B7-1 and PlGF-1 are two possible new biomarkers to identify fracture-associated trauma patients at higher risk of developing complications: a cohort study.

BACKGROUND: Around 10% of fractures lead to complications. With increasing fracture incidences in recent years, this poses a serious burden on the healthcare system, with increasing costs for treatment. In the present study, we aimed to identify potential 'new' blood markers to predict the development of post-surgical complications in trauma patients following a fracture. METHODS: A total of 292 trauma patients with a complete three-month follow-up were included in this cohort study. Blood samples were obtained from 244 of these patients. Two complication groups were distinguished based on the Clavien-Dindo (CD) classification: CD grade I and CD grade III groups were compared to the controls (CD 0). The Mann-Whitney U test was used to compare the complication groups to the control group. RESULTS: Analysis of the patients' data revealed that risk factors are dependent on sex. Both, males and females who developed a CD III complication showed elevated blood levels of B7-1 (p = 0.015 and p = 0.018, respectively) and PlGF-1 (p = 0.009 and p = 0.031, respectively), with B7-1 demonstrating greater sensitivity (B7-1: 0.706 (male) and 0.692 (female), PlGF-1: 0.647 (male) and 0.615 (female)). Further analysis of the questionnaires and medical data revealed the importance of additional risk factors. For males (CD 0: 133; CD I: 12; CD III: 18 patients) alcohol consumption was significantly increased for CD I and CD III compared to control with p = 0.009 and p = 0.007, respectively. For females (CD 0: 107; CD I: 10; CD III: 12 patients) a significantly increased average BMI [kg/m2] from 25.5 to 29.7 with CD III was observed, as well as an elevation from one to three comorbidities (p = 0.003). CONCLUSIONS: These two potential new blood markers hold promise for predicting complication development in trauma patients. Nevertheless, further studies are necessary to evaluate the diagnostic utility of B7-1 and PlGF-1 in predicting complications in trauma patients and consider sex differences before their possible use as routine clinical screening tools.

Cilostazol Stimulates Angiogenesis and Accelerates Fracture Healing in Aged Male and Female Mice by Increasing the Expression of PI3K and RUNX2.

Fracture healing in the aged is associated with a reduced healing capacity, which often results in delayed healing or non-union formation. Many factors may contribute to this deterioration of bone regeneration, including a reduced 'angiogenic trauma response'. The phosphodiesterase-3 (PDE-3) inhibitor cilostazol has been shown to exert pro-angiogenic and pro-osteogenic effects in preclinical studies. Therefore, we herein analyzed in a stable closed femoral fracture model whether this compound also promotes fracture healing in aged mice. Forty-two aged CD-1 mice (age: 16-18 months) were daily treated with 30 mg/kg body weight cilostazol (n = 21) or vehicle (control, n = 21) by oral gavage. At 2 and 5 weeks after fracture, the femora were analyzed by X-ray, biomechanics, micro-computed tomography (µCT), histology, immunohistochemistry, and Western blotting. These analyses revealed a significantly increased bending stiffness at 2 weeks (2.2 ± 0.4 vs. 4.3 ± 0.7 N/mm) and an enhanced bone formation at 5 weeks (4.4 ± 0.7 vs. 9.1 ± 0.7 mm3) in cilostazol-treated mice when compared to controls. This was associated with a higher number of newly formed CD31-positive microvessels (3.3 ± 0.9 vs. 5.5 ± 0.7 microvessels/HPF) as well as an elevated expression of phosphoinositide-3-kinase (PI3K) (3.6 ± 0.8 vs. 17.4 ± 5.5-pixel intensity × 104) and runt-related transcription factor (RUNX)2 (6.4 ± 1.2 vs. 18.2 ± 2.7-pixel intensity × 104) within the callus tissue. These findings indicate that cilostazol accelerates fracture healing in aged mice by stimulating angiogenesis and the expression of PI3K and RUNX2. Hence, cilostazol may represent a promising compound to promote bone regeneration in geriatric patients.

Clinical and radiological outcome following trauma-related reverse shoulder arthroplasty.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is a frequently used therapy for complex proximal humeral fractures and posttraumatic disorders. The present study's purpose was to assess the clinical and radiological outcome of primary and secondary RSA, and to analyze the impact of refixation of the greater tuberosity (GT). PATIENTS AND METHODS: 28 patients with primary fracture RSA and 18 patients with RSA due to posttraumatic disorders were examined with a mean clinical follow-up of 2.5 ± 1.73 years. Operative details and radiographs were retrospectively reviewed. Additional analyses were performed for healed and non-healed GT in primary RSA. RESULTS: Patients with fracture RSA had higher Constant-Murley score (CMS) than secondary RSA without reaching significance (p = 0.104). No significant difference was present for the quality of life measured by the Short Form 36 (SF 36) and the range of motion. In primary RSA, 78.6% GT healed anatomically. Compared to non-healed GT, patients with healed GT had a significantly higher CMS (p = 0.011), external rotation (p = 0.026) and forward flexion (p = 0.083), whereas DASH score was lower without a significant difference (p = 0.268). SF 36 showed no significant difference. Patients with healed GT had a more neutral glenoid version (p = 0.009). CONCLUSION: Superior range of motion and clinical outcome scores were present for anatomically healed GT. Therefore, refixation of the tuberosities is recommended. Secondary RSA can result in inferior results compared to primary RSA, so patients need to be adequately informed.

Are there associations between hip geometry and bone quality? An analysis on 3074 adults from a general population.

INTRODUCTION: Patients with reduced bone mineral density and altered hip geometry are susceptible for hip pathologies. Knowledge on associations between bone properties and hip geometric parameters might facilitate identification of patients at risk for hip pathologies. The aim of the present study was to identify associations of bone properties assessed by quantitative ultrasound (QUS) at the heel and hip geometric parameters like center-edge angle (CE), neck-shaft angle (NSA) and alpha angle. MATERIALS AND METHODS: Hip geometric parameters (CE, NSA and alpha angle) of 3074 participants from the population-based Study of Health in Pomerania were assessed on magnetic resonance imaging. QUS was performed on both calcanei providing broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness-index. Based on the stiffness-index the individual osteoporotic fracture risk (low, moderate or high) was determined. Associations between QUS-based and hip geometric parameters were calculated in linear regression models adjusted for age, sex, body height and weight. Interactions of QUS markers with age and sex on hip geometric parameters were tested. RESULTS: Significant inverse associations between BUA (ß = - 0.068), SOS (ß = - 0.024) as well as stiffness-index (ß = - 0.056) and CE were present, while fracture risk was positively associated with CE (ß for high = 1.28 and moderate = 2.54 vs. low fracture risk). Interactions between BUA and sex as well as between SOS and age were detected in the models for CE. Furthermore, there was an inverse relation between fracture risk and NSA that was restricted to the moderate risk (ß for moderate vs. low fracture risk = - 0.60). There were no significant associations between QUS parameters and alpha angle. CONCLUSIONS: In the general population, several associations between QUS-based bone properties or fracture risk and hip geometry are present. Less dysplastic hips had a lower stiffness-index and a higher fracture risk, whereas more valgus hips had a lower fracture risk.

Parathyroid hormone stimulates bone regeneration in an atrophic non-union model in aged mice.

BACKGROUND: Non-union formation still represents a major burden in trauma and orthopedic surgery. Moreover, aged patients are at an increased risk for bone healing failure. Parathyroid hormone (PTH) has been shown to accelerate fracture healing in young adult animals. However, there is no information whether PTH also stimulates bone regeneration in atrophic non-unions in the aged. Therefore, the aim of the present study was to analyze the effect of PTH on bone regeneration in an atrophic non-union model in aged CD-1 mice. METHODS: After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. The animals were treated daily with either 200 mg/kg body weight PTH 1-34 (n = 17) or saline (control; n = 17) subcutaneously. Bone regeneration was analyzed by means of X-ray, biomechanics, micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses. RESULTS: In PTH-treated animals bone formation was markedly improved when compared to controls. This was associated with an increased bending stiffness as well as a higher number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD31-positive microvessels within the callus tissue. Furthermore, PTH-treated aged animals showed a decreased inflammatory response, characterized by a lower number of MPO-positive granulocytes and CD68-positive macrophages within the bone defects when compared to controls. Additional Western blot analyses demonstrated a significantly higher expression of cyclooxygenase (COX)-2 and phosphoinositide 3-kinase (PI3K) in PTH-treated mice. CONCLUSION: Taken together, these findings indicate that PTH is an effective pharmacological compound for the treatment of non-union formation in aged animals.

Sildenafil, a phosphodiesterase-5 inhibitor, stimulates angiogenesis and bone regeneration in an atrophic non-union model in mice.

Non-union formation represents a major complication in trauma and orthopedic surgery. The phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been shown to exert pro-angiogenic and pro-osteogenic effects in vitro and in vivo. Therefore, the aim of the present study was to analyze the impact of sildenafil in an atrophic non-union model in mice. After creation of a 1.8 mm segmental defect, mice femora were stabilized by pin-clip fixation. Bone regeneration was analyzed by means of X-ray, biomechanics, photoacoustic and micro-computed tomography (µCT) imaging as well as histological, immunohistochemical and Western blot analyses at 2, 5 and 10 weeks after surgery. The animals were treated daily with either 5 mg/kg body weight sildenafil (n = 35) or saline (control; n = 35) per os. Bone formation was markedly improved in defects of sildenafil-treated mice when compared to controls. This was associated with a higher bending stiffness as well as an increased number of CD31-positive microvessels and a higher oxygen saturation within the callus tissue. Moreover, the bone defects of sildenafil-treated animals contained more tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and CD68-positive macrophages and exhibited a higher expression of the pro-angiogenic and pro-osteogenic markers cysteine rich protein (CYR)61 and vascular endothelial growth factor (VEGF) when compared to controls. These findings demonstrate that sildenafil acts as a potent stimulator of angiogenesis and bone regeneration in atrophic non-unions.

MRI-based torsion measurement of the lower limb is a reliable and valid alternative for CT measurement: a prospective study.

PURPOSE: The aim of this study was to compare MRI-based torsion measurements of the lower limb to a well-established CT-based assessment in a prospective inter- and intraindividual approach. METHODS: A total of 26 patients (age 28.8 years ± 11.0) were enrolled beginning in January 2021 until August 2022. Inclusion criteria were the clinical indication for torsion measurement of the lower limb. CT and MRI imaging were performed with a standard operating procedure, to ensure that all patients were examined in a standardized position. The examinations were planned on a coronal scout view based on prominent anatomical landmarks. Femoral and tibial torsion were measured individually. Torsion measurements were analysed twice: immediately after examination and after 3 weeks. Subsequently, intra-rater and parallel test reliability was calculated accordingly. RESULTS: High significant results for CT and MRI measurements for both tibia (MRI: r = 0.961; p ≤ 0.001; CT: r = 0.963; p ≤ 0.001) and femur (MRI: r = 0.980; p ≤ 0.001; CT: r = 0.979; p ≤ 0.001) were obtained by calculated intra-rater reliability, showing that measurements were highly consistent for MRI and CT, respectively. Parallel test reliability for time point 1 as well as time point 2 was also highly significant and ranged from r = 0.947 to r = 0.972 (all with p ≤ 0.001, respectively) for both tibia and femur, showing a high concordance between the two measurements. CONCLUSION: Measurement of tibial as well as femoral torsion was comparable for CT and MRI measurement. Therefore, this study supports MRI measurement as an equivalent alternative for CT measurement concerning torsional malalignment to reduce exposure to radiation. LEVEL OF EVIDENCE: Level II.

Work intensity and quality of life can be restored following double-level osteotomy in varus knee osteoarthritis.

PURPOSE: The purpose of this study was to assess changes in health-related quality of life (HRQL) and work intensity following double-level knee osteotomy (DLO). It was hypothesized that postoperative HRQL would be comparable to that of the general population and that work intensity can be restored in the short term. METHODS: Twenty-four patients (28 varus knees; mechanical tibiofemoral angle: -11.0 ± 3.0° (-6.0 to -17.0), age: 49.1 ± 9.5 (31-65) years) who underwent DLO were included. The duration the patients were unable to work was evaluated. HRQL was measured with the SF-36 questionnaire, which consists of a physical (PCS) and mental component summary score (MCS). The pre- to postoperative changes in the PCS and MCS were analysed. The PCS and MCS were also compared to those of the general population, who has a reference score value of 50 points. The work intensity measured with the REFA classification and the Tegner activity scale were assessed preoperatively and at the final postoperative follow-up examination (18.0 ± 10.0 (5-43) months). RESULTS: The duration that the patients were unable to work was 12.2 ± 4.4 (6-20) weeks. The PCS improved from 32.1 ± 11.3 (14.5-53.3) preoperatively to 54.6 ± 8.5 (25.2-63.7) (p < 0.001) at the final follow-up, and the MCS improved from 53.9 ± 11.1 (17.1-67.7) to 57.2 ± 3.1 (47.3-61.7) (n.s). The preoperative PCS was significantly lower than the reference score of the general population (p < 0.001), whereas the preoperative MCS was similar between the two groups (n.s.). At follow-up, no significant differences were observed between the PCS and the MCS of the patient group and those of the general population. Five patients who were unable to work prior to surgery due to knee symptoms returned to work with moderate (four patients) or even very heavy (one patient) workloads. The Tegner activity scale increased significantly from a median of 2.0 (0.0-5.0) to 4.0 (2.0-7.0) (p < 0.001). CONCLUSION: Our results demonstrate an improvement in quality of life and return to working activity following DLO in the short term. The HRQL can be improved by DLO in patients with varus knee osteoarthritis to the level of the general population. These results can assist surgeons in discussing realistic expectations when considering patients for DLO. LEVEL OF EVIDENCE: Study type: therapeutic, IV.

Reference values and influencing factors of the glenohumeral subluxation index: a study on 3004 participants.

BACKGROUND: The primary objective of this study was to examine the glenohumeral subluxation index (GHSI) in a large general population cohort and to define reference values. Glenohumeral subluxation is important in the development and prediction of pathological states of the shoulder joint and in total shoulder arthroplasty. Therefore, another objective was to examine the influence of age, sex, body mass index, and body height and weight on GHSI. METHODS: GHSI according to Walch was measured on bilateral magnetic resonance imaging of 3004 participants of the Study of Health in Pomerania (SHIP, aged 21-90 years). SHIP drew a sample of the adult general population of Pomerania (Northeastern Germany). Reference values for GHSI were assessed by quantile regression models. Associations of sex, age, and anthropometric markers with the GHSI were calculated by linear regression models. RESULTS: A reference range between 42% and 55% for men with a mean of 49% ± 4% was defined, while the upper reference limit for women was 1% higher (mean, 50% ± 4%). Age was inversely associated with the GHSI in males (P < 0.001), while no significant association in females was observed (P = .625). Body weight and body mass index were positively associated (P < .001) without effect modification by sex. Heavy mechanical oscillations on the upper extremity showed no significant association with GHSI (P = .268). CONCLUSION: The reference values for GHSI were expanded to a range of 42%-57% on magnetic resonance imaging. Several associations between GHSI and anthropometric properties are present. According to these associations, adjusted formulas are provided to enable individual, patient-specific diagnostics and therapy. Nevertheless, the clinical picture cannot be neglected.

Next step trauma and orthopaedic surgery: integration of augmented reality for reduction and nail implantation of tibial fractures.

INTRODUCTION: There is a tremendous scope of hardware and software development going on in augmented reality (AR), also in trauma and orthopaedic surgery. However, there are only a few systems available for intra-operative 3D imaging and guidance, most of them rely on peri- and intra-operative X-ray imaging. Especially in complex situations such as pelvic surgery or multifragmentary multilevel fractures, intra-operative 3D imaging and implant tracking systems have proven to be of great advantage for the outcome of the surgery and can help reduce X-ray exposure, at least for the surgical team (Ochs et al. in Injury 41:1297 1305, 2010). Yet, the current systems do not provide the ability to have a dynamic live view from the perspective of the surgeon. Our study describes a prototype AR-based system for live tracking which does not rely on X-rays. MATERIALS AND METHODS: A protype live-view intra-operative guidance system using an AR head-mounted device (HMD) was developed and tested on the implantation of a medullary nail in a tibia fracture model. Software algorithms that allow live view and tracking of the implant, fracture fragments and soft tissue without the intra-operative use of X-rays were derived. RESULTS: The implantation of a medullar tibia nail is possible while only relying on AR-guidance and live view without the intra-operative use of X-rays. CONCLUSIONS: The current paper describes a feasibility study with a prototype of an intra-operative dynamic live tracking and imaging system that does not require intra-operative use of X-rays and dynamically adjust to the perspective of the surgeons due to an AR HMD. To our knowledge, the current literature does not describe any similar systems. This could be the next step in surgical imaging and education and a promising way to improve patient care.

NET Formation Was Reduced via Exposure to Extremely Low-Frequency Pulsed Electromagnetic Fields.

Fracture-healing is a highly complex and timely orchestrated process. Non-healing fractures are still a major clinical problem and treatment remains difficult. A 16 Hz extremely low-frequency pulsed electromagnetic field (ELF-PEMF) was identified as non-invasive adjunct therapy supporting bone-healing by inducing reactive oxygen species (ROS) and Ca2+-influx. However, ROS and Ca2+-influx may stimulate neutrophils, the first cells arriving at the wounded site, to excessively form neutrophil extracellular traps (NETs), which negatively affects the healing process. Thus, this study aimed to evaluate the effect of this 16 Hz ELF-PEMF on NET formation. Neutrophils were isolated from healthy volunteers and exposed to different NET-stimuli and the 16 Hz ELF-PEMF. NETs were quantified using Sytox Green Assay and immunofluorescence, Ca2+-influx and ROS with fluorescence probes. In contrast to mesenchymal cells, ELF-PEMF exposure did not induce ROS and Ca2+-influx in neutrophils. ELF-PEMF exposure did not result in basal or enhanced PMA-induced NET formation but did reduce the amount of DNA released. Similarly, NET formation induced by LPS and H2O2 was reduced through exposure to ELF-PEMF. As ELF-PEMF exposure did not induce NET release or negatively affect neutrophils, the ELF-PEMF exposure can be started immediately after fracture treatment.

Revision surgery after failed surgical treatment of midshaft clavicle fractures is often associated with positive detection of bacteria.

BACKGROUND: Midshaft clavicle fractures are common, and the proportion of patients treated surgically has increased in recent years. With this increase in surgical treatments, the complication rate, for instance of infection, non-union, or implant failure, has also risen. This study evaluates the frequency of pathogen detection during revision surgeries occurring after a prior failed osteosynthesis of midshaft clavicle fractures. METHODS: All patients treated in our hospital with a prior failed surgical therapy of a clavicle midshaft fracture between January 2013 and March 2022 were screened. Epidemiological data, intraoperative tissue samples, sonication, and the type of revision surgery were assessed. A postoperative follow-up at a minimum of 6 month was defined and osseous consolidation was verified. RESULTS: Twenty-one patients (twelve male and eight female) were included with a mean age of 40.4 ± 14.1 years. Eleven of the patients showed pathogen detection (Group I), and seven remained without (Group II). A significant difference in age existed between Groups I and II (36.1 ± 12.8 and 51.6 ± 11.5, p ≤ 0.05). The three most common pathogens were Cutibacterium acnes (n = 7), Staphylococcus epidermidis (n = 4), and Staphylococcus sacchorlyticus (n = 3), respectively. Thirteen patients presented for a follow-up. In nine patients (69%), bone healing was detectable. Four patients received a second revision surgery. CONCLUSION: Revision surgery frequently shows pathogen detection without signs of infection. Cutibacterium acnes is the most common pathogen. Despite pathogen detection, bone healing can be achieved with revision surgery, although the rate of repeat revision surgeries is high.

Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: clinical outcome 10 years after joint-preserving surgery.

INTRODUCTION: Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively. MATERIALS AND METHODS: In a prospective case series, we operatively treated 12 consecutive patients (all males) after posterior shoulder dislocation with associated reverse Hill-Sachs lesion using joint-preserving techniques. Patients received surgery in a single center between January 2008 and December 2011. The joint-preserving surgical procedure was chosen depending on the defect size and bone quality. The following outcome-measures were analyzed: Constant-Score, DASH-Score, ROWE-Score, and SF-12. Results 1, 5, and 10 years postoperatively were compared. RESULTS: Out of 12 patients, ten patients (83.3%) were followed-up with a mean follow-up interval of 10.7 years (range 9.3-12.8). The mean patient age at the time of the last follow-up was 51 years (32-66). The outcome scores at the final follow-up were: Constant 92.5 (range 70.0-100), DASH 3.2 (0.0-10.8), ROWE 91.0 (85.0-100), and SF-12 87.8 (77.5-98.3). Clinical results had improved from 1 to 5 years postoperatively and showed a tendency for even further improvement after 10 years. CONCLUSIONS: Joint-preserving surgical therapy of posterior shoulder dislocation provides excellent results when the morphology of the reverse Hill-Sachs lesion is respected in surgical decision-making. TRIAL REGISTRATION: 223/2012BO2, 02 August 2010.

"Bring Your Own Device"-A New Approach to Wearable Outcome Assessment in Trauma.

Background and Objectives: Outcome data from wearable devices are increasingly used in both research and clinics. Traditionally, a dedicated device is chosen for a given study or clinical application to collect outcome data as soon as the patient is included in a study or undergoes a procedure. The current study introduces a new measurement strategy, whereby patients' own devices are utilized, allowing for both a pre-injury baseline measure and ability to show achievable results. Materials and Methods: Patients with a pre-existing musculoskeletal injury of the upper and lower extremity were included in this exploratory, proof-of-concept study. They were followed up for a minimum of 6 weeks after injury, and their wearable outcome data (from a smartphone and/or a body-worn sensor) were continuously acquired during this period. A descriptive analysis of the screening characteristics and the observed and achievable outcome patterns was performed. Results: A total of 432 patients was continuously screened for the study, and their screening was analyzed. The highest success rate for successful inclusion was in younger patients. Forty-eight patients were included in the analysis. The most prevalent outcome was step count. Three distinctive activity data patterns were observed: patients recovering, patients with slow or no recovery, and patients needing additional measures to determine treatment outcomes. Conclusions: Measuring outcomes in trauma patients with the Bring Your Own Device (BYOD) strategy is feasible. With this approach, patients were able to provide continuous activity data without any dedicated equipment given to them. The measurement technique is especially suited to particular patient groups. Our study's screening log and inclusion characteristics can help inform future studies wishing to employ the BYOD design.

The vascularization paradox of non-union formation.

Despite major research efforts to elucidate mechanisms of non-union formation, failed fracture healing remains a common complication in orthopedic surgery. Adequate vascularization has been recognized as a crucial factor for successful bone regeneration, as newly formed microvessels guarantee the supply of the callus tissue with vital oxygen, nutrients, and growth factors. Accordingly, a vast number of preclinical studies have focused on the development of vascularization strategies to stimulate fracture repair. However, recent evidence suggests that stimulation of blood vessel formation is an oversimplified approach to support bone regeneration. This review discusses the role of vascularization during bone regeneration and delineates a phenomenon, for which we coin the term "the vascularization paradox of non-union-formation". This view is based on the results of a variety of experimental studies that suggest that the callus tissue of non-unions is indeed densely vascularized and that pro-angiogenic mediators, such as vascular endothelial growth factor, are sufficiently expressed at the facture site. By gaining further insights into the molecular and cellular basis of non-union vascularization, it may be possible to develop more optimized treatment approaches or even prevent the non-union formation in the future.

Optimisation of the HepaRG cell line model for drug toxicity studies using two different cultivation conditions: advantages and limitations.

The HepaRG cell line represents a successful model for hepatotoxicity studies. These cells are of human origin and are differentiated in vitro into mature and functional hepatocyte-like cells. The objective of this research was to compare two different culture protocols, Sison-Young et al. 2017 (hereinafter referred as Sison) and Gripon et al. 2002 (hereinafter referred as Biopredic) for HepaRG cells in order to optimise this model for drug metabolism and toxicity testing studies. HepaRG cells obtained from the same batch were cultured according to the described protocols. Using both protocols, differentiated HepaRG cells retained their drug metabolic capacity (major phase I/II enzymes) and transporters, as well as their morphological characteristics. Morphologically, HepaRG cells cultured after the Biopredic protocol formed more apical membranes and small ductular-like structures, than those cultivated using the Sison protocol. Also, the efflux activity of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) as well as the activity of uridine-glucuronosyltransferase (UGT) and glutathione S-transferase (GST) were significantly reduced in HepaRG cultured using the Sison protocol. Applying well-established drug cocktails to measure cytochrome P450 (CYPs) activity, we found that production of the corresponding metabolites was hampered in Sison-cultured HepaRG cells, indicating that the activity of CYP1A2, CYP2C9, CYP3A4, CYP2B6 and CYP2C19 was significantly reduced. Moreover, HepaRG sensitivity to well-known drugs, namely diclofenac, amiodarone, imipramine and paracetamol, revealed some differences between the two culture protocols. Furthermore, the HepaRG cells can be maintained with higher viability and sufficient CYPs activity and expression (i.e. CYP3A4, CYP1A2 and CYP2B6) as well as liver-specific functions, using Biopredic compared with the Sison culture protocol. These maintained liver-specific functions might be dependent on the prolongation of the culture conditions in the case of the Biopredic protocol. In conclusion, based on the metabolic activity of HepaRG cells using the standard protocol from Biopredic, we believe that this protocol is optimal for investigating drug metabolism and pharmacokinetic screening studies.

Patients with combined pelvic and spinal injuries have worse clinical and operative outcomes than patients with isolated pelvic injuries analysis of the German Pelvic Registry.

BACKGROUND: Pelvic fractures are often associated with spine injury in polytrauma patients. This study aimed to determine whether concomitant spine injury influence the surgical outcome of pelvic fracture. METHODS: We performed a retrospective analysis of data of patients registered in the German Pelvic Registry between January 2003 and December 2017. Clinical characteristics, surgical parameters, and outcomes were compared between patients with isolated pelvic fracture (group A) and patients with pelvic fracture plus spine injury (group B). We also compared apart patients with isolated acetabular fracture (group C) versus patients with acetabular fracture plus spine injury (group D). RESULTS: Surgery for pelvic fracture was significantly more common in group B than in group A (38.3% vs. 36.6%; p = 0.0002), as also emergency pelvic stabilizations (9.5% vs. 6.7%; p < 0.0001). The mean time to emergency stabilization was longer in group B (137 ± 106 min vs. 113 ± 97 min; p < 0.0001), as well as the mean time until definitive stabilization of the pelvic fracture (7.3 ± 4 days vs. 5.4 ± 8.0 days; p = 0.147). The mean duration of treatment and the morbidity and mortality rates were all significantly higher in group B (p < 0.0001). Operation time was significantly shorter in group C than in group D (176 ± 81 min vs. 203 ± 119 min, p < 0.0001). Intraoperative blood loss was not significantly different between the two groups with acetabular injuries. Although preoperative acetabular fracture dislocation was slightly less common in group D, postoperative fracture dislocation was slightly more common. The distribution of Matta grades was significantly different between the two groups. Patients with isolated acetabular injuries were significantly less likely to have neurological deficit at discharge (94.5%; p < 0.0001). In-hospital complications were more common in patients with combined spine plus pelvic injuries (groups B and D) than in patients with isolated pelvic and acetabular injury (groups A and C). CONCLUSIONS: Delaying definitive surgical treatment of pelvic fractures due to spinal cord injury appears to have a negative impact on the outcome of pelvic fractures, especially on the quality of reduction of acetabular fractures.

Febrile-Range Hyperthermia Can Prevent Toxic Effects of Neutrophil Extracellular Traps on Mesenchymal Stem Cells.

Fracture healing is characterized by an inflammatory phase directly after fracture which has a strong impact on the healing outcome. Neutrophils are strong contributors here and can release neutrophil extracellular traps (NETs). NETs are found after trauma, originally thought to capture pathogens. However, they can lead to tissue damage and impede wound healing processes. Their role in fracture healing remains unclear. In this study, the effect of isolated NETs on the function of bone-forming mesenchymal stem cells (SCP-1 cells) was examined. NETs were isolated from stimulated healthy neutrophils and viability, migration, and differentiation of SCP-1 cells were analyzed after the addition of NETs. NETs severely impaired the viability of SCP-1 cells, induced necrosis and already nontoxic concentrations reduced migration significantly. Short-term incubation with NETs had a persistent negative effect on osteogenic differentiation, as measured by AP activity and matrix formation. The addition of DNase or protease inhibitors failed to reverse the negative effect of NETs, whereas a short febrile-range temperature treatment successfully reduced the toxicity and membrane destruction. Thus, the possible modification of the negative effects of NETs in fracture hematomas could be an interesting new target to improve bone healing, particularly in patients with chronic diseases such as diabetes.

Influence of axial limb rotation on radiographic lower limb alignment: a systematic review.

INTRODUCTION: The influence of limb malrotation on long-leg radiographs (LLR) is frequently discussed in literature. This systematic review aimed to describe the influence of limb rotation on alignment measurements alone and in combination with knee flexion, and determine its clinical impact. MATERIALS AND METHODS: A literature search was conducted in June 2021 using the databases MEDLINE, Cochrane, Web of Science (Clarivate Analytics), and Embase. The search term ((radiograph OR X-ray) AND (position OR rotation) AND limb alignment) was used. Database query, record screening, and study inclusion and exclusion were performed by two reviewers independently. Experimental studies (using either specimens or synthetic bones) or clinical studies (prospective or retrospective using radiographs of patients) analyzing the influence of limb rotation on anatomic and mechanical limb alignment measurements were included. Characteristics and results of the included studies were summarized, simplified, and grouped for comparison to answer the research question. Studies were compared descriptively, and no meta-analysis was performed. RESULTS: A total of 22 studies were included showing large heterogeneity, comprising studies with cadavers, patients, and synthetic bones. Most studies (7 out of 8) reported that external rotation (ER) causes less apparent valgus and leads to more varus and internal rotation (IR) causes more valgus and leads to less varus. However, there is no consensus on the extent of rotation influencing alignment measures. Studies reported about an average change of > 2° (n = 4) and < 2° (n = 4) hip-knee-ankle angle (HKA) between 15°IR and 15°ER. There is a consensus that the impact of rotation on mechanical alignment is higher if additional sagittal knee angulation, such as knee flexion, is present. All five studies analyzing the influence of rotation combined with knee flexion (5°-15°) showed an HKA change of > 2° between 15°IR and 15°ER. CONCLUSION: Malrotation is frequently present on LLR, possibly influencing the measured alignment especially in knees with extension deficit. Surgeons must consider this when measuring and treating deformities (high tibial osteotomy or total knee arthroplasties), and analyzing surgical outcomes. Especially in patients with osteoarthritis with knee extension deficits or postoperative swelling, the effect of malrotation is significantly greater.

[Case-based learning can improve the teaching quality in trauma surgery education : A survey analysis among medical students]. / Fallbasiertes Lernen kann die Lehrqualität im unfallchirurgischen Unterricht verbessern : Eine Umfrageanalyse unter Medizinstudierenden.

BACKGROUND: Medical education has always been challenging for students and teachers. Of growing importance is the promotion of knowledge of correlations and knowledge transfer from theoretical aspects into clinical practice. In order to achieve this aim, student-centered teaching concepts are increasingly being employed in the literature. OBJECTIVE: Can a trauma surgery practical seminar be improved by a case-based teaching concept? MATERIAL AND METHODS: For this purpose, standardized case studies and corresponding teaching materials, such as classification aids and treatment strategies, were made available to the students and lecturers. Using a two-staged evaluation the effects of the modified teaching design could be recorded and statistically analyzed. RESULTS: The seminar was considered to be relevant for the examinations. The teaching by the lecturers was found to be more competent and appeared more motivated. Overall, the seminar was rated better by the students. CONCLUSION: A case-based teaching concept can significantly improve the education in trauma surgery, when correctly and specifically implemented.