Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered

Seagrass collapse due to synergistic stressors is not anticipated by phenological changes

Seagrasses are globally declining and often their loss is due to synergies among stressors. We investigated the interactive effects of eutrophication and burial on the Mediterranean seagrass, Posidonia oceanica. A field experiment was conducted to estimate whether shoot survival depends on the interactive effects of three levels of intensity of both stressors and to identify early changes in plants (i.e., morphological, physiological and biochemical, and expression of stress-related genes) that may serve to detect signals of imminent shoot density collapse. Sediment burial and nutrient enrichment produced interactive effects on P. oceanica shoot survival, as high nutrient levels had the potential to accelerate the regression of the seagrass exposed to high burial (HB). After 11 weeks, HB in combination with either high or medium nutrient enrichment caused a shoot loss of about 60%. Changes in morphology were poor predictors of the seagrass decline. Likewise, few biochemical variables were associated with P. oceanica survival (the phenolics, ORAC and leaf δ34S). In contrast, the expression of target genes had the highest correlation with plant survival: photosynthetic genes (ATPa, psbD and psbA) were up-regulated in response to high burial, while carbon metabolism genes (CA-chl, PGK and GADPH) were down-regulated. Therefore, die-offs due to high sedimentation rate in eutrophic areas can only be anticipated by altered expression of stress-related genes that may warn the imminent seagrass collapse. Management of local stressors, such as nutrient pollution, may enhance seagrass resilience in the face of the intensification of extreme climate events, such as floods

Human CD133+ progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis and activation of Wnt signaling

We evaluated the healing potential of human fetal aorta–derived CD133(+) progenitor cells and their conditioned medium (CD133(+) CCM) in a new model of ischemic diabetic ulcer. Streptozotocin-induced diabetic mice underwent bilateral limb ischemia and wounding. One wound was covered with collagen containing 2×10(4) CD133(+) or CD133(−) cells or vehicle. The contralateral wound, covered with only collagen, served as control. Fetal CD133(+) cells expressed high levels of wingless (Wnt) genes, which were downregulated following differentiation into CD133(−) cells along with upregulation of Wnt antagonists secreted frizzled-related protein (sFRP)-1, -3, and -4. CD133(+) cells accelerated wound closure as compared with CD133(−) or vehicle and promoted angiogenesis through stimulation of endothelial cell proliferation, migration, and survival by paracrine effects. CD133(+) cells secreted high levels of vascular endothelial growth factor (VEGF)-A and interleukin (IL)-8. Consistently, CD133(+) CCM accelerated wound closure and reparative angiogenesis, with this action abrogated by coadministering the Wnt antagonist sFRP-1 or neutralizing antibodies against VEGF-A or IL-8. In vitro, these effects were recapitulated following exposure of high-glucose-primed human umbilical vein endothelial cells to CD133(+) CCM, resulting in stimulation of migration, angiogenesis-like network formation and induction of Wnt expression. The promigratory and proangiogenic effect of CD133(+) CCM was blunted by sFRP-1, as well as antibodies against VEGF-A or IL-8. CD133(+) cells stimulate wound healing by paracrine mechanisms that activate Wnt signaling pathway in recipients. These preclinical findings open new perspectives for the cure of diabetic ulcers

Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

Background: The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC. Results: In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity in vitro. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone. Conclusion: Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both in vitro and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib. \ua9 2012 Cavazzoni et al.; licensee BioMed Central Ltd

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p < 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p < 0.001). Viral coinfections, underlying clinical conditions, age 5-9 years and lymphopenia were statistically related to ICU admission (p < 0.05). Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission