Combat casualty care has made significant advances in recent years, including administration of blood products in far-forward locations. However, recent studies have shown blood transfusion to be a significant risk factor for infection and increased resource utilization in critically injured patients. We therefore sought to investigate the incidence of blood transfusion and its association with infection and resource utilization in combat casualties. Prospective data were collected and retrospectively reviewed on 210 critically injured patients admitted to the USNS Comfort over a 7-week period during the 2003 assault phase of Operation Iraqi Freedom. Patients were stratified by age, gender, and injury severity score (ISS). Multivariate regression analyses were used to assess blood transfusion and hematocrit (HCT) as independent risk factors for infection and intensive care unit (ICU) admission controlling for age, gender, and ISS. The study cohort had a mean age of 30 ± 2 years, a mean ISS of 14 ± 3, 84 per cent were male, and 88 per cent sustained penetrating trauma. Blood transfusion was required in 44 per cent (n = 93) of the study cohort. Transfused patients had a higher ISS (18 ± 4 vs. 10 ± 3, P < 0.01), a higher pulse rate (105 ± 4 vs. 93 ± 3, P < 0.0001), and a lower admission HCT (27 ± 1 vs. 33 ± 2, P < 0.0001) compared with patients not transfused. Patients receiving blood transfusion had an increased infection rate (69% vs. 18%, P < 0.0001), ICU admission rate (52% vs. 21%, P < 0.0001), and ICU length of stay (6.7 ± 2.1 days vs. 1.4 ± 0.5 days, P < 0.0001) compared with nontransfused patients. However, there was no significant difference in mortality between transfused and nontransfused patients. Multivariate binomial regression analysis identified blood transfusion and HCT as independent risk factors for infection (P < 0.01) and blood transfusion as an independent risk factor for ICU admission (P < 0.05). Combat casualties have a high incidence of blood transfusion. Blood transfusion is an independent risk factor for infection and increased resource utilization. Therefore, consideration should be given to the use of alternative blood substitutes and recombinant human erythropoietin in the treatment and management of combat casualties.

What exactly is untology? And why is it important for thinking about teaching effectively? In this article I argue that the most exciting opportunities for pursuing real change in pedagogical practices can be seen in the work of Jacques Rancière, especially in his controversial book The Ignorant Schoolmaster and (as this article traces) in his short essay “What Does It Mean to Be Un?” I argue that what is needed in educators today is an egalitarian aptitude for openness and what I am calling unlearning. Furthermore, through a close reading of Charles Baxter's short story “Gryphon,” I claim that the best teachers today are unqualified to teach. Thinking about qualification, as the current neoliberal regime would have us think about it—as a bankable phenomenon—misses the promise of education as a process of unlearning, unknowing and unbecoming. Education is untology.

BackgroundImmune checkpoint inhibitors (ICIs) are being investigated for their role as an adjunct in the multimodal treatment of oesophageal adenocarcinoma (OAC). The most appropriate time to incorporate ICIs remains unknown. Our study profiles systemic anti-tumour immunity perioperatively to help inform the optimal timing of ICIs into current standards of care for OAC patients.MethodsSystemic immunity in 11 OAC patients was phenotyped prior to oesophagectomy and on post-operative days (POD) 0, 1, 3, 7 and week 6 using flow cytometry. Longitudinal serological profiling was conducted by 54-plex-ELISA. The frequency of circulating lymphocytes, T cells, T helper cells and cytotoxic T lymphocytes was profiled longitudinally. The activation status of T cells was also assessed using CD69, CD27, CD62L and CD45RA as well as the proportion of T cell subsets in circulation, which included: naïve, central memory, effector memory and terminally differentiated effector memory T cells. This study also profiled the longitudinal alteration of immune checkpoint expression on circulating T cells, which included: PD-1, CTLA-4, TIGIT, TIM-3, LAG-3, PD-L1 and PD-L2. Damage-associated molecular patterns (calreticulin, HMGB1 and MIC-A/B) were also assessed.ResultsThe frequency of naïve T cells increased in circulation post-oesophagectomy from POD-0 to POD-7 (p<0.01) but returned to baseline at week 6. Effector memory T cells had decreased by POD7 but increased substantially by week 6 (p<0.05). A steady increase in activated circulating CD27+ T cells was observed from POD-0 to POD-7 (p<0.05). The percentage of PD-1+ and CTLA-4+ T cells peaked on POD-1 and was substantially decreased by week 6 (p<0.01). Th1 cytokines were decreased in the immediate post-operative setting with a reduction in IFN-Y, IL-12p40, CD28, CD40L and TNF Alpha. In addition to this IP-10 aka cxcl-10 which is an important chemokine ligand in recruiting anti-tumour TH1 cells and polarising the immune response to a Th1 phenotype is significantly reduced perioperatively. There is a simultaneous increase in Th2 cytokines in the immediate post-operative setting with a significant increase in IL4, IL10, IL16, IL1RA and MCP1 before returning to preoperative levels at week 6.ConclusionOur study highlights the prevailing immunophenotype and responses to surgery with a switch in balance towards a Th2 and potentially M2 phenotype and consequently, an immunosuppressive milieu. Therefore, orchestrating M2 reprogramming toward an M1 phenotype and similarly shifting the balance in favour of a Th1 phenotype would offer a potent therapeutic approach for augmenting tumourigenesis and promoting cancer regression. Consequently, this study paves the way for further studies and appropriate trial design are needed to interrogate the use of ICB as a trimodal approach with chemoradiotherapy and chemotherapy alone for locally advanced disease in the neoadjuvant and adjuvant setting to determine the optimal timing and subset of patients for their use in the era of precision targeted therapies.Disclosure InformationN.E. Donlon: None. M. Davern: None. A. Sheppard: None. F. O’Connell: None. S. Ramjit: None. C. Hayes: None. M. Mc Clean: None. H. Temperley: None. C. Butler: None. N. Ravi: None. C. Donohoe: None. J. O’ Sullivan: None. M.R. Dunne: None. J.V. Reynolds: None. J. Lysaght: None.