Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage.

Extensive subpial cortical demyelination is specific to multiple sclerosis.

Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue damage was associated with the extent of neuroaxonal damage. We studied a large cohort of patients diagnosed with demyelinating CNS diseases and non-demyelinating diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the meninges and the cortex. Included were patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), carcinomatous and lymphomatous meningitis and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using myelin protein immunohistochemistry, we found cortical demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each condition showed a disease-specific histopathological pattern. Remarkably, extensive ribbon-like subpial demyelination was only observed in MS, thus providing an important pathogenetic and diagnostic cue. Cortical oxidative injury was detected in both demyelinating and non-demyelinating CNS disorders. Our data demonstrate that meningeal and cortical inflammation alone accompanied by oxidative stress are not sufficient to generate the extensive subpial cortical demyelination found in MS, but require other MS-specific factors.

Not the usual suspects: human wound myiasis by phorids.

Infestation of animal tissues by dipteran larvae (myiasis) commonly occurs in many species, but it is unusual for humans in temperate regions. Nevertheless, human myiasis is regularly observed in many primary care facilities in the United States. Beyond medical issues associated with treating human myiasis, both the causal agent and the longevity of myiasis can have legal implications, for example, as evidence of neglect. Cases of human myiasis in the United States typically involve imported myiasis from torsalo, Dermatobia hominis (Linnaeus, Jr.) (Diptera: Oestridae), or facultative myiasis from calliphorids. Here, however, we report two cases of wound myiasis caused by phorid larvae occurred in southeastern Nebraska within 10 mo. Degree-day analysis indicates initial infestation occurred 2 and 3 d before discovery. There are few previous reports of phorid wound myiasis; so, the occurrence of two cases in so short a period suggests that phorids are more important than previously appreciated.

Fungal periapical abscess and the burn patient: A report of two cases of an unreported source for systemic infection.

Fungal infections in the intensive care unit are becoming a more common occurrence, especially in the care of the burn patient. Fungal infections in the critically burned patient, who by nature have a heightened inflammatory state and impaired immune response, have been found to carry a profound degree of morbidity and mortality. We present our experience in the care of severe thermal injuries; a series of patients with endodontic fungal infection which, as we found, pose a significant risk for the development of systemic infection and sepsis. Fungal periapical abscesses are a rare and, yet undescribed, potential source of systemic sepsis in the burn intensive care unit.

Multicenter postapproval clinical trial of Integra dermal regeneration template for burn treatment.

The safety and effectiveness of Integra Dermal Regeneration Template was evaluated in a postapproval study involving 216 burn injury patients who were treated at 13 burn care facilities in the United States. The mean total body surface area burned was 36.5% (range, 1-95%). Integra was applied to fresh, clean, surgically excised burn wounds. Within 2 to 3 weeks, the dermal layer regenerated, and a thin epidermal autograft was placed. The incidence of invasive infection at Integra-treated sites was 3.1% (95% confidence interval, 2.0-4.5%) and that of superficial infection 13.2% (95% confidence interval, 11.0-15.7%). Mean take rate of Integra was 76.2%; the median take rate was 95%. The mean take rate of epidermal autograft was 87.7%; the median take rate was 98%. This postapproval study further supports the conclusion that Integra is a safe and effective treatment modality in the hands of properly trained clinicians under conditions of routine clinical use at burn centers.

Reimbursement for out-of-state burn patients is not always lower than that for in-state patients at regional burn centers.

Because burn care in the United States is regionalized, burn patients are often transported across state lines to receive their burn treatment. The authors hypothesized that there are differences between in-state and out-of-state reimbursement for burn care. This project was conducted by the American Burn Association (ABA) Government Affairs Committee through the ABA Multicenter Trials Group. Participation was open to any member of the ABA. This retrospective observational study was approved by the institutional review boards of each participating institution. Subjects were identified using registry of each site, selecting patients hospitalized for burn injuries during FY2004-FY2006 of the hospitals. Once identified by the registry, the ID numbers were used to collect billing and reimbursement data from the financial offices. Data were sorted by age (adult and pediatric), location (in state and out of state), and payor source (Medicare, Medicaid, commercial, workers compensation, and self-pay). The rate of reimbursement was calculated based on charges and recoveries. Comparisons on data of each center were performed using Student's t-test with type I error <1%. Six facilities contributed data. A total of 4850 burn patients were reviewed, of whom 3941 were in-state burn patients and 909 were out-of-state burn patients. When the results from all six states were analyzed together, reimbursement for adults from Medicaid and Medicare was higher for in-state patients than for out-of-state patients. However, when analyzed by state, Medicare reimbursement between in-state and out-of-state patients did not differ significantly. In one state (Kansas), in-state Medicaid reimbursement was higher, but in two others (Arizona and Pennsylvania), in-state Medicaid reimbursement was lower than that for out-of-state reimbursement. Reimbursement for the care of children did not differ significantly based on state of residence. From these data, we conclude that there are indeed variations between in-state and out-of-state reimbursement, but those variations differ regionally. Indeed, in some cases, out-of-state reimbursement exceeds in-state reimbursement. Careful examination of these data is necessary before recommending policy change, although consideration should be given to a national policy that guarantees uniformity of reimbursement across all payors for burn patients regardless of their state of residence.

Effects of oxandrolone on outcome measures in the severely burned: a multicenter prospective randomized double-blind trial.

Severe burns induce pathophysiologic problems, among them catabolism of lean mass, leading to protracted hospitalization and prolonged recovery. Oxandrolone is an anabolic agent shown to decrease lean mass catabolism and improve wound healing in the severely burned patients. We enrolled 81 adult subjects with burns 20% to 60% TBSA in a multicenter trial testing the effects of oxandrolone on length of hospital stay. Subjects were randomized between oxandrolone 10 mg every 12 hours or placebo. The study was stopped halfway through projected enrollment because of a significant difference between groups found on planned interim analysis. We found that length of stay was shorter in the oxandrolone group (31.6 +/- 3.1 days) than placebo (43.3 +/- 5.3 days; P < .05). This difference strengthened when deaths were excluded and hospital stay was indexed to burn size (1.24 +/- 0.15 days/% TBSA burned vs 0.87 +/- 0.05 days/% TBSA burned, P < .05). We conclude that treatment using oxandrolone should be considered for use in the severely burned while hepatic transaminases are monitored.

Effect of blood transfusion on outcome after major burn injury: a multicenter study.

OBJECTIVE: To delineate blood transfusion practices and outcomes in patients with major burn injury. CONTEXT: Patients with major burn injury frequently require multiple blood transfusions; however, the effect of blood transfusion after major burn injury has had limited study. DESIGN: Multicenter retrospective cohort analysis. SETTING: Regional burn centers throughout the United States and Canada. PATIENT POPULATION: Patients admitted to a participating burn center from January 1 through December 31, 2002, with acute burn injuries of >or=20% total body surface area. OUTCOMES MEASURED: Outcome measurements included mortality, number of infections, length of stay, units of blood transfused in and out of the operating room, number of operations, and anticoagulant use. RESULTS: A total of 21 burn centers contributed data on 666 patients; 79% of patients survived and received a mean of 14 units of packed red blood cells during their hospitalization. Mortality was related to patient age, total body surface area burn, inhalation injury, number of units of blood transfused outside the operating room, and total number of transfusions. The number of infections per patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001). Patients on anticoagulation during hospitalization received more blood than patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). CONCLUSIONS: The number of transfusions received was associated with mortality and infectious episodes in patients with major burns even after factoring for indices of burn severity. The utilization of blood products in the treatment of major burn injury should be reserved for patients with a demonstrated physiologic need.