B I R T H T R A U M A F R O M T H E P E R S P E C T I V E O F P E R I N A T A L C O U N S E L L O R S : A M I N I F O C U S G R O U P S T U D Y

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Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway.

The CXCR4 receptor (Chemokine C-X-C motif receptor 4) is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). The CXCR4 ligand (CXCL12) stimulates CXCR4 promoting cell survival and proliferation, and may contribute to the tropism of leukemia cells towards lymphoid tissues. Therefore, strategies targeting CXCR4 may constitute an effective therapeutic approach for CLL. To address that question, we studied the effect of Ulocuplumab (BMS-936564), a fully human IgG4 anti-CXCR4 antibody, using a stroma--CLL cells co-culture model. We found that Ulocuplumab (BMS-936564) inhibited CXCL12 mediated CXCR4 activation-migration of CLL cells at nanomolar concentrations. This effect was comparable to AMD3100 (Plerixafor--Mozobil), a small molecule CXCR4 inhibitor. However, Ulocuplumab (BMS-936564) but not AMD3100 induced apoptosis in CLL at nanomolar concentrations in the presence or absence of stromal cell support. This pro-apoptotic effect was independent of CLL high-risk prognostic markers, was associated with production of reactive oxygen species and did not require caspase activation. Overall, these findings are evidence that Ulocuplumab (BMS-936564) has biological activity in CLL, highlight the relevance of the CXCR4-CXCL12 pathway as a therapeutic target in CLL, and provide biological rationale for ongoing clinical trials in CLL and other hematological malignancies

Burden and severity of children's hospitalizations by respiratory syncytial virus in Portugal, 2015-2018

Background Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children and is of considerable burden on healthcare systems. Our study aimed to evaluate ALRI hospitalizations related to RSV in children in Portugal. Methods We reviewed hospitalizations potentially related to RSV in children aged <5 years from 2015 to 2018, using anonymized administrative data covering all public hospital discharges in mainland Portugal. Three case definitions were considered: (a) RSV-specific, (b) (a) plus unspecified acute bronchiolitis (RSV-specific & Bronchiolitis), and (c) (b) plus unspecified ALRI (RSV-specific & ALRI). Results A total of 9697 RSV-specific hospitalizations were identified from 2015 to 2018—increasing to 26 062 for RSV-specific & ALRI hospitalizations—of which 74.7% were during seasons 2015/2016–2017/2018 (November–March). Mean hospitalization rates per season were, for RSV-specific, RSV-specific & Bronchiolitis, and RSV-specific & ALRI, respectively, 5.6, 9.4, and 11.8 per 1000 children aged <5 years and 13.4, 22.5, and 25.9 in children aged <2 years. Most RSV-specific hospitalizations occurred in healthy children (94.9%) and in children aged <2 years (96.3%). Annual direct costs of €2.4 million were estimated for RSV-specific hospitalizations—rising to €5.1 million for RSV-specific & ALRI—mostly driven by healthy children (87.6%). Conclusion RSV is accountable for a substantial number of hospitalizations in children, especially during their first year of life. Hospitalizations are mainly driven by healthy children. The variability of the potential RSV burden across case definitions highlights the need for a universal RSV surveillance system to guide prevention strategies

Turbidez atmosférica: resultados preliminares para Tucuruí (PA) e questões ligadas a sua avaliação.

Este estudo apresenta resultados preliminares sobre turbidez atmosférica - grau de atenuação da radiação solar por material particulado em suspensão - em Tucuruí, Pará

Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohort

Background: Pathological brain iron deposition has been implicated as a source of neurotoxic reactive oxygen species in Alzheimer (AD) and Parkinson diseases (PD). Iron metabolism is associated with the gene hemochromatosis (HFE Human genome nomenclature committee ID: 4886), and mutations in HFE are a cause of the iron mismetabolism disease, hemochromatosis. Several reports have tested the association of HFE variants with neurodegenerative diseases, such as AD and PD with conflicting results.Methods: Genotypes were analysed for the two most common variants of HFE in a series of 130 AD, 55 Mild Cognitive Impairment (MCI) and 132 PD patients. Additionally, a series of 115 healthy age-matched controls was also screened.Results: A statistically significant association was found in the PD group when compared to controls, showing that the presence of the C282Y variant allele may confer higher risk for developing the disease.Conclusion: Taken together these results suggest that the common variants in HFE may be a risk factor for PD, but not for AD in the Portuguese population

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care