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OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. METHODS: The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. RESULTS: The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). CONCLUSION: Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time. [ABSTRACT FROM AUTHOR]

Congestive heart failure (CHF) is a common and increasing problem among older persons. Symptoms associated with CHF include edema, fatigue, dyspnea, limited exercise tolerance, and significant activity limitation. Using a comprehensive review of literature, this article describes the public health burden arising out of CHF in the United States. It describes CHF in terms of functional limitation and disability in the elderly following the National Center for Medical Rehabilitation and Research (NCMRR) disability model. The use of home based interventions (HBI) to assist people with CHF is discussed. [ABSTRACT FROM AUTHOR]

Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-related toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI Aggregate Improvement Score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤-10., Objective: This study was a longitudinal assessment of patients with SA treated with biologic therapies to assess the trajectory of OCS-related toxicity and predictors of toxicity improvement., Methods: A total of 89 patients with SA had GTI assessments at baseline and after 1 and 3 years of biologic therapy., Results: At 3 years, daily prednisolone use continued to decrease (6.9 mg/day [4.0, 9.4] year 1 vs 0.8 mg/day [0.0, 3.7] year 3, P < .001), OCS-related toxicity continued to decline (AIS at 3 years -36 [-94, 19]), and 61% (54 of 89) met the AIS MCID. There was a significant positive correlation between toxicity outcomes at years 1 and 3 (ρ 0.65, P < .001). Nearly half (49%) met the AIS MCID at both years 1 and 3, but 29% of the cohort did not meet the AIS MCID at either time point. Toxicity change at year 1 was predictive of toxicity change at year 3 for 79%. Toxicity reduction was not proportional to OCS reduction; there were no prebiologic characteristics that predicted toxicity reduction., Conclusions: After 3 years of biologic treatment, 61% of patients with SA had clinically significant toxicity improvement. Individual toxicity outcomes at year 1 are associated with longitudinal outcomes, suggesting that for some, additional interventions are needed alongside OCS reduction to decrease morbidity., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) face excess mortality compared with the general population. Mortality in clinical epidemiology research is often examined using death certificate diagnosis codes; however, the sensitivity of such codes in AAV is unknown., Methods: We performed a retrospective cohort study using the Mass General Brigham AAV Cohort, including patients with AAV who died between 2002 and 2019. Causes of death were determined by electronic health record (EHR) review (reference gold standard) and via cause of death diagnosis codes on death certificates. We calculated the sensitivity of death certificate diagnosis codes for AAV., Results: Of 684 patients in the registry, 184 died, 92 (52 %) of whom had adequate EHR data available determine cause of death and 72 (40 %) of whom had both EHR and death certificate data available. Death due to AAV, infection, cardiovascular disease, and cancer occurred in 8 %, 29 %, 5 %, and 18 %, respectively, when ascertained by manual review, as opposed to 0 %, 11 %, 25 %, and 21 %, as determined by death certificates. The sensitivity of AAV diagnosis codes for AAV was 16.6 % (95 % CI: 10.5, 22.6) among all patients with death certificate data available., Conclusion: In a contemporary cohort of patients with AAV, infection was the most common cause of death, while death due to AAV itself was rare. We found a high degree of discordance between causes of death determined by manual review and death certificate diagnosis codes. Mortality research on AAV should include linkage to medical records data to reduce potential bias., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guy Katz reports financial support was provided by Rheumatology Research Foundation. Zachary S. Wallace reports financial support was provided by National Institutes of Health. Guy Katz reports financial support was provided by National Institutes of Health. Guy Katz reports a relationship with Sanofi that includes: funding grants. Guy Katz reports a relationship with GLG Consulting that includes: consulting or advisory. Guy Katz reports a relationship with Evolve Medical Education that includes: speaking and lecture fees. Guy Katz reports a relationship with NEJM Resident 360 that includes: speaking and lecture fees. Guy Katz reports a relationship with IgG4ward that includes: speaking and lecture fees. Guy Katz reports a relationship with Amgen Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Amgen Inc that includes: consulting or advisory and funding grants. Zachary S. Wallace reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Zachary S. Wallace reports a relationship with Sanofi that includes: consulting or advisory and funding grants. Zachary S. Wallace reports a relationship with Viela Bio that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Adicet Bio Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Horizon Therapeutics USA Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Zenas BioPharma that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Pharmaceutical Product Development that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Medpace Inc that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Novartis that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Shinogi that includes: consulting or advisory. Zachary S. Wallace reports a relationship with Visterra Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Patients with autoimmune blistering diseases (AIBDs) are often exposed to chronic glucocorticoid (GC) treatment with many side effects. Glucocorticoid-induced myopathy (GIM) is a well-established side effect, which particularly affects the proximal muscles. The Glucocorticoid Toxicity Index (GTI) is a validated global assessment tool which quantifies GC toxicity over time., Objectives: This study marks the first study which analyses GIM in patients with AIBDs. The objectives of this study were to utilize the GTI to investigate the nature and prevalence of GIM in AIBD patients and explore potential risk factors., Methods: This international cohort study was conducted in blistering disease clinics across Australia, China, Greece, Iran, Japan, the Philippines, Turkey and the United States of America between February 2019 and July 2023. The GTI tool was completed by a medical practitioner at each patient visit. Data related to glucocorticoid toxicity were entered into the Steritas GTI 2.0 to generate an aggregate improvement and cumulative worsening score at each visit., Results: The study included 139 patients. There were 132 episodes of myopathy, and 47.5% of patients developed muscle weakness at some point during the study period. Cumulative GC dose correlated positively with myopathy risk, while average dose and treatment duration were not significant. Older age, male gender and obesity more than doubled the likelihood of developing GIM., Conclusions: GIM is a common side effect experienced by AIBD patients on GC treatment. Muscle weakness is less likely to occur if cumulative GC dose is less than 0.75 mg/kg/day. Studies of exercise programs to mitigate myopathy and newer alternative treatments to reduce cumulative GC dose should be considered., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Objectives: Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease., Methods: We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia., Results: Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia., Conclusions: Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology., Competing Interests: Competing interests: The authors declare competing interests with the Rheumatology Research Foundation, NIH, Sanofi, Zenas, Amgen, Genentech, Sana, National Multiple Sclerosis Society, GlaxoSmithKline, Helmsley Charitable Trust, AstraZeneca, Bristol Myers Squibb, Novartis, Alexion Pharmaceuticals, ANI Pharmaceuticals, Aurinia Pharmaceuticals, Exagen Diagnostics, Kypha, Pfizer, UpToDate, The Rheumatology Education Group, Lupus Foundation of America-Heartland Chapter, St Louis Rheumatology Chapter, Lupus Research Alliance, National Scleroderma Foundation, AbbVie, Acepodia, Alpine Immune Sciences, Argenx, Connect Biopharma, CTI BioPharma, Horizon Therapeutics, iCell Gene Therapeutics, IQVIA, Prometheus Biosciences/Merck, Q32 Bio, Salvina Therapeutics, IgG4ward! Foundation, Achillion Pharmaceuticals, Annexon Pharmaceuticals, Arrowhead Pharmaceuticals, Autobahn Therapeutics, Avidity Partners, BioMarin Pharmaceuticals, Broadwing Bio, Celldex Therapeutics, 4D Molecular Therapeutics, HiBIO, Janssen, Kypha, Merck KGaA, Takeda Pharmaceuticals, Compliment Corporation, Gemini Therapeutics, Leducq Foundation, Be Bio Pharma, Paratus, Octagon Therapeutics, Ab Pro, Viela Bio, MedPace and BioCryst., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: IgG4-related disease is a multiorgan, relapsing, fibroinflammatory, immune-mediated disorder with no approved therapy. Inebilizumab targets and depletes CD19+ B cells and may be effective for treating patients with IgG4-related disease., Methods: In this phase 3, multicenter, double-blind, randomized, placebo-controlled trial, adults with active IgG4-related disease underwent randomization in a 1:1 ratio to receive inebilizumab (300-mg intravenous infusions on days 1 and 15 and week 26) or placebo for a 52-week treatment period. Participants in both groups received identical glucocorticoid tapers. Glucocorticoids were allowed to treat disease flares, but background immunosuppressants were not permitted. The primary end point was the first treated, adjudicated disease flare during the treatment period, assessed in a time-to-event analysis. Key secondary end points were the annualized flare rate and treatment-free and glucocorticoid-free complete remission., Results: A total of 135 participants with IgG4-related disease underwent randomization: 68 participants were assigned to receive inebilizumab and 67 were assigned to receive placebo. Treatment with inebilizumab reduced flare risk; 7 participants (10%) in the inebilizumab group had at least one flare, as compared with 40 participants (60%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.06 to 0.28; P<0.001). The annualized flare rate was lower with inebilizumab than with placebo (rate ratio, 0.14; 95% CI, 0.06 to 0.31; P<0.001). More participants in the inebilizumab group than in the placebo group had flare-free, treatment-free complete remission (odds ratio, 4.68; 95% CI, 2.21 to 9.91; P<0.001) and flare-free, glucocorticoid-free complete remission (odds ratio, 4.96; 95% CI, 2.34 to 10.52; P<0.001). Serious adverse events occurred during the treatment period in 12 of the participants (18%) who received inebilizumab and 6 of the participants (9%) who received placebo., Conclusions: Inebilizumab reduced the risk of flares of IgG4-related disease and increased the likelihood of flare-free complete remission at 1 year, confirming the role of CD19-targeted B-cell depletion as a potential treatment for IgG4-related disease. (Funded by Amgen; MITIGATE ClinicalTrials.gov number, NCT04540497.)., (Copyright © 2024 Massachusetts Medical Society.)

Abstract: Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition - and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objectives: The pediatric Glucocorticoid Toxicity Index (pGTI) is a new, pediatric-specific tool to quantify glucocorticoid (GC)-related morbidity in children. We evaluated the feasibility and construct validity of retrospective pGTI scoring in patients with pediatric-onset systemic lupus erythematosus (pSLE) and identified risk factors for cumulative toxicity., Methods: We conducted a retrospective cohort study of patients with pSLE treated with GCs at two pediatric centers (1999-2023). GC exposure was estimated using interval-averaged oral prednisone-equivalent dose and cumulative prednisone-equivalent dose. We scored change in GC toxicity every 6 months (±2) using a modified pGTI including 7 of 10 domains. We calculated the Cumulative Worsening Score (CWS), a continuous summation of toxicity accrued. Mixed effects linear regression was used to identify factors associated with CWS., Results: There were 126 patients with pSLE, including 88 with nephritis, with a median of 6 visits/patient. Nearly half (47 %) experienced toxicity in the Blood Pressure domain. Other common toxicities were mood disturbance (25 %), followed by increased body mass index (BMI), striae, and sleep disturbance (21 % each). Decreased growth velocity was observed in 18 %. There was modest correlation between cumulative GC dose and CWS (rho 0.3; p < 0.01). Greater cumulative toxicity was associated with younger age, elevated BMI, and rituximab use at the time of GC initiation, albeit indications for the latter were not captured., Conclusions: Patients with pSLE experience a high burden of GC toxicity, particularly related to blood pressure, BMI, sleep, and growth. Standardized, pediatric-specific GC toxicity assessment is feasible in real-world settings and can facilitate evaluation of strategies to reduce morbidity in children requiring chronic GC treatment., Competing Interests: Declaration of competing interest J.C.C previously received grant funding from GSK for investigator-driven research outside the scope of this work. Professor Stone's hospital, the Massachusetts General Hospital, owns the intellectual property of the pGTI. The worldwide licensing rights to the pGTI are controlled by Steritas, LLC. Professor Stone co-founded Steritas and is the chair of the Scientific Advisory Board but has no fiduciary responsibility at the company. The remaining co-authors have no other relevant financial conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: IgG4-related disease (IgG4-RD) can affect nearly any organ and is often treated with glucocorticoids, which contribute to organ damage and toxicity. Comorbidities and healthcare utilization in IgG4-RD are poorly understood., Methods: We conducted a cohort study using claims data from a US managed care organization. Incident IgG4-RD cases were identified using a validated algorithm; general population comparators were matched by age, sex, race/ethnicity and index date. The frequency of 21 expert-defined clinical outcomes associated with IgG4-RD or its treatment and healthcare-associated visits and costs were assessed 12 months before and 36 months after the index date (date of earliest IgG4-RD-related claim)., Results: There were 524 cases and 5240 comparators. Most cases received glucocorticoids prior to (64.0%) and after (85.1%) the index date. Nearly all outcomes, many being common glucocorticoid toxicities, occurred more frequently in cases vs comparators. During follow-up, the largest differences between cases and comparators were seen for gastroesophageal reflux disease (prevalence difference: +31.2%, P < 0.001), infections (+17.3%, P < 0.001), hypertension (+15.5%, P < 0.01) and diabetes mellitus (+15.0%, P < 0.001). The difference in malignancy increased during follow-up from +8.8% to +12.5% (P < 0.001). Some 17.4% of cases used pancreatic enzyme replacement therapy during follow-up. Over follow-up, cases were more often hospitalized (57.3% vs 17.2%, P < 0.01) and/or had an emergency room visit (72.0% vs 36.7%, P < 0.01); all costs were greater in cases than comparators., Conclusions: Patients with IgG4-RD are disproportionately affected by adverse outcomes, some of which may be preventable or modifiable with vigilant clinician monitoring. Glucocorticoid-sparing treatments may improve these outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: IgG4-related disease is a multiorgan fibroinflammatory disease considered to have an autoimmune origin. Case series describing individual organ involvement have suggested differences in phenotypic expression between males and females. We aimed to characterise differences in IgG4-related disease manifestations between male and female patients in a large single-centre cohort., Methods: In this retrospective, single-centre cohort study, patients were recruited from the Massachusetts General Hospital Rheumatology Clinic (Boston, MA, USA) and classified according to the American College of Rheumatology-European Alliance of Associations for Rheumatology (ACR-EULAR) classification criteria. Only patients satisfying the ACR-EULAR classification criteria were included in the study. Data on age at diagnosis, organ involvement at baseline, treatment status, and pre-treatment laboratory values were collected. Circulating plasmablasts and B-cell subsets were quantitated by flow cytometry. Active disease was defined by an IgG4-related disease Responder Index score of more than 0. Laboratory values were analysed for patients who were untreated at baseline and had active IgG4-related disease. The main outcomes were assessed in all participants with available data., Findings: Of the 564 participants enrolled in the Massachusetts General Hospital Rheumatology Clinic IgG4-related disease Registry, 328 fulfilled ACR-EULAR classification criteria and were included between January, 2008, and May, 2023. There was a strong male predominance (male:female ratio 2·2:1) with 226 (69%) males and 102 (31%) females, which contrasted markedly with our general rheumatology clinic population (0·4:1; p<0·001). The male predominance increased with each decade of life starting at age 40 years. On average, male patients were 5·5 years older at diagnosis than female patients (63·7 years vs 58·2 years; p=0·0031). We observed male patients to have higher ACR-EULAR classification criteria scores at baseline with a median score of 35·0 (IQR 28·0-46·0), compared with 29·5 (25·0-39·0) for females (p=0·0010). The proportion of male patients with pancreatic and renal involvement was almost double the proportion observed in female patients (50% of the male patients had pancreatic involvement, compared with about 26% of the female patients; p<0·0001). Male patients were more likely to have serological abnormalities at baseline. The distribution of IgG4 values differed significantly between male an female sexes, favouring higher values in males. We found that male patients with IgG4-related disease were more likely to have active B-cell responses in the blood as defined by plasmablast expansions., Interpretation: IgG4-related disease is unusual among autoimmune diseases in that it is more likely to affect males than females and to present with a striking sex-dependent organ distribution and degree of B-cell response. These findings highlight important variation between IgG4-related disease and other conditions generally believed to have an autoimmune basis. Most autoimmune diseases, by contrast to IgG4-related disease, demonstrate pronounced predilections for affecting females more frequently than males. Hypotheses surrounding the cause and pathophysiology of this condition need to consider this unusual sex distribution among patients with IgG4-related disease., Funding: National Institutes of Health, National Institute of Allergy and Infectious Diseases, Rheumatology Research Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases., Competing Interests: Declaration of interests YGHB reports honorarium from Otsuka-Visterra for continuing medical education and Grand Rounds lectures on autoimmune pancreatitis. ZSW reports consulting fees from Viela Bio, Zenas, Horizon, Sanofi, MedPace, BioCryst, and Amgen; and participation on a Data Safety Monitoring Board or Advisory Board for Sanofi, Horizon, Novartis, Shionogi, and Otsuka-Visterra. SP reports consultancy fees from Be Bio Pharma, Paratus, and Octagon Therapeutics; and stock options for Ab Pro, Be Bio Pharma, and Paratus. JHS reports consultancy fees from Acepodia, Alexion, Bristol Myers Squibb, Connect Biopharma, Horizon, iCell Gene Therapeutics, Q32, Sanofi, and ZenasBio; has a role as Principal Investigator in a phase 3 clinical trial (inebilizumab); and is a consultant for Horizon (now Amgen) on IgG4-related disease. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

A prompt response to glucocorticoids is a clinical hallmark of IgG4-related disease. However, manifestations characterised by prominent tissue fibrosis on histological examination can be less responsive to glucocorticoid therapy than other types of IgG4-related disease. These manifestations include retroperitoneal fibrosis, fibrosing mediastinitis, Riedel thyroiditis, orbital pseudotumor, and hypertrophic pachymeningitis, among others. To explain this discrepancy, a preliminary distinction into proliferative and fibrotic phenotypes of IgG4-related disease has been proposed on the basis of clinical presentation, pathological features, and response to immunosuppressive therapy. Implications of this classification for patient management remain an important area of investigation. In this Series paper, we aim to dissect the pathophysiology of tissue fibrosis in IgG4-related disease and discuss how clinicians should approach the management of fibrotic manifestations of IgG4-related disease based on the most recent diagnostic and therapeutic developments., Competing Interests: Declaration of interests EC has received consulting fees and honoraria from Horizon Therapeutics, Zenas Biopharma, and Falk Pharma; and participated on advisory boards for Horizon Therapeutics, Zenas Biopharma, Sanofi, and Falk Pharma outside of the present work. JHS has received consulting fees and honoraria from Bristol Myers Squibb, Amgen, Sanofi, and Zenas Biopharma; and received grants and research contracts from Bristo Myers Squibb, Amgen, and Sanofi outside the present work. EDT received consulting fees and honoraria from Horizon Therapeutics and Zenas Biopharma, and participated on advisory boards for Horizon Therapeutics, Zenas Biopharma, and Sanofi outside of the present work. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: To date, there has been no independent core lab angiographic analysis of patients with COVID-19 and STEMI. The study characterized the angiographic parameters of patients with COVID-19 and STEMI., Methods: Angiograms of patients with COVID-19 and STEMI from the North American COVID-19 Myocardial Infarction (NACMI) Registry were sent to a Core Laboratory in Vancouver, Canada. Culprit lesion(s), Thrombolysis In Myocardial Infarction (TIMI) flow, Thrombus Grade Burden (TGB), and percutaneous coronary intervention (PCI) outcome were assessed., Results: From 234 patients, 74% had one culprit lesion, 14% had multiple culprits and 12% had no culprit identified. Multivessel thrombotic disease and multivessel CAD were found in 27% and 53% of patients, respectively. Stent thrombosis accounted for 12% of the presentations and occurred in 55% of patients with previous coronary stents. Of the 182 who underwent PCI, 60 (33%) had unsuccessful PCI due to post-PCI TIMI flow <3 (43/60), residual high thrombus burden (41/60) and/or thrombus related complications (27/60). In-hospital mortality for successful, partially successful, and unsuccessful PCI was 14%, 13%, and 27%, respectively. Unsuccessful PCI was associated with increased risk of in-hospital mortality (risk ratio [RR] 1.96; 95% CI: 1.05-3.66, P = .03); in the adjusted model this estimate was attenuated (RR: 1.24; 95% CI: 0.65-2.34, P = .51)., Conclusion: In patients with COVID-19 and STEMI, thrombus burden was pervasive with notable rates of multivessel thrombotic disease and stent thrombosis. Post-PCI, persistent thrombus and sub-optimal TIMI 3 flow rates led to one-third of the PCI's being unsuccessful, which decreased over time but remained an important predictor of in-hospital mortality., Competing Interests: Disclosures The authors have no conflicts of interest to disclose in relation to this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: I have received consulting fees and honoraria from Bristol Myers Squibb, Amgen, Sanofi, and Zenas Biopharma; and received grants and research contracts from Bristol Myers Squibb, Amgen, and Sanofi outside the present work.

Immunoglobulin 4 (IgG4)-related disease is a chronic immune-mediated fibroinflammatory disorder. Involvement of the vascular system, including large- and medium-sized vessels, is increasingly recognized. The varied appearances of vascular involvement reflect the sequela of chronic inflammation and fibrosis and can include aortitis and periaortitis with resultant complications such as aneurysm formation and dissection. A diagnosis of IgG4-related large vessel involvement should be considered when there is known or suspected IgG4-related disease elsewhere. Other organs that are typically affected in IgG4-related disease include the lacrimal and salivary glands, thyroid, pancreas, biliary tree, lungs, kidneys, and meninges. Diagnosis typically requires careful correlation with clinical, imaging, serum, and pathologic findings. Patients may be managed with corticosteroid therapy or the anti-CD20 monoclonal antibody, rituximab, if needed. The varied clinical presentations and imaging features of large vessel involvement are discussed herein. Keywords: Vascular, Inflammation, Aorta, IgG4-related Vessel Involvement © RSNA, 2024.

Background: IgG4-related disease (IgG4-RD), an example of a type I immune disease, is an immune-mediated fibrotic disorder characterized by dysregulated resolution of severe inflammation and wound healing. However, truly dominant or pathognomonic autoantibodies related to IgG4-RD are not identified., Objective: We sought to perform single-cell RNA sequencing and T-cell receptor and B-cell receptor sequencing to obtain a comprehensive, unbiased view of tissue-infiltrating T and B cells., Methods: We performed unbiased single-cell RNA-sequencing analysis for the transcriptome and T-cell receptor sequencing and B-cell receptor sequencing on sorted CD3 + T or CD19 + B cells from affected tissues of patients with IgG4-RD. We also conducted quantitative analyses of CD3 + T-cell and CD19 + B-cell subsets in 68 patients with IgG4-RD and 30 patients with Sjögren syndrome., Results: Almost all clonally expanded T cells in these lesions were either Granzyme K (GZMK)-expressing CD4 + cytotoxic T cells or GZMK + CD8 + T cells. These GZMK-expressing cytotoxic T cells also expressed amphiregulin and TGF-β but did not express immune checkpoints, and the tissue-infiltrating CD8 + T cells were phenotypically heterogeneous. MKI67 + B cells and IgD - CD27 - CD11c - CXCR5 - double-negative 3 B cells were clonally expanded and infiltrated affected tissue lesions. GZMK + CD4 + cytotoxic T cells colocalized with MKI67 + B cells in the extrafollicular area from affected tissue sites., Conclusions: The above-mentioned cells likely participate in T-B collaborative events, suggesting possible avenues for targeted therapies. Our findings were validated using orthogonal approaches, including multicolor immunofluorescence and the use of comparator disease groups, to support the central role of cytotoxic CD4 + and CD8 + T cells expressing GZMK, amphiregulin, and TGF-β in the pathogenesis of inflammatory fibrotic disorders., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Introduction: Glucocorticoids (GCs) are associated with multiple toxicities that have substantial impact on patients. We conducted qualitative interviews with patients to identify the toxicities that are most relevant from their perspective, with the goal of creating a patient-reported companion measure to the Glucocorticoid Toxicity Index (GTI), a clinician-facing instrument., Methods: Thirty-one patients with recent or current GC use participated in concept elicitation interviews. Participants received GC treatment for myasthenia gravis, chronic inflammatory demyelinating polyradiculoneuropathy, vasculitis, or systemic lupus erythematosus. Transcripts were coded following a thematic analysis approach., Results: Participants reported more than 100 toxicities they believed to be associated with their GC medications. Common toxicities included weight gain (87%), increased appetite (84%), insomnia/sleep problems (77%), cognitive impairment/brain fog (71%), easy bruising (68%), anxiety (65%), irritability/short temper (65%), and osteoporosis (39%). These toxicities often centered on self-esteem, neuropsychiatric effects, skin toxicities, and musculoskeletal function. They can be categorized into domains such emphasizing neuropsychiatric, metabolic/endocrine, musculoskeletal, and dermatological effects, highlighting aspects of GC toxicity that patients are uniquely positioned to appreciate and report., Conclusion: Our results confirm that the toxicities associated with GCs are pervasive and diverse, with substantial impact on patients' lives. These data will be used to inform the development of a patient-reported outcome measure assessing GC toxicity. This patient-reported instrument will be designed to complement the clinician-reported GTI, facilitating a more detailed understanding of the nuances of change in GC toxicity., Competing Interests: Declaration of competing interest TAH and LSM are employed by Evidera, a company that received funding from argenx for time spent conducting this research. MNS is the CEO of Steritas, LLC, which holds the licensing rights to the Glucocorticoid Toxicity Index, and reports owning stock in Steritas (the intellectual property of the GTI is owned by the Massachusetts General Hospital). MNS is a co-founder of Steritas. JHS reports consulting fees from ChemoCentryx, Amgen, Roche/Genentech, Sanofi, Bristol-Myers Squib, AbbVie, InflaRx, Kyverna, Novartis, Q32Bio, Steritas, Zenas, Horizon, argenx, Spruce, PPD; owning stock in Steritas; commercial research grants from Roche/Genentech, Sanofi, Bristol-Myers Squib; royalties from UpToDate; non-commercial research grants from NIH/NIAID. JHS is a co-founder of Steritas and serves as the unpaid chair of the Scientific Advisory Board. He has no fiduciary responsibility at the company. GAP, VR, and DG are employees of argenx, who sponsored the study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies., Competing Interests: Declaration of interests AK reports being a site investigator in the ADVOCATE trial funded by ChemoCentryx (NCT02994927); received research support and consultancy fees from Otsuka and CSL Vifor; and received consultancy fees from Catalyst Biosciences, Walden Biosciences, GlaxoSmithKline, and Delta4. IMB consulted for Boehringer-Ingelheim, Novartis, Catalyst Biosciences, Toleranzia, Vera, and Hansa Biopharma; received educatonal grants from CSL Vifor; is the owner of BiPath; and is on the Board of Directors of the Renal Pathology Society. AB reports being a national principal investigator in the ADVOCATE trial funded by ChemoCentryx; and reports consultation fees and honoraria from AstraZeneca, Bayer, ChemoCentryx, Fresenius, MSD/Merck, and CSL Vifor. JHS reports being the co-principal investigator in the RAVE trial, an investigation of rituximab in ANCA-associated vasculitis funded by both the National Institute of Allergy and Infectious Diseases (NIAID) and Genentech; received funding from the National Institutes of Health (NIH)/NIAID (grant UM1AI144295) for an Autoimmunity Center of Excellence; reports consulting fees, payments, or honoraria from AbbVie, Amgen, Argenx, Bristol-Myers Squibb, Chemocentryx, Horizon Therapeutics, Kyverna Therapeutics, Novartis, PPD, Q32 Bio, Roche, Sana, Sanofi, Spruce Biosciences, Steritas, and Zenas BioPharma; chairs the scientific advisory board for Steritas (which licenses the Glucocorticoid Toxicity Index) but has no fiduciary role at the company; reports royalties from UpToDate; and JHS's hospital, the Massachusetts General Hospital, owns the intellectual property of the Glucocorticoid Toxicity Index. GMK reports no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Immunoglobulin G4-related disease (IgG4-RD) is a debilitating multiorgan disease characterized by recurring flares leading to organ dysfunction, decreased quality of life, and mortality. Glucocorticoids, the standard of care for IgG4-RD, are associated with substantial treatment-related toxicity. Inebilizumab, an antibody directed against CD19, mediates the rapid and durable depletion of CD19 + B cells thought to be involved in IgG4-RD pathogenesis. We describe the first international, prospective, double-blind, placebo-controlled trial to evaluate the safety and efficacy of B-cell depletion for flare prevention in IgG4-RD (MITIGATE)., Methods: The study was designed by an international panel of physicians with expertise in IgG4-RD. Critical trial design decisions included the selection of participants, definition of clinically meaningful primary and secondary endpoints, accommodation of standard of care, and development of flare diagnostic criteria. The study is approved for conduct in 22 countries., Planned Outcomes: The primary efficacy endpoint is time from randomization to the occurrence of the first centrally adjudicated and investigator-treated disease flare during the 1-year randomized controlled period. A set of novel, organ-specific flare diagnostic criteria were developed specifically for this trial, incorporating symptoms and signs, laboratory findings, imaging study results, and pathology data. MITIGATE aims to accrue 39 flares for the primary endpoint, which provides sufficient power to detect a relative risk reduction of 65% in the inebilizumab group. It is anticipated that enrollment of 160 participants will achieve this goal. Additional endpoints include safety, annualized flare rate, flare-free complete remission, quality-of-life measures, and cumulative glucocorticoid use. MITIGATE represents the first randomized, double-blind, placebo-controlled trial of any treatment strategy conducted in IgG4-RD. Data from this study will provide insights into the natural history and pathophysiology of IgG4-RD and the efficacy and safety of B-cell depletion as a therapeutic avenue., Trial Registration: NCT04540497., (© 2023. The Author(s).)

Purpose: To describe 6 cases and review the current state of knowledge of eosinophilic angiocentric fibrosis (EAF) involving the orbit., Design: Retrospective clinicopathologic case series and review of the current literature METHODS: Clinical records and histopathologic data of orbit-involving EAF were gathered between 2004 and 2022 from a single academic institution. The patients' presenting clinical symptoms and signs, laboratory data, radiographic studies, and management documentation were collected., Results: Retrospective review identified 6 novel cases, totaling 31 cases of EAF involving the orbit described as of this writing. Fourteen patients were male, and the average age of presentation was 49.8 years (range 25-78 years). Eighteen patients had concurrent sinonasal involvement, whereas 13 had primary orbital involvement. The median duration of symptoms prior to evaluation was 24 months, with nasal symptoms, proptosis, periorbital swelling, and pain being the most common presenting symptoms. The majority of patients underwent surgical debulking, as well as treatment with glucocorticoids and steroid-sparing agents, such as rituximab, with varied results., Conclusion: EAF involving the orbit is uncommon. The histopathologic findings include a perivascular, eosinophil-rich infiltrate and a pauci-inflammatory storiform type of fibrosis concentrated around small vessels. Orbital involvement usually results from local extension from adjacent sinuses, but primary orbital involvement has been described. Surgical debulking and immunosuppressive agents such as rituximab have been shown to stabilize disease., (Copyright © 2023 Elsevier Inc. All rights reserved.)