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•Activation of the NLRP3 inflammasome during nutrient starvation results in excessive interleukin-1β production by XIAP-deficient cells.•XIAP-deficient monocytes exhibit defective autophagic flux during nutrient starvation.

Children with well‐controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. Children with JIA who discontinued conventional synthetic or biologic disease‐modifying antirheumatic drugs for well‐controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P= 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22–18.78] and OR 2.74 [95% CI 1.62–4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72–0.95]). Approximately half of JIA flares post‐discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision‐making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.

The aim of this study was to quantify costs of hospital‐associated care for juvenile idiopathic arthritis (JIA), provide insights in patient‐level variation in costs, and investigate costs over time from the moment of JIA diagnosis. Results were reported for all JIA patients in general and by subtype.  This study was a single‐center, retrospective analysis of prospective data from electronic medical records of children with JIA, ages 0–18 years, between April 1, 2011 and March 31, 2019. Patient characteristics (age, sex, JIA subtype) and hospital‐based resource use (consultations, medication, radiology procedures, laboratory testing, surgeries, emergency department [ED] visits, hospital stays) were extracted and analyzed. Unit prices were obtained from Dutch reimbursement lists and pharmaceutical and hospital list prices. The analysis included 691 patients. The mean total cost of hospital care was €3,784/patient/year, of which €2,103 (55.6%) was attributable to medication. Other costs involved pediatric rheumatologist visits (€633/patient/year [16.7%]), hospital stays (€439/patient/year [11.6%]), other within‐hospital specialist visits (€324/patient/year [8.6%]), radiology procedures (€119/patient/year [3.1%]), laboratory tests (€114/patient/year [3.0%]), surgeries (€46/patient/year [1.2%]), and ED visits (€6/patient/year [0.2%]). Mean annual total costs varied between JIA subtypes and between individuals and were the highest for systemic JIA (€7,772/patient/year). Over the treatment course, costs were the highest in the first month after JIA diagnosis. Hospital care costs of JIA vary substantially between individuals, between subtypes, and over the treatment course. The highest annual costs were for systemic JIA, primarily attributable to medication (i.e., biologics). Costs of other hospital‐associated care were comparable regardless of subtype.

Objectives: To compare the age of onset of the pattern orientation reversal visual evoked potential (OR-VEP) in a group of very low birthweight (VLBW) premature infants with term infants matched [...]

Introduction: The aim of this work was to assess the impact of prolonged low immunoglobulin (IgG or IgM) serum concentrations on the potential cumulative serious infection (SI) risk in pediatric patients following rituximab treatment for granulomatosis with polyangiitis or microscopic polyangiitis (GPA/MPA) in PePRS. Methods: Patients aged ≥ 2 to &lt; 18 years received four weekly intravenous rituximab infusions of 375 mg/m2and concomitant glucocorticoid taper. After 6 months, patients could receive further rituximab and/or other immunosuppressants per investigator discretion. Immunoglobulin levels and SIs were assessed throughout the 4.5-year observation period. Prolonged low IgG or IgM was defined as below the lower limit of normal age-specific reference range for ≥ 4 months. Results: A total of 25 patients were included, of whom 19 (76%) had GPA and six (24%) had MPA; 18 (72%) had newly diagnosed disease and seven (28%) had relapsing disease. All 25 patients completed the rituximab induction regimen; 24 completed ≥ 18 months of follow-up. At month 18, eighteen patients (72%) had prolonged low IgG; 19 (76%), prolonged low IgM; and 15 (60%), both. Seven patients (28%) had nine SIs; one occurred during or after prolonged low IgG only, two during or after prolonged low IgM only, and six during or after concurrent prolonged low IgG and IgM. No patients died or discontinued the study due to SI. All patients had complete and sustained peripheral B-cell depletion for ≥ 6 months. Conclusions: The majority of pediatric patients who received rituximab for GPA/MPA with prolonged low immunoglobulin levels did not experience SIs. In patients with SIs, these events were manageable, and the number of SIs did not increase over time or with multiple rituximab treatments. These observations are consistent with the rituximab safety profile in adults with GPA/MPA. Trial registration: ClinicalTrials.gov identifier, NCT01750697.

* Objective: To determine the rate and estimate the cost of hospitalization in a defined urban homeless population. * Design: Retrospective chart review. * Setting: Kalihi-Palama Health Clinic Health Care for the Homeless Project, Hawaii State Hospital, and seven acute care hospitals in Honolulu, Hawaii. * Patients: A total of 1751 homeless clients contacted between 1 December 1988 and 30 November 1990. * Measurements and Main Results: A total of 1751 individuals were studied for an aggregate of 871.3 person-years. Five hundred sixty-four hospitalizations were identified: ninety-two to the state psychiatric hospital and 472 to acute care hospitals. The age- and sex-adjusted hospitalization rate for acute care hospitals was 542/1000 person-years (compared with the state rate of 96/1000 person-years). Homeless persons were admitted to acute care hospitals for 4766 days compared with a predicted 640 days. The age- and sex-adjusted rate of admission to the state psychiatric hospital was 105/1000 person-years (compared with the state rate of 0.8/1000 person-years). Homeless persons were admitted to the state psychiatric hospital for 3837 days compared with a predicted 139 days. * Conclusions: Homeless individuals in this study were hospitalized in acute care and psychiatric hospitals far more frequently than were members of the general population.

•Analysis of 46 adjunctive false lumen embolization (FLE) with thoracic endovascular repair (TEVAR) to 838 TEVAR alone•FLE/TEVAR offers unclear benefit in patients with chronic aortic dissections:○Similar incidence of postoperative complications, re-interventions, and aortic remodeling○Trend toward improved survival and increased rates of FL thrombosis in treated thoracic segment•Further investigation needed to determine most suitable FLE implementation in chronic aortic dissections

Introduction: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease, whose multifaceted care path can lead to significant expenditure for the healthcare system. We aim to assess the real-world healthcare resource use (HCRU) and associated cost for children with JIA in a single center in Canada. Methods: A single-center consecutive cohort of newly diagnosed patients with JIA attending the pediatric rheumatology clinic from 2011 to 2019 was identified using an administrative data algorithm and electronic medical charts. HCRU was estimated from six administrative health databases that included hospital admissions, emergency, outpatient care, practitioners’ visits, medication, and laboratory and imaging tests. Costs were assigned using appropriate sources. We reported the yearly overall and JIA-associated HCRU and costs 5 years prior to and 6 years after the first visit to the pediatric rheumatologist. The Zhao and Tian estimator was used to calculate cumulative mean costs over a 6-year timeframe. Results were stratified by disease subtype. Results: A total of 389 patients were identified. The yearly total overall mean costs per patient ranged between $804 and $4460 during the 5 years prior to the first visit to the pediatric rheumatologist and $8529 and $10,651 for the 6 years after. Medication cost, driven by use of biologic therapies, and outpatient visits were the greatest contributor to the total cost. The overall cumulative mean cost for 6 years of care was $48,649 per patient, while the JIA-associated cumulative mean cost was $26,820 per patient. During the first year of rheumatology care, systemic onset JIA had the highest cumulative mean overall cost, while oligoarticular JIA had the lowest cumulative mean cost. Conclusion: The care pathway for children with JIA can be expensive, and complex—and varies by JIA subtype. Although the yearly total mean cost per patient was constant, the distribution of costs changes over time with the introduction of biologic therapies later in the care pathway. This study provides a better understanding of the JIA costs profile and can help inform future economic studies.

Lymphedema is associated with significant morbidity and healthcare resource usage. Conventional therapy efficacy has been limited, with poor surgical salvage options. Preliminary studies have demonstrated that the use of advanced pneumatic compression devices (APCDs) improves clinical outcomes. However, limited evidence regarding their role in healthcare cost mitigation or health-related quality of life (QOL) is available.

Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.

Penetrating ulcers of the abdominal aorta (PUAA) are an increasingly common finding on abdominal imaging studies; however, their significance and natural history are not well described. This study's objective was to analyze the demographics, presentation, and outcomes of patients with a radiographic diagnosis of PUAA.

Hemolytic anemia resulting from IV Immunoglobulin (IVIG) treatment can be a serious complication, especially for those with underlying conditions with a high level of inflammation and after administration of high IVIG dosages, such as Kawasaki disease (KD), a multisystem vasculitis affecting young children. This hemolysis is caused by antibodies against blood groups A and B, but the precise mechanism for hemolysis is not known. We performed a single center, partly retrospective, partly prospective study of a cohort of 581 patients who received IVIG for treatment of KD from 2006 to 2013. Factors associated with hemolysis were identified through univariable and multivariable logistic regression. Six IVIG preparations were assayed for their hemolytic effect with serological and cellular assays to clarify the mechanism of red cell destruction. During the study period, a sudden increase in the incidence of hemolysis was observed, which coincided with the introduction of new IVIG preparations in North America that contained relatively high titers of anti-A and anti-B. These blood-group–specific antibodies were of the immunoglobulin G2 (IgG2) subclass and resulted in phagocytosis by monocyte-derived macrophages in an FcγRIIa-dependent manner. Phagocytosis was increased in the presence of proinflammatory mediators that mimicked the inflammatory state of KD. An increased frequency of severe hemolysis following IVIG administration was caused by ABO blood-group–specific IgG2 antibodies leading to FcγRIIa-dependent clearance of erythrocytes. This increase in adverse events necessitates a reconsideration of the criteria for maximum titer (1:64) of anti-A and anti-B in IVIG preparations.

Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real‐world effectiveness of simple JIAtreatment strategies recommended in current guidelines. Children with JIAwho were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success. A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when <5 joints were involved, with a 54.4% success rate (95% confidence interval [95% CI] 50.3–58.6). NSAIDs plus joint injections had a 64.7% success rate (95% CI59.8–69.7). Adding methotrexate to NSAIDs and/or joint injections (attempted 566 times) had a 60.5% success rate (95% CI55.7–65.3). In adjusted analyses, each additional active joint reduced chances of success for treatment with NSAIDs (odds ratio [OR] 0.90 [95% CI0.85–0.94]) and for methotrexate combinations (OR0.96 [95% CI0.94–0.99]). Each additional year after disease onset reduced chances of success for treatment with methotrexate combinations (OR0.83 [95% CI0.72–0.95]). These real‐world effectiveness estimates show that conventional nonbiologic treatment strategies that are recommended in current guidelines are effective in achieving treatment targets in many children with JIA.

Upper extremity deep venous thrombosis (UEDVT) and its associated complications are increasing in incidence, but management strategies are largely derived from experience treating lower extremity deep venous thrombosis (LEDVT). The purpose of this study is to examine our single institution's experience with in-hospital venous thromboembolism (VTE), specifically the characteristics and outcomes of the UEDVT population as it compares to LEDVT.

Identification of the incidence of juvenile idiopathic arthritis (JIA)–associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new‐onset uveitis following JIAdiagnosis and to identify associated risk factors. Data were reported every 6 months for 2 years, then yearly to 5 years. Incidence was determined by Kaplan‐Meier estimators with time of JIAdiagnosis as the reference point. Univariate log‐rank analysis identified risk factors and Cox regression determined independent predictors. In total, 1,183 patients who enrolled within 6 months of JIAdiagnosis met inclusion criteria, median age at diagnosis of 9.0 years (interquartile range [IQR] 3.8–12.9), median follow‐up of 35.2 months (IQR22.7–48.3). Of these patients, 87 developed uveitis after enrollment. The incidence of new‐onset uveitis was 2.8% per year (95% confidence interval [95% CI] 2.0–3.5) in the first 5 years. The annual incidence decreased during follow‐up but remained at 2.1% (95% CI0–4.5) in the fifth year, although confidence intervals overlapped. Uveitis was associated with young age (<7 years) at JIAdiagnosis (hazard ratio [HR] 8.29, P< 0.001), positive antinuclear antibody (ANA) test (HR3.20, P< 0.001), oligoarthritis (HR2.45, P= 0.002), polyarthritis rheumatoid factor negative (HR1.65, P= 0.002), and female sex (HR1.80, P= 0.02). In multivariable analysis, only young age at JIAdiagnosis and ANApositivity were independent predictors of uveitis. Vigilant uveitis screening should continue for at least 5 years after JIAdiagnosis, and priority for screening should be placed on young age (<7 years) at JIAdiagnosis and a positive ANAtest.