The Vega advanced third generation posterior stabilized total knee arthroplasty system enables the restoration of range of motion for high demanding daily activities - A 5-years follow-up study.

BACKGROUND: The Vega System® PS (Aesculap AG, Tuttlingen, Germany) is an advanced, third generation fixed implant that aims to mimic natural knee kinematics by optimizing pivotal motion while reducing surface stress. This study evaluated mid-term survival and clinical outcomes, including range of motion (ROM) of the modern posterior stabilized implant in order to analyse whether this biomechanically successful implant reaches good results in situ. METHODS: The first 100 patients to receive the Vega PS System for total knee arthroplasty were invited to take part in this single centre, single surgeon study. Of these, 84 patients were clinically assessed 5-6 years postoperatively. Data which was obtained during this follow-up examination included revision data, range of motion and clinical scores. RESULTS: The 5-year survival rate for exchange of any component was 97.6%, whereby two patients required replacement of the polyethylene gliding surface. Secondary patella resurfacing was performed in 7 patients. Significantly improved results in comparison to the preoperative state could be obtained at the follow-up: KOOS improved from 39.4 to 78.8, SF-12 PCS improved from 32.1 to 42 SF-12 MCS improved from 46 to 53.8 and patella pain improved from 2.7 to 0.3. The mean ROM of the 84 patients after 5 years was 133.1° and mean total KSS was 189.9. DISCUSSION & CONCLUSIONS: This study demonstrates a high survival rate of the Vega PS System® and significant improvements in clinical outcomes 5 years after implantation. The obtained mean ROM indicates that this implant provides good flexibility of the knee joint, allowing a high number of activities. However, due to the rate of secondary patella implantation, routine resurfacing of the patella for all PS TKA cases is highly recommended. CLINICAL TRIALS REGISTRATION: The study was registered at clinicaltrials.gov (NCT02802085).

In Vitro Comparison of 2 Clinically Applied Biomaterials for Autologous Chondrocyte Implantation: Injectable Hydrogel Versus Collagen Scaffold.

OBJECTIVE: In autologous chondrocyte implantation (ACI), there is no consensus about used bioscaffolds. The aim of this study was to perform an in vitro comparative analysis of 2 clinically applied biomaterials for cartilage lesion treatment. DESIGN: Monolayer expanded human chondrocytes (n = 6) were embedded in a collagen scaffold (CS) and a hyaluronic acid-based hydrogel (HA). Cells were cultured in chondropermissive medium supplemented with and without interleukin-10 (IL-10) and bone morphogenetic protein-2 (BMP-2). Gene expression of chondrogenic markers (COL1A1, COL2A1, COL10A1, ACAN, SOX9) was detected via quantitative real-time-polymerase chain reaction (RT-qPCR). Biosynthesis of matrix compounds, cell viability, morphology as well as migration from surrounding native bovine cartilage into cell-free scaffolds were analyzed histologically. Adhesion of the material to adjacent cartilage was investigated by a custom-made push-out test. RESULTS: The shift of COL1/2 ratio toward COL2A1 was more pronounced in HA, and cells displayed a more spherical morphology compared with CS. BMP-2 and IL-10 significantly increased COL2A1, SOX9, and ACAN expression, which was paralleled by enhanced staining of glycosaminoglycans (GAGs) and type 2 collagen in histological sections of CS and HA. COL10A1 was not significantly expressed in HA and CS. Better interfacial integration and enhanced cell invasion was observed in CS. Push-out tests using CS showed higher bonding strength to native cartilage. CONCLUSION: HA-based hydrogel revealed a more chondrocyte-like phenotype but only allowed limited cell invasion, whereas CS were advantageous in terms of cellular invasion and interfacial adhesion. These differences may be clinically relevant when treating cartilaginous or osteochondral defects.

Predicting tracheostomy in multiple injured patients with severe thoracic injury (AIS ≥ 3) with the new T3P-Score: a multivariable regression prediction analysis.

Multiple trauma patients with severe chest trauma are at increased risk for tracheostomy. While the risk factors associated with the need for tracheostomy are well established in the general critical care population, they have not yet been validated in a cohort of patients suffering severe thoracic trauma. This retrospective cohort study analysed data on patients aged 18 years or older who were admitted to one of the six participating academic level I trauma centres with multiple injuries, including severe thoracic trauma (AISThorax ≥ 3) between 2010 and 2014. A multivariable binary regression was used to identify predictor variables for tracheostomy and to develop the Tracheostomy in Thoracic Trauma Prediction Score (T3P-Score). The study included 1019 adult thoracic trauma patients, of whom 165 underwent tracheostomy during their intensive care unit (ICU) stay. Prehospital endotracheal intubation (adjusted OR [AOR]: 2.494, 95% CI [1.412; 4.405]), diagnosis of pneumonia during the ICU stay (AOR: 4.374, 95% CI [2.503; 7.642]), duration of mechanical ventilation (AOR: 1.008/hours of intubation, 95% CI [1.006; 1.009]), and an AISHead ≥ 3 (AOR 1.840, 95% CI [1.039; 3.261]) were independent risk factors for tracheostomy. Patients with sepsis had a lower risk of tracheostomy than patients without sepsis (AOR 0.486, 95% CI [0.253; 0.935]). The T3P-Score had high predictive validity for tracheostomy (ROCAUC = 0.938, 95% CI [0.920, 0.956]; Nagelkerke's R2 was 0.601). The T3P-Score's specificity was 0.68, and the sensitivity was 0.96. The severity of thoracic trauma did not predict the need for tracheostomy. Follow-up studies should validate the T3P-Score in external data sets and study the reasons for the reluctant use of tracheostomy in patients with severe thoracic trauma and subsequent sepsis.Trial registration: The study was applied for and registered a priori with the respective ethics committees.

Percutaneous thoraco-lumbar-sacral pedicle screw placement accuracy results from a multi-center, prospective clinical study using a skin marker-based optical navigation system.

STUDY DESIGN: Prospective multi-center study. OBJECTIVE: The study aimed to evaluate the accuracy of pedicle screw placement using a skin marker-based optical surgical navigation system for minimal invasive thoraco-lumbar-sacral pedicle screw placement. METHODS: The study was performed in a hybrid Operating Room with a video camera-based navigation system integrated in the imaging hardware. The patient was tracked with non-invasive skin markers while the instrument tracking was via an on-shaft optical marker pattern. The screw placement accuracy assessment was performed by three independent reviewers, using the Gertzbein grading. The screw placement time as well as the staff and patient radiation doses was also measured. RESULTS: In total, 211 screws in 39 patients were analyzed for screw placement accuracy. Of these 32.7% were in the thoracic region, 59.7% were in the lumbar region, and 7.6% were in the sacral region. An overall accuracy of 98.1% was achieved. No screws were deemed severely misplaced (Gertzbein grading 3). The average time for screw placement was 6 min and 25 secs (± 3 min 33 secs). The average operator radiation dose per subject was 40.3 µSv. The mean patient effective dose (ED) was 11.94 mSv. CONCLUSION: Skin marker-based ON can be used to achieve very accurate thoracolumbarsacral pedicle screw placements.

Retrospective Mid-Term Follow-Up of Posttraumatic and Iatrogenic Neurovascular Complications in Surgically Treated Paediatric Patients with Distal Humerus Fracture.

BACKGROUND: The purpose of the study was to investigate and describe neurovascular complications and mid-term clinical outcomes of operatively managed fractures of the distal humerus in a paediatric population. Neurovascular injuries are common in these fractures, but reports about their implications for mid-term clinical outcomes is sparse. METHODS: A single-centre retrospective study was conducted at a university teaching hospital investigating paediatric patients who underwent operative management of a distal humerus fracture between 2014 and 2018. Patient demographics, fracture classification, pre-, peri- and postoperative neurovascular complications were investigated. Mid-term follow up clinical examination and functional scoring using QuickDASH, the Broberg and Morrey Score (BMS), the Mayo Elbow Performance Score (MEPS) and the Numeric Rating Scale were performed. RESULTS: A total of 84 patients were identified, of which 34 met the inclusion criteria and were available for follow-up clinical examination. The average time to follow-up was 150 weeks (1049.44 days ± 448.54). Ten primary traumatic neurovascular complications were identified, the majority of which involved the median nerve. Primary traumatic dissection of the brachial artery was recorded in three patients. Secondary iatrogenic nerve injury was documented in five patients after previously normal clinical examination. At follow-up, the average QuickDASH score was 3.0 ± 4.3, BMS was 98.6 ± 3.4 and MEPS was 97.1 ± 3.3 points. CONCLUSIONS: The mid-term clinical outcome following surgical management of distal humerus fractures is excellent. There is, however, a considerable frequency of both primary and secondary neurovascular complications, which must be considered when opting to treat these injuries surgically.

Regenerative Potential of Platelet Concentrate Lysate in Mechanically Injured Cartilage and Matrix-Associated Chondrocyte Implantation In Vitro.

Adjuvant therapy in autologous chondrocyte implantation (ACI) can control the post-traumatic environment and guide graft maturation to support cartilage repair. To investigate both aspects, we examined potential chondro-regenerative effects of lysed platelet concentrate (PC) and supplementary interleukin 10 (IL-10) on mechanically injured cartilage and on clinically used ACI scaffolds. ACI remnants and human cartilage explants, which were applied to an uniaxial unconfined compression as injury model, were treated with human IL-10 and/or PC from thrombocyte concentrates. We analyzed nuclear blebbing/TUNEL, sGAG content, immunohistochemistry, and the expression of COL1A1, COL2A1, COL10A1, SOX9, and ACAN. Post-injuriously, PC was associated with less cell death, increased COL2A1 expression, and decreased COL10A1 expression and, interestingly, the combination with Il-10 or Il-10 alone had no additional effects, except on COL10A1, which was most effectively decreased by the combination of PC and Il-10. The expression of COL2A1 or SOX9 was statistically not modulated by these substances. In contrast, in chondrocytes in ACI grafts the combination of PC and IL-10 had the most pronounced effects on all parameters except ACAN. Thus, using adjuvants such as PC and IL-10, preferably in combination, is a promising strategy for enhancing repair and graft maturation of autologous transplanted chondrocytes after cartilage injury.

Does the time of the day affect multiple trauma care in hospitals? A retrospective analysis of data from the TraumaRegister DGU®.

BACKGROUND: Optimal multiple trauma care should be continuously provided during the day and night. Several studies have demonstrated worse outcomes and higher mortality in patients admitted at night. This study involved the analysis of a population of multiple trauma patients admitted at night and a comparison of various indicators of the quality of care at different admission times. METHODS: Data from 58,939 multiple trauma patients from 2007 to 2017 were analyzed retrospectively. All data were obtained from TraumaRegister DGU®. Patients were grouped by the time of their admission to the trauma center (6.00 am-11.59 am (morning), 12.00 pm-5.59 pm (afternoon), 6.00 pm-11.59 pm (evening), 0.00 am-5.59 am (night)). Incidences, patient demographics, injury patterns, trauma center levels and trauma care times and outcomes were evaluated. RESULTS: Fewer patients were admitted during the night (6.00 pm-11.59 pm: 18.8% of the patients, 0.00-5.59 am: 4.6% of the patients) than during the day. Patients who arrived between 0.00 am-5.59 am were younger (49.4 ± 22.8 years) and had a higher injury severity score (ISS) (21.4 ± 11.5) and lower Glasgow Coma Scale (GCS) score (11.6 ± 4.4) than those admitted during the day (12.00 pm-05.59 pm; age: 55.3 ± 21.6 years, ISS: 20.6 ± 11.4, GCS: 12.6 ± 4.0). Time in the trauma department and time to an emergency operation were only marginally different. Time to imaging was slightly prolonged during the night (0.00 am-5.59 am: X-ray 16.2 ± 19.8 min; CT scan 24.3 ± 18.1 min versus 12.00 pm- 5.59 pm: X-ray 15.4 ± 19.7 min; CT scan 22.5 ± 17.8 min), but the delay did not affect the outcome. The outcome was also not affected by level of the trauma center. There was no relevant difference in the Revised Injury Severity Classification II (RISC II) score or mortality rate between patients admitted during the day and at night. There were no differences in RISC II scores or mortality rates according to time period. Admission at night was not a predictor of a higher mortality rate. CONCLUSION: The patient population and injury severity vary between the day and night with regard to age, injury pattern and trauma mechanism. Despite the differences in these factors, arrival at night did not have a negative effect on the outcome.

Long-term Efficacy of Percutaneous Epidural Neurolysis of Adhesions in Chronic Lumbar Radicular Pain: 10 Year Follow-up of a Randomized Controlled Trial.

BACKGROUND: No long-term follow-up data exist in any treatment for chronic radicular pain occurring with disc pathology and after failed back surgery. A previous randomized controlled trial (RCT) has proven efficacy in short-term follow-up as an evidence-based effective therapeutic option. OBJECTIVES: Long term data is needed to determine the efficacy and cost- effectiveness of minimal invasive procedures. The present study reports 10 year follow-up results from the randomized trial. STUDY DESIGN: A prospective, randomized, placebo-controlled, interventional clinical trial. A power calculation was based on a previous feasibility trial. SETTING: University medical centers. METHODS: After a 4 year enrollment phase, 381 patients with chronic radicular pain persisting beyond 4 months, who failed conservative treatments, were screened. Ninety patients were enrolled. Patients were randomly assigned to receive percutaneous epidural lysis of adhesions or placebo with concealed allocation in permuted blocks of 4 to 8 patients each, and stratified by treatment center. The primary outcomes were a mean change of the Oswestry Disability Index (ODI) scores and Visual Analog Scale (VAS), one and 10 years after intervention. For each rating scale an analysis of variance with the within-patient factor time (baseline, one year follow-up, 10 year follow-up) and the between-patient factor treatment (lysis, placebo) was used. RESULTS: Homogeneity was shown at baseline between the groups. The ODI and VAS scores were significantly better one and 10 years in the lysis group vs the control group. The ODI in the lysis group improved from 55.3 ± 11.6 to 9.6 ± 9.3 after one year and to 11.7 ± 14.2 after 10 years. The placebo group also improved from 55.4 ± 11.5 to 30.7 ± 14.2 after one year and to 24.8 ± 12.0 after 10 years. The VAS improved from 6.7 ± 1.1 to 1.2 ± 1.1 after one year and to 1.5 ± 1.4 after 10 years in the lysis group and from 6.7 ± 1.1 to 2.8 ± 1.5 after one year and to 2.9 ± 1.3 after 10 years after placebo intervention. The statistical difference of the ODI and VAS between the treatment and control groups remain significant up to 10 years. No treatment-related severe adverse effects occurred within the 10 years, but minor transient neurological effects were seen directly after the intervention. LIMITATIONS: The long-term effects of single treatment components cannot be specified as no imaging examination was performed at 10 year follow-up. A large variety of unanalyzed noninvasive treatments were done within the 10 years. Some patients did not clearly remember the intervention after 10 years. Uncontrolled effects such as higher inhomogeneity of biometric properties, concomitant therapies, pain tolerance level, or just social effects could occur, but were not analyzed in the trial. CONCLUSION: This is the first 10 year follow-up report of a placebo-controlled RCT showing efficacy of the minimally invasive percutaneous adhesiolysis procedure for patients with chronic lumbosacral radicular pain. No alternative evidence-based treatment modality with 10 year follow-up is available to be recommended. This procedure should be considered as the first treatment option for patients with chronic lumbosacral radicular pain.

Missed hand and forearm injuries in multiple trauma patients: An analysis from the TraumaRegister DGU®.

PURPOSE: Multiple trauma patients have a high risk of missed injuries. The main point of our study was to provide new epidemiological data on hand and forearm injuries in multiple trauma with a focus on those that were missed. Therefore, we used the database of the TraumaRegister DGU®. METHODS: In this study, we evaluated anonymous data from 139931 patients aged 1-100 years with multiple trauma in the TraumaRegister DGU® of the German Society for Trauma Surgery from 2007 to 2017. Patients with hand and forearm injuries documented during hospital stay were identified and analyzed. We included fractures, dislocations, tendon injuries, nerve injuries and vessel injuries. Patients with missed hand and forearm injuries were compared with patients with primary diagnosed injuries in view of gender, age, ISS, Abbreviated Injury Score (AIS), Glasgow Coma Scale (GCS), Glasgow Outcome Scale (GOS), trauma mechanism type of injury, hospital stay, RISC II and mortality rate. Missed injuries were defined as injuries that were recently diagnosed and documented in the intensive care unit (ICU). RESULTS: A total of 50459 multiple trauma patients (36.1%) had hand or forearm injuries, and 89472 patients (63.9%) had neither. Patients with hand injuries were younger and were more often involved in car and motorcycle accidents. Severe head trauma was evaluated less frequently, and severe thorax trauma was evaluated more often in patients with hand injuries. The times of diagnosis of hand injuries were documented in 10971 cases. A total of 727 patients (6.6%) with missed hand injuries were registered. The most commonly missed injuries in multiple trauma were 104 carpal fractures/dislocations (11.2%), 195 nerve injuries (25.4%) and 54 tendon injuries (11.4%). Predisposing factors for missing injuries were multiple diagnoses, primary care in the first hospital and direct from emergency room transfer to the ICU. CONCLUSION: In contrast to previous findings, severely injured patients, especially those with head injuries and GCS of ≤8, were not predisposed to have missed hand injuries compared to patients without severe head trauma. Special attention should be paid to younger patients after traffic accidents with multiple diagnoses and direct transfer to the ICU.

[Hybrid operating room : Application in trauma surgery and orthopaedics]. / Der Hybridoperationssaal : Anwendung in Unfallchirurgie und Orthopädie.

BACKGROUND: For some years now, more and more hospitals in Germany have acquired so-called hybrid operating rooms. In these operating rooms it is possible to produce three-dimensional imaging during the operation. Originally developed for cardiovascular surgery, these rooms are increasingly being used for interdisciplinary purposes. Previous experiences in the use for trauma surgery and orthopedics has shown that three-dimensional imaging can have a positive effect on the success of surgery. OBJECTIVE: Can minimally invasive operations on the spine benefit intraoperatively from three-dimensional imaging with respect to operating times and results? METHODS: Minimally invasive operations on the spine performed at the UKSH Campus Kiel between 2015 and 2018 in the hybrid operating room were considered. These were compared to minimally invasive spinal surgery performed in conventional operating rooms. RESULTS: As is usual with the establishment of a new procedure, there are initially longer operating times. With regular use and appropriate training and experience of the personnel, the processes can be optimized. CONCLUSION: Due to the accuracy of the three-dimensional imaging, errors can be detected and eliminated at an early stage during the operation. Revisions are less frequent. In contrast, there is increased radiation exposure and sometimes longer operation and anesthesia times.

Accuracy of augmented reality surgical navigation for minimally invasive pedicle screw insertion in the thoracic and lumbar spine with a new tracking device.

BACKGROUND CONTEXT: Minimally invasive approaches are increasingly used in spine surgery. The purpose of navigation systems is to guide the surgeon and to reduce intraoperative x-ray exposure. PURPOSE: This study aimed to determine the feasibility and clinical accuracy of a navigation technology based on augmented reality surgical navigation (ARSN) for minimally invasive thoracic and lumbar pedicle screw instrumentation compared with standard fluoroscopy-guided minimally invasive technique. STUDY DESIGN/SETTING: Cadaveric laboratory study. METHODS: ARSN was installed in a hybrid operating room, consisting of a flat panel detector c-arm with two dimensional/three dimensional imaging capabilities and four integrated cameras in its frame. The surface-referenced navigation device does not require a bony reference but uses video cameras and optical markers applied to the patient's skin for tracking. In four cadavers, a total of 136 pedicle screws were inserted in thoracic and lumbar vertebrae. The accuracy was assessed by three independent raters in postoperative conventional computed tomography. RESULTS: The overall accuracy of ARSN was 94% compared with an accuracy of 88% for fluoroscopy. The difference was not statistically significant. In the thoracic region, accuracy with ARSN was 92% compared with 83% with fluoroscopy. With fluoroscopy, unsafe screws were observed in three normal cadavers and one with scoliosis. Using ARSN, unsafe screws were only observed in the scoliotic spine. No significant difference in the median of time for K-wire placement was recorded. As no intraoperative fluoroscopy was necessary in ARSN, the performing surgeon was not exposed to radiation. CONCLUSIONS: In this limited cadaveric study minimally invasive screw placement using ARSN was demonstrated to be feasible and as accurate as fluoroscopy. It did not require any additional navigation time or use of any intraoperative x-ray imaging, thereby potentially permitting surgery in a protective lead garment-free environment. A well-powered clinical study is needed to demonstrate a significant difference in the accuracy between the two methods. CLINICAL SIGNIFICANCE: ARSN offers real-time imaging of planned insertion paths, instrument tracking, and overlay of three dimensional bony anatomy and surface topography. The referencing procedure, by optical recognition of several skin markers is easy and does not require a solid bony reference as necessary for conventional navigation which saves time. Additionally, ARSN may foster the reduction of intraoperative x-ray exposure to spinal surgeons.

Pneumonia in severely injured patients with thoracic trauma: results of a retrospective observational multi-centre study.

BACKGROUND: While the incidence and aspects of pneumonia in ICU patients has been extensively discussed in the literature, studies on the occurrence of pneumonia in severely injured patients are rare. The aim of the present study is to elucidate factors associated with the occurrence of pneumonia in severely injured patients with thoracic trauma. SETTING: Level-I University Trauma Centres associated with the TraumaRegister DGU®. METHODS: A total of 1162 severely injured adult patients with thoracic trauma documented in the TraumaRegister DGU® (TR-DGU) were included in this study. Demographic data, injury severity, duration of mechanical ventilation (MV), duration of ICU stay, occurrence of pneumonia, bronchoalveolar lavage, aspiration, pathogen details, and incidences of mortality were evaluated. Statistical evaluation was performed using SPSS (Version 25.0, SPSS, Inc.) software. RESULTS: The overall incidence of pneumonia was 27.5%. Compared to patients without pneumonia, patients with pneumonia had sustained more severe injuries (mean ISS: 32.6 vs. 25.4), were older (mean age: 51.3 vs. 47.5) and spent longer periods under MV (mean: 368.9 h vs. 114.9 h). Age, sex (male), aspiration, and duration of MV were all independent predictors for pneumonia occurrence in a multivariate analysis. The cut-off point for duration of MV that best discriminated between patients who would and would not develop pneumonia during their hospital stay was 102 h. The extent of thoracic trauma (AISthorax), ISS, and presence of pulmonary comorbidities did not show significant associations to pneumonia incidence in our multivariate analysis. No significant difference in mortality between patients with and without pneumonia was observed. CONCLUSIONS: Likelihood of pneumonia increases with age, aspiration, and duration of MV. These parameters were not found to be associated with differences in outcomes between patients with and without pneumonia. Future studies should focus on independent parameters to more clearly identify severely injured subgroups with a high risk of developing pneumonia. LEVEL OF EVIDENCE: Level II - Retrospective medical record review.

A new multiple trauma model of the mouse.

BACKGROUND: Blunt trauma is the most frequent mechanism of injury in multiple trauma, commonly resulting from road traffic collisions or falls. Two of the most frequent injuries in patients with multiple trauma are chest trauma and extremity fracture. Several trauma mouse models combine chest trauma and head injury, but no trauma mouse model to date includes the combination of long bone fractures and chest trauma. Outcome is essentially determined by the combination of these injuries. In this study, we attempted to establish a reproducible novel multiple trauma model in mice that combines blunt trauma, major injuries and simple practicability. METHODS: Ninety-six male C57BL/6 N mice (n = 8/group) were subjected to trauma for isolated femur fracture and a combination of femur fracture and chest injury. Serum samples of mice were obtained by heart puncture at defined time points of 0 h (hour), 6 h, 12 h, 24 h, 3 d (days), and 7 d. RESULTS: A tendency toward reduced weight and temperature was observed at 24 h after chest trauma and femur fracture. Blood analyses revealed a decrease in hemoglobin during the first 24 h after trauma. Some animals were killed by heart puncture immediately after chest contusion; these animals showed the most severe lung contusion and hemorrhage. The extent of structural lung injury varied in different mice but was evident in all animals. Representative H&E-stained (Haematoxylin and Eosin-stained) paraffin lung sections of mice with multiple trauma revealed hemorrhage and an inflammatory immune response. Plasma samples of mice with chest trauma and femur fracture showed an up-regulation of IL-1ß (Interleukin-1ß), IL-6, IL-10, IL-12p70 and TNF-α (Tumor necrosis factor- α) compared with the control group. Mice with femur fracture and chest trauma showed a significant up-regulation of IL-6 compared to group with isolated femur fracture. CONCLUSIONS: The multiple trauma mouse model comprising chest trauma and femur fracture enables many analogies to clinical cases of multiple trauma in humans and demonstrates associated characteristic clinical and pathophysiological changes. This model is easy to perform, is economical and can be used for further research examining specific immunological questions.

Hepatocytes express the antimicrobial peptide HBD-2 after multiple trauma: an experimental study in human and mice.

BACKGROUND: Human-beta defensins (HBD) belong to the family of acute phase peptides and hold a broad antimicrobial spectrum that includes gram-positive and gram-negative bacteria. HBD are up-regulated after severe injuries but the source of posttraumatic HBD expression has not been focused on before. In the current study we analysed the role of liver tissue in expression of HBD after multiple trauma in human and mice. METHODS: HBD-2 expression has been detected in plasma samples of 32 multiple trauma patients (ISS > 16) over 14 days after trauma by ELISA. To investigate major sources of HBD-2, its expression and regulation in plasma samples, polymorphonuclear neutrophils (PMN) and human tissue samples of liver and skin were analysed by ELISA. As liver samples of trauma patients are hard to obtain we tried to review findings in an established trauma model. Plasma samples and liver samples of 56 male C57BL/6 N-mice with a thorax trauma and a femur fracture were analysed by ELISA, real-time PCR and immunohistochemistry for murine beta defensin 4 (MBD-4) and compared with the expression of control group without trauma. The induction of HBD-2 expression in cultured hepatocytes (Hep G2) was analysed after incubation with IL-6, supernatant of Staphylococcus aureus (SA) and Lipopolysaccharides (LPS). One possible signalling pathway was tested by blocking toll-like receptor 2 (TLR2) in hepatocytes. RESULTS: Compared to healthy control group, plasma of multiple traumatized patients and mice showed significantly higher defensin levels after trauma. Compared to skin cells, which are known for high beta defensin expression, liver tissue showed less HBD-2 expression, but higher HBD-2 expression compared to PMN. Immunhistochemical staining demonstrated upregulated MBD-4 in hepatocytes of traumatised mice. In HepG2 cells HBD-2 expression could be increased by stimulation with IL-6 and SA. Neutralization of HepG2 cells with αTLR2 showed reduced HBD-2 expression after stimulation with SA. CONCLUSION: Plasma samples of multiple traumatized patients showed high expression of HBD-2, which may protect the severely injured patient from overwhelming bacterial infection. Our data support the hypothesis that liver is one possible source for HBD-2 in plasma while posttraumatic inflammatory response.

Epidemiology of accidental hypothermia in polytrauma patients: An analysis of 15,230 patients of the TraumaRegister DGU.

BACKGROUND: Accidental hypothermia (AH) endangers the patient after polytrauma. Past studies have emphasized this entity as a major risk factor. The aim of this study was to describe the epidemiology of AH in major trauma considering the preclinical and clinical course. Predictors should be elucidated. METHODS: This is a retrospective investigation from the TraumaRegister DGU. Patients were documented in the period between 2002 and 2012. The study compared multiple-injured patients with or without hypothermic temperatures. Different groups of body core temperature were analyzed. Preclinical and clinical parameters were documented. RESULTS: Fifteen thousand two hundred thirty patients could be included. In 5,078 patients, temperature was below 36.0°C. Blunt trauma mechanisms surpassed penetrating injuries. The majority of patients sustained car accidents, accidents involving pedestrians, and falls from heights of greater than 3 m. Preclinical rescue procedures were extensively long in patients with low body temperature. Female gender, Glasgow Coma Scale score of 8 or less, nighttime, winter, motorcycle/bicycle accidents, Injury Severity Score 9 or greater, shock on site and in the emergency room, preclinical volume therapy, and time until admission to emergency room are significant risk factors to develop AH of 33°C. Volume management ranged between 1,453 ± 1,051 mL (33°C) and 1,058 ± 768 mL (36°C). Treatment in emergency room was extensively long. In further clinical course, severe AH advanced the clinical development of sepsis and multiple organ failure. The overall mortality inclined with decreasing body temperatures. CONCLUSIONS: Accidental hypothermia regularly occurred in polytrauma patients. Certain predictors exist, that is, female gender, which facilitate a body core temperature of 33°C. Preclinical and clinical courses match with other polytrauma studies. High incidence rates of sepsis, multiple organ failure, and mortality in hypothermic patients (33°C) demonstrate the severity of injury. Unfortunately, documentation of body core temperature remains challenging as the number of recorded hypothermic patients appears to be too small. We favor a strict focus on body core temperature on arrival in the emergency room. LEVEL OF EVIDENCE: Prognostic and epidemiological study, level III.

Local pamidronate influences fracture healing in a rodent femur fracture model: an experimental study.

BACKGROUND: Bisphosphonates are a main component in the therapy of osteoporosis and other bone resorptive diseases. Previous studies have shown a positive effect of systemically applied bisphosphonates on fracture healing. Nevertheless high doses are related to side effects like osteonecrosis of the jaw, nephrotoxis and gastrointestinal symptoms. In this study we investigated the effect of locally applied pamidronate on fracture healing. METHODS: In a rodent model a simple femur fracture was set in female Wistar rats. We performed intramedullary fixation of the fracture and placed a collagen matrix around the fracture area. One group was treated with pamidronate, the other group with placebo via the matrix. To investigate the volume and quality of the callus we used micro-CT (µCT) and histology after 14 and 28 days. RESULTS: Our results show a positive influence of local applied pamidronate on callus volume. After 14 days an insignificant increase of callus volume in the treated animals was seen. 28 days after trauma the increase of callus volume in the treatment group was significantly higher in comparison to the control group. Osteonecrosis was not seen. CONCLUSIONS: Locally applied bisphosphonates increase the callus volume in fracture healing.

Induced Hypothermia Preserves the Functional Enterocyte Mass in A Porcine Multiple Trauma Model: Retracted.

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) and the resulting multiple organ failure (MOF) following severe trauma are associated with increased morbidity and mortality. Due to intestinal mucosal lesions and gut barrier disorders, the intestine contributes decisively to how post-traumatic MOF develops. As mild therapeutic hypothermia has been found to have protective effects on post-traumatic organ injuries, we analysed its effects on the intestine. METHODS: In a porcine model, Forty pigs were assigned to four groups: sham or trauma groups each with two sub-groups receiving either hypothermia or normothermia. The trauma was a combined trauma of blunt chest trauma, liver laceration and haemorrhagic shock. Functional enterocyte mass and enterocyte necrosis were evaluated by measuring plasma citrulline and iFABP. Mucosal lesions were assessed using a semi-quantitative histological scoring system. RESULTS: In normothermic trauma animals, citrulline decreased significantly compared to both sham groups and to the hypothermic trauma group. However, citrulline levels did not differ significantly between the hypothermic trauma group and the hypothermic sham group. Although histological analysis demonstrated subepithelial lifting and mucosal oedema in the ileal mucosa of all trauma animals, the semi-quantitative score of the group treated with hypothermia was comparable to that of the hypothermic sham group. However, the score was significantly elevated in normothermic trauma animals in comparison to sham and hypothermic trauma animals. CONCLUSION: Induced hypothermia preserves the functional enterocyte mass after severe trauma. Therefore induced hypothermia might represent a therapeutic strategy to avoid posttraumatic organ dysfunction, although further studies regarding the safety and long-term effects are required. LEVEL OF EVIDENCE: Level III; therapeutic study.

The Use of Extracorporeal Membrane Oxygenation Systems in Severe Accidental Hypothermia After Drowning: A Centre Experience.

Cardiopulmonary failure because of drowning with accidental hypothermia (AH) remains a major task for emergency care physicians. In this case series, we describe our experience in nine patients with cardiopulmonary failure after drowning with AH less than 35°C, who were provided on an emergency basis with extracorporeal life support (ECLS) system or extracorporeal membrane oxygenation (ECMO). Conservative rewarming methods are not considered for this study. Preclinical conditions and protocols were gathered. Surgical reports and clinical data sets were collected. Median age was 24 years (range, 6-75 years). Six patients were male. Climatic conditions mostly showed cold to frosty weather. All cases had different preclinical rescue procedures. They reached the emergency department under cardiopulmonary resuscitation (CPR). Indications for ECLS were cardiac arrest, and in one case, pulmonary failure. Mean CPR duration was 60 min (range: 15-120 min). Before implantation, the median pH value was 6.9. Two patients could be successfully weaned from the systems. Cause of death was severe neurologic damage in six patients and cardiac failure in one patient. The use of ECLS/ECMO is a therapy option for a small range of patients with cardiopulmonary failure because of drowning with AH. Nevertheless, the interval of preclinical rescue remains extensively long.