Finally,

as a minor comment, the authors should pay more attention to accuracy in the citation of the pertinent literature. For example, reference #10 is claimed to support a statement Ixazomib on interleukins and cerebral edema, when in fact the citation refers to a publication on programmed cell death in nematodes. Several other examples of inadequate reference to the literature could be mentioned. Finally, the title chosen by the authors appears problematic. The authors claim to provide the “”missing link”" between molecular mechanisms and therapeutic concepts in TBI. Unfortunately, the review article fails to provide a bridge between the two entities. In addition, many of the current therapeutic approaches and promising new strategies in search of the pharmacological “”golden bullet”" are missing [2]. While alterations in gene expression

may be an interesting finding and promising target for future scientific approaches, we are still far from bringing the gene therapy concept from “”bench to bedside”" for an acute traumatic disorder such as TBI. In summary, we realize that providing an encompassing and scientifically accurate review on the topic represents a virtually impossible task. We are therefore grateful for the review by Veenith et al. [1] and we hope to contribute to the authors’ search of the “”missing link”" between molecular pathophysiology and new therapeutic concepts in TBI by the identification of additional pathways of interest (Fig. 1). References MK0683 nmr 1. Veenith T, Goon SH, Burnstein RM: Molecular mechanisms of traumatic brain injury – the missing link in management. World J Emerg Surg 2009,4(1):7.CrossRefPubMed 2. Beauchamp K, Mutlak H, Smith WR, Shohami E, Stahel PF: Pharmacology of traumatic brain injury: where is the “”golden bullet”"? Mol Med 2008,14(11–12):731–740.PubMed Competing interests The authors declare that they have no competing interests. Authors’ contributions MAF and PFS wrote the manuscript. WRS and SJM critically revised the paper. All authors approved the final version of this manuscript.”
“Background Polytraumatized patients often suffer from associated injuries of the spinal column following a major trauma

(1st hit) from direct and indirect mechanical forces that generated soft tissue-, organ injuries and fractures. The consecutive P-type ATPase host reaction is characterized by a local and systemic expression and release of a vast array of pro-inflammatory mediators [1–4] misbalancing the immune system often resulting in a systemic inflammatory response syndrome (SIRS). The extent of the trauma-induced first hit is the major prognostic parameter for the clinical outcome of the patient following multiple trauma. Nevertheless, secondary events including septic complications, and single or multiple organ dysfunction (MOD/MOF) like acute lung injury or acute respiratory distress syndrome (ARDS) determine the beneficial or adverse outcome of polytraumatized patients.