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  • 1
    In: Trauma Surgery & Acute Care Open, BMJ, Vol. 8, No. 1 ( 2023-05), p. e001014-
    Abstract: In 2020, firearm injuries surpassed automobile collisions as the leading cause of death in US children. Annual automobile fatalities have decreased during 40 years through a multipronged approach. To develop similarly targeted public health interventions to reduce firearm fatalities, there is a critical need to first characterize firearm injuries and their outcomes at a granular level. We sought to compare firearm injuries, outcomes, and types of shooters at trauma centers in four pediatric health systems across the USA. Methods We retrospectively extracted data from each institution’s trauma registry, paper and electronic health records. Study included all patients less than 19 years of age with a firearm injury between 2003 and 2018. Variables collected included demographics, intent, resources used, and emergency department and hospital disposition. Descriptive statistics were reported using medians and IQRs for continuous data and counts with percentages for categorical data. χ 2 test or Fisher’s exact test was conducted for categorical comparisons. Results Our cohort (n=1008, median age 14 years) was predominantly black and male. During the study period, there was an overall increase in firearm injuries, driven primarily by increases in the South (S) site (β=0.11 (SE 0.02), p= 〈 0.001) in the setting of stable rates in the West and decreasing rates in the Northeast and Mid-Atlantic sites (β=−0.15 (SE 0.04), p=0.002; β=−0.19 (SE0.04), p=0.001). Child age, race, insurance type, resource use, injury type, and shooter type all varied by regional site. Conclusion The incidence of firearm-related injuries seen at four sites during 15 years varied by site and region. The overall increase in firearm injuries was predominantly driven by the S site, where injuries were more often unintentional. This highlights the need for region-specific data to allow for the development of targeted interventions to impact the burden of injury. Level of Evidence: II, retrospective study
    Type of Medium: Online Resource
    ISSN: 2397-5776
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2856913-1
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  • 2
    In: Gut, BMJ, Vol. 71, No. 7 ( 2022-07), p. 1386-1398
    Abstract: Intrahepatic cholangiocarcinoma (iCCA) is rising in incidence, and at present, there are limited effective systemic therapies. iCCA tumours are infiltrated by stromal cells, with high prevalence of suppressive myeloid populations including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Here, we show that tumour-derived granulocyte–macrophage colony-stimulating factor (GM-CSF) and the host bone marrow is central for monopoiesis and potentiation of TAMs, and abrogation of this signalling axis facilitates antitumour immunity in a novel model of iCCA. Methods Blood and tumours were analysed from iCCA patients and controls. Treatment and correlative studies were performed in mice with autochthonous and established orthotopic iCCA tumours treated with anti-GM-CSF monoclonal antibody. Results Systemic elevation in circulating myeloid cells correlates with poor prognosis in patients with iCCA, and patients who undergo resection have a worse overall survival if tumours are more infiltrated with CD68 + TAMs. Mice with spontaneous iCCA demonstrate significant elevation of monocytic myeloid cells in the tumour microenvironment and immune compartments, and tumours overexpress GM-CSF. Blockade of GM-CSF with a monoclonal antibody decreased tumour growth and spread. Mice bearing orthotopic tumours treated with anti-GM-CSF demonstrate repolarisation of immunosuppressive TAMs and MDSCs, facilitating T cell response and tumour regression. GM-CSF blockade dampened inflammatory gene networks in tumours and TAMs. Human tumours with decreased GM-CSF expression exhibit improved overall survival after resection. Conclusions iCCA uses the GM-CSF-bone marrow axis to establish an immunosuppressive tumour microenvironment. Blockade of the GM-CSF axis promotes antitumour T cell immunity.
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
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    Language: English
    Publisher: BMJ
    Publication Date: 2022
    detail.hit.zdb_id: 1492637-4
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