Search

Purpose: There is no data that show if it is possible to determine if a curve is structural or non-structural or to assess flexibility of an adolescent idiopathic scoliosis (AIS) by recumbent images like a CT scan (CTS) instead of bending radiographs (BR). We investigated if the results of BR may be compared to those of CTS. Methods: We retrospectively analyzed prospectively collected data of patients with AIS in whom a selective spinal fusion was performed and in whom a CTS, BR, and full spine x-rays were made preoperatively. We measured the Cobb angles of the main and the minor curve in full spine x-ray, BR, and CTS. Results: After applying inclusion and exclusion criteria, 39 patients were included. We found a strong correlation (r = 0.806, p < 0.01) between the Cobb angle of the main curve in BR and the Cobb angle of the main curve in the CTS and between the Cobb angle of the minor curve in BR and the Cobb angle of the minor curve in the CTS (r = 0.601, p < 0.01). All patients with a minor curve of less than 25 degrees in the BR had a Cobb angle of less than 35 degrees in the CTS. Conclusion: Spinal curves showed a significant correlation between bending radiographs and recumbent images (CTS). In our group of patients, a Cobb angle of the minor curve of less than 35 degrees in the CTS indicated that this minor curve was non-structural. [ABSTRACT FROM AUTHOR]

Non-muscle invasive bladder cancer is a common tumour in men and women. In case of resistance to the standard therapeutic agents, gemcitabine can be used as off-label instillation therapy into the bladder. To reduce potential side effects, continuous efforts are made to optimise the therapeutic potential of drugs, thereby reducing the effective dose and consequently the pharmacological burden of the medication. We recently demonstrated that it is possible to significantly increase the therapeutic efficacy of mitomycin C against a bladder carcinoma cell line by exposure to non-toxic doses of blue light (453 nm). In the present study, we investigated whether the therapeutically supportive effect of blue light can be further enhanced by the additional use of the wavelength-specific photosensitiser riboflavin. We found that the gemcitabine-induced cytotoxicity of bladder cancer cell lines (BFTC-905, SW-1710, RT-112) was significantly enhanced by non-toxic doses of blue light in the presence of riboflavin. Enhanced cytotoxicity correlated with decreased levels of mitochondrial ATP synthesis and increased lipid peroxidation was most likely the result of increased oxidative stress. Due to these properties, blue light in combination with riboflavin could represent an effective therapy option with few side effects and increase the success of local treatment of bladder cancer, whereby the dose of the chemotherapeutic agent used and thus the chemical load could be significantly reduced with similar or improved therapeutic success. [ABSTRACT FROM AUTHOR]

Abstract: The adhesion of highly activated neutrophils to cerebral microvascular endothelial cells (MVECs) may contribute to disruption and hyperpermeability of the blood–brain barrier (BBB) after cardiac surgery with prolonged cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil-mediated BBB damage has not been investigated on the cellular level yet. Therefore, we studied the effects of neutrophils from cardiac surgery patients with CPB time <80min (group I; n=8) and >80min (group II; n=8) on the integrity of cultured porcine MVEC. Ex vivo, neutrophils of group II but not of group I significantly degraded the zonula adherens molecule β-catenin whereas VE-cadherin and occludin were not modified. The transendothelial electric resistance as a measure for the integrity of the endothelial monolayers was reduced over time in both groups. In conclusion, prolonged CPB time entails neutrophil-mediated decrease in MVEC β-catenin expression, and thus may be an important trigger for BBB disruption. [Copyright &y& Elsevier]

Background and aims: Osteosynthesis with the proximal femoral nail (PFN) features the advantages of high rotational stability of the head-neck fragment, an unreamed implantation technique and the possibility of static or dynamic distal locking. However, the use of the nail is technically ambitious and is accompanied by some risks of error, which can lead to failure of the osteosynthesis. In this paper we present the results of a critical analysis of mistakes that were made in our hospital during the introduction period of this implant. Patients and methods: We carried out a prospective analysis of the data of 121 consecutive patients who were suffering from trochanteric or subtrochanteric fracture between December 1997 and December 2000 and who had been treated with a PFN. Results: We identified intraoperative technical difficulties in 23 patients (19.1%). Seven cases showed postoperative local complications that required operative revision on six patients (4.9%). The main reasons for the failure of the operations involved were poor reduction and wrong choice of screws. Following our critical analysis, we were able to avoid those problems. Conclusions: When 31A fractures are to be stabilised with a PFN, the precise technical performance of the implantation represents the basic surgical requirement. Already present minor deviations will subsequently cause loosening of the implants and failure of the operation. [ABSTRACT FROM AUTHOR]

Background: The Calcaneus is the largest bone of the foot and the most frequent tarsal bone to be fractured. Overall, it causes round about 10 cases per 100,000 residents per year mainly in men. Especially displaced intra-articular calcaneus fractures often have early and late complications and its associated disability. There are various strategies for the treatment of displaced intra-articular calcaneus fractures, but the gold standard is still subject of a long-standing controversy. Minimally invasive procedures became more common in an attempt to reduce the high rate of complications associated with open reduction and internal fixation. With the increase in minimally invasive techniques, screw fixation also gained in significance. The current literature does not sufficiently elucidate whether the screw fixation is superior to other treatment options especially in relation to adverse events, health-related quality of life and postoperative pain. This study aims to investigate benefits and harms of treating displaced intra-articular calcaneus fractures (types II, III and IV according to Sanders) with screw fixation in adults. Methods: A systematic review will be conducted based on the principles described in the Cochrane Handbook. We will include adults with displaced intra-articular calcaneus fractures of Sanders type II, III and IV. The surgical method of screw fixation shall be compared to other surgical interventions to stabilise calcaneus fractures. Primary outcomes are serious adverse events, health-related quality of life and postoperative pain level. MEDLINE, CENTRAL, CINAHL, Web of Science and bibnet.org, ClinicalTrial.gov and the World Health Organization International Clinical Trials Registry Platform (ICTR) will be searched. Screening and data extraction will be performed by two authors independently. A third author will arbitrate disputes. Risk of Bias will be assessed with the Cochrane tool. Meta-analysis will be performed if participants, interventions, comparisons and outcomes are sufficiently similar to ensure a result that is clinically meaningful. Discussion: Due to the increasing use of minimally invasive techniques and the increasing use of screw fixation instead of open reduction and plate fixation, it is important to analyse the benefits and harms of screw fixation for calcaneus fractures. Screw fixation could, in the future, help to operate in a less invasive and tissue preserving manner while still achieving an adequate functional result for the patient Systematic review registration: CRD42021244695 [ABSTRACT FROM AUTHOR]

Background: Clinical trials investigating acetabular fractures are heterogeneous in their investigated outcomes and their corresponding measurements. Standardization may facilitate comparability and pooling of research results, which would lead to an increase in knowledge about the optimal treatment of acetabular fractures, resulting in long-term evidence-based treatment decisions and improvements in patient care. The aim of this systematic review is to identify the reported outcomes and their measurements from studies on treatments for acetabular fractures to develop a core outcome set which contains the most relevant outcome measures to be included in future studies. Methods: Studies published in English and German including patients aged 16 years and older, with a surgically treated acetabular fracture, will be included. Studies with nonsurgical treatment, pathologic fractures, polytraumatized patients, and patients younger than 16 years of age will be excluded because other outcomes may be of interest in these cases. Any prospective and retrospective study will be included. Systematic reviews will be excluded, but their included studies will be screened for eligibility. The literature will be searched on MEDLINE, CENTRAL, Web of Science, ClinicalTrials.gov, and WHO ICTRP. Risk of selective reporting of outcomes will be assessed using the Outcome Reporting Bias in Trials classification system. Heterogeneously defined outcomes that measure the same outcome will be grouped and subsequently categorized into outcome domains using the taxonomy of the Core Outcome Measures in Effectiveness Trials Initiative. Discussion: It is expected that a high number of studies will be included, and many outcomes will be identified using different definitions and measurement instruments. A limitation of this systematic review is that only previously investigated outcomes will be detected, thus disregarding potentially relevant outcomes. Systematic review registration: PROSPERO CRD42022357644 [ABSTRACT FROM AUTHOR]

The cellular mechanisms of burn conversion of heat damaged tissue are center of many studies. Even if the molecular mechanisms of heat-induced cell death are controversially discussed in the current literature, it is widely accepted that caspase-mediated apoptosis plays a central role. In the current study we wanted to develop further information on the nature of the mechanism of heat-induced cell death of fibroblasts in vitro. We found that heating of human fibroblast cultures (a 10 s rise from 37 °C to 67 °C followed by a 13 s cool down to 37 °C) resulted in the death of about 50% of the cells. However, the increase in cell death started with a delay, about one hour after exposure to heat, and reached the maximum after about five hours. The lack of clear evidence for an active involvement of effector caspase in the observed cell death mechanism and the lack of observation of the occurrence of hypodiploid nuclei contradict heat-induced cell death by caspase-mediated apoptosis. Moreover, a dominant heat-induced increase in PARP1 protein expression, which correlated with a time-delayed ATP synthesis inhibition, appearance of double-strand breaks and secondary necrosis, indicate a different type of cell death than apoptosis. Indeed, increased translocation of Apoptosis Inducing Factor (AIF) and Macrophage Migration Inhibitory Factor (MIF) into cell nuclei, which correlates with the mentioned enhanced PARP1 protein expression, indicate PARP1-induced, AIF-mediated and MIF-activated cell death. With regard to the molecular actors involved, the cellular processes and temporal sequences, the mode of cell death observed in our model is very similar to the cell death mechanism via Parthanatos described in the literature. • Results contradict heat-induced cell death by caspase-mediated apoptosis. • Results indicate a different heat induced cell death of fibroblasts than apoptosis. • Results indicate a heat-induced cell death via Parthanatos. [ABSTRACT FROM AUTHOR]

Introduction: When needed operative treatment of sacral fractures is mostly performed with percutaneous iliosacral screw fixation. The advantage of navigation in insertion of pedicle screws already could be shown by former investigations. The aim of this investigation was now to analyze which influence iliosacral screw placement guided by navigation has on duration of surgery, radiation exposure and accuracy of screw placement compared to the technique guided by fluoroscopy. Methods: 68 Consecutive patients with sacral fractures who have been treated by iliosacral screws were inclouded. Overall, 85 screws have been implanted in these patients. Beside of demographic data the duration of surgery, duration of radiation, dose of radiation and accuracy of screw placement were analyzed. Results: When iliosacral screw placement was guided by navigation instead of fluoroscopy the dose of radiation per inserted screw (155.0 cGy*cm2 vs. 469.4 cGy*cm2p < 0.0001) as well as the duration of radiation use (84.8 s vs. 147.5 s p < 0.0001) were significantly lower. The use of navigation lead to a significant reduction of duration of surgery (39.0 min vs. 60.1 min p < 0.01). The placement of the screws showed a significantly higher accuracy when performed by navigation (0 misplaced screws vs 6 misplaced screws—p < 0.0001). Conclusion: Based on these results minimal invasive iliosacral screw placement guided by navigation seems to be a safe procedure, which leads to a reduced exposure to radiation for the patient and the surgeon, a reduced duration of surgery as well as a higher accuracy of screw placement. [ABSTRACT FROM AUTHOR]

Summary: We examined incidence rates (IR) for all distal radius fracture (DRF) events based on inpatient and outpatient data from a large statutory health insurance in Germany. Of all DRF, 56% were treated as inpatients, and thus, 44% treated as outpatients. IR were higher in women than in men. Purpose: Although a distal radius fracture (DRF) is one of the most common fractures in the elderly population, epidemiological data are limited. Many studies examine only hospitalized patients, do not analyze time trends, or include only small populations. In this retrospective population-based observational study, routine data on inpatient and outpatient care of persons aged ≥ 60 years insured by a large statutory health insurance in Germany were analyzed from 2014 to 2018. Methods: DRF were identified by ICD-10 codes. All DRF events of an individual were considered with a corresponding individual washout period. Incidence rates (IR) and time trends were estimated assuming a Poisson distribution per 100,000 person-years, with 95% confidence intervals [95% CI] and age-sex standardization to the German population in 2018. Associations of calendar year, age, sex, and comorbidity with IR were examined using Poisson regression estimating incidence rate ratios (IRR) with CI. Results: The study population consists of 974,332 insured individuals, with 16,557 experiencing one or more DRF events during the observation period. A total of 17,705 DRF events occurred, of which 9961 (56.3%) were hospitalized. Standardized IR were 439 [424–453] (inpatient: 240 [230–251], outpatient: 199 [189–209]) in 2014 and 438 [423–452] (inpatient: 238 [227–249], outpatient: 200 [190–210]) in 2018. Female sex, older age, and comorbidity were associated with higher IR and adjusted Poisson regression showed no significant time trend (IRR overall 0.994 [0.983–1.006]). Conclusion: A relevant proportion of DRF were treated in outpatient settings, so both inpatient and outpatient data are necessary for a valid estimate. [ABSTRACT FROM AUTHOR]

Background: Soft tissue swelling assessment benefits from a reproducible and easy to use measurement method. Monitoring of the injured lower extremity is of clinical import during staged soft tissue management. Portable 3D scanners offer a novel and precise option to quantify and contrast the shapes and volumes of the injured and contralateral uninjured limbs. This study determined three regions of interest (ROI) within the lower extremity (lower leg, ankle and foot), that can be used to evaluate 3D volumetric assessment for staged soft tissue management in orthopedic and trauma surgery. Methods: Twelve healthy volunteers (24 legs) were included in this cohort study. Scans of all three ROI were recorded with a portable 3D scanner (Artec, 3D scanner EVA) and compared between the right and left leg using the software Artec Studio (Arctec Group, Luxemburg). Results: Mean volume of the right leg was 1926.64 ± 308.84 ml (mean ± SD). ROI: lower leg: 931.86 ± 236.15 ml; ankle: 201.56 ± 27.88 ml; foot: 793.21 ± 112.28 ml. Mean volume of the left leg was 1937.73 ± 329.51 ml. ROI: lower leg: 933.59 ± 251.12 ml; ankle: 201.53 ± 25.54 ml; foot: 802.62 ± 124.83 ml. There was no significant difference of the overall volume between right and left leg (p > 0.05; overall volume: △ difference: 29.5 ± 7.29 ml, p = 0.8; lower leg: △ difference: 21.5 ± 6.39 ml, p = 0.8; ankle: △ difference: 5.3 ± 2.11 ml, p = 0.4; △ difference: 16.33 ± 4.45 ml, p = 0.8. Conclusion: This pilot study defines three regions of interest of the lower leg and demonstrates no difference between the right and left side. Based on these ROI, further studies are needed to evaluate the clinical applicability of the scanner. [ABSTRACT FROM AUTHOR]

Introduction: Several scores were introduced to diagnose and to classify osteomyelitis in practice. Mouse models are often used to study the pathophysiology of bone infection and to test therapeutic strategies. Aim of the present study was to design a score to diagnose and quantify implant-associated infection in a murine experimental model.Materials and Methods: Four independent parameters were developed: existence of callus, consolidation of the fracture, structural changes of the medullary cavity and number of bacteria. The score was assessed in a standardized implant-associated mouse model with 35 BALB/c-mice. The left femur was osteotomized, fixed by a titanium locking plate and infection was induced by inoculation of Staphylococcus aureus into the fracture gap. For the sham group, the procedure was performed without inoculation of bacteria. The score was assessed on days 7, 14 and 28. Each item of the score showed lower values for the infection group compared to the controls after 4 weeks.Results: Regardless of the assessed time point, the overall total score was significantly higher in the control group compared to the infection group (p < 0.0001). Analysis revealed a sensitivity of 0.85, specificity of 1.0, negative predictive value of 0.67 and positive predictive value of 1.0.Conclusion: The proposed score assessing severity of fracture-related infection in an implant-associated murine model was easy to access, feasible to diagnose and estimate bone healing and infection in a murine bone infection with a high sensitivity. Therefore, this score might be a useful tool to quantify infection-related changes after fracture in further future preclinical studies. [ABSTRACT FROM AUTHOR]

Dupuytren's disease (DD) is a fibroproliferative disorder affecting the palmar fascia, causing functional restrictions of the hand and thereby limiting patients' daily lives. The disturbed and excessive myofibroblastogenesis, causing DD, is mainly induced by transforming growth factor (TGF)-β1. But, the extent to which impaired TGF-β1 release or TGF-β signal degradation is involved in pathologically altered myofibroblastogenesis in DD has been barely examined. Therefore, the complex in which TGF-β1 is secreted in the extracellular matrix to elicit its biological activity, and proteins such as plasmin, integrins, and matrix metalloproteinases (MMPs), which are involved in the TGF-β1 activation, were herein analyzed in DD-fibroblasts (DD-FBs). Additionally, TGF-β signal degradation via caveolin-1 was examined with 5-fluoruracil (5-FU) in detail. Gene expression analysis was performed via Western blot, PCR, and immunofluorescence analyses. As a surrogate parameter for disturbed myofibroblastogenesis, -smooth-muscle-actin (-SMA) expression was evaluated. It was demonstrated that latency-associated peptide (LAP)-TGF-β and latent TGF-β-binding protein (LTBP)-1 involved in TGF-β-complex building were significantly upregulated in DD. Plasmin a serinprotease responsible for the TGF-β release was significantly downregulated. The application of exogenous plasmin was able to inhibit disturbed myofibroblastogenesis, as measured via -SMA expression. Furthermore, a reduced TGF-β1 degradation was also involved in the pathological phenotype of DD, because caveolin-1 expression was significantly downregulated, and if rescued, myofibroblastogenesis was also inhibited. Therefore, our study demonstrates that a deficient release and degradation of TGF-β1 are important players in the pathological phenotype of DD and should be addressed in future research studies to improve DD therapy or other related fibrotic conditions. [ABSTRACT FROM AUTHOR]

Purpose: There is no data that shows if it is possible to determine if a curve is structural or non-structural or to assess flexibility of an adolescent idiopathic scoliosis (AIS) by magnetic resonance imaging (MRI) instead of bending radiographs (BR). We investigated if the results of BR may be compared to those of MRI. Methods: We retrospectively analyzed prospectively collected data of patients with AIS in whom a selective spinal fusion was performed and in whom a MRI, BR and full-spine X-rays were obtained preoperatively. We measured the Cobb angles of the main and of the minor curve in full-spine X-ray (FSR), BR and MRI and analyzed the degree of the intervertebral disk degeneration in the MRI. Results: After applying inclusion and exclusion criteria, 25 patients were included. We found a significant correlation (p < 0.05, Corr Coeff = 0.41) between the Cobb angle of the main curve in FSR and the Cobb angle of the main curve in the MRI and between the Cobb angle of the minor curve in FSR and the Cobb angle of the minor curve in the MRI (p < 0.001, Corr Coeff = 0.04). All patients with a minor curve of less than 25° in the BR had a Cobb angle of less than 30° in the MRI. Conclusion: Spinal curves showed a significant correlation between bending radiographs and recumbent images (MRI). In our group of patients, a Cobb angle of the minor curve of less than 30° in the MRI indicated that this minor curve was non-structural according to the classification of Lenke. [ABSTRACT FROM AUTHOR]

Trauma represents the leading cause of death among young people in western countries. Among the beneficial role of neutrophils in host defence, excessive priming and activation of neutrophils after major trauma lead to an overwhelming inflammatory response and secondary host tissue injury due to the release of toxic metabolites and enzymes. Hyperbaric oxygen (HBO) therapy has been proposed to possess antiinflammatory effects and might represent an appropriate therapeutic option to lower inflammation in a broad range of patients. Here, we studied the effects of HBO on the activity of neutrophils isolated from severely injured patients (days 1–2 after trauma), in fact on the production of reactive oxygen species (ROS) and release of neutrophil extracellular traps (NETs). We found exposure to HBO therapy to significantly diminish phorbol-12-myristate-13-acetate (PMA)-induced ROS production in neutrophils isolated from patients and healthy volunteers. At the same time, marked decrease in NETs release was found in control cells and a less pronounced reduction in patient neutrophils. Impaired ability to produce ROS following exposure to HBO was demonstrated to be linked to a strong downregulation of the activity of p38 MAPK. Only slight suppression of ERK activity could be found. In addition, HBO did not influence neutrophil chemotaxis or apoptosis, respectively. Collectively, this study shows for the first time that HBO therapy suppresses ROS production in inflammatory human neutrophils, and thus might impair ROS-dependent pathways, e.g. kinases activation and NETs release. Thus, HBO might represent a feasible therapy for patients suffering from systemic inflammation, including those with multiple trauma. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterize three regions of interest (ROI) around the knee with a portable 3D scanner (Artec 3D scanner EVA). Soft tissue topography assessment with an optimized, precise, and reproducible method may assist surgeons when managing soft tissue swelling in the post traumatic setting. Methods: 12 healthy volunteers (24 legs, 7 women, 5 man) were included in this study. The patient cohort showed a mean age of 27.1 years (SD±3), a mean weight of 70 kg (SD±13) and a mean height of 171 cm (SD±8.8). All scans were recorded by the same examiner in the same room and with the same scanner (Artec, 3 D scanner EVA). Three volume regions of interest (ROI) were defined: the distal femur (circumference measured between the of superior extent of the patella to 10 cm proximal), the knee joint (measured from the top of the patella to the tibial tuberosity) and the proximal tibia (tibial tuberosity to 10 cm distal). Results: The mean volume of the right leg was 3.901 l (I. distal femur: 1.63 l, knee joint: 1.33 l, proximal tibia: 1.10 l) and mean volume of the left leg was 3.910 l (I. distal femur: 1.66 l, knee joint: 1.34 l, proximal tibia: 1.12 l). The volume difference between the right and left leg was 0.094 l (SD ± 0.083 l) The Wilcoxon-Mann-Whitney test showed no significant differences of the volumes between the right and left leg. Conclusions: This study demonstrates that portable 3D scanning could be an accurate and reliable tool for orthopedics and trauma surgeons. Based on the ROIs of this pilot study, further studies are needed to test the significance for clinical applications for patients with an injured knee. [ABSTRACT FROM AUTHOR]

Locked antegrade or retrograde nailing of humeral shaft and proximal humerus fractures is a well etablished treatment option. Anatomic-morphological studies revealed a potential high risk of axillary nerve injury within proximal interlocking screw insertion. However, clinical experiences do not seem to confirm this, as there is a lack of interlocking screw insertion associated axillary lesions in literature. We report about a 69-year-old man with a humeral shaft fracture (AO-type 12-A3) stabilized by a retrograde implanted interlocking nail. Proximal interlocking screw insertion was performed in a posterior-to-anterior direction. The fracture healed uneventfully. In a follow-up examination 2 years later, an atrophy and paralysis of the deltoid muscle were visible. Electrophysiological evaluation confirmed an isolated axillary nerve injury. Nevertheless, the patient showed good functional recovery with almost free range of motion. Even for clinical practise proximal interlocking screw insertion is associated with a substantial risk of axillary nerve injury. Particularly for posterior-to-anterior screw insertion anatomic conditions should be considered. In spite of axillary nerve lesion, recovery of almost full shoulder function is possible by compensating the loss of deltoid function by rotator cuff muscles. [ABSTRACT FROM AUTHOR]

Dupuytren's disease (DD) is a fibroproliferative disorder of the palmar aponeurosis, which is characterized by a compound myofibrogenesis and evidenced by an increased expression of α-smooth muscle actin (α-SMA). In Dupuytren's tissue, higher levels of reactive oxygen species (ROS) are documented, stimulating the proliferation and differentiation of myofibroblasts. Our preliminary study demonstrates that α-SMA-expression is significantly inhibited by blue light irradiation in DD. The objective of this study was to investigate the beneficial effect of blue light irradiation and to elucidate the influence of ROS on myofibrogenesis in the pathogenesis of DD. Therefore, an in-vitro model of human DD fibroblasts was used. DD fibroblasts and control fibroblasts isolated from carpal tunnel syndrome (CTS) were daily irradiated with 40 J/cm2 (λ = 453 nm, 38 mW/cm2). Protein expression of ROS-modulating enzymes (Catalase, NOX4, SOD1, MnSOD) and α-SMA were determined, and additionally analysed after a pharmacological inhibition of the TGF-β1-signaling with SB431542. Furthermore, the protein expression of α-SMA as surrogate parameter for myofibrogenesis was evaluated after applying different concentrations of long-lasting ROS. It could be determined that the beneficial blue light irradiation, which inhibited myofibrogenesis, is mediated by a significant inhibition of catalase protein expression. This effect should be accompanied with an increased intracellular ROS level. Proof of evidence was an H2O2-application on DD fibroblasts, also leading to a decreased myofibrogenesis. Furthermore, it could be demonstrated that endogenous MnSOD was significantly downregulated in resting DD fibroblasts. If DD fibroblasts were treated with the pharmacological inhibitor SB431542, myofibrogenesis was inhibited, but MnSOD expression was simultaneously elevated, which ought to affect ROS level by raising intracellular H2O2 amount. Blue light irradiation as well as the pharmacological action of SB431542 in consequence mediates their beneficial effect on disturbed myofibrogenesis in DD by further increasing ROS level. The present study demonstrates the importance of intracellular ROS homeostasis in DD and illuminates the beneficial effect of blue light as a promising therapy option for DD. [ABSTRACT FROM AUTHOR]

The need for an autologous cell source for bone tissue engineering and medical applications has led researchers to explore multipotent mesenchymal stromal cells (MSC), which show stem cell plasticity, in various human tissues. However, MSC with different tissue origins vary in their biological properties and their capability for osteogenic differentiation. Furthermore, MSC-based therapies require large-scale ex vivo expansion, accompanied by cell type-specific replicative senescence, which affects osteogenic differentiation. To elucidate cell type-specific differences in the osteogenic differentiation potential and replicative senescence, we analysed the impact of BMP and TGF-β signaling in adipose-derived stromal cells (ASC), fibroblasts (FB), and dental pulp stromal cells (DSC). We used inhibitors of BMP and TGF-β signaling, such as SB431542, dorsomorphin and/or a supplemental addition of BMP-2. The expression of high-affinity binding receptors for BMP-2 and calcium deposition with alizarin red S were evaluated to assess osteogenic differentiation potential. Our study demonstrated that TGF-β signaling inhibits osteogenic differentiation of ASC, DSC and FB in the early cell culture passages. Moreover, DSC had the best osteogenic differentiation potential and an activation of BMP signaling with BMP-2 could further enhance this capacity. This phenomenon is likely due to an increased expression of activin receptor-like kinase-3 and -6. However, in DSC with replicative senescence (in cell culture passage 10), osteogenic differentiation sharply decreased, and the simultaneous use of BMP-2 and SB431542 did not result in further improvement of this process. In comparison, ASC retain a similar osteogenic differentiation potential regardless of whether they were in the early (cell culture passage 3) or later (cell culture passage 10) stages. Our study elucidated that ASC, DSC, and FB vary functionally in their osteogenic differentiation, depending on their tissue origin and replicative senescence. Therefore, our study provides important insights for cell-based therapies to optimize prospective bone tissue engineering strategies. [ABSTRACT FROM AUTHOR]

Background: Driving a motor vehicle needs a specific joint mobility and yet only limited knowledge exists regarding the necessary ankle range of motion. The goal of this study is to characterize the sequence and range of ankle motion.Methods: The arc of plantarflexion/dorsiflexion and supination/pronation was recorded in the right and left ankle using electrogoniometers while thirty laps were driven by fifteen healthy participants around a course in a manual transmission car with a left sided steering wheel. The driver was required to perform the following maneuvers during each lap: (I) Vehicle acceleration and gear change, (II) Sudden evasion, (III) Routine turning, (IV) Rapid turning, (V) Vehicle acceleration followed by emergency braking.Results: Driving required the right ankle to plantarflex 13±9 and dorsiflex 22±7 while supinating 15±7 degrees and pronating minimally. The left ankle plantarflexed 19±10and dorsiflexed 17±10 while supinating 15±7 degrees and pronating minimally. The right ankle dorsiflexed significantly more (p=0.00), and yet the left ankle had a significantly higher maximum plantarflexion and range of plantarflexion/dorsiflexion (p=0.00). Emergency braking resulted in a significantly higher maximum plantarflexion as well as plantarflexion/dorsiflexion range when compared to other maneuvers.Conclusion: This study describes the range of ankle motion identified to drive a car with a manual transmission and a left-sided steering wheel. The right and left ankle exhibit different arcs of motion during driving. This knowledge may assist when evaluating a patient's driving capability. Further studies are needed to investigate whether movement restrictions impair driving.Level Of Evidence: Basic science study. [ABSTRACT FROM AUTHOR]

β-Endorphin exerts a broad spectrum of physiological activity on mood, immune functions, pain management, reward effects, and behavioral stability. β-Endorphin is produced in certain neurons within the central and peripheral nervous system but also in the skin, especially in response to ultraviolet radiation. In the present study we have investigated the impact of visible blue light at λ = 453 nm (BL) on β-endorphin production of primary human skin keratinocytes (hKC) in-vitro as well as on systemic β-endorphin formation of whole-body exposed subjects in-vivo. We found that BL irradiation significantly enhanced both keratinocytic β-endorphin production of hKC cultures as well as systemic β-endorphin concentrations in light exposed healthy subjects. Interestingly, in hKC cultures elevated β-endorphin formation was paralleled by significantly increased levels of non-enzymatically generated nitric oxide (NO), whereas elevated systemic β-endorphin values of BL-exposed subjects were accompanied by enhanced systemic concentration of bioactive NO-derivates. These findings point to a pivotal role of NO in the molecular mechanism of the observed BL-induced effects, and indeed, exogenously applied NO was able to significantly enhance β-endorphin production in hKC cultures. Thus, our finding of BL-induced increases in systemic β-endorphin concentration in-vivo can be plausibly explained by an event sequence comprising 1.) BL-driven non-enzymatic formation of NO in the exposed skin tissue, 2.) systemic distribution of cutaneously produced NO in the form of bioactive nitroso compounds, 3.) a subsequent NO-dependent induction of β-endorphin synthesis in epidermal keratinocytes, and 4.) probably also a NO-dependent modulation of β-endorphin synthesis in specialized neurons within the central and peripheral nervous system. Image 1 • In addition to its essential role in vitamin D synthesis, the environmental factor sunlight, especially its ultraviolet (UV) fraction, also strongly affects the human psyche, e.g. by modulating the synthesis psychoactive mediators like β-endorphin. • Here we show for the first time with human skin keratinocyte cultures but also with whole-body-irradiated healthy volunteers that visible UV radiation-free blue light, which has a much lower risk for side effects than UV radiation, also can induce a significant increase in local as well as systemic production of β-endorphin. • The underlying mechanism comprises an enhanced local or systemic generation of nitric oxide (NO) via blue lightinduced decomposition of photo-labile NO derivates. • Thus, based on our findings, blue light might have a relevant clinical potential to serve as supportive measure in the therapy of several psychiatric disorders that might by modulated by β-endorphin. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the accuracy of preoperative templating in total hip arthroplasty (THA) using conventional 2-dimensional (2D) and computed tomography (CT)-based 3-dimensional (3D) measures. Methods: One hundred and sixteen consecutive primary THAs were analysed. The preoperative diagnosis was primary osteoarthritis in all cases. The 2D templating and the 3D templating were performed by two different residents. All templating results were available for the orthopaedic surgeon performing the procedure. Accuracies with regard to the predicted and actual implant sizes were determined for each procedure. Implantation of the size as planned was defined as "exact", whereas the use of components within one size larger or smaller (±1) as planned were defined as "accurate." Results: The 3D templating was significantly more accurate in predicting implant sizing compared to 2D templating for primary total hip arthroplasty (THA). The difference was statistically significant for the cup templating ("exact" p = 0.02; "accurate" p = 0.01) and for the stem templating ("exact" p = 0.04; "accurate" p = 0.01). Conclusion: Our results support the superiority of 3D templating over 2D templating in predicting implant size. [ABSTRACT FROM AUTHOR]

Cerament (Bonesupport Holding, Lund, Sweden) is a bioresorbable synthetic bone substitute consisting of calcium sulfate and hydroxyapatite which is successfully used as a bone graft in bone defects or in delayed and non-unions after fractures. Besides, calcium sulfate/ hydroxyapatite (CAS/HA) could have, attributed to its composition and osteoinductive properties, have great importance in the treatment of bone infections with critical size defects (CSD). Aim of the study was to evaluate the effects of antibiotic infused CAS/HA on inflammation and bone healing in an implant-associated osteitis mice model. In a standardized murine model, the left femur of 72 BALB/c mice were osteotomized, generating a CSD (2,5 mm) with stabilization through a 6-hole titanium locking plate. Osteitis has been induced through inoculation of Staphylococcus aureus (SA) into the fracture gap. To analyze the effect of CAS/HA, following groups were generated with either CAS/HA, CAS/HA with gentamycin (CAS/ HA-G) or CAS/HA with vancomycin (CAS/HA-V) insets placed into the osteotomy. Debridément and lavages were progressed on day 7 and 42 to determine the local bacterial growth and the immune reaction. Fracture healing was quantified on day 7 and 42 by x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of Interleukin (IL)– 6 and polymorphonuclear neutrophils (PMN) in lavage samples. Osteitis induced higher IL-6 and PMN-levels in the lavage samples on day 7. Both parameters showed a reduction in all groups on day 42. CAS/HA-V revealed a significant reduction of CFU and PMNs in lavage samples on day 42. A positive effect on bone healing could only be shown in non-infected mice. Whereas, application of mere CAS/HA in infected mice did show tendencies of bone destruction and lysis, independent of impregnation with antibiotics or not. Thus, application of CAS/HA in acute implant-associated infections is not recommended. In non-infectious environments or after infect-convalescence CAS/HA could albeit serve as a suggestive tool in trauma and orthopedic surgery. [ABSTRACT FROM AUTHOR]

Dupuytren’s contracture is a fibroproliferative disorder affecting the palmar fascia of the hand. Most affected are the ring fingers, and little fingers of middle-aged men. Symptomatic for this disease is the increased proliferation and differentiation of fibroblasts to myofibroblasts, which is accompanied by an elevated α-SMA expression. The present study evaluated the therapeutic benefit of blue light (λ = 453 nm, 38 mW/cm2, continuous radiance, spot size 10–12 cm2) as well as the molecular mechanism mediating this effect. It could be determined that blue light significantly diminished the induced α-SMA protein expression in both normal palmar fibroblasts and Duypuytren’s fibroblasts. The beneficial effect mediated by this irradiance, radiant exposure and wavelength was associated with an elevated reactive oxygen species generation. Furthermore, the data underlines the potential usefulness of blue light irradiation as a promising therapy option for Dupuytren’s disease, especially for relapse prevention, and may represent a useful strategy to treat further fibrotic diseases, such as keloids, hypertrophic scarring, and scleroderma. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy (HBO) is applied very successfully in treatment of various diseases such as chronic wounds. It has been already suggested as adjunctive treatment option for osteitis by immune- and fracture modulating effects. This study evaluates the importance of HBO in an early implant-associated localized osteitis caused by Staphylococcus aureus (SA) compared to the standard therapy. In a standardized murine model the left femur of 120 BALB/c mice were osteotomized and fixed by a titanium locking plate. Osteitis has been induced with a defined amount of SA into the fracture gap. Debridément and lavages were progressed on day 7, 14, 28 and 56 to determine the local bacterial growth and the immune reaction. Hyperbaric oxygen (2 ATA, 90%) was applied for 90 minutes on day 7 to 21 for those mice allocated to HBO therapy. To evaluate the effect of HBO therapy the following groups were analyzed: Two sham-groups (12 mice / group) with and without HBO therapy, two osteotomy groups (24 mice / group) with plate osteosynthesis of the femur with and without HBO therapy, and two osteotomy SA infection groups (24 mice / group) with and without HBO therapy. Fracture healing was also quantified on day 7, 14, 28 and 56 by a.p. x-ray and bone healing markers from blood samples. Progression of infection was assessed by estimation of colony-forming units (CFU) and immune response was analyzed by determination of polymorphonuclear neutrophils (PMN), Interleukin (IL) - 6, and the circulating free DNA (cfDNA) in lavage samples. Osteitis induced significantly higher IL-6, cfDNA- and PMN-levels in the lavage samples (on day 7 and 14, each p < 0.05). HBO-therapy did not have a significant influence on the CFU and immune response compared to the standard therapy (each p > 0.05). At the same time HBO-therapy was associated with a delayed bone healing assessed by x-ray radiography and a higher rate of non-union until day 28. In conclusion, osteitis led to significantly higher bacterial count and infection parameters. HBO-therapy neither had a beneficial influence on local infection nor on immune response or fracture healing compared to the standard therapy in an osteitis mouse model. [ABSTRACT FROM AUTHOR]

Excessive neutrophil activation accompanied by delayed apoptotic cell death in inflammatory conditions causes progressive damage of cells and tissues, leading to life-threatening multiple organ dysfunction syndrome. Previous work suggested that circulating serum factors during inflammation are critically involved in the suppression of neutrophil cell death although the identity of these antiapoptotic mediators remained elusive. In this study, we identified the acute phase protein α-1 Antitrypsin (AAT) as a potent suppressor of staurosporine (STS)-induced apoptosis in human neutrophils through a mechanism implicating caspases-independent pathways. We show here that serum levels of AAT, potentially in part released by stimulated neutrophils, are markedly elevated in major trauma patients suffering from systemic inflammatory response syndrome (SIRS). Notably, AAT depletion from serum increased sensitivity of human neutrophils for STS-induced cell death. In fact, AAT was demonstrated to confer intrinsic apoptosis resistance by preventing PKC/Akt inactivation and subsequent proteasomal degradation of antiapoptotic Mcl-1 protein in response to STS treatment. Neither MAP kinase ERK1/2 nor caspases were found to be involved in AAT-triggered antiapoptotic pathways in neutrophils. In summary, these results establish a novel pivotal role of circulating AAT in mediating survival by antagonizing the proapoptotic action of the PKC inhibitor STS and should be considered for AAT augmentation therapies in future. [ABSTRACT FROM AUTHOR]

Background: Severely displaced supracondylar fractures of the humerus in children are frequently associated with complications including neurovascular injuries, non-union, or compartment syndrome. In the current literature, no report exists about postoperative brachial artery entrapment in combination with an inconspicuous preoperative neurovascular examination.Case Presentation: We present a case of a 6-year-old white boy with a pulseless radial and ulnar artery after open reduction and internal fixation of a severely displaced supracondylar fracture of his right humerus (Gartland type III) using four K-wires. Remarkably, the preoperative neurovascular examination was inconspicuous. Doppler ultrasound of his brachial artery revealed no pulse when his elbow was in flexion and a faint pulse when it was in full extension 10 hours postoperatively. Revision surgery was performed immediately. On intraoperative examination, a kinking of his brachial artery caused by an entrapment of the tunica externa in the reduced fracture was seen and the artery was released by microsurgical arteriolysis immediately. At the final follow-up examination, positive palpable pulse with good capillary filling and, according to Flynn's criteria, an excellent recovery of elbow function was observed 3 months postoperatively.Conclusions: This case demonstrates a rare complication of postoperative artery entrapment with inconspicuous preoperative neurovascular examination. It strongly emphasizes the need for a standardized postoperative neurovascular assessment with fully flexed as well as fully extended elbow. [ABSTRACT FROM AUTHOR]

Bone defects remain a challenge for patients and orthopaedic surgeons. Autologous transfer of cancellous bone grafts remains the standard of care. However, in recent years various osteoinductive substitute materials, such as platelet rich plasma (PRP) and hyperbaric oxygen therapy (HBO) have been shown to improve bone healing. This study evaluates the effects of a combined application of PRP and HBO with autologous bone grafting in an animal model. In 48 New Zealand White rabbits bone defects at the radius were filled with autologous bone harvested at the iliac crest. This was combined with application of autologous PRP and/or HBO treatment for the duration of this study. After 3 and 6 weeks histomorphometric, immunohistochemical and radiologic evaluations were performed. All animals tolerated the treatment well. Improved bone regeneration was shown in all groups at 6 weeks compared to 3 weeks. Additional application of PRP and HBO resulted in an increase in new bone formation and increased neovascularization at 3 and 6 weeks. There was no statistical significant difference between PRP and HBO application in these regards. A combinatory use of PRP and HBO resulted in an increased bone regeneration and neovascularization compared to all other groups. This study provides evidence for an improvement of bone regeneration with the combinatory application of PRP and HBO to autologous cancellous bone grafts in a model of weight bearing bone defects in rabbits. Also synergistic effects of these two measures on angiogenesis were evident. [ABSTRACT FROM AUTHOR]

Human urothelial bladder carcinoma (uBC) is the second most tumor entity of the urogenital tract. As far as possible, therapy for non-muscle invasive uBC takes place as resection of the tumor tissue, followed by intravesical chemotherapy or immunotherapy. Because of the high recurrence rate of uBC, there is a need for improved efficiency in the treatment. In the present in vitro study we have evaluated a new approach to enhance the cytotoxic efficiency of Mitomycin C (MMC), which is commonly used for intravesical treatment of uBC on the relevant urothelial cancer cell line RT112. For that we used quasi-monochromatic blue light (453 ± 10 nm) at its non-toxic dose of 110 J/cm2 as an additive stimulus to enhance the therapeutic efficiency of MMC (10 μg/ml). We found, that blue light exposure of RT112 cells led to a very strong increase in intracellular production of reactive oxygen species (ROS) and to a significant reduction (p < 0.05) of all function parameters of mitochondrial respiration, including basal activity and ATP production. Although not being toxic when used as a single impact, together with MMC blue light strongly enhanced the therapeutic efficiency of MMC in the form of significantly enhanced cytotoxicity via apoptosis and secondary necrosis. Our results clearly show that blue light, most likely due to its ability to increase intracellular ROS production and reduce mitochondrial respiration, increased the cytotoxic efficiency of MMC and therefore might represent an effective, low-side-effect, and success-enhancing therapy option in the local treatment of bladder cancer. • Blue light enhances ROS production in human urothelial bladder carcinoma cells. • Blue light reduces mitochondrial respiration and ATP production in these tumor cells. • Both properties of Blue light enhance the cytotoxic efficiency of Mitomycin C. [ABSTRACT FROM AUTHOR]

Epidemiological data about pelvic fractures are limited. Until today, most studies only analyzed inpatient data. The purpose of this study was to estimate incidence rates of pelvic fractures in the German population aged 60 years or older, based on outpatient and inpatient data. We conducted a retrospective population-based observational study based on routine data from a large health insurance company in Germany. Age and sex-specific incidence rates of first fractures between 2008 and 2011 were calculated. We also standardized incidence rates with respect to age and sex in the German population. Multiple Poisson regression models were used to evaluate the association between the risk of first pelvic fracture as outcome and sex, age, calendar year and region as independent variables. The total number of patients with a first pelvic fracture corresponded to 8,041 and during the study period 5,978 insured persons needed inpatient treatment. Overall, the standardized incidence rate of all first pelvic fractures was 22.4 [95% CI 22.0–22.9] per 10,000 person-years, and the standardized incidence rate of inpatient treated fractures 16.5 [16.1–16.9]. Our adjusted regression analysis confirmed a significant sex (RR 2.38 [2.23–2.55], p < 0.001, men as reference) and age effect (higher risk with increasing age, p < 0.001) on first fracture risk. We found a slight association between calendar year (higher risk in later years compared to 2008, p = 0.0162) and first fracture risk and a further significant association with region (RR 0.92 [0.87–0.98], p = 0.006, Westfalen-Lippe as reference). The observed incidences are considerably higher than incidences described in the international literature, even if only inpatient treated pelvic fractures are regarded. Besides which, non-inclusion of outpatient data means that a relevant proportion of pelvic fractures are not taken into account. Prevention of low energy trauma among older people remains an important issue. [ABSTRACT FROM AUTHOR]

Objective: Already duringtheir studies, medical students should intensively train their clinical thinking and practice skills, enhancing their clinical expertise in theoretical and practical terms. Methods: Based on the findings of educational research, a new curriculum for clinical training was developed at Duesseldorf University, focussing on workplace-based teaching, learning and assessment Results: For students in their 3rd, 4th and 5th year of study, our curriculum is based on learning with patient complaint items in regard to multidisciplinar areas of out patient and in patient care. For this educational format, 123 complaint items were defined and their compatibility with diseases from various disciplines was tested. Based on the complaint of a specific case, students locate the underlying disease pattern, the differential diagnostic and therapeutical procedures and thereby deepen the required knowledge in the basic subjects. Study books have been created by the clinical departments to support this process. Learning is integrated in competence-oriented and workplace-based learning and assessment, offering a close-knit contact between students and doctors. Conclusion: The concept allows the integration of theory into practice and the integration of knowledge from the basic, clinical-theoretical and clinical subjects into clinical thinking and action. [ABSTRACT FROM AUTHOR]

The increasing incidence of implant-associated infections induced by Staphylococcus aureus (SA) in combination with growing resistance to conventional antibiotics requires novel therapeutic strategies. In the current study we present the first application of the biofilm-penetrating antimicrobial peptide lysostaphin in the context of bone infections. In a standardized implant-associated bone infection model in mice beta-irradiated lysostaphin-coated titanium plates were compared with uncoated plates. Coating of the implant was established with a poly(D,L)-lactide matrix (PDLLA) comprising lysostaphin formulated in a stabilizing and protecting solution (SPS). All mice were osteotomized and infected with a defined count of SA. Fractures were fixed with lysostaphin-coated locking plates. Plates uncoated or PDLLA-coated served as controls. All mice underwent debridement and lavage on Days 7, 14, 28 to determine the bacterial load and local immune reaction. Fracture healing was quantified by conventional radiography. On Day 7 bacterial growth in the lavages of mice with lysostaphin-coated plates showed a significantly lower count to the control groups. Moreover, in the lysostaphin-coated plate groups complete fracture healing were observed on Day 28. The fracture consolidation was accompanied by a diminished local immune reaction. However, control groups developed an osteitis with lysis or destruction of the bone and an evident local immune response. The presented approach of terminally sterilized lysostaphin-coated implants appears to be a promising therapeutic approach for low grade infection or as prophylactic strategy in high risk fracture care e.g. after severe open fractures. [ABSTRACT FROM AUTHOR]

Introduction Systemic capillary leak syndrome is a rare and life threatening disease characterized by periodic episodes of hypovolemic shock due to leakage of plasma from the intravascular to the extravascular space. It is associated with hemoconcentration, hypoalbuminemia, and generalized edema. We report the case of a patient with idiopathic systemic capillary leak syndrome who developed an unexpected and potentially fatal abdominal and four-limb compartment syndrome. This was successfully treated with fasciotomies and medical treatment including terbutaline, theophylline, and corticosteroids. To the best of our knowledge this is the first report of this kind in the literature. Case presentation A previously healthy 54-year-old Caucasian man presented to the emergency department of our internal medicine ward with a medical history of aggravation of general health related to dizziness, weight gain, and two syncopal attacks. Due to a massive emission of fluids and proteins from the intravascular to the extracellular compartments, he developed compartment syndromes in his upper and lower limbs and the abdominal compartment. The abdomen and all four limbs required decompression by a fasciotomy of both forearms, both thighs, both lower legs, and the abdomen within 24 hours after admission. After 60 days of treatment he was dismissed from the clinic. He was able to return to his previous occupation and reached the same level of athletic activity as before the illness. Conclusions Systemic capillary leak syndrome is a very rare disease that can lead to a fatal clinical outcome. It is important to be aware of the fatal complications that can be caused by this disease. Despite the fact that systemic capillary leak syndrome represents a very rare disease it is still important to be aware of life threatening complications, like compartment syndromes, which need surgical intervention. However, early diagnosis and interdisciplinary treatment can lead to a good clinical outcome. [ABSTRACT FROM AUTHOR]

One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting. [ABSTRACT FROM AUTHOR]

ABSTRACT Staphylococcus aureus (SA) is the most common causative agent for implant-associated osteitis. The present study characterizes a novel model of a low grade acute SA osteitis with bone defect in the femur which is stabilized by a titanium locking plate. Wild-type Balb/c mice were osteotomized, fixed by a locking plate and infected with SA. Mice underwent debridement 7 and 14 days later and were sacrificed at Day 28. At Days 7, 14, and 28 after inoculation local and systemic cell populations and IL-6 were analyzed. Fracture healing was quantified by radiography. The control group underwent the same procedure without infection. The bacterial load of implant-associated osteitis with biofilm formation was quantified by counting CFU and real-time PCR. Fracture healing determined by radiography was delayed in infected compared to non-infected mice. Throughout the investigation period CFU and leukocyte counts, as well as IL-6 levels were found to be significantly elevated in infected mice at the infection site but not systemically. Our murine model allows the detailed investigation of implant associated localized osteitis with biofilm producing SA and its influence on fracture healing. The model provides a tool to analyze therapeutic or prophylactic approaches to the problem of biofilm-associated osteitis. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:2013-2020, 2013 [ABSTRACT FROM AUTHOR]

Highlights: [•] In ischemia copper dissociates from its carrier proteins, i.e., albumin. [•] Free Cu2+ ions are reduced to Cu1+ by ascorbate, Fe2+ and/or GSH. [•] Copper-catalyzed NO formation from nitrite exerts biological activity. [•] Cu1+-catalyzed NO formation represents a new protective principle to ischemic stress. [Copyright &y& Elsevier]

Abstract: In the present work, we have examined the impact of an inorganic orthosilicic acid-releasing spun fiber fleece (SIFIB) on wound closure in a porcine wound model in vivo as well as on wound healing-relevant parameters in vitro. In vivo SIFIB was completely bio-degradable and had no negative effects on wound closure or the wound healing process. In the in vitro experiments, SIFIB had no negative effects on proliferation of human skin fibroblast (FB) and endothelial cell (EC) cultures but strongly retarded the growth of the human monocyte cell line THP-1, and effectively inhibited human skin keratinocyte (KC) proliferation, which based on significantly enhanced KC differentiation. Furthermore, SIFIB exhibited strong anti-inflammatory properties, which based on SIFIB-dependent inhibition of expression and activity of NF-кB and/or concomitant enhanced expression of IкB, a NF-кB-inhibiting protein. Additionally, SIFIB significantly inhibited TGFβ-induced fibroblast differentiation and collagen synthesis as well as effectively reduced TGF-β synthesis of activated fibroblasts. We have demonstrated wound healing-relevant biological activities of a silica-based bio-degradable inorganic material, which might represent a new therapeutic tool in the treatment of chronic wounds. [Copyright &y& Elsevier]

Purpose: A bilateral fixed-angle plate was biomechanically compared to the two currently preferred methods of osteosynthesis for transverse patella fractures. It was hypothesized that the new angle-stable implant would provide a secure and sustainable fracture fixation, superior to the established standard techniques. Methods: Twenty-one identical patellae made of polyurethane foam (Sawbones), osteotomized to create a transverse two-part fracture, were fixed with modified anterior tension wiring, cannulated lag screws with anterior tension wiring or bilateral polyaxial 2.7-mm fixed-angle plates. The testing protocol consisted of 10,000 repetitive cycles using a non-destructive physiological load between 100 and 300 N at a simulated knee flexion of 60°. Results: All 21 Sawbone-patellae sustained repetitive loading up to 10,000 cycles without failing. The anterior tension wire group displayed significant displacement of the fracture gap (0.7 ± 0.2 mm) during cyclic loading, while both lag screws with tension wiring and bilateral fixed-angle plates showed no fracture gap widening at all ( p < 0.01). Conclusion: The bilateral fixed-angle plate and cannulated lag screws with anterior tension wiring preserved a constantly reduced fracture gap over 10,000 tensile cycles in contrast to modified anterior tension wiring, which exhibited significant widening of the gap after initial loading. Results of in vitro testing indicate that bilateral fixed-angle plates provide sustainable fixation stability offering a promising new option in the treatment for transverse patella fractures. [ABSTRACT FROM AUTHOR]

Abstract: Topical application of nitric oxide (NO) has been shown to exert beneficial effects in the therapy of chronic wounds, impaired microcirculation, and skin infections. Nitrite acidified by ascorbic acid has been widely used in many studies as NO-donor system, unfortunately with inflammatory and toxic effects on the treated skin due to unregulated excessive NO generation, low pH and possible toxic side products. Here we describe an essentially modified nitrite based NO generating system that avoid the mentioned unwanted side effects on human skin by using a pH-stable acetate/acetic acid buffer with a skin neutral pH of 5.5 and sodium ascorbate. In order to overcome the shortcoming of lower NO yields due to the higher pH-value and low nitrite concentrations, we have determined additionally the influence of copper ions. To investigate the influence of different NO release and penetration kinetics on NO-induced toxicity, we have developed a fibroblast assay using cell culture plates with gas permeable bottoms. The results show clearly that the donor system can achieve a sustained NO generation without generating high peaks. Furthermore, the presence of Cu2+ ions enhances manifold NO generation of pH/ascorbate-induced nitrite decomposition, a mechanism comprising the reduction of Cu2+ ions to Cu1+ by ascorbate. Finally, we have found that apart from the NO dose the NO release kinetics had a significant influence of cell toxicity. Thus, application of comparable NO amounts within a time interval of 600s led to the development of variable cell toxicities, which predominantly depended on the NO concentration values generated in the first 200s. In summary, we here describe a novel nitrite-based NO-donor system that can provide well defined NO concentrations at skin neutral pH-values for side effect poor topical dermal application, i.e. in the therapy of chronic wounds and impaired microcirculation. [Copyright &y& Elsevier]

Purpose: Displaced tibial eminence fractures require surgical fixation in order to obtain a stable knee joint. Suture fixation with FiberWire(®) seems to be the most favorable therapeutic option. Biomechanical studies show failure of this technique most commonly due to a suture cutout with subsequent fracture of the tibial eminence fragment. The goal of this study is to compare the biomechanical properties of three different techniques of suture fixation using FiberWire(®).Methods: Bone mineral density was evaluated in 18 human knee specimens by pqCT, and three similar groups were formed. A standardized anterior tibial eminence fracture was created, and suture fixation was performed using one of three different techniques in 6 specimens each. Cyclic and destructive testing was conducted.Results: Significant differences between the three techniques could be shown neither in the cycles needed to achieve a steady state nor in a failure load or initial stiffness. Almost all specimens failed by suture cutout.Conclusion: The presented modification of the existing technique for suture fixation of tibial eminence fractures did not lead to an increased initial stability nor did it lower the rate of suture cutout. All tested suture techniques showed comparable initial stiffness and failure load. [ABSTRACT FROM AUTHOR]

Purpose: Displaced tibial eminence fractures require surgical fixation in order to obtain a stable knee joint. Suture fixation with FiberWire seems to be the most favorable therapeutic option. Biomechanical studies show failure of this technique most commonly due to a suture cutout with subsequent fracture of the tibial eminence fragment. The goal of this study is to compare the biomechanical properties of three different techniques of suture fixation using FiberWire. Methods: Bone mineral density was evaluated in 18 human knee specimens by pqCT, and three similar groups were formed. A standardized anterior tibial eminence fracture was created, and suture fixation was performed using one of three different techniques in 6 specimens each. Cyclic and destructive testing was conducted. Results: Significant differences between the three techniques could be shown neither in the cycles needed to achieve a steady state nor in a failure load or initial stiffness. Almost all specimens failed by suture cutout. Conclusion: The presented modification of the existing technique for suture fixation of tibial eminence fractures did not lead to an increased initial stability nor did it lower the rate of suture cutout. All tested suture techniques showed comparable initial stiffness and failure load. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to investigate trends over time in the mortality of elderly patients after femoral neck fractures treated with bipolar hemiarthroplasty. Methods: Altogether 487 cases of femoral neck fracture treated with bipolar hemiarthroplasty were observed during a 20-year period. Mortality rates were calculated for five years postoperatively. To account for the age distribution of the study population standardised mortality ratios (SMR) with respect to the age-specific mortality of the German population were determined and compared. Additional changes of the SMRs over time and the influence of the time delay before surgery on long-term mortality were evaluated. Results: Femoral neck fractures treated with bipolar hemiendoprosthesis have a significant impact on mortality. Postoperative mortality is increased in patients of all age groups, but the effect diminishes in higher age groups. The influence on mortality was significantly greater for men than for women. The SMR has decreased from 3.52 before 1995 to 1.2 after 2006. Since 2006 there is no longer an increase in mortality after surgical treatment of a femoral neck fracture compared to general German population of the same age. Conclusion: Femoral neck fractures treated with bipolar hemiendoprosthesis result in a significantly increased mortality, however in our population this impact has significantly decreased over time. The effect on mortality is less in women and higher age groups than in men and younger patients. No influence of the time between accident and surgery on mortality could be detected. [ABSTRACT FROM AUTHOR]

The demand to develop convergent technology platforms, such as bio-functionalized medical devices, is rapidly increasing. However, the loss of biological function of the effector molecules during sterilization represents a significant and general problem. Therefore, we have developed and characterized a nano-coating (NC) formulation capable of maintaining the functionality of proteins on biological-device combination products. As a proof of concept, the NC preserved the structural and functional integrity of an otherwise highly fragile antibody immobilized on polyurethane during deleterious sterilizing irradiation (≥ 25 kGy). The NC procedure enables straight-forward terminal sterilization of bio-functionalized materials while preserving optimal conditioning of the bioactive surface. [Copyright &y& Elsevier]

Delayed neutrophil apoptosis and overshooting neutrophil activity contribute to organ dysfunction and subsequent organ failure in sepsis. Here, we investigated apoptotic signaling pathways that are involved in the inhibition of spontaneous apoptosis in neutrophils isolated from major trauma patients with uneventful outcome as well as in those with sepsis development. DNA fragmentation in peripheral blood neutrophils showed an inverse correlation with the organ dysfunction at d 10 after trauma in all patients, supporting the important role of neutrophil apoptosis regulation for patient's outcome. The expression of the antiapoptotic Bcl-2 protein members A1 and Mcl-1 were found to be diminished in the septic patients at d 5 and d 10 after trauma. This decrease was also linked to an impaired intrinsic apoptosis resistance, which has been previously shown to occur in neutrophils during systemic inflammation. In patients with sepsis development, delayed neutrophil apoptosis was found to be associated with a disturbed extrinsic pathway, as demonstrated by reduced caspase-8 activity and Bid truncation. Notably, the expression of Dad1 protein, which is involved in protein N-glycosylation, was significantly increased in septic patients at d 10 after trauma. Taken together, our data demonstrate that neutrophil apoptosis is regulated by both the intrinsic and extrinsic pathway, depending on patient's outcome. These findings might provide a molecular basis for new strategies targeting cell death pathways in apoptosis-resistant neutrophils during systemic inflammation. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of acute subcutaneous Achilles tendon rupture remains challenging. Whereas the results of conservative and operative treatment are inconsistent, early mobilisation treatment seems to be beneficial. Besides suture repair, operative treatment using adhesives reveals promising results. Our hypothesis was that a gluing technique provides initial stability comparable to sutures.Methods: In a biomechanical study, 18 fresh frozen sheep Achilles tendons were used to compare the biomechanical properties of suture repair using PDS® II and Bunnell's technique to tendon gluing using BioGlue® and Tissucol®. Load to failure testing was performed.Results: Ultimate failure loads of sutures (146.2 ± 30.8 N) are significantly superior to the techniques using BioGlue® (38.4 ± 18.3 N; p <0.0001) or Tissucol® (4.7 ± 2.5 N; p <0.0001). Interestingly, no significant differences in stiffness were found between the application of BioGlue® and PDS® II.Conclusions: Suture repair provides significantly superior biomechanical properties compared to the use of both tested adhesives BioGlue® and Tissucol®. Based on the presented data we recommend the use of suture material for open Achilles tendon repair. [ABSTRACT FROM AUTHOR]

Purpose: Treatment of acute subcutaneous Achilles tendon rupture remains challenging. Whereas the results of conservative and operative treatment are inconsistent, early mobilisation treatment seems to be beneficial. Besides suture repair, operative treatment using adhesives reveals promising results. Our hypothesis was that a gluing technique provides initial stability comparable to sutures. Methods: In a biomechanical study, 18 fresh frozen sheep Achilles tendons were used to compare the biomechanical properties of suture repair using PDS® II and Bunnell's technique to tendon gluing using BioGlue® and Tissucol®. Load to failure testing was performed. Results: Ultimate failure loads of sutures (146.2 ± 30.8 N) are significantly superior to the techniques using BioGlue® (38.4 ± 18.3 N; p <0.0001) or Tissucol® (4.7 ± 2.5 N; p <0.0001). Interestingly, no significant differences in stiffness were found between the application of BioGlue® and PDS® II. Conclusions: Suture repair provides significantly superior biomechanical properties compared to the use of both tested adhesives BioGlue® and Tissucol®. Based on the presented data we recommend the use of suture material for open Achilles tendon repair. [ABSTRACT FROM AUTHOR]

Abstract: Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. [Copyright &y& Elsevier]

Introduction. Neutrophil extracellular traps (NET) consist of a DNA scaffold that can be destroyed by Deoxyribonuclease (DNase). Thus DNases are potential prerequisites for natural counter regulation of NETs formation. In the present study, we determined the relationship of NETs and DNase after major trauma. Methods. Thirty-nine major trauma patients, 14 with and 25 without sepsis development were enrolled in this prospective study. Levels of cell-free (cf)-DNA/NETs and DNase were quantified daily from admission until day 9 after admission. Results. Levels of cf-DNA/NETs in patients who developed sepsis were significantly increased after trauma. In the early septic phase, DNase values in septic patients were significantly increased compared to patients without sepsis (P < 0.05). cf-DNA/NETs values correlated to values of DNase in all trauma patients and patients with uneventful recovery (P < 0.01) but not in septic patients. Recombinant DNase efficiently degraded NETs released by stimulated neutrophils in a concentration-dependent manner in vitro. Conclusions. DNase degrades NETs in a concentration-dependent manner and therefore could have a potential regulatory effect on NET formation in neutrophils. This may inhibit the antibacterial effects of NETs or protect the tissue from autodestruction in inadequate NETs release in septic patients. [ABSTRACT FROM AUTHOR]

Introduction: A tibial nail with fixed-angle locking screws intends to combine the advantages of angular stability and intramedullary stabilization in extraarticular proximal tibial fractures. The goal of this study is to analyze if the angle stable tibial nail (ASN) is biomechanically more stable than an established conventional standard nail (CN). Methods: Two types of nails were compared on a series of ten matched pairs of human tibiae. After setting a proximal tibial defect fracture, the intramedullary stabilized tibiae were axially loaded starting from 100 N increasing in steps of 100 N after every 200 cycles until failure was reached. Failure was defined as deformation of the fracture gap, fracturing of the bone or the implant. Results: The two types of nails showed no significant difference in terms of maximum tolerated load, maximum cycles repeated or axial deformation of the bone-implant construct. The mean load at failure was 1,365 N for the CN and 1,195 N for the ASN. The mean axial deformation for conventional (19 mm) and angle stable nail (21 mm) did not differ significantly. Slightly less nail or screw loosening was noticed with the fixed-angle nail. Conclusion: No significant difference in stability between the two compared implants could be demonstrated. A trend could be shown indicating that the rate of nail loosening in the proximal osteotomized part of the bone was lower for the angle stable nail. This trend, however, could not be substantiated statistically. [ABSTRACT FROM AUTHOR]