The Role of Hyperglycemia in Burned Patients

Mecott, Gabriel A.; Al-Mousawi, Ahmed M.; Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

doi:10.1097/shk.0b013e3181af0494

Cited by 68 publications

(49 citation statements)

References 116 publications

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“…Our studies have shown that burn-induced cardiac dysfunction is associated with systemic and myocardial inflammation (5,54), abnormal iron homeostasis (4,55,63,76,83), and metabolism disorders (86,94). These findings in the rodent model are consistent with clinical observations (41,45,51,59). Recently, we have further demonstrated that burn induced several aspects of mitochondrial damage in the heart such as impairments of mitochondrial membrane integrity and oxidative damage (89).…”

supporting

confidence: 77%

Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs

Xiao

Wigginton

Maass

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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supporting

confidence: 77%

Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs

Xiao

Wigginton

Maass

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…In light of the fact that hyperglycaemia is a common pathophysiological event in burns, which precedes and predicts many of the subsequent adverse events (Gauglitz et al, 2008;Mecott et al, 2010;Finnerty et al, 2014;Jeschke et al, 2016;Ray et al, 2016), it was interesting to note that olaparib attenuated the burn-associated early hyperglycaemia in our current model. We interpret this finding as an indication that the overall stress response and/or the acute insulin resistance that develops in burns may be, at least in part, dependent on PARP.…”

Section: Figurementioning

confidence: 87%

The clinically used PARP inhibitor olaparib improves organ function, suppresses inflammatory responses and accelerates wound healing in a murine model of third‐degree burn injury

Ahmad

Oláh

Herndon

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEThe PARP inhibitor olaparib has recently been approved for human use for the therapy of cancer. Considering the role of PARP in critical illness, we tested the effect of olaparib in a murine model of burn injury, in order to begin exploring the feasibility of repurposing olaparib for the therapy of burn patients. EXPERIMENTAL APPROACHMice were subjected to scald burn injury and randomized into vehicle or olaparib (10 mg·kg À1 ·day À1 i.p.) groups. Outcome variables included indices of organ injury, clinical chemistry parameters, plasma levels of inflammatory mediators (at 24 h, 7 and 21 days) and burn wound size (at 21 days). KEY RESULTSOlaparib reduced myeloperoxidase levels in heart and lung homogenates and reduced malondialdehyde levels in all tissues 24 h post-burn. Olaparib also reduced circulating alkaline aminotransferase, amylase and blood urea nitrogen and creatinine levels, indicative of protection against hepatic, pancreatic and renal dysfunction. Pro-inflammatory mediator (TNF-α, IL-1β, IFN-γ, GCSF, GM-CSF, eotaxin, KC, MIP-1-α and IL-3, 6 and 12) levels as well as the levels of several mediators that are generally considered anti-inflammatory (IL-4, 10 and 13) were reduced by olaparib. Plasma troponin-I levels (an indicator of skeletal muscle damage) was also attenuated by olaparib. Finally, olaparib stimulated wound healing. CONCLUSIONS AND IMPLICATIONSThe clinically approved PARP inhibitor olaparib improves organ function, suppresses inflammatory responses and accelerates wound healing in murine burn injury. The data raise the potential utility of olaparib for severe burn injury.

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“…Serum blood glucose and hemoglobin (HgB)A1C values obtained basically in the emergency department at initial presentation were evaluated for each patient as clinical characteristicst. We defined hyperglycemia as more than 1 random blood glucose level ≥ 11.0 mmol/L [17]. Patients with any missing these blood glucose parameters were excluded from this study.…”

Section: Methodsmentioning

confidence: 99%

Impact of Admission Hyperglycemia on Stroke-Associated Pneumoniain Acute Cerebral Hemorrhage: A Retrospective Observational Study

Ren¹,

Yang²,

Li³

et al. 2015

OJEM

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Background: Hyperglycemia is always seen amongst acute intra-cerebral hemorrhage (ICH) and usually has been reported in literature and studied in relation to mortality and poor recovery. However, literature specific to stroke-associated pneumonia (SAP) on this topic is very small. Further, how to differentiate the predictive value of hyperglycemia with and without abnormal HbA1C in such patients is still a matter of debate and no universal consensus. We evaluated hyperglycemia as a marker for SAP in patients with ICH to assess its usefulness as a potential predictor. Materials and methods: Clinical characteristics for a sample of 551 patients with acute ICH were collected from the Beijing Tiantan Hospital of Capital Medical University, Beijing, China. Possible associated risk factors of SAP were reviewed. Hyperglycemia and HbA1C on admission were the main hypothetic predictor, SAP occurring within the first 7 days is the primary outcome. Results: The cohort study includes 551 hospitalized patients. The prevalence of hyperglycemia was 52.5% and SAP occurred in 147 (26.7%). The incidence of SAP was higher in the group with hyperglycemia than those without hyperglycemia (37.7% versus 14.5%, p < 0.01). Multivariate logistic regression analyses showed the SAP was significantly associated with hyperglycemia (OR, 2.48; 95% CI, 2.37 -5.72), in the subgroup analysis we found hyperglycemia with normal HgbA1C level (<6.5) had been shown to be significantly associated with increased incidence of SAP (OR, 3.86; 95%CI, 2.98 -6.72), however, hyperglycemia with high HgbA1C level (>6.5) (OR, 1.57; 95%CI, 0.81 -3.23) had not been shown to be associated with SAP. Conclusions: In this hospital-based co-hort of patients presenting with acute intra-hemorrhage, hyperglycemia on admission was associated significantly with SAP. The association was stronger for hyperglycemia with normal HgbA1C than for hyperglycemia with high HgbA1C. Hyperglycemia with normal HgbA1C might be a more sensitive predictor of early acute complication, such as SAP.

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The Role of Hyperglycemia in Burned Patients

Cited by 68 publications

References 116 publications

Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs

Estrogen-provided cardiac protection following burn trauma is mediated through a reduction in mitochondria-derived DAMPs

The clinically used PARP inhibitor olaparib improves organ function, suppresses inflammatory responses and accelerates wound healing in a murine model of third‐degree burn injury

Impact of Admission Hyperglycemia on Stroke-Associated Pneumoniain Acute Cerebral Hemorrhage: A Retrospective Observational Study

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