Motorcyclists and pillion passengers with open lower-limb fractures: a study using TARN data 2007-2014

Introduction We aimed to identify population demographics of motorcyclists and pillion passengers with isolated open lower-limb fractures, to ascertain the impact of the revised 2009 British Orthopaedic Association/British Association of Plastic Reconstructive and Aesthetic Surgeons joint standards for the management of open fractures of the lower limb (BOAST 4), in terms of time to skeletal stabilisation and soft-tissue coverage, and to observe any impact on patient movement. Methods Retrospective cohort data was collected by the Trauma Audit and Research Network (TARN). A longitudinal analysis was performed between two timeframes in England (pre-and post-BOAST 4 revision): 2007-2009 and 2010-2014. Results A total of 1564 motorcyclists and 64 pillion passengers were identified. Of these, 93% (1521/1628) were male. The median age for males was 30.5 years and 36.7 years for females. There was a statistically significant difference in the number of patients who underwent skeletal stabilisation (49% vs 65%, P < 0.0001), the time from injury to skeletal stabilisation (7.33 hours vs 14.3 hours, P < 0.0001) and the proportion receiving soft-tissue coverage (26% vs 43%, P < 0.0001). There was no difference in the time from injury to soft-tissue coverage (62.3 hours vs 63.7 hours, P = 0.726). The number of patients taken directly to a major trauma centre (or its equivalent) increased between the two timeframes (12.5% vs, 41%, P < 0.001). Conclusions Since the 2009 BOAST 4 revision, there has been no difference in the time taken from injury to soft-tissue coverage but the time from injury to skeletal stabilisation is longer. There has also been an increase in patient movement to centres offering joint orthopaedic and plastic care

Hippurate as a metabolomic marker of gut microbiome diversity: Modulation by diet and relationship to metabolic syndrome

Reduced gut microbiome diversity is associated with multiple disorders including metabolic syndrome (MetS) features, though metabolomic markers have not been investigated. Our objective was to identify blood metabolite markers of gut microbiome diversity, and explore their relationship with dietary intake and MetS. We examined associations between Shannon diversity and 292 metabolites profiled by the untargeted metabolomics provider Metabolon Inc. in 1529 females from TwinsUK using linear regressions adjusting for confounders and multiple testing (Bonferroni: P < 1.71 × 10−4). We replicated the top results in an independent sample of 420 individuals as well as discordant identical twin pairs and explored associations with self-reported intakes of 20 food groups. Longitudinal changes in circulating levels of the top metabolite, were examined for their association with food intake at baseline and with MetS at endpoint. Five metabolites were associated with microbiome diversity and replicated in the independent sample. Higher intakes of fruit and whole grains were associated with higher levels of hippurate cross-sectionally and longitudinally. An increasing hippurate trend was associated with reduced odds of having MetS (OR: 0.795[0.082]; P = 0.026). These data add further weight to the key role of the microbiome as a potential mediator of the impact of dietary intake on metabolic status and health

Lymphocyte Modulation with FTY720 Improves Hemorrhagic Shock Survival in Swine

The inflammatory response to severe traumatic injury results in significant morbidity and mortality. Lymphocytes have recently been identified as critical mediators of the early innate immune response to ischemia-reperfusion injury. Experimental manipulation of lymphocytes following hemorrhagic shock may prevent secondary immunologic injury in surgical and trauma patients. The objective of this study is to evaluate the lymphocyte sequestration agent FTY720 as an immunomodulator following experimental hemorrhagic shock in a swine liver injury model. Yorkshire swine were anesthetized and underwent a grade III liver injury with uncontrolled hemorrhage to induce hemorrhagic shock. Experimental groups were treated with a lymphocyte sequestration agent, FTY720, (n = 9) and compared to a vehicle control group (n = 9). Animals were observed over a 3 day survival period after hemorrhage. Circulating total leukocyte and neutrophil counts were measured. Central lymphocytes were evaluated with mesenteric lymph node and spleen immunohistochemistry (IHC) staining for CD3. Lung tissue infiltrating neutrophils were analyzed with myeloperoxidase (MPO) IHC staining. Relevant immune-related gene expression from liver tissue was quantified using RT-PCR. The overall survival was 22.2% in the vehicle control and 66.7% in the FTY720 groups (p = 0.081), and reperfusion survival (period after hemorrhage) was 25% in the vehicle control and 75% in the FTY720 groups (p = 0.047). CD3+ lymphocytes were significantly increased in mesenteric lymph nodes and spleen in the FTY720 group compared to vehicle control, indicating central lymphocyte sequestration. Lymphocyte disruption significantly decreased circulating and lung tissue infiltrating neutrophils, and decreased expression of liver immune-related gene expression in the FTY720 treated group. There were no observed infectious or wound healing complications. Lymphocyte sequestration with FTY720 improves survival in experimental hemorrhagic shock using a porcine liver injury model. These results support a novel and clinically relevant lymphocyte immunomodulation strategy to ameliorate secondary immune injury in hemorrhagic shock

Characterizing blood metabolomics profiles associated with self-reported food intakes in female twins

Using dietary biomarkers in nutritional epidemiological studies may better capture exposure and improve the level at which diet-disease associations can be established and explored. Here, we aimed to identify and evaluate reproducibility of novel biomarkers of reported habitual food intake using targeted and non-targeted metabolomic blood profiling in a large twin cohort. Reported intakes of 71 food groups, determined by FFQ, were assessed against 601 fasting blood metabolites in over 3500 adult female twins from the TwinsUK cohort. For each metabolite, linear regression analysis was undertaken in the discovery group (excluding MZ twin pairs discordant [≥1 SD apart] for food group intake) with each food group as a predictor adjusting for age, batch effects, BMI, family relatedness and multiple testing (1.17x10-6 = 0.05/[71 food groups x 601 detected metabolites]). Significant results were then replicated (non-targeted: P<0.05; targeted: same direction) in the MZ discordant twin group and results from both analyses meta-analyzed. We identified and replicated 180 significant associations with 39 food groups (P<1.17x10-6), overall consisting of 106 different metabolites (74 known and 32 unknown), including 73 novel associations. In particular we identified trans-4-hydroxyproline as a potential marker of red meat intake (0.075[0.009]; P = 1.08x10-17), ergothioneine as a marker of mushroom consumption (0.181[0.019]; P = 5.93x10-22), and three potential markers of fruit consumption (top association: apple and pears): including metabolites derived from gut bacterial transformation of phenolic compounds, 3-phenylpropionate (0.024[0.004]; P = 1.24x10-8) and indolepropionate (0.026[0.004]; P = 2.39x10-9), and threitol (0.033[0.003]; P = 1.69x10-21). With the largest nutritional metabolomics dataset to date, we have identified 73 novel candidate biomarkers of food intake for potential use in nutritional epidemiological studies. We compiled our findings into the DietMetab database (http://www.twinsuk.ac.uk/dietmetab-data/), an online tool to investigate our top associations

Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa: An fMRI Study

Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes

Pre- and syn-eruptive degassing and crystallisation processes of the 2010 and 2006 eruptions of Merapi volcano, Indonesia

The 2010 eruption of Merapi (VEI 4) was the volcano’s largest since 1872. In contrast to the prolonged and effusive dome-forming eruptions typical of Merapi’s recent activity, the 2010 eruption began explosively, before a new dome was rapidly emplaced. This new dome was subsequently destroyed by explosions, generating pyroclastic density currents (PDCs), predominantly consisting of dark coloured, dense blocks of basaltic andesite dome lava. A shift towards open-vent conditions in the later stages of the eruption culminated in multiple explosions and the generation of PDCs with conspicuous grey scoria and white pumice clasts resulting from sub-plinian convective column collapse. This paper presents geochemical data for melt inclusions and their clinopyroxene hosts extracted from dense dome lava, grey scoria and white pumice generated during the peak of the 2010 eruption. These are compared with clinopyroxene-hosted melt inclusions from scoriaceous dome fragments from the prolonged dome-forming 2006 eruption, to elucidate any relationship between pre-eruptive degassing and crystallisation processes and eruptive style. Secondary ion mass spectrometry analysis of volatiles (H2O, CO2) and light lithophile elements (Li, B, Be) is augmented by electron microprobe analysis of major elements and volatiles (Cl, S, F) in melt inclusions and groundmass glass. Geobarometric analysis shows that the clinopyroxene phenocrysts crystallised at depths of up to 20 km, with the greatest calculated depths associated with phenocrysts from the white pumice. Based on their volatile contents, melt inclusions have re-equilibrated during shallower storage and/or ascent, at depths of ~0.6–9.7 km, where the Merapi magma system is interpreted to be highly interconnected and not formed of discrete magma reservoirs. Melt inclusions enriched in Li show uniform “buffered” Cl concentrations, indicating the presence of an exsolved brine phase. Boron-enriched inclusions also support the presence of a brine phase, which helped to stabilise B in the melt. Calculations based on S concentrations in melt inclusions and groundmass glass require a degassing melt volume of 0.36 km3 in order to produce the mass of SO2 emitted during the 2010 eruption. This volume is approximately an order of magnitude higher than the erupted magma (DRE) volume. The transition between the contrasting eruptive styles in 2010 and 2006 is linked to changes in magmatic flux and changes in degassing style, with the explosive activity in 2010 driven by an influx of deep magma, which overwhelmed the shallower magma system and ascended rapidly, accompanied by closed-system degassing