Early major fracture care in polytrauma-priorities in the context of concomitant injuries: A Delphi consensus process and systematic review.

BACKGROUND: The timing of major fracture care in polytrauma patients has a relevant impact on outcomes. Yet, standardized treatment strategies with respect to concomitant injuries are rare. This study aims to provide expert recommendations regarding the timing of major fracture care in the presence of concomitant injuries to the brain, thorax, abdomen, spine/spinal cord, and vasculature, as well as multiple fractures. METHODS: This study used the Delphi method supported by a systematic review. The review was conducted in the Medline and EMBASE databases to identify relevant literature on the timing of fracture care for patients with the aforementioned injury patterns. Then, consensus statements were developed by 17 international multidisciplinary experts based on the available evidence. The statements underwent repeated adjustments in online- and in-person meetings and were finally voted on. An agreement of ≥75% was set as the threshold for consensus. The level of evidence of the identified publications was rated using the GRADE approach. RESULTS: A total of 12,476 publications were identified, and 73 were included. The majority of publications recommended early surgery (47/73). The threshold for early surgery was set within 24 hours in 45 publications. The expert panel developed 20 consensus statements and consensus >90% was achieved for all, with 15 reaching 100%. These statements define conditions and exceptions for early definitive fracture care in the presence of traumatic brain injury (n = 5), abdominal trauma (n = 4), thoracic trauma (n = 3), multiple extremity fractures (n = 3), spinal (cord) injuries (n = 3), and vascular injuries (n = 2). CONCLUSION: A total of 20 statements were developed on the timing of fracture fixation in patients with associated injuries. All statements agree that major fracture care should be initiated within 24 hours of admission and completed within that timeframe unless the clinical status or severe associated issues prevent the patient from going to the operating room. LEVEL OF EVIDENCE: Delphi-Consensus/Systematic Review; Level IV.

Redisplacement rate after bony hip reconstructive surgery in nonambulatory patients with cerebral palsy: a systematic review and meta-analysis.

Purpose: Up to 90% of nonambulatory patients with cerebral palsy (CP) experience hip displacement during their lifetime. Reconstructive surgery is recommended. Redisplacement rate is an outcome parameter. Methods: In a systematic literature review (MEDLINE, Embase and CENTRAL databases) until January 2023 we searched for reports with redisplacement rates after bony hip reconstructive surgery in nonambulatory patients. Quantitative data synthesis, subgroup analysis and meta-regression with moderators were carried out. Results: The pooled mean redisplacement rate was 16% (95% CI: 12-21%) with a prediction interval of 3-51% (Q: 149; df: 32; P < 0.001; I2: 78%; τ2: 0.67 and τ: 0.82) in 28 studies (1540 hips). Varus derotation osteotomy (VDRO) alone showed a higher redisplacement rate than VDRO + pelvic osteotomy (30% vs 12%, P < .0001). Mean age in the VDRO-alone subgroup was 7.1 years and in the combined group 9.5 years (P = .004). In meta-regression, lower redisplacement rates were observed with higher preoperative migration index (MI) (correlation coefficient: -0.0279; P = .0137), where comprehensive surgery was performed. Variance in true effects are explained by type of bone surgery (57%), preoperative MI (11%), age (5%) and MI for definition of failure (20%). No significant reduction in the redisplacement rate could be observed over the mid-years of studies (1977-2015). Conclusion: Our pooled data support the more extensive surgical approach in patients with high preoperative MI and emphasize the superiority of combined surgery. Studies should report a coordinated set of parameters and outcome classifications according to internationally accepted gradings to reduce redisplacement in future.

Lactate dehydrogenase can be used for differential diagnosis to identify patients with severe polytrauma with or without chest injury-A retrospective study.

BACKGROUND: Chest injury is an important factor regarding the prognosis of patients with polytrauma (PT), and the rapid diagnosis of chest injury is of utmost importance. Therefore, the current study focused on patients' physiology and laboratory findings to quickly identify PT patients with chest injury. METHOD: Data on 64 PT patients treated at a trauma center level I between June 2020 and August 2021 were retrospectively collected. The patients were divided into a PT group without chest injury (Group A) and a PT group including chest injury (Group B). The relationship between chest injury and the patients' baseline characteristics and biochemical markers was analyzed. RESULTS: Heart rate, respiration rate, Sequential Organ Failure Assessment (SOFA) score, glutamate oxaloacetate aminotransferase (GOT), glutamate pyruvate transaminase (GPT), creatine kinase MB (CK-MB), leucocytes, hemoglobin (Hb), platelets, urine output, lactate, and lactate dehydrogenase (LDH) in groups A and B exhibited statistically significant differences at certain time points. Multifactorial analysis showed that blood LDH levels at admission were associated with chest injury (P = 0.039, CI 95% 1.001, 1.022). CONCLUSION: LDH may be a promising indicator for screening for the presence of chest injury in patients with severe polytrauma.

Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography.

BACKGROUND: This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides. METHODS: 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area. RESULTS: BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group. CONCLUSION: Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.

Conservative treatment versus surgical reconstruction for ACL rupture: A systemic review.

Background: Anterior cruciate ligament (ACL) rupture is a prevalent sports injury with rising rates attributed to increased population participation in sports activities. ACL rupture can lead to severe knee complications including cartilage damage, torn meniscus, and osteoarthritis. Current treatment options include conservative measures and surgical interventions. However, debates persist regarding the optimal approach. Purpose: This analysis intended to compare the function, knee stability, and incidence rate of secondary surgery between conservative and surgical treatments in ACL rupture patients. Methods: A systematic search was performed via Embase, Ovid Medline, PubMed, Cochrane Library, Web of Science, and Google Scholar for reporting outcomes of conservative and surgical treatments after ACL rupture. The outcomes included patient-reported outcome measures (PROMs), knee stability, the need for secondary meniscal surgery, delayed ACL reconstruction surgery, and revision ACL reconstruction surgery. Outcomes were analyzed using mean differences or odd ratios (OR) with 95 % CIs. Results: 11 studies were included with 1516 patients. For PROMs, our evidence indicated no differences in KOOS Pain, KOOS Symptoms, KOOS Sport/Rec, KOOS ADL, and KOOS QOL. (all p > 0.05). for knee stability, pivot shift (OR, 0.14; p < 0.001), Lachman test (OR, 0.06; p < 0.001), and tibia translation (p < 0.001) were evaluated, and the available evidence favored surgical treatment over conservative treatment. For the incidence rate of any secondary surgery after the first diagnosis, the surgical group showed a lower rate of meniscal surgery with statistical significance (OR, 0.37; p < 0.001). The average rate of revision ACL reconstruction is 5.80 %, while the rate of delayed ACL reconstruction after conservative treatment is 18.51 %. Conclusion: Currently, there is insufficient empirical evidence to advocate a systematic surgical reconstruction for any patient who tore his ACL. This review found no differences in function outcomes between conservative and surgical treatments. Regarding knee stability and secondary meniscal surgery, the results prefer the surgical treatments. The occurrence rate of revision and delayed ACL reconstruction are non-negligible factors that must be fully understood by both surgeons and patients before choosing a suitable treatment.

Time to surgical stabilization of rib fractures: does it impact outcomes?

Objectives: Rib fractures are common, morbid, and potentially lethal. Intuitively, if interventions to mitigate downstream effects of rib fractures can be implemented early, likelihood of developing these complications should be reduced. Surgical stabilization of rib fractures (SSRF) is one therapeutic intervention shown to be useful for mitigating complications of these common fractures. Our aim was to investigate for association between time to SSRF and complications among patients with isolated rib fractures undergoing SSRF. Methods: The 2016-2019 American College of Surgeons Trauma Quality Improvement Program (TQIP) database was queried to identify patient >18 years with isolated thoracic injury undergoing SSRF. Patients were divided into three groups: SSRF ≤2 days, SSRF >2 days but <3 days, and SSRF >3 days. Poisson regression, and adjusting for demographic and clinical covariates, was used to evaluate the association between time to SSRF and the primary endpoint, in-hospital complications. Quantile regression was used to evaluate the effects of time to SSRF on the secondary endpoints, hospital and intensive care unit (ICU) length of stay (LOS). Results: Out of 2185 patients, 918 (42%) underwent SSRF <2 days, 432 (20%) underwent SSRF >2 days but <3 days, and 835 (38%) underwent SSRF >3 days. Hemothorax was more common among patients undergoing SSRF >3 days, otherwise all demographic and clinical variables were similar between groups. After adjusting for potential confounding, SSRF >3 days was associated with a threefold risk of composite in-hospital complications (adjusted incidence rate ratio: 3.15, 95% CI 1.76 to 5.62; p<0.001), a 4-day increase in total hospital LOS (change in median LOS: 4.09; 95% CI 3.69 to 4.49, p<0.001), and a nearly 2-day increase in median ICU LOS (change in median LOS: 1.70; 95% CI 1.32 to 2.08, p<0.001), compared with SSRF ≤2 days. Conclusion: Among patients undergoing SSRF in TQIP, earlier SSRF is associated with less in-hospital complications and shorter hospital stays. Standardization of time to SSRF as a trauma quality metric should be considered. Level of evidence: Level II, retrospective.

Orthopedic Frailty Score and adverse outcomes in patients with surgically managed isolated traumatic spinal injury.

Background: With an aging global population, the prevalence of frailty in patients with traumatic spinal injury (TSI) is steadily increasing. The aim of the current study is to evaluate the utility of the Orthopedic Frailty Score (OFS) in assessing the risk of adverse outcomes in patients with isolated TSI requiring surgery, with the hypothesis that frailer patients suffer from a disproportionately increased risk of these outcomes. Methods: The Trauma Quality Improvement Program database was queried for all adult patients (18 years or older) who suffered an isolated TSI due to blunt force trauma, between 2013 and 2019, and underwent spine surgery. Patients were categorized as non-frail (OFS 0), pre-frail (OFS 1), or frail (OFS ≥2). The association between the OFS and in-hospital mortality, complications, and failure to rescue (FTR) was determined using Poisson regression models, adjusted for potential confounding. Results: A total of 43 768 patients were included in the current investigation. After adjusting for confounding, frailty was associated with a more than doubling in the risk of in-hospital mortality (adjusted incidence rate ratio (IRR) (95% CI): 2.53 (2.04 to 3.12), p<0.001), a 25% higher overall risk of complications (adjusted IRR (95% CI): 1.25 (1.02 to 1.54), p=0.032), a doubling in the risk of FTR (adjusted IRR (95% CI): 2.00 (1.39 to 2.90), p<0.001), and a 10% increase in the risk of intensive care unit admission (adjusted IRR (95% CI): 1.10 (1.04 to 1.15), p=0.004), compared with non-frail patients. Conclusion: The findings indicate that the OFS could be an effective method for identifying frail patients with TSIs who are at a disproportionate risk of adverse events. Level of evidence: Level III.

Development of a Sampling and Storage Protocol of Extracellular Vesicles (EVs)-Establishment of the First EV Biobank for Polytraumatized Patients.

In the last few years, several studies have emphasized the existence of injury-specific EV "barcodes" that could have significant importance for the precise diagnosis of different organ injuries in polytrauma patients. To expand the research potential of the NTF (network trauma research) biobank of polytraumatized patients, the NTF research group decided to further establish a biobank for EVs. However, until now, the protocols for the isolation, characterization, and storage of EVs for biobank purposes have not been conceptualized. Plasma and serum samples from healthy volunteers (n = 10) were used. Three EV isolation methods of high relevance for the work with patients' samples (ultracentrifugation, size exclusion chromatography, and immune magnetic bead-based isolation) were compared. EVs were quantified using nanoparticle tracking analysis, EV proteins, and miRNAs. The effects of different isolation solutions; the long storage of samples (up to 3 years); and the sensibility of EVs to serial freezing-thawing cycles and different storage conditions (RT, 4/-20/-80 °C, dry ice) were evaluated. The SEC isolation method was considered the most suitable for EV biobanking. We did not find any difference in the quantity of EVs between serum and plasma-EVs. The importance of particle-free PBS as an isolation solution was confirmed. Plasma that has been frozen for a long time can also be used as a source of EVs. Serial freezing-thawing cycles were found to affect the mean size of EVs but not their amount. The storage of EV samples for 5 days on dry ice significantly reduced the EV protein concentration.

Electrical Stimulation of Mesenchymal Stem Cells as a Tool for Proliferation and Differentiation in Cartilage Tissue Engineering: A Scaffold-Based Approach.

Electrical stimulation (ES) is a widely discussed topic in the field of cartilage tissue engineering due to its ability to induce chondrogenic differentiation (CD) and proliferation. It shows promise as a potential therapy for osteoarthritis (OA). In this study, we stimulated mesenchymal stem cells (MSCs) incorporated into collagen hydrogel (CH) scaffolds, consisting of approximately 500,000 cells each, for 1 h per day using a 2.5 Vpp (119 mV/mm) 8 Hz sinusoidal signal. We compared the cell count, morphology, and CD on days 4, 7, and 10. The results indicate proliferation, with an increase ranging from 1.86 to 9.5-fold, particularly on day 7. Additionally, signs of CD were observed. The stimulated cells had a higher volume, while the stimulated scaffolds showed shrinkage. In the ES groups, up-regulation of collagen type 2 and aggrecan was found. In contrast, SOX9 was up-regulated in the control group, and MMP13 showed a strong up-regulation, indicating cell stress. In addition to lower stress levels, the control groups also showed a more spheroidic shape. Overall, scaffold-based ES has the potential to achieve multiple outcomes. However, finding the appropriate stimulation pattern is crucial for achieving successful chondrogenesis.

[Diagnostics of acute compartment syndrome : Current gold standard and the state of science of noninvasive assessment methods]. / Diagnostik des akuten Kompartmentsyndroms : Aktueller Goldstandard und Stand der Wissenschaft nichtinvasiver Messmethoden.

Acute compartment syndrome (ACS) is defined by a disorder of the microcirculation due to a persistent pathological pressure increase within a muscle compartment. The ischemia of the tissue leads to an initially reversible functional impairment and finally irreversible damage of the musculature, nerves and other structures. Based on the understanding of the pathophysiology, the current diagnostic concepts and treatment using the so-called dermatofasciotomy of the affected muscle compartments can be derived. In addition to the suspicion of a possible ACS based on the medical history of the patient, the findings of the clinical examination are decisive. This review article gives a summary of all the essential aspects of the diagnostics. In clinically uncertain cases and for monitoring, an objectification of the findings using instrument-based techniques is increasingly required. Nowadays, invasive needle pressure measurement is available; however, due to limited reliability, specificity and sensitivity, these measurements only represent an aid to decision guidance supporting or advising against the indications for dermatofasciotomy. The increasing demands on making a certain diagnosis and justification of a surgical intervention from a legal point of view, substantiate the numerous scientific efforts to develop noninvasive instrument-based diagnostics. These methods are based either on detection of increasing intracompartmental pressure or decreasing perfusion pressure and microcirculation. The various measurement principles are summarized in a lucid form.

Fracture haematoma proteomics.

Aims: The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods: A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results: The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion: The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma.

How Framing Bias Impacts Preferences for Innovation in Bone Tissue Engineering.

It is currently unknown if surgeons and biomaterial scientists &or tissue engineers (BS&orTE) process and evaluate information in similar or different (un)biased ways. For the gold standard of surgery to move "from bench to bedside," there must naturally be synergies between these key stakeholders' perspectives. Because only a small number of biomaterials and tissue engineering innovations have been translated into the clinic today, we hypothesized that this lack of translation is rooted in the psychology of surgeons and BS&orTE. Presently, both clinicians and researchers doubt the compatibility of surgery and research in their daily routines. This has led to the use of a metaphorical expression "squaring of the circle," which implies an unsolvable challenge. As bone tissue engineering belongs to the top five research areas in tissue engineering, we choose the field of bone defect treatment options for our bias study. Our study uses an online survey instrument for data capture such as incorporating a behavioral economics cognitive framing experiment methodology. Our study sample consisted of surgeons (n = 208) and BS&orTE (n = 59). And we used a convenience sampling method, with participants (conference attendants) being approached both in person and through email between October 22, 2022, and March 13, 2023. We find no distinct positive-negative cognitive framing differences by occupation. That is, any framing bias present in this surgical decision-making setting does not appear to differ significantly between surgeon and BS&orTE specialization. When we explored within-group differences by frames, we see statistically significant (p < 0.05) results for surgeons in the positive frame ranking autologous bone graft transplantation lower than surgeons in the negative frame. Furthermore, surgeons in the positive frame rank Ilizarov bone transport method higher than surgeons in the negative frame (p < 0.05).

[Current diagnostics and treatment of ankle sprains in German]. / Aktuelle Diagnostik und Behandlung der Sprunggelenks-Distorsion in Deutschland.

BACKGROUND: Ankle sprains are one of the most frequent injuries of the musculoskeletal system. The injury pattern determines the treatment and are crucial for the outcome. Nonoperative treatment is commonly recommended for isolated injuries of the lateral ligaments but no standard strategy exists in combined ankle ligament injuries. The goal of this national survey was to achieve an overview about the current diagnostic strategies and common treatment concepts in Germany. MATERIAL AND METHODS: All members of the German Society for Orthopaedics and Trauma Surgery (DGOU) were invited to participate in an anonymous survey about the diagnostic and therapeutic approach in cases of ankle sprains. The online survey consisted of 20 questions. Besides questions about the speciality and scope of activities the participants were ask to depict their diagnostic and therapeutic strategy. RESULTS: A total of 806 participants completed the survey. Most of them were orthopedic trauma surgeons and worked in a hospital. During the first presentation the anterior drawer test (89.5%) and the inversion/eversion test (81.6%) were most commonly used, 88.1% always make an X­ray examination and 26.5% an ultrasonography examination. Isolated injuries of the anterior fibulotalar ligament (LFTA) were treated nonoperatively by 99.7% of the participants, 78.8% recommend full weight bearing in an orthesis, 78.8% treat the complete rupture of the lateral ligaments without operation whereas 30.1% stated that they would treat a combined lateral ligaments rupture with an injury of the syndesmosis nonoperatively. DISCUSSION: Due to the heterogeneity of injury patterns after ankle sprain no consistent recommendations for diagnostics and treatment exist. The Ottawa ankle rules and ultrasonography were not often utilized despite of the good evidence. The isolated rupture of the LFTA is diagnosed and treated according to the national guidelines by most of the participants. In cases of combined injuries of the lateral and medial ankle ligaments the majority choose a nonoperative treatment strategy which is justified by the guidelines with a low level of evidence. Combined injuries of the syndesmosis and the lateral ankle ligaments were treated operatively, which also correlates with the recommendations in the literature. The standard care of ankle sprain in Germany is in accordance with the recommendations from the current literature.

Mass Spectrometry Reveals Molecular Effects of Citrulline Supplementation during Bone Fracture Healing in a Rat Model.

Bone fracture healing is a complex process in which specific molecular knowledge is still lacking. The citrulline-arginine-nitric oxide metabolism is one of the involved pathways, and its enrichment via citrulline supplementation can enhance fracture healing. This study investigated the molecular effects of citrulline supplementation during the different fracture healing phases in a rat model. Microcomputed tomography (µCT) was applied for the analysis of the fracture callus formation. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and liquid-chromatography tandem mass spectrometry (LC-MS/MS) were used for lipid and protein analyses, respectively. µCT analysis showed no significant differences in the fracture callus volume and volume fraction between the citrulline supplementation and control group. The observed lipid profiles for the citrulline supplementation and control group were distinct for the different fracture healing stages. The main contributing lipid classes were phosphatidylcholines (PCs) and lysophosphatidylcholines (LPCs). The changing effect of citrulline supplementation throughout fracture healing was indicated by changes in the differentially expressed proteins between the groups. Pathway analysis showed an enhancement of fracture healing in the citrulline supplementation group in comparison to the control group via improved angiogenesis and earlier formation of the soft and hard callus. This study showed the molecular effects on lipids, proteins, and pathways associated with citrulline supplementation during bone fracture healing, even though no effect was visible with µCT.

Systemic acylcarnitine levels are affected in response to multiple injuries and hemorrhagic shock: An analysis of lipidomic changes in a standardized porcine model.

INTRODUCTION: Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with hemorrhagic shock. METHODS: Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements of tissue perfusion. Longitudinal analyses were performed with linear mixed models, and Spearman's correlations were calculated. A p value of 0.05 was defined as threshold for statistical significance. RESULTS: From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant ( p < 0.001) twofold increase after hemorrhagic shock in group polytrauma that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess ( p = 0.005), but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery ( p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase ( p < 0.001, p < 0.001). CONCLUSION: Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation.

European society for trauma and emergency surgery member-identified research priorities in emergency surgery: a roadmap for future clinical research opportunities.

BACKGROUND: European Society for Trauma and Emergency Surgery (ESTES) is the European community of clinicians providing care to the injured and critically ill surgical patient. ESTES has several interlinked missions - (1) the promotion of optimal emergency surgical care through networked advocacy, (2) promulgation of relevant clinical cognitive and technical skills, and (3) the advancement of scientific inquiry that closes knowledge gaps, iteratively improves upon surgical and perioperative practice, and guides decision-making rooted in scientific evidence. Faced with multitudinous opportunities for clinical research, ESTES undertook an exercise to determine member priorities for surgical research in the short-to-medium term; these research priorities were presented to a panel of experts to inform a 'road map' narrative review which anchored these research priorities in the contemporary surgical literature. METHODS: Individual ESTES members in active emergency surgery practice were polled as a representative sample of end-users and were asked to rank potential areas of future research according to their personal perceptions of priority. Using the modified eDelphi method, an invited panel of ESTES-associated experts in academic emergency surgery then crafted a narrative review highlighting potential research priorities for the Society. RESULTS: Seventy-two responding ESTES members from 23 countries provided feedback to guide the modified eDelphi expert consensus narrative review. Experts then crafted evidence-based mini-reviews highlighting knowledge gaps and areas of interest for future clinical research in emergency surgery: timing of surgery, inter-hospital transfer, diagnostic imaging in emergency surgery, the role of minimally-invasive surgical techniques and Enhanced Recovery After Surgery (ERAS) protocols, patient-reported outcome measures, risk-stratification methods, disparities in access to care, geriatric outcomes, data registry and snapshot audit evaluations, emerging technologies interrogation, and the delivery and benchmarking of emergency surgical training. CONCLUSIONS: This manuscript presents the priorities for future clinical research in academic emergency surgery as determined by a sample of the membership of ESTES. While the precise basis for prioritization was not evident, it may be anchored in disease prevalence, controversy around aspects of current patient care, or indeed the identification of a knowledge gap. These expert-crafted evidence-based mini-reviews provide useful insights that may guide the direction of future academic emergency surgery research efforts.

Porcine Mandibular Bone Marrow-Derived Mesenchymal Stem Cell (BMSC)-Derived Extracellular Vesicles Can Promote the Osteogenic Differentiation Capacity of Porcine Tibial-Derived BMSCs.

OBJECTIVE: Existing research suggests that bone marrow-derived mesenchymal stem cells (BMSCs) may promote endogenous bone repair. This may be through the secretion of factors that stimulate repair processes or directly through differentiation into osteoblast-progenitor cells. However, the osteogenic potential of BMSCs varies among different tissue sources (e.g., mandibular versus long BMSCs). The main aim of this study was to investigate the difference in osteogenic differentiation capacity between mandibular BMSCs (mBMSCs) and tibial BMSCs (tBMSCs). MATERIALS AND METHODS: Bioinformatics analysis of the GSE81430 dataset taken from the Gene Expression Omnibus (GEO) database was performed using GEO2R. BMSCs were isolated from mandibular and tibial bone marrow tissue samples. Healthy pigs (n = 3) (registered at the State Office for Nature, Environment, and Consumer Protection, North Rhine-Westphalia (LANUV) 81-02.04.2020.A215) were used for this purpose. Cell morphology and osteogenic differentiation were evaluated in mBMSCs and tBMSCs. The expression levels of toll-like receptor 4 (TLR4) and nuclear transcription factor κB (NF-κB) were analyzed using quantitative polymerase chain reaction (qPCR) and Western blot (WB), respectively. In addition, mBMSC-derived extracellular vesicles (mBMSC-EVs) were gained and used as osteogenic stimuli for tBMSCs. Cell morphology and osteogenic differentiation capacity were assessed after mBMSC-EV stimulation. RESULTS: Bioinformatic analysis indicated that the difference in the activation of the TLR4/NF-κB pathway was more pronounced compared to all other examined genes. Specifically, this demonstrated significant downregulation, whereas only 5-7 upregulated genes displayed significant variances. The mBMSC group showed stronger osteogenic differentiation capacity compared to the tBMSC group, confirmed via ALP, ARS, and von Kossa staining. Furthermore, qPCR and WB analysis revealed a significant decrease in the expression of the TLR4/NF-κB pathway in the mBMSC group compared to the tBMSC group (TLR4 fold changes: mBMSCs vs. tBMSCs p < 0.05; NF-κB fold changes: mBMSCs vs. tBMSCs p < 0.05). The osteogenic differentiation capacity was enhanced, and qPCR and WB analysis revealed a significant decrease in the expression of TLR4 and NF-κB in the tBMSC group with mBMSC-EVs added compared to tBMSCs alone (TLR4 fold changes: p < 0.05; NF-κB fold changes: p < 0.05). CONCLUSION: Our results indicate that mBMSC-EVs can promote the osteogenic differentiation of tBMSCs in vitro. The results also provide insights into the osteogenic mechanism of mBMSCs via TLR4/NF-κB signaling pathway activation. This discovery promises a fresh perspective on the treatment of bone fractures or malunions, potentially offering a novel therapeutic method.

In vivo study to assess fat embolism resulting from the Reamer-Irrigator-Aspirator 2 system compared to a novel aspirator-based concept for intramedullary bone graft harvesting.

INTRODUCTION: Fat embolism (FE) following intramedullary (IM) reaming can cause severe pulmonary complications and sudden death. Recently, a new harvesting concept was introduced in which a novel aspirator is used first for bone marrow (BM) aspiration and then for subsequent aspiration of morselized endosteal bone during sequential reaming (A + R + A). In contrast to the established Reamer-Irrigator-Aspirator (RIA) 2 system, the new A + R + A concept allows for the evacuation of fatty BM prior to reaming. In this study, we hypothesized that the risk of FE, associated coagulopathic reactions and pulmonary FE would be comparable between the RIA 2 system and the A + R + A concept. MATERIALS AND METHODS: Intramedullary bone graft was harvested from intact femora of 16 Merino sheep (age: 1-2 years) with either the RIA 2 system (n = 8) or the A + R + A concept (n = 8). Fat intravasation was monitored with the Gurd test, coagulopathic response with D-dimer blood level concentration and pulmonary FE with histological evaluation of the lungs. RESULTS: The total number and average size of intravasated fat particles was similar between groups (p = 0.13 and p = 0.98, respectively). D-dimer concentration did not significantly increase within 4 h after completion of surgery (RIA 2: p = 0.82; A + R + A: p = 0.23), with an interaction effect similar between groups (p = 0.65). The average lung area covered with fat globules was similar between groups (p = 0.17). CONCLUSIONS: The use of the RIA 2 system and the novel A + R + A harvesting concept which consists of BM evacuation followed by sequential IM reaming and aspiration of endosteal bone, resulted in only minor fat intravasation, coagulopathic reactions and pulmonary FE, with no significant differences between the groups. Our results, therefore, suggest that both the RIA 2 system and the new A + R + A concept are comparable technologies in terms of FE-related complications.