Multi-modal assessment of a cardiac stem cell therapy reveals distinct modulation of regional scar properties.

BACKGROUND: The initial idea of functional tissue replacement has shifted to the concept that injected cells positively modulate myocardial healing by a non-specific immune response of the transplanted cells within the target tissue. This alleged local modification of the scar requires assessment of regional properties of the left ventricular wall in addition to commonly applied measures of global morphological and functional parameters. Hence, we aimed at investigating the effect of cardiac cell therapy with cardiovascular progenitor cells, so-called cardiac induced cells, on both global and regional properties of the left ventricle by a multimodal imaging approach in a mouse model. METHODS: Myocardial infarction was induced in mice by ligation of the left anterior descending artery, the therapy group received an intramyocardial injection of 1 × 106 cardiac induced cells suspended in matrigel, the control group received matrigel only. [18F]FDG positron emission tomography imaging was performed after 17 days, to assess regional glucose metabolism. Three weeks after myocardial infarction, cardiac magnetic resonance imaging was performed for morphological and functional assessment of the left ventricle. Following these measurements, hearts were excised for histological examinations. RESULTS: Cell therapy had no significant effect on global morphological parameters. Similarly, there was no difference in scar size and capillary density between therapy and control group. However, there was a significant improvement in contractile function of the left ventricle - left ventricular ejection fraction, stroke volume and cardiac output. Regional analysis of the left ventricle identified changes of wall properties in the scar area as the putative mechanism. Cell therapy reduced the thinning of the scar and significantly improved its radial contractility. Furthermore, the metabolic defect, assessed by [18F]FDG, was significantly reduced by the cell therapy. CONCLUSION: Our data support the relevance of extending the assessment of global left ventricular parameters by a structured regional wall analysis for the evaluation of therapies targeting at modulation of healing myocardium. This approach will enable a deeper understanding of mechanisms underlying the effect of experimental regenerative therapies, thus paving the way for a successful translation into clinical application.

Learning from terrorist mass casualty incidents: a global survey.

BACKGROUND: Reports published directly after terrorist mass casualty incidents frequently fail to capture difficulties that may have been encountered. An anonymised consensus-based platform may enable discussion and collaboration on the challenges faced. Our aim was to identify where to focus improvement for future responses. METHODS: We conducted a mixed methods study by email of clinicians' experiences of leading during terrorist mass casualty incidents. An initial survey identified features that worked well, or failed to, during terrorist mass casualty incidents plus ongoing challenges and changes that were implemented as a result. A follow-up, quantitative survey measured agreement between responses within each of the themes using a Likert scale. RESULTS: Thirty-three participants responded from 22 hospitals that had received casualties from a terrorist incident, representing 17 cities in low-middle, middle and high income countries. The first survey identified themes of sufficient (sometimes abundant) human resource, although coordination of staff was a challenge. Difficulties highlighted were communication, security, and management of blast injuries. The most frequently implemented changes were education on specific injuries, revising future plans and preparatory exercises. Persisting challenges were lack of time allocated to training and psychological well-being. The follow-up survey recorded highest agreement amongst correspondents on the need for re-triage at hospital (90% agreement), coordination roles (85% agreement), flexibility (100% agreement), and large-scale exercises (95% agreement). CONCLUSION: This survey collates international experience gained from clinicians managing terrorist mass casualty incidents. The organisation of human response, rather than consumption of physical supplies, emerged as the main finding. NHSH Clinical Effectiveness Unit project registration number: 2020/21-036.

E-scooter incidents in Berlin: an evaluation of risk factors and injury patterns.

BACKGROUND: E-scooters have emerged as a frequently used vehicle in German cities due to their high availability and easy access. However, investigations about the causes and mechanisms of E-scooter incidents and their trauma-specific consequences are rare. METHODS: We analysed all patients involved in E-scooter incidents from June to December 2019 who presented to four inner-city EDs in Berlin. The prospective data included patient-related and incident-related data, information on injury patterns and therapy, responses in a voluntary questionnaire concerning E-scooter use and general traffic experience. RESULTS: 248 patients (129 males; median age 29 years (5-81)) were included: 41% were tourists and 4% were children. Most incidents (71%) occurred between July and September 2019, the majority occurring at weekends (58%). The injury pattern was mostly multifocal, affecting the lower (42%) and upper limbs (37%) and the head (40%). Traumatic brain injury was associated with alcohol consumption. Inpatient admission was recorded in 25%, surgery in 23%. CONCLUSION: This study has defined the incidence of injury related to E-scooter use in a major European city. Stricter laws governing the use of E-scooters, the wearing of helmets and technical modifications to the E-scooter platforms might decrease E-scooter-associated incidents and resulting injuries in the future. TRIAL REGISTRATION NUMBER: German Clinical Trials Registry (DRKS00018061).

SARS-CoV-2 antigen rapid immunoassay for diagnosis of COVID-19 in the emergency department.

BACKGROUND: In the emergency department (ED) setting, rapid testing for SARS-CoV-2 is likely associated with advantages to patients and healthcare workers, for example, enabling early but rationale use of limited isolation resources. Most recently, several SARS-CoV-2 rapid point-of-care antigen tests (AGTEST) became available. There is a growing need for data regarding their clinical utility and performance in the diagnosis of SARS-CoV-2 infection in the real life setting EDs. METHODS: We implemented AGTEST (here: Roche/SD Biosensor) in all four adult and the one paediatric EDs at Charité - Universitätsmedizin Berlin in our diagnostic testing strategy. Test indication was limited to symptomatic suspected COVID-19 patients. Detailed written instructions on who to test were distributed and testing personnel were trained in proper specimen collection and handling. In each suspected COVID-19 patient, two sequential deep oro-nasopharyngeal swabs were obtained for viral tests. The first swab was collected for nucleic acid testing through SARS-CoV-2 real-time reverse transcriptase (rt)-PCR diagnostic panel (PCRTEST) in the central laboratory. The second swab was collected to perform the AGTEST. Analysis of routine data was prospectively planned and data were retrieved from the medical records after the inclusion period in the adult or paediatric ED. Diagnostic performance was calculated using the PCRTEST as reference standard. False negative and false positive AGTEST results were analysed individually and compared with viral concentrations derived from the calibrated PCRTEST. RESULTS: We included n = 483 patients including n = 202 from the paediatric ED. N = 10 patients had to be excluded due to missing data and finally n = 473 patients were analysed. In the adult cohort, the sensitivity of the AGTEST was 75.3 (95%CI: 65.8/83.4)% and the specificity was 100 (95%CI: 98.4/100)% with a SARS-CoV-2 prevalence of 32.8%; the positive predictive value was 100 (95%CI: 95.7/100)% and the negative predictive value 89.2 (95%CI: 84.5/93.9)%. In the paediatric cohort, the sensitivity was 72.0 (95%CI: 53.3/86.7)%, the specificity was 99.4 (95%CI:97.3/99.9)% with a prevalence of 12.4%; the positive predictive value was 94.7 (95%CI: 78.3/99.7)% and the negative predictive value was 96.2 (95%CI:92.7/98.3)%. Thus, n = 22 adult and n = 7 paediatric patients showed false negative AGTEST results and only one false positive AGTEST occurred, in the paediatric cohort. Calculated viral concentrations from the rt-PCR lay between 3.16 and 9.51 log10 RNA copies/mL buffer. All false negative patients in the adult ED cohort, who had confirmed symptom onset at least seven days earlier had less than 5 × 105 RNA copies/mL buffer. CONCLUSIONS: We conclude that the use of AGTEST among symptomatic patients in the emergency setting is useful for the early identification of COVID-19, but patients who test negative require confirmation by PCRTEST and must stay isolated until this result becomes available. Adult patients with a false negative AGTEST and symptom onset at least one week earlier have typically a low SARS-CoV-2 RNA concentration and are likely no longer infectious.

[18F]fallypride-PET/CT Analysis of the Dopamine D2/D3 Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection.

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D2/D3 receptor (D2/D3R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [18F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D2/D3R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D2/D3R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D2/D3R.

Non-traumatic incidental findings in patients undergoing whole-body computed tomography at initial emergency admission.

OBJECTIVE: To evaluate the number, localisation and importance of non-traumatic incidental findings (IFs) in patients with suspected or obvious multiple trauma undergoing whole-body CT (WBCT) in a level-1 trauma centre. METHODS: Between January 2009 and December 2013, a total of 2440 patients with trauma undergoing WBCT at admission to a level-1 trauma centre of a university hospital were retrospectively analysed, through imaging IFs unrelated to trauma with the radiological reports. All IFs were grouped into four categories according to their clinical relevance. Category 1: urgent treatment or further clarification needed; category 2: further examination and follow-up within 3-6 months required; category 3: findings with no immediate consequences for the treatment of the patient but of potential relevance in the future; category 4: harmless findings. RESULTS: Altogether, 5440 IFs in 2440 patients (1735 male, 705 female; mean age 45.1 years) were documented. In 204 patients (8.4%) urgent category 1 findings were reported, 766 patients (31.4%) had category 2 findings, 1236 patients (50.7%) had category 3 findings and 1173 patients (48.1%) had category 4 findings. Most IFs were detected in the abdomen/pelvis (42.5%). 602 (24.7%) of the patients had no IFs. CONCLUSIONS: WBCT scans of unrelated trauma patients demonstrate a high rate of IF. A substantial percentage (8.4%) of patients had urgent category 1IFs and a high percentage (31.4%) had category 2 IFs requiring a follow-up. This high number of patients with polytrauma undergoing WBCT, having IFs of high relevance, poses a major challenge for the level-1 trauma centre in the acute and postacute management of these patients.

One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet.

Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the longterm side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the proinflammatory cytokines interleukin 1ß and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor of Punc11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as anatomical magnetic resonance imaging and positron emission tomography-computed tomography. Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent side effects including tumor formation or chronic inflammation.

[Ultra-high-field MRI in the Chicken Embryo in Ovo - a Model for Experimental Ophthalmology]. / Ultrahochfeld-MRT am Hühnerembryo in ovo ­ ein Modell für die experimentelle Ophthalmologie.

Ultra-high-field MRI (UHF-MRI) is an outstanding technique for non-invasive and non-destructive imaging of soft tissues and can provide versatile contrasts and high resolution in the µm range. In vivo imaging of the embryonal chick eye with its filigree anatomical structures imposes these requirements. However, due to the short embryonal development cycle, chicken are a favourite animal model for embryonal research studies. Ultra-high-field MRI allows repeated and longitudinal in ovo investigations on the same embryo. In the present study, the limitations and opportunities of in ovo MR-imaging at 7 T were evaluated and the process of eye growth was described in detail.

MR microscopy of the human fetal upper extremity - a proof-of-principle study.

BACKGROUND: Current knowledge of the human fetal and embryonic development relies on early descriptive studies of humans and from experimental studies of laboratory animals and embryos. Taking the upper extremity as an example, this study explores the potential of magnetic resonance microscopy (MRM) for the assessment of the development of the fetal upper extremity and discusses its correlation with histological findings. METHODS: Ex vivo MRM at 7.1 T (Clin Scan, Bruker Biospin, Germany) was performed in 10 human specimens at 8 to 12 weeks of gestational age (GA). In-plane resolution was 20 µm with a slice thickness of 70 µm. MRM was followed by histological work-up of the specimens. MRM images were then correlated with conventional histology with a focus on the presence of chondrification and ossification. RESULTS: Ossification of the upper human extremity is detectable at 8 weeks GA in the humerus and the long bones of the forearm. There is excellent correlation for location and size of ossification between MRM and conventional histology. MRM imaging is in accordance with historical studies. CONCLUSION: Ex vivo MRM for the non-invasive assessment of the embryonic and fetal development of the upper human extremity is feasible. It may provide an accurate complementary tool for the evaluation of embryological development.

Computed tomography in trauma patients using iterative reconstruction: reducing radiation exposure without loss of image quality.

BACKGROUND: Rising numbers of computed tomography (CT) examinations worldwide have led to a focus on dose reduction in the latest developments in CT technology. Iterative reconstruction (IR) models bear the potential to effectively reduce dose while maintaining adequate image quality. PURPOSE: To assess the impact of adaptive statistical iterative reconstruction (ASIR) technique on dose reduction and image quality in a dedicated whole body CT (WBCT) protocol for trauma patients. MATERIAL AND METHODS: A total of 122 subjects with multiple trauma was prospectively included in our study. Subjects who had to undergo a WBCT following a severe trauma were randomly assigned to two different groups: Group A was examined with an ASIR protocol for the body series (n = 64), group B (n = 58) was examined using a standard filtered back projection (FBP) protocol. Image quality was assessed both quantitatively by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNRs) and qualitatively by two observers who evaluated image quality using a 5-point scale system. Applied dose was analyzed as CTDIvol (mGy), total DLP (mGyxcm), and effective dose (mSv). RESULTS: Applied dose for the body series in group A was about 23% lower than in group B (P < 0.05). SNR and CNRs for different tissues were not significantly different. Subjective image quality ratings were excellent and showed no significant difference, with a high inter-reader agreement. CONCLUSION: ASIR contributes to a relevant dose reduction without any loss of image quality in a dedicated WBCT protocol for patients with multiple trauma.

Accuracy of a custom physical activity and knee angle measurement sensor system for patients with neuromuscular disorders and gait abnormalities.

Long-term assessment of ambulatory behavior and joint motion are valuable tools for the evaluation of therapy effectiveness in patients with neuromuscular disorders and gait abnormalities. Even though there are several tools available to quantify ambulatory behavior in a home environment, reliable measurement of joint motion is still limited to laboratory tests. The aim of this study was to develop and evaluate a novel inertial sensor system for ambulatory behavior and joint motion measurement in the everyday environment. An algorithm for behavior classification, step detection, and knee angle calculation was developed. The validation protocol consisted of simulated daily activities in a laboratory environment. The tests were performed with ten healthy subjects and eleven patients with multiple sclerosis. Activity classification showed comparable performance to commercially available activPAL sensors. Step detection with our sensor system was more accurate. The calculated flexion-extension angle of the knee joint showed a root mean square error of less than 5° compared with results obtained using an electro-mechanical goniometer. This new system combines ambulatory behavior assessment and knee angle measurement for long-term measurement periods in a home environment. The wearable sensor system demonstrated high validity for behavior classification and knee joint angle measurement in a laboratory setting.

Evaluation of osseointegration of titanium alloyed implants modified by plasma polymerization.

By means of plasma polymerization, positively charged, nanometre-thin coatings can be applied to implant surfaces. The aim of the present study was to quantify the adhesion of human bone cells in vitro and to evaluate the bone ongrowth in vivo, on titanium surfaces modified by plasma polymer coatings. Different implant surface configurations were examined: titanium alloy (Ti6Al4V) coated with plasma-polymerized allylamine (PPAAm) and plasma-polymerized ethylenediamine (PPEDA) versus uncoated. Shear stress on human osteoblast-like MG-63 cells was investigated in vitro using a spinning disc device. Furthermore, bone-to-implant contact (BIC) was evaluated in vivo. Custom-made conical titanium implants were inserted at the medial tibia of female Sprague-Dawley rats. After a follow-up of six weeks, the BIC was determined by means of histomorphometry. The quantification of cell adhesion showed a significantly higher shear stress for MG-63 cells on PPAAm and PPEDA compared to uncoated Ti6Al4V. Uncoated titanium alloyed implants showed the lowest BIC (40.4%). Implants with PPAAm coating revealed a clear but not significant increase of the BIC (58.5%) and implants with PPEDA a significantly increased BIC (63.7%). In conclusion, plasma polymer coatings demonstrate enhanced cell adhesion and bone ongrowth compared to uncoated titanium surfaces.

7 Tesla MRI Liver Fat Quantification in Mice: Data Quality Assessment.

PURPOSE: The objective of this study was to evaluate the robustness of proton density fat fraction (PDFF) data determined by magnetic resonance imaging (MRI) and spectroscopy (MRS) via spatially resolved error estimation. MATERIALS AND METHODS: Using standard T2* relaxation time measurement protocols, in-vivo and ex-vivo MRI data with water and fat nominally in phase or out of phase relative to each other were acquired on a 7 T small animal scanner. Based on a total of 24 different echo times, PDFF maps were calculated in a magnitude-based approach. After identification of the decisive error-prone variables, pixel-wise error estimation was performed by simple propagation of uncertainty. The method was then used to evaluate PDFF data acquired for an explanted mouse liver and an in vivo mouse liver measurement. RESULTS: The determined error maps helped excluding measurement errors as cause of unexpected local PDFF variations in the explanted liver. For in vivo measurements, severe error maps gave rise to doubts in the acquired PDFF maps and triggered an in-depth analysis of possible causes, yielding abdominal movement or bladder filling as in vivo occurring reasons for the increased errors. CONCLUSION: The combination of pixel-wise acquisition of PDFF data and the corresponding error maps allows for a more specific, spatially resolved evaluation of the PDFF value reliability.

Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer.

Preclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds.

Effects of wearing different personal equipment on force distribution at the plantar surface of the foot.

BACKGROUND: The wearing of personal equipment can cause specific changes in muscle activity and posture. In the present study, we investigated the influence of differences in equipment related weight loading and load distribution on plantar pressure. In addition, we studied functional effects of wearing different equipment with a particular focus on relevant changes in foot shape. METHODS: Static and dynamic pedobarography were performed on 31 male soldiers carrying increasing weights consisting of different items of equipment. RESULTS: The pressure acting on the plantar surface of the foot increased with higher loading, both under static and dynamic conditions (p < 0.05). We observed an increase in the contact area (p < 0.05) and an influence of load distribution through different ways to carry the rifle. CONCLUSIONS: The wearing of heavier weights leads to an increase in plantar pressure and contact area. This may be caused by flattening of the transverse and longitudinal arches. The effects are more evident in subjects with flat feet deformities which seem to flatten at an earlier load condition with a greater amount compared to subjects with normal arches. Improving load distribution should be a main goal in the development of military equipment in order to prevent injuries or functional disorders of the lower extremity.

A model of implant-associated infection in the tibial metaphysis of rats.

OBJECTIVE: Implant-associated infections remain serious complications in orthopaedic and trauma surgery. A main scientific focus has thus been drawn to the development of anti-infective implant coatings. Animal models of implant-associated infections are considered helpful in the in vivo testing of new anti-infective implant coatings. The aim of the present study was to evaluate a novel animal model for generation of implant-associated infections in the tibial metaphysis of rats. MATERIALS AND METHODS: A custom-made conical implant made of Ti6Al4V was inserted bilaterally at the medial proximal tibia of 26 female Sprague-Dawley rats. Staphylococcus aureus in amounts spanning four orders of magnitude and each suspended in 15 µ l phosphate buffered saline (PBS) was inoculated into the inner cavity of the implant after the implantation into the defined position. Controls were treated accordingly with PBS alone. Animals were then followed for six weeks until sacrifice. Implant-associated infection was evaluated by microbiological investigation using swabs and determination of viable bacteria in the bone around the implant and the biofilm on the implants after sonification. RESULTS: Irrespective of the initial inoculum, all animals in the various groups harbored viable bacteria in the intraoperative swabs as well as the sonication fluid of the implant and the bone samples. No correlation could be established between initially inoculated CFU and population sizes on implant surfaces at sacrifice. However, a significantly higher viable count was observed from peri-implant bone samples for animals inoculated with 10(6) CFU. Macroscopic signs of animal infection (pus and abscess formation) were only observed for implants inoculated with at least 10(5) CFU S. aureus. DISCUSSION/CONCLUSION: The results demonstrate the feasibility of this novel animal model to induce an implant-associated infection in the metaphysis of rats, even with comparatively low bacterial inocula. The specific design of the implant allows an application of bacteria in reproducible numbers at well-defined contact sites to the animal bone.

Closed reduction of distal radius fractures: does instability mean irreducibility?

INTRODUCTION: The belief that not all distal radius fractures can be initially anatomically reduced with conservative means is rising. The aim of this study was to examine whether adequate reduction with a closed reduction technique is possible and to assess the importance of each step. MATERIALS AND METHODS: We prospectively enrolled 63 distal radius fractures (62 patients). A standardized reduction technique was implemented. Reduction was radiologically evaluated in hanging traction, after reduction, and in plaster. Subgroup analysis was performed for fracture-dependent and fracture-independent factors on their influence on reduction. RESULTS: The mean radiological values (radial inclination, dorsal tilt, ulnar variance) showed near anatomic reduction of all fractures in plaster. Fracture severity according to AO classification, initial displacement, number of instability criteria and patient age did not affect the reduction outcome. CONCLUSIONS: All types of enrolled fractures were nearly anatomically reduced. This contradicts the opinion that some "severe" fractures are too unstable to be initially reduced by closed means.

The FRISK (Fracture Risk)-A New Tool to Indicate the Probability of Fractures.

Increasing patient inflow into the emergency department makes it necessary to optimize triage management. The scope of this work was to determine simple factors that could detect fractures in patients without the need for specialized personnel. Between 2014 and 2015, 798 patients were admitted to an orthopedic emergency department and prospectively included in the study. The patients received a questionnaire before contacting the doctor. Objective and subjective data were evaluated to determine fracture risk for the upper and lower extremities. The highest risk for fractures in one region was the hip (73.21%; n = 56), followed by the wrist (60.32%; n = 63) and the femoral shaft (4 of 7, 57.14%; n = 7). The regions with the lowest risk were the knee (8.41%; n = 107), the ankle (18.29%; n = 164), and the forearm shaft (30.00%; n = 10). Age was a predictor for fracture: patients older than 59 years had a risk greater than 59.26%, and patients older than 90 years had a risk greater than 83.33%. The functional questions could exclude fractures. Three factors seem to be able to predict fracture risk: the injured region, the patient's age, and a functional question. They can be used for a probatory heuristic that needs to be proven in a prospective way.

Management of major bleeding for anticoagulated patients in the Emergency Department: an European experts consensus statement.

An increasing number of patients presenting to the emergency department (ED) with life-threatening bleeding are using oral anticoagulants, such as warfarin, Factor IIa and Factor Xa inhibitors. Achieving rapid and controlled haemostasis is critically important to save the patient's life. This multidisciplinary consensus paper provides a systematic and pragmatic approach to the management of anticoagulated patients with severe bleeding at the ED. Repletion and reversal management of the specific anticoagulants is described in detail. For patients on vitamin K antagonists, the administration of vitamin K and repletion of clotting factors with four-factor prothrombin complex concentrate provides real-time ability to stop the bleeding. For patients using a direct oral anticoagulant, specific antidotes are necessary to reverse the anticoagulative effect. For patients receiving the thrombin inhibitor dabigatran, treatment with idarucizamab has been demonstrated to reverse the hypocoagulable state. For patients receiving a factor Xa inhibitor (apixaban or rivaroxaban), andexanet alfa is the indicated antidote in patients with major bleeding. Lastly, specific treatment strategies are discussed in patients using anticoagulants with major traumatic bleeding, intracranial haemorrhage or gastrointestinal bleeding.

MR microscopy of the developing upper extremity of the chicken in ovo using 7 Tesla MRI.

MR microscopy (MRM) is known as ultra-high-field (UHF) magnetic resonance imaging with an in-plane spatial resolution of <100 µm, yields highly resolved non-invasive anatomical imaging and allows longitudinal assessment of embryonic avian development. The aim of the present study was to evaluate the feasibility of in vivo anatomical MRI assessment of the developing upper extremity of the chicken. Thirty-eight fertilized chicken eggs were examined at 7 Tesla acquiring high-resolution T2-weighted images with an in-plane resolution of 74 × 74 µm. To reduce motion artefacts, the eggs were moderately cooled before and during MRI. Development of the upper extremity was anatomically and quantitatively assessed. Chondrification and ossification on MRI were correlated with histological examination. MRM allowed the identification of the embryo from stage D5 onwards. First chondrification of the upper extremity was visible at stage D7, and the differentiation of the forearm was possible from stage D9 throughout the developmental period with excellent correlation to histology. MRM also allowed the differentiation between cortical and medullary bone as well as the detection of chondrified areas. UHF MRM allows the in vivo and in ovo evaluation of the upper limb during embryonic development and provides non-invasive longitudinal anatomical information. This technique allows longitudinal studies of the same embryo during the developmental period and may therefore provide further insights into the development of the upper extremity. With improved coil technique and increasing availability of UHF MR systems, there is great potential regarding several research topics in experimental musculoskeletal radiology.