Agnes Burris

Association of mitochondrial allele 4216c with increased risk for sepsis-related organ dysfunction and shock after burn injury

Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15% of their total body surface area or greater than or equal to 5% full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score ≥16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95% confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.

Epidemiology and outcomes of pediatric burns over 35 years at Parkland Hospital

BACKGROUND Since opening its doors in 1962, the Parkland Burn Center has played an important role in improving the care of burned children through basic and clinical research while also sponsoring community prevention programs. The aim of our study was to retrospectively analyze the characteristics and outcomes of pediatric burns at a single institution over 35 years. STUDY DESIGN The institutional burn database, which contains data from January 1974 until August 2010, was retrospectively reviewed. Patients older than 18 years of age were excluded. Patient age, cause of burn, total body surface area (TBSA), depth of burn, and patient outcomes were collected. Demographics were compared with regional census data. RESULTS Over 35 years, 5748 pediatric patients were admitted with a thermal injury. Males comprised roughly two-thirds (66.2%) of admissions. Although the annual admission rate has risen, the incidence of pediatric burn admissions, particularly among Hispanic and African American children has declined. The most common causes of admission were scald (42%), flame (29%), and contact burns (10%). Both the median length of hospitalization and burn size have decreased over time (r(2)=0.75 and 0.62, respectively). Mortality was significantly correlated with inhalation injury, size of burn, and history of abuse. It was negatively correlated with year of admission. CONCLUSIONS Over 35 years in North Texas, the median burn size and incidence of pediatric burn admissions has decreased. Concomitantly, length of stay and mortality have also decreased.

Epistatic interactions are critical to gene-association studies: PAI-1 and risk for mortality after burn injury.

Replication of statistically significant associations between single nucleotide polymorphisms (SNPs) and disease phenotypes has been problematic. One reason for conflicting observations may be failure to consider confounding factors, including gene–gene (epistatic) interactions. Our experience with the insertion/deletion polymorphism at -688 in the promoter region of plasminogen activator inhibitor (PAI-1) seems to support this contention and may foreshadow problems for genome-wide association scans, which tend to use unadjusted analytical methodologies. One hundred forty-nine patients with ≥15% total body surface area (TBSA) burns, without significant nonburn-related trauma (injury severity score ≤16), traumatic or anoxic brain injury or spinal cord injury who survived >48 hours postadmission were enrolled under a protocol approved by the UT Southwestern and Parkland Hospital IRBs. Clinical data were collected prospectively and candidate polymorphisms in PAI-1 (-688), toll-like receptor 4 (+896), CD14 (-159), tumor necrosis factor-&agr; (-308), and interleukin-6 (-174) were genotyped. The PAI-1 SNP was significantly associated (P-value for trend = 0.036) with risk for death when evaluated in isolation by unadjusted analysis. However, after adjustment for potential confounders using multiple logistic regression, only age, full-thickness burn size, and CD14 genotype (as previously reported) were associated with increased mortality. Genetic association analyses should be adjusted for interactions between multiple SNPs, injury or disease characteristics, and demographic variables. Increasingly sophisticated analytical methods will be required as gene-mapping studies transition from a candidate-gene based approach to genome-wide association scans.

Obesity and outcomes following burns in the pediatric population

PURPOSE While obesity is associated with increased mortality and decreased functional outcomes in adult burn patients, the ramifications of larger than average body size in the pediatric burn population are less well understood. The present study examines whether obesity was associated with poor outcomes following pediatric burn injuries. METHODS Thermal injury data for patients ≤ 18 years of age admitted to a Level III burn center over ten years (n=536) was analyzed. Obesity was defined as ≥ 95 th percentile of weight for height according to the WHO growth charts (<2 years of age) or BMI for age according to the CDC growth charts (2-18 years of age). Outcomes were compared between thermally injured obese (n=154) and non-obese (n=382) children. All data was collected in accordance with IRB regulations. RESULTS Obese and non-obese thermally-injured children did not differ in TBSA, percentage of full thickness burn, or overall mortality. However, these groups were significantly different with respect to age (obese=7.16 ± 0.46 years, non-obese=9.38 ± 0.32 years, p<0.001) and days requiring mechanical ventilation (obese=4.89 ± 1.3 days, non-obese=2.67 ± 0.49 days, p<0.05). For thermally injured children admitted to the BICU without inhalation injury (n=175); the obese (n=46) and non-obese (n=129) did not differ significantly with respect to age, TBSA, percentage of full thickness burn or other outcome measures. However, significant differences between these groups were noted for ICU LOS (obese=18.59 ± 5.18 days, non-obese=9.51 ± 1.82 days, p<0.05) and number of days requiring mechanical ventilation (obese=11.65 ± 3.91 days, non-obese=3.92 ± 0.85 days, p<0.05). CONCLUSION These data show thermally-injured obese pediatric patients required longer and more intensive medical support in the form of BICU care and respiratory intervention. Counter to findings in adult populations, differences in mortality were not observed. Collectively, these findings suggest obesity as a risk factor for increased morbidity in the pediatric burn population.

Adult burn patients: the role of religion in recovery--should we be doing more?

Burn patients often require prolonged periods of physical, emotional, and social recovery. Previous research has shown that when burn patients are given an opportunity to talk about what helps them cope, they frequently credit their religious faith or God. More than 350 studies have examined the association of religion and health. The majority found that religious people are physically healthier, lead better lifestyles, and consume fewer health resources. In addition, many seriously ill patients use religious beliefs to cope with their illness. Religious involvement is a widespread practice that often predicts successful coping with physical illness. It has been suggested that physicians acknowledge and respect the spiritual lives of their patients and, in doing so, may increase patient trust and positively impact patient care. We hope to raise awareness among burn surgeons and burn units about the role of religion and recovery in burn patients. In hopes of illustrating patient willingness to discuss religion with their caregivers and willingness to have religion addressed as part of care, a survey tool was developed and administered under a protocol by the institutional review board of our institution to all adult burn patients, capable of giving consent, with burns greater than 10% TBSA who were admitted to our acute care floor. They were approached near the time of discharge to consent and participate. Fiftythree patients completed the 17-question survey. Eighty-three percent of respondents were men, and 17% were women. Racial distribution included 65% Caucasian, 8% African American, and 27% Hispanic. Only 11 (20%) of patients reported at least once a week church attendance. Thirty-two (59%) patients reported attending church once in awhile or not at all. Sixty-eight percent answered in the positive to the question of whether addressing their religious and spiritual needs was important in their recovery and that this area should be part of medical care. By unit protocol, every patient has the opportunity for pastoral visitation, unless refused. Pastoral care visits occurred for 37 patients (70%). Thirty-one of the 37 (84%) patients receiving pastoral care considered visitation helpful in recovery. Of patients who answered these questions, 17 of 26 (65%) wanted their doctor to talk to them about religion, and 21 of 28 (75%) wanted to pray with their doctor. Although only a preliminary survey of the subject, the results indicate at least a willingness to discuss religious issues with caregivers. An obvious bias is present simply in an individual’s willingness to complete a survey regarding religion. Although what seemed particularly telling was the fact that although the majority of patients admitted to attending regular church services before burn injury infrequently, or not at all, the majority of participants considered addressing religious needs important in recovery. Previous studies have shown that when given the opportunity to talk about what helps them cope with the pain of injury, patients frequently credit their religious faith. A recent report revealed that 77% of hospitalized patients wanted physicians to consider their spiritual needs as part of their care. Numerous studies have revealed improved outcomes in ill patients who participate in religious activities. The current review is intended to add to the dialogue in support of a more holistic approach to patient care and to raise awareness of an issue that is often dismissed as trivial in view of complex and sometimes life-threatening medical problems. It seems inherently clear and unnecessary to state that physicians should be particularly aware of and attentive to important issues from the patient’s viewpoint. If not sensitive to this viewpoint, a patient may From the *Department of Surgery and †Pastoral Care, Parkland Memorial Hospital and ‡Department of Surgery, UT Southwestern Medical Center, Dallas, Texas. Address correspondence to Brett D. Arnoldo, MD, Department of Surgery, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9158. Copyright

Pediatric burn care

Abstract One third of patients with significant burn injuries are children who are injured in what are nearly always preventable incidents. These extremely painful and often scarring bunts are enormous stressors to patients and their families. Children are easily devastated by the burst injury and are often less able to respond to it than au adult. Pediatric burn injury provides multiple problems in early diagnosis and management. Although the entire cutaneous injury is easily visualized severity is frequently underestimated by caregivers and by the patients family. Management pitfalls in children will be discussed including correct estimation of horn size and depth, fluid resuscitation and fluid maintenance vascular access, airway management, and thermal homeostasis.