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Follicular helper-like γδ T cells promote plasma cell differentiation in Behçet’s disease
Get PDF Objectives Behçet’s disease (BD) is a systemic vasculitis characterized by recurrent oral and genital ulcers. The disease can manifest diverse phenotypes -such as mucocutaneous, ocular BD- with an uncertain role for autoantibodies in disease pathogenesis. Altered γδT-cell and B-cell phenotypes have been widely reported in BD, but it remains unknown whether these lineages can interact to promote autoantibody production. Methods This study included 75 patients with a BD diagnosis, alongside 41 healthy control (HC) volunteers. We performed ex vivo flow-cytometric profiling of blood γδT and B cells, established a cell culture system to investigate plasma cell generation in vitro , and quantified anti-HSP60 autoantibody levels in BD and HC participants’ serum and cell culture supernatants. Results BD patients with active disease displayed a significant increase in the frequency of cells CXCR5 + PD-1 + Vδ2 T cells resembling a follicular helper-like functional state. Upon stimulation, Vδ2 T cells from BD patients showed increased expression of ICOS and CXCR5, induced significant B cell proliferation, and promoted differentiation of plasma cells in vitro . Cultures of cells from BD patients contained increased levels of multiple cytokines that can support plasma cell differentiation (IL-4, IL-10, IL-17, CXCL13, TNF-α, IFN-γ). Anti-HSP60 autoantibodies were significantly enriched in blood serum from BD patients with active disease as well as the supernatants of patient-derived cell cultures compared to the healthy volunteer cell cultures. Conclusion Our findings suggest that γδT cells may enhance B-cell differentiation into antibody-producing plasma cells in BD patients with mucocutaneous and ocular clinical phenotypes. </jats:sec
Nobody can be immune to the deaths of this girl, her family, and the paramedics who tried to save her.
No full textPrevalence and outcomes of recorded dementia vary by data source: a population cohort study of 133,407 older adults
No full textLifetime effects of adherence to cardiovascular and diabetes medications in Spain: a modelling study in a population cohort of 152,117 patients
Get PDFOptimal strategies for treatment discontinuation in MOG antibody-associated disease.
Get PDFIt is not known what the relapse risk is after immunomodulatory treatment discontinuation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Evidence suggests "at least" 3 months of oral corticosteroids reduces the relapse risk after a single attack and that it may be possible to stop maintenance treatment in relapsing stable disease but the optimal duration of treatment is unknown. We therefore aimed to investigate relapse outcomes following maintenance treatment discontinuation. We conducted a cohort study of MOGAD patients seen in the Oxford Neuromyelitis Optica Highly Specialised Service between January 2010 and May 2025. Patients with MOGAD, at least 12 months follow-up, and who commenced and then discontinued maintenance treatment were included. Associations of factors including treatment duration prior to discontinuation, disease course at discontinuation (after a single attack/monophasic or relapsing course) and MOG IgG1 status on live cell-based assay were investigated. Primary outcome was time-to-relapse following treatment discontinuation. Cox regression was used. We included 190 MOGAD patients with 236 discontinued treatment intervals. 150 (63.6%) discontinuations were after a single attack and before a first relapse when disease course was monophasic, and 86 (36.4%) discontinuations occurred in patients who had a relapsing disease course. Most patients used corticosteroids alone (84.7% IT intervals), and non-steroid IT were used in 15.2% of IT intervals either alone or in combination with steroids. Post-discontinuation relapse occurred after 92 (39.0%) discontinuations at a median time of 5.4 (interquartile range 1.4-20.1) months after treatment cessation. Those who relapsed were more likely to have a relapsing course at time of discontinuation (50% vs 27.8%, P=0.001) and a positive/low positive pre-discontinuation MOG IgG1 result (89.8% vs 71.5%, P=0.005). In multivariable analysis, a relapsing course at time of discontinuation was associated with an elevated relapse risk (hazard ratio 1.95, 95% confidence interval 1.25-3.06, P=0.003). Overall, prolonged treatment durations prior to discontinuation beyond 3 months significantly reduced relapse risk. Optimal treatment durations were estimated as at least 10-18 months for patients treated after their onset attack and 20-30 months for relapsing patients, following which treatment discontinuation could be considered in patients who were relapse-free on treatment. Identifying the relapse risk when discontinuing maintenance immunomodulatory treatment in MOGAD should aid management decisions in patients presenting with their first attack and also in those on longer-term treatment for relapsing disease. Our findings, from a cohort predominantly treated with steroids, provide evidence to inform joint decision-making for stable patients who are considering treatment cessation
Global education and training in geriatrics: mapping transnational initiatives and their complementarities.
Get PDFPURPOSE: To map and characterise major transnational initiatives in geriatrics education and training, and explore complementarities as a basis for a more integrated and equitable global framework. METHODS: A mapping exercise and expert consultation were undertaken by the European Geriatric Medicine Society (EuGMS) Special Interest Group on Education and Training between January and October 2025, including a meeting of international experts during the Twenty-First EuGMS Congress in Reykjavík. Eligible initiatives operated across national borders with an explicit mandate in education and training related to geriatrics and were not confined to a specific topic or subspecialty. Each initiative was profiled by scope, target audience, and contributions, and classified within a three-tier framework: (1) foundational capacity-building, (2) professional and interprofessional development, and (3) leadership and specialist advancement. RESULTS: Seventeen initiatives were identified. Tier 1 included the International Federation on Ageing (IFA), International Institute on Ageing, United Nations-Malta (INIA), PAHO's ACAPEM (Basic), ASEAN's Centre for Active Ageing and Innovation (ASEAN-ACAI), IAGG's e-Training in Gerontology and Geriatrics (e-TRIGGER) programmes, WHO's Integrated Care for Older People (WHO ICOPE approach), and AfriAGE. Tier 2 included the IAGG, EuGMS, EICA, PROGRAMMING CA2112, Victorian Geriatric Medicine Training Programme (VGMTP), and ACAPEM (Intermediate); and Tier 3 was represented by leadership academies (EAMA, ALMA, MEAMA/MENAAA, and AAMA), and UEMS-GMS. CONCLUSION: Collectively, these programmes form a considerably disjointed but potentially complementary global ecosystem for geriatrics education. Greater mutual awareness and alignment, anchored in equity and interprofessional inclusion, could enhance efficiency and sustainability in developing the global geriatrics workforce
Genetic determinants of Multiple Sclerosis susceptibility in diverse ancestral backgrounds
No full textTime to diagnosis for breast, cervical and colorectal cancer in Zimbabwe and South Africa: a cross-sectional study.
No full textINTRODUCTION: Shorter time to diagnosis may lead to better cancer outcomes in Southern Africa. This study measured the time from symptoms to first healthcare visit (patient interval; PI) and diagnosis (diagnostic interval; DI) and associated factors for breast, cervical and colorectal cancer in Zimbabwe and South Africa (SA). METHODS: A cross-sectional survey collected data on socio-demographics, cancer awareness, barriers to seeking care, symptoms, healthcare visits and diagnosis after recent cancer diagnosis. Cox regression was used to determine factors associated with PI and DI. RESULTS: This study included 1021 participants (Zimbabwe 396, SA 625). Symptom and risk factor recall was low. Median PIs were shorter than DIs across cancers and regions. For breast cancer, those reporting more health-seeking barriers had longer PIs (Zimbabwe HR 0.801, 95% CI 0.703 to 0.913; SA HR 0.885, 95% CI 0.817 to 0.958), while greater emotional response to symptoms was associated with a shorter PI (Zimbabwe HR 1.194, 95% CI 1.101 to 1.295; SA HR 1.145, 95% CI 1.079 to 1.216). Interpreting a cervical symptom as serious (Zimbabwe) was associated with a shorter PI. DIs were longer in less-resourced regions and increased with number of healthcare visits before diagnosis. Significantly shorter DIs occurred when the first provider was a clinic doctor or specialist compared with a clinic nurse. CONCLUSIONS: Efforts to improve timely cancer diagnosis in Zimbabwe and SA should focus on supporting primary healthcare providers in managing and referring symptomatic patients, enhancing cancer symptom awareness and interpretation, and addressing barriers to care