To the best of our knowledge, this is the first cross-sectional study collecting various anthropometric, biochemical and clinical data to evaluate nutritional status and body composition in a large variety of post-surgical patients with DWH. The mono-center study was performed within clinical routine ensuring that all patients received comparable medical therapy, care and dietetic measures. Thus, the evaluation of selected clinical and biochemical markers may provide indication for the failure of WH.
Despite the fact that most patients were normal weight, overweight or obese and had calf and upper arm circumferences within the reference range (Table 1), general malnutrition according to SGA was prevalent in most patients (Table 2). Parameters reflecting long-term (albumin) and short-term (prealbumin) protein supply (Table 3, Figure 1) were in the lower normal range. Hence, general malnutrition which has been proposed to favor DWH  may have contributed to the development of DWH.
Mean plasma concentrations of ascorbic acid, 25(OH)D3, β-carotene and selenium (Table 3) were below the reference values and 59 - 86% of the patients had a deficiency in these micronutrients (Figure 1). Since post-traumatic and post-surgical metabolic events, such as inflammation [23, 24] and oxidative stress , may generally contribute to lower plasma levels of ascorbic acid and β-carotene, low plasma status of these micronutrients in trauma patients with DWH may be a concomitant phenomenon considering increased levels of CRP, MDA, and peroxides. While it may not be the reason for the development of DWH, it nevertheless should be considered that the plasma level of micronutrients does not necessarily reflect the micronutrient status in the wounded tissue with respect to substrate fluxes to the wound area. Such fluxes have been observed in rats for free amino acids during early wound healing period, leading to a relative lack of arginine in whole body . Thirty percent of the patients exhibited an insufficient serum zinc status (Figure 1). Comparably low concentrations of zinc transporters, such as albumin and prealbumin, (Table 3) may at least partly explain this observation. Another line of reasoning is the acute phase response (APR) itself [27, 28]. Elevated concentrations of acute phase proteins, such as CRP and interleukin-6, are known to increase the expression of the zinc importer Zip14  which leads to a fast zinc redistribution to organs . Zorilla et al. showed that the serum zinc level is predictive for WH [5, 31]. They determined the serum zinc level in preoperative patients before elective hip replacement which may explain the different results obtained in our study (post-surgical analysis). In contrast to other micronutrients, such as retinol, ascorbic acid, and zinc, selenium does not have a direct physiological function in WH. However, as a cofactor of glutathione peroxidase, selenium may reduce oxidative stress in patients with DWH . Thus, the high prevalence of selenium concentrations below the reference range in patients with DWH (Figure 1) may contribute to DWH . Insufficient serum 25(OH)D3 concentrations were observed in most of our patients (Figure 1). Since Miller et al.  observed an inverse association between serum vitamin D levels and inflammatory response following hip fracture, low 25(OH)D3 concentrations in our patients may result from APR-mediated inflammation. Moreover, immobilization of the patients may contribute to the low vitamin D status due to the lack of UV-induced endogenous synthesis.
Disturbances in the redox state are discussed to be risk factors for delayed WH . Since direct measurements of the short-lived reactive oxygen species require laborious and expensive techniques, such as electron paramagnetic resonance, indirect methods are used in routine clinical setting to detect an imbalance between pro- and antioxidants . This includes analysis of peroxidation products, such as MDA and peroxides, analysis of single antioxidants (e.g., ascorbic acid, α-tocopherol, β-carotene)  and analysis of total antioxidant capacity reflecting the synergistic action between endogenous (albumin, uric acid) and nutritive (ascorbic acid, α-tocopherol and β-carotene) antioxidants . Oxidative stress in patients with DWH was indicated by increased concentrations of peroxides compared to healthy adults. TEAC was lower in patients with DWH than in healthy controls (Table 5), probably due to lower concentrations of several endogenous (e.g., albumin) and exogenous antioxidants like ascorbic acid (Table 3) with a high contribution to plasma antioxidant capacity. Despite the relatively low specificity of MDA, , the increased values of MDA suggest an increased lipid peroxidation in patients with DWH, which is in line with increased peroxides and reduced TEAC.
The strength of this study is the broad variety of biochemical, anthropometric, and clinical parameters which provides a detailed picture on the micronutrient status of trauma patients with DWH. Unfortunately, data on the quantity and quality of the diet considering energy, protein, and micronutrients of interest and data on the kind and dose of supplemented micronutrients were not collected. Hence, the impact of the nutritional intake on the nutritional status of our patients cannot be assessed. The most serious limitation of our study refers to the study design as a cross-sectional study which does not allow any conclusion whether DWH originated from nutritional deficiency or not. A further limitation refers to the high prevalence of vascular diseases, diabetes mellitus and wound infections (Table 4), which are known risk factors for DWH . Hence, effects on WH from these classic risk factors cannot be ruled out. Due to these limitations, it is difficult to judge the role of selected micronutrients for WH in vivo. In future studies with a prospective design, participants should be comparable with regard to classic risk factors for DWH (e.g., diabetes mellitus). Also, more attention should be paid to time-dependent changes following trauma and/or surgery.