Hospitalization and Mortality Due to Infection Among Children and Adolescents With Systemic Lupus Erythematosus in the United States.

OBJECTIVE: We aimed to determine the frequency and types of infections in hospitalized children with childhood-onset systemic lupus erythematosus (cSLE), and to identify risk factors for intensive care unit (ICU) admission and mortality. METHODS: We conducted a retrospective study of youth aged 2 to 21 years using International Classification of Diseases (ICD) codes for SLE assigned during admission to a hospital participating in the Pediatric Health Information System, a database of United States children's hospitals, from 2009 to 2021. Generalized linear mixed effects models were used to identify risk factors for ICU admission and mortality among children hospitalized with infection. RESULTS: We identified 8588 children with cSLE and ≥ 1 hospitalization. Among this cohort, there were 26,269 hospitalizations, of which 13% had codes for infections, a proportion that increased over time (P = 0.04). Bacterial pneumonia was the most common hospitalized infection. In-hospital mortality occurred in 0.4% (n = 103) of cSLE hospitalizations for any indication and 2% of hospitalizations for infection (n = 60). The highest mortality rates occurred with Pneumocystis jirovecii pneumonia (21%) and other fungal infections (21%). Lupus nephritis (LN) and endstage renal disease (ESRD) were associated with increased odds of ICU admission (odds ratio [OR] 1.47 [95% CI 1.2-1.8] and OR 2.40 [95% CI 1.7-3.4]) among children admitted for serious infection. ESRD was associated with higher mortality (OR 2.34 [95% CI 1.1-4.9]). CONCLUSION: Hospitalizations with ICD codes for infection comprised a small proportion of cSLE admissions but accounted for the majority of mortality. The proportion of hospitalizations for infection increased over time. LN and ESRD were risk factors for poor outcomes.

Insurance Status and Tumor Necrosis Factor Inhibitor Initiation Among Children With Juvenile Idiopathic Arthritis in the CARRA Registry.

OBJECTIVE: Prompt escalation to tumor necrosis factor inhibitors (TNFis) is recommended for children with juvenile idiopathic arthritis (JIA) and ongoing disease activity despite treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). It is unknown whether these recommendations are equitably followed for children with different insurance types. We assessed the association of insurance coverage on the odds and timing of TNFi use. METHODS: We conducted a retrospective study of children with newly diagnosed JIA in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. We compared the odds of starting a TNFi in the first year and time from cDMARD to TNFi initiation between those with public and private insurance. RESULTS: We identified 1086 children with new JIA diagnoses. Publicly insured children had significantly higher active joint counts and parent/patient global assessment scores at the enrollment visit. They were also more likely to have polyarticular arthritis compared to those with private insurance. Odds of any TNFi use in the first year did not differ between publicly and privately insured children. Publicly insured children were escalated from cDMARD to TNFi more quickly than privately insured children. CONCLUSION: Children who were publicly insured had more severe disease and polyarticular involvement at registry enrollment compared to those who were privately insured. Whereas overall TNFi use did not differ between children with different insurance types, publicly insured children were escalated more quickly, consistent with their increased disease severity. Further research is needed to determine why insurance coverage type is associated with disease severity, including how other socioeconomic factors affect presentation to care.

Real-world use and outcomes of belimumab in childhood-onset lupus: A single-center retrospective study.

BACKGROUND: Studies of real-world effectiveness of belimumab in adults with systemic lupus erythematosus have shown improved disease control and decreased oral glucocorticoid use. However, belimumab use outside of clinical trial settings has not been well studied in childhood-onset systemic lupus erythematosus (cSLE). We aimed to characterize indications for belimumab use and evaluate oral glucocorticoid doses and disease activity scores in the year following belimumab initiation at a single, large pediatric rheumatology center. METHODS: We included children and young adults with cSLE who received ≥ 1 dose of belimumab. Repeated measures one-way ANOVA was used to compare SLEDAI-2K scores and prednisone-equivalent daily oral glucocorticoid doses at baseline, 6 months, and 12 months after belimumab initiation for those who continued therapy for a year. RESULTS: We identified 21 patients with cSLE who received ≥ 1 dose of belimumab. The median disease duration at belimumab initiation was 30.8 months [IQR 21.0-79.1]. At the time of belimumab initiation, 100% of patients were taking an antimalarial, 81% were on oral glucocorticoids, and 91% were on at least one conventional DMARD. Thirteen patients (62%) continued belimumab for ≥6 months and 11 (52%) for ≥12 months. Among those continuing belimumab for ≥12 months, median [IQR] oral prednisone daily doses in milligrams at baseline, 6 months, and 12 months were 12.5 [7.5-17.5], 9 [6.25-10], and 5 [5-9.5], p = 0.037, and median [IQR] SLEDAI-2K scores at baseline, 6 months, and 12 months were 8 [5.5-10.5], 6 [3.5-10], and 6 [6-8.5], p = 0.548, respectively. CONCLUSIONS: In our cohort of pediatric patients with lupus and moderate disease activity treated with belimumab for ≥12 months, daily oral glucocorticoid doses were significantly lower 6 and 12 months after belimumab initiation than baseline. Use in patients with active nephritis was uncommon. Further research is needed in a large, multicenter cohort to determine the real-world effectiveness of belimumab in children and develop guidelines for use.

New-onset hypogammaglobulinaemia and infectious complications associated with rituximab use in childhood-onset rheumatic diseases.

OBJECTIVE: To investigate the incidence and risk factors for hypogammaglobulinaemia and infectious complications associated with rituximab treatment in childhood-onset rheumatic diseases. METHODS: We performed a single-centre retrospective study of patients (n = 85) treated at Boston Children's Hospital (BCH) from 2009 to 2019. Study subjects included patients (ages 6-24 years) who received rituximab for the treatment of a childhood-onset rheumatic disease. RESULTS: New-onset hypogammaglobulinaemia developed in 23 (27.1%) patients within 18 months of rituximab induction treatment. Twenty-two patients (25.9%) developed at least one infectious complication in the 18 months following the first rituximab infusion; of these, 11 (50%) had serious infections requiring inpatient treatment. After adjusting for potential confounders, exposure to pulse corticosteroid therapy in the month prior to rituximab use was a significant predictor of both new-onset hypogammaglobulinaemia (odds ratio [OR] 3.94; 95% CI: 1.07, 16.0; P = 0.044) and infectious complications (OR 15.3; 95% CI: 3.04, 126.8; P = 0.003). Post-rituximab hypogammaglobulinaemia was the strongest predictor of serious infectious complications (OR 7.89; 95% CI: 1.41, 65.6; P = 0.028). Younger age at rituximab use was also a significant predictor of new-onset hypogammaglobulinaemia (OR 0.83; 95% CI: 0.70, 0.97; P = 0.021). Compared with other rheumatic diseases, patients with vasculitis had a higher likelihood of developing infectious complications, including serious infections. CONCLUSION: Although rituximab was well tolerated in terms of infectious complications in the majority of patients with childhood-onset rheumatic diseases, a substantial proportion developed new-onset hypogammaglobulinaemia and infectious complications following treatment. Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinaemia and infections in paediatric patients with rheumatic conditions.

Clinical features of multisystem inflammatory syndrome in children.

PURPOSE OF REVIEW: To review diagnosis, clinical characteristics and treatment of multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RECENT FINDINGS: MIS-C emerged in spring 2020 as a hyperinflammatory syndrome following SARS-CoV-2 exposure in children. Despite growing awareness of MIS-C, diagnosis remains challenging due to the range of phenotypes and severity. Fever accompanied by shock, cardiac dysfunction, gastrointestinal symptoms, or mucocutaneous signs suggestive of Kawasaki disease, especially in the presence of known or suspected coronavirus disease 2019 exposure, should trigger consideration of MIS-C. However, clinical presentations are highly varied and may overlap with other infectious diseases. Clinicians must maintain a high index of suspicion for MIS-C and be aware that patients may develop coronary artery aneurysms and myocarditis even with few or no Kawasaki disease symptoms. More precise diagnostic criteria and specific biomarkers are needed to aid diagnosis. Intravenous immunoglobulin (IVIG) is first-line therapy, and steroids should be considered as initial adjunctive treatment for patients with severe manifestations or other risk factors. Prompt treatment is essential, as patients may worsen acutely, though overall prognosis is reassuring. SUMMARY: MIS-C associated with SARS-CoV-2 has varied clinical manifestations. Clinicians must be aware of the common presentation and potential for decompensation and cardiac sequalae to guide appropriate evaluation and treatment.

Risk factors associated with Pneumocystis jirovecii pneumonia in juvenile myositis in North America.

OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is associated with significant morbidity and mortality in adult myositis patients; however, there are few studies examining PJP in juvenile myositis [juvenile idiopathic inflammatory myopathy (JIIM)]. The purpose of this study was to determine the risk factors and clinical phenotypes associated with PJP in JIIM. METHODS: An research electronic data capture (REDCap) questionnaire regarding myositis features, disease course, medications and PJP infection characteristics was completed by treating physicians for 13 JIIM patients who developed PJP (PJP+) from the USA and Canada. Myositis features and medications were compared with 147 JIIM patients without PJP (PJP-) from similar geographic regions who enrolled in National Institutes of Health natural history studies. RESULTS: PJP+ patients were more often of Asian ancestry than PJP- patients [odds ratio (OR) 8.7; 95% CI 1.3, 57.9]. Anti- melanoma differentiation associated protein 5 (MDA5) autoantibodies (OR 12.5; 95% CI 3.0, 52.4), digital infarcts (OR 43.8; 95% CI 4.2, 460.2), skin ulcerations (OR 12.0; 95% CI 3.5, 41.2) and interstitial lung disease (OR 10.6; 95% CI 2.1, 53.9) were more frequent in PJP+ patients. Before PJP diagnosis, patients more frequently received pulse steroids, rituximab and more immunosuppressive therapy compared with PJP- patients. Seven PJP+ patients were admitted to the intensive care unit and four patients died due to PJP or its complications. CONCLUSIONS: PJP is a severe infection in JIIM that can be associated with mortality. Having PJP was associated with more immunosuppressive therapy, anti-MDA5 autoantibodies, Asian race and certain clinical features, including digital infarcts, cutaneous ulcerations and interstitial lung disease. Prophylaxis for PJP should be considered in juvenile myositis patients with these features.

Mesenteric tumour deposits arising from small-intestine neuroendocrine tumours are frequently associated with fibrosis and IgG4-expressing plasma cells.

AIMS: Mesenteric tumour deposits frequently occur in small-intestine neuroendocrine tumours. In many instances, these mesenteric tumour deposits are surrounded by a dense fibrotic stroma and have associated lymphoplasmacytic inflammation. The aim of this study was to examine whether mesenteric tumour deposits in patients with small-intestine NETs neuroendocrine tumours show histological and immunophenotypic overlap with IgG4-related sclerosing mesenteritis. METHODS AND RESULTS: Sixty-six mesenteric tumour deposits from 66 patients with small-intestine neuroendocrine tumours with blocks available for further studies were identified from our archives. Cases were assessed for clinicopathological features and the presence of IgG4-positive and IgG-positive plasma cells by immunohistochemistry. Ratios of IgG4-positive to IgG-positive plasma cells were calculated. Seventeen mesenteric tumour deposits (26%) showed >40 IgG4-positive plasma cells per high-power field, and the majority of cases (68%) showed at least some staining of IgG4-positive plasma cells. Mesenteric tumour deposits with >20 IgG4-positive plasma cells per high-power field tended to be larger (25.9 ± 13.0 mm versus 18.6 ± 15.8 mm; P = 0.07), and had more IgG-positive plasma cells (88 ± 24 versus 36 ± 37; P < 0.01) and a higher IgG4-positive/IgG-positive plasma cell ratio (0.66 ± 0.18 versus 0.17 ± 0.25; P < 0.01). All but one mesenteric tumour deposit with >20 IgG4-positve plasma cells had a ratio of >40%. CONCLUSIONS: IgG4 expression is frequent in mesenteric tumour deposits from small-intestine neuroendocrine tumours. Undersampling of tumour on biopsies of mesenteric tumour deposits could potentially cause diagnostic confusion with IgG4-related sclerosing mesenteritis.

Human Papillomavirus-Driven Squamous Lesions: High-Risk Genotype Found in Conjunctival Papillomas, Dysplasia, and Carcinoma.

BACKGROUND: Human papillomavirus (HPV) is a causative agent for intraepithelial squamous neoplasms, particularly on mucosal surfaces. HPV has a well-established association with squamous cell carcinoma (SCC) of the oropharynx and genital tract, and recent studies suggest a potential role in ocular and periocular squamous neoplasms. Multiple high-risk HPV genotypes are associated with histologically similar squamous neoplasms, and some HPV genotypes have been differentially associated with high- or low-grade lesions. METHODS: Squamous lesions were screened with immunohistochemical markers p16 and Ki-67 to compare expression in conjunctival papillomas (n = 21) to papillomas with high-grade dysplasia, SCC in situ, and invasive SCC (n = 40). Polymerase chain reaction was performed using the Roche COBAS HPV assay to identify the 14 most common high-risk HPV genotypes. RESULTS: Compared with squamous papillomas, the lesions showing high-grade dysplasia or worse expressed p16 with greater intensity and in a greater percentage of the lesion. A trend toward mild Ki-67 expression in papillomas versus marked Ki-67 expression in high-grade squamous lesions was also observed. HPV-16 was present in 7 of the SCC in situ and invasive SCC lesions but none of the papillomas. CONCLUSIONS: HPV may have an important role in squamous lesions of the conjunctiva. In addition to positive polymerase chain reaction results, strong and diffuse p16 expression with marked Ki-67 is strongly suggestive of an HPV-driven lesion.

Effects of epinephrine exposure on contractile performance of compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) during hypoxia.

Hypoxia results in elevated circulating epinephrine for many fish species, and this is likely important for maintaining cardiac function. The aims of this study were to assess how hypoxia impacts contractile responses of ventricular compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) and to assess how and if epinephrine may protect myocardial performance from a depressive effect of hypoxia. Work output and maximum contraction rate of isolated preparations of spongy and compact ventricular myocardium from rainbow trout were measured. Tissues were exposed to the blood PO2 that they experience in vivo during environmental normoxia and hypoxia and also to low (5 nM) and high (500 nM) levels of epinephrine in 100% air saturation (PO2 20.2 kPa) and during hypoxia (PO2 2 kPa, 10% air saturation). It was hypothesized that hypoxia would result in a decrease in work output and maximum contraction rate in both tissue types, but that epinephrine exposure would mitigate the effect. Hypoxia resulted in a decline in net work output of both tissue types, but a decline in maximum contraction rate of only compact myocardium. Epinephrine restored the maximum contraction rate of compact myocardium in hypoxia, appeared to slightly enhance work output of only compact myocardium in air saturation but surprisingly not during hypoxia, and restored net work of hypoxic spongy myocardium toward normoxic levels. These results indicate hypoxia has a similar depressive effect on both layers of ventricular myocardium, but that high epinephrine may be important for maintaining inotropy in spongy myocardium and chronotropy in compact myocardium during hypoxia.

A study of metastatic carcinoma found in hernia sacs between 2006 and 2012 at one institution.

Hernia sacs are generally regarded as routine specimens in the daily practice of surgical pathology. However, unexpected findings including carcinoma can occasionally arise in these seemingly benign specimens. To ascertain the prevalence of metastatic carcinoma found within hernia sacs and to determine the importance of routine histologic examination of hernia sacs, we conducted a retrospective study of all hernia sacs with a diagnosis of metastatic carcinoma reported in our hospital system between January 2006 and December 2012. Of 3117 total herniorrhaphy specimens between 2006 and 2012, 11 (0.35%) were found to have metastatic carcinoma. Interestingly, in 3 cases, the initial diagnosis of cancer was made during histologic examination of the hernia sac. Metastatic carcinoma in hernia sacs is a rare occurrence; however, it is encountered in routine practice. It is recommended that herniorrhaphy specimens not be discarded and, instead, be regarded as peritoneal biopsies for routine histologic examination.

Temporal evaluation of efficacy and quality of tissue repair upon laser-activated sealing.

Injuries caused by surgical incisions or traumatic lacerations compromise the structural and functional integrity of skin. Immediate approximation and robust repair of skin are critical to minimize occurrences of dehiscence and infection that can lead to impaired healing and further complication. Light-activated skin sealing has emerged as an alternative to sutures, staples, and superficial adhesives, which do not integrate with tissues and are prone to scarring and infection. Here, we evaluate both shorter- and longer-term efficacy of tissue repair response following laser-activated sealing of full-thickness skin incisions in immunocompetent mice and compare them to the efficacy seen with sutures. Laser-activated sealants (LASEs) in which, indocyanine green was embedded within silk fibroin films, were used to form viscous pastes and applied over wound edges. A hand-held, near-infrared laser was applied over the incision, and conversion of the light energy to heat by the LASE facilitated rapid photothermal sealing of the wound in approximately 1 min. Tissue repair with LASEs was evaluated using functional recovery (transepidermal water loss), biomechanical recovery (tensile strength), tissue visualization (ultrasound [US] and photoacoustic imaging [PAI]), and histology, and compared with that seen in sutures. Our studies indicate that LASEs promoted earlier recovery of barrier and mechanical function of healed skin compared to suture-closed incisions. Visualization of sealed skin using US and PAI indicated integration of the LASE with the tissue. Histological analyses of LASE-sealed skin sections showed reduced neutrophil and increased proresolution macrophages on Days 2 and 7 postclosure of incisions, without an increase in scarring or fibrosis. Together, our studies show that simple fabrication and application methods combined with rapid sealing of wound edges with improved histological outcomes make LASE a promising alternative for management of incisional wounds and lacerations.

Incidence and Risk Factors for Eosinophilia and Lung Disease in Biologic-Exposed Children With Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: Although interleukin-1 (IL-1)/IL-6 inhibitors are effective therapies for systemic juvenile idiopathic arthritis (JIA), some patients develop eosinophilia and lung disease during treatment. This study was undertaken to retrospectively evaluate incidence and risk factors for eosinophilia and describe lung disease outcomes in IL-1/IL-6 inhibitor-exposed patients with systemic JIA. METHODS: Among JIA patients at our institution exposed to interleukin-1 (IL-1)/IL-6 inhibitors (1995-2022), we compared incidence rate of eosinophilia in systemic JIA compared to other JIA, stratified by medication class (IL-1/IL-6 inhibitors, other cytokine inhibitors, methotrexate). We used Cox models to identify predictors of eosinophilia during IL-1/IL-6 inhibitor use and summarized treatment changes and outcomes after eosinophilia, including lung disease. HLA typing was performed on a clinical or research basis. RESULTS: There were 264 new medication exposures in 75 patients with systemic JIA and 41 patients with other JIA. A total of 49% of patients with systemic JIA with HLA typing (n = 45) were positive for HLA-DRB1*15 alleles. Eosinophilia was common during IL-1/IL-6 inhibitor use and did not differ by systemic JIA compared to other JIA (0.08 and 0.07 per person-year, respectively; P = 0.30). Among systemic JIA patients, pretreatment macrophage activation syndrome (MAS) was associated with a higher rate of subsequent eosinophilia on biologic therapy (unadjusted hazard ratio 3.2 [95% confidence interval 1.2-8.3]). A total of 4 of 5 patients who switched therapy within 10 weeks of eosinophilia experienced disease flare compared to none of the patients who continued the original therapy. A total of 8 of 25 patients with pulmonary evaluations had lung disease, and all had severe manifestations of systemic JIA (MAS, intensive care unit stay). One death was attributed to systemic JIA-lung disease. CONCLUSION: Eosinophilia is common in JIA patients using IL-1/IL-6 inhibitors. Severe disease may be associated with eosinophilia and lung disease in systemic JIA.

Association of Race and Ethnicity With Medication Use for Pediatric Lupus in the Childhood Arthritis and Rheumatology Research Alliance Registry.

OBJECTIVE: Black and Hispanic children with pediatric lupus (pSLE) have higher morbidity and mortality than non-Hispanic White children. The extent to which differences in outcomes are due to treatment disparities, including medication use, is unknown. We aimed to determine whether medication use in pSLE is associated with race and ethnicity in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. METHODS: Patients with pSLE enrolled in the CARRA Registry from 2017 to 2020 were included. Multivariable mixed-effect logistic regression, adjusted for site of care, was used to compare use of antimalarials, high-dose oral glucocorticoids, and rituximab in Black and Hispanic children. RESULTS: We identified 639 children with pSLE, of whom 480 had at least 1 year of follow-up. At enrollment, 89% of patients were prescribed an antimalarial and 50% were on high-dose glucocorticoids. Of those with 1 year of follow-up, 12% received rituximab. Nephritis, shorter disease duration, and higher Systemic Lupus Erythematosus Disease Activity Index 2000 scores were associated with high-dose glucocorticoid use. Antimalarial use was higher among those with nephritis and lower in children with no insurance. Rituximab use was associated with Black race in the fixed-effects model but not when adjusted for site of care. CONCLUSION: We identified differences in medication use by race and insurance status. Site of care was associated with the racial differences observed in rituximab use. Further research is needed to optimize pSLE treatments particularly where use is highly variable, including glucocorticoid dosing and use of rituximab, and understand the impact of practice variation on disparities in pSLE outcomes.

Development and implementation of the ECHO model in a school setting to address youth electronic cigarette use in Kansas: A protocol.

Introduction: Schools remain at the frontlines of addressing issues, such as e-cigarette use, that impact students. Despite e-cigarette use remaining a significant public health concern in the U.S., schools have limited resources (e.g., staff, capacity, programming) to address it, especially in rural and frontier areas. This ECHO Pilot Project aimed to build capacity and equip schools and school staff in the state of Kansas to address high rates of youth e-cigarette use by providing prevention support and information on best practices for e-cigarette cessation. Methods and analysis: The pilot used the established Project ECHO model to disseminate evidence-based strategies for e-cigarette prevention and cessation among youth to schools across Kansas. The pilot selected 20 interdisciplinary school teams representing both rural and urban middle and high schools across the state to participate in seven ECHO sessions. ECHO sessions proceeded throughout Fall 2021, with the final session in Spring 2022. School participants completed pre-post surveys as well as component-specific surveys following each ECHO session. In addition, each school team created an individualized action plan to comprehensively address e-cigarette use at their school based on the information provided throughout the ECHO. Survey data, school tobacco/nicotine policies, and action plans will be analyzed to assess process and final outcomes. Discussion: If successful, this pilot will demonstrate that the ECHO model is an effective platform for building school staff knowledge and skills to implement evidence-based strategies in both urban and rural settings. It is anticipated that the pilot will build capacity and equip schools and school staff to address high rates of youth e-cigarette use by providing support for school-based prevention programs and referrals for e-cigarette cessation which will lessen the burden of nicotine-related problems in Kansas schools and communities. Finally, the pilot will provide evidence that the ECHO model can be successfully and equitably applied in a school setting and may be a viable method for addressing other public health-related issues faced by schools.

Longitudinal assessment of preparation for care transition among adolescents and young adults with rheumatologic disease: a single-center pilot study.

Adolescents and young adults (AYA) with rheumatologic diseases are at high risk for poor outcomes and gaps in care when transitioning from pediatric to adult care. However, tools for evaluating transition readiness and assessing the impact of transition interventions are limited. We implemented a written transition policy at our pediatric rheumatology center and evaluated preparation for transition among AYA 16 and older before and after distribution. 31 of 77 patients completed the follow-up survey (response rate 40%). Patient report of transition counseling increased following written transition policy implementation, though these results were not statistically significant in our small cohort. Most follow-up respondents (n = 19, 61%) had not yet completed care transfer; 4 (13%) had arranged a visit with an adult rheumatologist and 8 (26%) had fully transitioned to adult care. Those who successfully completed care transfer were older, had completed higher levels of education, and had significantly higher baseline transition preparation scores compared to those with no transfer arranged or planned visit only. Our single-center pilot study demonstrated that longitudinal assessment of transition preparation is feasible and that scores are significantly associated with care transfer outcomes. Tracking transition preparation over time may provide practices with information on areas of highest need for transition guidance and predict successful transfer among AYA with rheumatologic disease.

Differentiating multisystem inflammatory syndrome in children: a single-centre retrospective cohort study.

OBJECTIVE: Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other febrile illnesses, hindering prompt and accurate diagnosis. The objectives of this study were to identify clinical and laboratory findings that distinguished MIS-C from febrile illnesses in which MIS-C was considered but ultimately excluded, and to examine the diseases that most often mimicked MIS-C in a tertiary medical centre. STUDY DESIGN: We identified all children hospitalised with fever who were evaluated for MIS-C at our centre and compared clinical signs and symptoms, SARS-CoV-2 status and laboratory studies between those with and without MIS-C. Multivariable logistic LASSO (least absolute shrinkage and selection operator) regression was used to identify the most discriminative presenting features of MIS-C. RESULTS: We identified 50 confirmed MIS-C cases (MIS-C+) and 68 children evaluated for, but ultimately not diagnosed with, MIS-C (MIS-C-). In univariable analysis, conjunctivitis, abdominal pain, fatigue, hypoxaemia, tachypnoea and hypotension at presentation were significantly more common among MIS-C+ patients. MIS-C+ and MIS-C- patients had similar elevations in C-reactive protein (CRP), but were differentiated by thrombocytopenia, lymphopenia, and elevated ferritin, neutrophil/lymphocyte ratio, BNP and troponin. In multivariable analysis, predictors of MIS-C included age, neutrophil/lymphocyte ratio, platelets, conjunctivitis, oral mucosa changes, abdominal pain and hypotension. CONCLUSIONS: Among hospitalised children undergoing evaluation for MIS-C, children with MIS-C were older, more likely to present with conjunctivitis, oral mucosa changes, abdominal pain and hypotension, and had higher neutrophil/lymphocyte ratios and lower platelet counts. These data may be helpful for discrimination of MIS-C from other febrile illnesses, including bacterial lymphadenitis and acute viral infection, with overlapping features.

Pediatric to Adult Transition Literature: Scoping Review and Rheumatology Research Prioritization Survey Results.

The transition from pediatric to adult care is the focus of growing research. It is important to identify how to direct future research efforts for maximum effect. Our goals were to perform a scoping review of the transition literature, highlight gaps in transition research, and offer stakeholder guidance on the importance and feasibility of research questions designed to fill identified gaps. The transition literature on rheumatic diseases and other common pediatric-onset chronic diseases was grouped and summarized. Based on the findings, a survey was developed and disseminated to pediatric rheumatologists and young adults with rheumatic diseases as well as their caregivers. The transitional care needs of patients, healthcare teams, and caregivers is well described in the literature. While various transition readiness scales exist, no longitudinal posttransfer study confirms their predictive validity. Multiple outcome measures are used alone or in combination to define a successful transition or intervention. Multimodal interventions are most effective at improving transition-related outcomes. How broader health policy affects transition is poorly studied. Research questions that ranked highest for importance and feasibility included those related to identifying and tracking persons with psychosocial vulnerabilities or other risk factors for poor outcomes. Interventions surrounding improving self-efficacy and health literacy were also ranked highly. In contrast to healthcare teams (n = 107), young adults/caregivers (n = 23) prioritized research surrounding improved work, school, or social function. The relevant transition literature is summarized and future research questions prioritized, including the creation of processes to identify and support young adults vulnerable to poor outcomes.