Explore the vast range of titles available.

Objectives The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Methods Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. Results The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00–4.06): 102 (2.13% 95% CI 1.73–2.56) with stroke and 81 (1.68% 95% CI 1.33–2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet’s disease (9.5%, 95% CI 5.79–14.37), polyarteritis nodosa (6.2%, 95% CI 3.25–10.61), and Takayasu’s arteritis (6.0%, 95% CI 4.30–8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09–3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20–3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05–9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01–2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. Conclusion CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet’s. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

Different vasculitic syndromes present in different age groups. Immunoglobulin (Ig)A vasculitis and Kawasaki disease usually present in children whereas giant cell arteritis (GCA) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually present in the middle aged/elderly. In Northern Europe, granulomatosis with polyangiitis (GPA; Wegener’s) is commoner than microscopic polyangiitis (MPA) and MPA is more common than eosinophilic granulomatosis with polyangiitis (EPGA; Churg−Strauss syndrome). In Southern Europe, MPA is commoner than GPA and in Japan MPA is much more common than GPA. Major differences exist worldwide in ANCA specificity which are not entirely related to different phenotypes. GPA, like GCA, has a cyclical pattern of onset suggesting possible infection as an aetiological agent. International studies have given important clues to possible aetiology including silica dust and infection and genetic influences, as shown by the recently published genome-wide association study which revealed that single-nucleotide polymorphisms associate more strongly with ANCA than clinical syndromes. A brief description of the main clinical features of ANCA-associated vasculitis is also given.

The many forms of vasculitis are characterized by inflammation of blood vessels, leading to potentially long-term sequelae including vision loss, aneurysm formation and kidney failure. Accurate estimation of the incidence and prevalence has been hampered by the absence of reliable diagnostic criteria and the rarity of these conditions; however, much progress has been made over the past two decades, although data are still lacking from many parts of the world including the Indian subcontinent, China, Africa and South America. Giant cell arteritis occurs in those aged 50 years and over and seems to mainly affect persons of northern European ancestry, whereas Takayasu arteritis occurs mainly in those aged under 40 years. By contrast, Kawasaki disease mainly occurs in children aged under 5 years and is most common in children of Asian ancestry, and IgA vasculitis occurs in children and adolescents. Although much less common than giant cell arteritis, the different forms of antineutrophil cytoplasmic antibody-associated vasculitis are being increasingly recognized in most populations and occur more frequently with increasing age. Behçet syndrome occurs most commonly along the ancient silk road between Europe and China. Much work needs to be done to better understand the influence of ethnicity, geographical location, environment and social factors on the development of vasculitis.Vasculitis, inflammation of the blood vessels, takes many forms and can affect every organ system, potentially causing kidney failure, vision loss and death. This Review describes current knowledge on the global incidence and prevalence patterns for various types of vasculitis.

Background Following a knowledge management analysis, Médecins Sans Frontières (MSF) – a medical humanitarian non-governmental organisation (NGO) – identified significant loss of medical knowledge from the field, owing primarily to the absence of a platform on which to share clinical lessons learned in humanitarian and resource-limited settings (HRLS). Wishing to address these missed opportunities to retain important scientific and pragmatic knowledge, the NGO has begun to actively encourage its clinicians to publish case reports/series that bring new and/or practical insights of benefit to patients and population groups. In parallel, we wished to obtain a clearer understanding of how case reports (CRs)/series can best play their role as ‘first-line evidence’ from HRLS, especially in areas suffering from a significant lack of data. Methods We developed a survey with closed and open questions on ‘The value of CRs from HRLS’ to explore primarily (1) the reasons why this form of evidence from HRLS is often lacking, (2) what makes a case report/series worth sharing with the wider global health community, and (3) how we can ensure that published case reports/series reach their target audience. Results Over a 6-month period, 1115 health professionals responded to the survey. Participants included clinicians and public health specialists from all over the world, with a majority based in Africa. The main reason cited for the dearth of CRs from HRLS was that practitioners are simply not writing and/or submitting reports (as versus having their papers rejected) due mainly to (1) a lack of skills and (2) time constraints. A large majority of respondents felt the CRs are a valuable tool for HRLS given their ability to discuss how cases are managed with rudimentary means as well as to draw attention to emerging or underestimated public health problems and neglected populations. Conclusion We conclude that the clinical knowledge gained in resource-challenged settings is being underutilised in the interest of patients and global health. Consequently, clinicians in HRLS need greater access to basic training in scientific investigation and writing in addition to awareness as to the potential value of sharing their clinical experience with a view to broadening evidence production from high-income to low-income settings.

ObjectiveTo examine the performance in adults of the European Alliance of Associations for Rheumatology (EULAR)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 classification criteria for IgA vasculitis (IgAV).MethodsThe EULAR/PReS/Ankara 2008 classification criteria for IgAV were applied to patients enrolled in an international observational cohort which included patients with IgAV and comparators with other forms of small-vessel and medium-vessel vasculitis. After the initial assessment of the performance of the criteria, possible revisions to increase the performance were tested. The revised criteria were then assessed in an independent validation cohort within a multicentre Turkish vasculitis registry.ResultsThe dataset consisted of 178 IgAV cases and 1705 comparators. The Ankara 2008 criteria require skin involvement plus one of the following four criteria: abdominal pain, a biopsy showing IgA deposition, arthritis or arthralgia, or renal involvement (any haematuria and/or proteinuria). The specificity of the criteria improved when a positive test for anti-neutrophil cytoplasmic autoantibody or blood cryoglobulins was considered an exclusion criterion. The revised criteria had a sensitivity of 76.4% (95% CI 69.8% to 82.2%) and a specificity of 94.5% (95.0% CI 93.4% to 95.1%). In the validation set, the sensitivity and specificity of the revised criteria were 97.8% (95% CI 94.0% to 99.0%) and 85.0% (95.0% CI 78.0% to 90.0%), respectively.ConclusionThe revised EULAR/PReS-endorsed Ankara 2008 IgAV classification criteria perform well in adults with IgAV and are appropriate for use in clinical research.

Purpose of ReviewPlasma exchange (PLEX) is often recommended as an adjunctive therapy for patients with ANCA-associated vasculitis (AAV) in the setting of rapidly progressive glomerulonephritis or diffuse alveolar haemorrhage. Since ANCAs are pathogenic, it seems a reasonable and justified approach to remove them through therapeutic PLEX, as despite advances in immunosuppressive therapy regimens, AAV is associated with significant morbidity and death. However, the association between ANCA levels and mortality or disease activity is uncertain. In addition, any treatment must be judged on the potential risks and benefits of its use. Here, we summarise the current data on PLEX usage in patients with AAV.Recent FindingsThe largest randomised trial to date the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) study failed to show added benefit for PLEX on the prevention of death or end-stage renal failure (ESRF) for the management of patients with severe AAV. However, there is a possibility that PLEX delays dialysis dependence and ESRF in the early stages of the disease. Regardless of whether this is only for 3 to 12 months, this could be of clinical significance and a substantial improvement in patient’s quality of life.SummaryCost utility analysis and trials including patient-centred outcomes are required to evaluate the use of PLEX. Furthermore, ascertaining those at high risk of developing ESRF could help identify those who may benefit from PLEX the most, and further insights are required in setting of diffuse alveolar haemorrhage.

Background The genetic contribution to the aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is not well defined. Across different autoimmune diseases some genes with immunomodulatory roles, such as PTPN22 , are frequently associated with multiple diseases, whereas specific HLA associations, such as HLA-B27 , tend to be disease restricted. We studied ten candidate loci on the basis of their immunoregulatory role and prior associations with type 1 diabetes (T1D). These included PTPN22 , CTLA4 and CD226 , which have previously been associated with AAV. Methods We genotyped the following 11 SNPs, from 10 loci, in 641 AAV patients using TaqMan genotyping: rs2476601 in PTPN22 , rs1990760 in IFIH1 , rs3087243 in CTLA4 , rs2069763 in IL2 , rs10877012 in CYP27B1 , rs2292239 in ERBB3 , rs3184504 in SH2B3 , rs12708716 in CLEC16A , rs1893217 and rs478582 in PTPN2 and rs763361 in CD226 . Where possible, we performed a meta-analysis with previous analyses. Results Both CTLA4 rs3087243 and PTPN22 rs2476601 showed association with AAV, P = 6.4 × 10 -3 and P = 1.4 × 10 -4 respectively. The minor allele (A) of CTLA4 rs3087243 is protective (odds ratio = 0.84), whereas the minor allele (A) of PTPN22 rs2476601 confers susceptibility (odds ratio = 1.40). These results confirmed previously described associations with AAV. After meta-analysis, the PTPN22 rs2476601 association was further strengthened (combined P = 4.2 × 10 -7 , odds ratio of 1.48 for the A allele). The other 9 SNPs, including rs763361 in CD226 , showed no association with AAV. Conclusion Our study of T1D associated SNPs in AAV has confirmed CTLA4 and PTPN22 as susceptibility loci in AAV. These genes encode two key regulators of the immune response and are associated with many autoimmune diseases, including T1D, autoimmune thyroid disease, celiac disease, rheumatoid arthritis, and now AAV.

To report the annual incidence of primary large vessel vasculitis (LVV) in the adult population of Norfolk County, UK, including giant cell arteritis (GCA) (in those ≥50 years) and Takayasu arteritis (TAK). Individuals diagnosed by histology or imaging who lived in NR1-NR30 postcode districts were included. Validated criteria from 1990 and 2022 were applied for final classification. Population data were available from the Office of National Statistics, UK. 270 individuals were diagnosed with primary LVV over 4.7 million person-years. The annual incidence (95% CI) of primary LVV was 57.5 (50.8, 64.7)/million person-years in the adult population. 227 and 244 individuals were diagnosed with GCA over ~2.5 million person-years using 1990 and 2022 criteria, respectively. The annual incidence (95% CI) of GCA was 91.6 (80.0, 104.3)/million person-years aged ≥50 years using 1990 criteria and 98.4 (86.4, 111.6)/million person-years aged ≥50 years using 2022 criteria. 13 and 2 individuals were diagnosed with TAK over 4.7 million person-years. The annual incidence (95% CI) of TAK was 2.8 (1.5, 4.7)/million person-years using 1990 criteria and 0.4 (0.0, 1.4)/million person-years using 2022 criteria, in the adult population. The incidence of GCA rose sharply in 2017 coincident with the introduction of a fast-track pathway and fell during the pandemic when the pathway was disrupted. This is the first study that reports the incidence of objectively verified primary LVV in the adult population. The incidence of GCA may be affected by the availability of diagnostic pathways. The use of the 2022 classification criteria results in a rise in the classification of GCA and fall in that of TAK.

We cloned two hemoglobin genes from Arabidopsis thaliana. One gene, AHB1, is related in sequence to the family of nonsymbiotic hemoglobin genes previously identified in a number of plant species (class 1). The second hemoglobin gene, AHB2, represents a class of nonsymbiotic hemoglobin (class 2) related in sequence to the symbiotic hemoglobin genes of legumes and Casuarina. The properties of these two hemoglobins suggest that the two families of nonsymbiotic hemoglobins may differ in function from each other and from the symbiotic hemoglobins. AHB1 is induced, in both roots and rosette leaves, by low oxygen levels. Recombinant AHB1 has an oxygen affinity so high as to make it unlikely to function as an oxygen transporter. AHB2 is expressed at a low level in rosette leaves and is low temperature-inducible. AHB2 protein has a lower affinity for oxygen than AHB1 but is similar to AHB1 in having an unusually low, pH-sensitive oxygen off-rate.