Advanced therapy medicinal products are a rapidly expanding drug class based on genes, cells, and tissues, transforming the treatment of diseases, including haematologic cancers and genetic disorders, such as sickle cell disease and haemophilia. This review highlights that successful clinical implementation requires coordinated national strategies, regulatory support, sustainable funding, robust clinical and production infrastructure, and trained specialised personnel to ensure timely, safe, and equitable patient access.
In this case report, we present an instance of an atypical femur fracture in a patient receiving denosumab treatment. Due to MRI-verified severe lateral recess stenosis, her symptoms are misinterpreted because of nerve root affection and treated as such with surgical decompression. Not until postoperatively was the atypical femur fracture of the left leg diagnosed and finally treated. With this case report, we aim to raise awareness of atypical femur fracture as a differential diagnosis for nerve root affection and explore the possible connection between denosumab and atypical femur fracture.
Background Restorative Brain–Computer Interfaces (BCI) that combine motor imagery with visual feedback and functional electrical stimulation (FES) may offer much-needed treatment alternatives for patients with severely impaired upper limb (UL) function after a stroke. Objectives This study aimed to examine if BCI-based training, combining motor imagery with FES targeting finger/wrist extensors, is more effective in improving severely impaired UL motor function than conventional therapy in the subacute phase after stroke, and if patients with preserved cortical-spinal tract (CST) integrity benefit more from BCI training. Methods Forty patients with severe UL paresis (< 13 on Action Research Arm Test (ARAT) were randomized to either a 12-session BCI training as part of their rehabilitation or conventional UL rehabilitation. BCI sessions were conducted 3–4 times weekly for 3–4 weeks. At baseline, Transcranial Magnetic Stimulation (TMS) was performed to examine CST integrity. The main endpoint was the ARAT at 3 months post-stroke. A binominal logistic regression was conducted to examine the effect of treatment group and CST integrity on achieving meaningful improvement. In the BCI group, electroencephalographic (EEG) data were analyzed to investigate changes in event-related desynchronization (ERD) during the course of therapy. Results Data from 35 patients (15 in the BCI group and 20 in the control group) were analyzed at 3-month follow-up. Few patients (10/35) improved above the minimally clinically important difference of 6 points on ARAT, 5/15 in the BCI group, 5/20 in control. An independent-samples Mann–Whitney U test revealed no differences between the two groups, p = 0.382. In the logistic regression only CST integrity was a significant predictor for improving UL motor function, p = 0.007. The EEG analysis showed significant changes in ERD of the affected hemisphere and its lateralization only during unaffected UL motor imagery at the end of the therapy. Conclusion This is the first RCT examining BCI training in the subacute phase where only patients with severe UL paresis were included. Though more patients in the BCI group improved relative to the group size, the difference between the groups was not significant. In the present study, preserved CTS integrity was much more vital for UL improvement than which type of intervention the patients received. Larger studies including only patients with some preserved CST integrity should be attempted.
