Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors.
Introduction: Discussions regarding withdrawal of life support after burn injury are challenging and complex. Often, providers may facilitate this discussion when the extent of injury makes survival highly unlikely or when the patient's condition deteriorates during resuscitation. Few papers have evaluated withdrawal of life support in burn patients. We therefore sought to determine the predictor of withdrawal of life support (WLS) in a regional burn center. Methods:We conducted a retrospective analysis of all burn patients from 2002 to 2012. Patient characteristics included age, gender, burn mechanism, percentage total body surface area (%TBSA) burned, presence of inhalation injury, hospital length of stay, and pre-existing comorbidities. Patients < 17 years of age and patients with unknown disposition were excluded. Patients were categorized into three cohorts: Alive till discharge (Alive), death by withdrawal of life support (WLS), or death despite ongoing life support (DLS). DLS patients were then excluded from the study population. Multivariate logistic regression was used to estimate predictors of WLS.Results: 8,371 patients were included for analysis: 8134 Alive, 237 WLS. Females had an increased odd of WLS compared to males (OR 2.03, 95% CI 1.18 -3.48; p = 0.010). Based on higher CCI, patients with pre-existing comorbidities had an increased odd of WLS (OR 1.28, 95% CI 1.08 -1.52; p = 0.005). There was a significantly increased odds for WLS (OR 1.09, 95% CI 1.06 -1.12; p < 0.001) with increasing age. Similarly, there was an increased odd for WLS (OR 1.08, 95% CI 1.07 -1.51; p < 0.001) with increasing %TBSA. An increased odd of WLS (OR 2.47, 95% CI 1.05 -5.78; p = 0.038) was also found in patients with inhalation injury. Conclusion:The decision to withdraw life support is a complex and difficult decision. Our current understanding of predictors of withdrawal of life support suggests that they mirror those
Racial and ethnic disparities in access to inpatient rehabilitation have been previously described for various injury groups; however, no studies have evaluated whether such disparities exist among burn patients. Their aim was to determine if racial disparities in discharge destination (inpatient rehabilitation, skilled nursing facility, home with home health, or home) following burn injury existed in this single-institution study. A retrospective analysis of all adult burn patients admitted to UNC Jaycee Burn Center from 2002 to 2012 was conducted. Patient characteristics included age, gender, burn mechanism, insurance status, percentage total body surface area (%TBSA) burned, presence of inhalation injury, and hospital length of stay. Patients were categorized into one of three mutually exclusive racial or ethnic groups: White, Hispanic, or Black. Propensity score weighting followed by ordered logistic regression was performed in the analytical sample and in a subgroup analysis of patients with severe burns (TBSA > 20%). For analysis, 4198 patients were included: 2661 White, 340 Hispanic, and 1197 Black. Propensity weighting resulted in covariate balance among racial groups. Black patients (OR: 1.58, 95% CI: 1.23-2.03; P < .001) were more likely than Whites to be discharged to a higher level of rehabilitation, whereas Hispanics were less likely (OR: 0.78, 95% CI: 0.38-1.58; P = .448). In their subgroup analysis, Black (OR: 1.88, 95% CI: 1.07-3.28; P = .026) and Hispanic (OR: 1.53, 95% CI: 0.31-7.51; P = .603) patients were more likely to discharge to a higher level of rehabilitation than White patients. Racial and ethnic disparities in discharge destination to a higher level of rehabilitative services among burn-injured patients exist particularly for Hispanic patients but not for Black or White burn patient groups. Further studies are needed to elucidate the potential sources of these disparities specifically for Hispanic patients.
Amputation following burn injury is rare. Previous studies describe the risk of amputation after electrical burn injuries. Therefore, we describe the distribution of amputations and evaluate risk factors for amputation following burn injury at a large regional burn center. We conducted a retrospective analysis of patients ≥17 years admitted from January 2002 to December 2015. Patients who did and did not undergo an amputation procedure were compared. A multivariate logistic regression model was used to determine the risk factors for amputation. Amputations were further categorized by extremity location and type (major, minor) for comparison. Of the 8313 patients included for analysis, 1.4% had at least one amputation (n = 119). Amputees were older (46.7 ± 17.4 years) than nonamputees (42.6 ± 16.8 years; P = .009). The majority of amputees were white (47.9%) followed by black (39.5%) when compared with nonamputees (white: 57.1%, black: 27.3%; P = .012). The most common burn etiology for amputees was flame (41.2%) followed by electrical (23.5%) and other (21.9%). Black race (odds ratio [OR]: 2.29; 95% confidence interval [CI]: 1.22–4.30; P = .010), electric (OR: 13.54; 95% CI: 6.23–29.45; P < .001) and increased %TBSA (OR: 1.03; 95% CI: 1.02–1.05; P < .001) were associated with amputation. Burn etiology, the presence of preexisting comorbidities, black race, and increased %TBSA increase the odds of post burn injury. The role of race on the risk of amputation requires further study.
Introduction: Intentional burn injury outcomes are usually more severe, have a high mortality and are seen more often in low and middle-income countries. This study will examine the epidemiological characteristics of intentional burn injury patients and mortality outcomes at a regional Burn Center. Methods: This is a retrospective study of 11,977 patients admitted to a regional Burn center from 2002 to 2015.Variables analyzed were basic demographics (sex, age, and race), total body surface area of burn (%TBSA), presence of inhalation injury, Charlson comorbidity index, intent of injury, mortality, and hospital and ICU length of stay (LOS). Chi-square tests, bivariate analysis and logistic regression models were utilized to determine the effect of burn intent on outcomes. Results: Eleven thousand eight hundred and twenty-three (n = 11,823) adult and pediatric patients from 2002 to 2015 were included in the study. Three hundred and forty-eight (n = 348, 2.9%) patients had intentional burn injuries (IBI). Patients with IBI were younger, 26.5 AE 20 years compared to the non-intentional burn injury (NIBI) group (32 AE 22 years, p < 0.001). Mean %TBSA was significantly higher in the IBI vs. NIBI group at 14.6 AE 20 vs. 6.4 AE 10%, p < 0.001, respectively. Overall, Non-whites (n = 230, 66%) were more likely to have IBI, p < 0.001. Inhalation injury and mortality were statistically significant in the IBI group compared to the NIBI group, (n = 54,16%) vs. (n = 30, 9%) and (n = 649,6%) vs. (n = 329,2.9%), p < 0.001, respectively. Multivariate logistic regression did not show any significant increase in odds of mortality based on burn intent. In subgroup analysis of self-inflicted (SIB) vs. assault burns, SIB patients were significantly older, 38 years (AE14.7) vs. 22.4 years (AE20.5), p < 0.001 and had a higher %TBSA, 26.5 (AE29.6) vs. 10.3 (AE13.6), p < 0.001. Seventy three percent (n = 187, 73%) of assault burn patients were Nonwhite and Whites were more likely to incur self-inflicted burns, (n = 53% p < 0.001). Conclusion:We show that patients with intentional burn injuries have an associated increased %TBSA and inhalation injury without increased adjusted odds for mortality.Intentional burns increase health care expenditures. Violence prevention initiatives and access to mental health providers may be beneficial in reducing intentional burn injury burden.
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