Inflammation Of Blood Vessels Research Articles

Case report: Propylthiouracil-induced serious side effect: Perinuclear antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis?

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare disease characterized by the inflammation and destruction of small blood vessels and circulating ANCAs. Drugs such as antithyroid drugs (ATDs), especially propylthiouracil (PTU), have been used for the production of ANCAs and cause the development of drug-induced AAV. The pathogenesis of this disease is unclear but could be related to the physiological processes affecting the degradation of neutrophil extracellular traps (NETs). At present, PTU is widely used in patients with Graves' disease (GD) who are preparing for pregnancy and whose condition has not been controlled. Once drug-induced AAV has occurred with important organ damage, considering NETs have a significant role in the immune system, whether the cessation of drugs could stop the progression of organ damage is unclear, and a consensus regarding standard treatment has not been established. In this case report, a female patient who planned pregnancy was hospitalized with multiple joint pain, impaired renal function, and hematuria. Immunofluorescence of the renal biopsy demonstrated spherical and diffuse mesangial distribution of IgA (3+). Autoimmune serology demonstrated positivity for autoantibodies against p-ANCA and an anti-MPO titer 74.72 RU/mL. She was diagnosed with PTU-induced p-ANCA-associated and IgA-associated vasculitis (IgAV). The patient accepted low doses of glucocorticoid, immunosuppressive therapy and RAI treatment. Both her kidney function and thyroid function remained were on the mend. The authors believe that this type of patient needs to fully consider their pregnancy preparation needs, suspend pregnancy when a small chance of GD remission is indicated, and avoid the use of drugs with reproductive toxicity and other serious adverse events. The multidisciplinary combination therapy of low-dose glucocorticoids and immunosuppressants combined with iodine radiotherapy is one reasonable scheme. At the same time, it is necessary to eliminate the organ damage caused by other reasons. This report provides a clinical treatment basis for patients with drug-induced vasculitis manifestations who cannot receive an accurate diagnosis.

Converging paths: Microneedle-based dual intervention of IL-23/IL-17 axis and granuloma formation in rheumatoid nodules

Rheumatoid nodules (RNs) are an extra-articular manifestation of rheumatoid arthritis and are frequently observed in patients with autoimmune and inflammatory conditions. The development of RNs involves several stages, including inflammation of blood vessels, cell death triggered by medications, and infiltration of inflammatory cells leading to nodule formation. Recent studies highlight the importance of the IL-23/IL-17 axis and the migration of chronic inflammatory cells in this process, forming palisading granulomas. Current treatments often fail to manage RNs effectively because they tend to reoccur and appear in multiple locations. This study proposes a new therapeutic strategy combining corticosteroid treatment with gene silencing therapy using small interfering RNA (siRNA) targeting IL-23. Targeting these inflammatory pathways simultaneously aims to reduce both the size and number of nodules, potentially shortening the treatment duration. An innovative delivery system utilizing lipid-polymer hybrid nanoparticles (LPNs) and hyaluronic acid-based dissolving microneedles (MNs) is proposed to be developed. The LPNs will be designed with DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and DSPE-PEG (distearoyl-phosphoethanolamine-polyethylene glycol) as the lipid core, along with poly-lactic-co-glycolic acid (PLGA) polymer. These MN patches would improve the skin’s permeability, allowing LPN carrying the siRNA and corticosteroid to penetrate effectively. This non-invasive approach is expected to enhance the diffusion of LPNs into the skin, thereby increasing the availability of the therapeutic payload. Therefore, we hypothesize that targeting the IL-23/IL-17 axis and granuloma formation with the synergistic combination of targeted therapy and advanced delivery technology will revolutionize the treatment of RNs.

Overview of childhood vasculitis.

Pediatric vasculitis and adult vasculitis differ in several aspects. While both involve inflammation of blood vessels, pediatric vasculitis tends to present with distinct clinical features and may involve different types of blood vessels compared to adult vasculitis. Despite its relatively rare occurrence compared to adult vasculitis, pediatric vasculitis warrants careful attention due to its potential for profound and diverse clinical manifestations, ranging from mild cutaneous symptoms to life-threatening systemic complications. Childhood vasculitis should be suspected in children who present symptoms attributable to systemic inflammation and complications arising from multi-organ dysfunction. However, achieving a diagnosis necessitates thorough exclusion of alternative conditions manifesting similar symptoms and findings. Hence, children suspected of vasculitis should undergo meticulous history-taking, comprehensive physical examination, and requisite laboratory investigations, imaging studies, and sometimes tissue biopsies to elucidate the diagnosis. Early detection and treatment of childhood vasculitis are crucial, as the condition can affect various organs and potentially lead to life-threatening complications or long-term sequelae in adulthood if left untreated. This review aimed to provide an exhaustive overview of childhood vasculitis, outlining its epidemiology, classification, clinical presentation, diagnostic modalities, therapeutic strategies and outcome.

Antineutrophil cytoplasmic antibody-associated vasculitis.

This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules. Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans. Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies.

#675 Application of ANCA-associated vasculitis Histopathological Classification and Renal Risk Score for prediction of end-stage kidney disease

Abstract Background and Aims Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease predominantly characterized by inflammation of small-sized blood vessels along with the presence of circulating ANCA. The kidney is frequently involved and, even though immunosuppressive therapy has dramatically improved the outcome of AAV patients, a significant proportion of patients progress to end-stage kidney disease (ESKD). Therefore, establishing and validating tools to predict renal outcomes in patients with AAV is crucial. Here we analyzed the application of two tools in predicting kidney survival in a Portuguese single-center cohort with AAV. Method We conducted a retrospective cohort study at a tertiary-care hospital in Portugal (Hospital de São João, Porto), from December 2010 to June 2023. Patients with a kidney biopsy-proven AAV were included. Serological ANCA-negative patients and patients with overlap syndromes, such as AAV in combination with anti-glomerular basement membrane disease, were excluded. Based on electronic records, information on demographics and clinical variables were collected. Kidney biopsies were reviewed to calculate: Berden histopathological classification and the Brix Renal Risk Score (RRS). Kidney survival was defined as the time from diagnosis to the need for kidney replacement therapy. A Kaplan-Meier analysis was performed to compare kidney survival based on the mentioned classifications. Results Fifty-one patients were enrolled, 78% (n = 40) of whom were positive for myeloperoxidase (MPO). The majority were men (61%, n = 31) with a mean age of 65 (± 12) years and a mean serum creatinine of 4.59 mg/dL (± 2.74) at diagnosis. During a median follow-up of 39 (IQR, 7-84) months, 20 patients (39%) progressed to end-stage kidney disease (ESKD), 10 patients (20%) died with preserved renal function and 21 patients (41%) did not need hemodialysis. Concerning Berden classification, 13 patients with a crescentic class, 4 patients with a mixed class and 3 patients with a sclerotic class developed ESKD. After 48 months of follow-up, renal survival was 100%, 90%, 61% and 26.7% in the focal, mixed, crescentic and sclerotic class groups, respectively. Berden classification did not correlate with kidney survival (p = 0.211). Concerning RRS, 10 patients in the high-risk group and 5 patients in the medium-risk group developed ESKD. After 48 months of follow-up, renal survival was 100% in the low-risk group, 85.7% in the medium-risk group, and 41.6% in the high-risk group. A correlation was established between kidney survival and RRS score (p = 0.003). Conclusion In our cohort RRS was predictive of ESKD, contrary to Berden histopathological classification. The information derived from these risk models strongly add to standard biochemical and clinical data. Patients with higher risk of ESKD need close follow-up and a tailored treatment plan regarding preparation for renal replacement therapy.

#3068 Fibrosis and CD-163+ macrophages: making a difference between MPO-AAV and PR3-AAV

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis characterized by inflammation of small blood vessels, with the kidney being one of the most affected organs. Its pathogenesis is a complex, multifactorial process involving inflammation and fibrosis in which macrophages play a crucial role. Macrophages are plastic cells that can change their phenotype in response to their environment. Infiltration of CD163+ macrophages (anti-inflammatory) in the interstitium and glomeruli is observed in AAV patients. Clinical and demographic differences between PR3-AAV and MPO-AAV were observed. We observed that interstitial fibrosis (IFTA) is more pronounced in MPO-AAV than in PR3-AAV. We aimed to investigate the differences in CD163+ macrophage infiltration and interstitial fibrosis between PR3-AAV and MPO-AAV. Method Retrospective single-center study of 80 AAV patients (66 MPO-AAV and 14 PR3-AAV) diagnosed by renal biopsy with at least 1 year of follow-up. Clinical and laboratory variables, ANCA type and renal/patient survival were evaluated. 26 human kidney tissue samples (13 MPO-AAV and 13 PR3-AAV) were stained for CD163+ by immunohistochemistry and immunofluorescence, and trichrome-stained biopsy slides were used to measure the degree of fibrosis. Histomorphometric quantification was performed using MetaMorph® software in both cases. Data analysis was performed under standard conditions. Statistical significance was defined as P values less than 0.05. All P values were 2-sided. Results CD163+ macrophages infiltration in the interstitial space was greater in MPO-AAV than PR3-AAV with statistical significance (p < 0.001), observing an average infiltration area of 0.333% in MPO-AAV than 0.116% in PR3-AAV. Furthermore, IFTA was higher at diagnosis in MPO-AAV (35.35%) than in PR3-AAV (31.21%) at the diagnosis with a p = 0.03. However, a correlation between IF and CD163+ macrophages infiltration was not possible to stablish. Conclusion We have observed an increased macrophage infiltrate with an anti-inflammatory and reparative phenotype that is higher at diagnosis in ANCAS-MPO compared to ANCAS-PR3, the same difference occurs with respect to interstitial fibrosis. Since the study population is small, no correlations between fibrosis and CD163 macrophage infiltration have yet been found.

Impact of nutritional risk factors on the development of multiple sclerosis

The literature review considers the data on the assessment of the influence of alimentary factors on the development of a severe neurological disease - multiple sclerosis (MS). MS is a polyetiologic disease, the risk of development of which is influenced by both infectious (Epstein-Barr virus, herpes simplex virus, influenza virus, etc.) and noninfectious factors (genetic predisposition, smoking, geographic region of residence, etc.). MS is a progressive demyelinating disease of the central nervous system (CNS), which leads to neurodegeneration accompanied by a variety of clinical manifestations. The pathogenesis of MS is characterized by immune-mediated damage to the myelin sheaths of nerve fibers, which is manifested by inflammation, neurosynaptic damage, and destruction of white matter, axons, and blood vessels. Rapid non-evolutionary dietary and lifestyle changes, which are driven by urbanization, industrialization and globalization of the food market, are leading to an increase in most chronic non-communicable diseases, including MS. The effects induced by alimentary factors are due to changes in the microbial composition of the gastrointestinal tract (GIT), immune cell function, enzyme systems functioning, etc. The aim of the work is to study the influence of micro/macronutrients, as well as the nature of the diet on the risk of MS development, to assess the role of nutrition in the primary prevention of MS. It has been shown that a diet characterized by a high content of animal fats and trans-isomers of fatty acids (TFA), increased consumption of meat products, but low content of vegetables, fruits and whole-grain products is associated with a higher risk of MS development. Regular inclusion in the diet of sources of polyunsaturated fatty acids (PUFAs) (vegetable oils, seeds, nuts, marine fish) and vitamin D (fatty fish, caviar, butter, egg yolk) leads to lower relapse rates and less new brain lesions among MS patients. The literature review was conducted using open sources posted in electronic databases: PubMed, Medline, Scopus, Google Scholar, World Bank publications, WHO, eLibrary, Cyberleninka, Web of Science.

Association of Diabetic Peripheral Neuropathy with Micronutrients.

Diabetes mellitus (DM) is a common metabolic disorder that has been defined by hyperglycemia. Diabetic patients usually have high levels of oxidative stress. Mitochondrial dysfunction and inflammation of blood vessels are associated with a greater need for micronutrients in diabetic patients. These micronutrients may have an association with the complications in diabetics. The purpose of this study was to show the association of diabetic peripheral neuropathy (DPN) with levels of micronutrients such as copper (Cu), zinc (Zn), magnesium (Mg), and vitamin B12 (Vit B12). This cross-sectional study was conducted in the Department of Medicine, Lala Lajpat Rai Memorial Medical College, Meerut. A total of 130 randomly selected cases of confirmed type-2 diabetic patients were included in this study. DPN cases were identified using the Michigan neuropathy screening instrument. Out of 130 diabetic patients, 28 patients were found to have diabetic neuropathy. The level of various micronutrients was assessed and correlated with the development of DPN. The association of DPN with Zn (p-value of 0.02) and Vit B12 (p-value of 0.008) was found to be significant, whereas Cu (p-value of 0.57) and Mg (p-value of 0.24) were found to be insignificant.

A Systematic Review of Perinuclear Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Following Coronavirus Disease 2019 Vaccination: A 2024 Update.

Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is an immune-mediated kidney disease characterized by the inflammation of small blood vessels in the kidney, leading to renal impairment and potentially irreversible damage. Concerns have been raised over the reports of myeloperoxidase/perinuclear (MPO/p) ANCA GN following the coronavirus disease 2019 (COVID-19) vaccination. Our study provides a comprehensive insight into perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) GN after COVID-19 vaccination. We conducted a comprehensive literature search on PubMed, Cochrane Library, and EMBASE using the Medical Subject Headings (MeSH) terms related to "covid-19 vaccine," "glomerulonephritis," "p-ANCA," and "MPO-ANCA" up to March 5, 2024, to include cases of p-ANCA-associated GN following COVID-19 vaccination. Of the 4,102 articles, we included 29, reporting 35 patients demonstrating COVID-19 vaccine-induced p-ANCA GN, with 23 (65.7%) females and a median age of 69 years (mean ± SD = 63.22 ± 16). Twenty-six (74.28%) patients received the mRNA vaccine (Pfizer = 19, Moderna = 7). Seventeen (48.57%) patients presented with p-ANCA GN after the second dose of the COVID-19 vaccine, with a median gap of 19 days (1-84 days). Constitutional symptoms (54.28%) and acute kidney injury (42.85%) were the most reported initial presentations, and elevated serum creatinine (mean peak serum creatinine = 4.98 ± 5.02 mg/dL), hematuria, and proteinuria were the laboratory findings. MPO/p-ANCA was positive in 31 (88.6%) patients. All patients underwent renal biopsy, and crescentic GN was the most common finding among 27 (77.14%) patients. Management of p-ANCA GN included steroids in 30 (85.71%) patients, followed by rituximab (28.57%), and plasmapheresis (22.86%). Most patients responded well to treatment, with complete remission in 29 (82.86%) and relapse in four (11.42%) patients. Two patients did not achieve remission and became dialysis dependent. ANCA-associated GN is a rare and life-threatening complication of the COVID-19 vaccine, necessitating urgent evaluation and management. COVID-19 vaccine-induced p-ANCA GN should be included in the differential diagnoses of patients presenting with kidney injury after vaccination.

Low platelet count at diagnosis of anti-neutrophil cytoplasmic antibody-associated vasculitis is correlated with the severity of disease and renal prognosis

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease that involves inflammation of blood vessels. There is increasing evidence that platelets play a crucial role not only in hemostasis but also in inflammation and innate immunity. In this study, we explored the relationship between platelet count, clinical characteristics, and the prognosis of patients with AAV. We divided 187 patients into two groups based on their platelet count. Clinicopathological data and prognostic information were retrospectively gathered from medical records. Univariate and multivariate regression analyses were used to identify risk factors for prognosis, including end-stage renal disease (ESRD) and mortality. The cutoff point for platelet count was set at 264.5 × 109/L, as determined by the receiver operating characteristic (ROC) curve for predicting progression to ESRD in patients with AAV. We observed patients with low platelet count (platelets < 264.5 × 109/L) had lower leukocytes, hemoglobin, complement, acute reactants, and worse renal function (P for eGFR < 0.001). They were also more likely to progress to ESRD or death compared to the high platelet count group (platelets > 264.5 × 109/L) (P < 0.0001, P = 0.0338, respectively). Low platelet count was potentially an independent predictor of poor renal prognosis in the multivariate regression analysis [HR 1.670 (95% CI 1.019–2.515), P = 0.014]. Lower platelet count at diagnosis is associated with more severe clinical characteristics and impaired renal function. Therefore, platelet count may be an accessible prognostic indicator for renal outcomes in patients with AAV.

Layer-by-layer assembly of quercetin-loaded zein/γPGA/low-molecular-weight chitosan/fucoidan nanosystem for targeting inflamed blood vessels

Chitosan acts as a versatile carrier in polymeric nanoparticle (NP) for diverse drug administration routes. Delivery of antioxidants, such as quercetin (Qu) showcases potent antioxidant and anti-inflammatory properties for reduction of various cardiovascular diseases, but low water solubility limits uptake. To address this, we developed a novel layer-by-layer zein/gamma-polyglutamic acid (γPGA)/low-molecular-weight chitosan (LC)/fucoidan NP for encapsulating Qu and targeting inflamed vessel endothelial cells. We used zein (Z) and γPGA (r) to encapsulate Qu (Qu-Zr NP) exhibited notably higher encapsulation efficiency compared to zein alone. Qu-Zr NP coated with LC (Qu-ZrLC2 NP) shows a lower particle size (193.2 ± 2.9 nm), and a higher zeta potential value (35.2 ± 0.4 mV) by zeta potential and transmission electron microscopy analysis. After coating Qu-ZrLC2 NP with fucoidan, Qu-ZrLC2Fa NP presented particle size (225.16 ± 0.92 nm), zeta potential (−25.66 ± 0.51 mV) and maintained antioxidant activity. Further analysis revealed that Qu-ZrLC2Fa NP were targeted and taken up by HUVEC cells and EA.hy926 endothelial cells. Notably, we observed Qu-ZrLC2Fa NP targeting zebrafish vessels and isoproterenol-induced inflamed vessels of rat. Our layer-by-layer formulated zein/γPGA/LC/fucoidan NP show promise as a targeted delivery system for water-insoluble drugs. Qu-ZrLC2Fa NP exhibit potential as an anti-inflammatory therapeutic for blood vessels.

Anti- hemorrhoids potential of selected medicinal plants used in treatment of Hemorrhoids: A revie

Hemorrhoids (Piles) are an inflammation of blood vessels around the anal canal. When the anal cushions are displaced during defecation, piles are formed. The purpose of this study is to document traditional knowledge and medicinal plants used in pile therapy in Nigeria. This study is to establish the usage of beneficial medicinal herbs to cure hemorrhoids and provides a foundation for future research to identify effective and economical anti-hemorrhoid medications.

Association between polymorphism at codon 469 of the ICAM-1 gene and Henoch-Schönlein purpura in an Iranian cohort

Henoch-Schönlein purpura (HSP) is a common form of IgA1-mediated blood vessel inflammation affecting mainly children. Intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms have been shown to be associated with HSP in different populations; in this study, we investigated its potential association and influence on the development of severe complications in Iranian HSP patients. Twenty-three patients diagnosed with IgAV/HSP according to the criteria of the American College of Rheumatology (ACR) with 53 age- and sex-matched control subjects were referred to us. Cases and controls were genotyped using Sanger sequencing. Based on our research data, we found an association between codon 469 K/E of the ICAM1 gene and risk of HSP. Our results revealed that KK genotype and allele K are more common in control than in the HSP group, therefore the subjects with KK genotype are protected against HSP. Our data also suggested that the genotype EE is associated with higher risk of HSP progression compared to KK genotype.

Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

脑小血管病与炎症的密切关系

脑小血管病与炎症的密切关系

MicroRNAs (miRNAs) role in hypertension: pathogenesis and promising therapeutics.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a crucial role in regulating various cellular processes, including cell proliferation, differentiation, apoptosis, and disease development. Recent studies have highlighted the importance of miRNAs in the development and progression of essential hypertension, a common form of high blood pressure that affects millions of individuals worldwide. The molecular mechanisms by which miRNAs regulate hypertension are complex and multifaceted. MiRNAs target the 3' untranslated regions of mRNA molecules, thereby regulating the synthesis of specific proteins involved in cardiovascular function. For instance, miRNAs are known to regulate the expression of genes involved in blood vessel tone, cardiac function, and inflammation. The growing body of research on miRNAs in hypertension has highlighted their potential as therapeutic targets for managing this condition. Studies have shown that miRNA-based therapies can modulate the expression of key genes involved in hypertension, leading to improvements in blood pressure and cardiovascular function. However, more research is needed to fully understand the mechanisms of miRNA-mediated hypertension and to develop effective therapeutic strategies. In summary, this review highlights the current understanding of the role of miRNAs in essential hypertension, including their molecular mechanisms and potential therapeutic applications. Further research is needed to fully understand the impact of miRNAs on hypertension and to develop new treatments for this common and debilitating condition.

A projected cost-utility analysis of avacopan for the treatment of antineutrophil cytoplasmic antibody-associated vasculitis in Spain

ABSTRACT Background Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain. Methods A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results. Results Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR. Conclusions Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.

Cardiac valvular involvement in granulomatosis with polyangiitis in long-term observation

Introduction and objectivesGranulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis and is characterized by inflammation of blood vessels. The aim of the present study was to assess cardiac valvular changes in patients with GPA in a cohort of 105 patients followed for a mean of six years. MethodsWe followed 105 patients (mean age 50.4 years, 67 female) for a mean of 6.2±1.3 years. Echocardiography and laboratory tests were performed in all patients. ResultsAt baseline, 43% of patients were diagnosed with aortic regurgitation (AR), which was the most common valvular lesion. Moreover, it was the only valvular involvement that significantly increased during observation (p=0.01). In a multivariate model, only D-dimer level was a predictor of AR in this group of patients (OR 8.0 (95% CI: 1.7–38.2, p=0.01). ConclusionsInvolvement of the heart valves is a common finding in patients with GPA, but significant valvular disease is a rare complication. The most common valvular disease in this group of patients is AR. Aortic valves are also the most prone to degeneration in the course of the vasculitis.

Current Immunosuppressive Treatment for Takayasu Arteritis.

Takayasu arteritis (TAK) is a rare disease characterized by inflammation of large blood vessels, which results in vascular stenosis, occlusion, and aneurysm formation. The principal treatment has been glucocorticoids, but the recent emergence of biological disease-modifying anti-rheumatic drugs (bDMARDs), represented by tocilizumab (TCZ), has significantly changed the treatment landscape. Both cardiologists and cardiovascular surgeons will encounter patients receiving these drugs who require catheterization, other invasive procedures, or surgery. Several bDMARDs have shown promise against TAK in clinical studies and their use is expected to increase in the future. Janus kinase inhibitors may also be effective. Here, we review the evidence supporting the use of TCZ and other immunosuppressants in TAK and provides an update on their status as well as the relevant guidelines.

Apohemoglobin-Haptoglobin Complex Improves Cardiac and Pulmonary Function in Homozygous Townes (HbSS Townes) Mice

The constant ischemia-reperfusion injury and the release of hemoglobin and heme in patients with sickle cell disease (SCD) can affect the heart, lungs, and vasculature. While treatments have improved survival, cardiovascular complications are becoming more prevalent, including pulmonary hypertension and left ventricular diastolic dysfunction. Pulmonary hypertension is associated with increased mortality risk and linked to intravascular hemolysis, leg ulcers, renal insufficiency, iron overload, and liver dysfunction. Chronic anemia leads to heart chamber dilation and left ventricular mass increase, often accompanied by left ventricular diastolic dysfunction, both impacting exercise capacity. Additionally, it can cause Acute Chest Syndrome (ACS), which is characterized by inflammation and blockage of small blood vessels in the lungs. In some cases, the heart may enlarge (cardiomegaly) due to the increased workload it faces in pumping blood through narrowed or obstructed blood vessels. Sudden death is also emerging as a concern, necessitating further cardiac investigations and risk assessment for effective management. These issues are speculated to result from the high amount of hemoglobin and heme released into circulation. In this study, a synthetic protein scavenger for heme and Hb, the apohemoglobin (apoHb) was stabilized with haptoglobin (Hp) to create the apoHb-Hp complex, was used to study the cardiac and pulmonary changes in SCD mice resulting from heme and Hb. Homozygous Townes (HbSS Townes) mice (B6; 129-Hbatm1(HBA)Tow Hbbtm2(HBG1,HBB)Tow/Hbbtm3(HBG1,HBB)Tow/J) were used as the murine model of SCD, and HbAA Townes mice (homozygous for Hbatm1(HBA)Tow and Hbbtm3(HBG1,HBB)Tow) were used as the phenotypically controls. The results conclusively illustrate the benefits of using apohb-Hb, as it improves cardiac output, decreases pulmonary hypertension, and alleviates the immune response that is expected. In conclusion, our study provides strong evidence supporting the significant cardiovascular implication of heme and hemoglobin. We have demonstrated that apoHb-Hp complex effectively neutralizes these harmful activities, rendering these heme and free Hb nonreactive, leading to a marked reduction in hemolysis induced endothelial activation. These findings have important implications, suggesting that apoHb-Hp complex plays a protective role for cardiac and pulmonary cells exposed to elevated levels of heme and free Hb, a condition commonly seen in SCD. Furthermore, our study's consistency with prior research reinforces the role of apoHb-Hp complex in preventing P-selectin expression. Our SCD mouse model experiments reveal that apoHb-Hp complex effectively ameliorates vaso-occlusion, regardless of whether the vaso-occlusion was triggered by Hb or heme-independent factors like hypoxia-reoxygenation. Notably, the apoHb-Hp complex also demonstrated some efficacy, indicating that the protective effect extends beyond simple heme clearance and TLR4 signaling inhibition. While our results are promising, further experiments are required to gain a deeper understanding of the apoHb-Hp complex activity in both clearance-dependent and independent mechanisms of resolving vaso-occlusion. Overall, our research highlights the potential therapeutic value of the apoHb-Hp complex in combating the detrimental effects of Hb and heme, and offers valuable insights into its protective role in managing vaso-occlusive events associated with conditions like SCD.