Non-vitamin K antagonist oral anticoagulants (NOACs) have a favorable benefit-risk profile compared with vitamin K antagonists. However, the lack of specific reversal agents has made the management of some patients receiving long-term treatment with NOACs problematic in emergency situations such as major bleeding events or urgent procedures. Idarucizumab, a fully humanized Fab antibody fragment that binds specifically and with high affinity to dabigatran, was recently approved for use in adult patients treated with dabigatran when rapid reversal of its anticoagulant effect is required. Clinical experience with idarucizumab is currently limited. We report 11 real-life clinical cases in which idarucizumab was used after multidisciplinary consultation in a variety of emergency situations including severe postoperative bleeding, emergency high-bleeding-risk surgery (hip/spine surgery and neurosurgery), invasive diagnostic testing (lumbar puncture), intracranial bleeding (pre-pontine subarachnoid hemorrhage and lobar intracerebral hemorrhage) and thrombolysis with recombinant tissue plasminogen activator for acute ischemic stroke. This case series illustrates the role of idarucizumab in improving patient safety in rare emergency situations requiring rapid reversal of the anticoagulant effect of dabigatran, while highlighting the importance of information and education about the availability and appropriate use of this recently approved specific reversal agent.

Introduction: Epidemiological studies show that increased physical activity is linked to a lower risk of breast cancer and mortality. As a result, physical activity can significantly improve patients' quality of life (QOL) both during and after therapy.Many breast cancer patients demonstrate a decrease in cognitive capacity, referred to as the symptom-complex cancer related cognitive impairment (CRCI). Most frequently reported impairments are mild to moderate deficits in processing speed, attention, memory, and executive functions. Cognitive symptoms persist for months or even years, following medical treatment in roughly 35% of afflicted people, impairing everyday functioning, limiting the ability to return to work, and lowering the overall QOL. Recent studies point toward a key role of inflammatory pathways in the CRCI genesis. Attention to physical activity as a potential supportive care option is therefore increasing. However, evidence for the positive effects of exercise on preventing CRCI is still lacking.Patients and Methods: Against this background, the prospective, two-arm, 1:1 randomized, controlled trial investigates the influence of first line chemotherapy accompanied by exercise training on preventing CRCI in 126 patients with breast cancer at the local University Hospital. The study will evaluate biomarkers and secondary assessments suspected to be involved in the pathogenesis of CRCI in addition to objective (primary outcome) and subjective cognitive function. CRCI is believed to be connected to either functional and/or morphological hippocampal damage due to chemotherapy. Thus, cerebral magnetic resonance imaging (MRI) and hippocampal volume measurements are performed. Furthermore, a specific neuropsychological test battery for breast cancer patients has been developed to detect early signs of cognitive impairments in patients and to be integrated into practice.Discussion: This study will explore how a long-term supervised exercise intervention program might prevent CRCI, enables optimization of supportive care and objectifies limits of psychological and physical resilience in breast cancer patients during and after chemotherapy treatment.Trial Registration: ClinicalTrials.gov: Identifier: NCT04789187. Registered on 09 March 2021.

Visually evoked potentials (VEPs) are widely used for diagnoses of different neurological diseases. Interestingly, there is limited research about the impact of the stimulus color onto the evoked response. Therefore, in our study we investigated the possibility of automatically classifying the stimulus color. The visual stimuli were selected to be red/black and green/black checkerboard patterns with equal light density. Both of these stimuli were presented in a random manner to nine subjects, while the electroencephalogram was recorded at the occipital lobe. After pre-processing and aligning the evoked potentials, an artificial neural network with one hidden layer was used to investigate the general possibility to automatically classify the stimulus color in three different settings. First, color classification with individually trained models, color classification with a common model, and color classification for each individual volunteer with a model trained on the data of the remaining subjects. With an average accuracy (ACC) of 0.83, the best results were achieved for the individually trained model. Also, the second (mean ACC = 0.76) and third experiments (mean ACC = 0.71) indicated a reasonable predictive accuracy across all subjects. Consequently, machine learning tools are able to appropriately classify stimuli colors based on VEPs. Although further studies are needed to improve the classification performance of our approach, this opens new fields of applications for VEPs.

Background: The main objective of the Cerebrolysin REGistry Study in Stroke 2 (C-REGS2) was to systematically record the routine clinical use of Cerebrolysin in patients with moderate ischemic stroke (IS) following the principles of a prospective controlled effectiveness study (CES) to compare its effectiveness in terms of functional recovery to patients treated with standard therapy alone. Methods: C-REGS2 used an open-label, prospective controlled comparative effectiveness design aligning with the Target Trial Emulation Framework (TTEF) and the GRACE principles for high-quality observational studies based on the principles of high-quality comparative effectiveness research (HQCER) to capture treatment effects in clinical practice. The study was conducted in 16 countries worldwide between April 2018 and April 2024. Moderate IS was defined as baseline NIH Stroke Scale (NIHSS) score 8–15. Treatment modalities and concomitant medications were according to local standards. The methodology included rigorous pre-specified analysis and tight risk-based centralized monitoring, to ensure minimal enrollment bias, maximize data quality and overall reliability of trial results. The compared patient groups were standardized using a restricted cohort design and non-parametric multilevel stratification following the Good Research for Comparative Effectiveness (GRACE) principles. The primary endpoint was ordinal analysis of the modified Rankin Scale (mRS) at 90 days after stroke onset. Secondary endpoints were the ordinal NIH Stroke Scale (NIHSS) at day 21 and 90 after stroke onset, the ordinal mRS at 21 days after IS, the proportion of patients with excellent recovery (mRS 0–1) as well as the proportion of patients with functional independence (mRS 0–2) at 90 days after stroke onset and the ordinal analysis of Montreal Cognitive Assessment (MoCA) scale at 90 days after IS. Results: Out of 1865 enrolled patients, the target population (TP) comprised 1769 patients (1021 Cerebrolysin-treated and 748 controls). The median NIHSS at baseline was 10.0. Median Cerebrolysin dose was 30 ml, median treatment duration was 10 days. Cerebrolysin was superior to standard therapy in the primary endpoint independently to prior thrombolysis (MW 0.6157; confidence interval (CI) 0.5910–0.6404; P < 0.0001) as well as in all secondary endpoints: mRS at day 21 (MW 0.6065, 95% CI 0.5811–0.6319, P < 0.0001), NIHSS at day 21 (MW 0.5792; 95% CI 0.5576–0.6008; P < 0.0001) and NIHSS at day 90 (MW 0.5781; CI 0.5561–0.6002; P < 0.0001). Additional pre-specified secondary endpoints (proportion of patients with excellent recovery and functional independence) showed moderate superiority for Cerebrolysin. The ordinal MoCA showed superiority for Cerebrolysin in the TP (MW 0.5530; CI 0.5282–0.5778; P < 0.0001) with more pronounced effects in the subgroup with cognitive impairments at baseline (Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) ⩾ 3.3). No differences in safety measures were recorded. The study is notable for its robust data integrity, with valid entries of 90.9% for the primary 90 day mRS assessment with multilevel case mix standardization and an overall dropout rate to the final visit of only 5.7%. Conclusion: The results of the C-REGS2 study showed the effectiveness and safety of Cerebrolysin treatment for moderate acute IS in real-world clinical practice.

Background and purpose: Cerebral sinus venous thrombosis (CSVT) is a rare but life-threatening disease and its diagnosis remains challenging. Blood biomarkers, including D-Dimer are currently not recommended in guidelines. Soluble endothelial receptor proteins (sICAM-1, sPECAM-1 and sVCAM-1) have been shown to be promising diagnostic biomarkers in deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, we examined endothelial receptor proteins as potential biomarkers for detecting CSVT. Methods: In this bi-centre, prospective study, we quantified D-Dimer as well as sICAM-1, sPECAM-1 and sVCAM-1 in plasma of patients with clinically suspected CSVT managed in the neurological emergency department (ED) of a tertiary care hospital. All patients underwent cerebral magnetic resonance imaging (MRI) and were followed up after 3, 6 and 12 months to detect thrombus resolution. Results: Twenty-four out of 75 (32%) patients with clinically suspected CSVT presenting with headache to the ED were diagnosed with acute CSVT. These patients had a mean age of 45 ± 16 years and 78% were female. In patients with CSVT, mean baseline D-dimer (p < 0.001) and sPECAM-1 (p < 0.001) were significantly higher compared to patients without CSVT. The combination of D-Dimer and sPECAM-1 yielded the best ROC-AUC (0.994; < 0.001) with a negative predictive value of 95.7% and a positive predictive value of 95.5%. In addition, higher baseline sPECAM-1 levels (> 198 ng/ml) on admission were associated with delayed venous thrombus resolution at 3 months (AUC = 0.83). Conclusion: sPECAM-1 in combination with D-Dimer should be used to improve the diagnostic accuracy of acute CSVT and sPECAM-1 may predict long-term outcome of CSVT. Confirmatory results are needed in other settings in order to show their value in the management concept of CSVT patients.