GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: We are very uncertain about the estimate a Sensitivity analysis excluding trials published as abstracts did not change the overall mortality e ect estimate b The outcome was upgraded from low to moderate quality of evidence because most trials had moderate risk of bias c The outcome was upgraded from moderate to high quality of evidence because most trials had low risk of bias

Given the number of centers and subjects included in the database, these findings provide a robust description of current practice regarding the use of high-frequency oscillatory ventilation for pediatric hypoxic respiratory failure. Patients with severe hypoxic respiratory failure and immunocompromise had the highest mortality risk, and those with respiratory syncytial virus had the lowest. A means of identifying the risk of 30-day mortality for subjects can be obtained by identifying the underlying disease and oxygenation index on conventional ventilation preceding the initiation of high-frequency oscillatory ventilation.

SummaryAcute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effect of inhaled nitric oxide. There was no statistically significant effect of inhaled nitric oxide on longest follow-up mortality (inhaled nitric oxide group 250/654 deaths (38.2%) vs. control group 221/589 deaths (37.5%; relative risk (95% CI) 1.04 (0.9-1.19)). We found a significant improvement in PaO 2 /F I O 2 ratio at 24 h (mean difference (95% CI) 15.91 (8.25-23.56)), but not at 48 h or 72 h, while four trials indicated improved oxygenation in the inhaled nitric oxide group at 96 h (mean difference (95% CI) 14.51 (3.64-25.38)). There were no statistically significant differences in ventilator-free days, duration of mechanical ventilation, resolution of multi-organ failure, quality of life, length of stay in intensive care unit or hospital, cost-benefit analysis and methaemoglobin and nitrogen dioxide levels. There was an increased risk of renal impairment (risk ratio (95% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may induce renal impairment.

Most children with a SARS-CoV-2 infection are asymptomatic or exhibit mild symptoms. However, a small number of children develop features of substantial inflammation temporarily related to the COVID-19 also called multisystem inflammatory syndrome in children (MIS-C) or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS), clinically similar to Kawasaki disease, toxic shock syndrome and hemophagocytic lymphohistiocytosis (HLH). It is well-known that genetic pre-disposition plays an important role in virally-triggered diseases such as Epstein-Barr virus (EBV)-associated HLH, while this has not yet been established for patients with MIS-C. Here we describe a male patient fulfilling the diagnostic criteria of MIS-C, who was initially treated according to current consensus guidelines. Presence of hypofibrinogenemia, normal lymphocyte counts and C-reactive protein, but substantial hyperferritinemia distinguish this patient from others with MIS-C. The clinical course following initial presentation with acute respiratory distress syndrome was marked by fatal liver failure in the context of EBV-associated HLH despite treatment with steroids, intravenous immunoglobulins, interleukin (IL)-1 receptor blockade and eventually HLH-directed treatment. X-linked lymphoproliferative disease type 1 (XLP1), a subtype of primary HLH was diagnosed in this patient post-mortem. This case report highlights the importance of including HLH in the differential diagnosis in MIS-C with severe disease course to allow specific, risk-adapted treatment and genetic counseling.

Purpose Malignant stroke is a life-threatening emergency, with a high mortality rate (1–3). Despite strong evidence showing decreased morbidity and mortality in the adult population, decompressive hemicraniectomy (DCH) has been scarcely reported in the pediatric stroke population, and its indication remains controversial, while it could be a potential lifesaving option. Methods and results We performed an extensive literature review on pediatric malignant arterial ischemic stroke (pmAIS) and selected 26 articles reporting 97 cases. Gathering the data together, a 67% mortality rate is observed without decompressive therapy, contrasting with a 95.4% survival rate with it. The median modified Rankin score (mRS) is 2.1 after surgery with a mean follow-up of 31.8 months. For the 33% of children who survived without surgery, the mRS is 3 at a mean follow-up of 19 months. As an illustrative case, we report on a 2-year-old girl who presented a cardioembolic right middle cerebral artery stroke with subsequent malignant edema and ongoing cerebral transtentorial herniation in the course of a severe myocarditis requiring ECMO support. A DCH was done 32 h after symptom onset. At the age of 5 years, she exhibits an mRS of 3. Conclusion Pediatric stroke with malignant edema is a severe condition with high mortality rate if left untreated and often long-lasting consequences. DCH might minimize the vicious circle of cerebral swelling, increasing intracranial pressure and brain ischemia. Our literature review underscores DCH as an efficient therapeutic measure management of pmAIS even when performed after a significant delay; however, long-lasting morbidities remain high.