ROHHAD syndrome without rapid-onset obesity: A diagnosis challenge.

Background: ROHHAD syndrome (Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation) is rare. Rapid-onset morbid obesity is usually the first recognizable sign of this syndrome, however a subset of patients develop ROHHAD syndrome without obesity. The prevalence of this entity is currently unknown. Alteration of respiratory control as well as dysautonomic disorders often have a fatal outcome, thus early recognition of this syndrome is essential. Material and methods: A retrospective, observational, multicenter study including all cases of ROHHAD without rapid-onset obesity diagnosed in France from 2000 to 2020. Results: Four patients were identified. Median age at diagnosis was 8 years 10 months. Median body mass index was 17.4 kg/m2. Signs of autonomic dysfunction presented first, followed by hypothalamic disorders. All four patients had sleep apnea syndrome. Hypoventilation led to the diagnosis. Three of the four children received ventilatory support, all four received hormone replacement therapy, and two received psychotropic treatment. One child in our cohort died at 2 years 10 months old. For the three surviving patients, median duration of follow-up was 7.4 years. Conclusion: ROHHAD syndrome without rapid-onset obesity is a particular entity, appearing later than ROHHAD with obesity. This entity should be considered in the presence of dysautonomia disorders without brain damage. Likewise, the occurrence of a hypothalamic syndrome with no identified etiology requires a sleep study to search for apnea and hypoventilation. The identification of ROHHAD syndrome without rapid-onset obesity is a clinical challenge, with major implications for patient prognosis.

Welfare Resilience at the Onset of the COVID-19 Pandemic in a Selection of European Countries: Impact on Public Finance and Household Incomes.

This paper assesses the impact on household incomes of the COVID-19 pandemic and governments' policy responses in April 2020 in four large and severely hit EU countries: Belgium, Italy, Spain and the UK. We provide comparative evidence on the level of relative and absolute welfare resilience at the onset of the pandemic, by creating counterfactual scenarios using the European tax-benefit model EUROMOD combined with COVID-19-related household surveys and timely labor market data. We find that income poverty increased in all countries due to the pandemic while inequality remained broadly the same. Differences in the impact of policies across countries arose from four main sources: the asymmetric dimension of the shock by country, the different protection offered by each tax-benefit system, the diverse design of discretionary measures and differences in the household level circumstances and living arrangements of individuals at risk of income loss in each country.

Quick-Wee versus bladder stimulation to collect midstream urine from precontinent infants under 1 year of age: a study protocol for a randomised controlled trial (ES.Stimquick.U).

INTRODUCTION: Urinary tract infections occur in around 1%-4% of boys and 3%-8% of girls under 2 years old. Diagnosis is difficult because of non-specific symptoms and the risk of urine analysis contamination depending on the sampling method used for precontinent infants. The American Academy of Pediatrics recommend transurethral catheterisation and suprapubic aspiration because of a low contamination rate but these techniques are invasive. On the other hand, while the National Institute for Health and Care Excellence advocate clean catch urine for its minimal invasiveness and acceptable contamination rate, it is difficult to accomplish in precontinent infants. Two recent methods have been described: the Quick-Wee method by Kaufman et al (suprapubic stimulation with cold saline-soaked gauze); and bladder stimulation by Herreros et al then by Tran et al (pubic tapping alternating with lumbar massage). This study aims to compare the effectiveness in collecting midstream urine by bladder stimulation vs the Quick-Wee method in infants under 1 year, before walking. METHODS AND ANALYSIS: This study is a multicentre randomised controlled trial of 230 infants under 1 year and before walking who need urine analysis, conducted in four paediatric emergency departments in France. Patients will be randomised into two groups: bladder stimulation and Quick-Wee method.The primary endpoint will be the success rate of voiding at least 2 mL of urine in less than 5 min.Secondary outcomes are the time to collect at least 2 mL of urine, comfort, quality of urine and the risk factors associated with failure of the two techniques. ETHICS AND DISSEMINATION: The study protocol was approved by the French national ethic committee (consultative committee of the protection of persons). The results of the study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical Trials Registry - NCT04587999. DATE AND PROTOCOL VERSION IDENTIFIER: October 2020, V.1.

Clinical Aspects of STAT3 Gain-of-Function Germline Mutations: A Systematic Review.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF) germline mutations have been recently described. A comprehensive overview of this early-onset multiorgan autoimmune and lymphoproliferative disease has not yet been compiled. OBJECTIVE: We have conducted a systematic review of published STAT3 GOF cases to describe clinical, diagnostic, and therapeutic aspects of the disease. METHODS: A systematic review including articles published before October 10, 2018, in PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed. We described cases of patients with STAT3 GOF germline mutations with genetic analysis and a concordant phenotype if functional analyses were not performed for the mutation. RESULTS: The search identified 18 publications describing 42 unique patients. Twenty-eight different mutations were described. Onset of disease was very early with an average age of 3 (0.5-5) years. The most frequent manifestations were autoimmune cytopenias (28 of 42), lymphoproliferation (27 of 42), enteropathy (24 of 42), interstitial lung disease (15 of 42), thyroiditis (13 of 42), diabetes (10 of 42), and postnatal growth failure (15 of 21). Immunodeficiency was not always a predominant feature. Most patients required significant immunosuppressive therapy. Five patients received hematopoietic stem cell transplantation, and 4 died from complications. Improvement of symptoms was observed for 8 of 9 patients who received targeted biotherapies. CONCLUSIONS: STAT3 GOF syndrome is a new clinical entity to consider when confronted with a patient with early-onset polyautoimmunity, lymphoproliferation, and growth failure. At this time, precise therapeutic guidelines are lacking, but use of anti-IL-6 receptor and JAK inhibitor biologics is an attractive possibility.