Purpose: In polytrauma patients, injuries involving the extremities are frequently seen. Treatment concepts vary from early definitive care to temporary fixation and delayed definite stabilization. This analysis therefor aims to illuminate the impact of timing for operative stabilization of extremity fractures on outcome factors in adult polytrauma patients. Methods: We searched PubMed and Cochrane CENTRAL to identify studies from inception of each database to 14 September 2022. We included systematic reviews and RCTs comparing immediate versus delayed operative fracture stabilization and early definite care versus primary external fixation in adult polytrauma patients. Results: Five randomized controlled trials were included, with a total of 335 patients. The analysis found no statistically significant difference in overall mortality or improvement in ICU admission between early (< 24 h) and late fracture stabilization. Comparing femoral nailing and external fixation, findings showed that femoral nailing reduce ICU length of stay and duration of invasive mechanical ventilation. Conclusion: The results indicate that immediate surgical treatment by nailing is superior to delayed treatment or a staged surgical approach in stable polytrauma patients with long-bone fractures. As there is a lack of clear evidence regarding the optimal timing for definitive operative stabilization of extremity fractures in polytrauma patients, further high-quality studies are essential to enhance the certainty of evidence and provide more conclusive treatment algorithms.

Background: Infections are common complications in critical care, particularly in patients with severe multiple trauma, who are at elevated risk due to trauma-induced immunological changes. The heterogeneity of trauma patients complicates their initial assessment, yet timely recognition of patients at risk is crucial for guiding therapy and preventive measures. This study evaluated risk factors for sepsis and pneumonia in multiple trauma patients, incorporating a novel parameter: cell-derived extracellular particles (EPs) in plasma. Methods: Severely injured multiple trauma patients aged 18-80 years with an injury severity score (ISS) ≥16 were included. Patient- and injury-related parameters were assessed at the injury site, admission and during clinical course. EP counts in plasma were meaasured at admission using intravesicular staining. Key variables from the first 24 hours were analyzed to develop an early risk assessment score. Results: Among 124 patients, 16 developed pneumonia, and 29 developed sepsis. Pneumonia was associated with significantly lower Glasgow Coma Scale scores and intubation rates at the injury site and elevated Sequential Organ Failure Assessment (SOFA) scores at admission. Sepsis correlated with higher ISS, increased 24-hour transfusion rates, lower leukocyte counts on day one, and decreased levels of small EPs in plasma at admission. These variables formed the weighted Sepsis as Trauma Outcome Prediction (STOP) score. A STOP score > 3 had a positive predictive value of 59.4% within 24-hours upon admission to the emergency department for subsequent sepsis development. Conclusion: The risk of pneumonia in severely injured trauma patients was linked to impaired consciousness and preexisting organ-dysfunctions at admission. High-risk sepsis patients could be identified on day one following trauma using the STOP score, which incorporates ISS, 24-hours transfusion rates, leukocyte counts at day one, and small EP rates at admission. This novel scoring system could facilitate targeted therapeutic and preventive strategies for distinguishing high-risk populations.

Aims: Polytraumatized patients with severe limb injuries often develop complications, which are influenced by the surgical treatment strategy. For the initial fracture stabilization, Early Total Care (ETC) and Damage Control Orthopedics (DCO) are competing concepts, with the treatment choice depending on the patient’s condition. Clear guidance factors remain lacking. Our study aimed to compare the effects of ETC and DCO strategies on fracture healing and functional gait behaviour in a rat multiple-trauma model.Methods: A standardized rat multiple-trauma model was established, which included haemorrhagic shock, blunt chest trauma, and a femur fracture with subsequent reduction and fixation by group-specific operative strategies. Adult Sprague-Dawley male rats (n = 45) were randomly allocated to three groups: Sham (n = 9), ETC (primary intramedullary nailing (IN); n = 18), and DCO-IN (external fixation with conversion to IN at day 6 after the trauma; n = 18). Postoperative gait changes at different timepoints were analyzed using the CatWalk system. At seven, 21, and 42 days, the animals were euthanized to assess bone formation of the femur fracture histologically and via micro-CT. Biomechanical stability was assessed by a three-point bending test.Results: Fixation conversion surgery in the DCO-IN group decreased callus formation, resulting in delayed fracture healing with reduced callus quality and poorer biomechanical properties compared to the ETC group. The DCO-IN group also exhibited poorer weightbearing and locomotor-function rehabilitation compared to the ETC group, consistent with the impaired fracture healing process.Conclusion: These results demonstrate that conversion of the fixation method in the DCO strategy delays the callus formation process up to six weeks after trauma, potentially contributing to delayed rehabilitation and higher risk of nonunion in multiple-trauma patients. DCO should be limited to patients with contraindications for ETC, underlining the need for clear identification factors.Cite this article: Bone Joint Res 2025;14(7):619–632.

Bone fracture activates the immune system and induces inflammation crucial for fracture healing but may also affect trauma-distant organs like the liver. Acute alcohol intoxication (AAI) dysregulates immune responses and affects organ damage post-trauma. However, the bone–liver axis and alcohol’s role in this process remain poorly understood. This study explores liver inflammation and damage following fracture, with and without prior AAI. Twenty-four male C57BL/6J mice were randomly assigned to four groups (n = 6) and received either NaCl (control) or 35% ethanol via gavage. Mice underwent femur osteotomy with external fixation or sham surgery. After 24 h, liver damage was assessed using hematoxylin–eosin and activated caspase-3 staining. Liver inflammation was evaluated through CXCL1 and polymorphonuclear leukocyte (PMNL) immunostaining, cytokine gene and protein expression analyses, and immune cell profiling in the liver via flow cytometry. Western blotting assessed NF-κB and Wnt signaling. Neither fracture alone nor with AAI caused significant liver damage. However, fracture significantly increased PMNL infiltration and altered monocyte populations, effects that were amplified by AAI. The hepatic neutrophil-to-monocyte ratio significantly decreased after fracture and was absent in the fracture AAI group. CXCL1 increased post-fracture, while MCP-1 and IL-10 decreased significantly, with AAI further significantly amplifying these changes. Wnt1 and Wnt3a levels increased significantly after fracture and were further strongly elevated by AAI. AAI completely abolished fracture-induced significant β-catenin reduction and significantly increased its phosphorylation, effects that potentially involve an AAI-induced β-catenin stabilization as well as its increased degradation. NF-κB activation was significantly decreased, while A20 expression significantly increased after fracture and AAI. Fracture influences the inflammatory liver response and signaling pathways, effects which were further modulated by AAI.

Grundlage für das Forschungsprojekt ist die Frage nach der optimalen Versorgungsstrategie in der Frakturbehandlung langer Röhrenknochen polytraumatisierter Patienten. Article published online: 10 November 2025 © 2025. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Fractures of long bones such as the femur are a common and serious health concern in the elderly, triggering immune responses essential for healing but also affecting remote organs like the liver. With age, the risk of fractures and immune imbalance increases, raising the likelihood of organ damage, infections, and mortality. To better understand age-dependent hepatic responses to bone injury, this study investigates early immune responses in the liver following femoral osteotomy, used here as a reproducible model of fracture. In a mouse model, young (17–26 weeks old) and aged (64–72 weeks old) male C57BL/6J mice received a femoral osteotomy with external fixation (Fx) or a corresponding sham procedure. After 24 h, inflammation, apoptosis, tissue damage, and immune responsiveness of the liver were analyzed. Aged sham animals exhibited a higher inflammatory state in sham-operated animals (neutrophil infiltration, tumor necrosis factor (TNF), interleukin (IL)-1b, chemokine (C-X-C motif) ligand 1 (CXCL1)), without corresponding increases in caspase-3-positive cells, activation of c-Jun N-terminal kinase (JNK), expression of sirtuin (SIRT) 1 or 3, or the receptor for advanced glycation end products (RAGE). Fx did not increase liver damage in young mice but showed a trend toward greater damage in aged mice. Fx significantly increased hepatic neutrophil infiltration and CXCL1 as well as TNF concentrations in both age groups. Aged mice showed weaker activation of pro- and anti-inflammatory signaling pathways after osteotomy, with reduced RAGE expression, JNK activation, and less pronounced induction of SIRT1 and SIRT3. In summary, femur osteotomy induced liver inflammation in both young and aged animals; however, older animals exhibit higher apoptosis and a superimposed inflammatory response on top of already elevated baseline inflammation in sham conditions. Further, they did not adequately activate key regulators like RAGE, SIRT1, and JNK, which coordinate inflammation and repair. Observed dysregulations may underlie the increased vulnerability to post-traumatic complications in the elderly. Understanding these age-related deficits is essential to improving therapeutic strategies. Graphical abstract