Innate-Like Lymphocytes Are Immediate Participants in the Hyper-Acute Immune Response to Trauma and Hemorrhagic Shock.

Adverse outcomes following severe traumatic injury are frequently attributed to a state of immunological dysfunction acquired during treatment and recovery. Recent genomic evidence however, suggests that the trajectory toward development of multiple organ dysfunction syndrome (MODS) is already in play at admission (<2 h following injury). Improved understanding of the molecular events during the hyper-acute immunological response to trauma, <2 h following injury, may reveal opportunities to ameliorate organ injury and expedite recovery. Lymphocytes have not previously been considered key participants in this early response; however, two observations in human trauma patients namely, raised populations of circulating NKT and NK cells during the hyper-acute phase and persistent lymphopenia beyond 48 h show association with the development of MODS during recovery. These highlight the need for greater understanding of lymphocyte function in the hyper-acute phase of inflammation. An exploratory study was therefore conducted in a well-established murine model of trauma and hemorrhagic shock (T&HS) to investigate (1) the development of lymphopenia in the murine model and (2) the phenotypic and functional changes of three innate-like lymphocyte subsets, NK1.1+ CD3-, NK1.1+ CD3+, γδTCR+ CD3+ cells, focusing on the first 6 h following injury. Rapid changes in phenotype and function were demonstrated in these cells within blood and spleen, but responses in lung tissue lagged behind. This study describes the immediacy of the innate-like lymphocyte response to trauma in different body compartments and considers new lines for further investigation to develop our understanding of MODS pathogenesis.

Correction: Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1002352.].

Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage.

Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr), at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. CONCLUSIONS: We have shown that the release of mtDNA is sufficient for the development of multiple organ injury. MtDNA concentrations likely peak at different points in the early postinjury phase dependent on the degree of isolated trauma vs combined trauma and hemorrhagic shock. HDMBr scavenging of circulating mtDNA (and nuclear DNA, nDNA) is associated with rescue from severe multiple organ injury in the animal model. This suggests that HDMBr could have utility in rescue from human trauma-induced MODS.

Signatures of inflammation and impending multiple organ dysfunction in the hyperacute phase of trauma: A prospective cohort study.

BACKGROUND: Severe trauma induces a widespread response of the immune system. This "genomic storm" can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS. METHODS AND FINDINGS: We performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses. In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts. CONCLUSIONS: In this study, we showed how the hyperacute postinjury time window contained a focused, specific signature of the response to critical injury that led to widespread genomic activation. A transcriptomic signature for later development of MODS was present in this hyperacute window; it showed a strong signal for cell death and survival pathways and implicated NK cells and neutrophil populations in this differential response.

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1+ cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1+ cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1+ cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1+ cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut.

Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients.

BACKGROUND: Early survival following severe injury has been improved with refined resuscitation strategies. Multiple organ dysfunction syndrome (MODS) is common among this fragile group of patients leading to prolonged hospital stay and late mortality. MODS after trauma is widely attributed to dysregulated inflammation but the precise mechanics of this response and its influence on organ injury are incompletely understood. This study was conducted to investigate the relationship between early lymphocyte responses and the development of MODS during admission. METHODS: During a 24-month period, trauma patients were recruited from an urban major trauma centre to an ongoing, observational cohort study. Admission blood samples were obtained within 2 h of injury and before in-hospital intervention, including blood transfusion. The study population was predominantly male with a blunt mechanism of injury. Lymphocyte subset populations including T helper, cytotoxic T cells, NK cells and γδ T cells were identified using flow cytometry. Early cytokine release and lymphocyte count during the first 7 days of admission were also examined. RESULTS: This study demonstrated that trauma patients who developed MODS had an increased population of NK dim cells (MODS vs no MODS: 22 % vs 13 %, p < 0.01) and reduced γδ-low T cells (MODS vs no MODS: 0.02 (0.01-0.03) vs 0.09 (0.06-0.12) × 10^9/L, p < 0.01) at admission. Critically injured patients who developed MODS (n = 27) had higher interferon gamma (IFN-γ) concentrations at admission, compared with patients of matched injury severity and shock (n = 60) who did not develop MODS (MODS vs no MODS: 4.1 (1.8-9.0) vs 1.0 (0.6-1.8) pg/ml, p = 0.01). Lymphopenia was observed within 24 h of injury and was persistent in those who developed MODS. Patients with a lymphocyte count of 0.5 × 10(9)/L or less at 48 h, had a 45 % mortality rate. CONCLUSIONS: This study provides evidence of lymphocyte activation within 2 h of injury, as demonstrated by increased NK dim cells, reduced γδ-low T lymphocytes and high blood IFN-γ concentration. These changes are associated with the development of MODS and lymphopenia. The study reveals new opportunities for investigation to characterise the cellular response to trauma and examine its influence on recovery.

What helps or hinders the transformation from a major tertiary center to a major trauma center? Identifying barriers and enablers using the Theoretical Domains Framework.

BACKGROUND: Major Trauma Centers (MTCs), as part of a trauma system, improve survival and functional outcomes from injury. Developing such centers from current teaching hospitals is likely to generate diverse beliefs amongst staff. These may act as barriers or enablers. Prior identification of these may make the service development process more efficient. The importance of applying theory to systematically identify barriers and enablers to changing clinical practice in emergency medicine has been emphasized. This study systematically explored theory-based barriers and enablers towards implementing the transformation of a tertiary hospital into a MTC. Our goal was to demonstrate the use of a replicable method to identify targets that could be addressed to achieve a successful transformation from an organization evolved to provide a particular type of clinical care into a clinical system with different demands, requirements and expectations. METHODS: The Theoretical Domains Framework (TDF) is a tool designed to elicit and analyze beliefs affecting behavior. Semi-structured interviews based around the TDF were conducted in a major tertiary hospital in Scotland due to become a MTC with a purposive sample of major stakeholders including clinicians and nurses from specialties involved in trauma care, clinical managers and administration. Belief statements were identified through qualitative analysis, and assessed for importance according to prevalence, discordance and evidence base. RESULTS AND DISCUSSION: 1728 utterances were recorded and coded into 91 belief statements. 58 were classified as important barriers/enablers. There were major concerns about resource demands, with optimism conditional on these being met. Distracting priorities abound within the Emergency Department. Better communication is needed. Staff motivation is high and they should be engaged in skills development and developing performance improvement processes. CONCLUSIONS: This study presents a systematic and replicable method of identifying theory-based barriers and enablers towards complex service development. It identifies multiple barriers/enablers that may serve as a basis for developing an implementation intervention to enhance the development of MTCs. This method can be used to address similar challenges in developing specialist centers or implementing clinical practice change in emergency care across both developing and developed countries.

Paediatric laparoscopic hernia repair: Ex vivo skills in the reduced training era.

INTRODUCTION: Changes to surgical working hours have resulted in shorter training times and fewer learning opportunities. Tools that develop surgical skills ex-vivo are of particular interest in this era. Laparoscopic skills are regarded as essential by many for modern paediatric surgery practice. Several generic skills models have been reported and validated. However, there is limited evidence regarding the role of procedure specific models. Here, a laparoscopic paediatric hernia repair model is trialled with surgical trainees and their competence compared with consultant colleagues. PATIENTS AND METHODS: An ex-vivo paediatric inguinal hernia repair model was devised. Surgical trainees from 5 specialist centres were recruited and performed multiple standardised repairs. RESULTS: 23 trainees performed 192 repairs. Experts performed 10 repairs for comparison. Trainees were timed performing the repair and their accuracy measured. With repeated attempts trainee's timings and accuracy improved until by the 10 th repair they were no different from benchmark consultant scores. CONCLUSION: A simple, procedure specific ex-vivo training model has been evaluated for laparoscopic hernia training in paediatric surgery. The results suggest improvements in competence with repetition. Trainee and benchmark consultant scores are no different by the 10 th trainee attempt. We conclude that this model may have a valuable role in the training and assessment of future paediatric surgeons.

Trauma-induced secondary cardiac injury is associated with hyperacute elevations in inflammatory cytokines.

INTRODUCTION: Clinical evidence supports the existence of a trauma-induced secondary cardiac injury. Experimental research suggests inflammation as a possible mechanism. The study aimed to determine if there was an early association between inflammation and secondary cardiac injury in trauma patients. METHODS: A cohort study of critically injured patients between January 2008 and January 2010 was undertaken. Levels of the cardiac biomarkers troponin I and heart-specific fatty acid-binding protein and the cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1ß, and IL-8 were measured on admission to hospital, and again at 24 and 72 h. Participants were reviewed for adverse cardiac events (ACEs) and in-hospital mortality. RESULTS: Of 135 patients recruited, 18 (13%) had an ACE. Patients with ACEs had higher admission plasma levels of TNF-α (5.4 vs. 3.8 pg/mL; P = 0.03), IL-6 (140 vs. 58.9 pg/mL, P = 0.009), and IL-8 (19.3 vs. 9.1 pg/mL, P = 0.03) compared with those without events. Hour 24 cytokines were not associated with events, but IL-8 (14.5 vs. 5.8 pg/mL; P = 0.01) and IL-1ß (0.55 vs. 0.19 pg/mL; P = 0.04) were higher in patients with ACEs at 72 hours. Admission IL-6 was independently associated with heart-specific fatty acid-binding protein increase (P < 0.05). Patients who presented with an elevated troponin I combined with either an elevated TNF-α (relative risk [RR], 11.0; 95% confidence interval [CI], 1.8-66.9; P = 0.015), elevated IL-6 (RR, 17.3; 95% CI, 2.9-101.4; P = 0.001), or elevated IL-8 (RR, 15.0; 95% CI, 3.1-72.9; P = 0.008) were at the highest risk of in-hospital death when compared with individuals with normal biomarker and cytokine values. CONCLUSIONS: There is an association between hyperacute elevations in inflammatory cytokines with cardiac injury and ACEs in critically injured patients. Biomarker evidence of cardiac injury and inflammation on admission is associated with a higher risk of in-hospital death.

Circulating histones are mediators of trauma-associated lung injury.

RATIONALE: Acute lung injury is a common complication after severe trauma, which predisposes patients to multiple organ failure. This syndrome largely accounts for the late mortality that arises and despite many theories, the pathological mechanism is not fully understood. Discovery of histone-induced toxicity in mice presents a new dimension for elucidating the underlying pathophysiology. OBJECTIVES: To investigate the pathological roles of circulating histones in trauma-induced lung injury. METHODS: Circulating histone levels in patients with severe trauma were determined and correlated with respiratory failure and Sequential Organ Failure Assessment (SOFA) scores. Their cause-effect relationship was studied using cells and mouse models. MEASUREMENTS AND MAIN RESULTS: In a cohort of 52 patients with severe nonthoracic blunt trauma, circulating histones surged immediately after trauma to levels that were toxic to cultured endothelial cells. The high levels were significantly associated with the incidence of acute lung injury and SOFA scores, as well as markers of endothelial damage and coagulation activation. In in vitro systems, histones damaged endothelial cells, stimulated cytokine release, and induced neutrophil extracellular trap formation and myeloperoxidase release. Cellular toxicity resulted from their direct membrane interaction and resultant calcium influx. In mouse models, cytokines and markers for endothelial damage and coagulation activation significantly increased immediately after trauma or histone infusion. Pathological examinations showed that lungs were the predominantly affected organ with edema, hemorrhage, microvascular thrombosis, and neutrophil congestion. An anti-histone antibody could reduce these changes and protect mice from histone-induced lethality. CONCLUSIONS: This study elucidates a new mechanism for acute lung injury after severe trauma and proposes that circulating histones are viable therapeutic targets for improving survival outcomes in patients.

Coagulation system changes associated with susceptibility to infection in trauma patients.

BACKGROUND: Infection following trauma is associated with increased morbidity and mortality and is common following severe hemorrhage. There is a strong interaction between the coagulation and immunity. The objective of this study was to establish if there was an association between changes in coagulation status after hemorrhage and the subsequent incidence of infection. METHODS: Prospective cohort study of adult injured patients presenting to a major trauma center during a 2-year period. Blood was drawn at 24 hours following admission and analyzed using functional thromboelastography testing and laboratory defined tests of coagulation and blood count. Patients were followed up for infectious episodes while in the hospital using Center for Disease Control definitions. RESULTS: A total of 158 patients were recruited; 71 (45%) developed infection and were older (44 years vs. 32 years, p = 0.01) and more severely injured (Injury Severity Score [ISS], 25 vs.10; p < 0.01). White blood cell counts at 24 hours were normal, and there was no difference between groups (both 9.6 × 10/(9)L). Protein C was lower in those with infection (70.2 IU/dL vs. 83.3 IU/dL, p = 0.02), with a dose-dependent increase in infection as levels of protein C decreased. Plasmin activation at 24 hours was also strongly associated with infection plasmin-antiplasmin (infection vs. no infection, 6,156 µg/L vs. 3,324 µg/L, p = 0.03). The infection cohort had overall 12% lower procoagulant levels (varied between factor VIII 6.4% and factor II 16.2%). CONCLUSION: There is a strong association between the status of the coagulation system after 24 hours and the development of infection following trauma. Improved early coagulation management may decrease infection rates in this patient group. LEVEL OF EVIDENCE: Prognostic prospective study, level III.

Major trauma and urban cyclists: physiological status and injury profile.

INTRODUCTION: Pedal cycling in cities has the potential to deliver significant health and economic benefits for individuals and society. Safety is the main concern for potential cyclists although the statistical risk of death is low. Little is known about the severity of injuries sustained by city cyclists and their outcome. AIM: The aim of this study was to characterise the physiological status and injury profile of cyclists admitted to our urban major trauma centre (MTC). METHODS: Database analysis of cyclist casualties between 2004 and 2009. The physiological parameters examined were admission systolic blood pressure (SBP), admission base deficit and prehospital Glasgow Coma Scale. RESULTS: 265 cyclists required full trauma-team activation. 82% were injured during a collision with a motorised vehicle. The majority (73%) had collided with a car or a heavy goods vehicle (HGV). These casualties formed the cohort for further analysis. Cyclists who collided with an HGV were more severely injured and had a higher mortality rate. Low SBP and high base deficit indicate that haemorrhagic shock is a key feature of HGV casualties. CONCLUSION: Collision with any vehicle can result in death or serious injury to a cyclist. Injury patterns vary with the type of vehicle involved. HGVs were associated with severe injuries and death as a result of uncontrollable haemorrhage. Awareness of this injury profile may aid prehospital management and expedite transfer to MTC care. Rapid haemorrhage control may salvage some, but not all, of these casualties. The need for continued collision prevention strategies and long-term outcome data collection in trauma patients is highlighted.

Gastroschisis: a multi-centre comparison of management and outcome.

BACKGROUND: Anecdotal evidence and a handful of literature reports suggest that the outcome for infants born with gastroschisis in many African countries is poor when compared to Western nations. We wished to evaluate current management strategies and outcomes in African and Western units that treat infants with gastroschisis. PATIENTS AND METHODS: We conducted a retrospective review of case-notes for infants with gastroschisis who presented to a hospital between 1 January 2004 and 31 December 2007. There were five participating centres, divided for analysis into an African cohort (three centres) and a Western cohort (two centres). RESULTS: Fewer infants presented to a hospital with gastroschisis in the African cohort when compared to the Western cohort, particularly when the size of catchment area of each hospital was taken into account. The physiological state of the infant on presentation and management strategy varied widely between centres. Primary closure, preformed silo and surgical silo with delayed closure were all utilised in the African cohort. Use of the preformed silo and delayed abdominal wall closure was the strategy of choice in the Western cohort. The 30-day mortality was 23% and 1% respectively. This primary outcome measure varied considerably in the African cohort but was the same in the two Western units. CONCLUSIONS: Gastroschisis in the African cohort was characterised by fewer infants presenting to a hospital and a more variable outcome when compared to the Western cohort. A detailed epidemiological study to determine the incidence of gastroschisis in African countries may provide valuable information. In addition, interventions such as prompt resuscitation, safe neonatal transfer, the use of the preformed silo and parenteral nutrition could improve outcomes in infants with gastroschisis.

Functional definition and characterization of acute traumatic coagulopathy.

OBJECTIVE: To identify an appropriate diagnostic tool for the early diagnosis of acute traumatic coagulopathy and validate this modality through prediction of transfusion requirements in trauma hemorrhage. DESIGN: Prospective observational cohort study. SETTING: Level 1 trauma center. PATIENTS: Adult trauma patients who met the local criteria for full trauma team activation. Exclusion criteria included emergency department arrival >2 hrs after injury, >2000 mL of intravenous fluid before emergency department arrival, or transfer from another hospital. INTERVENTIONS: None. MEASUREMENTS: Blood was collected on arrival in the emergency department and analyzed with laboratory prothrombin time, point-of-care prothrombin time, and rotational thromboelastometry. Prothrombin time ratio was calculated and acute traumatic coagulopathy defined as laboratory prothrombin time ratio >1.2. Transfusion requirements were recorded for the first 12 hrs following admission. MAIN RESULTS: Three hundred patients were included in the study. Laboratory prothrombin time results were available at a median of 78 (62-103) mins. Point-of-care prothrombin time ratio had reduced agreement with laboratory prothrombin time ratio in patients with acute traumatic coagulopathy, with 29% false-negative results. In acute traumatic coagulopathy, the rotational thromboelastometry clot amplitude at 5 mins was diminished by 42%, and this persisted throughout clot maturation. Rotational thromboelastometry clotting time was not significantly prolonged. Clot amplitude at a 5-min threshold of ≤35 mm had a detection rate of 77% for acute traumatic coagulopathy with a false-positive rate of 13%. Patients with clot amplitude at 5 mins ≤35 mm were more likely to receive red cell (46% vs. 17%, p < .001) and plasma (37% vs. 11%, p < .001) transfusions. The clot amplitude at 5 mins could identify patients who would require massive transfusion (detection rate of 71%, vs. 43% for prothrombin time ratio >1.2, p < .001). CONCLUSIONS: In trauma hemorrhage, prothrombin time ratio is not rapidly available from the laboratory and point-of-care devices can be inaccurate. Acute traumatic coagulopathy is functionally characterized by a reduction in clot strength. With a threshold of clot amplitude at 5 mins of ≤35 mm, rotational thromboelastometry can identify acute traumatic coagulopathy at 5 mins and predict the need for massive transfusion.

Hemostatic effects of fresh frozen plasma may be maximal at red cell ratios of 1:2.

BACKGROUND: Damage control resuscitation targets acute traumatic coagulopathy with the early administration of high-dose fresh frozen plasma (FFP). FFP is administered empirically and as a ratio with the number of packed red blood cells (PRBC). There is controversy over the optimal FFP:PRBC ratio with respect to outcomes, and their hemostatic effects have not been studied. We report preliminary findings on the effects of different FFP:PRBC ratios on coagulation. METHODS: This is a prospective observational cohort study of trauma patients requiring >4 U of PRBCs. Blood was drawn before and after each 4-U PRBC interval for prothrombin time and analysis by rotational thromboelastometry. Interval change in coagulation parameters were compared with the FFP:PRBC ratio received during each interval. RESULTS: Sixty 4-U PRBC intervals from 50 patients were available for analysis. All measures of coagulation deteriorated with low FFP:PRBC ratios (<1:2). Maximal hemostatic effect was observed in the 1:2 to 3:4 group: 12% decrease in prothrombin time (p=0.006), 56% decrease in clotting time (p=0.047), and 38% increase in maximum clot firmness (p=0.024). Transfusion with ≥1:1 ratio did not confer any additional improvement. There was a marked variability in response to FFP, and hemostatic function deteriorated in some patients exposed to 1:1 ratios. The beneficial effects of plasma were confined to patients with coagulopathy. CONCLUSIONS: Interim results from this prospective study suggest that FFP:PRBC ratios of ≥1:1 do not confer any additional advantage over ratios of 1:2 to 3:4. Hemostatic benefits of plasma therapy are limited to patients with coagulopathy.

Recruitment in urology: a national survey in the UK.

PURPOSE: Urology is one of the most common specialties chosen by surgical trainees. This study set out to determine what factors influence the decision in pursuing a career in urology as opposed to other surgical specialties. MATERIALS AND METHODS: A questionnaire was mailed to 844 urologists of various career levels within the UK. Subjects were asked to document the top three factors that influenced their choice of urology as a career. Specifically, they were asked whether their undergraduate teaching was an influence. RESULTS: Completed surveys were received from 362 respondents. Less than one-third of the respondents were influenced by their undergraduate urology exposure. The top five reasons cited for pursing a career in urology were: (i) a positive role model; (ii) postgraduate urology experience; (iii) the wide variety of procedures encompassing open and endoscopic work; (iv) the lifestyle; and (v) the pleasant personalities of urologists when compared with other specialties. CONCLUSIONS: This is the first study if its kind to establish the factors influencing career choices. As urology continues to be eroded from undergraduate curricula, the data support the view that undergraduate urology exposure is not the most influential factor.