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.

To better understand how patient-specific alterations in the synovial fluid composition and its viscosity affect cartilage friction of samples with mild and advanced signs of degeneration. Synovial fluid, mild and advanced degenerated cartilage samples were collected from twelve patients undergoing knee replacement surgery. Friction tests were performed under simulated gait conditions, with each sample lubricated with its patient-specific synovial fluid. Cartilage degeneration was assessed macroscopically and microscopically. Synovial fluid samples were analyzed for viscosity and biochemical composition and the Spearman method was used to assess relationships between all parameters. Friction of mildly degenerated cartilage samples negatively correlated with the proteoglycan 4 concentration in the synovial fluid (µ_endStance: ρ = -0.9, 95% CI [-1.0, -0.8], p < 0.01), µ_endSwing: ρ = -0.7, 95% CI [-0.9, -0.3], p = 0.01). For advanced degenerated samples, significant positive correlations were found between friction during swing phase of gait (µ_endSwing) and synovial fluid viscosity values (η^{0.01(25 °C)}: ρ = -0.7, 95% CI [-0.9, -0.2], p = 0.01; η^{1000(25 °C)}: ρ = -0.8, 95% CI [-0.9, -0.4], p = < 0.01). The impact of SF alterations on AC friction depends on the tissue's degeneration severity. These findings might provide valuable information when selecting appropriate patient populations and timing of treatment options, particularly tribosupplementation approaches, which address the knee joint's tribology.

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.

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