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BACKGROUND/OBJECTIVES: The aim was to compare ophthalmic diagnoses made by veterinarians to a deep learning (artificial intelligence) software tool which was developed to aid in the diagnosis of equine ophthalmic diseases. As equine ophthalmology is a very specialised field in equine medicine, the tool may be able to help in diagnosing equine ophthalmic emergencies such as uveitis. STUDY DESIGN: In silico tool development and assessment of diagnostic performance. METHODS: A deep learning tool which was developed and trained for classification of equine ophthalmic diseases was tested with 40 photographs displaying various equine ophthalmic diseases. The same data set was shown to different groups of veterinarians (equine, small animal, mixed practice, other) using an opinion poll to compare the results and evaluate the performance of the programme. Convolutional Neural Networks (CNN) were trained on 2346 photographs of equine eyes, which were augmented to 9384 images. Two hundred and sixty-one separate unmodified images were used to evaluate the trained network. The trained deep learning tool was used on 40 photographs of equine eyes (10 healthy, 12 uveitis, 18 other diseases). An opinion poll was used to evaluate the diagnostic performance of 148 veterinarians in comparison to the software tool. RESULTS: The probability for the correct answer was 93% for the AI programme. Equine veterinarians answered correctly in 76%, whereas other veterinarians reached 67% probability for the correct diagnosis. MAIN LIMITATIONS: Diagnosis was solely based on images of equine eyes without the possibility to evaluate the inner eye. CONCLUSIONS: The deep learning tool proved to be at least equivalent to veterinarians in assessing ophthalmic diseases in photographs. We therefore conclude that the software tool may be useful in detecting potential emergency cases. In this context, blindness in horses may be prevented as the horse can receive accurate treatment or can be sent to an equine hospital. Furthermore, the tool gives less experienced veterinarians the opportunity to differentiate between uveitis and other ocular anterior segment disease and to support them in their decision-making regarding treatment.
ABSTRACT
Osteoarthritis (OA) most frequently affects the knee joint and is associated with an elevated expression of cytokines and extracellular cartilage matrix (ECM), degrading enzymes such as matrix metalloproteinases (MMPs). Differences in gene expression of the intra-articularly located infrapatellar fat pad (IPFP) and other fatty tissue suggest its autonomous function, yet its role in OA pathogenesis remains unknown. Human IPFPs and articular cartilage were collected from OA patients undergoing total knee arthroplasty, and biopsies from the IPFP of healthy patients harvested during knee arthroscopy served as controls (CO). Isolated chondrocytes were co-cultured with either osteoarthritic (OA) or CO-IPFPs in a transwell system. Chondrocyte expression of MMP1, -3, -13, type 1 and 2 collagens, interleukin IL1ß, IL6, IL10, and tumor necrosis factor TNFα was analyzed by RTD-PCR at day 0 and day 2, and TNFα secretion was analyzed by ELISA. The cytokine release in IPFPs was assessed by an array. Results: Both IPFPs (CO, OA) significantly reduced the expression of type 2 collagen and TNFα in chondrocytes. On the other hand, only CO-IPFP suppressed the expression of type 1 collagen and significantly induced the MMP13 expression. On the contrary, IL1ß and IL6 were significantly induced when exposed to OA-IPFP. Conclusions: The partial loss of the suppressive effect on type 1 collagen gene expression found for OA-IPFP shows the pathological remodeling and dedifferentiation potential of the OA-IPFP on the chondrocytes. However, the significant suppression of TNFα implies that the OA- and CO-IPFP could also exhibit a protective role in the knee joint, preventing the progress of inflammation.
Subject(s)
Cytokines , Osteoarthritis, Knee , Humans , Cytokines/metabolism , Chondrocytes/metabolism , Osteoarthritis, Knee/metabolism , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Collagen Type I/metabolism , Knee Joint/pathology , Adipose Tissue/metabolismABSTRACT
BACKGROUND: This primary analysis evaluated the "PREVenting the impairment of primary Osteoarthritis by high-impact long-term Physical exercise regimen-Psychological Adherence Program" (PrevOP-PAP), designed to support patients with osteoarthritis of the knee (OAK) to engage in regular moderate-to-vigorous physical activity (MVPA) to reduce OAK symptoms (WOMAC scores). Theory-based on the health action process approach (HAPA), the intervention targeted volitional precursors of MVPA change: action and coping planning, maintenance and recovery self-efficacy, action control, and social network formation. We hypothesized that compared to an active control condition, increases in MVPA at the end of the 12-month intervention would translate into lower WOMAC scores at 24 months in the intervention condition. METHODS: Participants with radiographically verified moderate OAK (N = 241; 62.66% female; M(SD) = 65.60(7.61) years) were randomly assigned to the intervention (51%) or the active control condition. WOMAC scores (24 months) were the primary -, accelerometer-assessed MVPA (12 months) the key secondary outcomes. The PrevOP-PAP was a 12-month intervention with computer-assisted face-to-face and phone-based sessions designed to increase HAPA-proposed volitional precursors of MVPA change (up to 24 months; secondary outcomes). Intent-to-treat analyses included multiple regression and manifest path models. RESULTS: MVPA (12 months) did not mediate effects of the PrevOP-PAP on WOMAC scores (24 months). Compared to the active control condition, WOMAC scores (24 months) were lower in the intervention condition, but this effect did not remain stable in sensitivity analyses (b(SE) = -8.41(4.66), 95%-CI [-17.53; 0.71]). However, exploratory analyses revealed significantly stronger reductions in WOMAC-pain (24 months) in the intervention condition (b(SE) = -2.99(1.18), 95%-CI [-5.36; -0.63]). Groups did not differ in MVPA at 12 months (b(SE) = -3.78(3.42), 95%-CI [-10.80; 2.58]). Of the proposed precursors of MVPA change, action planning was higher in the intervention than in the control condition (24 months; b(SE) = 0.64(0.26), 95%-CI [0.14; 1.15]). CONCLUSIONS: Compared to an active control condition, the PrevOP-PAP did not produce reliable effects on WOMAC scores and none on preceding MVPA. Of the HAPA-proposed volitional precursors, only action planning was sustainably increased. Future interventions should use m-health applications to digitally support long-term changes in proposed volitional precursors of MVPA change. TRIAL REGISTRATION: German Clinical Trials Register; https://drks.de/search/de/trial/DRKS00009677 ; also available at http://apps.who.int/trialsearch/ ; registration number: DRKS00009677; date of registration: 26/01/2016.
Subject(s)
Osteoarthritis, Knee , Humans , Female , Male , Osteoarthritis, Knee/therapy , Osteoarthritis, Knee/psychology , Exercise/psychology , Pain , Self Efficacy , TelephoneABSTRACT
Infections are prevalent after spinal cord injury (SCI), constitute the main cause of death and are a rehabilitation confounder associated with impaired recovery. We hypothesize that SCI causes an acquired lesion-dependent (neurogenic) immune suppression as an underlying mechanism to facilitate infections. The international prospective multicentre cohort study (SCIentinel; protocol registration DRKS00000122; n = 111 patients) was designed to distinguish neurogenic from general trauma-related effects on the immune system. Therefore, SCI patient groups differing by neurological level, i.e. high SCI [thoracic (Th)4 or higher]; low SCI (Th5 or lower) and severity (complete SCI; incomplete SCI), were compared with a reference group of vertebral fracture (VF) patients without SCI. The primary outcome was quantitative monocytic Human Leukocyte Antigen-DR expression (mHLA-DR, synonym MHC II), a validated marker for immune suppression in critically ill patients associated with infection susceptibility. mHLA-DR was assessed from Day 1 to 10 weeks after injury by applying standardized flow cytometry procedures. Secondary outcomes were leucocyte subpopulation counts, serum immunoglobulin levels and clinically defined infections. Linear mixed models with multiple imputation were applied to evaluate group differences of logarithmic-transformed parameters. Mean quantitative mHLA-DR [ln (antibodies/cell)] levels at the primary end point 84 h after injury indicated an immune suppressive state below the normative values of 9.62 in all groups, which further differed in its dimension by neurological level: high SCI [8.95 (98.3% confidence interval, CI: 8.63; 9.26), n = 41], low SCI [9.05 (98.3% CI: 8.73; 9.36), n = 29], and VF without SCI [9.25 (98.3% CI: 8.97; 9.53), n = 41, P = 0.003]. Post hoc analysis accounting for SCI severity revealed the strongest mHLA-DR decrease [8.79 (95% CI: 8.50; 9.08)] in the complete, high SCI group, further demonstrating delayed mHLA-DR recovery [9.08 (95% CI: 8.82; 9.38)] and showing a difference from the VF controls of -0.43 (95% CI: -0.66; -0.20) at 14 days. Complete, high SCI patients also revealed constantly lower serum immunoglobulin G [-0.27 (95% CI: -0.45; -0.10)] and immunoglobulin A [-0.25 (95% CI: -0.49; -0.01)] levels [ln (g/l × 1000)] up to 10 weeks after injury. Low mHLA-DR levels in the range of borderline immunoparalysis (below 9.21) were positively associated with the occurrence and earlier onset of infections, which is consistent with results from studies on stroke or major surgery. Spinal cord injured patients can acquire a secondary, neurogenic immune deficiency syndrome characterized by reduced mHLA-DR expression and relative hypogammaglobulinaemia (combined cellular and humoral immune deficiency). mHLA-DR expression provides a basis to stratify infection-risk in patients with SCI.
Subject(s)
HLA-DR Antigens , Spinal Cord Injuries , Humans , Cohort Studies , Prospective Studies , Spinal Cord Injuries/complications , Syndrome , MonocytesABSTRACT
Procalcitonin (PCT) and C-reactive protein (CRP) are considered markers used in clinical practice to differentiate bacterial infections from autoimmune origin. Here we evaluate a rare case of a male patient diagnosed with juvenile idiopathic arthritis. The patient presented repeatedly to our department with atraumatic femoral head necrosis, traumatic medial femoral neck fracture and peri-implant femoral fracture. While undergoing repeated surgical interventions including a removal of osteosynthesis material and total endoprosthesis of his right hip including double subtrochanteric osteotomy, the patient developed drastically increasing infection parameters of PCT and CRP. After a completely inconspicuous revision we revealed the untypical genesis of a rheumatic cause. Consequently, we emphasize this etiology to be considered in further decision making for trauma surgery.
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BACKGROUND: Due to recent developments in artificial intelligence, deep learning, and smart-device-technology, diagnostic software may be developed which can be executed offline as an app on smartphones using their high-resolution cameras and increasing processing power to directly analyse photos taken on the device. OBJECTIVES: A software tool was developed to aid in the diagnosis of equine ophthalmic diseases, especially uveitis. STUDY DESIGN: Prospective comparison of software and clinical diagnoses. METHODS: A deep learning approach for image classification was used to train software by analysing photographs of equine eyes to make a statement on whether the horse was displaying signs of uveitis or other ophthalmic diseases. Four basis networks of different sizes (MobileNetV2, InceptionV3, VGG16, VGG19) with modified top-layers were evaluated. Convolutional Neural Networks (CNN) were trained on 2346 pictures of equine eyes, which were augmented to 9384 images. 261 separate unmodified images were used to evaluate the performance of the trained network. RESULTS: Cross validation showed accuracy of 99.82% on training data and 96.66% on validation data when distinguishing between three categories (uveitis, other ophthalmic diseases, healthy). MAIN LIMITATIONS: One source of selection bias for the artificial intelligence presumably was the increased pupil size, which was mainly present in horses with ophthalmic diseases due to the use of mydriatics, and was not homogeneously dispersed in all categories of the dataset. CONCLUSIONS: Our system for detection of equine uveitis is unique and novel and can differentiate between uveitis and other equine ophthalmic diseases. Its development also serves as a proof-of-concept for image-based detection of ophthalmic diseases in general and as a basis for its further use and expansion.
Subject(s)
Horse Diseases , Uveitis , Animals , Artificial Intelligence , Horse Diseases/diagnosis , Horses , Neural Networks, Computer , Uveitis/diagnosis , Uveitis/veterinaryABSTRACT
Intervertebral disc (IVD) herniation and degeneration is a major source of back pain. In order to regenerate a herniated and degenerated disc, closure of the anulus fibrosus (AF) is of crucial importance. For molecular characterization of AF, genome-wide Affymetrix HG-U133plus2.0 microarrays of native AF and cultured cells were investigated. To evaluate if cells derived from degenerated AF are able to initiate gene expression of a regenerative pattern of extracellular matrix (ECM) molecules, cultivated cells were stimulated with bone morphogenetic protein 2 (BMP2), transforming growth factor ß1 (TGFß1) or tumor necrosis factor-α (TNFα) for 24 h. Comparative microarray analysis of native AF tissues showed 788 genes with a significantly different gene expression with 213 genes more highly expressed in mild and 575 genes in severe degenerated AF tissue. Mild degenerated native AF tissues showed a higher gene expression of common cartilage ECM genes, whereas severe degenerated AF tissues expressed genes known from degenerative processes, including matrix metalloproteinases (MMP) and bone associated genes. During monolayer cultivation, only 164 differentially expressed genes were found. The cells dedifferentiated and altered their gene expression profile. RTD-PCR analyses of BMP2- and TGFß1-stimulated cells from mild and severe degenerated AF tissue after 24 h showed an increased expression of cartilage associated genes. TNFα stimulation increased MMP1, 3, and 13 expression. Cells derived from mild and severe degenerated tissues could be stimulated to a comparable extent. These results give hope that regeneration of mildly but also strongly degenerated disc tissue is possible.
Subject(s)
Annulus Fibrosus/metabolism , Extracellular Matrix/metabolism , Gene Expression Regulation/genetics , Intervertebral Disc Degeneration/metabolism , Intervertebral Disc Displacement/metabolism , Intervertebral Disc/metabolism , Annulus Fibrosus/pathology , Bone Morphogenetic Protein 2/pharmacology , Cells, Cultured , Extracellular Matrix/genetics , Gene Expression Profiling , Gene Expression Regulation/drug effects , Humans , Intervertebral Disc/pathology , Intervertebral Disc Degeneration/genetics , Intervertebral Disc Degeneration/pathology , Intervertebral Disc Displacement/genetics , Intervertebral Disc Displacement/pathology , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 3/metabolism , Oligonucleotide Array Sequence Analysis , Regeneration/drug effects , Regeneration/genetics , Transforming Growth Factor beta1/pharmacology , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
BACKGROUND: Regular physical activity (PA) was found to alleviate pain and improve functioning among patients with osteoarthritis of the knee (OAK). Heightened health demands due to OAK severity, body mass index (BMI), and depressive symptoms may require self-regulatory strategies to engage in more PA. Research on willpower-the capacity to exert self-control-suggests that believing that willpower is a nonlimited rather than a limited resource predicts effective self-regulation specifically when demands are high. The present study examines the association of OAK patients' willpower beliefs with their daily PA as a function of health demands. METHODS: To identify the moderating role of OAK severity (WOMAC), BMI, and depressive symptoms (CES-D) on the link between willpower beliefs and objectively assessed PA over a 7-day period, baseline data of a registered randomized controlled trial with 243 patients (Mage = 65.47 years, SD = 0.49) were examined in secondary analyses. RESULTS: Moderation analyses revealed that overall positive associations of willpower beliefs with PA were further qualified by OAK severity, BMI, and depressive symptoms. When patients faced less health demands, believing that willpower is nonlimited was associated with more PA. When health demands were higher, willpower beliefs were not associated with PA. CONCLUSION: OAK patients' willpower beliefs were associated with PA. However, facing more health demands seemed to erase this beneficial link. Improving willpower beliefs by way of intervention may help to shed more light on predictive direction and ways to overcome barriers to regular physical activity.
Subject(s)
Exercise/physiology , Osteoarthritis, Knee/physiopathology , Volition , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Self-ControlABSTRACT
Muscle fibre cross-sectional area (CSA) is an important biomedical measure used to determine the structural composition of skeletal muscle, and it is relevant for tackling research questions in many different fields of research. To date, time consuming and tedious manual delineation of muscle fibres is often used to determine the CSA. Few methods are able to automatically detect muscle fibres in muscle fibre cross-sections to quantify CSA due to challenges posed by variation of brightness and noise in the staining images. In this paper, we introduce the supervised learning-computer vision combined pipeline (SLCV), a robust semi-automatic pipeline for muscle fibre detection, which combines supervised learning (SL) with computer vision (CV). SLCV is adaptable to different staining methods and is quickly and intuitively tunable by the user. We are the first to perform an error analysis with respect to cell count and area, based on which we compare SLCV to the best purely CV-based pipeline in order to identify the contribution of SL and CV steps to muscle fibre detection. Our results obtained on 27 fluorescence-stained cross-sectional images of varying staining quality suggest that combining SL and CV performs significantly better than both SL-based and CV-based methods with regards to both the cell separation- and the area reconstruction error. Furthermore, applying SLCV to our test set images yielded fibre detection results of very high quality, with average sensitivity values of 0.93 or higher on different cluster sizes and an average Dice similarity coefficient of 0.9778.
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Tumours involving Pacinian corpuscles are rare. The literature identifies two main pathological disorders: the Pacinian corpuscle neuroma or hyperplasia and the Pacinian corpuscle neurofibroma. Published data are confusing and at times conflicting. This systematic review summarizes the available data in order to support clinicians in the differential diagnosis with other tumours responsible for unclear symptoms in the hands and fingers. We identified 67 pertinent articles. Although some similarities have been described, the two tumours have relevant differences, specifically when comparing age of the patient, location, symptoms, characteristic of a mass, and aetiology. All these factors should be taken into account in order to improve diagnostic accuracy. Despite the low incidence of unsuccessful surgeries, extraordinary measures are occasionally necessary to achieve complete resolution of symptoms.
Subject(s)
Hand/innervation , Hand/pathology , Neuroma/pathology , Pacinian Corpuscles/pathology , Diagnosis, Differential , Humans , Hyperplasia/pathology , Neurofibroma/pathologyABSTRACT
Osteoarthritis (OA) is the most common cause of disability in ageing societies, with no effective therapies available to date. Two preclinical models are widely used to validate novel OA interventions (MCL-MM and DMM). Our aim is to discern disease dynamics in these models to provide a clear timeline in which various pathological changes occur. OA was surgically induced in mice by destabilisation of the medial meniscus. Analysis of OA progression revealed that the intensity and duration of chondrocyte loss and cartilage lesion formation were significantly different in MCL-MM vs DMM. Firstly, apoptosis was seen prior to week two and was narrowly restricted to the weight bearing area. Four weeks post injury the magnitude of apoptosis led to a 40-60% reduction of chondrocytes in the non-calcified zone. Secondly, the progression of cell loss preceded the structural changes of the cartilage spatio-temporally. Lastly, while proteoglycan loss was similar in both models, collagen type II degradation only occurred more prominently in MCL-MM. Dynamics of chondrocyte loss and lesion formation in preclinical models has important implications for validating new therapeutic strategies. Our work could be helpful in assessing the feasibility and expected response of the DMM- and the MCL-MM models to chondrocyte mediated therapies.
Subject(s)
Cartilage, Articular/physiopathology , Chondrocytes/pathology , Menisci, Tibial/physiopathology , Osteoarthritis/physiopathology , Animals , Apoptosis/genetics , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Collagen Type II/metabolism , Disease Models, Animal , Humans , Menisci, Tibial/metabolism , Mice , Mice, Inbred C57BL , Osteoarthritis/genetics , Osteoarthritis/surgery , Proteoglycans/genetics , Proteoglycans/metabolism , Proteolysis , Weight-Bearing/physiologyABSTRACT
BACKGROUND: The present randomized controlled trial, which is crossed with the "PREVenting the impairment of primary Osteoarthritis by high impact long-term Physical exercise regimen" Main Medical Trial (PrevOP-MMT), aims to evaluate a psychological adherence program (PrevOP-PAP), and is designed to support persons with knee osteoarthritis (OAK) in the uptake and maintenance of regular physical activity to reduce OAK symptoms. The PrevOP-PAP is based on the Health Action Process Approach (HAPA), a social-cognitive theory predicting health behavior change in individuals, extended here by social network characteristics and social exchange processes. It is expected that participants with OAK receiving the PrevOP-PAP will maintain higher levels of regular physical activity throughout a 24-month period and consequently report lower levels of OAK symptoms than participants of an active control condition. METHODS: A total of N = 240 participants with medically verified moderate OAK will be randomly assigned to an intervention condition (PrevOP-PAP-I; 50%) or an active control condition (PrevOP-PAP-CTRL). The PrevOP-PAP-I includes a motivational intervention, repeated self-regulation interventions, and a network creation intervention delivered over 12 months. Modes of intervention delivery include a paper-pencil motivation leaflet with a quiz, a computer-assisted face-to-face intervention, four computer assisted phone-based interventions, and activity calendars. The PrevOP-PAP-CTRL includes the motivational intervention only. Primary outcome will be OAK symptoms. Secondary outcomes include objectively and subjectively measured physical activity and indicators of quality of life. Other outcomes are HAPA-derived self-regulatory indicators as well as proposed social network and social exchange mechanisms of health behavior change. Assessments take place at baseline, 6 months, 12 months, 18 months, and 24 months following baseline. DISCUSSION: Based on the extended HAPA, this study seeks to reveal the self-regulatory and social mechanisms of the uptake and maintenance of physical activity and their relation to disease symptoms in persons with OAK. The design and evaluation of this program are intended to become a yardstick for future development and implementation of digitalized psychological adherence programs in this population. TRIAL REGISTRATION: German Clinical Trials Register; also available at http://apps.who.int/trialsearch/ ; registration number: DRKS00009677 ; date of registration: 26 January 2016.
Subject(s)
Exercise/physiology , Exercise/psychology , Health Behavior/physiology , Osteoarthritis, Knee/psychology , Osteoarthritis, Knee/therapy , Patient Compliance/psychology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Motivation/physiology , Secondary Prevention/methodsABSTRACT
BACKGROUND: Ipsilateral femoral shaft and neck fractures are rare injuries, affecting mostly young patients who sustained high-energy traumas. In 19-50% of cases, the femoral fracture is misdiagnosed or overlooked at the initial presentation, with reportedly increased risk of complications such as non-union and avascular necrosis. We present a case of an ipsilateral femoral neck and shaft fracture, which was missed at initial presentation despite radiographic and computed tomography (CT) scan evaluation. CASE PRESENTATION: A 56-year old female was admitted to our institution following a high-energy trauma (fall from 6 m). Initial radiographic and CT scan evaluation revealed a displaced femoral shaft fracture but no other femoral fractures were detected. Closed reduction and external fixation of the femoral shaft fracture was performed in the emergency setting. Follow-up radiologic evaluations revealed an ipsilateral laterally displaced femoral neck fracture. Despite cephalomedullary nail fixation of both fractures performed on the third day from the initial injury, the patient developed a non-union of the femoral neck fracture, which led to cut-out of the lag screw with associated varus failure of the femoral neck fracture requiring surgical revision and implant of a bipolar hemiarthroplasty at one year follow up. The postoperative course was uneventful and the patient had a full long-term recovery. CONCLUSION: This case report exemplifies the need to maintain the highest level of suspiciousness for the concomitant presence of an ipsilateral femoral neck fracture when treating polytraumatized patients who sustained a femoral shaft fracture as a consequence of a high-energy trauma. Furthermore, the pre-operative standardized radiological evaluation (plain x-ray and CT scan) might not always help in ruling out these fractures. It is therefore necessary to adopt additional standardized radiographic protocols not only in the pre-operative but also in the intra-operative and immediate post-operative settings.
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INTRODUCTION: Inflammatory processes driven by cytokines play a crucial role during osteoarthritis (OA) progression. Dendritic polyglycerol sulfate (dPGS) was analyzed in vitro for its effects on articular chondrocytes, cartilage and cytokines involved in the OA process. METHODS: The metabolic activity of cultured human articular chondrocytes stimulated for 24 h with dPGS (10(-3)-10(-6) mol/L) was monitored using AlamarBlue(®) assay. The dPGS uptake was studied using fluorescence labeled nanoparticles. Further, chondrocytes were either treated with 10(-6) M dPGS, TNFα (10 ng/mL) alone or with a combination of both. The influence on extracellular matrix components, pro- and anti-inflammatory cytokines, matrix metalloproteinase (MMP)1 and the anaphylatoxin receptor C3aR was analyzed by RTD-PCR, flow cytometry and ELISA. RESULTS: Even at higher dosages (10(-3) mol/L), dPGS did not influence chondrocytes viability. Uptake of dPGS was successfully monitored in human articular chondrocytes and synovial fibroblasts, penetration into cartilage chips was up to ~50 µm. Cellular treatment with dPGS had no effect on synthesis of pro-inflammatory cytokines TNFα and IL-6, but expression of the anti-inflammatory IL-10 was upregulated. Cotreatment with TNFα and dPGS reduced the TNFα level, while IL-1ß, IL-6 and IL-10 expression did not change. Collagen type II gene expression was significantly reduced after preincubating cells with dPGS, but remained unaffected at the protein level. CONCLUSION: Results indicate that dPGS could play a role in regulation of cytokines associated with the inflammatory aspect of OA progression.
Subject(s)
Chondrocytes/drug effects , Dendrimers/pharmacology , Glycerol/pharmacology , Polymers/pharmacology , Aged , Aged, 80 and over , Animals , Cartilage, Articular/cytology , Cell Line , Cells, Cultured , Chondrocytes/metabolism , Collagen Type II/genetics , Collagen Type II/metabolism , Cytokines/metabolism , Extracellular Matrix/metabolism , Female , Fibroblasts/metabolism , Gene Expression Regulation/drug effects , Humans , Male , Mice , Middle Aged , SwineABSTRACT
BACKGROUND: Whole-body multislice computed tomography (WB-MSCT) has become an important diagnostic tool in the early treatment phase of severely injured patients. The optimal moment of WB-MSCT's use during this treatment phase remains unclear. Many trauma centers use WB-MSCT in addition to conventional radiographs, while some trauma centers use WB-MSCT as the only radiological tool. The aim of this study was to determine the differences between these two protocols and to answer the question of whether conventional radiographs can still be used in the safe treatment of polytrauma patients. METHODS: Patients from the TraumaRegister DGU® with an injury severity score (ISS) of ≥16 were included. Group I received conventional radiographs and focused assessment with sonography in trauma (FAST) prior to a WB-MSCT, and group II received an initial WB-MSCT and FAST. Both groups were compared concerning treatment time and outcome. RESULTS: A total of 3,995 patients in group I were compared to 4,025 patients in group II. There were no differences in ISS (29.97 vs. 29.94), gender (male: 73.5% vs. 72.8%), age (45.47 vs. 45.12 years), or calculated mortality (21.41% vs. 21.44%). Time needed in the resuscitation room was slightly longer in group I (72 vs. 64 min); the durations until admittance to the ICU and arrival to the OR were not significantly different between the groups. There was no difference in mortality (18.2% vs. 18.4%) or the standardized mortality ratio (SMR) (0.85 vs. 0.86). CONCLUSIONS: WB-MSCT plays an inherent role in the treatment of multiple-injured patients. However, the use of WB-MSCT as the only diagnostic method in the resuscitation room is not needed. Conventional radiographs and FAST followed by WB-MSCT can be performed in the early resuscitation phase without impairing patient outcomes. This approach enables the emergency room team to perform life-saving procedures - chest-tube insertion, laparotomy, cardiopulmonary resuscitation -immediately and simultaneous. Nevertheless, randomized multi-center trials are needed to determine the comparability and effectiveness of these algorithms.
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To overcome the limited intrinsic cartilage repair, autologous chondrocyte or bone-marrow-derived mesenchymal stromal cell (BM-MSC) was implanted into cartilage defects. For this purpose suitable biocompatible scaffolds are needed to provide cell retention, chondrogenesis and initial mechanical stability. The present study should indicate whether a recently developed highly porous alginate (Alg) foam scaffold supplemented with chondroitin sulfate (CS) allows the attachment, survival and chondrogenesis of BM-MSCs and articular chondrocytes. The foams were prepared using a freeze-drying method; some of them were supplemented with CS and subsequently characterized for porosity, biodegradation and mechanical profile. BM-MSCs were cultured for 1-2 weeks on the scaffold either under chondrogenic or maintenance conditions. Cell vitality assays, histology, glycosaminoglycan (sGAG) assay, and type II and I collagen immunolabelings were performed to monitor cell growth and extracellular matrix (ECM) synthesis in the scaffolds. Scaffolds had a high porosity ~93-95% with a mean pore sizes of 237±48 µm (Alg) and 197±61 µm (Alg/CS). Incorporation of CS increased mechanical strength of the foams providing gradually CS release over 7 days. Most of the cells survived in the scaffolds. BM-MSCs and articular chondrocytes formed rounded clusters within the scaffold pores. The BM-MSCs, irrespective of whether cultured under non/chondrogenic conditions and chondrocytes produced an ECM containing sGAGs, and types II and I collagen. Total collagen and sGAG contents were higher in differentiated BM-MSC cultures supplemented with CS than in CS-free foams after 14 days. The cell cluster formation induced by the scaffolds might stimulate chondrogenesis via initial intense cell-cell contacts.
Subject(s)
Alginates/pharmacology , Chondrogenesis/drug effects , Chondroitin Sulfates/pharmacology , Mesenchymal Stem Cells/cytology , Aged , Aged, 80 and over , Cartilage, Articular/cytology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Chondrocytes/cytology , Collagen Type I/metabolism , Collagen Type II/metabolism , DNA/metabolism , Female , Glucuronic Acid/pharmacology , Glycosaminoglycans/metabolism , Hexuronic Acids/pharmacology , Humans , Male , Mesenchymal Stem Cells/drug effects , Middle Aged , Porosity , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Tissue Scaffolds/chemistryABSTRACT
Chondrogenic differentiated mesenchymal stromal cells (MSCs) are a promising cell source for articular cartilage repair. This study was undertaken to determine the effectiveness of two three-dimensional (3D) culture systems for chondrogenic MSC differentiation in comparison to primary chondrocytes and to assess the effect of Interleukin (IL)-10 and Tumor Necrosis Factor (TNF)α on chondrogenesis by MSCs in 3D high-density (H-D) culture. MSCs were isolated from femur spongiosa, characterized using a set of typical markers and introduced in scaffold-free H-D cultures or non-woven polyglycolic acid (PGA) scaffolds for chondrogenic differentiation. H-D cultures were stimulated with recombinant IL-10, TNFα, TNFα + IL-10 or remained untreated. Gene and protein expression of type II collagen, aggrecan, sox9 and TNFα were examined. MSCs expressed typical cell surface markers and revealed multipotency. Chondrogenic differentiated cells expressed cartilage-specific markers in both culture systems but to a lower extent when compared with articular chondrocytes. Chondrogenesis was more pronounced in PGA compared with H-D culture. IL-10 and/or TNFα did not impair the chondrogenic differentiation of MSCs. Moreover, in most of the investigated samples, despite not reaching significance level, IL-10 had a stimulatory effect on the type II collagen, aggrecan and TNFα expression when compared with the respective controls.
Subject(s)
Chondrocytes/cytology , Chondrogenesis , Interleukin-10/pharmacology , Mesenchymal Stem Cells/cytology , Tumor Necrosis Factor-alpha/metabolism , Aggrecans/genetics , Aggrecans/metabolism , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/metabolism , Collagen Type II/genetics , Collagen Type II/metabolism , Humans , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Polyglycolic Acid/pharmacology , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Study Design Case report and review of the literature. Objectives Case report of a traumatic dissection of all major brain-supplying arteries resulting from a horseback-riding accident. Overview of the literature on diagnostic and therapeutic recommendations. Methods Case presentation. For the discussion, handpicked articles and PubMed database research with the keywords "dissection," "vertebral artery," "spine trauma," "computed tomography," "magnetic resonance imaging," and "angiography" were used. Results Despite high-energy induced acute lesion of all four cervical arteries, this 45-year-old patient did not demonstrate signs of microemboli nor suffer from stroke. Conclusion In case of high-energy trauma of the head and/or the neck, emergency physicians must consider traumatic cervical artery dissection (TCAD). Thus, emergency care algorithms should routinely include computed tomography angiography and magnetic resonance imaging. Although the incidence of TCAD-induced stroke is low, antiplatelet therapy is recommended in the presence of TCAD.
ABSTRACT
In diffuse idiopathic skeletal hyperostosis (DISH), recurrence of hyperostosis after surgical removal is common. While both non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy have been used in the prevention of heterotopic ossification, only NSAIDs have been applied for prophylaxis in DISH. As a previously undescribed prophylaxis of recurrence in DISH, we report a case treated with local radiotherapy.