Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study.

BACKGROUND AND OBJECTIVE: Evidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established. PATIENTS AND METHODS: To examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children's hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG + anakinra). RESULTS: Among 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG + anakinra group, of which 9 (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG + anakinra group were enriched in a CV shock phenotype (p = 0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG + anakinra group exhibited improvements in fever and cardiac function with or without CS. No significant adverse events were observed, and no differences in IL-1ß levels were found among MIS-C patients in the IVIG + anakinra group. CONCLUSIONS: Anakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of severe MIS-C.

Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) patients are unique, with hallmarks of Mendelian disorders (early-onset and severe disease) and thus are an ideal population for genetic investigation of SLE. In this study, we use the transmission disequilibrium test (TDT), a family-based genetic association analysis that employs robust methodology, to analyze whole genome sequencing data. We aim to identify novel genetic associations in an ancestrally diverse, international cSLE cohort. Forty-two cSLE patients and 84 unaffected parents from 3 countries underwent whole genome sequencing. First, we performed TDT with single nucleotide variant (SNV)-based (common variants) using PLINK 1.9, and gene-based (rare variants) analyses using Efficient and Parallelizable Association Container Toolbox (EPACTS) and rare variant TDT (rvTDT), which applies multiple gene-based burden tests adapted for TDT, including the burden of rare variants test. Applying the GWAS standard threshold (5.0 × 10-8) to common variants, our SNV-based analysis did not return any genome-wide significant SNVs. The rare variant gene-based TDT analysis identified many novel genes significantly enriched in cSLE patients, including HNRNPUL2, a DNA repair protein, and DNAH11, a ciliary movement protein, among others. Our approach identifies several novel SLE susceptibility genes in an ancestrally diverse childhood-onset lupus cohort.

Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort.

Lupus nephritis (LN) is a life-threatening manifestation of systemic lupus erythematosus (SLE) and is more common in children than adults. The epidemiology and management of childhood-onset SLE (cSLE) have changed over time, prompting the need to reassess expected outcomes. The purpose of this study is to use the Childhood Arthritis and Rheumatology Research Alliance (CARRA) prospective registry to validate historical principles of LN in a contemporary, real-world cohort. After an extensive literature review, six principles of LN in cSLE were identified. The CARRA registry was queried to evaluate these principles in determining the rate of LN in cSLE, median time from cSLE diagnosis to LN, short-term renal outcomes, and frequency of rituximab as an induction therapy. Of the 677 cSLE patients in the CARRA registry, 32% had documented LN. Decline in kidney function was more common in Black cSLE patients than non-Black patients (p = 0.04). Black race was associated with worse short-term renal outcomes. In short-term follow up, most children with LN had unchanged or improved kidney function, and end stage kidney disease (ESKD) was rare. Ongoing follow-up of cSLE patients in the CARRA registry will be necessary to evaluate long-term outcomes to inform risk, management, and prognosis of LN in cSLE.

Perception-based effects of clinical exposure to osteopathic manipulative treatment on first- and second-year osteopathic medical students.

CONTEXT: Little research has been done regarding osteopathic medical students' clinical exposure to osteopathic manipulative treatment (OMT). Most existing research focuses on third- and fourth-year students. OBJECTIVE: To determine the effects of clinical exposure to OMT on first- and second-year osteopathic medical students by assessing the same population's perceptions of OMT. METHODS: In the present survey-based study, conducted at the New York Institute of Technology College of Osteopathic Medicine, first- and second-year osteopathic medical students were administered an electronic survey containing 18 multiple-choice questions. The first 2 questions were demographic. The next 6 questions had participants identify what, if any, clinical exposure to OMT they had, including clinical shadowing, the MedPrep program, and the Summer Student American Academy of Osteopathy Osteopathic Manipulative Medicine Preceptorship program. The 10 questions that followed assessed the participant's perception of OMT: (1) understanding, (2) attitude toward OMT, (3) scope of practice of OMT, and (4) intention to use OMT in future clinical practice. The survey used the statistically validated Likert scale for all of the scaled questions. Analysis was performed using the Pearson χ(2) test and the Fisher exact test. RESULTS: Of the 600 students who were sent surveys, 364 replied, for a response rate of 60.7%. There was an association with students' anticipated use of OMT in their future clinical practice and the following types of clinical exposures to OMT: MedPrep (P=.04), Summer Student American Academy of Osteopathy Osteopathic Manipulative Medicine Preceptorship (P=.04), extracurricular OMT didactics (P=.048), and shadowing a physician performing OMT before attending osteopathic medical school (P=.007). Being treated with OMT had no association with anticipated future use of OMT. More OMT clinical exposures were associated with more positive responses to the perception questions ([Formula: see text], P<.001). CONCLUSION: Participants with clinical exposure to OMT before entering clinical training were more likely to plan to use OMT in future practice. Early clinical exposure to OMT before or during the first 2 years of osteopathic medical school was associated with a positive perception of OMT.