Introduction: Understanding the prevalence of multiple sclerosis (MS) provides information for healthcare planning and helps identify trends and patterns of disease occurrence. For Switzerland, the number of persons with MS (pwMS) was last estimated at approximately 15,000 in 2016. The study's objectives were to update estimates of MS prevalence and characterise the change in MS prevalence in Switzerland between 2016 and 2021, the last year with complete administrative data.
View Article and Find Full Text PDFPrimary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threatening immunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV).
View Article and Find Full Text PDFRemote longitudinal studies are on the rise and promise to increase reach and reduce participation barriers in chronic disease research. However, maintaining long-term retention in these studies remains challenging. Early identification of participants with different patterns of long-term retention offers the opportunity for tailored survey adaptations.
View Article and Find Full Text PDFCRAC channels enable calcium entry from the extracellular space in response to a variety of stimuli and are crucial for gene expression and granule exocytosis in lymphocytes. Here we find that Syntaxin11, a Q-SNARE, associated with FHLH4 disease in human patients, directly binds Orai1, the pore forming subunit of CRAC channels. Syntaxin11 depletion strongly inhibited SOCE, CRAC currents, IL-2 expression and cytotoxicity in cell lines and FHLH4 patient T lymphocytes.
View Article and Find Full Text PDFTransition metal-catalyzed cross-couplings have great potential to furnish complex ethers; however, challenges in the C(sp)-O functionalization step have precluded general methods. Here, we describe computationally guided transition metal-ligand design that positions a hydrogen-bond acceptor anion at the reactive site to promote functionalization. A general cross-coupling of primary, secondary, and tertiary aliphatic alcohols with terminal olefins to furnish >130 ethers is achieved.
View Article and Find Full Text PDFBackground: While potential risk factors for multiple sclerosis (MS) have been extensively researched, it remains unclear how persons with MS theorize about their MS. Such theories may affect mental health and treatment adherence. Using natural language processing techniques, we investigated large-scale text data about theories that persons with MS have about the causes of their disease.
View Article and Find Full Text PDFSYNTAXIN-11 (STX11) is a SNARE protein that mediates the fusion of cytotoxic granules with the plasma membrane at the immunological synapses of CD8 T or NK cells. Autosomal recessive inheritance of deleterious STX11 variants impairs cytotoxic granule exocytosis, causing familial hemophagocytic lymphohistiocytosis type 4 (FHL-4). In several FHL-4 patients, we also observed hypogammaglobulinemia, elevated frequencies of naive B cells, and increased double-negative DN2:DN1 B cell ratios, indicating a hitherto unrecognized role of STX11 in humoral immunity.
View Article and Find Full Text PDFThe diagnosis of cardiac sarcoidosis, particularly in its isolated cardiac form, represents a major challenge due to non-specific symptoms and the limited sensitivity and specificity of basic cardiac investigations. MRI and metabolic PET-CT are important elements in the diagnostic process. Corticosteroids remain the cornerstone for the treatment of the inflammatory phase, in association with biological agents and steroid-sparing therapies.
View Article and Find Full Text PDFA pregnant woman presented with an asthma attack with a poor clinical evolution, requiring intubation. Medications traditionally used for the treatment of asthma in non-pregnant patients (short-acting beta-2 agonists, short-acting muscarinic antagonists, systemic corticosteroids) are considered safe during pregnancy, except for epinephrine. A systematic obstetrical evaluation is a key component in the evaluation and management of an asthmatic crisis during pregnancy.
View Article and Find Full Text PDFBackground: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder characterized by a life-threatening cytokine storm and immunopathology. Familial HLH type 3 (FHL3) accounts for approximately 30% of all inborn HLH cases worldwide. It is caused by mutations in the UNC13D gene that result in impaired degranulation of cytotoxic vesicles and hence compromised T-cell- and natural killer-cell-mediated killing.
View Article and Find Full Text PDFInterferon-γ (IFNγ) is an important mediator of cellular immune responses, but high systemic levels of this cytokine are associated with immunopathology. IFNγ binds to its receptor (IFNγR) and to extracellular matrix (ECM) via four positively charged C-terminal amino acids (KRKR), the ECM-binding domain (EBD). Across evolution, IFNγ is not well conserved, but the EBD is highly conserved, suggesting a critical function.
View Article and Find Full Text PDFAccording to PubMed statistics when writing this review, the year 2022 is expected to mark the first dip in the number of articles published in relation to the Covid-19 pandemic. This review, without any mention to Sars-CoV-2, highlight this transition and addresses many topics in internal medicine: gastroenterology, cardiology, endocrinology, respiratory medicine, infectious diseases and venous access. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles that have caught our attention, summarized and commented for you, which should change our daily practice.
View Article and Find Full Text PDFPrimary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by impaired lymphocyte cytotoxicity. First-line therapeutic regimens directed against activated immune cells or secreted cytokines show limited efficacy since they do not target the underlying immunological problem: defective lymphocyte cytotoxicity causing prolonged immune stimulation. A potential rescue strategy would be the adoptive transfer of ex vivo gene-corrected autologous T cells.
View Article and Find Full Text PDF