Retrospective Study of Patients With SJS/TEN Treated at a Tertiary Burn Unit in Canada: Overview of 17 Years of Treatment.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are adverse drug reactions. OBJECTIVES: To learn about the clinical characteristics of patients with SJS/TEN including treatments provided, outcomes, and mortality. METHODS: We conducted a retrospective chart review of patients who were hospitalized with the diagnosis of SJS/TEN at the Ross Tilley Burn Center between the years 1999 and 2015. RESULTS: A total of 43 patients were identified with a mean age of 54 ± 19 (58, 18-85). The most common offending medications were allopurinol and carbamazepine. The overall mortality rate in our study is 21% with the most common causes of death being multiorgan failure and sepsis. The majority of our patients had oral (84%), ocular (79%), and genital (60%) involvement during hospitalization. Our data revealed that combination treatment involving oral corticosteroids with intravenous immunoglobulin (IVIG) had the highest mortality rate in our study since 55% (6/11) of patients who were treated in this manner passed away compared to 11% (2/18) of patients passing away who were treated with solely IVIG and 33% (1/3) who were treated with only supportive care. Our study also demonstrates the addition of etanercept and cyclosporine treatment in the second time period we studied: 2008-2015 versus the earlier time period of 1999-2007. None of the patients in our study who were treated with therapies including cyclosporine and/or etanercept passed away. CONCLUSIONS: Our study sheds light on a possible beneficial role of cyclosporine and etanercept for the treatment of SJS and TEN and reinforces the necessity of a multidisciplinary care team for patients.

Glucose Control in Severely Burned Patients Using Metformin: An Interim Safety and Efficacy Analysis of a Phase II Randomized Controlled Trial.

OBJECTIVE: To determine whether metformin can achieve glucose control no worse than insulin (noninferiority) without the danger of hypoglycemia (superiority). In addition, to assess whether metformin has any additional effects on lipolysis and inflammation that will enhance burn recovery (superiority). SUMMARY BACKGROUND DATA: Hyperglycemia and insulin resistance after burn injury are associated with increased morbidity and mortality. Insulin administration improves postburn infections, severity of sepsis, and morbidity, but also causes a 4-5-fold increase in hypoglycemia, which is associated with a 9-fold increase in mortality. METHODS: Severely burned adult patients with burns over 20% total body surface area (TBSA) burn were prospectively randomized in this Phase II clinical trial to either metformin or insulin (standard of care) treatment. Primary outcomes were glucose levels and incidence of hypoglycemia. Secondary outcomes included glucose and fat metabolism, and clinical outcomes. RESULTS: Forty-four patients were enrolled in this Phase II clinical trial, 18 metformin and 26 insulin patients. Demographics, burn size, concomitant injuries, and mortality were comparable between both groups. Metformin controlled blood glucose as equally as insulin with no difference between the 2 treatment groups, P > 0.05. While there was a 15% incidence of hypoglycemia in the insulin group, there was only 1 mild hypoglycemic episode (6%) in the metformin group, P < 0.05. Oral glucose tolerance tests at discharge revealed that metformin significantly improved insulin sensitivity, P < 0.05. Furthermore, metformin had a strong antilipolytic effect after burn injury when compared with insulin and was associated with significantly reduced inflammation, P < 0.05. CONCLUSIONS: Metformin decreases glucose equally as effective as insulin without causing hypoglycemia, with additional benefits including improved insulin resistance and decreased endogenous insulin synthesis when compared with insulin controls. These results indicate that metformin is safe in burn patients and further supports the use of metformin in severely burned patients for postburn control of hyperglycemia and insulin resistance.

Burned Adults Develop Profound Glucose Intolerance.

OBJECTIVES: Metabolic alterations after burn injury have been well described in children; however, in adult patients, glucose metabolism and insulin sensitivity are essentially unknown. We sought to characterize metabolic alterations and insulin resistance after burn injury and determine their magnitude and persistence at discharge. DESIGN: Prospective, cohort study. SETTING: Tertiary burn centre. PATIENTS: Nondiabetic adults with an acute burn involving greater than or equal to 20% total body surface area. INTERVENTIONS: An oral glucose tolerance test was administered at discharge. MEASUREMENTS AND MAIN RESULTS: Glucose, insulin, and C-peptide levels were measured to derive surrogate measures of insulin resistance and ß-cell function, including quantitative insulin sensitivity check index, homeostasis model assessment of ß-cell function, homeostasis model assessment of insulin sensitivity, homeostasis model assessment of insulin resistance, and the composite whole-body insulin sensitivity index. Patients were grouped according to the degree of glucose tolerance: normal glucose tolerance, impaired fasting glucose/impaired glucose tolerance, or diabetes. Forty-five adults, 44 ± 15 years old and with 38% ± 14% total body surface area burned, underwent an oral glucose tolerance test at discharge. Median quantitative insulin sensitivity check index (0.348 [0.332-0.375]) and median homeostasis model assessment of insulin resistance (1.13 [0.69-1.45]) were abnormal, indicating insulin resistance and impaired insulin production at discharge. Two-thirds of patients (n = 28) met criteria for impaired fasting glucose/impaired glucose tolerance or diabetes. CONCLUSIONS: We have demonstrated that burn-injured adults remain hyperglycemic, are insulin resistant, and express defects in insulin secretion at discharge. Patients with lower burn severity (total body surface area, 20-30%) express similar metabolic alterations as patients with larger burns (total body surface area, ≥ 30%). Glucose tolerance testing at discharge offers an opportunity for early identification of burn patients who may be at high risk of prediabetes and diabetes. Our findings demonstrated that two-thirds of burn patients had some degree of glucose intolerance. With this in mind, surveillance of glucose intolerance post discharge should be considered. As hyperglycemia and insulin resistance are associated with poor outcomes, studies should focus on how long these profound alterations persist.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Severe Physical Complications among Survivors of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

INTRODUCTION: Few studies have reported the physical complications among Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) survivors. OBJECTIVE: The aim of this study was to comprehensively characterize the physical complications among SJS/TEN survivors and to learn about patients' perspectives of surviving SJS/TEN. METHODS: SJS/TEN survivors older than 18 years of age were assessed by different methods: a medical interview; a questionnaire assessing patients' perspectives; thorough skin, oral mucous membrane, and ophthalmic examinations; and a retrospective assessment of medical records. RESULTS: Our cohort consisted of 17 patients with a mean time of 51.6 ± 74.7 months (median 9, range 1-228) following SJS/TEN. The most common physical complications identified in the medical examination were post-inflammatory skin changes (77%), cutaneous scars (46%), dry eyes (44%), symblepharon, and chronic ocular surface inflammation (33% each). Novel physical sequelae included chronic fatigue (76%) and pruritus (53%). We also found a novel association between the number of mucous membranes affected in the acute phase of SJS/TEN and hair loss during the 6 months following hospital discharge; hair loss was reported in 88% of the group of patients who had three or more mucous membranes affected versus 29% of patients who had less than three mucous membranes involved (p = 0.0406). Following hospital discharge due to SJS/TEN, 59% of patients were followed by a dermatologist, although 88% had dermatological complications; 6% were followed by an ophthalmologist, even though 67% had ophthalmological complications; and 6% of female survivors were followed by a gynecologist, even though 27% had gynecological complications. CONCLUSION: Survivors of SJS/TEN suffer from severe physical complications impacting their health and lives that are mostly under recognized and not sufficiently treated by medical professionals.

Genome scan for familial abdominal aortic aneurysm using sex and family history as covariates suggests genetic heterogeneity and identifies linkage to chromosome 19q13.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a relatively common disease, with 1% to 2% of the population harboring aneurysms. Genetic risk factors are likely to contribute to the development of AAAs, although no such risk factors have been identified. METHODS AND RESULTS: We performed a whole-genome scan of AAA using affected-relative-pair (ARP) linkage analysis that includes covariates to allow for genetic heterogeneity. We found strong evidence of linkage (logarithm of odds [LOD] score=4.64) to a region near marker D19S433 at 51.88 centimorgans (cM) on chromosome 19 with 36 families (75 ARPs) when including sex and the number of affected first-degree relatives of the proband (N(aff)) as covariates. We then genotyped 83 additional families for the same markers and typed additional markers for all families and obtained a LOD score of 4.75 (P=0.00014) with sex, N(aff), and their interaction as covariates near marker D19S416 (58.69 cM). We also identified a region on chromosome 4 with a LOD score of 3.73 (P=0.0012) near marker D4S1644 using the same covariate model as for chromosome 19. CONCLUSIONS: Our results provide evidence for genetic heterogeneity and the presence of susceptibility loci for AAA on chromosomes 19q13 and 4q31.

Pathophysiologic Response to Burns in the Elderly.

Over the last decades advancements have improved survival and outcomes of severely burned patients except one population, elderly. The Lethal Dose 50 (LD50) burn size in elderly has remained the same over the past three decades, and so has morbidity and mortality, despite the increased demand for elderly burn care. The objective of this study is to gain insights on why elderly burn patients have had such a poor outcome when compared to adult burn patients. The significance of this project is that to this date, burn care providers recognize the extreme poor outcome of elderly, but the reason remains unclear. In this prospective translational trial, we have determined clinical, metabolic, inflammatory, immune, and skin healing aspects. We found that elderly have a profound increased mortality, more premorbid conditions, and stay at the hospital for longer, p < 0.05. Interestingly, we could not find a higher incidence of infection or sepsis in elderly, p > 0.05, but a significant increased incidence of multi organ failure, p < 0.05. These clinical outcomes were associated with a delayed hypermetabolic response, increased hyperglycemic and hyperlipidemic responses, inversed inflammatory response, immune-compromisation and substantial delay in wound healing predominantly due to alteration in characteristics of progenitor cells, p < 0.05. In summary, elderly have substantially different responses to burns when compared to adults associated with increased morbidity and mortality. This study indicates that these responses are complex and not linear, requiring a multi-modal approach to improve the outcome of severely burned elderly.