Belumosudil for the treatment of chronic graft-versus-host disease: a single center real-world experience
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Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment – a retrospective, German-Swiss multicenter real-world data analysis
Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval. The patient cohort had a long history of cGvHD (median 44 months) and was heavily pretreated (median 4 prior lines). The overall response rate was 42% (95%CI, 25–60%) including organ responses in all organs except the liver (n = 2). The median time to response was 3 months (range, 1–9 months) and 8 of 14 patients (57%) had a durable response at last follow-up. One-third of patients had at least a 50% reduction in concomitant corticosteroid dosage. Median failure-free survival and median overall survival were 16.5 and 23.1 months, respectively. Adverse events ≥CTCAE grade 3 were reported in 27% of patients, with a predominance of infectious events, including one fatal course. The results are consistent with previous prospective trials including a favorable safety profile, while acknowledging the challenges of a heavily pretreated patient cohort.
Human neural dynamics of real-world and imagined navigation
The ability to form episodic memories and later imagine them is integral to the human experience, influencing our recollection of the past and envisioning of the future. While rodent studies suggest the medial temporal lobe, especially the hippocampus, is involved in these functions, its role in human imagination remains uncertain. In human participants, imaginations can be explicitly instructed and reported. Here we investigate hippocampal theta oscillations during real-world and imagined navigation using motion capture and intracranial electroencephalographic recordings from individuals with chronically implanted medial temporal lobe electrodes. Our results revealed intermittent theta dynamics, particularly within the hippocampus, encoding spatial information and partitioning navigational routes into linear segments during real-world navigation. During imagined navigation, theta dynamics exhibited similar patterns despite the absence of external cues. A statistical model successfully reconstructed real-world and imagined positions, providing insights into the neural mechanisms underlying human navigation and imagination, with implications for understanding memory in real-world settings.
Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia
X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients.
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder — recommendations from ECTRIMS and the EBMT
Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing–remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD). Furthermore, treatment and monitoring protocols, rehabilitation and other supportive care before and after AHSCT need to be optimized. To address these issues, we convened a European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop in partnership with the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party, in which evidence and key questions were presented and discussed by experts in these diseases and in AHSCT. Based on the workshop output and subsequent written interactions, this Consensus Statement provides practical guidance and recommendations on the use of AHSCT in MS and NMOSD. Recommendations are based on the available evidence, or on consensus when evidence was insufficient. We summarize the key evidence, report the final recommendations, and identify areas for further research.
Evolution of temporomandibular joint reconstruction: from autologous tissue transplantation to alloplastic joint replacement
The reconstruction of the temporomandibular joint presents a multifaceted clinical challenge in the realm of head and neck surgery, underscored by its relatively infrequent occurrence and the lack of comprehensive clinical guidelines. This review aims to elucidate the available approaches for TMJ reconstruction, with a particular emphasis on recent groundbreaking advancements. The current spectrum of TMJ reconstruction integrates diverse surgical techniques, such as costochondral grafting, coronoid process grafting, revascularized fibula transfer, transport distraction osteogenesis, and alloplastic TMJ replacement. Despite the available options, a singular, universally accepted ‘gold standard’ for reconstructive techniques or materials remains elusive in this field. Our review comprehensively summarizes the current available methods of TMJ reconstruction, focusing on both autologous and alloplastic prostheses. It delves into the differences of each surgical technique and outlines the implications of recent technological advances, such as 3D printing, which hold the promise of enhancing surgical precision and patient outcomes. This evolutionary progress aims not only to improve the immediate results of reconstruction but also to ensure the long-term health and functionality of the TMJ, thereby improving the quality of life for patients with end-stage TMJ disorders.
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