Innovative blood transfusion strategies to address global blood deserts: a consensus statement from the Blood Delivery via Emerging Strategies for Emergency Remote Transfusion (Blood DESERT) Coalition.

In rural settings worldwide, many people live in effective blood deserts without access to any blood transfusion. The traditional system of blood banking is logistically complex and expensive for many resource-restricted settings and demands innovative and multidisciplinary solutions. 17 international experts in medicine, industry, and policy participated in an exploratory process with a 2-day hybrid seminar centred on three promising innovative strategies for blood transfusions in blood deserts: civilian walking blood banks, intraoperative autotransfusion, and drone-based blood delivery. Participant working groups conducted literature reviews and interviews to develop three white papers focused on the current state and knowledge gaps of each innovation. Seminar discussion focused on defining blood deserts and developing innovation-specific implementation agendas with key research and policy priorities for future work. Moving forward, advocates should prioritise the identification of blood deserts and address the context-specific challenges for these innovations to alleviate the ongoing crisis in blood deserts.

Predictors of Pneumonitis After Conventionally Fractionated Radiotherapy for Locally Advanced Lung Cancer.

PURPOSE: Multiple factors influence the risk of developing pneumonitis after radiation therapy (RT) for lung cancer, but few resources exist to guide clinicians in predicting risk in an individual patient treated with modern techniques. We analyzed toxicity data from a state-wide consortium to develop an integrated pneumonitis risk model. METHODS AND MATERIALS: All patients (N = 1302) received conventionally fractionated RT for stage II-III non-small cell lung cancer between April 2012 and July 2019. Pneumonitis occurring within 6 months of treatment was graded by local practitioners and collected prospectively from 27 academic and community clinics participating in a state-wide quality consortium. Pneumonitis was modeled as either grade ≥2 (G2+) or grade ≥3 (G3+). Logistic regression models were fit to quantify univariable associations with dose and clinical factors, and stepwise Akaike information criterion-based modeling was used to build multivariable prediction models. RESULTS: The overall rate of pneumonitis of any grade in the 6 months following RT was 16% (208 cases). Seven percent of cases (n = 94) were G2+ and <1% (n = 11) were G3+. Adjusting for incomplete follow-up, estimated rates for G2+ and G3+ were 14% and 2%, respectively. In univariate analyses, gEUD, V5, V10, V20, V30, and mean lung dose (MLD) were positively associated with G2+ pneumonitis risk, whereas current smoking status was associated with lower odds of pneumonitis. G2+ pneumonitis risk of ≥22% was independently predicted by MLD of ≥20 Gy, V20 of ≥35%, and V5 of ≥75%. In multivariate analyses, the lung V5 metric remained a significant predictor of G2+ pneumonitis, even when controlling for MLD, despite their close correlation. For G3+ pneumonitis, MLD and V20 were statistically significant predictors. Number of patient comorbidities was an independent predictor of G3+, but not G2+ pneumonitis. CONCLUSIONS: We present an analysis of pneumonitis risk after definitive RT for lung cancer using a large, prospective dataset. We incorporate comorbidity burden, smoking status, and dosimetric parameters in an integrated risk model. These data may guide clinicians in assessing pneumonitis risk in individual patients.

Toll-Like Receptor-9 (TLR9) is Requisite for Acute Inflammatory Response and Injury Following Lung Contusion.

Lung contusion (LC) is a significant risk factor for the development of acute respiratory distress syndrome. Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs, which are prevalent in microbial but not vertebrate genomic DNA, leading to innate and acquired immune responses. TLR9 signaling has recently been implicated as a critical component of the inflammatory response following lung injury. The aim of the present study was to evaluate the contribution of TLR9 signaling to the acute physiologic changes following LC. Nonlethal unilateral closed-chest LC was induced in TLR9 (-/-) and wild-type (WT) mice. The mice were sacrificed at 5, 24, 48, and 72-h time points. The extent of injury was assessed by measuring bronchoalveolar lavage, cells (cytospin), albumin (permeability injury), and cytokines (inflammation). Following LC, only the TLR9 (-/-) mice showed significant reductions in the levels of albumin; release of pro-inflammatory cytokines IL-1ß, IL-6, and Keratinocyte chemoattractant; production of macrophage chemoattractant protein 5; and recruitment of alveolar macrophages and neutrophil infiltration. Histological evaluation demonstrated significantly worse injury at all-time points for WT mice. Macrophages, isolated from TLR9 (-/-) mice, exhibited increased phagocytic activity at 24 h after LC compared with those isolated from WT mice. TLR9, therefore, appears to be functionally important in the development of progressive lung injury and inflammation following LC. Our findings provide a new framework for understanding the pathogenesis of lung injury and suggest blockade of TLR9 as a new therapeutic strategy for the treatment of LC-induced lung injury.