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Background/purpose: Impaired healing is a feared complication with devastating outcomes for each patient. Most studies focus on geriatric fracture fixation and assess well known risk factors such as infections. However, risk factors, others than infections, and impaired healing of proximal femur fractures in non-geriatric adults are marginally assessed. Therefore, this study aimed to identify non-infection related risk factors for impaired fracture healing of proximal femur fractures in non-geriatric trauma patients., Methods: This study included non-geriatric patients (aged 69 years and younger) who were treated between 2013 and 2020 at one academic Level 1 trauma center due to a proximal femur fracture (PFF). Patients were stratified according to AO/OTA classification. Delayed union was defined as failed callus formation on 3 out of 4 cortices after 3 to 6 months. Nonunion was defined as lack of callus-formation after 6 months, material breakage, or requirement of revision surgery. Patient follow up was 12 months., Results: This study included 150 patients. Delayed union was observed in 32 (21.3%) patients and nonunion with subsequent revision surgery occurred in 14 (9.3%). With an increasing fracture classification (31 A1 up to 31 A3 type fractures), there was a significantly higher rate of delayed union. Additionally, open reduction and internal fixation (ORIF) (OR 6.17, (95% CI 1.54 to 24.70, p ≤ 0.01)) and diabetes mellitus type II (DM) (OR 5.74, (95% CI 1.39 to 23.72, p = 0.016)), were independent risk factors for delayed union. The rate of nonunion was independent of fracture morphology, patient's characteristics or comorbidities., Conclusion: Increasing fracture complexity, ORIF and diabetes were found to be associated with delayed union of intertrochanteric femur fractures in non-geriatric patients. However, these factors were not associated with the development of nonunion., (© 2023. The Author(s).)

Objectives: The 2 main forms of treatment for distal femur fractures are locked lateral plating and retrograde nailing. The goal of this trial was to determine whether there are significant differences in outcomes between these forms of treatment., Design: Multicenter randomized controlled trial., Setting: Twenty academic trauma centers., Patients/participants: One hundred sixty patients with distal femur fractures were enrolled. One hundred twenty-six patients were followed 12 months. Patients were randomized to plating in 62 cases and intramedullary nailing in 64 cases., Intervention: Lateral locked plating or retrograde intramedullary nailing., Main Outcome Measurements: Functional scoring including Short Musculoskeletal Functional Assessment, bother index, EQ Health, and EQ Index. Secondary measures included alignment, operative time, range of motion, union rate, walking ability, ability to manage stairs, and number and type of adverse events., Results: Functional testing showed no difference between the groups. Both groups were still significantly affected by their fracture 12 months after injury. There was more coronal plane valgus in the plating group, which approached statistical significance. Range of motion, walking ability, and ability to manage stairs were similar between the groups. Rate and type of adverse events were not statistically different between the groups., Conclusions: Both lateral locked plating and retrograde intramedullary nailing are reasonable surgical options for these fractures. Patients continue to improve over the course of the year after injury but remain impaired 1 year postoperatively., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Soft tissue injury and soft tissue injury as risk factors for nonunion following trochanteric femur fractures (TFF) are marginally investigated. The aim of this study was to identify risk factors for impaired fracture healing in geriatric trauma patients with TFF following surgical treatment with a femoral nail., Methods: This retrospective cohort study included geriatric trauma patients (aged > 70 years) with TFF who were treated with femoral nailing. Fractures were classified according to AO/OTA. Nonunion was defined as lack of callus-formation after 6 months, material breakage, and requirement of revision surgery. Risk factors for nonunion included variables of clinical interest (injury pattern, demographics, comorbidities), as well as type of approach (open versus closed) and were assessed with uni- and multivariate regression analyses., Results: This study included 225 geriatric trauma patients. Nonunion was significantly more frequently following AO/OTA 31A3 fractures (N = 10, 23.3%) compared with AO/OTA type 31A2 (N = 6, 6.9%) or AO/OTA 31A1 (N = 3, 3.2%, p < 0.001). Type 31A3 fractures had an increased risk for nonunion compared with type 31A1 (OR 10.3 95%CI 2.2 to 48.9, p = 0.003). Open reduction was not associated with increased risk for nonunion (OR 0.9, 95%CI 0.1 to 6.1. p = 0.942) as was not the use of cerclage (OR 1.0, 95%CI 0.2 to 6.5, p = 0.995). Factors such as osteoporosis, polytrauma or diabetes were not associated with delayed union or nonunion., Conclusion: The fracture morphology of TFF is an independent risk factor for nonunion in geriatric patients. The reduction technique is not associated with increased risk for nonunion, despite increased soft tissue damage following open reduction., (© 2022. The Author(s).)

The local inflammatory impact of different reaming protocols in intramedullary nailing has been sparsely investigated. We examined the effect of different reaming protocols on fracture hematoma (FH) immunological characteristics in pigs. To do so, a standardized midshaft femur fracture was induced in adult male pigs. Fractures were treated with conventional reamed femoral nailing (group RFN, n = 6); unreamed femoral nailing (group UFN, n = 6); reaming with a Reamer Irrigator Aspirator device (group RIA, n = 12). Animals were observed for 6 h and FH was collected. FH-cell apoptosis and neutrophil receptor expression (Mac-1/CD11b and FcγRIII/CD16) were studied by flow cytometry and local temperature changes were analyzed. The study demonstrates that apoptosis-rates of FH-immune cells were significantly lower in group RIA (3.50 ± 0.53%) when compared with non-RIA groups: (group UFN 12.50 ± 5.22%, p = 0.028 UFN vs. RIA), (group RFN 13.30 ± 3.18%, p < 0.001, RFN vs. RIA). Further, RIA-FH showed lower neutrophil CD11b/CD16 expression when compared with RFN (mean difference of 43.0% median fluorescence intensity (MFI), p = 0.02; and mean difference of 35.3% MFI, p = 0.04, respectively). Finally, RIA induced a transient local hypothermia and hypothermia negatively correlated with both FH-immune cell apoptosis and neutrophil activation. In conclusion, immunologic changes observed in FH appear to be modified by certain reaming techniques. Irrigation during reaming was associated with transient local hypothermia, decreased apoptosis, and reduced neutrophil activation. Further study is warranted to examine whether the rinsing effect of RIA, specific tissue removal by reaming, or thermal effects predominantly determine local inflammatory changes during reaming., (© 2022 The Authors. Journal of Orthopaedic Research#x000AE; published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Purpose: Intramedullary nailing (IMN) of fractures is associated with increased rates of inflammatory complications. The pathological mechanism underlying this phenomenon is unclear. However, polymorphonuclear granulocytes (PMNs) seem to play an important role. We hypothesized that a femur fracture and standardized IMN in pigs is associated with altered appearance of PMNs in circulation and enhanced activation status of these cells., Methods: A porcine model including a femur fracture and IMN was utilized. Animals were randomized for control [anesthesia + mechanical ventilation only (A/MV)] and intervention [A/MV and unilateral femur fracture (FF) + IMN] conditions. PMN numbers and responsiveness, integrin (CD11b), L-selectin (CD62L) and Fcγ-receptor (CD16 and CD32)-expression levels were measured by flowcytometry of blood samples. Animals were observed for 72 h., Results: Circulatory PMN numbers did not differ between groups. Early PMN-responsiveness was retained after insult. PMN-CD11b expression increased significantly upon insult and peaked after 24 h, whereas CD11b in control animals remained unaltered (P = 0.016). PMN-CD16 expression levels in the FF + IMN-group rose gradually over time and were significantly higher compared with control animals, after 48 h (P = 0.016) and 72 h (P = 0.032). PMN-CD62L and CD32 expression did not differ significantly between conditions., Conclusion: This study reveals that a femur fracture and subsequent IMN in a controlled setting in pigs is associated with enhanced activation status of circulatory PMNs, preserved PMN-responsiveness and unaltered circulatory PMN-presence. Indicating that monotrauma plus IMN is a specific and substantial stimulus for the cellular immune system. Early alterations of circulatory PMN receptor expression dynamics may be predictive for the intensity of the post traumatic response., (© 2021. The Author(s).)

Purpose: Treatment strategies for femoral fracture stabilisation are well known to have a significant impact on the patient's outcome. Therefore, the optimal choices for both the type of initial fracture stabilisation (external fixation/EF, early total care/ETC, conservative treatment/TC) and the best time point for conversion from temporary to definitive fixation are challenging factors., Patients: Patients aged ≥ 16 years with moderate and severe trauma documented in the TraumaRegister DGU ® between 2002 and 2018 were retrospectively analysed. Demographics, ISS, surgical treatment strategy (ETC vs. EF vs. TC), time for conversion to definitive care, complication (MOF, sepsis) and survival rates were analysed., Results: In total, 13,091 trauma patients were included. EF patients more often sustained high-energy trauma (car: 43.1 vs. 29.5%, p < 0.001), were younger (40.6 vs. 48.1 years, p < 0.001), were more severely injured (ISS 25.4 vs. 19.1 pts., p < 0.001), and had higher sepsis (11.8 vs. 5.4%, p < 0.001) and MOF rates (33.1 vs. 16.0%, p < 0.001) compared to ETC patients. A shift from ETC to EF was observed. The time until conversion decreased for femoral fractures from 9 to 8 days within the observation period. Sepsis incidences decreased in EF (20.3 to 12.3%, p < 0.001) and ETC (9.1-4.8%, p < 0.001) patients., Conclusions: Our results show the changes in the surgical treatment of severely injured patients with femur fractures over a period of almost two decades caused by the introduction of modern surgical strategies (e.g., Safe Definitive Surgery). It remains unclear which subgroups of trauma patients benefit most from these strategies., (© 2021. The Author(s).)

Case: A 36-year-old patient with chronic alcohol abuse and previous medical history of total hip arthroplasty suffered a fracture of the femoral shaft. During osteosynthesis, a milky fluid similar to purulent discharge emerged at multiple locations. Immediate Gram stains were negative, and the surgery was performed as planned. Laboratory tests showed massive elevated levels of triglycerides. During further workup, chylomicronemia syndrome was diagnosed., Conclusion: This case report shows that chylomicronemia syndrome can have an appearance during surgery similar to a purulent infection. Immediate Gram stains and laboratory work can identify the reason., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B468)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Musculoskeletal injuries are the most common reason for surgery in severely injured patients. In addition to direct cardiac damage after physical trauma, there is rising evidence that trauma induces secondary cardiac structural and functional damage. Previous research associates hip fractures with the appearance of coronary heart disease: As 25% of elderly patients developed a major adverse cardiac event after hip fracture. 20 male pigs underwent femur fracture with operative stabilization via nailing (unreamed, reamed, RIA I and a new RIA II; each group n = 5). Blood samples were collected 6 h after trauma and the concentration of troponin I and heart-type fatty acid binding protein (HFABP) as biomarkers for EMD were measured. At baseline and 6 h after trauma, transesophageal ECHO (TOE) was performed; and invasive arterial and left ventricular blood pressure were measured to evaluate the cardiac function after femur fracture. A systemic elevation of troponin I and HFABP indicate an early myocardial damage after femur fracture in pigs. Furthermore, various changes in systolic (ejection fraction and cardiac output) and diastolic (left ventricular end-diastolic pressure, mitral valve deceleration time and E/A ratio) parameters illustrate the functional impairment of the heart. These findings were accompanied by the development of valvular dysfunction (pulmonary and tricuspid valve). To the best of our knowledge, we described for the first time the development of functional impairment of the heart in the context of EMD after long bone fracture in pigs. Next to troponin and HFABP elevation, alterations in the systolic and diastolic function occurred and were accompanied by pulmonary and tricuspid valvular insufficiency. Regarding EMD, none of the fracture stabilization techniques (unreamed nailing, reaming, RIA I and RIA II) was superior.

Introduction: The effects of reaming for preparation of intramedullary fixation in long bone fractures have been widely studied. We compared pulmonary and systemic effects between conventional reaming with reamer irrigator aspirator and unreamed nailing in an acute porcine trauma model with a standardized femur fracture., Materials and Methods: In a standardized porcine model, (moderate blunt chest trauma, abdominal injury and femoral shaft fracture), the femur was submitted to intramedullary nailing after resuscitation and normalization of pulmonary function. The treatment groups included 3 reamer types (Group RFN: conventional reaming with Synream; group RIA1; reamer irrigator aspirator, version 2005; group RIA 2; reamer irrigator aspirator, version 2019) and were compared to unreamed femoral nailing (Group UFN). Pulmonary function measurements included arterial partial carbon-dioxide pressure (paCO 2 [kPa]) (baseline, post reaming, 2,4,6 h) and volumetric measures of contusion in chest computer tomography (CT) (at 6 hrs.). Systemic inflammatory response was measured at baseline and every second hour until six hours after trauma., Results: This study included 24 male animals, mean weight 50.76 ± 4.1 kg n = 6 per group). Group RFN developed a significantly higher partial CO 2 (pCO 2 ) at one hour after reaming when compared with all other groups (7.4 ± 0.4 kPa versus 5.4 ± 0.6 RIA 1, 5.6 ± 0.4 RIA 2, and 5.5 ± 0.5 UFN, p < 0.001), along with a had lower pO 2 (12.3 ± 1.3 kPa versus 17.2 ± 1.9 RIA 1, 17.4 ± 1.6 RIA 2, and 16.4 ± 0.7 UFN, p < 0.001) and the degree of pulmonary hyperdense changes in the CT analysis was higher in RFN (485.2 ± 98.5 cm 3 versus 344.4 ± 74.4 cm 3 RIA 1 and 335.2 ± 58.1 cm 3 RIA 2, p < 0.01). The inflammatory reaction was lowest in both RIA groups when compared with group RFN or UFN (p < 0.001)., Conclusion: Both RIA 1 and RIA 2 protect the lung from reaming induced dysfunction and have no systemic inflammatory effects, while the negative effects were more sustained after reamed or unreamed nailing. Both RIA 1 and RIA II appear to be of value in terms of a Safe Definitive Surgery (SDS) strategy., Competing Interests: Declaration of Competing Interest No conflicts of interest, (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In the stabilization of femoral fractures in mono- and polytrauma, clinical practice has shown better care through intramedullary nailing. However, the reason why this is the case is not fully understood. In addition to concomitant injuries, the immunological aspect is increasingly coming to the fore. Neutrophil granulocytes (PMNL), in particular next to other immunological cell types, seem to be associated with the fracture healing processes. For this reason, the early phase after fracture (up to 72 h after trauma) near the fracture zone in muscle tissue was investigated in a pig model., Material and Methods: A mono- and polytrauma pig model (sole femur fracture or blunt thoracic trauma, hemorrhagic shock, liver laceration, and femur fracture) was used to demonstrate the immunological situation through muscle biopsies and their analysis by histology and qRT-PCR during a 72 h follow-up phase. Two stabilization methods were used (intramedullary nail vs. external fixator) and compared with a nontraumatized sham group., Results: Monotrauma shows higher PMNL numbers in muscle tissue compared with polytrauma (15.52 ± 5.39 mono vs. 8.23 ± 3.36 poly; p = 0.013), regardless of the treatment strategy. In contrast, polytrauma shows a longer lasting invasion of PMNL (24 h vs. 72 h). At 24 h in the case of monotrauma, the fracture treated with external fixation shows more PMNL than the fracture treated with intramedullary nailing (p = 0.026). This difference cannot be determined in polytrauma probably caused by a generalized immune response. Both monotrauma and polytrauma show a delayed PMNL increase in the muscle tissue of the uninjured side. The use of intramedullary nailing in monotrauma resulted in a significant increase in IL-6 (2 h after trauma) and IL-8 (24 and 48 h after trauma) transcription., Conclusion: The reduction of PMNL invasion into the nearby muscle tissue of a monotrauma femur fracture stabilized by intramedullary nailing supports the advantages found in everyday clinical practice and therefore underlines the usage of nailing. For the polytrauma situation, the fixation seems to play a minor role, possibly due to a generalized immune reaction.

Introduction: Excessive activation of the immune response after femoral fractures and fracture fixation is potentially associated with the development of systemic and local complications, particularly in multiple trauma patients. A dysregulated function of neutrophils, the most prevailing immune cells in circulation, has been discussed as a central pathophysiological background for these unfavourable post-traumatic courses. Our aim was to investigate alterations in activity and functionality as expressed by the cell surface receptor dynamics of circulatory neutrophils after femoral fracture and intramedullary stabilization., Material and Methods: After intramedullary stabilization, an isolated femur fracture was induced in 18 Sprague-Dawley rats. Animals were terminated at different time points, i.e. after 3 (n = 5, group 3d), 7 (n = 5, group 7d) and 14 (n = 5, Group 14d) days and grouped accordingly. Additionally, baseline measurements were performed in one control animal per study group (n = 3) after anaesthesia induction and termination, without prior intramedullary nailing and fracture induction. The numbers and cell surface expression of CD11b, CD11a, CD62 L, and CD49d of circulating neutrophils were compared between groups., Results: Neutrophil numbers were significantly reduced at 3 days compared with baseline measurements (1.2 × 10 5 vs. 6.3 × 10 5 cells/mL, p < 0.01). By day 7, neutrophil counts significantly increased back to homeostatic levels (p < 0.05). At day 3, CD11b-expression was significantly reduced, whereas CD11a-expression was increased compared with the baseline measurements (p < 0.05). At day 7, the circulatory neutrophil pool exhibited a unique CD11b high /CD11a high -neutrophil subset showing a significantly increased co-expression of CD49d. The expression of CD62 L did not change significantly throughout the experiment compared with baseline measurements., Conclusions: This descriptive small animal fracture study is the first to show that an intramedullary stabilized femur fracture is associated with a temporary reduction in circulatory neutrophil count and concurrent changes in circulatory neutrophil function. Moreover, we demonstrated that the restoration to homeostatic neutrophil activation status occurs concomitantly with the appearance of a novel neutrophil subtype (CD11b high /CD11a high ) in circulation. Our fundamental new findings of the changes in circulatory neutrophil count and functionality after trauma form an excellent basis for future studies to further elucidate the role of neutrophils as activators and regulators of different post-traumatic processes, potentially resulting in local (e.g., fracture healing disturbances) or systemic (e.g., MODS) complications. This might result in the development of specific therapies to reduce adverse outcomes after trauma., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Background: Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus non-reamed femoral nailing) on cardiac alterations was studied., Experimental Approach: 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro., Results: After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1 protein. Furthermore, cardiac alterations were observed predominantly in pigs that were treated by non-reamed intramedullary reaming. The polytrauma-cocktail impaired the viability of HL-1 cells in vitro, which was accompanied by a release of troponin I and HFABP., Discussion: Multiple trauma induced cardiac structural alterations in vivo, which might contribute to the development of early myocardial damage (EMD). This study also revealed that reamed femoral nailing (reamed) is associated with more prominent immunological cardiac alterations compared to nailing without reaming (non-reamed). This suggests that the choice of the initial fracture treatment strategy might be crucial for the overall outcome as well as for any post-traumatic cardiac consequences., Competing Interests: the authors have declared that no competing interests exist.

Purpose: Dysregulation of polymorphonuclear neutrophil (PMN) biology is associated with the development of inflammatory complications after trauma, such as acute respiratory distress syndrome (ARDS). It has been demonstrated that intramedullary nailing is both associated with altered pulmonary neutrophil deposition and the occurrence of ARDS. This standardized study aimed to characterize the long-term remote neutrophil response in the lungs in case of a femur fracture and intramedullary nailing., Methods: A standardized rat model including intramedullary nailing and a femur fracture was utilized. Groups were terminated after observation times of three, seven and 14 days. Neutrophils were isolated from lung parenchyma and broncho-alveolar lavage fluid (BALF) and analyzed by flow cytometry. Absolute neutrophil numbers as well as membrane expression levels of CD11b, CD62L, and CD11a were compared., Results: Pulmonary neutrophil numbers were increased 3 days after intervention. Membrane expression levels of CD11b (P < 0.01), CD62L (P < 0.01), and CD11a (P = 0.06) on parenchymal PMNs increased as well after 3 days. Thereafter, values restored gradually to physiological levels. Furthermore, neutrophil activation status patterns between parenchymal and BALF neutrophil pools did not correlate., Conclusions: The current study demonstrates that IMN and a femur fracture are associated with transient increased pulmonary PMN deposition, as well as a specific pattern of activation characterized by temporary increased selectin and integrin receptor expression on pulmonary neutrophils. This phenomenon might play an important role in the pathomechanism of ARDS after IMN. Moreover, we found striking differences between parenchymal and BALF-neutrophil populations, demonstrating the limited readout potential of BALF analysis to investigate the entire pulmonary neutrophil pool.

Aim: Severely injured patients experience substantial immunological stress upon traumatic insult. Next to the direct local tissue injury also other organs, which are not directly injured such as liver and lung, are frequently affected by a so-called remote organ damage (ROD) after trauma. Thus, we studied the inflammatory response of lung and liver either after isolated femur fracture as example for ROD, or after multiple trauma in a porcine polytrauma model., Methods: Twenty-four male pigs (Sus scrofa) underwent either isolated standardized femoral fracture (monotrauma, MT, n = 12) or polytrauma (PT, n = 12). PT consisted of a femur fracture, lung contusion, liver laceration, hemorrhagic shock, subsequent resuscitation and surgical fracture fixation. Six animals served as controls (sham). After 72 h inflammatory changes were determined by analyses of the interleukin (IL)-6 gene expression and tissue infiltration of polymorphonuclear leukocyte (PMN, myeloperoxidase staining). ROD in MT, and lung as well as liver damage in PT were assessed histologically by hematoxylin-eosin staining. Expression of phosphorylated p65 NF-κB was evaluated by immunohistology., Results: IL-6 increased in lungs and liver in both groups MT and PT, respectively, compared to sham. Similarly, PMN infiltration of the lungs and liver increased significantly after both MT and PT compared to sham. Histological evaluation demonstrated tissue damage notably in lungs after MT, while tissue damage after PT was found in both lung and liver after PT. p65 NF-κB tended to an increase upon MT, and was significantly enhanced after PT in both tissues., Conclusion: Our data indicate that remote organ damage after MT notably in lungs was associated with an enhanced inflammatory response. Severe polytrauma substantially intensifies this response and organ damage in the underlying model.

Introduction: The local circulatory changes induced by intramedullary reaming are not fully understood. This study aimed to analyse the short-term local microcirculation associated with different surgical strategies in a porcine model with a mid-shaft fracture., Methods: German landrace pigs were subjected to a standardised femoral fracture under standard anaesthesia and intensive care monitoring. One group was subjected to intramedullary reaming and nailing (nail group), while a second group was stabilised with external fixation (fix ex group). Microcirculation [e.g. relative blood flow (flow), oxygen saturation and relative haemoglobin concentration] was measured in the vastus lateralis muscle adjacent to the fracture using an O2C (oxygen to see, LEA Medizintechnik GMBH) device at 0 (before fracture, baseline), 6 (90-min posttreatment), 24, 48 and 72 h., Results: A total of 24 male pigs were used (nail group, n = 12; fix ex group, n = 12). During the observation period, a significant increase of flow was found at 6 (P = 0.048), 48 (P = 0.023) and 72 h (P = 0.042) in comparison with baseline levels. Local oxygen delivery was significantly higher at 48 (P = 0.017) and 72 h (P = 0.021) in animals in the nail group compared to animals in the external fixation group., Conclusion: This study used a standardised porcine femoral fracture model and determined a significant increase in local blood microcirculation (e.g. flow and oxygen delivery) in animals treated with intramedullary reaming compared to external fixation. These changes may be of importance for fracture healing and local and systemic inflammatory responses. Further studies in this area are justified.

Fat embolism is common in patients with major fractures, but leads to devastating consequences, named fat embolism syndrome (FES) in some. Despite advances in treatment strategies regarding the timing of definitive fixation of major fractures, FES still occurs in patients. In this overview, current literature is reviewed and optimal treatment strategies for patients with multiple traumatic injuries, including major fractures, are discussed. Considering the multifactorial etiology of FES, including mechanical and biochemical pathways, FES cannot be prevented in all patients. However, screening for symptoms of FES should be standard in the pre-operative work-up of these patients, prior to definitive fixation of major fractures., (Copyright © 2017. Published by Elsevier Ltd.)

Background: A broad range of systemic complications has been described to occur in patients with open major fractures. Various causes have been claimed to play a role. We therefore surveyed a nationwide trauma registry to assess risk factors associated with closed and various types of open femur fractures., Methods: This was a cohort study in a nationwide population-based prospective database. Inclusion criteria for selection from database are as follows: individuals with femur fracture, age 16 years or older, and survival until primary admission. Main groups included closed and open femur fracture. Patient demographics, injury severity (New Injury Severity Score), surgical fracture management, length of stay, and systemic complications (e.g., multiple organ failure [MOF], sepsis, mortality) were collected and statistically analyzed using SPSS statistics. Multivariate regression analysis was performed to stratify subgroups for the degree of open soft-tissue injury according to Gustilo and Anderson., Results: Among 32,582 documented trauma victims (January 1, 2002, to December 31, 2010), a total of 5,761 met the inclusion criteria. Main groups: 4,423 closed (76.8%) and 1,338 open femur fractures (23.2%). Open fractures subgroups were divided into I° (334, 28.1%), II° (526, 44.3%), and III° (328, 27.6%). Open fractures were associated with an increased risk of prehospital hemorrhagic shock (p = 0.01), higher resuscitation requirements (p < 0.001), MOF (p = 0.001), and longer in-hospital (p < 0.001) and intensive care stay (p = 0.001). While New Injury Severity Score values showed a minor increase per subgroup, the prevalence of MOF, sepsis, and mortality multiplied with the degree of open soft-tissue injury. Especially patients with Type III open femur fractures received mass transfusions (28.2%, p < 0.001), and mass transfusions were identified as independent predictor for sepsis (odds ratio [OR], 2.393; 95% confidence interval [CI], 1.821-3.143; p < 0.001) and MOF (OR, 2.966; 95% CI, 2.409-3.651; p < 0.001). Our data also indicate an increased mortality in patients with open femur managed outside Level I trauma centers (OR, 1.358; 95% CI, 1.018-1.812; p = 0.037)., Conclusion: Open femur fractures are associated with higher in-hospital complications related to incidence of MOF, associated intensive care unit stay, and hospital days when compared with closed femur fractures. For prevention of in-hospital complications, prompt hemorrhage control, surgical fracture fixation, cautious blood management, and triage to a Level I trauma center must be considered., Level of Evidence: Epidemiologic/prognostic study, level II.

Objectives: Third-generation cephalomedullary nails currently represent the gold standard in the treatment of unstable trochanteric femur fractures. Recently, an extramedullary rotationally stable screw-anchor system (RoSA) has been developed. It was designed to combine the benefits of screw and blade and to improve stability using a locked trochanteric stabilizing plate (TSP). The purpose of this study was to compare the biomechanical behavior of RoSA/TSP and the proximal femoral nail antirotation (PFNA)., Methods: Standardized AO/OTA 31A2.2 fractures were induced by an oscillating saw in 10 paired human specimens (n = 20; mean age = 85 years; range: 71-96 years). The fractures were stabilized by either the RoSA/TSP (Koenigsee Implants, Allendorf, Germany) or the PFNA (DePuy Synthes, Zuchwil, Switzerland). Femurs were positioned in 25 degrees of adduction and 10 degrees of posterior flexion and were cyclically loaded with axial sinusoidal pattern at 0.5 Hz, starting at 300 N, with stepwise increase by 300 N every 500 cycles until bone-implant failure occurred. After every load step, the samples were measured visually and radiographically. Femoral head migration was assessed., Results: The stiffness at the load up to the clinically relevant load step of 1800 N (639 ± 378 N/mm (RoSA/TSP) vs. 673 ± 227 N/mm (PFNA); P = 0.542) was comparable, as was the failure load (3000 ± 787 N vs. 3780 ± 874 N; P = 0.059). Up to 1800 N, no femoral head rotation, head migration, or femoral neck shortening were observed either for RoSA/TSP or PFNA. Whereas failure of the PFNA subsumed fractures of the greater trochanter and the lateral wall, a posterior femoral neck fracture with a significantly increased femoral neck shortening (1.7 mm vs. 0 mm; P = 0.012) was the cause of failure with RoSA/TSP. This specific kind of failure was induced by a femoral neck weakening caused by the posterior TSP stabilizing screw., Conclusions: There was no significant difference in biomechanical properties between the RoSA/TSP and the PFNA for the fracture pattern tested. However, failure modes differed between the 2 implants with greater femoral neck shortening observed in the RoSA/TSP group.

Orthopaedic trauma is an increasingly common problem in geriatric patients. As demands of daily life and recreational activities are increasing in these patients, surgeons need to be able to manage geriatric fractures to achieve good functional results. Reduced bone quality in the elderly presents a considerable challenge and may preclude the use of established surgical stabilisation techniques that are performed in younger trauma patients. Furthermore, pre-existing medical conditions and considerable comorbidities in the elderly could complicate standard surgical procedures that younger patients would be offered. In this respect, application of external fixators represents a validated, minimally-invasive treatment opportunity. This review article summarises the use of external fixation in geriatric trauma patients for wrist fractures, proximal femoral fractures, pelvic fractures, and ankle fractures. Modern modifications, like pin coating with hydroxyapatite, and aspects of pin care will be discussed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Locked minimally invasive plating and fourth generation nailing potentially could reduce the complication rate in the treatment of trochanteric femur fractures by its rotational stability and providing better lateral cortical support. The purpose of this study was (1) to compare the biomechanical properties of the Percutaneous compression plate (PCCP) and the Intertan nail (IT) with regards to implant failure and (2) to assess dynamic stability coefficients in an unstable AO/OTA 31A2.2 fracture model., Methods: In paired femurs, a standardised unstable trochanteric femur fracture was induced by an oscillating saw. The fractures were stabilised by either the PCCP (Orthofix, McKinney, TX, USA) or the IT (Smith & Nephew, Memphis, TN, USA). All femurs were loaded with 300N, followed by an increase in load until failure using 300N each time (2000 cycles each, 0.5Hz). After every load step the samples were assessed visually and radiographically. We measured migration and performed a survival analysis., Results: 16 fractures were induced in 8 paired human specimens (mean age: 84 years, 61-100 years). The mean stiffness (PCCP vs. IT: 249±124N/mm vs. 273±153N/mm; p=0.737) was comparable. The IT proved superior to the PCCP with regard to the number of cycles reached before failure occurred (PCCP vs. IT: 12,691±4733 vs. 15,313±4875 cycles; p=0.023). Except for a higher axial migration of the IT at failure point (PCCP vs. IT: 1.3mm vs. 4.3mm; p=0.028) there were no differences between the intra- and extramedullary implants, not even in terms of rotational stability along the femoral neck axis. A fracture of the femoral neck caused test abortion in both implants in most cases., Conclusion: This study showed a superiority of the IT compared with the PCCP with regards to number of cycles achieved under sequential load increases for unstable trochanteric femur fractures. The stiffness was comparable. Both implants showed a high rotational stability and a support of the lateral wall., Study Type: Biomechanical study., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Musculoskeletal injuries induce systemic inflammation which often impairs lung function contributing to morbidity. IL-10 has been shown to have a beneficial effect on immune dysfunction and organ damage after different traumatic insults. We sought to investigate the effect of inhalative IL-10 administration on the systemic and pulmonary inflammatory response in a small animal model of bilateral femoral fracture., Materials and Methods: Male C57/BL6 mice (6 animals per group) were subjected to bilateral femoral fracture and intramedullary nailing followed by inhalative administration of either 50μL PBS (Fx group) or 50μg/kg recombinant mouse IL-10 dissolved in 50μL PBS (FxIL-10 group). All animals were sacrificed at 6, 24, or 72h after fracture induction. Blood samples were collected and analyzed for IL-6, IL-10, KC, and MCP-1 (CCL2) plasma concentrations by Bio-Plex Pro™ assays. Pulmonary infiltration by neutrophils was assessed by myeloperoxidase (MPO) activity (ELISA) and histological analysis of lung tissue. Pulmonary ICAM-1 expression (immunohistochemistry), and pulmonary IL-6 levels (ELISA) were determined., Results: Inhalative IL-10 administration showed a decrease in the pulmonary infiltration by neutrophils. A significant decrease in the expression of the adhesion molecule ICAM-1 after local IL-10 application was observed. In contrast, local IL-10 administration did not show a significant effect on the systemic inflammatory response., Conclusion: Our findings suggest that inhalative IL-10 administration may beneficially modulate the pulmonary microenvironment, in which IL-10 effect on the local ICAM-1 expression seems to play a central role., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Dehydroepiandrosterone (DHEA) has been shown to have immunomodulatory effects after hemorrhage and sepsis. The present study analyzes whether DHEA is also involved in the mediation of inflammatory stimuli induced by bilateral femoral shaft fracture., Methods: Male C57/BL6 mice (6 per group) were subjected to closed bilateral femoral shaft fracture with intramedullary nailing followed by administration of either 25 mg/kg/24 h DHEA diluted in saline with 0.1% ethanol or saline with 0.1% ethanol. The sham group was treated by isolated intramedullary nailing without fracture. Animals were sacrificed after 6, 24, or 72 h. Serum TNFα, IL-1β, IL-6, IL-10, MCP-1, and KC concentrations were measured by Bio-Plex ProTm analysis. Acute pulmonary inflammation was assessed by histology, pulmonary myeloperoxidase (MPO) activity, and pulmonary IL-6 concentration., Results: DHEA was associated with a decrease in the systemic inflammatory response induced by bilateral femoral fracture, especially systemic IL-6 (322.2 vs. 62.5 pg/mL; P = 0.01), IL-1β (1,422.6 vs. 754.1 pg/mL; P = 0.05), and MCP-1 (219.4 vs. 44.1 pg/mL; P >0.01) levels. No changes in pulmonary inflammation were measured., Conclusion: We conclude that DHEA may be a treatment option to reduce systemic inflammation following musculoskeletal injuries although the pulmonary inflammatory reaction was not affected.

Introduction: Open supracondylar femur fractures are rare, complex injuries which occur in polytrauma patients and are complicated by bone loss, contamination, compromised soft tissues, and poor host condition. The purpose of this study is to demonstrate a successful treatment protocol for these challenging injuries., Methods: A consecutive series of 15 open supracondylar femur fractures in 14 polytrauma patients (ages 16-75, mean 41) were treated at one Level I trauma centre by a single surgeon. Fracture patterns included seven AO/OTA Type C2 and eight Type C3 fractures. All fractures were open and classified by Gustillo/Anderson as type IIIA (10 fractures) and type IIIB (five fractures). Stage I was performed within 24h and included thorough open fracture care and early definitive fixation with a laterally based locking device and antibiotic bead placement. Stage II was performed several months later (average 3.6 months) when the soft tissue envelope had revascularized and the polytrauma patient had recovered from their other injuries. Stage II consisted of either an anterior incision or subvastus approach to the distal femur, bone grafting, BMP application, and addition of medial column support to create rigid fixation., Results: All fractures (15/15) healed uneventfully. Union was determined by absence of pain and radiographic union in 3/4 cortices. Mean time to union was 4 months. There were no deep infections and alignment was maintained (average tibiofemoral angel of 5° of valgus) although several limbs were complicated by knee stiffness., Conclusions: Healing of open supracondylar femur fractures with critical sized bone defects requires diligent surgical timing in order to optimise the host and wound bed. Thorough initial debridement and early definitive fixation halt ongoing soft tissue injury, restores length and alignment, and allow for sterilisation of the wound. After patients have recovered from their other injuries and the soft tissue sleeve has revascularized, bone grafting with BMP supplementation and medial column plating allows for rigid fixation of the femur and offers the biology these fracture patterns require for successful union without infection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The rotationally stable screw-anchor plate system (RoSA) is unique in using a novel screw-blade combination. This investigation tested the hypothesis whether RoSA is advantageous over the sliding hip screw plate system (SHS) with regard to stiffness, failure load, displacement, and migration in stable trochanteric femur fractures (OTA 31A1.1)., Methods: Thirteen femur pairs (mean age = 79 years; range, 64-92 years) received implants of either the RoSA or SHS (Koenigsee Implants, Allendorf, Germany). Beginning with 300 N and under consecutive 300 N load-increase steps (2000 cycles, 0.5 Hz) the femurs were cycled until failure. Specimens were evaluated for fragment displacement in both frontal and rotational planes and for migration. A survival analysis was carried out., Results: With regard to stiffness (526 ± 195 N/mm vs 358 ± 143 N/mm; P = 0.006) and the failure load (2838 ± 781 N vs 2262 ± 863 N; P = 0.012), the RoSA proved superior to the SHS. Furthermore, RoSA demonstrated higher rotational stability in comparison to the SHS (1800 N: 0 ± 0 degrees vs 1.1 ± 1.3 degrees; P = 0.015; failure point: 0 ± 0 degrees vs 2.3 ± 2.6 degrees; P = 0.008), measuring rotation about femoral neck axis over time. Whereas cutout occurred only in the RoSA system (n = 3; P = 0.110), the SHS underwent plastic deformation in 7 cases (n = 7; P = 0.003). In one case (7%), the insertion of the RoSA blade resulted in iatrogenic cut-through caused by a jamming of the screw and the blade., Conclusions: The fixation of stable trochanteric femur fractures with RoSA in cadavers led to greater primary stability under cyclic load, with significant advantages with regard to stiffness, failure load, and rotational stability, compared with the SHS. A detrimental effect was its migration tendency, which began at 1800 N and occurred in the cranial direction. A meticulous insertion technique was a prerequisite to avoid iatrogenic perforation of the femoral head. Our results will have to be substantiated by further biomechanical and clinical trials using an optimized RoSA system.

Objective: The aim was this study was to analyze the risk factors for reoperation after internal fixation of intertrochanteric fractures of the femur using the percutaneous compression plate (PCCP)., Design: This was a retrospective cohort study., Setting: The study was conducted at the University Hospital., Patients and Methods: Patients with intertrochanteric femur fractures who underwent internal fixation with a PCCP were included in this study. We investigated potential risk factors such as age, gender, body mass index, comorbidities of the patients (American Society of Anesthetist classification), type of fracture (AO/OTA classification), experience of the surgeons (in terms of the number of surgical procedures with the PCCP device), tip-apex distance (TAD), and operation time. The procedures were performed by 10 surgeons. Logistic regression was used to assess potential predictors for the need of reoperation., Results: Of the 96 patients with 96 intertrochanteric fractures, 8 underwent reoperation due to local complications (8.3%). The most frequent complication was complete or imminent cutting out of the upper cervical screw (N = 5; 5.2%). Five of the 8 risk factors that were associated with reoperation in the initial univariable analyses with a P value of <0.20 were retained in a multivariable logistic regression model, including, age, body mass index, TAD, experience of the surgeons, and operation time. Of these, only the factor TAD proved to be a significant predictor for reoperation (P = 0.027, odds ratio = 1.089, 95% confidence interval 1.01-1.175)., Conclusions: Our data show that the surgeon-related risk factors (number of operations, operation time, TAD) seem to be more relevant for the reoperation rate after internal fixation with the PCCP device when compared with the patient-related risk factors. This finding indicates a substantial learning curve for this technically demanding procedure., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Introduction: Bilateral femoral shaft fractures have been reported to be an independent risk factor for morbidity and mortality; however, the value of these studies is limited due to small sample sizes and the timing of these studies before the establishment of damage control orthopaedics. The objective of this study was to compare the incidence of morbidity and mortality in patients with bilateral vs. unilateral femoral shaft fractures in the era of damage control orthopaedics., Methods: Retrospective analysis of the TraumaRegister DGU from 2002 to 2005. Inclusion criteria were uni- or bilateral femoral shaft fractures and complete demographic data documentation. Univariate data analysis and logistic regression analysis were performed with SPSS., Results: Between 2002 and 2005, 776 patients with unilateral and 118 patients with bilateral femoral shaft fractures were identified. Patients with bilateral femoral shaft fractures had a significantly higher Injury Severity Score (ISS) (29.5 vs. 25.7 points), a significantly higher incidence of pulmonary (34.7% vs. 20.6%) and multiple organ failure (25.0% vs. 14.6%) as well as a significantly higher mortality rate (16.9% vs. 9.4%). In the overall patient population, early total care (ETC) was significantly more often performed in patients with unilateral femoral shaft fractures (50.9% vs. 33.6%). Logistic regression analysis revealed no significant association between bilateral femoral shaft fractures and multiple organ failure or mortality; however, bilateral femoral shaft fractures are an independent risk factor for pulmonary failure. Subgroup analysis revealed that the impact of the bilateral femoral shaft fracture was especially pronounced in patients with an ISS<25 points., Discussion: Bilateral femoral shaft fractures are an independent risk factor for pulmonary failure but not for multiple organ failure or mortality. The impact of the additional femoral shaft fracture for pulmonary failure appears to be especially pronounced in the less severely injured patients, whose injuries are often underestimated when stratified with the ISS. Patients with bilateral femoral shaft fractures have significantly more often severe abdominal injuries as well as severe blood loss which may account for the increased mortality rate. Therefore, the presence of bilateral femoral shaft fractures should be recognised as an increased risk for systemic complications., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: The long-term clinical status of surviving patients with multiple injuries has not been well described. The aim of this study was to evaluate the long-term outcome of acetabular and lower limb injuries., Methods: Patients treated at a Level I trauma center at least 10 years before participation in this study were invited for a follow-up physical examination. Six hundred thirty-seven patients were examined. Inclusion criteria are as follows: Injury Severity Score ≥16 Points;treatment in a Level I trauma center; and injuries of the lower limb: fractures of the acetabulum, proximal femur, femoral shaft,knee joint, and tibial shaft. Exclusion criteria are as follows: incomplete follow-up examination, amputations, ankle and foot fractures, and patients older than 60 years and younger than 3 years. The follow-up examination included the following parameters:range of motion, pain, limping, successful rehabilitation, and outcome scores., Results: Of 525 patients with fractures of the acetabulum and lower limb, 229 patients fulfilled the inclusion criteria. Mean age: 24.9 (range,3–60) years; Injury Severity Score: 19.66 (range, 16–43). The most frequent rates of ongoing local pain were stated by patients with fractures of the acetabulum (50%) and the proximal femur (45%). Moreover, the incidence of abnormal gait was significantly lower in patients with femoral shaft fractures when compared with the patients with fractures of the acetabulum (3.7% vs. 35%;p 0.0001), proximal femur (3.7% vs. 20%; p≤ 0.006), and tibial shaft (3.7% vs. 14.7%; p = 0.023)., Conclusions: Our results demonstrate a better long-term outcome in patients with femur shaft fractures, whereas patients with articular fractures and proximal femur fractures were associated with poorer outcomes. Fracture location is determining factor for long-term outcome, (Copyright © 2012 by Lippincott Williams & Wilkins)

Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces caspase-1 activation and promotes interleukin (IL)-1β and IL-18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, damage-associated molecular patterns, such as those released after injury, have been shown to activate the inflammasome and caspase-1 through the NOD-like receptor (NLR) NLRP3. However, the role of the inflammasome in organ injury after HS and trauma is unknown. We therefore investigated inflammatory responses and end-organ injury in wild-type (WT) and caspase-1(-/-)mice in our model of HS with bilateral femur fracture (HS/BFF). We found that caspase-1(-/-) mice had higher levels of systemic inflammatory cytokines than WT mice. This result corresponded to higher levels of liver damage, cell death and neutrophil influx in caspase-1(-/-) liver compared with WT, although there was no difference in lung damage between experimental groups. To determine if hepatoprotection also depended on NLRP3, we subjected NLRP3(-/-) mice to HS/BFF, but found inflammatory responses and liver damage in these mice was similar to WT. Hepatoprotection was also not due to caspase-1-dependent cytokines, IL-1β and IL-18. Altogether, these data suggest that caspase-1 is hepatoprotective, in part through regulation of cell death pathways in the liver after major trauma, and that caspase-1 activation after HS/BFF does not depend on NLRP3. These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF).

Background: Post-traumatic inflammatory changes have been identified as major causes of altered organ function and failure. Both hemorrhage and soft tissue damage induce these inflammatory changes. Exposure to heterologous bone in animal models has recently been shown to mimic this inflammatory response in a stable and reproducible fashion. This follow-up study tests the hypothesis that inflammatory responses are comparable between a novel trauma model ("pseudofracture", PFx) and a bilateral femur fracture (BFF) model., Materials and Methods: In C57BL/6 mice, markers for remote organ dysfunction and inflammatory responses were compared in four groups (control/sham/BFF/PFx) at the time points 2, 4, and 6 h., Results: Hepatocellular damage in BFF and PFx was highly comparable in extent and evolution, as shown by similar levels of NFkappaB activation and plasma ALT. Pulmonary inflammatory responses were also comparably elevated in both trauma models as early as 2 h after trauma as measured by myeloperoxidase activity (MPO). Muscle damage was provoked in both BFF and PFx mice over the time course, although BFF induced significantly higher AST and CK levels. IL-6 levels were also similar with early and sustained increases over time in both trauma models., Conclusions: Both BFF and PFx create similar reproducible inflammatory and remote organ responses. PFx will be a useful model to study longer term inflammatory effects that cannot be studied using BFF., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study was performed to analyze the role of hemorrhage-induced hypotension in the induction of systemic inflammation and remote organ dysfunction. Male C57/BL6 mice (6- to 10-week old and 20-30 g) were used. Animals were either subjected to pseudo-fracture [PF; standardized soft-tissue injury and injection of crushed bone, PF group: n = 9], or PF combined with hemorrhagic shock (HS + PF group: n = 6). Endpoint was 6 h. Systemic inflammation was assessed by IL-6 and IL-10 levels. Myeloperoxidase (MPO) and NF-κB activity in the lung and liver tissue were obtained to assess remote organ damage. The increases of systemic cytokines are similar for animals subjected to PF and PF + HS (IL-6: 189 pg/ml ± 32.5 vs. 160 pg/ml ± 5.3; IL-10: 60.3 pg/ml ± 15.8 vs. 88 pg/ml ± 32.4). Furthermore, the features (ALT; NF-κB) of liver injury are equally elevated in mice subjected to PF (76.9 U/L ± 4.5) and HS + PF (80 U/L ± 5.5). Lung injury, addressed by MPO activity was more severe in group HS + PF (2.95 ng/ml ± 0.32) than in group PF (1.21 ng/ml ± 0.2). Both PF and additional HS cause a systemic inflammatory response. In addition, hemorrhage seems to be associated with remote affects on the lung., (Copyright © 2010 Orthopaedic Research Society.)

Background: High mobility group box-1 (HMGB-1), a recently identified inflammatory cytokine, is implicated in the pathogenesis of several inflammatory, infective and neoplastic processes. Patterns of expression following blunt trauma have not been adequately reported in the literature. This study aimed to quantify the serum concentrations of HMGB-1 following blunt trauma, and assess its relationship with the more established interleukin 6 (IL-6)., Patients and Methods: 20 patients with median injury severity score 17 (range 9-36) sustaining closed diaphyseal fractures of the femur treated by intramedullary nailing were included in the study. Serum concentrations of HMGB-1 and IL-6 were measured at several time points during their treatment., Results: A strong correlation was observed between admission and day 1 post-op concentrations of IL-6 and both the injury severity score (ISS) and the requirement for intensive care unit treatment. Serum concentrations of HMGB-1 did not demonstrate such a correlation. Around day 3 when IL-6 concentrations begin to fall, serum HMGB-1 concentrations were observed to increase., Conclusions: IL-6 concentration measured early after admission is again shown to be strongly associated with overall injury severity and requirement for intensive care unit treatment. In contrast, HMGB-1 appears to be a late inflammatory mediator with levels becoming elevated once serum concentrations of IL-6 begin to fall. However, we were unable to demonstrate any relationship with injury severity or requirement for ICU care at any stage. These preliminary findings may form the basis for future research in this area., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Post-traumatic complications commonly seen on intensive care units include sepsis and associated disorders, which are accompanied by alterations in inflammatory cytokine expression patterns and in activation of neutrophils. Hyperglycaemia, often occurring after trauma and sepsis, is a further risk factor for morbidity and mortality among critically ill people. Clinical investigations have suggested that strict glycaemic control by insulin titration reduces overall mortality. This study aimed to further elucidate the pathophysiological and immunomodulative actions of insulin. Femoral fracture was induced in a murine model, followed by 1h of haemorrhage. Two days after the first hit, sepsis was induced by caecal ligation and puncture (CLP). In control animals, laparotomy only was performed. Insulin in two different concentrations (10IU or 20IU) or vehicle was administered daily. Insulin therapy was associated with improvement of clinical parameters, slightly improved survival rates and, in lungs and liver, fewer infiltrating neutrophils and reduced IL-6 and IL-10 mRNA expression. These results suggested that, in this animal model, insulin had a direct anti-inflammatory effect that was independent of modulation of blood glucose levels.

Successful intramedullary nailing of difficult femoral fractures is predicated on achieving and maintaining reduction before reaming and implant insertion. Closed and percutaneous strategies are emphasized which preserve fracture biology and encourage primary union. However, open techniques are sometimes necessary to avoid postoperative deformity.

Remote and systemic inflammatory responses after long bone fractures have been well described, but the mechanisms underlying these changes remain unexplained. We hypothesized that bone components locally exposed to injured soft tissue are capable of inducing a systemic inflammatory response associated with acute lung injury, and that this inflammatory cascade requires Toll-like receptor 4 (TLR-4) signaling. Accordingly, male C3H/HeOuJ (TLR-4-competent) and C3H/HeJ (TLR-4-mutant) mice were injected with various bone components (bone marrow cells, bone marrow supernatant, and bone suspension, respectively) in bilaterally injured thigh muscles and euthanized after 6 h. Serum TNF-alpha, IL-6, and IL-10 levels, and pulmonary myeloperoxidase activity was measured using specific enzyme-linked immunosorbent assay kits. Pulmonary permeability changes were assessed with bronchoalveolar lavage. Local exposure of bone components to injured soft tissue induced systemic inflammation and acute lung injury in TLR-4-competent, but not in TLR-4-mutant, animals. These findings suggest that bone components contribute to systemic inflammation and acute lung injury after long bone fractures via TLR-4 signaling and support the notion of a central role for TLR-4 in sensing tissue damage.

In the treatment of polytrauma patients, multiple studies have shown how the timing and the type of the initial surgery of long bone fractures influence the incidence of systemic complications. Database analyses documented that unduly long surgical procedures undertaken early after trauma increase the risk of acute respiratory distress syndrome (ARDS), especially when femoral shaft fractures are stabilized. Animal research and prospective clinical studies also support the fact that the type of stabilization of a femoral shaft fracture may influence the systemic response to trauma. Reamed intramedullary reaming and nailing for a femoral shaft fracture is associated with an increased risk of pulmonary fat embolization from the medullary canal. This can result in pulmonary compromise if certain cofactors are also present. Modified reamers have been developed to reduce this side effect. The mediating effects are immunologic changes, varying according to the magnitude of the surgical procedure. Pro-inflammatory markers (e.g., Interleukins) may be used to assess the inflammatory response to injury as well as the magnitude of surgery and the systemic impact induced by surgery. Serum levels of such markers can be used clinically to tailor the amount of surgery that is performed to the clinical condition of the patient. The potentially negative impact of excessive surgery in high-risk patients can be avoided by using a new grading system for the assessment of the clinical status of the injured patient. Most recently, a large prospective randomized multicenter study has documented that this grading system is effective for identifying these borderline patients, and that in the borderline patient a staged surgical approach, such as temporary femoral stabilization with an external fixator, reduces the incidence of systemic complications. This work has changed the surgical management of multiply injured patients toward an approach that is tailored to the clinical condition of the patient, as indicated by well-defined clinical parameters as well as objective measurements of serum cytokine levels., ((c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Recently, increasing emphasis is being placed upon assessment of the inflammatory status of the patient. Serum inflammatory cytokines, particularly IL-6, have been used as an adjunct to this assessment. Another method uses a combination of simple laboratory and clinical data to provide an assessment of the patient's current level of systemic inflammation, the SIRS. The aim of this study was to investigate, in a group of adult trauma patients, the relationship between the interleukin-6 (IL-6) concentration, the systemic inflammatory response score (SIRS) and outcome., Methods: In patients with femoral shaft fracture, serum IL-6 levels and clinical parameters were recorded prospectively on admission and on days 1, 3, 5, and 7. Clinical course, the SIRS score and complications were documented. Nonparametric tests were used to assess relationships between variables and receiver operator characteristic (ROC) curves were used to examine their predictive values. Significance was assumed at the p < 0.05 level., Results: Forty-eight patients were included in the final analysis, with a median new injury severity score (NISS) of 31.5 (range, 9-75). The presence of a "SIRS state" detected early (day 1 and 3) positively correlated with the IL-6 measurement from the same period (p < 0.001). ROC curve analysis revealed elevated IL-6 to be significantly diagnostic of a SIRS state (p < 0.001) at all times. Early (days 0 and 1), an IL-6 value above 200 pg/dL diagnosed a SIRS state with an 83% sensitivity and a 75% specificity (area under ROC curve 0.76, p < 0.0001). Both a SIRS state and an IL-6 > 300 pg/mL was associated with a significantly increased risk of complication (pneumonia, MOF, death). Both systems were found to be significantly diagnostic of these complications using ROC curve analysis., Conclusions: The IL-6 concentration and SIRS score are useful adjuncts to clinical evaluation of the injured patient. In the early phase, they are closely correlated with the NISS and each other. A cutoff value of 200 pg/dL was shown to be significantly diagnostic of a SIRS state. Significant correlations between adverse events and both the IL-6 level and SIRS state are demonstrated.

Objectives: The storage of preformed cytokines in soft tissue as well as the immunocompetence of adipocytes has been reported. We hypothesized that fracture-associated soft tissue injury plays a pivotal role in the induction of systemic inflammation and remote organ dysfunction after fracture., Materials and Methods: Male C57/BL6 mice sustained either severe soft tissue injury to both thighs (STI), bilateral femur fracture with minimal soft tissue injury (Fx), or the combination of both (Fx+STI) and were euthanized 6 hours after injury. Serum cytokine concentrations were measured using the Luminex multiplexing platform, and serum ALT levels were measured with the Vitros 950 Chemistry System. Hepatic myeloperoxidase activity, a marker for polymorphonuclear cell infiltration, and hepatic IL-6 levels were determined using ELISA kits. Hepatic permeability changes were assessed via measurement of edema formation., Results: STI as well as Fx both induced significantly elevated serum IL-6 and L-10 levels as compared with Sham animals (P < 0.05). Further, serum IL-6 and IL-10 levels were significantly higher after STI as compared with Fx (P < 0.05). Serum KC and MCP-1 levels were significantly elevated after STI but not after Fx (P < 0.05). STI as well as Fx resulted in significantly increased serum ALT levels and hepatic polymorphonuclear cell infiltration. The combination of both injuries resulted in further increased systemic inflammatory mediators as well as marked liver inflammation and dysfunction represented by significantly elevated serum ALT levels, hepatic polymorphonuclear cell infiltration, hepatic IL-6 concentrations, and hepatic edema formation as compared with Sham animals (P < 0.05)., Conclusions: Although STI and Fx both induced a systemic inflammatory response, this was more pronounced after STI. However, the combination of both injuries (Fx+STI) was required to induce marked liver dysfunction. Our data indicate that fracture-associated soft tissue injury is a major contributor to the systemic inflammatory response after bilateral femur fracture. This should be recognized especially in multiply injured patients, who are susceptible to systemic inflammation with remote organ dysfunction.

The interaction between the complex pattern of cytokine release and remote organ dysfunction after trauma is incompletely understood. The aim of this study was to investigate the pattern of cytokine release and its association with the evolution of remote organ dysfunction after bilateral femur fracture. Male C57/BL6 mice were euthanized at six different time points (1-6 h) after bilateral femur fracture. Serum cytokine concentrations were measured with the Luminex multiplexing platform, and serum alanine aminotransferase levels were measured with the Vitros 950 Chemistry System. Hepatic and pulmonary myeloperoxidase activity was determined with an enzyme-linked immunosorbent assay kit. Permeability changes of the lung were assessed via bronchoalveolar lavage, and those of the liver via assessment of edema formation. Serum TNF-alpha was unchanged in the fracture group throughout the experiment. Serum IL-6 and keratinocyte levels peaked at 5 h postinjury, whereas IL-10 levels peaked at 2 and 6 h. A brief IL-1beta peak was observed at 3 h after fracture. Hepatic and pulmonary myeloperoxidase activity was significantly elevated within 1 h after trauma. Hepatic permeability was significantly increased within 2 h, and pulmonary permeability was significantly increased within 6 h after injury. Serum alanine aminotransferase levels peaked at 3 and 5 h postinjury. The pattern of serum IL-6, keratinocyte, IL-10, and IL-1beta release was dynamic, whereas no significant elevations in TNF-alpha were observed. The early hepatic and pulmonary infiltration of polymorphonuclear cells occurred in the absence of significantly elevated serum cytokine levels, suggesting that either early minor changes with an unbalance in inflammatory mediators or locally produced cytokines may initiate this process.

We asked whether coagulopathy worsened during femoral intramedullary nailing in the presence of lung contusion and hemorrhagic shock and whether reamed or unreamed nailing influenced these results. In 30 Merino sheep, we induced hemorrhagic shock and/or standardized lung contusion followed by femoral nailing. Six groups of five each were assigned as follows: thoracotomy control groups treated with reamed or unreamed nailing, lung contusion groups treated with reamed or unreamed nailing, and shock and lung contusion groups treated with reamed or unreamed nailing. After lung contusion alone (first hit), the serum values of antithrombin III, factor V, and fibrinogen were considerably altered after reamed and unreamed femoral nailing (second hit) 4 hours postoperatively. In the lung contusion and shock groups, we found a substantial reduction for all serum coagulative parameters between baseline and fixation after reamed and unreamed nailing. The magnitude of the first hit is increased if hemorrhagic shock is added to a lung contusion determined by hemostatic reactions. The magnitude of the injury appears equally important as the type of subsequent surgery and should be considered in planning for fracture fixation in patients at high risk for complications.

Objectives: The timing of definitive fixation for major fractures in patients with multiple injuries is controversial. To address this gap, we randomized patients with blunt multiple injuries to either initial definitive stabilization of the femur shaft with an intramedullary nail or an external fixateur with later conversion to an intermedullary nail and documented the postoperative clinical condition., Methods: Multiply injured patients with femoral shaft fractures were randomized to either initial (<24 hours) intramedullary femoral nailing or external fixation and later conversion to an intramedullary nail. Inclusion: New Injury Severity Score >16 points, or 3 fractures and Abbreviated Injury Scale score > or =2 points and another injury (Abbreviated Injury Scale score > or =2 points), and age 18 to 65 years. Exclusion: patients in unstable or critical condition. Patients were graded as stable or borderline (increased risk of systemic complications)., Outcomes: : Incidence of acute lung injuries., Results: Ten European Centers, 165 patients, mean age 32.7 +/- 11.7 years. Group intramedullary nailing, n = 94; group external fixation, n = 71. Preoperatively, 121 patients were stable and 44 patients were in borderline condition. After adjusting for differences in initial injury severity between the 2 treatment groups, the odds of developing acute lung injury were 6.69 times greater in borderline patients who underwent intramedullary nailing in comparison with those who underwent external fixation, P < 0.05., Conclusion: Intramedullary stabilization of the femur fracture can affect the outcome in patients with multiple injuries. In stable patients, primary femoral nailing is associated with shorter ventilation time. In borderline patients, it is associated with a higher incidence of lung dysfunctions when compared with those who underwent external fixation and later conversion to intermedullary nail. Therefore, the preoperative condition should be when deciding on the type of initial fixation to perform in patients with multiple blunt injuries.

Few data are available in the literature regarding fat embolism in cases of bilateral femoral and pathological femoral fractures. The incidence of bilateral femoral fractures ranges from 2-9.5% of the total number of patients with femoral fractures, and they usually occur in high energy trauma and multi-trauma patients. Although injury severity scores tend to underestimate the severity of these injuries, fat embolism seems to occur in increased frequency ranging from 4.8-7.5%. Intramedullary nailing, which is the preferred surgical treatment, triggers a systemic inflammatory response that poses an additional burden to pulmonary function. In addition, the femur is a common site of metastatic bone disease. The treatment of impending and actual pathological fractures is complicated by increased rates of lung damage due to various factors. Fat embolism during treatment--mainly with intramedullary nails--generally seems to range from 0-10%.

Intramedullary nailing is the preferred treatment method for stabilizing femoral diaphyseal fractures. Despite its superior biomechanical advantages over other implants, its use, particularly in selected groups of patients, has been questioned because of the possible harmful systemic effects of intramedullary reaming. The increase in intramedullary canal pressure during intramedullary nailing can result in intravasation of bone marrow and fat into the venous blood system. The subsequent consequences can be fat embolism syndrome (FES), adult respiratory distress syndrome (ARDS), and multiple organ failure. The lung seems to be the primary target for fat embolization and for the mediated effects primed by inflammatory reactions. In laboratory studies, both reamed and unreamed intramedullary nailing has been shown to alter selected pulmonary variables. Although transient, this effect appears to be more prominent with reamed than unreamed techniques. Additional studies are required to determine whether a subgroup of trauma patients is adversely affected by intramedullary reaming, thus necessitating other fixation techniques.

Objectives: To determine infection rates after damage control orthopaedics (DCO) and primary intramedullary nailing (1' IMN) in multiply injured patients with femoral shaft fracture., Design: Retrospective case analysis., Setting: Level I trauma center., Patients: All patients with New Injury Severity Score (NISS) >20 and femoral shaft fracture (AO 32-) treated in our unit between 1996 and 2002., Intervention: Damage control orthopaedics, defined as primary external fixation of the femoral shaft fracture and subsequent conversion to an intramedullary nail, or primary IMN., Main Outcome Measurements: Rates of infection classified as contamination (positive swabs with no clinical change), superficial, deep (requiring surgery), and removal of hardware (those requiring removal of femoral instrumentation or amputation)., Results: A total of 173 patients with 192 fractures were included; 111 fractures were treated by DCO and 81 by primary IMN. Mean follow-up was 19.1 months [median, 16.7, range, 1 (patient died)-67 months]. DCO patients had a significantly higher NISS and more grade III open fractures (P<0.001). IMN procedures took a median of 150 minutes compared with 85 minutes for DCO (P<0.0001). Although wound contamination (including contaminated pin sites) was more common in the DCO group (P<0.05), the risk of infectious complications was equivalent (P=0.86). Contamination was significantly more likely when conversion to IMN occurred after more than 14 days (P<0.05); however, this did not lead to more clinically relevant infections. Logistic regression analysis showed that although a DCO approach was not associated with infection, delay before conversion in the DCO group might be [P=0.002 for contamination and removal of hardware, P=0.065 for serious infection (deep or worse), not significant for other infection outcomes]. Grade III open injury also was significantly associated with serious infection in all patients (P<0.05)., Conclusions: Infection rates after DCO for femoral fractures are comparable to those after primary IMN. We see no contraindication to the implementation of a damage control approach for severely injured patients with femoral shaft fracture where appropriate. Pin-site contamination was more common where the fixator was in place for more than 2 weeks. For patients treated by using a DCO approach, conversion to definitive fixation should be performed in a timely fashion.

Intramedullary nailing is the treatment of choice for patients with femoral shaft fractures. However, there is an ongoing debate in multiple trauma patients with associated lung contusion when primary or secondary definitive stabilisation of the long bone fracture should be performed, as nailing is thought to play an important role in the pathogenesis of adult respiratory distress syndrome (ARDS). In a standardised sheep model, this study aimed to quantify the development of acute pulmonary endothelial changes, to assess the activation of polymorphonuclear leucocytes (PMNL) and to observe the effects on the coagulation system associated with the reamed nailing procedure. Furthermore, the effect of coexisting lung contusion in an experimental model was evaluated. The animals were randomly assigned to one of four different groups (6 animals/group). In control groups, only a sham operation (thoracotomy) was performed, whereas in study groups, lung contusion was induced prior to femoral stabilisation either by external fixation or reamed femoral nailing. Using bronchoalveolar lavage (BAL) pulmonary permeability changes were quantified and PMNL activation was assessed by chemiluminescence. Additionally PMNL diapedesis and interstitial lung oedema were determined by histological analysis. All animals were sacrificed 4 h after the start of the femoral instrumentation. Without an associated lung injury, instrumentation of the femoral canal with the reamed nailing technique induced a transient increase in pulmonary permeability. In the face of an induced lung contusion, reamed femoral nailing resulted in significant increases in PMNL activation, pulmonary permeability and interstitial lung oedema, compared with external fixation. Without pulmonary contusion, reaming of the femoral canal was associated with a transient increase in pulmonary permeability. This was exacerbated in the presence of lung contusion along with increased PMNL activation. External fixation did not provoke similar changes. The findings of this study support the view that reaming of the femoral canal should be avoided in polytrauma patients with severe chest trauma as it could act as an additional stimulus for adverse outcome. Temporary external fixation appears to be a safe method for fracture stabilisation until inflammatory and coagulatory disturbances after trauma have been normalized.

Background: Recently, there has been a move away from early total care in patients with severe, multiple injuries to damage control orthopedics (DCO) in an attempt to limit the physiologic insult resulting from operative treatment after trauma. For femoral shaft fracture, this entails initial external fixation and subsequent conversion to an intramedullary nail (IMN). We sought to quantify the inflammatory response to initial surgery and conversion and link this to subsequent organ dysfunction and complications., Methods: Patients with femoral shaft fracture and a New Injury Severity Score of 20 or more were included. Data were retrospectively collected for 4 days at admission and at exchange procedure (external fixation to intramedullary nail), and the Systemic Inflammatory Response Syndrome (SIRS) score and the Marshall multiorgan dysfunction score were calculated., Results: One hundred seventy-four patients met the inclusion criteria. The DCO group had significantly more severe injuries (New Injury Severity Score of 25.4 vs. 36.2, p < 0.0001) and significantly more head and thoracic injuries (both p < 0.0001). The mean SIRS score was significantly higher in the IMN group, from 12 hours until 72 hours postoperatively (p < 0.05). The mean peak postoperative SIRS score was significantly higher in the IMN group than in the DCO group, at the primary procedure and at conversion, as was the time with an SIRS score greater than 1. At conversion in the DCO group, the preoperative SIRS score correlated with magnitude and duration of elevation in the SIRS and multiorgan dysfunction scores (p < 0.0001)., Conclusion: It would appear that despite more severe injuries in the DCO group, patients had a smaller, shorter postoperative SIRS and did not suffer significantly more pronounced organ failure than the IMN group. DCO patients undergoing conversion while their SIRS score was raised suffered the most pronounced subsequent inflammatory response and organ failure. According to these data, DCO treatment was associated with a lesser systemic inflammatory response than early total care for femur fractures. The inflammatory status of the patient may be a useful adjunct in clinical decision making regarding the timing of conversion to an intramedullary device.

The main feature of osteogenesis imperfecta is an excessive fragility and deformability of the bones owing to reduced mass and bone quality. This leads to angular deformity and frequent fractures. These fractures usually heal rapidly, and conservative treatment is the norm. In displaced and unstable fractures, elastic intramedullary nailing is a treatment option. We report a case of a 3-year-old child with osteogenesis imperfecta type I who suffered an undisplaced femoral shaft fracture in the presence of a preexisting 32 degrees femoral antecurvation. This deformity greatly increases the risk of a refracture due to the pathological induction of stress risers. Therefore, fracture treatment by unreamed elastic intramedullary nailing was combined with simultaneous correction osteotomy, resulting in anatomic alignment and uncomplicated fracture healing. The single-stage surgical stabilization performed allowed rapid mobilization along with a decreased likelihood of refracture.