An "On Demand" canakinumab regimen for treating children with Colchicine-Resistant familial Mediterranean fever - A multicentre study.

OBJECTIVES: Canakinumab, a human monoclonal antibody targeted at interleukin-1 beta, has demonstrated safety and efficacy in preventing familial Mediterranean fever (FMF) attacks among individuals with colchicine-resistant (crFMF). The manufacturer orders prescribe monthly subcutaneous injections. However, a subset of our patients is treated with an "canakinumab on demand " (COD) strategy, with wider intervals between drug administrations. Therefore, we aimed to compare disease activity and drug safety between COD and "canakinumab fixed frequency" (CFF) policies. METHODS: This retrospective study collected data from three Israeli paediatric rheumatology centres, of children with crFMF who were treated with canakinumab. Epidemiological and clinical parameters, cumulative drug dosages, and adverse events were compared between children treated by both policies. RESULTS: Twenty-five (49 %) children were treated according to COD policy and 26 according to CFF policy. Demographic parameters and most of the disease features did not differ significantly between the groups. Both groups showed significant reduction in attacks after canakinumab introduction. The median number (interquartile range) of attacks per month did not differ significantly between the COD and CFF groups (0.33 (0.08, 0.58) and 0.13 (0, 0.5), respectively, p = 0.485 (even though, per definition, COD patients presumably had an attack before receiving the second canakinumab dose). The mean monthly dose was lower for the COD than the CFF group (1.13 ± 1.13 vs. 3.16 ± 1.46 mg/kg, p < 0.001). Adverse events were similar between the groups. CONCLUSION: For individuals with crFMF, COD compared to CFF policy can achieve similar efficacy and safety, with a lower accumulated canakinumab dose, rendering it less immunosuppressive and less expensive.

PFAPA flares observed during COVID outbreak: can emotional stress trigger PFAPA attacks? A multicenter cohort study.

OBJECTIVE: It is common knowledge among clinicians who treat PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) patients that emotional stress can trigger PFAPA attacks similarly to other autoinflammatory diseases. However, it has never been proved scientifically. Our aim was to examine whether emotional stress serves as a trigger for PFAPA attacks. METHODS: Patients aged 3-12 years, with active PFAPA, from two Israeli medical centers were enrolled to this study. Patient's parents were reached via phone calls in two occasions: a stressful period related to the COVID-19 pandemic restrictions and a less stressful period. In both times they were asked to report occurrence of PFAPA attacks in the preceding 2 weeks. The relative stress levels of the two periods were validated by an emotional distress scale questionnaire. The significance level was set at 0.05. RESULTS: Mean age was 7.28 ± 2.7 for the 99 paediatric patients enrolled in the study. Scores for the mean emotional distress questionnaire were statistically significant higher in the stressful period compared to the less stressful period (35.6 ± 8.1 vs. 32.1 ±7.7, respectively, P = 0.047). In the stressful period, 41 (38.7%) reported at least one attack during the preceding 2 weeks, compared to 24 (22.6%) in the less stressful period (p = 0.017). CONCLUSION: PFAPA flares during COVID-19 outbreak are described. This study is the first to suggest that emotional stress is associated with PFAPA attacks.

Persistent pulmonary air leak in the pediatric intensive care unit: Characteristics and outcomes.

BACKGROUND: Persistent air leak (PAL) complicates various lung pathologies in children. The clinical characteristics and outcomes of children hospitalized in the pediatric intensive care unit (PICU) with PAL are not well described. We aimed to elucidate the course of disease among PICU hospitalized children with PAL. METHODS: A retrospective cohort study of all PICU-admitted children aged 0-18 years diagnosed with pneumothorax complicated by PAL, between January 2005 and February 2020 was conducted at a tertiary center. PAL was defined as a continuous air leak of more than 48 h. RESULTS: PAL complicated the course of 4.8% (38/788) of children hospitalized in the PICU with pneumothorax. Two were excluded due to missing data. Of 36 children included, PAL was secondary to bacterial pneumonia in 56%, acute respiratory distress syndrome (ARDS) in 31%, lung surgery in 11%, and spontaneous pneumothorax in 3%. Compared to non-ARDS causes, children with ARDS required more drains (median, range: 4, 3-11 vs. 2, 1-7; p < .001) and mechanical ventilation (100% vs. 12%; p < .001), and had a higher mortality (64% vs. 0%; p < .001). All children with bacterial pneumonia survived to discharge, with a median air leak duration of 14 days (range 3-72 days). Most of which (90%) were managed conservatively, by continuous chest drainage. CONCLUSION: Bacterial pneumonia was the leading cause of PAL in this cohort. PAL secondary to ARDS was associated with a worse outcome. In contrast, non-ARDS PAL was successfully managed conservatively, in most cases.

Performance of 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in a paediatric population-a multicentre study.

OBJECTIVES: The European League Against Rheumatism and American College of Rheumatology 2019 (EULAR/ACR-19) criteria for the diagnosis of SLE were recently published, with the stated goal of maintaining the level of sensitivity and raising the level of specificity for classification of SLE in adults. The aim of this study is to examine their application to juvenile SLE (jSLE) patients. METHODS: In this multicentre study the charts of jSLE patients from three tertiary medical centres were reviewed and compared with patients with non-jSLE diagnosis. Paediatric rheumatologists, blinded to the original diagnosis, reviewed and diagnosed all cases. Paediatric patients' clinical and laboratory data were retrospectively extracted and then examined with regard to how they met the new and old criteria. RESULTS: Included were 225 patients (112 jSLE, 113 non-SLE). When applied to juvenile SLE classification, the sensitivity of the new EULAR/ACR-19 criteria was 0.96 (95% CI: 0.9, 0.99) and the specificity was 0.89 (95% CI: 0.82, 0.94). These were comparable to the SLICC criteria. The sensitivity of the EULAR/ACR-19 criteria improves over time and was 0.83 12 months following disease onset, reaching 0.96 after longer than 24 months. CONCLUSION: Among a cohort of jSLE patients, sensitivity of the new EULAR/ACR-19 criteria was found to be high and specificity may have improved slightly compared with the SLICC-12 criteria. We support the use of the new classification criteria for paediatric patients in future jSLE studies, but it should be noted that its specificity is lower than for adults.

Q Fever and Kingella kingae Endocarditis in a Toddler: A Rare Coinfection Case.

A toddler after tetralogy of Fallot graft repair in infancy was diagnosed with endocarditis. Blood cultures were positive for Kingella kingae and serology was positive Coxiella burnetii. He was treated medically and surgically. A postoperative specimen polymerase chain reaction confirmed a coinfection. A comprehensive patient history was imperative for identification of an unlikely infection at this age.

Unclear Implications: Commentary on Norton and Ariely (2011).

Despite the suggestiveness of their empirical findings, I argue that the implications of Norton and Ariely's work are unclear, both morally and politically.