Plasma and cerebrospinal fluid concentrations of neurofilament light protein correlate in patients with idiopathic normal pressure hydrocephalus.

BACKGROUND: Neurofilament light chain protein (NFL), a marker of neuronal axonal degeneration, is increased in cerebrospinal fluid (CSF) of patients with idiopathic normal pressure hydrocephalus (iNPH). Assays for analysis of NFL in plasma are now widely available but plasma NFL has not been reported in iNPH patients. Our aim was to examine plasma NFL in iNPH patients and to evaluate the correlation between plasma and CSF levels, and whether NFL levels are associated with clinical symptoms and outcome after shunt surgery. METHODS: Fifty iNPH patients with median age 73 who had their symptoms assessed with the iNPH scale and plasma and CSF NFL sampled pre- and median 9 months post-operatively. CSF plasma was compared with 50 healthy controls (HC) matched for age and gender. Concentrations of NFL were determined in plasma using an in-house Simoa method and in CSF using a commercially available ELISA method. RESULTS: Plasma NFL was elevated in patients with iNPH compared to HC (iNPH: 45 (30-64) pg/mL; HC: 33 (26-50) (median; Q1-Q3), p = 0.029). Plasma and CSF NFL concentrations correlated in iNPH patients both pre- and postoperatively (r = 0.67 and 0.72, p < 0.001). We found only weak correlations between plasma or CSF NFL and clinical symptoms and no associations with outcome. A postoperative NFL increase was seen in CSF but not in plasma. CONCLUSIONS: Plasma NFL is increased in iNPH patients and concentrations correlate with CSF NFL implying that plasma NFL can be used to assess evidence of axonal degeneration in iNPH. This finding opens a window for plasma samples to be used in future studies of other biomarkers in iNPH. NFL is probably not a very useful marker of symptomatology or for prediction of outcome in iNPH.

Factor XIII activity at onset of labour and association with postpartum haemorrhage: an exploratory post-hoc study.

BACKGROUND: Platelets, fibrinogen and factor XIII (FXIII) are required to form a stable clot in case of haemorrhage. The aims of this study were to evaluate a possible association between FXIII activity at the onset of labour and postpartum haemorrhage (PPH), and to ascertain whether FXIII activity at labour onset differs from after delivery. METHODS: FXIII activity in 239 women with PPH (blood loss >1 L) and in 76 women without PPH was compared, as was activity before and after delivery in a third group of 80 women. RESULTS: FXIII activity at onset of labour was significantly lower in the PPH group compared with the control group (mean ±â€¯SD 0.98 ±â€¯0.20 vs 1.05 ±â€¯0.17 kIU/L; P=0.0006). The difference was significantly greater in subgroups having vaginal delivery with no oxytocin stimulation or uterine exploration (absolute difference 0.131; 95% CI 0.055 to 0.206), compared with a subgroup experiencing any complication (0.04; 95% CI -0.023 to 0.104; interaction P-value 0.098). There was a weak but statistically significant inverse correlation between FXIII and estimated blood loss (r=-0.25; P=0.030) in the control group but not the PPH group. There was no significant difference between FXIII activity at onset of labour and after delivery (mean ±â€¯SD 1.03 ±â€¯0.17 vs 1.04 ±â€¯0.19 kIU/L; P=0.093). CONCLUSIONS: At the onset of labour women with a subsequent PPH had significantly lower mean FXIII activity than that of women without PPH. This difference was small and within normal limits. FXIII activity did not change during normal delivery. The importance of FXIII during PPH requires study.

Effects of fibrinogen supplementation on clot formation in blood samples from cardiac surgery patients before and after tranexamic acid administration.

OBJECTIVES: To investigate if supplementation with fibrinogen concentrate to blood samples collected after tranexamic acid administration improve clot formation more than what can be achieved with fibrinogen in the absence of tranexamic acid. BACKGROUND: It is not known if the combination of fibrinogen and tranexamic acid has additional effects than what can be achieved individually. METHODS: Four blood samples were collected from 15 coronary artery bypass patients. Two samples were collected before surgery, before and after 2 g tranexamic acid was administered. The preoperative samples were diluted to haematocrit 21%. Two samples were collected after surgery, before and after a second dose of 2 g tranexamic acid. Fibrinogen concentrate corresponding to a dose of 3 g in a 70-kg patient was added to the samples. Platelet-independent clotting time and maximum clot firmness assessed by thromboelastometry (ROTEM-FIBTEM®) were compared between the samples. RESULTS: Administration of tranexamic acid shortened clotting time marginally (-6%) before surgery, P = 0·029) but did not influence clot firmness. Fibrinogen concentrate shortened clotting time (-14% before and -12% after surgery, both P = 0·003) and increased clot firmness (+51 and +39%, both P < 0·001). The effects of fibrinogen did not differ before and after tranexamic acid administration. Fibrinolysis was not detected in any sample. CONCLUSIONS: The results of this in vitro study suggest that the enhancing effects of fibrinogen on clot firmness in blood samples from cardiac surgery patients are not further increased in the presence of tranexamic acid. Further studies on patients with ongoing bleeding and/or hyperfibrinolysis are necessary to validate the results.

Predisposing Factors for Re-interventions with Additional Iliac Stent Grafts After Endovascular Aortic Repair.

BACKGROUND: Endoleaks of type Ib and III are relatively common causes of re-intervention after EVAR. The aim was to determine underlying causes and identify anatomical factors associated with these re-interventions. METHODS: A total of 444 patients with standard bifurcated stent grafts were included in a retrospective observational study. Patients requiring additional iliac stent grafts (n = 24) were compared to those who did not (n = 420). Pre- and post-operative CT examinations were reviewed in patients with additional iliac stents. Reasons for re-interventions were defined as migration (>5 mm at the distal end or at interconnections), progression of disease (iliac artery diameter exceeding graft diameter), inadequate distal seal length at primary repair, or a combination of these factors. RESULTS: Twenty-four patients received 31 additional grafts in 30 limbs after a median 46 months (range 2-92 months). Five re-interventions (21%) were due to rupture. Re-intervened limbs had a larger iliac artery diameter 18 mm (25th and 75th percentile 20-25) versus 15 mm (13-18 mm), p < .001. The degree of iliac limb oversizing at primary EVAR was lower in re-intervened patients (11% (8-18%) versus 18% (12-26%), p = .003). In re-intervened patients, iliac attachment zones were shorter in treated limbs than in untreated 23 mm (11-34) versus 34 mm (25-44), p < .001). Sixteen of 31 re-interventions (51%) were caused by migration (10 at the distal landing site, 6 at interconnections), nine of 31 (29%) by disease progression, and nine of 31 (29%) had inadequate initial stent graft placement. Three of 31 re-interventions (10%) were done as proactive procedures. CONCLUSIONS: Additional iliac stent grafting occurred late after primary repair; a considerable number were caused by rupture. A low degree of oversizing, migration at the distal landing site, separation of stent graft interconnections, disease progression at the distal landing site, and inadequate initial stent graft placement may all contribute. Patients with large iliac dimensions and short attachment zones may need a larger degree of oversizing and more vigorous surveillance.

Preoperative platelet function predicts perioperative bleeding complications in ticagrelor-treated cardiac surgery patients: a prospective observational study.

BACKGROUND: Treatment with P2Y12 receptor antagonists increases the risk for perioperative bleeding, but there is individual variation in the antiplatelet effect and time to offset of this effect. We investigated whether preoperative platelet function predicts the risk of bleeding complications in ticagrelor-treated cardiac surgery patients. METHODS: Ninety patients with ticagrelor treatment within <5 days of surgery were included in a prospective observational study. Preoperative platelet aggregation was assessed with impedance aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating peptide (TRAP) as initiators. Severe bleeding complications were registered using a new universal definition of perioperative bleeding. The accuracy of aggregability tests for predicting severe bleeding was assessed using receiver operating characteristic (ROC) curves, which also identified optimal cut-off values with respect to sensitivity and specificity, based on Youden's index. RESULTS: The median time from the last ticagrelor dose to surgery was 35 (range 4-108) h. The accuracy of platelet function tests to predict severe bleeding was highest for ADP [area under the ROC curve 0.73 (95% confidence interval 0.63-0.84, P<0.001); TRAP 0.61 (0.49-0.74); AA 0.53 (0.40-0.66)]. The optimal cut-off for ADP-induced aggregation was 22 U. In subjects with ADP-induced aggregation below the cut-off value, 24/38 (61%) developed severe bleeding compared with 8/52 (14%) when aggregation was at or above the cut-off value (P<0.001). The positive and negative predictive values for this cut-off value were 63 and 85%, respectively. CONCLUSIONS: Preoperative ADP-induced platelet aggregability predicts the risk for severe bleeding complications in ticagrelor-treated cardiac surgery patients.

Amyloid mis-metabolism in idiopathic normal pressure hydrocephalus.

BACKGROUND: Patients with idiopathic normal pressure hydrocephalus (iNPH) have reduced cerebrospinal fluid (CSF) concentrations of amyloid-ß (Aß) and α- and ß-cleaved soluble forms of amyloid precursor protein (sAPPα and sAPPß). The aims of this study were to examine if changes could also be seen in the CSF for secreted metabolites of APP-like protein 1 (APLP1) and to explore the prognostic value of amyloid-related CSF biomarkers, as well as markers of neuronal injury and astroglial activation, as regards to clinical outcome after shunt surgery. METHODS: Twenty patients diagnosed with iNPH, 10 improved and 10 unchanged by shunt surgery, and 20 neurologically healthy controls were included. All patients were examined clinically prior to surgery and at 6-month follow-up after surgery using the iNPH scale. Lumbar puncture was performed pre-operatively. CSF samples were analyzed for neurofilament light (NFL), Aß isoforms Aß38, Aß40 and Aß42, sAPPα, sAPPß, APLP1 ß-derived peptides APL1ß25, APL1ß 27 and APL1ß 28 and YKL40 by immunochemical methods. RESULTS: The concentrations of all soluble forms of APP, all Aß isoforms and APL1ß28 were lower, whilst APL1ß25 and APL1ß27 were higher in the CSF of iNPH patients compared to controls. There was no difference in biomarker concentrations between patients who improved after surgery and those who remained unchanged. CONCLUSIONS: The reduced CSF concentrations of Aß38, Aß40, Aß42, sAPPα and sAPPß suggest that APP expression could be downregulated in iNPH. In contrast, APLP1 concentration in the CSF seems relatively unchanged. The increase of APL1ß25 and APL1ß27 in combination with a slight decreased APL1ß28 could be caused by more available γ-secretase due to reduced availability of its primary substrate, APP. The data did not support the use of these markers as indicators of shunt responsiveness.

Displacement Forces in Stent Grafts: Influence of Diameter Variation and Curvature Asymmetry.

OBJECTIVES: Long-term durability after endovascular aortic repair is influenced by stent graft migration causing types I and III endoleaks. Flow induced displacement forces have been shown to have the potential to cause migration. In this study, the influence of the distal diameter of iliac limb stent grafts and the shape of graft curvature on flow induced displacement forces, were investigated. METHODS: In an experimental pulsatile flow model mimicking aortic conditions in vivo, flow induced displacement forces at the proximal and distal ends of iliac limb stent grafts were studied at different angles (0-90°) and perfusion pressures (145/80, 170/90, 195/100 mmHg). Bell-bottomed, tapered, and non-tapered stent grafts and also asymmetric stent graft curvatures at 90° bend were studied. Measurements of graft movement were performed at all studied angulations and graft shapes. RESULTS: For all stent graft diameters, flow induced displacement forces increased with higher pressure and increased stent graft angulation. Forces in the bell-bottom graft were considerably higher than in tapered and non-tapered grafts, with a markedly elevated peak force at the distal end (proximal end, 2.3 ± 0.06 N and distal end, 6.9 ± 0.05 N compared with 1.7 ± 0.08 N and 1.6 ± 0.08 N in non-tapered grafts; p < .001 both). Peak forces in tapered and non-tapered grafts were not significantly different between the proximal and distal end. In asymmetric stent graft curvatures, a significant increase in displacement forces was observed in the attachment zone that was closest to the stent graft bend. Graft movement increased with greater displacement forces. CONCLUSION: Flow induced displacement forces in iliac limb stent grafts are significant and are influenced by distal stent graft diameter and the shape of the graft curvature. The displacement forces are particularly high at the large distal end of bell-bottom grafts. Wide iliac arteries treated with bell-bottom stent grafts may require more vigilant surveillance and improved stent graft fixation.

Cell saver processing mitigates the negative effects of wound blood on platelet function.

BACKGROUND: Wound blood is highly activated and has poor haemostatic properties. Recent data suggest that retransfusion of unwashed wound blood may impair haemostasis. We hypothesized that cell saver processing of wound blood before retransfusion reduces the negative effects. METHODS: Wound blood was collected from 16 cardiac surgery patients during cardiopulmonary bypass. One portion of the wound blood was processed in a cell saver and one portion left unprocessed. Increasing amounts of unprocessed blood (10% and 20% of the systemic blood volume) or corresponding volumes of processed blood were added ex vivo to whole blood samples from the same patient. Clot formation was assessed by modified thromboelastometry (ROTEM(®) ) and platelet function with impedance aggregometry (Multiplate(®) ). RESULTS: Addition of unprocessed wound blood significantly impaired clot formation and platelet aggregability. Cell saver processing before addition did not influence clot formation but abolished completely the negative effects of wound blood on platelet aggregability tested with all agonists. Median adenosine diphosphate-induced platelet aggregation was 51 (25th and 75th percentiles 42-69) when 20% processed cardiotomy suction blood was added vs. 34 (24-52) U when 20% unprocessed blood was added, P < 0.001. The corresponding figures for arachidonic acid-, thrombin receptor activating peptide- and collagen-induced aggregation was 21 (17-51) vs. 13 (10-25) U, 112 (87-128) vs. 78 (65-103) U and 58 (50-73) vs. 33 (28-44) U, respectively, all P < 0.001). CONCLUSION: The results suggest that cell saver processing before retransfusion mitigates the negative effects of wound blood on platelet function despite that cell saver processing reduces platelet count.

Perioperative monitoring of platelet function in paediatric cardiac surgery by thromboelastometry, or platelet aggregometry?

BACKGROUND: Impaired platelet function increases the risk of bleeding complications in cardiac surgery. Reliable assessment of platelet function can improve treatment. We investigated whether thromboelastometry detects clinically significant preoperative, perioperative, and postoperative adenosine diphosphate (ADP)-dependent platelet dysfunction in paediatric cardiac surgery patients. METHODS: Fifty-seven children were included in a single-centre prospective observational study. Clot formation (modified rotational thromboelastometry with heparinase, HEPTEM) and platelet aggregation (multiple electrode aggregometry) were analysed at five time points before, during, and after surgery. The accuracy of thromboelastometric indices of platelet function [maximal clot firmness (MCF) and clot formation time (CFT)] to detect ADP-dependent platelet dysfunction (defined as ADP-induced aggregation ≤30 units) was calculated with receiver operating characteristics analysis, which also identified optimal cut-off levels. Positive and negative predictive values for the identified cut-off levels (CFT≥166 s; MCF≤43 mm) to detect platelet function were determined. RESULTS: The MCF and CFT were highly accurate in predicting platelet dysfunction during cardiopulmonary bypass [CPB; area under the aggregation curve 0.89 (95% confidence interval 0.80-0.97) and 0.86 (0.77-0.96), respectively] but not immediately after CPB [0.64 (0.48-0.79) and 0.67 (0.52-0.82), respectively] or on arrival at the intensive care unit [0.53 (0.37-0.69) and 0.60 (0.44-0.77), respectively]. The positive and negative predictive values were acceptable during CPB (87 and 67%, respectively, for MCF≤43 mm; 80 and 100% for CFT≥166 s) but markedly lower after surgery. CONCLUSION: In paediatric cardiac surgery, thromboelastometry has acceptable ability to detect ADP-dependent platelet dysfunction during, but not after, CPB.

Preoperative supplementation with fibrinogen concentrate in cardiac surgery: A randomized controlled study.

BACKGROUND: Bleeding remains a severe complication in cardiac surgery. Several studies have found an association between the preoperative plasma concentration of fibrinogen and postoperative bleeding in cardiac surgery patients. This raises the question of whether preoperative supplementation with fibrinogen concentrate can reduce postoperative blood loss. METHODS: An investigator-initiated, prospective, randomized double-blind placebo-controlled study, was performed in 48 low-risk, coronary artery bypass grafting patients. Subjects were randomized to infusion of 2 g fibrinogen or placebo immediately before surgery, after induction of anaesthesia. The primary endpoint was blood loss during the first 12 h postoperatively. Secondary endpoints included the proportion of transfused subjects, the number of transfused allogeneic blood products (red blood cells, plasma and platelets), and haemoglobin concentration after surgery. Student's t-test and Mann-Whitney U-test was used to compare continuous data and χ(2)-test to compare categorical data between groups. RESULTS: Median postoperative bleeding was not significantly different between the fibrinogen and placebo groups [650 (25/75th percentile 500‒835) ml compared with 730 (543‒980) ml, P=0.29]. The proportion of transfused subjects (33 vs 29%, P=0.76), number of perioperative transfusions of allogeneic blood products (0 (0-2 vs 0 (0-3), P=0.76) and haemoglobin concentration 24 h after surgery (107 (sd 11) vs 100 (12) g L-1, P=0.07) were not significantly different between the fibrinogen and placebo group, respectively. CONCLUSION: Preoperative supplementation with 2 g fibrinogen concentrate did not significantly influence postoperative bleeding, in coronary artery bypass grafting patients without documented hypofibrinogenaemia. CLINICAL TRIAL REGISTRATION: NCT 00968045.

Triclosan-coated sutures and sternal wound infections: a prospective randomized clinical trial.

Surgical site infection is a common complication following cardiac surgery. Triclosan-coated sutures have been shown to reduce the rate of infections in various surgical wounds, including wounds after vein harvesting in coronary artery bypass grafting patients. Our purpose was to compare the rate of infections in sternotomy wounds closed with triclosan-coated or conventional sutures. A total of 357 patients that underwent coronary artery bypass grafting were included in a prospective randomized double-blind single-center study. The patients were randomized to closure of the sternal wound with either triclosan-coated sutures (Vicryl Plus and Monocryl Plus, Ethicon, Inc., Somerville, NJ, USA) (n = 179) or identical sutures without triclosan (n = 178). Patients were followed up after 30 days (clinical visit) and 60 days (telephone interview). The primary endpoint was the prevalence of sternal wound infection according to the Centers for Disease Control and Prevention (CDC) criteria. The demographics in both groups were comparable, including age, gender, body mass index, and rate of diabetes and smoking. Sternal wound infection was diagnosed in 43 patients; 23 (12.8%) sutured with triclosan-coated sutures compared to 20 (11.2%) sutured without triclosan (p = 0.640). Most infections were superficial (n = 36, 10.1%), while 7 (2.0%) were deep sternal wound infections. There were 16 positive cultures in the triclosan group and 17 in the non-coated suture group (p = 0.842). The most commonly identified main pathogens were Staphylococcus aureus (45.4%) and coagulase-negative staphylococci (36.4%). Skin closure with triclosan-coated sutures did not reduce the rate of sternal wound infection after coronary artery bypass grafting. (clinicaltrials.gov: NCT01212315).

Fibrinogen plasma concentration before delivery is not associated with postpartum haemorrhage: a prospective observational study.

BACKGROUND: Low plasma fibrinogen concentration has been linked to postpartum haemorrhage. The primary aim of this study was to assess whether fibrinogen concentration at admission before labour is associated with severe postpartum haemorrhage. Secondary aims were to describe fibrinogen concentration before and after labour and to identify predictors for severe postpartum haemorrhage. METHODS: 1951 healthy women were included in a prospective observational study. Fibrinogen concentration was determined at admission to the labour ward and in a subgroup of women (n=80) also after the placenta was delivered. Bleeding volume postpartum was estimated by weighing surgical sponges and pads and by measuring collected blood. Predictors for severe postpartum haemorrhage (>1000 ml) were identified with bivariate and multivariate regression analyses. RESULTS: Mean fibrinogen concentration was 5.3 (SD 0.8) g litre(-) (1). Median estimated blood loss was 450 (range 70-4400) ml and 250 (12.8%) women bled >1000 ml. Fibrinogen concentration was not correlated with postpartum haemorrhage in the entire cohort (r(s)=0.003, P=0.90) or in any subgroup. Fibrinogen concentration was not associated with bleeding >1000 ml (odds ratio 1.01 (CI 95% 0.85-1.19), P=0.93) and did not differ significantly before and after delivery. Oxytocin stimulation, instrumental delivery, Caesarean section and exploration of uterus were identified as independent predictors of haemorrhage >1000 ml. CONCLUSIONS: Fibrinogen plasma concentration at admission before labour does not predict severe postpartum haemorrhage in a general obstetric population. Fibrinogen concentration does not decrease significantly during normal labour. Excessive postpartum bleeding is mainly as a result of obstetric complications.

Pre-operative fibrinogen supplementation in cardiac surgery patients: an evaluation of different trigger values.

BACKGROUND: Pre-operative fibrinogen levels are negatively associated with postoperative bleeding in cardiac surgery patients. The guidelines of the European Society of Anaesthesiology consider the possibility of a prophylactic pre-operative supplementation in patients with fibrinogen levels<`3.8 g/l. The present study is a reanalysis of published data aimed to define the diagnostic accuracy of different values of pre-operative fibrinogen levels in predicting severe post-operative bleeding. METHODS: Data were retrieved for 2154 patients in four different studies. Severe bleeding (SB) was defined as a post-operative chest drain output>1 l/12 h. Diagnostic accuracy for prediction of SB was tested at three cutoff values of pre-operative fibrinogen (2.5 g/l, 3.0 g/l, and 3.8 g/l). RESULTS: At all the three cutoff values, pre-operative fibrinogen levels had an excellent negative predictive value, ranging from 86% to 100%. Conversely, the positive predictive value was poor at all the cutoff levels: 12% (3.8 g/l), 14% (3.0 g/l), and 19% (2.5 g/l). Overall, the accuracy of pre-operative fibrinogen levels for the prediction of SB was poor. A strategy based on pre-operative fibrinogen supplementation would lead to inappropriate treatment in > 80% of the treated patients. Overall, a trigger value of 3.8 g/l would result in an inappropriate treatment in 52% of the patients, of 3.0 g/l in 20% of the patients, and of 2.5 g/l in 4% of the patients. CONCLUSION: Correction of pre-operative fibrinogen levels below 3.8 g/l would lead to an excessive rate of inappropriate interventions. Values below 2.5 g/l could be considered.

Platelet count and function in paediatric cardiac surgery: a prospective observational study.

BACKGROUND: Platelet deficiency, impaired platelet function, or both increase the risk of bleeding complications. We assessed platelet count and function during and after paediatric cardiac surgery. Secondary aims included the effect of modified ultrafiltration, identification of factors associated with platelet dysfunction, and to assess associations between platelet function and transfusion requirements. METHODS: Fifty-seven patients were included in a prospective observational study. Platelet count and platelet function (multiple-electrode impedance aggregometry) were analysed before and during cardiopulmonary bypass (CPB), after modified ultrafiltration, on arrival at the intensive care unit, and on the first postoperative day. Intraoperative transfusions of blood products were registered. RESULTS: Both platelet count and platelet aggregation were markedly reduced during surgery with the greatest reduction at the end of CPB. On postoperative day 1, platelet count was still reduced by 50%, while platelet aggregation had returned to-or above-preoperative levels. There were only moderate correlations between platelet count and platelet aggregation. Modified ultrafiltration had no significant influence on platelet count or aggregation. Young age, low weight, and long operation time were associated with poor platelet aggregation during surgery, while young age, low weight, high preoperative haemoglobin levels, and low preoperative platelet count were associated with poor aggregation after operation. Patients with impaired platelet function during CPB had markedly increased intraoperative transfusion requirements. CONCLUSIONS: Platelet count and platelet aggregation are markedly reduced during and immediately after paediatric cardiac surgery, especially in neonates. The recovery in aggregation is faster than that in platelet count. Intraoperative platelet dysfunction is associated with increased transfusion requirements.

International comparisons of the management of patients with non-ST segment elevation acute myocardial infarction in the United Kingdom, Sweden, and the United States: The MINAP/NICOR, SWEDEHEART/RIKS-HIA, and ACTION Registry-GWTG/NCDR registries.

OBJECTIVES: To compare management of patients with acute non-ST segment elevation myocardial infarction (NSTEMI) in three developed countries with national ongoing registries. BACKGROUND: Results from clinical trials suggest significant variation in care across the world. However, international comparisons in "real world" registries are limited. METHODS: We compared the use of in-hospital procedures and discharge medications for patients admitted with NSTEMI from 2007 to 2010 using the unselective MINAP/NICOR [England and Wales (UK); n=137,009], the unselective SWEDEHEART/RIKS-HIA (Sweden; n=45,069), and the selective ACTION Registry-GWTG/NCDR [United States (US); n=147,438] clinical registries. RESULTS: Patients enrolled among the three registries were generally similar except those in the US who were younger but had higher rates of smoking, diabetes, hypertension, prior heart failure, and prior MI than in Sweden or in UK. Angiography and percutaneous coronary intervention (PCI) were performed more often in the US (76% and 44%) and Sweden (65% and 42%) relative to the UK (32% and 22%). Discharge betablockers were also prescribed more often in the US (89%) and Sweden (89%) than in the UK (76%). In contrast, discharge statins, angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), and dual antiplatelet agents (among those not receiving PCI) were higher in the UK (92%, 79%, and 71%) than in the US (85%, 65%, 41%) and Sweden (81%, 69%, and 49%). CONCLUSIONS: The care for patients with NSTEMI differed substantially among the three countries. These differences in care among countries provide an opportunity for future comparative effectiveness research as well as identify opportunities for global quality improvement.

Displacement forces in iliac landing zones and stent graft interconnections in endovascular aortic repair: an experimental study.

OBJECTIVES: Stent graft migration influences the long-term durability of endovascular aortic repair. Flow-induced displacement forces acting on the attachment zones may contribute to migration. Proximal fixation of aortic stent grafts has been improved by using hooks, while distal fixation and stent graft interconnections depend on self-expansion forces only. We hypothesized that flow-induced displacement forces would be significant at the distal end, and would correlate with graft movements. METHODS: As part of an experimental study, an iliac limb stent graft was inserted in a pulsatile flow model similar to aortic in vivo conditions, and fixed-mounted at its proximal and distal ends to strain gauge load cells. Peak displacement forces at both ends and pulsatile graft movement were recorded at different graft angulations (0-90°), perfusion pressures (145/80, 170/90, or 195/100 mmHg), and stroke frequencies (60-100 b.p.m.). RESULTS: Flow-induced forces were of the same magnitude at the proximal and distal end of the stent graft (peak 1.8 N). Both the forces and graft movement increased with angulation and perfusion pressure, but not with stroke rate. Graft movement reached a maximum of 0.29 ± 0.01 mm per stroke despite fixed ends. There were strong correlations between proximal and distal displacement forces (r = 0.97, p < .001), and between displacement forces and graft movement (r = 0.98, p < .001). CONCLUSIONS: Pulsatile flow through a tubular untapered stent graft causes forces of similar magnitude at both ends and induces pulsatile graft movements in its unsupported mid-section. Peak forces are close to those previously reported to be required to extract a stent graft. The forces and movements increase with increasing graft angulation and perfusion pressure. Improved anchoring of the distal end of stent grafts may be considered.

Major obstetric haemorrhage: monitoring with thromboelastography, laboratory analyses or both?

BACKGROUND: Haemorrhage is a common cause of morbidity and mortality in the obstetric population. The aim of this study was to compare the use of thromboelastography and laboratory analyses to evaluate haemostasis during major obstetric haemorrhage. A secondary aim was to evaluate correlations between the results of thromboelastography, laboratory analyses and estimated blood loss. METHODS: Forty-five women with major obstetric haemorrhage and 49 women with blood loss <600 mL were included. The following thromboelastography analyses were performed: time to start of clotting (TEG-R), time to 20 mm of clot firmness (TEG-K), rate of clot growth (TEG-Angle), maximum amplitude of clot (TEG-MA) and lysis after 30 min (TEG-LY30). In addition, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin and D-dimer were measured. RESULTS: Thromboelastography variables reflecting clot stability and fibrinolysis were decreased in women with massive obstetric haemorrhage compared to women with normal bleeding, while clot initiation was accelerated. Laboratory analyses also showed impaired haemostasis with the most pronounced differences in platelet count, fibrinogen concentration and antithrombin activity. The strongest correlations existed between fibrinogen and TEG-MA and between estimated blood loss and TEG-MA, fibrinogen and antithrombin, respectively. CONCLUSIONS: Impaired haemostasis, demonstrated by thromboelastography and laboratory analyses, was found after an estimated blood loss of 2000 mL. Thromboelastography provides faster results than standard laboratory testing which is advantageous in the setting of on-going obstetric haemorrhage. However, laboratory analyses found greater differences in coagulation variables, which correlated better with estimated blood loss.

Effects of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid, clopidogrel, or ticagrelor.

BACKGROUND: Transfusion of platelet concentrate is often used to treat bleeding in patients on platelet inhibitors, but little is known about its efficacy between different inhibitors. We assessed the effect of ex vivo platelet supplementation on platelet aggregability in blood samples from patients treated with acetylsalicylic acid (ASA), clopidogrel, or ticagrelor. METHODS: Platelet aggregability was investigated with multiple electrode aggregometry with adenosine diphosphate (ADP), arachidonic acid (to assess ASA-dependent aggregability), and thrombin receptor activating peptide-6 (TRAP) as activators in whole-blood samples from patients treated with ASA (n=10), ASA+clopidogrel (n=15), or ASA+ticagrelor (n=15), and from healthy controls (n=10). Aggregability was measured before and after supplementation of AB0-compatible fresh apheresis platelets (+46, +92, and +138×10(9) litre(-1)). RESULTS: Both ASA-dependent and ADP-dependent aggregability improved in a dose-dependent fashion after platelet supplementation. ASA-dependent aggregability was completely restored in all patient groups, but there was only a small improvement in ADP-dependent aggregability in patients on dual antiplatelet therapy. There was less effect of platelet supplementation on ADP- and ASA-dependent aggregability in ticagrelor-treated patients than in clopidogrel-treated patients [3.9 (95% confidence interval 1.6-6.3) vs 9.0 (5.2-12.8) AU×min (P=0.021) and 48 (36-59) vs 69 (60-78) AU×min (P=0.004), respectively, at the highest platelet dose]. CONCLUSIONS: Platelet supplementation improved platelet aggregability independently of antiplatelet therapy. The effect on ADP-dependent platelet inhibition was limited however. Reduced effect of platelet transfusion is more likely within 2 h of drug intake in patients treated with ASA+ticagrelor compared with ASA+clopidogrel.