Trauma care: Finding a better way

Alam, Hasan B.

doi:10.1371/journal.pmed.1002350

Cited by 10 publications

(6 citation statements)

References 40 publications

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Section: Discussionmentioning

confidence: 99%

“…Haemorrhage and/or TBI are the leading cause of death in the prehospital phase of care (Alam, 2017 ), with most deaths occuring within a few hours after trauma despite recent advances in trauma care (Alam, 2017 ; Brohi et al, 2019 ; CRASH‐2 trial collaborators et al, 2010 ). Approximately 90% of battlefield casualties die in the prehospital environment, with 85% of these prehospital deaths due to bleeding, and of those about 25% are deemed potentially survivable (Alam, 2017 ; Eastridge et al, 2012 ). Furthermore, although patients with TH may survive the initial injury by means of haemorrhage control and resuscitation, they may still succumb to a complex series of inflammatory events ending in multi‐organ failure that is the major contributor to late mortality (Arbore & Kemper, 2016 ; De Blasio et al, 2019 ; Hepburn et al, 2007 ; Lord et al, 2014 ; Mannucci & Levi, 2007 ).…”

Section: Discussionmentioning

confidence: 99%

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Immunopathology of terminal complement activation and complement C5 blockade creating a pro‐survival and organ‐protective phenotype in trauma

Yang

Nunn

et al. 2022

British J Pharmacology

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Background and Purpose: Traumatic haemorrhage (TH) is the leading cause of potentially preventable deaths that occur during the prehospital phase of care. No effective pharmacological therapeutics are available for critical TH patients yet. Here, we identify terminal complement activation (TCA) as a therapeutic target in combat casualties and evaluate the efficacy of a TCA inhibitor (nomacopan) on organ damage and survival in vivo.Experimental Approach: Complement activation products and cytokines were analysed in plasma from 54 combat casualties. The correlations between activated complement pathway(s) and the clinical outcomes in trauma patients were assessed.Nomacopan was administered to rats subjected to lethal TH (blast injury and haemorrhagic shock). Effects of nomacopan on TH were determined using survival rate, organ damage, physiological parameters, and laboratory profiles.Key Results: Early TCA was associated with systemic inflammatory responses and clinical outcomes in this trauma cohort. Lethal TH in the untreated rats induced early TCA that correlated with the severity of tissue damage and mortality. The addition of nomacopan to a damage-control resuscitation (DCR) protocol significantly inhibited TCA, decreased local and systemic inflammatory responses, improved haemodynamics and metabolism, attenuated tissue and organ damage, and increased survival. Conclusion and Implications:Previous findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro-survival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunopathology of terminal complement activation and complement C5 blockade creating a pro‐survival and organ‐protective phenotype in trauma

Yang

Nunn

et al. 2022

British J Pharmacology

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“…Indeed, moderate states of hypothermia are common in clinical practice. Along those lines, therapeutic hypothermia has been associated with beneficial outcomes in patients following out-ofhospital cardiac arrest [218]. Moreover, animal studies demonstrate improved neurological outcome [219,220].…”

Section: Emergency Medicinementioning

confidence: 99%

Winter is coming: the future of cryopreservation

et al. 2021

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The preservative effects of low temperature on biological materials have been long recognised, and cryopreservation is now widely used in biomedicine, including in organ transplantation, regenerative medicine and drug discovery. The lack of organs for transplantation constitutes a major medical challenge, stemming largely from the inability to preserve donated organs until a suitable recipient is found. Here, we review the latest cryopreservation methods and applications. We describe the main challenges—scaling up to large volumes and complex tissues, preventing ice formation and mitigating cryoprotectant toxicity—discuss advantages and disadvantages of current methods and outline prospects for the future of the field.

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“…Hemorrhage is a leading cause of preventable deaths, and it is responsible for 1.5 million trauma-related fatalities worldwide annually 1 2. Among those who survive the initial hemorrhage, long-term outcomes remain poor 2 3.…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock

Bhatti

Williams

Kathawate

et al. 2019

Trauma Surg Acute Care Open

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BackgroundIsoform-specific histone deacetylase inhibitors (HDACIs) MC1568 and ACY1083 are comparable to the non-selective HDACI valproic acid (VPA) in improving survival in rodents undergoing lethal hemorrhage. However, the organ-specific properties of isoform-specific HDACIs have not been fully evaluated. Also, whether they can act synergistically is not known. We hypothesized that isoform-specific HDACIs are superior to VPA in attenuating intestinal injury and act synergistically when coadministered.MethodsSprague Dawley rats were hemorrhaged (40% of total blood volume) and randomized to receive (n=4 per group) (1) MC1568 (5 mg/kg), (2) ACY1083 (30 mg/kg), (3) MC1568+ACY1083 (combination: 5 mg/kg + 30 mg/kg, respectively), (4) VPA (250 mg/kg), or (5) normal saline (NS; vehicle; 250 μL). Animals were observed for 3 hours, after which blood samples were collected and samples of the ileum were harvested. Expression of interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and cytokine-induced neutrophil chemoattractant 1 (CINC-1) was assessed in the tissues using enzyme-linked immunosorbent assay. Intestinal cleaved caspase 3 (c-caspase 3) levels were assessed as a marker of apoptosis, and histologic sections of the ileum were examined for signs of bowel injury. Levels of IL-1β and TNF-α were also measured in the serum as global markers of inflammation.ResultsTreatments with MC1568, ACY1083, MC1568+ACY1083, and VPA were associated with decreased IL-1β levels in the intestine and serum compared with NS. IL-1β and TNF-α levels were significantly lower in the ACY1083 group compared with the VPA group. CINC-1 levels were significantly lower in the isoform-specific HDACI groups compared with the NS; however, no significant differences were seen with VPA. All treatment groups had a lower expression of intestinal c-caspase 3 compared with NS. Furthermore, MC1568 and ACY1083 groups had lower apoptosis compared with the VPA group. Bowel injury scores were significantly lower in the isoform-specific HDACI groups compared with the NS group; however, the attenuation in the VPA-treated animals did not reach statistical significance.DiscussionIsoform-specific HDACIs provide superior intestinal protection compared with VPA in a rodent model of hemorrhagic shock.Level of evidencePreclinical study.

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Trauma care: Finding a better way

Abstract: In a Perspective, Hasan Alam discusses emerging treatment approaches in trauma care.

Cited by 10 publications

References 40 publications

Immunopathology of terminal complement activation and complement C5 blockade creating a pro‐survival and organ‐protective phenotype in trauma

Immunopathology of terminal complement activation and complement C5 blockade creating a pro‐survival and organ‐protective phenotype in trauma

Winter is coming: the future of cryopreservation

Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock

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