Cervical spine fracture patterns mandating screening to rule out blunt cerebrovascular injury

BACKGROUND: Aggressive screening for blunt cerebrovascular injury (BCVI) and prompt anticoagulation for documented injuries has resulted in a significant reduction in ischemic neurologic events. An association between vertebral artery injuries (VAIs) and specific cervical spine fracture patterns has been suggested; however, current screening guidelines would subject all patients with cervical spine fractures to imaging because no distinction has been made for carotid artery injuries (CAIs). We hypothesized that specific cervical spine fracture patterns that warrant screening evaluation exist, hence limiting unwarranted diagnostic imaging. METHODS: Patients undergoing screening for BCVI on the basis of injury patterns and mechanism have been prospectively followed at our regional trauma center since January 1996. RESULTS: During the study period from January 1996 to January 2005, there were 17,007 blunt trauma admissions. Twenty-three patients presented with symptoms of BCVI. Screening angiography was performed in 766 patients (4.5%), and diagnosed 258 (34%) patients with BCVI. One hundred twenty-five patients with BCVI had cervical spine fractures; 18 patients had isolated CAI; 84 had isolated VAI, and 23 had combined CAI and VAI. Eight patients with VAI had minor cervical fractures but underwent screening for other injury patterns. Fractures in the remaining patients with BCVI were 1 of 3 patterns. Subluxations in 56 (48%) patients, C1 to C3 cervical spine fractures in 42 (36%), or extension of the fracture through the foramen transversarium in 19 (16%). Cervical spine fractures were the sole indication for screening in 90% of the study population. Screening yield of all patients admitted with 1 of these 3 fracture patterns was 37%. CONCLUSIONS: Blunt cerebrovascular injury is associated with complex cervical spine fractures that include subluxation, extension into the foramen transversarium, or upper C1 to C3 fractures. Patients sustaining such cervical fractures should undergo prompt screening.     

Epidemiology of Urban Trauma Deaths: A Comprehensive Reassessment 10 Years Later

Background We conducted a comprehensive analysis of the epidemiology of trauma deaths in our urban county during a one-year period a decade ago. In the interim we have implemented a statewide trauma system, initiated a number of injury-prevention programs, and have had a major public effort to reduce drug traffic and related gangs. Consequently, we have reassessed the regional trauma mortality to ascertain the impact of these measures and to search for new injury patterns. Methods Trauma deaths occurring within our urban county from January 1 through December 31, 2002 were reviewed for mechanism, demographics, and cause of fatal injury; cases were identified using death certificates from the Colorado Department of Public Health. We compared these data to the trauma fatalities occurring during 1992. Results During the 2002 study period, there were 420 injury-related deaths. Most of the patients were men (296 patients, 70%), with a mean age of 47.3 years (median age, 42 years). The three predominant mechanisms of fatal injury were transport-related (180 patients, 43%), intentional (99 patients, 24%), and falls (86 patients, 20%). Comparison between 1992 and 2002 showed significant increases in the percentage of transport-related and fall-related deaths, and a significant reduction in intentional fatal injuries. There was also a shift in the percentage of deaths occurring in the first 24 h to delayed times. The death rate per capita in Denver County declined from 0.081 in 1992 to 0.060 in 2002. Conclusions Along with a decrease in the per capita death rate, the major mechanisms of patient’s deaths changed substantively over the decade 1992–2002; there was a shift from intentional injuries to transport-related deaths as the predominant etiology of trauma related deaths. Recognition of such injury patterns will direct future injury-prevention efforts and coordination of citywide trauma care.     

ATP potentiates neurotransmission in the rat trigeminal subnucleus caudalis

Ionotropic purine receptors (P2X) have been implicated in nociceptive neurotransmission. In this study, we examine the actions of the P2X receptor agonist alpha,beta methylene adenosine 5'-triphosphate on excitatory neurotransmission in neurons in the deep and superficial laminae of the trigeminal spinal subnucleus caudalis (Vc), which receives nociceptive inputs from the craniofacial region. Alpha, beta methylene adenosine 5'-triphosphate caused an increase in spontaneous excitatory neurotransmission (miniature excitatory postsynaptic currents) in neurons in deep but not superficial laminae of Vc; this effect could be inhibited by the P2X receptor antagonist 2,3-O-2,4,6-trinitrophenyl-ATP. Conversely, the TRPV1 agonist capsaicin caused an increase in miniature excitatory postsynaptic currents in neurons in the superficial but not deep laminae. These data suggest that alpha,beta methylene adenosine 5'-triphosphate acts on presynaptic terminals to increase glutamatergic neurotransmission in deep Vc neurons.     

Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death

The purpose of this study was to analyze the possible effects of machine perfusion (MP) versus cold storage (CS) on delayed graft function (DGF) and early graft survival in expanded criteria donor kidneys (ECD). As part of the previously reported international randomized controlled trial 91 consecutive heart‐beating deceased ECDs – defined according to the United Network of Organ Sharing definition – were included in the study. From each donor one kidney was randomized to MP and the contralateral kidney to CS. All recipients were followed for 1 year. The primary endpoint was DGF. Secondary endpoints included primary nonfunction and graft survival. DGF occurred in 27 patients in the CS group (29.7%) and in 20 patients in the MP group (22%). Using the logistic regression model MP significantly reduced the risk of DGF compared with CS (OR 0.460, P = 0.047). The incidence of nonfunction in the CS group (12%) was four times higher than in the MP group (3%) (P = 0.04). One‐year graft survival was significantly higher in machine perfused kidneys compared with cold stored kidneys (92.3% vs. 80.2%, P = 0.02). In the present study, MP preservation clearly reduced the risk of DGF and improved 1‐year graft survival and function in ECD kidneys. (Current Controlled Trials number: ISRCTN83876362).     

Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries

OBJECTIVE: To prepare, sequence and analyse adult human cartilage cDNA libraries to study the gene expression pattern between normal and osteoarthritic cartilage. METHODS: Poly A(+)RNA from adult human normal and osteoarthritic articular cartilage was isolated and used to prepare cDNA libraries. Approximately 5000 ESTs from each library were sequenced and analysed using bioinformatic tools. The expression of select genes was confirmed by Northern blot and in situ hybridization analysis. RESULTS: Multiple gene families including several classical cartilage matrix protein encoding genes were identified. Approximately 28-40% of the genes sequenced from these libraries were novel, while half of the genes encoded known proteins and 4-6% of the genes encoded novel homologs of known proteins. Several known genes, whose expression has not been reported previously in cartilage, were also identified. We have confirmed the cartilage expression of three known (CTGF, CTGF-L and clusterin) and two novel homologs of known genes (PCPE-2 and Gal-Nac transferase) by Northern blot and in situ hybridization analysis. CONCLUSION: This is the first report of the preparation and sequencing of cDNA libraries from adult human normal and osteoarthritic articular cartilage. Further analysis of genes identified from these libraries may provide molecular targets for diagnosis and/or treatment of osteoarthritis (OA).     

Outcome and Hepatic Hemodynamics in Liver Transplant Patients with Portal Vein Arterialization

Few cases of successful portal vein arterialization in orthotopic and auxiliary liver transplantation have been reported. AIM: To evaluate the effect of portal vein arterialization on hepatic hemodynamics and long-term clinical outcome in three patients undergoing liver transplantation. METHODS: Two patients with extensive splanchnic venous thrombosis received an orthotopic liver transplant and one with fulminant hepatic failure received an auxiliary heterotopic graft. Portal vein arterialization was performed in all cases. RESULTS: One patient died 4 months after transplant and two are still alive. Auxiliary liver graft was removed 3 months post-transplant when complete native liver regeneration was achieved. Immediate post-transplant liver function was excellent in all cases. Only one patient developed encephalopathy and variceal bleeding owing to prehepatic portal hypertension secondary to arterioportal fistula 14 months after transplant. He was successfully treated by embolization of the hepatic artery. Hepatic hemodynamic measurements demonstrated a normal pressure gradient between wedged and free hepatic venous pressures in all cases. Liver biopsy showed acceptable graft architecture in two cases and microsteatosis in one. CONCLUSIONS: Liver transplantation with portal vein arterialization is an acceptable salvage alternative when insufficient portal venous flow to the graft is present. The double arterial supply does not imply changes in hepatic hemodynamics, at least in the early months post-transplant.     

The practice of venous thromboembolism prophylaxis in the major trauma patient

BACKGROUND: The incidence of venous thromboembolism (VTE) without prophylaxis is as high as 80% after major trauma. Initiation of prophylaxis is often delayed because of concerns of injury-associated bleeding. As the effect of delays in the initiation of prophylaxis on VTE rates is unknown, we set out to evaluate the relationship between late initiation of prophylaxis and VTE. METHODS: Data were derived from a multicenter prospective cohort study evaluating clinical outcomes in adults with hemorrhagic shock after injury. Analyses were limited to patients with an Intensive Care Unit length of stay >or=7 days. The rate of VTE was estimated as a function of the time to initiation of pharmacologic prophylaxis. A multivariate stepwise logistic regression model was used to evaluate factors associated with late initiation. RESULTS: There were 315 subjects who met inclusion criteria; 34 patients (11%) experienced a VTE within the first 28 days. Prophylaxis was initiated within 48 hours of injury in 25% of patients, and another one-quarter had no prophylaxis for at least 7 days after injury. Early prophylaxis was associated with a 5% risk of VTE, whereas delay beyond 4 days was associated with three times that risk (risk ratio, 3.0, 95% CI [1.4-6.5]). Factors associated with late (>4 days) initiation of prophylaxis included severe head injury, absence of comorbidities, and massive transfusion, whereas the presence of a severe lower extremity fracture was associated with early prophylaxis. CONCLUSIONS: Clinicians are reticent to begin timely VTE prophylaxis in critically injured patients. Patients are without VTE prophylaxis for half of all days within the first week of admission and this delay in the initiation of prophylaxis is associated with a threefold greater risk of VTE. The relative risks and benefits of early VTE prophylaxis need to be defined to better direct practice in this high-risk population.     

In situ preservation of kidneys from donors after cardiac death: results and complications

OBJECTIVES: To describe the results and complications of in situ preservation (ISP) of kidneys from donors after cardiac death (DCD). BACKGROUND: DCD donors are increasingly being used to expand the pool of donor kidneys. ISP reduces warm ischemic injury which is associated with DCD donation. METHODS: Insertion of a double-balloon triple-lumen catheter allows selective perfusion of the abdominal aorta to preserve the kidneys in situ. From January 2001 until August 2005, 133 ISP procedures were initiated in our procurement area. RESULTS: Fifty-six (42%) ISP procedures led to transplantation; in the remaining 77 cases (58%), the donation procedure was abandoned or both kidneys were discarded because of ISP complications (n = 31), poor graft quality (n = 23), no consent for donation (n = 13), medical contraindications (n = 8), or unknown cause (n = 2). Increasing donor age (odds ratio (OR) 1.06 per year, P < 0.001) and uncontrolled DCD donation (OR 5.4, P < 0.001) were independently correlated with ISP complications. After transplantation, prolonged double-balloon triple-lumen catheter insertion time was an independent predictor of graft failure (OR 2.0, P = 0.05). Selected controlled DCD donors were managed by rapid laparotomy and direct aortic cannulation; graft survival of these kidneys was superior to kidneys from controlled DCD donors managed by ISP. CONCLUSIONS: A minority of initiated ISP procedures led to transplantation, resulting in a high workload compared with donation after brain death. The association between increasing catheter insertion time and inferior graft outcome emphasizes the need for fast and effective surgery. Therefore, rapid laparotomy with direct aortic cannulation is preferred over ISP in controlled DCD donation. Despite these limitations, we have expanded our donor pool 3- to 4-fold by procuring DCD kidneys that were preserved in situ.     

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.     

Acute traumatic spinal cord injury, 1993-2000A population-based assessment of methylprednisolone administration and hospitalization

BACKGROUND: Administration of methylprednisolone sodium succinate (MPSS) after acute traumatic spinal cord injury (TSCI) is controversial. This study compared differences in acute care charge, hospital stay, and related variables as a function of MPSS receipt. METHODS: Determinants of MPSS administration were examined after acute TSCI for South Carolina patients during the period 1993 to 2000 in a multivariate logistic regression model. RESULTS: Administration of MPSS was documented for 48.7% of 1,227 randomly selected patients with TSCI. Patients admitted via trauma centers and emergency departments were more likely to receive MPSS (trama center level 1 odds ratio [OR], 4.06; 95% CI confidence interval [CI], 2.11-7.83; emergency department OR, 1.64; 95% CI, 1.20-2.23). Hospital charge and length of stay were significantly higher for MPSS recipients. CONCLUSIONS: The study findings indicate MPSS use is associated with higher acute care charges and longer hospital stays. These findings suggest the need for outcome studies to assess the long-term benefits of MPSS administration.