GCS score of 15 with an area under the curve of 0.88 (95% CI 0.82 to 0.93). Thirty-two patients with traumatic brain injury (30%) had lesions on CT. The area under these curves for discriminating patients with CT lesions versus those without CT lesions was 0.79 (95% CI 0.69 to 0.89). Moreover, the receiver operating characteristic curve for distinguishing neurosurgical intervention from no neurosurgical intervention yielded an area under the curve of 0.87 (95% CI 0.77 to 0.96). CONCLUSION GFAP-BDP is detectable in serum within an hour of injury and is associated with measures of injury severity, including the GCS score, CT lesions, and neurosurgical intervention. Further study is required to validate these findings before clinical application.

Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.

BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL ± standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13–15 and 10 with GCS score 9–12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82–0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81–0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (±0.254) and 1.618 (±0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62–0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76–0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. LEVEL OF EVIDENCE: II, prognostic study.

GFAP out-performs S100β in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions.

Both glial fibrillary acidic protein (GFAP) and S100β are found in glial cells and are released into serum following a traumatic brain injury (TBI), however, the clinical utility of S100β as a biomarker has been questioned because of its release from bone. This study examined the ability of GFAP and S100β to detect intracranial lesions on computed tomography (CT) in trauma patients and also assessed biomarker performance in patients with fractures and extracranial injuries on head CT. This prospective cohort study enrolled a convenience sample of adult trauma patients at a Level I trauma center with and without mild or moderate traumatic brain injury (MMTBI). Serum samples were obtained within 4 h of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 397 general trauma patients enrolled: 209 (53%) had a MMTBI and 188 (47%) had trauma without MMTBI. Of the 262 patients with a head CT, 20 (8%) had intracranial lesions. There were 137 (35%) trauma patients who sustained extracranial fractures below the head to the torso and extremities. Levels of S100β were significantly higher in patients with fractures, compared with those without fractures (p<0.001) whether MMTBI was present or not. However, GFAP levels were not significantly affected by the presence of fractures (p>0.05). The area under the receiver operating characteristics curve (AUC) for predicting intracranial lesions on CT for GFAP was 0.84 (0.73-0.95) and for S100β was 0.78 (0.67-0.89). However, in the presence of extracranial fractures, the AUC for GFAP increased to 0.93 (0.86-1.00) and for S100β decreased to 0.75 (0.61-0.88). In a general trauma population, GFAP out-performed S100β in detecting intracranial CT lesions, particularly in the setting of extracranial fractures.

Cefdinir vs. cephalexin for mild to moderate uncomplicated skin and skin structure infections in adolescents and adults.

ABSTRACT Objectives: To compare the efficacy and safety of cefdinir to that of cephalexin in adolescents and adults with mild to moderate uncomplicated skin and skin structure infections (USSSI). Research design and methods: This was an investigator-blinded, multicenter study in which patients at least 13 years of age with USSSI were randomized to receive 10 days of cefdinir 300 mg twice daily (BID) or cephalexin 250 mg four times daily (QID). Patients were evaluated at baseline, by telephone on Days 3–5, and during office visits on Days 12–14 (end-of-therapy [EOT] visit) and Days 17–24 (test-of-cure [TOC] visit). Main outcome measures: Clinical response was evaluated at the TOC visit. Patient reported outcomes, including a usefulness questionnaire, were also assessed. Results: Three hundred and ninety-one patients were treated. The treatment groups were well matched with regard to demographic characteristics and types of infection. Abscess(es) (26%), wound infection (24%), and cellulitis (21%) were the most common infections. At the TOC visit, the clinical cure rate for both treatment groups was 89% (151/170 for cefdinir and 154/174 for cephalexin) in clinically evaluable patients (95% CI for difference in cure rates [–6.7 to 7.3]). In the intent-to-treat analysis, cure rates were 83% for cefdinir vs. 82% for cephalexin. Clinical cure rates for infections caused by methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus were 93% (37/40) and 92% (35/38) for cefdinir vs. 91% (29/32) and 90% (37/41) for cephalexin ( p > 0.999 comparing treatment groups for MSSA; p > 0.999 for MRSA). The usefulness questionnaire demonstrated that cefdinir was more highly rated in the mean composite score (87.4 vs. 83.6, p = 0.04), with the difference primarily due to the respondents’ preference for the convenience of taking the study medication (mean score 93.5 vs. 74.1 for cephalexin, p < 0.001). The study had the following limitations: the requirement for culture at baseline likely skewed the enrollment of patients towards those with abscesses; the results of culture in patients with USSSIs are often non-specific; in some patients entering the study with a diagnosis of cellulitis, the cellulitis was associated with an abscess; and, incision and drainage (I&D), spontaneous drainage, and needle aspiration are likely to have contributed to clinical response for purulent infections, and in particular MRSA-associated infections. Both study drugs were well tolerated. The most common treatment-related adverse events were diarrhea (10% cefdinir, 4% cephalexin, p = 0.017), nausea (3% and 6%, respectively, p = 0.203), and vaginal mycosis (3% and 6% of females, respectively, p = 0.500). Conclusions: This study demonstrated that empiric coverage of USSSIs with cephalosporin therapy remains an appropriate clinical strategy. MRSA infections responded well in both arms of the study, suggesting that the choice of a cephalosporin did not adversely affect patient outcome. However, cephalosporins do not have accepted, clinically relevant in vitro activity against MRSA. Hence, the clinical response rates seen in this study against MRSA infections must be interpreted with caution. Cefdinir was more highly rated than cephalexin in a composite usefulness assessment.Introduction

Evaluation of a New High-viscosity Octylcyanoacrylate Tissue Adhesive for Laceration Repair: A Randomized, Clinical Trial

OBJECTIVE Tissue adhesives have recently been approved for skin closure. Their low viscosity may result in inadvertent migration. The authors compared the tendency of the adhesive to migrate after laceration closure with a high- or low-viscosity octylcyanoacrylate (OCA). METHODS This was a randomized, clinical trial set in university and community-based emergency departments. Participants included patients with simple traumatic lacerations. Patients were randomized to laceration closure with low- or high-viscosity OCA tissue adhesive. The outcome measured was immediate adhesive migration (interobserver agreement, kappa = 0.90). Data analysis was performed with proportions compared with chi-square and Fishers exact tests. RESULTS Eighty-four patients were randomized to low- (n = 42) or high- (n = 42) viscosity OCA tissue adhesive. Groups were similar in baseline patient and wound characteristics. The high-viscosity OCA was less likely to migrate than the lower-viscosity agent (21% vs. 78%, p < 0.001; odds ratio = 0.3, 95% confidence interval = 0.1 to 0.5). The proportion of patients who noted a sensation of heat during OCA application was higher in the high-viscosity groups (44% vs. 26% respectively, p = 0.11); however, all such patients in both groups would use the device again. At 14 days, there were no wound infections in either group. There was one dehiscence in the high-viscosity group. CONCLUSIONS The high-viscosity OCA tissue adhesive was less likely to migrate than the lower-viscosity device. Wound dehiscence and infection rates were acceptably low in both treatment groups.

Middle ear pressure and symptoms after skydiving.

OBJECTIVES Altitude-related otic barotrauma and its symptoms have been identified from air-travel, scuba diving, and hyperbaric chambers, but not in skydiving. It is not known whether skydiving-related otic barotrauma could cause symptoms severe enough for medical attention or be implicated in skydiving-related accidents. This study assessed the effect of altitude change on middle ear pressures in skydivers by comparing changes in pressure before and after a skydive, pressure changes in those who developed middle ear symptoms vs. those who did not, and pressures in those who attempted equalization vs. not. METHODS This prospective observational cohort enrolled skydivers on random days in Deland, FL. A tympanometer was used to measure middle ear pressures in decapascals (daPa) on the ground before and after skydiving. RESULTS Average middle ear pressures in 69 subjects were significantly different before (-23.5 daPa) and after (-70.5 daPa) the skydive. There were 13 subjects (18.8%) who had middle ear symptoms after descent, but there were no statistically significant differences in ear pressure changes in those with (-57.5 daPa) and without (-44.2 daPa) symptoms after their jump. There was, however, a significant difference in pressure in those jumpers who did (-32.7 daPa) and did not (-75.7 daPa) equalize successfully after their jump. CONCLUSIONS Rapid skydiving descent from high altitudes causes negative middle ear pressure changes. The ability to equalize ear pressures after a jump had a large impact on the change in ear pressure. However, the change in middle ear pressure was not associated with the presence of middle ear symptoms.