Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV.
...We conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity.
Overall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay.
Our findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings.
PROSPERO CRD42019154761.
RAS mutations are frequently observed in childhood B‐cell acute lymphoblastic leukemia (B‐ALL) and previous studies have yielded conflicting results as to whether they are associated with a poor ...outcome. We and others have demonstrated that the mitogen‐activated protein kinase–extracellular signal‐regulated kinase (MAPK) pathway can be activated through epigenetic mechanisms in the absence of RAS pathway mutations. Herein, we examined whether MAPK activation, as determined by measuring phosphorylated extracellular signal‐regulated kinase (pERK) levels in 80 diagnostic patient samples using phosphoflow cytometry, could be used as a prognostic biomarker for pediatric B‐ALL. The mean fluorescence intensity of pERK (MFI) was measured at baseline and after exogenous stimulation with or without pretreatment with the mitogen‐activated protein kinase kinase (MEK) inhibitor trametinib. Activation levels (MFI stimulated/MFI baseline) ranged from 0.76 to 4.40 (median = 1.26), and inhibition indexes (MFI stimulated/MFI trametinib stimulated) ranged from 0.439 to 5.640 (median = 1.30), with no significant difference between patients with wildtype versus mutant RAS for either. Logistic regression demonstrated that neither MAPK activation levels nor RAS mutation status at diagnosis alone or in combination was prognostic of outcome. However, 35% of RAS wildtype samples showed MAPK inhibition indexes greater than the median, thus raising the possibility that therapeutic strategies to inhibit MAPK activation may not be restricted to patients whose blasts display Ras pathway defects.
Summary
Over 50% of patients with systemic LCH are not cured with front‐line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with ...clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAFV600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long‐term efficacy, late toxicities, relative cost and patient‐reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.
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