Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures

Gold OABackground: With an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective). Methods Test subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever. Results THR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections. Conclusions The most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care

Large Scale Structures, Symmetry, and Universality in Sandpiles

We introduce a sandpile model where, at each unstable site, all grains are transferred randomly to downstream neighbors. The model is local and conservative, but not Abelian. This does not appear to change the universality class for the avalanches in the self-organized critical state. It does, however, introduce long-range spatial correlations within the metastable states. We find large scale networks of occupied sites whose density vanishes in the thermodynamic limit, for d>1.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Let

Total hip and knee replacement surgery results in changes in leukocyte and endothelial markers

<p>Abstract</p> <p>Background</p> <p>It is estimated that over 8 million people in the United Kingdom suffer from osteoarthritis. These patients may require orthopaedic surgical intervention to help alleviate their clinical condition. Investigations presented here was to test the hypothesis that total hip replacement (THR) and total knee replacement (TKR) orthopaedic surgery result in changes to leukocyte and endothelial markers thus increasing inflammatory reactions postoperatively.</p> <p>Methods</p> <p>During this 'pilot study', ten test subjects were all scheduled for THR or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1) and CD62L cell surface expression, intracellular production of H₂O₂and elastase were measured as markers of leukocyte function. Von Willebrand factor (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured as markers of endothelial activation.</p> <p>Results</p> <p>The results obtained during this study demonstrate that THR and TKR orthopaedic surgery result in similar changes of leukocyte and endothelial markers, suggestive of increased inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in a leukocytosis, this being demonstrated by an increase in the total leukocyte concentration following surgery. Evidence of leukocyte activation was demonstrated by a decrease in CD62L expression and an increase in CD11b expression by neutrophils and monocytes respectively. An increase in the intracellular H₂O₂production by neutrophils and monocytes and in the leukocyte elastase concentrations was also evident of leukocyte activation following orthopaedic surgery. With respect to endothelial activation, increases in vWF and sICAM-1 concentrations were demonstrated following surgery.</p> <p>Conclusion</p> <p>In general it appeared that most of the leukocyte and endothelial markers measured during these studies peaked between days 1-3 postoperatively. It is proposed that by allowing orthopaedic surgeons access to alternative laboratory markers such as CD11b, H₂O₂and elastase, CD62L, vWF and sICAM-1, an accurate assessment of the extent of inflammation due to surgery <it>per se </it>could be made. Ultimately, the leukocyte and endothelial markers assessed during this investigation may have a role in monitoring potential infectious complications that can occur during the postoperative period.</p

Mild episodes of tourniquet-induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers

<p>Abstract</p> <p>Background</p> <p>Monocytes and neutrophils are examples of phagocytic leukocytes, with neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes and neutrophils have been implicated to play a key role in the development of ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte-endothelial cell interactions. In this pilot study we hypothesised that mild episodes of tourniquet induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers.</p> <p>Methods</p> <p>Ten healthy human volunteers were recruited after informed consent. None had any history of cardiovascular disease with each subject volunteer participating in the study for a 24 hour period. Six venous blood samples were collected from each subject volunteer at baseline, 10 minutes ischaemia, 5, 15, 30, 60 minutes and 24 hours reperfusion, by means of a cannula from the ante-cubital fossa. Monocyte and neutrophil leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. The cell surface expression of CD62L (L-selectin), CD11b and the intracellular production of hydrogen peroxide (H₂O₂) were measured via flow cytometry. C-reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma concentrations of D-dimer and von Willebrand factor (vWF) were measured using enzyme-linked fluorescent assays (ELFA).</p> <p>Results</p> <p>During ischaemia-reperfusion injury, there was a decrease in CD62L and an increase in CD11b cell surface expression for both monocytes and neutrophils, with changes in the measured parameters reaching statistical significance (p =< 0.05). A significant decrease in peripheral blood leukocyte concentration was observed during this process, which was measured to assess the degree of leukocyte trapping in the micro-circulation (p =< 0.001). There was an increase in the intracellular production of H₂O₂production by leukocyte sub-populations, which was measured as a marker of leukocyte activation. Intracellular production of H₂O₂in monocytes during ischaemia-reperfusion injury reached statistical significance (p = 0.014), although similar trends were observed with neutrophils these did not reach statistical significance. CRP was measured to assess the inflammatory response following mild episodes of ischaemia-reperfusion injury and resulted in a significant increase in the CRP concentration (p =< 0.001). There were also increased plasma concentrations of D-dimer and a trend towards elevated vWF levels, which were measured as markers of coagulation activation and endothelial damage respectively. Although significant changes in D-dimer concentrations were observed during ischaemia-reperfusion injury (p = 0.007), measurement of the vWF did not reach statistical significance.</p> <p>Conclusion</p> <p>Tourniquet induced forearm ischaemia-reperfusion injury results in increased adhesiveness, trapping and activation of leukocytes. We report that, even following a mild ischaemic insult, this leukocyte response is immediately followed by evidence of increased inflammatory response, coagulation activity and endothelial damage. These results may have important implications and this pilot study may lead to a series of trials that shed light on the mechanisms of ischaemia-reperfusion injury, including potential points of therapeutic intervention for pathophysiological conditions.</p

Global biogeographic patterns of avian morphological diversity

Understanding the biogeographical patterns, and evolutionary and environmental drivers, underpinning morphological diversity are key for determining its origins and conservation. Using a comprehensive set of continuous morphological traits extracted from museum collections of 8353 bird species, including geometric morphometric beak shape data, we find that avian morphological diversity is unevenly distributed globally, even after controlling for species richness, with exceptionally dense packing of species in hyper-diverse tropical hotspots. At the regional level, these areas also have high morphological variance, with species exhibiting high phenotypic diversity. Evolutionary history likely plays a key role in shaping these patterns, with evolutionarily old species contributing to niche expansion, and young species contributing to niche packing. Taken together, these results imply that the tropics are both ‘cradles’ and ‘museums’ of phenotypic diversity

Rationalization of the X-ray photoelectron spectroscopy of aluminium phosphates synthesized from different precursors

The aim of this paper is to clarify the assignments of X-ray photoelectron spectra of aluminium phosphate materials prepared from the reaction of phosphoric acid with three different aluminium precursors [Al(OH)3, Al(NO3)3 and AlCl3] at different annealing temperatures. The materials prepared have been studied by X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), infrared spectroscopy and high-resolution solid-state 31P NMR spectroscopy. A progressive polymerization from orthophosphate to metaphosphates is observed by XRD, ATR-FTIR and solid state 31P NMR, and on this basis the oxygen states observed in the XP spectra at 532.3 eV and 533.7 eV are assigned to P–O–Al and P–O–P environments, respectively. The presence of cyclic polyphosphates at the surface of the samples is also evident

Early development of structural networks and the impact of prematurity on brain connectivity

Preterm infants are at high risk of neurodevelopmental impairment, which may be due to altered development of brain connectivity. We aimed to (i) assess structural brain development from 25 to 45 weeks gestational age (GA) using graph theoretical approaches and (ii) test the hypothesis that preterm birth results in altered white matter network topology. Sixty-five infants underwent MRI between 25(+3) and 45(+6) weeks GA. Structural networks were constructed using constrained spherical deconvolution tractography and were weighted by measures of white matter microstructure (fractional anisotropy, neurite density and orientation dispersion index). We observed regional differences in brain maturation, with connections to and from deep grey matter showing most rapid developmental changes during this period. Intra-frontal, frontal to cingulate, frontal to caudate and inter-hemispheric connections matured more slowly. We demonstrated a core of key connections that was not affected by GA at birth. However, local connectivity involving thalamus, cerebellum, superior frontal lobe, cingulate gyrus and short range cortico-cortical connections was related to the degree of prematurity and contributed to altered global topology of the structural brain network. The relative preservation of core connections at the expense of local connections may support more effective use of impaired white matter reserve following preterm birth

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase; and ryanodine, a diterpenoid that modulates Ca2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca2+ dynamics. Cytosolic Ca2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental observations qualitatively, as well as quantitatively within a range of physiological parametric values. The model also illustrated how increased intercellular coupling led to smooth muscle coordination and the genesis of vascular tone