Association of red blood cells and plasma transfusion versus red blood cell transfusion only with survival for treatment of major traumatic hemorrhage in prehospital setting in England: a multicenter study.

BACKGROUND: In-hospital acute resuscitation in trauma has evolved toward early and balanced transfusion resuscitation with red blood cells (RBC) and plasma being transfused in equal ratios. Being able to deliver this ratio in prehospital environments is a challenge. A combined component, like leukocyte-depleted red cell and plasma (RCP), could facilitate early prehospital resuscitation with RBC and plasma, while at the same time improving logistics for the team. However, there is limited evidence on the clinical benefits of RCP. OBJECTIVE: To compare prehospital transfusion of combined RCP versus RBC alone or RBC and plasma separately (RBC + P) on mortality in trauma bleeding patients. METHODS: Data were collected prospectively on patients who received prehospital transfusion (RBC + thawed plasma/Lyoplas or RCP) for traumatic hemorrhage from six prehospital services in England (2018-2020). Retrospective data on patients who transfused RBC from 2015 to 2018 were included for comparison. The association between transfusion arms and 24-h and 30-day mortality, adjusting for age, injury mechanism, age, prehospital heart rate and blood pressure, was evaluated using generalized estimating equations. RESULTS: Out of 970 recruited patients, 909 fulfilled the study criteria (RBC + P = 391, RCP = 295, RBC = 223). RBC + P patients were older (mean age 42 vs 35 years for RCP and RBC), and 80% had a blunt injury (RCP = 52%, RBC = 56%). RCP and RBC + P were associated with lower odds of death at 24-h, compared to RBC alone (adjusted odds ratio [aOR] 0.69 [95%CI: 0.52; 0.92] and 0.60 [95%CI: 0.32; 1.13], respectively). The lower odds of death for RBC + P and RCP vs RBC were driven by penetrating injury (aOR 0.22 [95%CI: 0.10; 0.53] and 0.39 [95%CI: 0.20; 0.76], respectively). There was no association between RCP or RBC + P with 30-day survival vs RBC. CONCLUSION: Prehospital plasma transfusion for penetrating injury was associated with lower odds of death at 24-h compared to RBC alone. Large trials are needed to confirm these findings.

Exertional heat illness in half marathon runners: experiences of the Great North Run.

Exertional heat illness is a potentially fatal condition. Large numbers of competitors in the Great North Run are affected annually. This article briefly discusses the patient demographics, presentation and treatment of large numbers of patients with a simple, effective regime.

The Y deletion gr/gr and susceptibility to testicular germ cell tumor.

Testicular germ cell tumor (TGCT) is the most common cancer in young men. Despite a considerable familial component to TGCT risk, no genetic change that confers increased risk has been substantiated to date. The human Y chromosome carries a number of genes specifically involved in male germ cell development, and deletion of the AZFc region at Yq11 is the most common known genetic cause of infertility. Recently, a 1.6-Mb deletion of the Y chromosome that removes part of the AZFc region--known as the "gr/gr" deletion--has been associated with infertility. In epidemiological studies, male infertility has shown an association with TGCT that is out of proportion with what can be explained by tumor effects. Thus, we hypothesized that the gr/gr deletion may be associated with TGCT. Using logistic modeling, we analyzed this deletion in a large series of TGCT cases with and without a family history of TGCT. The gr/gr deletion was present in 3.0% (13/431) of TGCT cases with a family history, 2% (28/1,376) of TGCT cases without a family history, and 1.3% (33/2,599) of unaffected males. Presence of the gr/gr deletion was associated with a twofold increased risk of TGCT (adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI] 1.3-3.6; P = .005) and a threefold increased risk of TGCT among patients with a positive family history (aOR 3.2; 95% CI 1.5-6.7; P = .0027). The gr/gr deletion was more strongly associated with seminoma (aOR 3.0; 95% CI 1.6-5.4; P = .0004) than with nonseminoma TGCT (aOR 1.5; 95% CI 0.72-3.0; P = .29). These data indicate that the Y microdeletion gr/gr is a rare, low-penetrance allele that confers susceptibility to TGCT.

Mutations of the BRAF gene in human cancer.

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma.