Minimal invasive long PHILOS®-plate osteosynthesis in metadiaphyseal fractures of the proximal humerus.

Minimal invasive plate osteosynthesis (MIPO) not only meets the criteria of a "biological" osteosynthesis by minimising invasivity as well as iatrogenic soft tissue damage, but can also provide adequate stability for fracture healing and early functional aftertreatment. Up to date, only few publications report on MIPO of humeral shaft fractures mainly using the anterolateral deltopectoral approach for proximal plate insertion. Objective of the present study was to assess the feasibility and clinical outcome of MIPO for metadiaphyseal fractures of the proximal humerus through a lateral approach using angular stable long PHILOS(®)-plates. We retrospectively evaluated 29 patients (mean age 77 years, range 48-95 years) with displaced metadiaphyseal fractures of the proximal humerus treated with MIPO technique. For the first time, an angular stable long PHILOS(®)-plate through a lateral deltoid-split approach proximally and a brachialis/brachioradialis intermuscular approach with exposure of the radial nerve distally, were used. There were no infections and no iatrogenic injuries to the axillary and radial nerve. One patient showed subacromial impingement and one patient had to be reoperated for redislocation of the distal fragment with screw breakage, which was most likely due to incorrect screw placement. This patient was successfully operated using the same method and implant. Besides one patient who refused further follow-up, 28 patients could be followed up to a mean of 8 months (range 3-12 months) each with an entirely healed fracture. Furthermore, patient's quality of life was documented using the SF-36 questionnaire. Comparison with published United States normative data showed no significant deficits in the physical as well as in the mental domains 8 months after MIPO. Minimal invasive long PHILOS(®)-plate osteosynthesis using a combined lateral deltoid-split and brachialis/brachioradialis intermuscular approach proved to be a safe procedure for the treatment of metadiaphyseal fractures of the proximal humerus with low morbidity and full restoration of quality of life in these elderly patients.

Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice.

Cerebral inflammation involves molecular cascades contributing to progressive damage after traumatic brain injury (TBI). The chemokine CC ligand-2 (CCL2) (formerly monocyte chemoattractant protein-1, MCP-1) is implicated in macrophage recruitment into damaged parenchyma after TBI. This study analyzed the presence of CCL2 in human TBI, and further investigated the role of CCL2 in physiological and cellular mechanisms of secondary brain damage after TBI. Sustained elevation of CCL2 was detected in the cerebrospinal fluid (CSF) of severe TBI patients for 10 days after trauma, and in cortical homogenates of C57Bl/6 mice, peaking at 4 to 12 h after closed head injury (CHI). Neurological outcome, lesion volume, macrophage/microglia infiltration, astrogliosis, and the cerebral cytokine network were thus examined in CCL2-deficient (-/-) mice subjected to CHI. We found that CCL2-/- mice showed altered production of multiple cytokines acutely (2 to 24 h); however, this did not affect lesion size or cell death within the first week after CHI. In contrast, by 2 and 4 weeks, a delayed reduction in lesion volume, macrophage accumulation, and astrogliosis were observed in the injured cortex and ipsilateral thalamus of CCL2-/- mice, corresponding to improved functional recovery as compared with wild-type mice after CHI. Our findings confirm the significant role of CCL2 in mediating post-traumatic secondary brain damage.

Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds.

BACKGROUND: Clinical observations are suggesting accelerated granulation tissue formation in traumatic wounds treated with vacuum-assisted closure (VAC). Aim of this study was to determine the impact of VAC therapy versus alternative Epigard application on local inflammation and neovascularization in traumatic soft tissue wounds. METHODS: Thirty-two patients with traumatic wounds requiring temporary coverage (VAC n = 16; Epigard n = 16) were included. At each change of dressing, samples of wound fluid and serum were collected (n = 80). The cytokines interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 were measured by ELISA. Wound biopsies were examined histologically for inflammatory cells and degree of neovascularization present. RESULTS: All cytokines were found to be elevated in wound fluids during both VAC and Epigard treatment, whereas serum concentrations were negligible or not detectable. In wound fluids, significantly higher IL-8 (p < 0.001) and VEGF (p < 0.05) levels were detected during VAC therapy. Furthermore, histologic examination revealed increased neovascularization (p < 0.05) illustrated by CD31 and von Willebrand factor immunohistochemistry in wound biopsies of VAC treatment. In addition, there was an accumulation of neutrophils as well as an augmented expression of VEGF (p < 0.005) in VAC wound biopsies. CONCLUSION: This study suggests that VAC therapy of traumatic wounds leads to increased local IL-8 and VEGF concentrations, which may trigger accumulation of neutrophils and angiogenesis and thus, accelerate neovascularization.

Soft Tissue Management in Open Fractures of the Lower Leg: The Role of Vacuum Therapy.

The management of severe open fractures of the lower leg continues to challenge the treating surgeon. Major difficulties include high infection rates as well as adequate temporary soft tissue coverage. In the past, these injuries were commonly associated with loss of the extremity. Today, vacuum therapy provides not only safe temporary wound coverage but also conditioning of the soft tissues until definitive wound closure. Amongst other advantages, bacterial clearance and increased formation of granulation tissue are attributed to vacuum therapy, making it an extremely attractive tool in the field of wound healing. However, despite its clinical significance, which is underlined by a constantly increasing range of indications, there is a substantial lack of basic research and well-designed studies documenting the superiority of vacuum therapy compared to alternative wound dressings. Vacuum therapy has been approved as an adjunct in the treatment of severe open fractures of the lower leg, complementing repeated surgical debridement and soft tissue coverage by microvascular flaps, which are still crucial in the treatment of these limb-threatening injuries. Vacuum therapy has in general proven useful in the management of soft tissue injuries and, since it is generally well tolerated and has low complication rates, it is fast becoming the gold standard for temporary wound coverage in the treatment of severe open fractures of the lower leg.

The chemokine fractalkine in patients with severe traumatic brain injury and a mouse model of closed head injury.

The potential role of the chemokine Fractalkine (CX3CL1) in the pathophysiology of traumatic brain injury (TBI) was investigated in patients with head trauma and in mice after experimental cortical contusion. In control individuals, soluble (s)Fractalkine was present at low concentrations in cerebrospinal fluid (CSF) (12.6 to 57.3 pg/mL) but at much higher levels in serum (21,288 to 74,548 pg/mL). Elevation of sFractalkine in CSF of TBI patients was observed during the whole study period (means: 29.92 to 535.33 pg/mL), whereas serum levels remained within normal ranges (means: 3,100 to 59,159 pg/mL). Based on these differences, a possible passage of sFractalkine from blood to CSF was supported by the strong correlation between blood-brain barrier dysfunction (according to the CSF-/serum-albumin quotient) and sFractalkine concentrations in CSF (R = 0.706; P < 0.01). In the brain of mice subjected to closed head injury, neither Fractalkine protein nor mRNA were found to be augmented; however, Fractalkine receptor (CX3CR1) mRNA steadily increased peaking at 1 week postinjury (P < 0.05, one-way analysis of variance). This possibly implies the receptor to be the key factor determining the action of constitutively expressed Fractalkine. Altogether, these data suggest that the Fractalkine-CX3CR1 protein system may be involved in the inflammatory response to TBI, particularly for the accumulation of leukocytes in the injured parenchyma.

Central nervous system-targeted complement inhibition mediates neuroprotection after closed head injury in transgenic mice.

The role of intracerebral complement activation after traumatic brain injury remains unclear. In this study, the authors demonstrate that transgenic mice with astrocyte-targeted expression of the soluble complement inhibitor sCrry have a significantly reduced neurologic impairment and improved blood-brain barrier function after closed head injury compared with wild-type C57BL/6 littermates. This work further implicates the complement system as a participant in secondary progression of brain damage after head trauma and provides a strong rationale for future studies of posttraumatic pharmacologic complement inhibition.

Inflammatory response in acute traumatic brain injury: a double-edged sword.

Inflammation is an important part of the pathophysiology of traumatic brain injury. Although the central nervous system differs from the other organs because of the almost complete isolation from the blood stream mediated by the blood-brain barrier, the main steps characterizing the immune activation within the brain follow a scenario similar to that in other organs. The key players in these processes are the numerous immune mediators released within minutes of the primary injury. They guide a sequence of events including expression of adhesion molecules, cellular infiltration, and additional secretion of inflammatory molecules and growth factors, resulting in either regeneration or cell death. The question is this: to what extent is inflammation beneficial for the injured brain tissue, and how does it contribute to secondary brain damage and progressive neuronal loss? This review briefly reports recent evidence supporting the dual, the beneficial, or the deleterious role of neuroinflammation after traumatic brain injury.

Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury.

Proinflammatory cytokines are important mediators of neuroinflammation after traumatic brain injury. The role of interleukin (IL)-18, a new member of the IL-1 family, in brain trauma has not been reported to date. The authors investigated the posttraumatic release of IL-18 in murine brains following experimental closed head injury (CHI) and in CSF of CHI patients. In the mouse model, intracerebral IL-18 was induced within 24 hours by ether anesthesia and sham operation. Significantly elevated levels of IL-18 were detected at 7 days after CHI and in human CSF up to 10 days after trauma. Published data imply that IL-18 may play a pathophysiological role in inflammatory CNS diseases; therefore its inhibition may ameliorate outcome after CHI. To evaluate the functional aspects of IL-18 in the injured brain, mice were injected systemically with IL-18-binding protein (IL-18BP), a specific inhibitor of IL-18, 1 hour after trauma. IL-18BP-treated mice showed a significantly improved neurological recovery by 7 days, accompanied by attenuated intracerebral IL-18 levels. This demonstrates that inhibition of IL-18 is associated with improved recovery. However, brain edema at 24 hours was not influenced by IL-18BP, suggesting that inflammatory mediators other than IL-18 induce the early detrimental effects of intracerebral inflammation.