Influence of surgical stabilization of clavicle fractures in multiply-injured patients with thoracic trauma.

Thoracic trauma has decisive influence on the outcome of multiply-injured patients and is often associated with clavicle fractures. The affected patients are prone to lung dysfunction and multiple organ failure. A multi-center, retrospective analysis of patient records documented in the TraumaRegister DGU was performed to assess the influence of surgical stabilization of clavicle fractures in patients with thoracic trauma. A total of 3,209 patients were included in the analysis. In 1362 patients (42%) the clavicle fracture was treated operatively after 7.1 ± 5.3 days. Surgically treated patients had a significant reduction in lung failure (p = 0.013, OR = 0.74), multiple organ failure (p = 0.001, OR = 0.64), intubation time (p = 0.004; -1.81 days) and length of hospital stay (p = 0.014; -1.51 days) compared to non-operative treatment. Moreover, surgical fixation of the clavicle within five days following hospital admission significantly reduced the rates of lung failure (p = 0.01, OR = 0.62), multiple organ failure (p = 0.01, OR = 0.59) and length of hospital stay (p = 0.01; -2.1 days). Based on our results, multiply-injured patients with thoracic trauma and concomitant clavicle fracture may benefit significantly from surgical stabilization of a clavicle fracture, especially when surgery is performed within the first five days after hospital admission.

Possible advantages of early stabilization of spinal fractures in multiply injured patients with leading thoracic trauma - analysis based on the TraumaRegister DGU®.

BACKGROUND: Major trauma often comprises fractures of the thoracolumbar spine and these are often accompanied by relevant thoracic trauma. Major complications can be ascribed to substantial simultaneous trauma to the chest and concomitant immobilization due to spinal instability, pain or neurological dysfunction, impairing the respiratory system individually and together. Thus, we proposed that an early stabilization of thoracolumbar spine fractures will result in significant benefits regarding respiratory organ function, multiple organ failure and length of ICU / hospital stay. METHODS: Patients documented in the TraumaRegister DGU®, aged ≥16 years, ISS ≥ 16, AISThorax ≥ 3 with a concomitant thoracic and / or lumbar spine injury severity (AISSpine) ≥ 3 were analyzed. Penetrating injuries and severe injuries to head, abdomen or extremities (AIS ≥ 3) led to patient exclusion. Groups with fractures of the lumbar (LS) or thoracic spine (TS) were formed according to the severity of spinal trauma (AISspine): AISLS = 3, AISLS = 4-5, AISTS = 3 and AISTS = 4-5, respectively. RESULTS: 1740 patients remained for analysis, with 1338 (76.9%) undergoing spinal surgery within their hospital stay. 976 (72.9%) had spine surgery within the first 72 h, 362 (27.1%) later on. Patients with injuries to the thoracic spine (AISTS = 3) or lumbar spine (AISLS = 3) significantly benefit from early surgical intervention concerning ventilation time (AISLS = 3 only), ARDS, multiple organ failure, sepsis rate (AISTS = 3 only), length of stay in the intensive care unit and length of hospital stay. In multiple injured patients with at least severe thoracic spine trauma (AISTS ≥ 4) early surgery showed a significantly shorter ventilation time, decreased sepsis rate as well as shorter time spend in the ICU and in hospital. CONCLUSIONS: Multiply injured patients with at least serious thoracic trauma (AISThorax ≥ 3) and accompanying spine trauma can significantly benefit from early spine stabilization within the first 72 h after hospital admission. Based on the presented data, primary spine surgery within 72 h for fracture stabilization in multiply injured patients with leading thoracic trauma, especially in patients suffering from fractures of the thoracic spine, seems to be beneficial.

Significant benefits in survival by the use of surgery combined with radiotherapy for retroperitoneal soft tissue sarcoma.

BACKGROUND: To report the effect of intraoperative electron beam radiotherapy (IOERT) and external beam radiotherapy (EBRT) in addition to surgery as well as to evaluate the role of resectable local recurrence for long-term prognosis. METHODS: In 53 patients who underwent surgery for retroperitoneal soft tissue sarcoma (RSTS) from 2001 to 2014 prognostic and epidemiologic factors were reviewed retrospectively to analyze their impact on survival and recurrence. RESULTS: Twenty three patients (50%) had surgery plus radiotherapy, 23 (50%) had surgery only. Histology showed 73.9% liposarcoma, 15.2% leiomyosarcoma and 6.5% pleomorphic undifferentiated sarcoma respectively. Low grade sarcoma were observed in 52.2%, high grade sarcoma in 47.8%. The latter showed a trend towards a decreased 5-year survival rate (p = 0.125). Margin status was: R0: 60.9%, R1: 23.9%, R2: 15.2%; leading to significant changes in 5-year survival rate (R0: 77.6%; R1: 70.0%; R2: 42.9%; p = 0.03). Age younger than 55 years significantly improved 5-year survival rate (p = 0.039). Patients receiving resection of multiple sarcoma recurrence showed an almost identical improved 5-year survival rate compared to patients without recurrence (no recurrence: 100.0%; single recurrence: 35.0%; multiple recurrence: 91.7%; p = 0.001). Surgery plus radiotherapy led to significantly improved survival (p = 0.04). CONCLUSIONS: There is a significant benefit in terms of 5-year survival after surgery plus some form of radiotherapy and a good prognosis for patients when the recurrence from RSTS was resected. Age older than 55 years and incomplete resection lowered 5-year survival rate significantly.

Human endothelial progenitor cells induce extracellular signal-regulated kinase-dependent differentiation of mesenchymal stem cells into smooth muscle cells upon cocultivation.

Neovascularization represents an important issue in tissue-engineering applications, since survival of implanted cells strongly relies on sufficient oxygen and nutrient supply. We have recently observed that human bone marrow-derived mesenchymal stem cells (MSCs) support neovessel formation originating from coimplanted endothelial cells (ECs) in vivo, suggesting that MSCs may function as perivascular cells by investing and stabilizing nascent EC-derived neovessels. In this study, we investigated EC-induced mural cell differentiation of MSCs in vitro. For this purpose, endothelial progenitor cells (EPCs) from two different origins, namely adult peripheral blood (pbEPCs) and neonatal cord blood (cbEPCs), or human umbilical vein endothelial cells (HUVECs), were cocultured with human MSCs to analyze the effect on MSC differentiation toward a smooth muscle cell (SMC)/pericyte phenotype. EPCs as well as HUVECs increased alpha-smooth muscle actin expression in MSCs upon cocultivation in a time-dependent manner. This effect was strongly dependent on direct cell-to-cell contact and extracellular signal-regulated kinase (ERK) signaling, but was not mediated by heterotypic gap junction communication. Beyond enhanced SMC marker gene expression in MSCs, EPCs also enhanced the functional characteristics of cocultured MSCs by increasing their ability to attach to EC tubes in vitro. In conclusion, our study has shown that EPCs from adult peripheral blood as well as from cord blood commit cocultivated MSCs toward an SMC/pericyte phenotype in a cell-contact- and ERK-dependent manner.

Up-regulation of alkaline phosphatase expression in human primary osteoblasts by cocultivation with primary endothelial cells is mediated by p38 mitogen-activated protein kinase-dependent mRNA stabilization.

For the regeneration of bone in tissue engineering applications, it is essential to provide cues that support neovascularization. This can be achieved by cell-based therapies using mature endothelial cells (ECs) or endothelial progenitor cells. In this context, ECs were used in various in vivo studies in combination with primary osteoblasts to enhance neovascularization of bone grafts. In a previous study, we have shown that cocultivation of human primary ECs and human primary osteoblasts (hOBs) leads to a cell contact-dependent up-regulation of alkaline phosphatase (ALP) expression in osteoblasts, indicating that cocultivated ECs may support osteogenic differentiation and osteoblastic cell functions. In the present study, we investigated this effect in more detail, revealing a time and cell number dependency of EC-mediated up-regulation of the early osteoblastic marker ALP, whereas osteocalcin, a late marker of osteogenesis, was down-regulated. The effect on ALP expression was bidirectional specific for both cell types. Functional inhibition of gap junctional communication between ECs and hOBs by 18alpha-glycyrrhetinic acid had only a weak suppressive effect on EC-mediated ALP up-regulation. In contrast, inhibition of p38 mitogen-activated protein kinase nearly completely prevented the EC-mediated stimulation of osteoblastic ALP expression. To investigate the molecular mechanism underlying the ALP up-regulation, we examined the effect of EC cocultivation on osteoblastic ALP promoter activity as well as mRNA stability. Cocultivation of ECs with hOBs significantly elevated the half-life of osteoblastic ALP mRNA without affecting its promoter activity. In summary, our data show that EC-mediated up-regulation of osteoblastic ALP expression is cell-type specific and is posttranscriptionally regulated via p38 mitogen-activated protein kinase-dependent mRNA turn-over.