Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate-to-severe atopic dermatitis treated with dupilumab.

BACKGROUND: Dupilumab is approved for moderate-severe atopic dermatitis (AD) in patients aged ≥6 months by the US Food and Drug Administration and Health Canada; however, there are little real-world data because providers have limited practical experience with this recently approved therapy. OBJECTIVES: To describe the real-world effectiveness and safety in patients aged <12 years with moderate-severe AD currently receiving or previously having received dupilumab. METHODS: A multicenter retrospective study was conducted at six Canadian sites. Cases were divided into Group 1 ≤2 years old, Group 2 >2 to <6 years old, and Group 3 ≥6 to <12 years old. Medical history and details of dupilumab treatment were collected. The primary outcome was to measure the improvement in eczema area and severity index. Secondary outcomes examined included the children's dermatology life quality index/infant's dermatitis quality of life, peak pruritus numerical rating scale, and delay to dupilumab access for patients who were considered off-label for dupilumab due to their age. RESULTS: Sixty three pediatric patients (37 males) with moderate-to-severe AD were included; the mean age was 6.4 years old (range: 2-11) when dupilumab treatment was started. Overall, 75% (36/48) achieved EASI-75% and 71% (34/48) achieved EASI-90. EASI-75 and EASI-90 were achieved in 90% (17/19) and 73% (12/19) in patients <6 years old, and 76% (22/29) and 59% (17/29) in patients >6 years old, respectively. No serious adverse events were reported. CONCLUSIONS: Dupilumab is safe and effective for patients under the age of 12. However, even for experienced providers, access to the medication was challenging.

Kinetic analysis of electron flux in cytochrome P450 reductases reveals differences in rate-determining steps in plant and mammalian enzymes.

Herein, we compare the kinetic properties of CPR from Arabidopsis thaliana (ATR2), with CPR from Artemisia annua (aaCPR) and human CPR (hCPR). While all three CPR forms elicit comparable rates for cytochrome c(3+) turnover, NADPH reduction of the FAD cofactor is ∼50-fold faster in aaCPR and ATR2 compared to hCPR, with a kobs of ∼500 s(-1) (6 °C). Stopped-flow analysis of the isolated FAD-domains reveals that NADP(+)-FADH2 charge-transfer complex formation is also significantly faster in the plant enzymes, but the rate of its decay is comparable for all three proteins. In hCPR, transfer of a hydride ion from NADPH to FAD is tightly coupled to subsequent FAD to FMN electron transfer, indicating that the former catalytic event is slow relative to the latter. In contrast, interflavin electron transfer is slower than NADPH hydride transfer in aaCPR and ATR2, occurring with an observed rate constant of ∼50 s(-1). Finally, the transfer of electrons from FMN to cytochrome c(3+) is rapid (>10(3) s(-1)) in all three enzymes and does not limit catalytic turnover. In combination, the data reveal differences in rate-determining steps between plant CPR and their mammalian equivalent in mediating the flux of reducing equivalents from NADPH to external electron acceptors.

Reactive infectious mucocutaneous eruption - repeat etanercept after intravenous immunoglobulin: A case report.

Reactive infectious mucocutaneous eruption is a recently distinguished mucosal-predominant blistering eruption triggered by respiratory infections. We describe a previously healthy 11-year-old Black female with rapidly progressive mucocutaneous blistering after prodromal respiratory infection symptoms. Reactive infectious mucocutaneous eruption was suspected and treated with systemic corticosteroids followed by etanercept. Twenty-four hours after etanercept, the diagnosis of multisystem inflammatory syndrome in children was raised and intravenous immunoglobulin was given. Rapidly worsening mucocutaneous disease ensued but was controlled by a second dose of etanercept. Our case highlights the following: (1) the novel observation of possible interaction/neutralization of etanercept by intravenous immunoglobulin, (2) the challenging differential diagnosis of multisystem inflammatory syndrome in children for reactive infectious mucocutaneous eruption patients in the Coronavirus disease 2019 (COVID-19) pandemic, and (3) the role of early treatment to prevent dyspigmentation.

What lies downstream? A case of superior vena cava syndrome presenting in the dermatology clinic: A case report.

A 75-year-old female presented with a 1 year history of a firm, diffusely swollen, and erythematous facial plaque. She had preceding unsuccessful investigations and treatment for angioedema. Full-skin examination revealed multiple prominent varicosities on the chest and abdomen. Superior vena cava syndrome was suspected. Solid facial edema (Morbihan's syndrome) and various infiltrates included in the differential diagnosis were ruled out with a skin biopsy. Chest computed tomography confirmed a complete superior vena cava thrombosis. Extensive workup for associated malignancy has to date been unremarkable, and as yet an underlying cause remains to be found.

First Nations Elders' perspectives of engagement in community programs in Nak'azdli Whut'en, British Columbia, Canada.

OBJECTIVES: Meaningful social engagement is important to reduce risk for social isolation and loneliness. First Nations Elders are a unique group and little knowledge currently exists of their preferred forms of social interaction. The objective of this study was to describe the types of programs Nak'azdli Elders desire, identify barriers to participation, and improve creation of programs that address Elders' needs and interests. METHODS: This project was co-created by the Nak'azdli Health Centre and Elders, located in Northern British Columbia, with support from academic partners when and where asked. An advisory committee selected participants perceived as able to complete the survey and available for interviewing. Participants were interviewed orally in English or Carrier in their homes or at a drop-in centre, by a well-respected Nak'azdli Elder. The Elder entered participant responses (including self-reported health, awareness and utilization for existing programs, and preferences for new programs) into a paper-based survey. Descriptive and content analysis were conducted. RESULTS: Nak'azdli Elders (N = 38) were interested in wisdom sharing, social programs, and health-related activities. Elders wanted to be actively engaged in programs/activity selection, helping organize programs, knowledge sharing, skills, and stories. Barriers to participation included lack of transportation, personal health concerns, scheduling conflicts, and lack of knowledge about programs/activities. CONCLUSION: Nak'azdli Elders were interested in culturally relevant programs involving sharing cultural knowledge, teachings, and/or language with younger generations. Elders wanted to be engaged in all stages of activities, including planning, participation, and evaluation. Future programs should prioritize community collaboration and co-creation with Elders.