Fibrinogen in the initial resuscitation of severe trauma (FiiRST): a randomized feasibility trial.

BACKGROUND: Decreased plasma fibrinogen concentration shortly after injury is associated with higher blood transfusion needs and mortality. In North America and the UK, cryoprecipitate transfusion is the standard-of-care for fibrinogen supplementation during acute haemorrhage, which often occurs late during trauma resuscitation. Alternatively, fibrinogen concentrate (FC) can be beneficial in trauma resuscitation. However, the feasibility of its early infusion, efficacy and safety remain undetermined. The objective of this trial was to evaluate the feasibility, effect on clinical and laboratory outcomes and complications of early infusion of FC in trauma. METHODS: Fifty hypotensive (systolic arterial pressure ≤100 mm Hg) adult patients requiring blood transfusion were randomly assigned to either 6 g of FC or placebo, between Oct 2014 and Nov 2015 at a tertiary trauma centre. The primary outcome, feasibility, was assessed by the proportion of patients receiving the intervention (FC or placebo) within one h of hospital arrival. Plasma fibrinogen concentration was measured, and 28-day mortality and incidence of thromboembolic events were assessed. RESULTS: Overall, 96% (43/45) [95% CI 86-99%] of patients received the intervention within one h; 95% and 96% in the FC and placebo groups, respectively (P=1.00). Plasma fibrinogen concentrations remained higher in the FC group up to 12 h after admission with the largest difference at three h (2.9 mg dL - 1 vs. 1.8 mg dL - 1; P<0.01). The 28-day mortality and thromboembolic complications were similar between groups. CONCLUSIONS: Early infusion of FC is feasible and increases plasma fibrinogen concentration during trauma resuscitation. Larger trials are justified.

Assessment of animal African trypanosomiasis (AAT) vulnerability in cattle-owning communities of sub-Saharan Africa.

BACKGROUND: Animal African trypanosomiasis (AAT) is one of the biggest constraints to livestock production and a threat to food security in sub-Saharan Africa. In order to optimise the allocation of resources for AAT control, decision makers need to target geographic areas where control programmes are most likely to be successful and sustainable and select control methods that will maximise the benefits obtained from resources invested. METHODS: The overall approach to classifying cattle-owning communities in terms of AAT vulnerability was based on the selection of key variables collected through field surveys in five sub-Saharan Africa countries followed by a formal Multiple Correspondence Analysis (MCA) to identify factors explaining the variations between areas. To categorise the communities in terms of AAT vulnerability profiles, Hierarchical Cluster Analysis (HCA) was performed. RESULTS: Three clusters of community vulnerability profiles were identified based on farmers' beliefs with respect to trypanosomiasis control within the five countries studied. Cluster 1 communities, mainly identified in Cameroon, reported constant AAT burden, had large trypanosensitive (average herd size = 57) communal grazing cattle herds. Livestock (cattle and small ruminants) were reportedly the primary source of income in the majority of these cattle-owning households (87.0%). Cluster 2 communities identified mainly in Burkina Faso and Zambia, with some Ethiopian communities had moderate herd sizes (average = 16) and some trypanotolerant breeds (31.7%) practicing communal grazing. In these communities there were some concerns regarding the development of trypanocide resistance. Crops were the primary income source while communities in this cluster incurred some financial losses due to diminished draft power. The third cluster contained mainly Ugandan and Ethiopian communities which were mixed farmers with smaller herd sizes (average = 8). The costs spent diagnosing and treating AAT were moderate here. CONCLUSIONS: Understanding how cattle-owners are affected by AAT and their efforts to manage the disease is critical to the design of suitable locally-adapted control programmes. It is expected that the results could inform priority setting and the development of tailored recommendations for AAT control strategies.

Response of Adult Plum Curculios (Coleoptera: Curculionidae) to Contrasting Shades in Field and Laboratory Experiments.

The responses of adult plum curculios, Conotrachelus nenuphar (Herbst), to visual stimuli were assessed in field and laboratory conditions to evaluate the hypothesis that adult captures should increase when traps visually contrast with a lighter horizon, such as the sky. Release-recapture field studies tested whether adult responses to traps were influenced by the trap's visual contrast with background on the horizon. Results at four sites showed that significantly more adults were captured in traps with woodlots behind them, refuting the hypothesis. Laboratory tests in environmental conditions of 315 lux or less observed the movement of adults between intervals. These showed that significantly more females and males relocated in areas marked with black. This effect occurred when adults were presented with black surfaces, stripes, or lines. The black shade used correlated with lower reflected lux (<110), and when in conditions of ≤ 10 lux, significant adult relocation on black was not observed. These results suggest that adults arrest in or move toward areas with low reflected lux. The laboratory and field results combined suggest that higher adult captures in traps correlated with the largest areas of low lux on the horizon. The results imply that trap placement should take reflected lux from all nearby objects into account and that even in small patterns on traps, variance in shade or reflected lux may permit manipulation of plum curculio movement.

Internal Quality Control Practices in Coagulation Laboratories: recommendations based on a patterns-of-practice survey.

INTRODUCTION: Internal quality control (IQC) procedures are crucial for ensuring accurate patient test results. The IQMH Centre for Proficiency Testing conducted a web-based survey to gather information on the current IQC practices in coagulation testing. METHODS: A questionnaire was distributed to 174 Ontario laboratories licensed to perform prothrombin time (PT) and activated partial thromboplastin time (APTT). RESULTS: All laboratories reported using two levels of commercial QC (CQC); 12% incorporate pooled patient plasma into their IQC program; >68% run CQC at the beginning of each shift; 56% following maintenance, with reagent changes, during a shift, or with every repeat sample; 6% only run CQC at the beginning of the day and 25% when the instruments have been idle for a defined period of time. IQC run frequency was determined by manufacturer recommendations (71%) but also influenced by the stability of test (27%), clinical impact of an incorrect test result (25%), and sample's batch number (10%). IQC was monitored using preset limits based on standard deviation (66%), precision goals (46%), or allowable performance limits (36%). 95% use multirules. Failure actions include repeating the IQC (90%) and reporting patient results; if repeat passes, 42% perform repeat analysis of all patient samples from last acceptable IQC. CONCLUSION: Variability exists in coagulation IQC practices among Ontario clinical laboratories. The recommendations presented here would be useful in encouraging standardized IQC practices.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Comparing the emergence of northern strain plum Curculio larvae from multiple fruit varieties.

Increasing restrictions on chemical pesticide use in orchards have encouraged the use of alternative strategies to control the northern strain of the plum curculio, Conotrachelus nenuphar (Herbst). Some of these strategies target larvae as they emerge from fruit, so existing models for larval emergence from fruit were evaluated for accuracy while examining the effect of multiple larvae and fruit type on emergence timing. Larval head width growth rate was established and used to gauge larval development. Larval emergence timing, quantified as degree-days (base 11.1 degrees C), was recorded in tart cherries on trees, and emergence timing was recorded in multiple apple varieties both in cyclical field conditions and in constant laboratory conditions. Ovipositing females and fruit were isolated, so larvae in a fruit were all siblings. Adult emergences from pupation in soil were recorded in the laboratory and compared with existing model predictions. Model predictions did not accurately reflect the timing of larval or adult emergence, and future incorporation of factors that could improve models are discussed. Colder conditions and changing host fruit type had no significant effect on larval emergence timing but changing host fruit type correlated with a shorter pupation interval. Results suggested that females preferred to oviposit on multiple fruit rather than lay multiple eggs in one fruit. Higher numbers of larvae per fruit did not significantly alter the timing of first larval emergence, although more larvae per fruit resulted in a significantly longer emergence period in apples.

Precise and low-cost monitoring of plum curculio (Coleoptera: Curculionidae) pest activity in pyramid traps with cameras.

Incorporating camera systems into insect traps potentially benefits insect phenology modeling, nonlethal insect monitoring, and research into the automated identification of traps counts. Cameras originally for monitoring mammals were instead adapted to monitor the entrance to pyramid traps designed to capture the plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae). Using released curculios, two new trap designs (v.I and v.II) were field-tested alongside conventional pyramid traps at one site in autumn 2010 and at four sites in autumn 2012. The traps were evaluated on the basis of battery power, ease-of-maintenance, adaptability, required-user-skills, cost (including labor), and accuracy-of-results. The v.II design fully surpassed expectations, except that some trapped curculios were not photographed. In 2012, 13 of the 24 traps recorded every curculio entering the traps during the 18-d study period, and in traps where some curculios were not photographed, over 90% of the omissions could be explained by component failure or external interference with the motion sensor. Significantly more curculios entered the camera traps between 1800 and 0000 hours. When compared with conventional pyramid traps, the v.I traps collected a similar number of curculios. Two observed but not significant trends were that the v.I traps collected twice as many plum curculios as the v.II traps, while at the same time the v.II traps collected more than twice as many photos per plum curculio as the v.I traps. The research demonstrates that low-cost, precise monitoring of field insect populations is feasible without requiring extensive technical expertise.

Intra-aortic balloon pump for hemodynamic support in hepatobiliary surgery: report of a case.

The intra-aortic balloon pump (IABP) can be used transiently to improve cardiac function mechanically, in patients with severe cardiomyopathy and heart failure refractory to medical therapy. In the field of surgery, the IABP is most commonly used for patients with myocardial infarction, congestive heart failure, or other chronic cardiac conditions, who are undergoing cardiac surgery. Conversely, it is rarely used in hepatobiliary surgery, with only two reports found in the literature, excluding cases of emergency cholecystectomy. We describe how we used an IABP successfully during surgery to repair a transected bile duct in a patient with peripartum cardiomyopathy.

Hypercoagulability after trauma: hemostatic changes and relationship to venous thromboembolism.

BACKGROUND: Major trauma induces a hypercoagulable state, which is frequently complicated by pathological thrombosis. However the sequential changes in coagulation markers and their relationship to clinical thrombosis have been poorly characterized. METHODS: We measured several markers of in vivo coagulation and fibrinolysis and their regulation serially for 2 weeks after multi-system trauma in a prospective cohort of patients who received no anticoagulant prophylaxis. Asymptomatic deep vein thrombosis (DVT) was assessed by routine bilateral venography between day 12 and 14. Clinically suspected DVT and pulmonary embolism (PE) were investigated in a standardized manner. RESULTS: Among the 135 cohort patients the overall venous thromboembolism (VTE) rate was 59%. Markers of thrombin generation were markedly increased within 24 hours of injury, remained persistently elevated for about 5 days and then decreased by day 14. No early compensatory increase in Tissue Factor Pathway Inhibitor (TFPI) or the complex of Factor Xa and TFPI (FXa-TFPI) was seen; FXa-TFPI remained depressed throughout the study. There was no inverse relationship demonstrated between markers of thrombin generation and thrombin regulation. Acquired APC resistance and hypofibrinolysis did not appear to be important contributors to hypercoagulability after trauma. None of the coagulation markers were independently predictive of VTE. Increasing age was the only significant, independent predictor of VTE. CONCLUSION: Major trauma leads to significantly increased and persistent thrombin generation with disruption of its regulation. Coagulation markers do not appear to add independent predictive value in detecting VTE. Increasing age is the most important clinical predictor of VTE after trauma.

Experimental infection studies of UK Culicoides species midges with bluetongue virus serotypes 8 and 9.

This paper describes a rapid, standardised method for testing the susceptibility to bluetongue virus (BTV) of northern Palaearctic Culicoides species midges that can be used to assess the competence of both field-caught and laboratory-infected midges. The method has been used to show that Culicoides scoticus can replicate btv serotype 8 and BTV serotype 9 strains to more than 3 log(10) TCID50/midge, the first evidence of the potential of this species to transmit BTV.

IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients.

Inosine 5'-monophosphate dehydrogenase 1 (IMPDH1) catalyzes the rate-limiting step of the de novo pathway for purine synthesis and is a major target of the immunosuppressive drug mycophenolic acid (MPA). Few variants of the IMPDH1 gene have been reported. The objective of this study was to identify and characterize IMPDH1 variants to determine whether genetic variation contributes to differences in MPA response and toxicity in transplant patients. Seventeen genetic variants were identified in the IMPDH1 gene with allele frequencies ranging from 0.2 to 42.7%. In this study, 191 kidney transplant patients who received mycophenolate mofetil were genotyped for IMPDH1. Two single-nucleotide polymorphisms, rs2278293 and rs2278294, were significantly associated with the incidence of biopsy-proven acute rejection in the first year post-transplantation. Future studies of the multifactorial nature of acute rejection must consider IMPDH1 polymorphisms in MPA-treated patients.

Comparison of renal allograft outcomes in combined liver-kidney transplantation versus subsequent kidney transplantation in liver transplant recipients: Analysis of UNOS Database.

BACKGROUND: There may be an allograft-enhancing effect by the liver on the renal allograft in the setting of simultaneous combined liver-kidney transplantation (CLKT) from the same donor. This study was performed to investigate whether an existing liver allograft could protect a kidney allograft from immunologic injury due to histoincompatibility in liver transplant recipients who received sequential kidney transplantation (KALT). METHODS: Using the United Network for Organ Sharing database covering January 1996 to December 2003, outcomes of 352 KALT were compared to 1,136 CLKT. Incidence of acute and chronic rejection and rejection-free renal graft survival was compared between two groups. RESULTS: Renal half-life of KALT allografts was shorter than CLKT group (6.6+/-0.9 vs. 11.7+/-1.3 years, P < 0.001). Incidence of chronic rejection in KALT group was higher than CLKT group (4.6 vs. 1.2%, P < 0.001). One and three-year rejection-free renal graft survival of KALT and CLKT groups were different (77% and 67% KALT vs. 85% and 78% CLKT, respectively; P < 0.001). Among human leukocyte antigen mismatched and sensitized patients, rejection-free renal graft survival of KALT group was inferior to the CLKT group (75% at 1 year and 61% 3 years vs. 86% at 1 year and 79% 3 years, P < 0.001). CONCLUSION: Liver allograft provided renal graft immunoprotection if both organs are transplanted simultaneously (immunogenetic identity), but not for kidneys transplanted subsequently.

Prospective evaluation of vascular complications after liver transplantation: comparison of conventional and microbubble contrast-enhanced US.

PURPOSE: To prospectively compare diagnostic performance of conventional Doppler ultrasonography (US) and microbubble contrast material-enhanced US for assessment of vascular complications after liver transplantation, with clinical follow-up or angiography as reference standard. MATERIALS AND METHODS: This study was approved by institutional review board and was HIPAA compliant. Written informed consent was obtained. Seventy-two patients (49 men, 23 women; average age, 52.3 years) were included in this study. Patients who had undergone liver transplantation underwent conventional color Doppler and contrast-enhanced US of the liver. Quality of hepatic artery (HA) and portal vein (PV) visualization, contrast material arrival time, and time for complete evaluation of vasculature were compared for both techniques. McNemar test was used to compare vascular flow visualization scores; Student t test was used to compare mean study times with both techniques. Patients without HA flow at Doppler US underwent angiography; those with flow were followed up clinically. McNemar test was used to compare sensitivity of both techniques. RESULTS: Contrast-enhanced US helped significantly improve flow visualization in hepatic vessels (P < .001). Mean contrast material arrival time was 13.7 seconds +/- 3.8 (standard deviation) in proper HA and 20.7 seconds +/- 6.3 in PV. Mean study time decreased from 27.4 minutes +/- 13.9 to 9.3 minutes +/- 4.5 (P < .01). Doppler US failed to depict HA flow in eight patients; contrast-enhanced US showed flow in six and no flow in two of these patients. Follow-up results confirmed contrast-enhanced US findings. Sensitivity, specificity, and accuracy for Doppler US were 91.3%, 100%, and 91.5%, respectively. Sensitivity, specificity, and accuracy of contrast-enhanced US were all 100%. Sensitivity and accuracy values of the two techniques were significantly different (P < .014); there was no significant difference in specificity (P > .99) CONCLUSION: Contrast-enhanced US helped improve flow visualization in the HA and PV, decrease scanning time, and correctly differentiate between thrombosis and a patent artery in patients without HA flow at conventional Doppler US.

Expanding the donor kidney pool: utility of renal allografts procured in a setting of uncontrolled cardiac death.

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys. From January 1995 to December 2004, 75,865 kidney-alone transplants from donation after brain death (DBD) donors and 2136 transplants from DCD donors were reported to the United Network for Organ Sharing. Among the DCD transplants, 1814 were from controlled and 216 from uncontrolled DCD donors. The log-rank test was used to compare survival curves. The incidence of delayed graft function in controlled DCD (cDCD) was 42% and in uDCD kidneys was 51%, compared to only 24% in kidneys from DBD donors (p < 0.001). The overall graft and patient survival of DCD donors was similar to that of DBD donor kidneys (p = 0.66; p = 0.88). Despite longer donor warm and cold ischemic times, overall graft and patient survival of uDCD donors was comparable to that of cDCD donors (p = 0.65, p = 0.99). Concerted efforts should be focused on procurement of uDCD donors, which can provide another source of quality deceased donor kidneys.