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Anticoagulant management after emergency surgery or major bleeding in anticoagulated patients — results of the prospective RADOA registry
No full textBackground: Major bleeding or emergency surgery are the most frequently observed emergency situations in patients anticoagulated with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). The restart of anticoagulation after these situations is a therapeutic dilemma.
Methods: The prospective RADOA registry is an observational, noninterventional multicenter registry that documents the management of severe bleeding or emergency surgery in patients treated with VKAs or DOACs. In this substudy, we analyzed time point, type, and dosage of anticoagulant resumption after emergency situations.
Results: Overall, 78 emergency surgery patients and 193 major bleeding patients were analyzed. Median age was similar in the VKA- and DOAC-treated groups (emergency surgery: 77 years, major bleeding: 79 years). Anticoagulants were restarted significantly earlier after emergency surgery compared to major bleeding, with no difference between the VKA and DOAC groups. While patients after cardiothoracic surgery received UFH intravenously, patients with trauma or having received abdominal surgery were mainly treated with prophylactic LMWH s.c.. After major bleeding, the majority of patients were treated with prophylactic LMWH. None of the patients in the emergency surgery group and 17% (4/24) of the major bleeding group with recurrent bleeding (12%, 24/193) experienced recurrent bleeding after restart of anticoagulation. Thromboembolism occurred rarely in both patient groups (emergency surgery: 3%, major bleeding 4%).
Conclusions: Time points of restart, type, and dosage of anticoagulants are highly diverse in this high-risk patient population. Resumption of prophylactic anticoagulation is associated with a low risk of thrombosis and should be initiated as soon as possible
Advanced prompt engineering in emergency medicine and anesthesia: enhancing simulation-based e-Learning
No full textMedical education is rapidly evolving with the integration of artificial intelligence (AI), particularly through the application of generative AI to create dynamic learning environments. This paper examines the transformative role of prompt engineering in enhancing simulation-based learning in emergency medicine. By enabling the generation of realistic, context-specific clinical case scenarios, prompt engineering fosters critical thinking and decision-making skills among medical trainees. To guide systematic implementation, we introduce the PROMPT Framework, a structured methodology for designing, evaluating, and refining prompts in AI-driven simulations, while incorporating essential ethical considerations. Furthermore, we emphasize the importance of developing specialized AI models tailored to regional guidelines, standard operating procedures, and educational contexts to ensure relevance and alignment with current standards and practices. The framework aims to provide a structured approach for engaging with AI-generated medical content, allowing learners to reflect on clinical reasoning, critically assess AI-generated recommendations, and consider the potential role of AI tools in medical training workflows. Additionally, we acknowledge certain challenges associated with the use of AI in education, such as maintaining reliability and addressing potential biases in AI outputs. Our study explores how AI-driven simulations could contribute to scalability and adaptability in medical education, potentially offering structured methods for healthcare professionals to engage with generative AI in training contexts
Spatial characterization of woody species diversity in tropical savannas using GEDI and optical data
No full textDeveloping the capacity to monitor species diversity worldwide is of great importance in halting biodiversity loss. To this end, remote sensing plays a unique role. In this study, we evaluate the potential of Global Ecosystem Dynamics Investigation (GEDI) data, combined with conventional satellite optical imagery and climate reanalysis data, to predict in situ alpha diversity (Species richness, Simpson index, and Shannon index) among tree species. Data from Sentinel-2 optical imagery, ERA-5 climate data, SRTM-DEM imagery, and simulated GEDI data were selected for the characterization of diversity in four study areas. The integration of ancillary data can improve biodiversity metrics predictions. Random Forest (RF) regression models were suitable for estimating tree species diversity indices from remote sensing variables. From these models, we generated diversity index maps for the entire Cerrado using all GEDI data available in orbit. For all models, the structural metric Foliage Height Diversity (FHD) was selected; the Renormalized Difference Vegetation Index (RDVI) was also selected in all species diversity models. For the Shannon model, two GEDI variables were selected. Overall, the models indicated performances for species diversity ranging from (R = 0.24 to 0.56). In terms of RMSE%, the Shannon model had the lowest value among the diversity indices (31.98%). Our results suggested that the developed models are valuable tools for assessing species diversity in tropical savanna ecosystems, although each model can be chosen based on the objectives of a given study, the target amount of performance/error, and the availability of data
The complexity of malignant glioma treatment
No full textSimple Summary
This review describes the dynamic influence of the tumor microenvironment during treatment of malignant glioma. The mechanism behind five hallmarks are outlined: glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. A multimodal immunotherapy treatment plan is proposed, explaining how each hallmark can be targeted over time. Repeated tumor monitoring is deemed vital to alter the treatment plan when needed.
Abstract
Malignant glioma is a highly aggressive, therapeutically non-responsive, and deadly disease with a unique tumor microenvironment (TME). Of the 14 currently recognized and described cancer hallmarks, five are especially implicated in malignant glioma and targetable with repurposed drugs: cancer stem-like cells, in general, and glioma stem-like cells in particular (GSCs), vascularization and hypoxia, metabolic reprogramming, tumor-promoting inflammation and sustained proliferative signaling. Each hallmark drives malignant glioma development, both individually and through interactions with other hallmarks, in which the TME plays a critical role. To combat the aggressive malignant glioma spatio-temporal heterogeneity driven by TME interactions, and to overcome its therapeutic challenges, a combined treatment strategy including anticancer therapies, repurposed drugs and multimodal immunotherapy should be the aim for future treatment approaches
Biomechanical performance and handling of mineral–organic adhesive bone cements based on magnesium under clinical test conditions
No full textBackground/Objectives: Biomineral adhesive bone adhesives composed of phosphoserine combined with magnesium oxides or phosphates exhibit exceptional adhesive properties. This study evaluates two experimental mineral–organic cementitious adhesives in a clinical test setup, investigating their potential for fracture reduction and simultaneous defect filling.
Methods: The two experimental adhesives (Groups B and C) and a standard hydroxyapatite cement (Group A, reference) underwent compressive strength testing, shear strength testing, and screw pullout tests as part of a first biomechanical characterization. Furthermore, all materials were tested in a porcine tibial split depression fracture model, where they served both for fracture reduction and for filling the metaphyseal bone defect, supplementary to plate osteosynthesis. Fracture stability was assessed under cyclic loading in a materials testing machine.
Results: The OPLS (O-phospho-L-serine) containing adhesive (Group B) demonstrated the highest compressive strength as well as the highest shear strength. All three materials showed comparable maximum pullout forces. Both experimental adhesives (Groups B and C) exhibited higher pullout stiffness compared to the standard cement (Group A). In the fracture model, no significant differences in displacement under cyclic loading were observed between groups.
Conclusions: The biomineral adhesive bone adhesives (Groups B and C) demonstrated biomechanical advantages in axial compression, adhesive (shear) strength, and screw fixation compared to the standard hydroxyapatite cement (Group A). Furthermore, they achieved comparable stabilization of metaphyseal fractures under clinically relevant dynamic loading conditions
Experimental and mathematical model of platelet hemostasis kinetics
No full textUpon activation, platelets undergo rapid phenotypic transitions to maintain hemostasis, yet the kinetics governing these transitions remain poorly quantified. We present an integrated experimental and mathematical model describing platelet transitions between resting, activated, aggregating, inhibited, and exhausted phenotypes, determined by experiment rate constants for these reactions. Theoretical simulations of platelet transitions accurately describe the independently determined experimental read-out. Platelet aggregation under the conditions used directly correlates with the activation of αIIbβ3 integrins, demonstrating that the parameters of platelet aggregation achieved by the laser diffraction technique can be used for the evaluation of the rapid activation and deactivation kinetics of αIIbβ3 integrins. We demonstrate that platelet desensitization occurs at multiple activation stages, with distinct kinetic profiles for shape change and integrin deactivation. We also show that even 5 s of receptor-mediated PKA activation (iloprost) is sufficient for a complete inhibition of ADP-induced platelet aggregation. However, when iloprost was added after platelet stimulation by ADP, platelet activation was not fully inhibited, and after 180 s, aggregation became irreversible. The presented data help to understand the mechanisms of platelet transition between different phenotypes. The model effectively characterizes key physiological phenotypes and can serve as a modular framework for integration into more comprehensive models
Detection of local prostate cancer recurrence from PET/CT scans using deep learning
No full textSimple Summary
Prostate cancer is a leading cause of cancer-related deaths in men around the world. A type of imaging technique called positron emission tomography (PET), which uses a special scan to detect cancer, has shown great promise in identifying recurring prostate cancer and spread to other parts of the body. In this study, we created a computer-based model that uses PET scan images to predict if prostate cancer has come back after treatment. To improve the model’s performance, we tried different methods, such as focusing on different parts of the image, adding extra information from the patient’s medical history, and including details about whether the patient had prior surgery to remove the prostate. These efforts led to an accuracy of 77% in predicting cancer recurrence. While this accuracy was lower than the desired 90%, the model still showed significant improvement. Many approaches were tested, each helping to improve the model. The results of this study are an important step forward in developing tools that can reliably detect cancer recurrence in the prostate area. However, more research is required to further improve the model’s accuracy and make it more useful for doctors in real-life situations.
Abstract
Background: Prostate cancer (PC) is a leading cause of cancer-related deaths in men worldwide. PSMA-directed positron emission tomography (PET) has shown promising results in detecting recurrent PC and metastasis, improving the accuracy of diagnosis and treatment planning. To evaluate an artificial intelligence (AI) model based on [F]-prostate specific membrane antigen (PSMA)-1007 PET datasets for the detection of local recurrence in patients with prostate cancer.
Methods: We retrospectively analyzed 1404 [F]-PSMA-1007 PET/CTs from patients with histologically confirmed prostate cancer. Artificial neural networks were trained to recognize the presence of local recurrence based on the PET data. First, the hyperparameters were optimized for an initial model (model A). Subsequently, the bladder was localized using an already published model and a model (model B) was trained only on a 20 cm cube around the bladder. Finally, two separate models were trained on the same section depending on the prostatectomy status (model C (post-prostatectomy) and model D (non-operated)).
Results: Model A achieved an accuracy of 56% on the validation data. By restricting the region to the area around the bladder, Model B achieved a validation accuracy of 71%. When validating the specialized models according to prostatectomy status, model C achieved an accuracy of 77% and model D an accuracy of 77%. All models achieved accuracies of almost 100% on the training data, indicating overfitting. Conclusions: For the presented task, 1404 examinations were insufficient to reach an accuracy of over 90% even when employing data augmentation, including additional metadata and performing automated hyperparameter optimization. The low F1-score and AUC values indicate that none of the presented models produce reliable results. However, we will facilitate future research and the development of better models by openly sharing our source code and all pre-trained models for transfer learning
Enhancing anti-tumor immunity through intratumoral combination therapy with amphiphilic conjugates of oxaliplatin and imidazoquinoline TLR7/8 agonist
No full textThe efficacy of conventional chemotherapy does not only rely on the cytotoxic action of the drug compound itself. Indeed, proper drug-induced immunogenic cell death (ICD) can stimulate immunosurveillance and mount a systemic anti-tumor response. We aimed to further amplify the therapeutic activity of oxaliplatin (OxPt) chemotherapy-induced ICD by combining this with an imidazoquinoline (IMDQ) TLR7/8 agonist. We hypothesized that innate immune activation by TLR7/8 activation primes the immune system against tumor neoantigens, thereby mounting tumor-specific T cell responses that contribute to killing primary tumor cells and distal metastases. To this end, we initially synthesized a covalent conjugate of OxPt, an imidazoquinoline TLR7/8 agonist ( i.e. , IMDQ), and an alkyl lipid. We hypothesized that such a lipidated conjugate would, upon intratumoral injection, increase the residence time in the tumor and reduce systemic dissemination and, hence, off-target toxicity. Whereas combination therapy with OxPt and IMDQ in native form improved, relative to single treatment, the anti-tumor efficacy against the primary treated tumor and a secondary distal tumor, this was not the case for OxPt–IMDQ-lipid conjugate therapy. We then altered the molecular design of the combination therapy and synthesized amphiphilic OxPt and IMDQ conjugates, comprising a cholesteryl motif and a hydrophilic poly(ethylene glycol) (PEG) chain. Intratumoral combination therapy with OxPt-PEG-cholesteryl and IMDQ-PEG-cholesteryl reduced, compared to native drug compounds, systemic innate inflammatory responses, and more efficiently eradicated primary and distal tumors. Furthermore, we found that combination therapy with OxPt-PEG-cholesteryl and IMDQ-PEG-cholesteryl induced antigen-specific anti-tumor responses and high infiltration levels of CD8+ T cells into the tumor
Patient shielding in ultra-high-resolution cone-beam CT of the upper extremity with a twin robotic X-ray system
No full textBackground/Objectives: Gantry-free cone-beam CT (CBCT) allows for ultra-high-resolution (UHR) upper extremity imaging in a comfortable tableside position. The aim of this study was to assess the organ-specific radiation burden and the effect of dedicated lead shielding in the UHR-CBCT of the wrist and elbow.
Methods: A modified Alderson-Rando phantom was scanned with the tableside UHR-CBCT mode of a twin robotic X-ray system employing identical scan parameters for wrist and elbow imaging. An ion chamber was used in conjunction with an electrometer to obtain representative organ dose measurements for the eye lens, thyroid gland, breast tissue, and abdomen. All measurements were performed with and without lead shielding.
Results: Irrespective of the examined upper extremity joint, the highest absorbed dose among the assessed organs was determined for the eye lens (wrist imaging: 0.10 ± 0.01 mGy, elbow imaging: 0.12 ± 0.01 mGy). The most effective organ dose reduction by means of shielding in wrist CBCT was achieved for the thyroid gland (−17%). In elbow CBCT, the abdomen (−48%) and the ipsilateral breast (−39%) benefited particularly from shield protection.
Conclusions: Although shielding was more effective in elbow than wrist scans, the overall impact in terms of absolute dose reduction was marginal
Diagnosis and Treatment of Hypophosphatasia
No full textHypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of tissue-nonspecific alkaline phosphatase (TNAP) caused by variants in the ALPL gene. Disease manifestations encompass skeletal hypomineralization with rickets and lung hypoplasia, vitamin B6-dependent seizures, craniosynostosis, and premature loss of deciduous teeth. The clinical presentation can comprise failure to thrive with muscular hypotonia, delayed motor development, and gait disturbances later in childhood. In adults, pseudofractures are a characteristic indicator of severely compromised enzyme activity, but non-canonical symptoms like generalized musculoskeletal pain, weakness, and fatigue, frequently accompanied by neuropsychiatric and gastrointestinal issues are increasingly recognized as key findings in patients with HPP. The diagnosis is based on clinical manifestations in combination with persistently low alkaline phosphatase (ALP) activity, elevated levels of ALP substrates, specifically inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), and genetic confirmation of a causative ALPL variant. Considering the wide range of manifestations, treatment must be multimodal and tailored to individual needs. The multidisciplinary team for comprehensive management of HPP patients should include expertise to ensure disease state metabolic and musculoskeletal treatment, dental care, neurological and neurosurgical surveillance, pain management, physical therapy, and psychological care. Asfotase alfa as first-in-class enzyme replacement therapy (ERT) for HPP has been shown to improve survival, rickets, and functional outcomes in severely affected children, but further research is needed to refine how enzyme replacement can also address emerging manifestations of the disease. Prospectively, further elucidating the pathophysiology behind the diverse clinical manifestations of HPP is instrumental for improving diagnostic concepts, establishing novel means for substituting enzyme activity, and developing integrative, multimodal care