Predicting Genitourinary Injuries in Polytraumatized Patients-Development of the GUIPP Scoring System.

BACKGROUND: The genitourinary system is not as commonly affected as many other organ systems in severely injured patients. Although a delayed and missed diagnosis of genitourinary injuries (GUIs) can severely compromise long-term outcomes, these injuries are frequently overlooked. Therefore, we present a scoring system designed to assist emergency physicians in diagnosing GUIs in severely injured patients. METHODS: The data were obtained from the TraumaRegister DGU® from the years 2015-2021. All severely injured patients (ISS ≥ 16) ≥16 years of age and treated in Germany, Austria, or Switzerland were included in this study. We excluded patients who were transferred out early (48 h), and all patients with isolated traumatic brain injury. After the univariate analysis of the relevant predictive factors, we developed a scoring system using a binary logistic regression model. RESULTS: A total of 70,467 patients were included in this study, of which 4760 (6.8%) sustained a GUI. Male patients (OR: 1.31, 95% CI [1.22, 1.41]) injured in motorcycle accidents (OR: 1.70, 95% CI [1.55, 1.87]), who were under 60 years of age (OR: 1.59, 95% CI [1.49, 1.71]) and had sustained injuries in multiple body regions (OR: 6.63, 95% CI [5.88, 7.47]), and suffered severe pelvic girdle injuries (OR: 2.58, 95% CI [2.29, 2.91]) had the highest odds of sustaining a GUI. With these predictive factors combined, a novel scoring system, the GUIPP score, was developed. It showed good validity, with an AUC of 0.722 (95% CI [0.71; 0.73]). CONCLUSION: Predicting GUI in severely injured patients remains a challenge for treating physicians, but is extremely important to prevent poor outcomes for affected patients. The GUIPP score can be utilized to initiate appropriate diagnostic steps early on in order to reduce the delayed and missed diagnosis of GUI, with scores ≥ 9 points making GUIs very likely.

Treatment strategies for complex ankle fractures-current developments summarized in a narrative review.

Background and Objective: Ankle fractures occur frequently in patients throughout all ages. Due to the many pitfalls associated with their treatment, complex ankle and especially tibial pilon fractures remain a challenge for surgeons. As there is still need for improvement in treating complex ankle fractures and treatment options are steadily increasing this review aims to summarize current practice and aims to highlight current developments by reviewing the literature. Methods: We conducted a thorough search of PubMed database in December 2022 to identify relevant articles on complex ankle and tibial pilon fractures. Articles in English and German were included in this study. Key Contents and Findings: Complication rates, especially wound infection are still high, emphasizing the need for careful preoperative planning. Soft tissue management is crucial to reduce complication rates and will often dictate the treatment plan utilized. Open reduction and internal fixation (ORIF) remains the treatment of choice. Nevertheless, in select cases alternative methods such as external fixation, tibiotalocalcaneal nailing or conservative treatment need to be considered as well. Furthermore, additional treatment options such as arthroscopically assisted surgery might help to improve functional outcome after complex ankle fractures. The incidence of complex ankle fractures in geriatric patients keeps rising with our aging population. This group of patients demands particular care and further high-quality studies are needed to warrant best results. Conclusions: However, more randomized controlled trials are need in order to enhance evidence of newly developed treatment options.

The outcome of severely injured patients following traumatic brain injury is affected by gender-A retrospective, multicenter, matched-pair analysis utilizing data of the TraumaRegister DGU®.

Introduction: Traumatic brain injury (TBI) causes a major health-concern globally. Gender-dependent differences in mortality outcome after TBI have been controversially discussed. Materials and methods: We conducted a retrospective, multicenter, matched-pair analysis using data collected by the TraumaRegister DGU® of the German Trauma Society between 2009 and 2020. All patients after severe trauma with the leading injury of TBI (AIS ≥ 3), above 18 years of age were included. Thereby, 42,034 cases were identified. We used 12 different matching criteria to ensure highly accurate matching and were able to match 11,738 pairs of one female and one male patient. Results: Average age at injury was 67.5 ± 19.6 years in women and 66.7 ± 19.1 years in men. Mean Injury Severity Score (ISS) was 21.3 ± 8.1 in women and 21.6 ± 8.2 in men. While women were more likely to die within the first week after trauma, the mortality was significantly higher in men overall (30.8 vs. 29.2%, p < 0.002). Women were less likely to suffer from multi organ failure (MOF) (27.5 vs. 33.0%) or sepsis (4.5 vs. 7.1%). When comparing younger (≤ 45-years) and older (> 45 years) patients, overall mortality was lower in men (13.1% men vs. 13.4% women) in the younger age group, but in the older group mortality was lower in women (33.8% men vs. 31.8% women). Discussion: Gender-specific differences in the clinical outcome of severely injured patients with leading TBI could be detected. While women are overall characterized by an advantage in survival, this feature is not equally reproducible in premenopausal women. Therefore, the exact pathophysiological reasons for the described survival advantages of women will have to be explored in further prospective clinical studies.

Positive Predictive Factors for Urogenital Injuries in Severely Injured Patients with Pelvic and Spinal Fractures: Introducing the UPPS Scoring System.

Background and Objectives: Although urogenital injuries are common in severely injured patients, their diagnosis is often delayed. Predicting genitourinary injuries (GUI), especially in the immediate stages post injury, remains a challenge. This study aims to evaluate and determine positive predictive factors for the presence of GUI in polytrauma patients. Subsequently, these factors shall be used to develop an easy-to-use scoring system, deployable directly in the emergency setting. Materials and Methods: This study evaluates all severely injured patients with an Injury Severity Score (ISS) ≥ 16 admitted to the emergency departments of two German university hospitals between 2016 and 2020. These patients were retrospectively scanned for injuries of the thoracic and/or lumbar spine and/or the pelvic girdle. Demographic data was analyzed alongside trauma mechanism, type of injuries, mortality, length of hospital stays, surgeries, laboratory results, and urological treatment. Subgroup analysis was performed to compare patients with and without GUIs using t-tests. Conducting a binary logistic regression model, the significant factors were combined to create a scoring system, which was further analyzed for accuracy. Results: In total, 413 patients with an average ISS of 33.8 ± 15.0 were identified, and 47 patients (11.4%) sustained urogenital injuries with an average Abbreviated Injury Scale (AIS) score of 2.3 ± 1.1 (range: 1−5). The severity of the pelvic girdle injury correlated with the presence of urogenital injuries (p = 0.002), while there was no correlation with spinal injuries. Moreover, most GUIs resulted from motorcycle accidents (p < 0.001) and 87.2% of these patients were male. Patients with GUI were significantly more likely to show macrohematuria (p < 0.001) on admission and were more severely injured overall (ISS > 34). There was no significant difference in the length of intensive care unit (ICU) stay, the days until discharge, or death rates. Conclusions: Factors or circumstances which reliably predict the presence of GUI were found to include the male sex, a motorcycle accident, high severity of pelvic girdle fractures, macrohematuria on admission to the emergency department, and an ISS > 34. With these findings, we introduce the 'Urotrauma in Polytrauma patients with Pelvic and/or Spinal injuries' (UPPS) score for easier prediction of GUI in the emergency setting.

Traumatic Brain Injury Induces a Differential Immune Response in Polytrauma Patients; Prospective Analysis of CD69 Expression on T Cells and Platelet Expansion.

BACKGROUND: Accidents and injuries are the leading causes of mortality in young people. CD4+ regulatory T cells (CD4+ Tregs), Th17 cells and platelets could be identified as key players in post-traumatic immunological dysfunction, which is a common cause of late mortality in trauma patients. The mechanisms of activation of these cell types and their interaction remain mostly unclear. Since CD69 is not only a leukocyte marker but has also immunoregulatory functions, we postulate a role for CD69 after trauma. The present study investigates the expression of CD69 on CD4+ Tregs and Th17 cells, as well as the posttraumatic expansion of platelets and hemostatic function. Subgroup analysis was performed to assess the differences between polytrauma patients with and without severe traumatic brain injury (TBI). METHODS: In this non-interventional prospective clinical trial, we analyzed sequential blood samples over a period of 10 days from 30 patients after multiple traumas with an ISS ≥ 16. Platelet function was assessed by rotational thromboelastometry (ROTEM analysis). CD4+ Tregs and Th17 cells were stained with surface markers and analyzed by flow cytometry. RESULTS: We were able to demonstrate a significantly increased expression of CD69 on CD4+ Tregs after trauma. Subgroup analysis revealed that the absence of severe TBI is associated with a significantly higher expression of CD69 on CD4+ Tregs and on Th17 cells. Platelets expanded and showed signs of dysfunction, while an overall tendency of posttraumatic hypercoagulation was detected. CONCLUSIONS: Our results support the concept of injury-specific immune responses and add to a further understanding of the complex pathophysiology of post-traumatic immune dysfunction.

The Clinical Impact of Platelets on Post-Injury Serum Creatinine Concentration in Multiple Trauma Patients: A Retrospective Cohort Study.

Background and objective: Platelets contribute to the immunological response after multiple trauma. To determine the clinical impact, this study analyzes the association between platelets and creatinine concentration as an indicator of kidney function in polytraumatized patients. Methods: We investigated all patients presenting an Injury Severity Score (ISS) ≥16 for a 2-year period at our trauma center. Platelet counts and creatinine concentrations were analyzed, and correlation analysis was performed within 10 days after multiple trauma. Results: 83 patients with a median ISS of 22 were included. Platelet count was decreased on day 3 (p ≤ 0.001) and increased on day 10 (p ≤ 0.001). Platelet count was elevated on day 10 in younger patients and diminished in severely injured patients (ISS ≥35) on day 1 (p = 0.012) and day 3 (p = 0.011). Creatinine concentration was decreased on day 1 (p = 0.003) and day 10 (p ≤ 0.001) in female patients. Age (p = 0.01), male sex (p = 0.004), and injury severity (p = 0.014) were identified as factors for increased creatinine concentration on day 1, whereas platelets (p = 0.046) were associated with decreased creatinine concentrations on day 5 after multiple trauma. Conclusions: Kinetics of platelet count and creatinine concentration are influenced by age, gender, and trauma severity. There was no clear correlation between platelet counts and creatinine concentration. However, platelets seem to have a modulating effect on creatinine concentrations in the vulnerable phase after trauma.

Correlation between Platelet Count and Lung Dysfunction in Multiple Trauma Patients-A Retrospective Cohort Analysis.

(1) Background: Current findings emphasize the potential contribution of platelets to the immunological response after severe trauma. As clinical relevance remains unclear, this study aims to analyze the correlation between platelets and lung dysfunction in severely injured patients. (2) Methods: We retrospectively enrolled all multiple trauma patients presenting to our level 1 trauma center from 2015 to 2016 with an Injury-Severity Score (ISS) ≥ 16. Apart from demographic data, platelet counts and PaO2/FiO2 as an approximate indicator for lung physiology were analyzed and correlated on subsequent days after admission. (3) Results: 83 patients with a median ISS of 22 (IQR 18-36) were included. Compared to day 1, platelet counts were decreased on day 3 (p ≤ 0.001). Platelet counts were significantly lower on day 3 in patients with an ISS ≥ 35 (p = 0.011). There were no differences regarding PaO2/FiO2 index. Correlation analysis revealed a positive link between increased platelet counts and PaO2/FiO2 index on day 1 only in severely injured patients (p = 0.007). (4) Conclusions: This work supports the concept of platelets modulating the posttraumatic immune response by affecting lung dysfunction in the early phase after multiple trauma in dependence of injury severity. Our findings contribute to the understanding of the impact of platelets on systemic processes in multiple trauma patients.

Clinical and Radiological Outcome of Vancouver B2 Fracture Treated With Open Reduction and Internal Fixation. A Multicenter Cohort Analysis.

OBJECTIVES: To determine whether open reduction and internal fixation (ORIF) of periprosthetic Vancouver B2 fractures can lead to successful fracture healing in selected patients, when attention is given to the surgical exposure and the creation of a balanced extramedullary construct. DESIGN: Retrospective. SETTING: Two Level-1 trauma centers in Germany and United Kingdom. METHODS: Patients with a B2 fracture receiving solely ORIF using a polyaxial locking plate were included for analysis. Patients with other fracture types, or treated with other methods, or with follow-up less than 12 months were excluded. Clinical characteristics, including the Charlson index, the American Society for Anesthesiologists score, and their preinjury functional levels, were recorded. Main outcome measures were 1-year mortality, revision rate, and radiological healing according to the Beals-Tower criteria. RESULTS: A total of 32 patients (mean age ,79 ± 12 years) were enrolled. Six patients died within the first year (1-year mortality: 19%), and 5 were unavailable for follow-up studies. The remaining 21 patients had a mean follow-up of 30 months. Of 21, 20 had an excellent/good result using the criteria of Beals-Tower. One patient required revision surgery due to loosening and secondary subsidence of the stem. CONCLUSION: ORIF can be offered to selected patients suffering from B2 fractures, especially if their functional demand is limited, and perioperative risk high for revision arthroplasty. In this challenging cohort of patients, ORIF was a safe and effective therapeutic option. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

[Retropharyngeal tendinitis : Rare differential diagnosis of acute neck pain]. / Retropharyngeale Tendinitis : Seltene Differenzialdiagnose bei akuten Nackenschmerzen.

Atraumatic neck pain is a frequent reason for patients to attend the emergency department (ED). It remains a challenge for the treating physician to rule out possible life-threatening causes, such as a retropharyngeal abscess, meningitis or septic spondylodiscitis. Herein, we report the rare case of a patient suffering from retropharyngeal tendinitis. This rare cause of atraumatic neck pain is characterized by a significant decrease in the range of motion of the cervical spine, elevated infection parameters and pathognomonic MRI findings. In addition to presenting the rare case of retropharyngeal tendinitis, we also review selected previous case reports and thereby not only raise awareness for this rare disease but also suggest the best practice for treatment.

Platelets differentially modulate CD4+ Treg activation via GPIIa/IIIb-, fibrinogen-, and PAR4-dependent pathways.

CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.

The posttraumatic response of CD4+ regulatory T cells is modulated by direct cell-cell contact via CD40L- and P-selectin-dependent pathways.

CD4+ FoxP3+ regulatory T cells (CD4+ Tregs) are important for the posttraumatic anti-inflammatory host response. As described previously, platelets are able to modulate CD4+ Treg activity in a reciprocally activating interaction following injury. The underlying mechanisms of the posttraumatic interaction between platelets and CD4+ Tregs remain unclear. We investigated the potential influence of CD40L and P-selectin, molecules known to be involved in direct cell contact of these cell types. In a murine burn injury model, the potential interaction pathways were addressed using CD40L- and P-selectin-deficient mice. Draining lymph nodes were harvested following trauma (1 h) and following a sham procedure. Early rapid activation of CD4+ Tregs was assessed by phospho-flow cytometry (signaling molecules (p)PKC-δ and (p)ZAP-70). Platelet function was analyzed performing rotational thromboelastometry (ROTEM). We hypothesized that disruption of the direct cell-cell contact via CD40L and P-selectin would affect posttraumatic activation of CD4+ Tregs and influence the hemostatic function of platelets. Indeed, while injury induced early activation of CD4+ Tregs in wild-type mice (ZAP-70: p = 0.13, pZAP-70: p < 0.05, PKC-δ: p < 0.05, pPKC-δ: p < 0.05), disruption of CD40L-dependent interaction (ZAP-70: p = 0.57, pZAP-70: p = 0.68, PKC-δ: p = 0.68, pPKC-δ: p = 0.9) or P-selectin-dependent interaction (ZAP-70: p = 0.78, pZAP-70: p = 0.58, PKC-δ: p = 0.81, pPKC-δ: p = 0.73) resulted in reduced posttraumatic activation. Furthermore, hemostatic function was impaired towards hypocoagulability in either deficiency. Our results suggest that the posttraumatic activation of CD4+ Tregs and hemostatic function of platelets are affected by direct cell-cell-signaling via CD40L and P-selectin.

The potential of adipokines in identifying multiple trauma patients at risk of developing multiple organ dysfunction syndrome.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) and the consecutive multiple organ failure (MOF) are severe and dreaded complications with a high mortality in multiple trauma patients. The aim of this study was to investigate the potential of the adipokines leptin, resistin, interleukin-17A and interleukin-33 as possible biomarkers in the early posttraumatic inflammatory response and for identifying severely traumatized patients at risk of developing MODS. METHODS: In total, 14 multiple trauma patients with an injury severity score (ISS) ≥ 16 as well as a control group of 14 non-multiple trauma patients were included in this study and blood samples were taken at the time points 0, 6, 24, 48 and 72 h after admission. For the trauma patients, the SIRS and Denver MOF score were determined daily. The quantitative measurement of the plasma concentrations of the adipokines was performed using ELISA. RESULTS: In the statistical analysis, the multiple trauma patients showed statistically significant higher plasma concentrations of leptin, resistin, IL-17A and IL-33 compared to the control group. In addition, there was a statistically significant positive correlation between the concentrations of resistin, IL-17A and IL-33 and the corresponding SIRS scores and between the concentrations of resistin, IL-17A and IL-33 and the corresponding Denver MOF scores. Finally, ROC curve analysis revealed that the adipokines leptin and IL-17A are suitable diagnostic markers for the discrimination between multiple trauma patients with and without MOF. CONCLUSIONS: Leptin and IL-17A could be suitable diagnostic markers to identify severely injured patients with a developing SIRS and MOF earlier, to adjust surgical therapy planning and intensive care.

Potential Targets to Mitigate Trauma- or Sepsis-Induced Immune Suppression.

In sepsis and trauma, pathogens and injured tissue provoke a systemic inflammatory reaction which can lead to overwhelming inflammation. Concurrent with the innate hyperinflammatory response is adaptive immune suppression that can become chronic. A current key issue today is that patients who undergo intensive medical care after sepsis or trauma have a high mortality rate after being discharged. This high mortality is thought to be associated with persistent immunosuppression. Knowledge about the pathophysiology leading to this state remains fragmented. Immunosuppressive cytokines play an essential role in mediating and upholding immunosuppression in these patients. Specifically, the cytokines Interleukin-10 (IL-10), Transforming Growth Factor-ß (TGF-ß) and Thymic stromal lymphopoietin (TSLP) are reported to have potent immunosuppressive capacities. Here, we review their ability to suppress inflammation, their dynamics in sepsis and trauma and what drives the pathologic release of these cytokines. They do exert paradoxical effects under certain conditions, which makes it necessary to evaluate their functions in the context of dynamic changes post-sepsis and trauma. Several drugs modulating their functions are currently in clinical trials in the treatment of other pathologies. We provide an overview of the current literature on the effects of IL-10, TGF-ß and TSLP in sepsis and trauma and suggest therapeutic approaches for their modulation.

Outcome after polyaxial locking plate osteosynthesis in proximal tibia fractures: a prospective clinical trial.

BACKGROUND: The aim of this study was to evaluate the clinical and/or radiologic outcome using different polyaxial locking plates for the treatment of proximal tibia fractures, the Non-Contact-Briding plate (NCB-PT®) by Zimmer or the Variable Angle Locking Compression Plate (VA-LCP®) by Synthes. METHODS: This study enrolled 28 patients with proximal tibia fractures (AO/ OTA 41 B-C) and indication for locking plate osteosynthesis. All patients were treated with a polyaxial locking plate system. Depending on the fracture morphology, patients were either treated with a NCB-PT® or VA-LCP®. The implant was chosen according to the surgeon's experience and preference, in case of a higher degree of comminution the tendency was observed to use the NCB-PT® plate. After a time interval of 12 months postoperative we conducted clinical (e.g. range of motion, the Rasmussen score) and radiological (e.g. primary/secondary loss of reduction) follow-ups. RESULTS: Patients provided with the NCB-PT® (9 patients) showed longer operation time, use of longer implants, longer interval from injury to surgery and lower clinical scores after the 12 months follow-up compared with the VA-LCP® group (19 patients). Interestingly, the results showed no significant differences regarding the clinical and radiologic outcome. CONCLUSIONS: The small number of patients as well as the heterogeneity of fractures constitute a limitation of this study. Nevertheless, the differentiated use of implants is associated with comparable clinical and radiological outcomes. This trial emphasizes the need for further prospective randomised trials with higher patient numbers. TRIAL REGISTRATION: Retrospectively registered 21.12.2020. Registration number NCT04680247 .

[Distal femoral fractures]. / Distale Femurfrakturen.

With a prevalence of approximately 0.4%, distal femoral fractures are a rare entity. Nevertheless, due to the high mortality rates, which are comparable to proximal femoral fractures, these fractures are highly important. The clinical symptoms are often quite striking. In combination with preoperative computed tomography (CT) and if necessary, supplemented by CT angiography, the morphological situation can be assessed and the decision making facilitated. There are several different treatment options and the appropriate one should be selected for each individual case. The use of external fixation of the complete knee joint in the sense of damage control surgery, is useful. For definitive treatment retrograde intramedullary nailing and locking plates with angle stable screws are the main options. Modern angle stable and anatomically preformed implants enable surgical treatment using minimally invasive approaches to protect the soft tissues, with a better overall outcome.

Scald Injury-Induced T Cell Dysfunction Can Be Mitigated by Gr1+ Cell Depletion and Blockage of CD47/CD172a Signaling.

Infection is a common and severe complication of burn injury: Sepsis accounts for 47% of postburn mortality. Burn-induced T cell suppression likely contributes to the increased infection susceptibility in burn patients. However, little is known about the kinetics of T cell dysfunction after burn and its underlying mechanisms. In this study, we show in a murine scald injury model that T cell activation of both CD4+ and CD8+ T cells as well as T cell cytokine production is suppressed acutely and persistently for at least 11 days after burn injury. Purified T cells from scald-injured mice exhibit normal T cell functions, indicating an extrinsically mediated defect. We further show that T cell dysfunction after burn appears to be cell-to-cell contact dependent and can be ameliorated by depletion of myeloid-derived suppressor cells. These cells expand after burn injury, particularly a subset expressing the checkpoint inhibitor CD172a, and infiltrate germinal centers. Expression of CD172a appears to be driven by ingestion of immature reticulocytes. Immature reticulocytes are drastically increased in the spleen of scald mice and may contribute to immunosuppression through more direct mechanisms as well. Overall, our study newly identifies two cell populations, myeloid-derived suppressor cells and immature reticulocytes, as well as the CD47/CD172a-signaling pathways as mediators of T cell suppressors after burn and thus opens up new research opportunities in the search for new therapies to combat increased infection susceptibility and the associated morbidity and mortality in burn victims.

Treatment of fracture-related infection of the lower extremity with antibiotic-eluting ceramic bone substitutes: case series of 35 patients and literature review.

INTRODUCTION: The current treatment concepts of fracture-related infection (FRI) [Consensus Conference (Anti-Infection Task Force (AITF)) on the definition of acute or chronic osteomyelitis (cOM)] are associated with unsolved challenges and problems, underlining the need for ongoing medical research. METHOD: Literature review of treatments for FRI and description of own cases. RESULTS: We could include eight papers with 394 patients reporting treatments and outcome in FRI. The infection was resolved in 92.9% (mean) of all treatments. The mean follow-up was 25 months with a persistent non-union in 7% of the patients. We diagnosed 35 (19f/16m; 56.4 ± 18.6 years) patients with bone infections anatomically allocated to the proximal and distal femur (12×), the pelvis (2×), distal tibia (3×), tibial diaphysis (11×), the ankle joint (4×) and calcaneus (3×). These 35 patients were treated (1) with surgical debridement; (2) with antibiotic-eluting ceramic bone substitutes; (3) bone stabilization (including nail fixation, arthrodesis nails, plates, or external ring fixation), (4) optionally negative pressure wound therapy (NPWT) and (5) optionally soft tissue closure with local or free flaps. The mean follow-up time was 14.9 ± 10.6 months (min/max: 2/40 month). The overall recurrence rate is low (8.5%, 3/35). Prolonged wound secretion was observed in six cases (17.1%, 6/35). The overall number of surgeries was a median of 2.5. CONCLUSION: The results in the literature and in our case series are explicitly promising regarding the treatment of posttraumatic fracture-related infection.

Trauma Induces Interleukin-17A Expression on Th17 Cells and CD4+ Regulatory T Cells as Well as Platelet Dysfunction.

Background: The organism's immune response to trauma is distinctively controlled, its dysregulation leading to severe post-traumatic complications. Platelets, CD4+ regulatory T cells (CD4+ Tregs) and T helper 17 (Th17) cells have been identified to participate in the post-traumatic immune response. Unfortunately, little is known about their exact role and potential interdependency in humans. Aims of this clinical trial were to phenotype the human immune response following injury and to identify risk factors rendering the host more susceptible to trauma induced injury. Methods: This non-interventional prospective clinical trial enrolled patients following multiple trauma, follow up was conducted for 10 days. Peripheral blood CD4+ Tregs and Th17 cells were analyzed using flow cytometry to determine Interleukin 17A (IL-17A) expression. Hemostasis and platelet function were assessed with rotational thromboelastometry (ROTEM®). Subgroup analysis was conducted for the factors gender, age, and trauma severity. Results and Conclusion: This is the first clinical trial to phenotype the immune response following trauma, focusing on platelets, and the adaptive immune response. We discovered a novel increased IL-17A expression on Th17 cells and on CD4+ Tregs following trauma and describe the kinetics of the immune response. The IL-17A response on CD4+ Tregs challenges the ascribed role of CD4+ Tregs to be solely counter inflammatory in this setting. Furthermore, despite a rising number of platelets, ROTEM analysis shows post-traumatic platelet dysfunction. Subgroup analysis revealed gender, age, and trauma severity as influencing factors for several of the analyzed parameters.

The posttraumatic activation of CD4+ T regulatory cells is modulated by TNFR2- and TLR4-dependent pathways, but not by IL-10.

Platelets modulate the immune system following injury by interacting with CD4+ T regulatory cells (CD4+ Tregs). The underlying mechanisms remain unsolved. We hypothesize paracrine interactions via Tumor necrosis factor-alpha (TNFα)-, Toll like receptor-4 (TLR4)-, and Interleukin-10 (IL-10). In the murine burn injury model, CD4+ Treg activation pathways were selectively addressed using TNFR2-, TLR4- and IL-10-deficient mice. The CD4+ Treg signalling molecule PKC-θ was analyzed using phospho-flow cytometry to detect rapid cell activation. Thromboelastometry (ROTEM®) was used to assess platelet activation. Injury induced significant early activation of CD4+ Tregs, disruption of TNFR2 and TLR4 activation pathways resulted in lower activity. The disruption of IL-10 crosstalk had no significant impact. Selective disruption of paracrine interactions is associated with changes in posttraumatic hemostasis parameters. TNFR2- and TLR4-dependent pathways modulate the activation of CD4+ Tregs following trauma. In contrast, we did not observe a role of IL-10 in the posttraumatic activation of CD4+ Tregs. ONE SENTENCE SUMMARY: TLR4- and TNFR2-dependent mechanisms, but not IL-10-dependent pathways, modulate the anti-inflammatory response of CD4+ Tregs following trauma.