Latest news with #ANCA
Medscape
07-07-2025
- Health
- Medscape
Fast Five Quiz: Management of MPA
Microscopic polyangiitis (MPA) represents one category within the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), alongside granulomatosis with polyangiitis (GPA) and eosinophilic GPA (EGPA). MPA is associated with distinct presentations, organ involvement, and worse prognosis than EGPA and GPA; treatment strategies must be customized according to disease severity, affected organs, and individual patient characteristics. What do you know about the management of MPA? Check your knowledge with this quick quiz. Although renal involvement is common in ANCA vasculitis owing to a high concentration of blood vessels, subtypes of ANCA vasculitis have distinct patterns of extrarenal involvement. These varying clinical presentations correlate with different antibody profiles: MPA commonly associates with myeloperoxidase (MPO) serology while GPA generally presents with proteinase 3 (PR3) serology. Following renal involvement, the pulmonary system is a commonly involved organ system in MPA; cutaneous involvement and neurologic manifestations are also common. MPA typically shows fewer manifestations in the ear, nose, and throat region and eyes than other subtypes. Cardiovascular system and gastrointestinal system involvement are more often seen in EGPA, though patients with MPA can experience cardiovascular and gastrointestinal symptoms. Learn more about renal involvement in MPA. The latest Kidney Disease Improving Global Outcomes (KDIGO) and European Alliance of Associations for Rheumatology (EULAR) guidelines recommend beginning plasma exchange in patients with MPA when serum creatinine rises above > 300 µmol/L (equivalent to 3.4 mg/dL, as stated by KDIGO). This is supported by a recent meta-analysis that reported plasma exchange reduces the risk for end-stage kidney disease at 12 months; the same serum creatinine level for initiation was recommended by the researchers. However, they noted that plasma exchange was not found to improve the combined endpoint of "death and/or end-stage kidney disease." Additionally, KDIGO also recommends plasma exchange for patients requiring dialysis or those with diffuse alveolar hemorrhage and hypoxemia, but EULAR specifically recommends against routine use of plasma exchange for diffuse alveolar hemorrhage in patients with MPA and GPA. Learn more about creatinine monitoring in MPA. The latest KDIGO guidelines recommend considering discontinuation of immunosuppressive therapy in patients with MPA who have remained on dialysis for 3 months without extrarenal disease manifestations. This approach acknowledges that patients with MPO-ANCA-associated vasculitis (which is most strongly associated with MPA) who have kidney failure without involvement of other organs face minimal relapse risk. Supporting this, the EULAR cites research demonstrating that patients who are dependent on dialysis and in remission without immunosuppression are significantly more likely to experience serious infectious or cardiovascular complications from continued treatment than suffer disease recurrence; they specifically recommend weighing benefits and harms in continuing immunosuppressive therapy in the MPA subtype of ANCA. Learn more about immunosuppressive therapy in MPA. According to a recent review citing data from KDIGO, patients with MPA typically have the worst kidney prognosis due to the chronic damage associated with this subtype. Further, patients with EGPA less often have kidney involvement than GPA or MPA and usually have better kidney prognosis. Kidney prognosis is generally worse in patients with MPA than those with GPA as well. KDIGO also cites previously developed prognostic scoring systems (which include sclerotic, focal, crescentic, and mixed class), depending on most of the glomeruli histology. For example, focal class (> 50% normal glomeruli) is associated with a favorable outcome, while sclerotic class (≥ 50% sclerotic glomeruli) is associated with poorer outcomes. Learn more about prognosis in MPA. Both KDIGO and EULAR guidelines recommend a tapering schedule of 4-5 months after initiating glucocorticoids in patients with MPA, reaching a reduced dose (listed as " 5 mg prednisolone equivalent" per day) by that point. Tapering schedule is generally based on weight and disease severity. For example, for patients weighing > 75 kg (165 lb), EULAR suggests starting at 75 mg, then tapering to 40 mg by week 2, then lowering the dose by approximately 25% every 2 weeks until reaching 5 mg by week 19. This is the same tapering schedule recommended by KDIGO; the full tapering schedule for this weight and others can be found here. Clinical evidence supporting this strategy comes from the PEXIVAS trial, which demonstrated that lowering steroid exposure by 40% during the initial 6 months maintained therapeutic effectiveness while significantly decreasing serious infection rates compared to conventional dosing. This accelerated reduction strategy effectively balances inflammatory control with minimizing steroid-related complications. Learn more about glucocorticoids in MPA.
Medscape
03-07-2025
- Health
- Medscape
Fast Five Quiz: Management of GPA
Granulomatosis with polyangiitis (GPA) is a variant of anti-neutrophil cytoplasmic antibody ( ANCA)-associated vasculitis that most commonly presents with proteinase 3 (PR3) serology and distinct clinical features that necessitates swift identification and therapeutic intervention. Prompt treatment plays a crucial role in minimizing permanent organ damage, particularly in the renal and pulmonary systems. What do you know about the management of GPA? Check your knowledge with this quick quiz. The latest guidelines from the Kidney Disease Improving Global Outcomes (KDIGO) and European Alliance of Associations for Rheumatology (EULAR) both recommend initiating immunosuppressive therapy in patients with suspected PR3 positive ANCA vasculitis, which is indicative of GPA, even if clinicians are still awaiting biopsy results. Further, EULAR specifically acknowledges that collecting biopsies might not be feasible for each patient with ANCA vasculitis and treatment should 'not be delayed while awaiting histological information.' Learn more about biopsy for GPA. KDIGO recommends maintaining therapeutic intervention for 18 months to 4 years following successful remission, which is similar to the EULAR guidelines recommending maintenance therapy for 24-48 months in patients with GPA. They also state, 'longer duration of therapy should be considered in relapsing patients or those with an increased risk of relapse, but should be balanced against patient preferences and risks of continuing immunosuppression.' Learn more about remission maintenance in GPA. Infection is a significant concern in ANCA vasculitis, especially regarding immunosuppressive therapies including glucocorticoids that are used to manage the clinical manifestations of the disease. Recent research has shown that chronic nasal carriage of S aureus is significantly higher in patients with the GPA subtype; it has also been shown to be associated with increased endonasal activity and risk for relapse. Although M catarrhalis, H influenzae, and S pneumoniae do not appear to have a specific association with GPA, data have shown that infection is among the most common causes of death in GPA. Learn more about infection in GPA. Data indicate that the GPA subtype is an independent risk factor for disease recurrence. Additionally, KDIGO also considers lower serum creatinine, more extensive disease, PR3 histology (which is associated with higher relapse rates than MPO-positive disease commonly seen in MPA) and ear, nose, and throat involvement as 'baseline factors' for disease recurrence. Factors after diagnosis include history of relapse, ANCA positivity at the end of induction, and rise in ANCA. Treatment-related relapse factors include lower cyclophosphamide exposure, immunosuppressive withdrawal, and glucocorticoid withdrawal. Learn more about prognosis in GPA. To ensure disease does not recur into the transplanted tissue, KDIGO specifically recommends delaying kidney transplantation until patients have achieved complete clinical remission for at least 6 months. Further, ANCA positivity or negativity should not factor into this decision, with KDIGO stating, 'the persistence of ANCA should not delay transplantation.' Although a serum creatinine of > 4 mg/dL is a significant predictor of relapse, guidelines recommend considering combination of a monoclonal antibody and an alkylating agent for this indication. Similarly, induction and maintenance of dialysis should also be done under various separate conditions. Learn more about kidney transplantation for GPA. Editor's Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
Hamilton Spectator
26-06-2025
- Business
- Hamilton Spectator
Contentious Anmore South proposal withdrawn by developer on eve of public hearing
The contentious Anmore South proposal is officially on ice. Just hours before a public hearing to Anmore's Official Community Plan (OCP), Icona Properties announced it was withdrawing the application. 'It's become clear that our proposal, though supported by many, has also caused division. This was never our intent. In fact, it's the opposite of what we set out to do,' said Icona's CEO Greg Moore. 'We've made the decision to withdraw our current application for Anmore South. This break will allow us to explore a path forward that brings more unity than discord. 'Our sincere hope is that this step will help ease tensions and create the space for a collaborative, community-driven solution.' The Village of Anmore's council chambers erupted in cheers and claps after a resident read Moore's message to a crowd of hundreds of residents. The application was recently advanced to a public hearing by a 4-1 vote earlier this month. But despite a scaled back development proposal – 1,750 residential units, down from 2,200 – council's debate was marked by a divided and frustrated public gallery. Residents have long expressed concerns that the 151-acre development is out of step with Anmore's rural character and that the public consultation process has been insufficient. Several neighbourhood groups have recently pushed for a referendum on the development, which has been resisted by council. One such group, the Anmore Neighbours Community Association (ANCA), even formally warned the village on May 15 that it intended to pursue legal action if the OCP amendment process for Anmore South continued unchanged. ANCA's lawyers accused the village of procedural fairness breaches, councillor bias, democratic suppression, and infringing on freedom of expression under the Canadian Charter of Rights and Freedoms. Neighbouring municipalities have also weighed in. Port Moody submitted a formal letter criticizing the lack of infrastructure planning – particularly with respect to traffic, utilities, and emergency services –and raised alarms about environmental risks, especially given the sensitive ecosystems near the site. The Village of Belcarra offered a similar critique. Dialogue around the Anmore South proposal has been fraught with division since engagement first began in 2021. Accusations of NIMBYism, disinformation, and corruption have been frequent and recurring. Council received 63 written submissions regarding the OCP amendment, which would have changed the land use designation to allow for the development. While most of the correspondence was opposed to the land use change, many residents offered support, citing more affordable options and options for downsizing seniors. One Anmore renter, Juan Gaviria, said he was deeply concerned by the 'toxic environment' surrounding the development process. He said that he supported the amendment because it offered tangible benefits like improved infrastructure, expanded recreational amenities, new facilities, and diversified housing types. 'It is a sad state of affairs when fear and aggression overshadow reasoned, respectful discourse,' Gaviria said. 'Despite holding a full-time professional job and running a business, I cannot afford to purchase a home in Anmore.' Jordan Birch, speaking for his family of six, said he was 'disgusted' by Anmore's NIMBYism and neighbourhood associations, which he described as 'seeding doubt and division' in the community. He noted that over 42 percent of the land is dedicated to parks and conservation, that the project would expand the municipal tax base, and connect Anmore to Metro Vancouver's servicing. 'The Anmore South Neighbourhood Plan is a once-in-a-generation opportunity to build a resilient community,' Birch said. 'I am appalled by those who disguise their opposition as community care, ignoring the long-term consequences of blocking progress.' After receiving word that Icona had rescinded its application, Mayor John McEwen released a statement on the village website, stating the village chose not to proceed with the hearing. 'Needless to say, this came as a surprise, and we are still confirming details of icona's intentions,' McEwen said. 'I do not know what will be considered next for Anmore South, as it is up to the applicant.' McEwen added that council legally had to consider the application, and acted in 'good faith,' and pushed for neighbourhood plan and community engagement beyond what was required. Error! Sorry, there was an error processing your request. There was a problem with the recaptcha. Please try again. You may unsubscribe at any time. By signing up, you agree to our terms of use and privacy policy . This site is protected by reCAPTCHA and the Google privacy policy and terms of service apply. Want more of the latest from us? Sign up for more at our newsletter page .
Medscape
22-05-2025
- Health
- Medscape
Novel Neutrophil Subset Predicts Relapse in ANCA Vasculitis
Researchers in Japan showed that a unique neutrophil subset, characterized by type II interferon signature genes (T2ISG), along with elevated levels of interferon gamma in the blood, can predict the risk for relapse in patients with new-onset microscopic polyangiitis (MPA). METHODOLOGY: Researchers conducted single-cell transcriptome and surface proteome analyses of peripheral white blood cells from patients with new-onset MPA to study neutrophil dynamics in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. They collected 179,664 peripheral white blood cells from six patients with new-onset MPA (three women; average age, 74 years) and seven healthy donors (four women; average age, 67 years). Patient samples were taken before starting immunosuppressive therapy. Interferon gamma concentrations in the serum were measured for 37 patients with MPA, of whom 24 had new-onset disease and 13 had started receiving treatment. TAKEAWAY: Compared with healthy donors, patients with MPA showed higher proportions of two distinct neutrophil populations: Immature neutrophil and T2ISG neutrophil populations. Certain differentially expressed genes in the neutrophils of patients with MPA vs healthy donors were linked to interferon gamma signaling. The T2ISG neutrophil subset differentiated from mature neutrophils upon stimulation with interferon gamma and tumor necrosis factor. This subset was characterized by the surface exposure of pathogenic molecules that may contribute to neutrophil-mediated inflammation in MPA. Of the six patients with new-onset MPA, those who showed higher proportions of the T2ISG neutrophil subset exhibited persistent vasculitis symptoms. Elevated serum concentrations of interferon gamma at the onset of vasculitis were associated with subsequent relapses. Among the patients with new-onset disease, those who had the highest serum interferon gamma concentrations experienced relapses despite treatment. A model based on serum interferon gamma, myeloperoxidase-ANCA, and C-reactive protein levels efficiently predicted the risk for relapse before the initiation of immunosuppressive treatment (area under the curve, 0.84; sensitivity, 93%; specificity, 78%). IN PRACTICE: 'Our work elucidates neutrophil dynamics at the single-cell level and suggests a potential biomarker for predicting relapse in MPA,' the authors of the study wrote. SOURCE: This study was led by Masayuki Nishide and Kei Nishimura, Osaka University, Osaka, Japan. It was published online on April 24, 2025, in Nature Communications . LIMITATIONS: This study recruited only Japanese patients, which may limit the evaluation of racial differences. The absence of neutrophil profiles from other diseases made it unclear whether the identified profile was specific to MPA. The interferon gamma signaling pathway may be a common feature in the pathophysiology of various forms of ANCA-associated vasculitis. DISCLOSURES: This study received financial support from multiple organizations, including the Japan Society for the Promotion of Science, the Japan Science and Technology Agency, and the Japan Agency for Medical Research and Development. Several authors reported receiving grants, being employed by, and/or holding stocks in a pharmaceutical company.
Hamilton Spectator
22-05-2025
- Politics
- Hamilton Spectator
Anmore group threatens legal action against village over Anmore South development
The Village of Anmore has been threatened with a legal action over its handling of the contentious Anmore South development, with the Anmore Neighbours Community Association (ANCA) alleging procedural and constitutional violations. In a May 15 letter addressed to Mayor John McEwen and council, ANCA's lawyers accuses the village of bias, democratic suppression, and violations of free expression under the Canadian Charter of Rights and Freedoms. The letter warns that unless the Official Community Plan (OCP) amendment process is halted and corrected, ANCA will petition the B.C. Supreme Court to quash any resulting decision. 'If the village chooses to ignore (these complaints) and forge ahead with the OCP amendment, it can expect a legal proceeding brought by ANCA, and perhaps others, to set the decision aside,' ANCA's lawyers stated. The Anmore South project, proposed by Icona Properties, aims to transform 151-acres on the municipality's southwest border into a mixed-use development with approximately 2,200 units, commercial space, a community centre, parks, and a connection to Metro Vancouver's wastewater system. Anmore's population could nearly triple over the next 25 years if council were to approve an amendment to its official community plan changing the designation of the lands from rural to urban. The Village of Anmore did not respond to a request for comment by press time. Accusations of bias ANCA claimed three of the five Anmore councillors – Mayor John McEwen and Couns. Polly Krier, and Kim Trowbridge – have 'prejudged' their decision on the OCP amendment by publicly endorsing the proposed 'preferred plan' before a public hearing has occurred. Several statements from the councillors are provided. ANCA argued that those statements show their 'minds are made up' regarding the OCP amendment. 'The public hearing itself is pointless – the mayor and these councillors will sit and listen to suggestions, but not whether to vote 'yes' or 'no' on the amendment, which is the vote that will come before them,' the letter stated. Earlier this year, McEwen said it would be a loss if only single-family homes were built in the area. 'I think the key thing that we have to remember is, this land is going to be developed at some point,' McEwen said at a February meeting. 'I've said very publicly, I certainly don't want it to go RS-1 the way some areas of the other village have.' Council has discussed development of the Anmore South site since it was designated as a special study area in 2007. More recently, council discussed three visions for the land, including one pitch for approximately 3,500 units. ANCA cited several Supreme Court of Canada decisions, arguing the legal standard for disqualifying a member of council from participating in a decision is if they are no longer capable of being persuaded. It further claims the councillors have shown to prejudge the amendment decision by rushing the process through despite late completion of a consultant reports, an incomplete neighbourhood plan, and treating the first and second reading of the bylaw as routine 'housekeeping' steps. The letter urged all three representatives to recuse themselves from further deliberations, warning that if they do not, any vote on the OCP amendment will be legally tainted. Because this recusal would leave council without quorum, ANCA suggested the village seek direction from the court to allow the decision to proceed with a modified quorum. ANCA stated it would expect Mayor McEwen's participation to be conditional on a court order requiring him to consider public input 'with as open a mind as possible.' Accusations of Charter breaches The municipality is also being accused of suppressing political dissent regarding Anmore South by unreasonably limiting free expression at council meetings and through local signage restrictions. ANCA highlighted recent changes to the village's procedure bylaw , which bar comments on any topic that may be the subject of a future public hearing. They state this 'broadly drafted' clause is unconstitutional because it stifles political expression on pending issues before they are formally up for debate. The bylaw was invoked during the May 6 council meeting, when residents were barred from raising questions about Anmore South during question period, while the developer and two opposing delegations were permitted to speak about the project during the same meeting. ANCA contended this inconsistent application shows the bylaw is being enforced in a discriminatory manner and suppressing community opposition while giving the developer a platform. Icona CEO Greg Moore defended the consultation process, noting that 28 public engagement events have been held since 2021. The ANCA letter also raised concerns about a zoning bylaw which restricts residential signage to only certain types such as real estate or home business signs. Political signage is not permitted, even on private property. While the bylaw is in place to limit visual pollution, ANCA claimed it is being used as a way to prohibit 'political expression on a matter of fundamental importance to the community.' According to the letter, ANCA has received reports that village staff have removed signs opposing Anmore South, while leaving up other signs that also contravene the bylaw. ANCA argued this suggests 'discretionary unfairness' and points to an active effort by the village to suppress opposition to Anmore South. The letter is calling on council to delay the public hearing and OCP amendment decision by 'at minimum several months' until both the procedure bylaw and zoning bylaw are amended to comply with Charter protections. Only after residents are given a 'reasonable period' for unrestricted political expression, should the amendment return to council for a vote, ANCA stated. The letter follows several months of escalating tension around the Anmore South proposal, with groups like ANCA and the Anmore Residents Association describing the process as 'developer-dominated,' and calling for a referendum to decide the project's fate.
