Formant frequency discrimination with a fine structure sound coding strategy for cochlear implants.

Recent sound coding strategies for cochlear implants (CI) have focused on the transmission of temporal fine structure to the CI recipient. To date, knowledge about the effects of fine structure coding in electrical hearing is poorly charactarized. The aim of this study was to examine whether the presence of temporal fine structure coding affects how the CI recipient perceives sound. This was done by comparing two sound coding strategies with different temporal fine structure coverage in a longitudinal cross-over setting. The more recent FS4 coding strategy provides fine structure coding on typically four apical stimulation channels compared to FSP with usually one or two fine structure channels. 34 adult CI patients with a minimum CI experience of one year were included. All subjects were fitted according to clinical routine and used both coding strategies for three months in a randomized sequence. Formant frequency discrimination thresholds (FFDT) were measured to assess the ability to resolve timbre information. Further outcome measures included a monosyllables test in quiet and the speech reception threshold of an adaptive matrix sentence test in noise (Oldenburger sentence test). In addition, the subjective sound quality was assessed using visual analogue scales and a sound quality questionnaire after each three months period. The extended fine structure range of FS4 yields FFDT similar to FSP for formants occurring in the frequency range only covered by FS4. There is a significant interaction (p = 0.048) between the extent of fine structure coverage in FSP and the improvement in FFDT in favour of FS4 for these stimuli. FS4 Speech perception in noise and quiet was similar with both coding strategies. Sound quality was rated heterogeneously showing that both strategies represent valuable options for CI fitting to allow for best possible individual optimization.

Effects of clopidogrel with or without aspirin on the generation of extracellular vesicles in the microcirculation and in venous blood: A randomized placebo controlled trial.

BACKGROUND: Dual-antiplatelet therapy (DAPT) is a standard strategy in acute coronary heart disease; however, it confers a considerable bleeding risk. Single-antiplatelet therapy (SAPT) inhibits haemostatic system activation ex vivo to a similar extent as DAPT. Extracellular vesicles (EV) are procoagulant and contribute to haemostatic system activation. We aimed to investigate the effect of DAPT compared with SAPT on EV. METHODS: In a randomized, double-blind, placebo-controlled trial, 44 healthy volunteers received DAPT (clopidogrel + aspirin) or SAPT (clopidogrel + placebo) for 7 days. Blood was obtained from a standardized microvascular injury and through venipuncture at baseline (BL) and at 2 h, 24 h, and 8 days after treatment initiation. The number, origin, and surface expression of EV were assessed using flow cytometry. Data are given as median (quartiles). Non-parametric tests were used to evaluate the short-term (BL vs 2 h) and long-term differences (2 h to 8 days), as well as the differences between treatment groups. RESULTS: There was no difference either in the short-term effects on the number (×103 mL-1) of EV in microvascular blood between DAPT [BL: 1433 (653; 3184) vs 2 h: 862 (545; 2026), p = 0.39] and SAPT [(BL: 614 (552; 1402) vs 2 h: 1079 (781; 1538), p = 0.75)] or in the long-term effects. DAPT and SAPT did not exhibit differential short-term effects on the number and proportion (36% and 27% vs 55% and 36%) of platelet-derived EV. DAPT and SAPT resulted in a significant short-term increase in phosphatidylserine expression in microvascular blood. The effects of DAPT and SAPT on EV in venous blood were similar to those in microvascular blood. CONCLUSION: DAPT and SAPT have comparable effects on the amount, origin, and surface characteristics of EV.

Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. METHODS: Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. RESULTS: Serum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. CONCLUSIONS: Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.

Pelvic reconstruction following resection of malignant bone tumours using a stemmed acetabular pedestal cup.

AIMS: Pelvic reconstruction after the resection of a tumour around the acetabulum is a challenging procedure due to the complex anatomy and biomechanics. Several pelvic endoprostheses have been introduced, but the rates of complication remain high. Our aim was to review the use of a stemmed acetabular pedestal cup in the management of these patients. PATIENTS AND METHODS: The study involved 48 patients who underwent periacetabular reconstruction using a stemmed pedestal cup (Schoellner cup; Zimmer Biomet Inc., Warsaw, Indiana) between 2000 and 2013. The indications for treatment included a primary bone tumour in 27 patients and metastatic disease in 21 patients. The mean age of the patients at the time of surgery was 52 years (16 to 83). RESULTS: At a median follow-up of 6.6 years (95% confidence interval 4.6 to 8.2), local control was achieved in all patients; 19 patients had died (16 of disease). Complications occurred in 19 patients (40%), of which deep infection was the most common, affecting eight patients (17%). Seven patients (15%) had a dislocation of the hip. Aseptic loosening was found in three patients (6%). Two (4%) underwent hindquarter amputation for non-oncological reasons. The risk of revision, with death being treated as a competing event, was 28% at one year, 39% at five years and 48% at ten years post-operatively. The mean Musculoskeletal Tumour Society Score at final follow-up was 71% (27% to 93%). CONCLUSION: This type of reconstruction is a satisfactory option for the treatment of patients with a periacetabular tumour. There remains, however, a high rate of complication, which may be reduced by future modifications of the device such as silver coating and tripolar articulation. Cite this article: Bone Joint J 2017;99-B:841-8.

The outcome of the surgical treatment of pelvic chondrosarcomas: a competing risk analysis of 58 tumours from a single centre.

AIMS: Few studies dealing with chondrosarcoma of the pelvis are currently available. Different data about the overall survival and prognostic factors have been published but without a detailed analysis of surgery-related complications. We aimed to analyse the outcome of a series of pelvic chondrosarcomas treated at a single institution, with particular attention to the prognostic factors. Based on a competing risk model, our objective was to identify risk factors for the development of complications. PATIENTS AND METHODS: In a retrospective single-centre study, 58 chondrosarcomas (26 patients alive, 32 patients dead) of the pelvis were reviewed. The mean follow-up was 13 years (one week to 23.1 years). RESULTS: A total of 26 patients (45%) were alive and 32 patients (55%) had died. Overall survival was 76%, 55% and 45% at one, five and ten years post-operatively, respectively. In a competing risk model the cumulative risk of the development of a surgery-related complication was 64% at six months and 69% at one year, post-operatively, respectively. Endoprosthetic reconstruction was a significant risk factor for the development of complications (p = 0.006). Complications were not significantly related to age or the location or grade of the tumour (p = 0.823, p = 0.976, p = 0.858). The development of complications did not have a negative effect on survival (p = 0.147). CONCLUSION: This is the first study with competing risk analysis of surgery-related complications in patients with a pelvic chondrosarcoma. The surgery in these patients remains prone to complications. Endoprosthetic reconstruction significantly increases the risk of the development of complications (p = 0.006). A competing risk model showed that the development of complications does not have a negative influence on overall survival (p = 0.147). An aggressive, surgical resection with the goal of achieving wide margins whenever possible remains the mainstay of treatment. Cite this article: Bone Joint J 2017;99-B:686-96.

Survival, failure modes and function of combined distal femur and proximal tibia reconstruction following tumor resection.

BACKGROUND: Tumor spread to the knee joint or skip metastasis to the adjacent bones of the knee require reconstruction with combined distal femur and proximal tibia replacements. The literature on implant survival and failure modes with this type of reconstruction is sparse. The goals of this study were to determine the implant survival, the different failure modes and the functional outcome of this megaendoprosthetic reconstruction. PATIENTS AND METHODS: Thirty-nine patients with combined distal femur and proximal tibia reconstruction were retrospectively reviewed. Median follow-up was 8.8 years (quartiles 4.7-15.5 years). Twenty-one patients received combined distal femur and proximal tibia reconstruction as a primary mode of reconstruction, 18 patients as revision surgery after failed tumor prosthesis. For survival estimations, competing risk analyses were performed. RESULTS: The revision-free survival at five years was 42% (95% CI 22%-56%) and implant survival with exchange of the original implant was 54% (95% CI 35%-68%). Five-year revision-free survival for soft tissue failure was 72% (95% CI 52%-84%), for infection 67% (95% CI 48%-80%), for structural failure 82% (95% CI 63%-91%), for aseptic loosening and tumor progression 97% (95% CI 82%-99%), respectively. Patients with revision surgery had higher risk for infection (p < 0.001), structural failure (p = 0.037) and shorter revision-free- (p = 0.025) and implant-survival (p = 0.006). Limb survival at 20 years was 94%. Mean musculoskeletal Tumor Society score was 76%. CONCLUSION: Despite high failure rates with short revision-free survivals, combined distal femur and proximal tibia reconstruction achieved longtime limb survival in the majority of patients with satisfying function.

A connection between neurovascular conflicts within the cerebellopontine angle and vestibular neuritis, a case controlled cohort study.

This retrospective, observer blinded case-control study aims to compare the prevalence of neurovascular conflicts (NVCs) of the vestibulocochlear nerve and the anterior inferior cerebellar artery (AICA) in patients presenting with clinical signs of acute vestibular neuritis with and without subsequent objective vestibular function loss (VFL). 58 acute cases of clinically suspected acute vestibular neuritis were investigated with same day cranial MRI at a tertiary referral centre and compared to 61 asymptomatic controls. The prevalence of NVCs in cases with objective VFL were also compared to cases without VFL. Radiologists described the NVC as "no contact" (Grade 0), "contact < 2 mm" (Grade 1), "contact > 2 mm" (Grade 2) and "vascular loop presence" (Grade 3) without knowledge of neurotological data. Neurotological data was collected without knowledge of MRI findings. Vestibular function was tested by bithermic caloric irrigation. 26 cases (45%) showed caloric VFL (Group A), whereas 32 (55%) exhibited no VFL (Group B). Group A included 13 cases with NVCs (50%), Group B included 26 NVC cases (82%) (p = 0.012) and the control group included 16 individuals (26%) (p < 0.001 for comparison of all 3 groups). Group B had a significantly higher NVC-Grading than Group A (p = 0.009). There was no statistically significant association between NVCs and either SNHL or tinnitus (p > 0.05). Our results suggest that patients presenting with clinical signs of acute vestibular neuritis who show symmetrical caloric vestibular function test results have a significantly higher NVC prevalence in the cerebellopontine angle.

PO-63 - Exhausted platelets in cancer patients with high risk of venous thromboembolism and poor prognosis.

INTRODUCTION: Platelets play a crucial role in cancer development, progression and metastatic spread of malignancy. In vitro data show that cancer cells have the ability to activate platelets, and clinical studies found increased levels of platelet activation markers in cancer patients. Moreover, platelets are thought to be involved in the development of venous thromboembolism (VTE) in cancer patients, a frequent complication of malignant disease associated with high morbidity and mortality. AIM: In this study, we aimed to examine the activation status of platelets in cancer patients and investigate the association with risk of future venous thromboembolism (VTE) and mortality. MATERIALS AND METHODS: In a prospective observational cohort study of cancer patients we measured pre-chemotherapy platelet P-selectin and glycoprotein (GP) IIb/IIIa expression and monocyte-platelet aggregates (MPA) in vivo and in response to ex vivo stimulation of the platelet activation receptors protease-activated receptor (PAR) -1, -4, and GPVI by whole blood flow cytometry. Primary and secondary endpoints of the study were occurrence of objectively confirmed VTE and death during 2-year follow-up, respectively. RESULTS: Out of 62 patients (median age [interquartile range, IQR]: 63 [54-70] years, 48% female) with cancers of the pancreas (n=19), lung (n=18), brain (n=14), colon (n=8) and stomach (n=3), 9 (14.5%) developed VTE and 32 (51.6%) died. P-selectin, activated GPIIb/IIIa expression and MPA formation did not significantly differ between tumor sites (Kruskal Wallis test). Reduced platelet responsiveness to PAR-1 and GPVI stimulation was associated with a higher risk of VTE (hazard ratio [HR] per decile increase in %P-selectin positive platelets: 0.73 [95% confidence interval: 0.56-0.92, p=0.007] and 0.77 [0.59-0.98, p=0.034], respectively; Table 1). Further, lower platelet P-selectin and activated GPIIb/IIIa expression in vivo and in response to PAR-1, -4 and GPVI stimulation, but not MPA formation, were associated with a higher risk of death (Table 1). CONCLUSIONS: Cancer patients with a poor prognosis had degranulated platelets, presumably as a consequence of previous activation. Our data suggest that platelets' continuous activation and thus exhaustion is involved in cancer-associated VTE and cancer mortality.

Longitudinal analysis of hemostasis biomarkers in cancer patients during antitumor treatment.

UNLABELLED: ESSENTIALS: Hemostasis biomarkers impact thrombosis occurrence and survival in cancer patients. We performed a longitudinal analysis of hemostatic parameters in 112 cancer patients. Hemostatic parameters are associated with disease state, patients' prognosis, and the risk of VTE. The procoagulant state exists not only at diagnosis, but also during the course of disease. BACKGROUND: Hemostasis biomarkers are known to have an impact on venous thromboembolism (VTE) occurrence and survival in cancer patients. OBJECTIVES: As there are almost no data on longitudinal changes, we aimed to evaluate those in the present prospective observational study during chemotherapy and the course of disease. PATIENTS/METHODS: Patients with cancer of the brain (n = 39), lung (n = 41), colon (n = 15) or pancreas (n = 17) were included before initiation of antitumor therapy. Blood samples for determination of factor VIII, thrombin peak height, D-dimer, F1 + 2 , fibrinogen and soluble P-selectin (sP-selectin) were drawn on a monthly basis. The study endpoints were death, VTE occurrence, or completion of the study period. RESULTS: Overall, 546 blood samples of 112 patients were analyzed. D-dimer and sP-selectin levels were significantly higher in patients with distant metastasis than in those without. Patients with complete remission had significantly lower levels of F1 + 2 , D-dimer and fibrinogen. Peak height thrombin levels showed a decrease over time in all tumor types. Levels of biomarkers behaved differently in the various tumor types. Patients who developed VTE (n = 14) showed increasing levels of FVIII, sP-selectin, and D-dimer. At the last blood sampling time-point before VTE occurrence, in 13 patients the D-dimer level was above the median, and in seven of these patients it was even above the 75th percentile; however, the individual course was highly variable. Regarding survival, steadily increased FVIII, sP-selectin and D-dimer levels were associated with higher mortality. CONCLUSIONS: Hemostatic parameters show an association with disease state, prognosis, and the risk of VTE, not only at diagnosis, but also during the course of antineoplastic treatment.

Effects of P2Y12 receptor inhibition with or without aspirin on hemostatic system activation: a randomized trial in healthy subjects.

UNLABELLED: ESSENTIALS: In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in ß-thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy. BACKGROUND: Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor. OBJECTIVES: To compare the effects of dual and single antiplatelet therapies on hemostatic system activation. PATIENTS/METHODS: In a randomized, parallel-group, double-blind, placebo-controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d(-1) ) and aspirin (100 mg d(-1) ) or placebo for 7 days; An additional 44 volunteers received single-dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. ß-Thromboglobulin (ß-TG [IU L(-1) ]) and prothrombin fragment 1.2 (f1.2 [nmol L(-1) ]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time. RESULTS: Clopidogrel plus aspirin and clopidogrel plus placebo reduced ß-TG by a GMR of 0.51 (0.42-0.63) and 0.54 (0.46-0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased ß-TG by a GMR of 0.38 (0.26-0.57) and 0.47 (0.31-0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45-0.75) and 0.55 (0.38-0.80); clopidogrel did not. Over 24 h, no difference in ß-TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -2.9 [-9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.5 [-11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -4.2 [-10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.6 [-10.9 to 3.7]). CONCLUSIONS: P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent.

Estimating risk of venous thromboembolism in patients with cancer in the presence of competing mortality.

BACKGROUND: In studies on cancer-associated venous thromboembolism (VTE), patients not only are at risk for VTE but also may die from their underlying malignancy. OBJECTIVES: In this competing-risk (CR) scenario, we systematically compared the performance of standard (Kaplan-Meier estimator [1-KM]), log-rank test, and Cox model) and specific CR methods for time-to-VTE analysis. PATIENTS AND METHODS: Cancer patients (1542) were prospectively followed for a median of 24 months. VTE occurred in 112 (7.3%) patients, and 572 (37.1%) patients died. RESULTS: In comparison with the CR method, 1-KM slightly overestimated the cumulative incidence of VTE (cumulative VTE incidence at 12 and 24 months [1-KM vs. CR]: 7.22% vs. 6.74%, and 8.40% vs. 7.54%, respectively). Greater bias was revealed in tumor entities with high early mortality (e.g., pancreatic cancer, n = 99, 24-month cumulative VTE incidence: 28.37% vs. 19.30%). Comparing the (subdistribution) hazard of VTE between patients with low and high baseline D-dimer, the Cox model yielded a higher estimate than the corresponding CR model (hazard vs. subdistribution hazard ratio [95% CI] 2.85 [1.92-4.21] vs. 2.47 [1.67-3.65]). For this comparison, the log-rank test yielded a higher test statistic and smaller P-value than Gray's test (χ(2) on 1 degree of freedom: 29.88 vs. 21.34). CONCLUSION: In patients with cancer who are at risk for VTE and death, standard and CR methods for time-to-VTE analysis can generate differing results. For 1-KM, the magnitude of bias is a direct function of competing mortality. Consequently, bias tends to be negligible in cancer patient populations with low mortality but can be considerable in populations at high risk of death.

The association of the Thr715Pro P-selectin genotype with levels of P-selectin in platelet concentrates.

BACKGROUND AND OBJECTIVES: P-selectin is stored in the alpha granules of platelets and in the Weibel Palade bodies of endothelial cells; upon activation, it is translocated to the cell surface and released into the plasma in soluble form. One variant of the P-selectin gene, the Thr715Pro polymorphism, is strongly associated with the plasma levels of soluble P-selectin. In platelet concentrates soluble P-selectin can be regarded mainly platelet derived. MATERIALS AND METHODS: The relation of the genotype with soluble P-selectin, platelet expressed P-selectin and the sum of all forms of P-selectin - comprising soluble P-selectin, platelet surface P-selectin and P-selectin from the alpha granules - was assessed in fresh whole blood and in apheresis platelets suspended in 35% plasma/65% SSP+ obtained from 89 platelet donors. RESULTS: Levels of total P-selectin were genotype associated (P = 0·025); likewise, in fresh whole blood there was an association of soluble P-selectin with genotype (P = 0·02). In platelets suspended in additive solution, however, levels of the storage-associated or TRAP-6 agonist induced increase of platelets' P-selectin were not associated with the genotype. A correlation between levels of soluble P-selectin and surface expression of P-selectin was observed on day 3 of storage in Thr715Thr individuals (P < 0·0001), but not in heterozygotes (Thr715Pro, P = 0·2). CONCLUSION: The donors' genotype has only little influence on levels of soluble P-selectin in apheresis platelets suspended in 35% plasma/65% SSP+.

Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients.

Cytokines have been found to be elevated in cancer patients and have been associated with worse prognosis in single tumour entities. We investigated the association of eight different cytokines with venous thromboembolism (VTE) and prognosis in cancer patients. The Vienna Cancer and Thrombosis Study (CATS), a prospective study, includes patients with newly diagnosed tumour or disease progression. Patients with an overt infection are excluded. Study end-points are VTE, death, loss to follow-up or study completion. Interleukin (IL) serum levels were measured using the xMAP technology developed by Luminex. Among 726 included patients, no associations between IL levels and VTE were found, with the exception of a trend for IL-1ß and IL-6 in pancreatic cancer. Elevated levels of IL-6 [as continuous variable per double increase hazard ratio (HR) = 1·07, 95% confidence interval (CI) = 1·027-1·114, P = 0·001, IL-8 (HR = 1·12, 95% CI = 1·062-1·170, P < 0·001) and IL-11 (HR = 1·37, 95% CI = 1·103-1·709, P = 0·005] were associated with worse survival. In subgroup analyses based on tumour type, colon carcinoma patients, who had higher IL-6 levels, showed a shorter survival (HR = 2·405, 95% CI = 1·252-4·618, P = 0·008). A significant association of elevated IL-10 levels with a decrease in survival (HR = 1·824, 95% CI = 1·098-3·031, P = 0·020) was seen among patients with lung cancer. No correlation between VTE and IL levels was found, but higher IL-6, IL-8 and IL-11 levels were associated with worse survival in cancer patients. Further, elevated IL-6 levels might be a prognostic marker in colorectal cancer and elevated IL-10 levels in lung cancer patients.

Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery.

BACKGROUND: Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS: We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringer's lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS: The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS: Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

The discriminatory capacity of BMD measurements by DXA and dual X-ray and laser (DXL) at the calcaneus including clinical risk factors for detecting patients with vertebral fractures.

UNLABELLED: Osteoporotic fracture risk depends on bone mineral density (BMD) and clinical risk factors (CRF). Five hundred and eighty-eight untreated female and male outpatient subjects were evaluated, 160 with vertebral fractures. BMD was measured both by using calcaneal dual X-ray and laser (DXL) and dual-energy X-ray absorptiometry (DXA), and CRF were evaluated. Detection frequencies for different BMD methods with or without CRF are presented. INTRODUCTION: Osteoporotic fracture risk depends on bone mineral density and clinical risk factors. DXA of the spine/hip is considered a gold standard for BMD assessment, but due to degenerative conditions, particularly among the older population, assessment of BMD at the lumbar spine has been shown to be of limited significance. Portable calcaneal dual X-ray technology and laser can be an easily obtainable alternative. METHODS: Vertebral fractures were evaluated in a baseline analysis of 588 females and males (median age 64.4, range 17.6-93.1 years), comparing BMD measurements by using DXL and DXA and CRF with/without BMD. One hundred and sixty subjects had radiological verified vertebral fractures. Area under receiver-operating characteristic curves (AUROCC) and univariate and multiple logistic regressions were calculated. RESULTS: AUROCC for detection of vertebral fractures was comparable for DXL at calcaneus and DXA at femoral neck (DXL 0.665 and DXA 0.670). Odds ratio for prevalent vertebral fracture was generally weak for DXA femoral neck (0.613) and DXL (0.521). Univariate logistic regression among CRF without BMD revealed age, prevalent fragility fracture, and body mass index significantly associated with prevalent vertebral fracture (AUROCC = 0.805). Combining BMD and CRF, a prognostic improvement in case of DXA at femoral neck (AUROCC 0.869, p = 0.02), DXL at calcaneus (AUROCC 0.869, p = 0.059), and DXA at total hip (AUROCC 0.861, p = 0.06) was observed. CONCLUSIONS: DXL was similarly sensitive compared with DXA for identification of subjects with vertebral fragility fractures, and combination of CRF with BMD by DXL or DXA further increased the discriminatory capacity for detection of patients susceptible to vertebral fracture.

Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients.

BACKGROUND: Tissue factor (TF) expression by tumors contributes to tumor growth. Release of TF-positive microparticles (MPs) may contribute to venous thromboembolism (VTE). OBJECTIVES: To conduct a prospective cohort study to determine whether elevated MP-associated TF (MP-TF) activity is predictive of VTE and mortality in four cancer types. PATIENTS/METHODS: We determined MP-TF activity in pancreatic, gastric, colorectal and brain cancer patients. We used a chromogenic endpoint assay for all patients and also a chromogenic kinetic assay for patients with pancreatic and brain cancer. RESULTS: During follow-up, 12/60 (20%) pancreatic, 6/43 (14%) gastric, 12/126 (10%) colorectal and 19/119 (16%) brain cancer patients developed VTE; 46/60 (77%), 30/43 (70%), 47/126 (37%) and 67/119 (56%), respectively, died. MP-TF activity levels were highest in pancreatic cancer. We did not find a statistically significant association of MP-TF activity with the risk of VTE in any of the four cancer types by using two statistical methods. An association of MP-TF activity with the risk of mortality was detected in pancreatic cancer with the endpoint assay (hazard ratio [HR] 1.8 and 95% confidence interval [CI] 1.4-2.3 per doubling of activity, P < 0.001) and the kinetic assay (HR 1.2, 95% CI 1.1-1.4, P < 0.001); adjustment for type of treatment was not performed. In pancreatic cancer, MP-TF activity correlated with D-dimer level (endpoint assay, r = 0.51; chromogenic assay, r = 0.48), and a correlation between assays (r = 0.61) was found. CONCLUSION: MP-TF activity was not associated with future VTE in pancreatic, gastric, colorectal and brain cancer. However, we found a strong association of MP-TF activity with mortality in pancreatic cancer. MP-TF activity might be reflective of an aggressive pancreatic cancer phenotype.

Mortality and inherited thrombophilia: results from the European Prospective Cohort on Thrombophilia.

BACKGROUND: Data on the survival of individuals with hereditary thrombophilia are rare and only come from retrospective studies. OBJECTIVE: The aim of the present study was to assess mortality in individuals with known thrombophilia with and without a history of thrombosis in comparison to a control group. PATIENTS/METHODS: The European Prospective Cohort on Thrombophilia (EPCOT) study is a prospective, multi-center observational study performed to assess the risk of thrombosis in persons with inherited thrombophilia. In an extension of the present study, the vital status was assessed in 1240 individuals with thrombophilia (mean age 40.9 years, 59% women, 196 with antithrombin, 341 with protein C, 276 with protein S-deficiency, 330 with factor (F)V Leiden and 97 with combined defects, and 62% with a history of venous thrombosis [VT]) and 875 controls (mean age 42.5 years, 48% women, 7% with a history of VT). RESULTS: Seventy-two individuals with thrombophilia and 45 controls died during follow-up. The risk of death, adjusted for gender, thrombosis history and center, was not associated with thrombophilia (hazard ratio [HR] thrombophilia individuals vs. controls: 1.09, 95% confidence interval [CI] 0.66-1.78). When individuals with thrombophilia were evaluated separately, a history of thrombosis was not associated with mortality: the risk of death after adjustment for gender, anticoagulation and center was HR 0.79 (95% CI, 0.41-1.54). CONCLUSIONS: No increased risk of death in individuals with thrombophilia, not even in those with a history of thrombosis, was observed.

Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis.

Severe aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation.

Evaluation of stroke volume variation obtained by arterial pulse contour analysis to predict fluid responsiveness intraoperatively.

BACKGROUND: Fluid management guided by oesophageal Doppler monitor has been reported to improve perioperative outcome. Stroke volume variation (SVV) is considered a reliable clinical predictor of fluid responsiveness. Consequently, the aim of the present trial was to evaluate the accuracy of SVV determined by arterial pulse contour (APCO) analysis, using the FloTrac/Vigileo system, to predict fluid responsiveness as measured by the oesophageal Doppler. METHODS: Patients undergoing major abdominal surgery received intraoperative fluid management guided by oesophageal Doppler monitoring. Fluid boluses of 250 ml each were administered in case of a decrease in corrected flow time (FTc) to <350 ms. Patients were connected to a monitoring device, obtaining SVV by APCO. Haemodynamic variables were recorded before and after fluid bolus application. Fluid responsiveness was defined as an increase in stroke volume index >10%. The ability of SVV to predict fluid responsiveness was assessed by calculation of the area under the receiver operating characteristic (ROC) curve. RESULTS: Twenty patients received 67 fluid boluses. Fifty-two of the 67 fluid boluses administered resulted in fluid responsiveness. SVV achieved an area under the ROC curve of 0.512 [confidence interval (CI) 0.32-0.70]. A cut-off point for fluid responsiveness was found for SVV > or =8.5% (sensitivity: 77%; specificity: 43%; positive predictive value: 84%; and negative predictive value: 33%). CONCLUSIONS: This prospective, interventional observer-blinded study demonstrates that SVV obtained by APCO, using the FloTrac/Vigileo system, is not a reliable predictor of fluid responsiveness in the setting of major abdominal surgery.