Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension

BACKGROUND: Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. MATERIALS AND METHODS: Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. RESULTS: Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. CONCLUSION: Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension

The adherence to initial processes of care in elderly patients with acute venous thromboembolism.

BACKGROUND We aimed to assess whether elderly patients with acute venous thromboembolism (VTE) receive recommended initial processes of care and to identify predictors of process adherence. METHODS We prospectively studied in- and outpatients aged ≥65 years with acute symptomatic VTE in a multicenter cohort study from nine Swiss university- and non-university hospitals between September 2009 and March 2011. We systematically assessed whether initial processes of care, which are recommended by the 2008 American College of Chest Physicians guidelines, were performed in each patient. We used multivariable logistic models to identify patient factors independently associated with process adherence. RESULTS Our cohort comprised 950 patients (mean age 76 years). Of these, 86% (645/750) received parenteral anticoagulation for ≥5 days, 54% (405/750) had oral anticoagulation started on the first treatment day, and 37% (274/750) had an international normalized ratio (INR) ≥2 for ≥24 hours before parenteral anticoagulation was discontinued. Overall, 35% (53/153) of patients with cancer received low-molecular-weight heparin monotherapy and 72% (304/423) of patients with symptomatic deep vein thrombosis were prescribed compression stockings. In multivariate analyses, symptomatic pulmonary embolism, hospital-acquired VTE, and concomitant antiplatelet therapy were associated with a significantly lower anticoagulation-related process adherence. CONCLUSIONS Adherence to several recommended processes of care was suboptimal in elderly patients with VTE. Quality of care interventions should particularly focus on processes with low adherence, such as the prescription of continued low-molecular-weight heparin therapy in patients with cancer and the achievement of an INR ≥2 for ≥24 hours before parenteral anticoagulants are stopped.

Fibrinolysis for patients with intermediate-risk pulmonary embolism

BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

The effects of cardiac output and pulmonary arterial hypertension on volumetric capnography derived-variables during normoxia and hypoxia

The aim of this study was to test the effect of cardiac output (CO) and pulmonary artery hypertension (PHT) on volumetric capnography (VCap) derived-variables. Nine pigs were mechanically ventilated using fixed ventilatory settings. Two steps of PHT were induced by IV infusion of a thromboxane analogue: PHT25 [mean pulmonary arterial pressure (MPAP) of 25 mmHg] and PHT40 (MPAP of 40 mmHg). CO was increased by 50 % from baseline (COup) with an infusion of dobutamine ≥5 μg kg(-1) min(-1) and decreased by 40 % from baseline (COdown) infusing sodium nitroglycerine ≥30 μg kg(-1) min(-1) plus esmolol 500 μg kg(-1) min(-1). Another state of PHT and COdown was induced by severe hypoxemia (FiO2 0.07). Invasive hemodynamic data and VCap were recorded and compared before and after each step using a mixed random effects model. Compared to baseline, the normalized slope of phase III (SnIII) increased by 32 % in PHT25 and by 22 % in PHT40. SnIII decreased non-significantly by 4 % with COdown. A combination of PHT and COdown associated with severe hypoxemia increased SnIII by 28 % compared to baseline. The elimination of CO2 per breath decreased by 7 % in PHT40 and by 12 % in COdown but increased only slightly with COup. Dead space variables did not change significantly along the protocol. At constant ventilation and body metabolism, pulmonary artery hypertension and decreases in CO had the biggest effects on the SnIII of the volumetric capnogram and on the elimination of CO2.

Microfabric memory of vein quartz for strain localization in detachment faults: A case study on the Simplon fault zone

This manuscript deals with the adaptation of quartz-microfabrics to changing physical deformation conditions, and discusses their preservation potential during subsequent retrograde deformation. Using microstructural analysis, a sequence of recrystallization processes in quartz, ranging from Grain-Boundary Migration Recrystallization (GBM) over Subgrain-Rotation Recrystallization (SGR) to Bulging Nucleation (BLG) is detected for the Simplon fault zone (SFZ) from the low strain rim towards the internal high strain part of the large-scale shear zone. Based on: (i) the retrograde cooling path; (ii) estimates of deformation temperatures; and (iii) spatial variation of dynamic recrystallization processes and different microstructural characteristics, continuous strain localization with decreasing temperature is inferred. In contrast to the recrystallization microstructures, crystallographic preferred orientations (CPO) have a longer memory. CPO patterns indicative of prism and rhomb glide systems in mylonitic quartz veins, overprinted at low temperatures (�400 �C), suggest inheritance of a high-temperature deformation. In this way, microstructural, textural and geochemical analyses provide information for several million years of the deformation history. The reasons for such incomplete resetting of the rock texture is that strain localization is caused by change in effective viscosity contrasts related to temporal large- and small-scale temperature changes during the evolution of such a long-lived shear zone. The spatially resolved, quantitative investigation of quartz microfabrics and associated recrystallization processes therefore provide great potential for an improved understanding of the geodynamics of large-scale shear zones.

The VEINES-QOL/Sym questionnaire is a reliable and valid disease-specific quality of life measure for deep vein thrombosis in elderly patients.

PURPOSE To prospectively evaluate the psychometric properties of the Venous Insufficiency Epidemiological and Economic Study (VEINES-QOL/Sym) questionnaire, an instrument to measure disease-specific quality of life and symptoms in elderly patients with deep vein thrombosis (DVT), and to validate a German version of the questionnaire. METHODS In a prospective multicenter cohort study of patients aged ≥ 65 years with acute venous thromboembolism, we used standard psychometric tests and criteria to evaluate the reliability, validity, and responsiveness of the VEINES-QOL/Sym in patients with acute symptomatic DVT. We also performed an exploratory factor analysis. RESULTS Overall, 352 French- and German-speaking patients were enrolled (response rate of 87 %). Both language versions of the VEINES-QOL/Sym showed good acceptability (missing data, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations), validity (convergent, discriminant, known-groups differences), and responsiveness to clinical change over time in elderly patients with DVT. The exploratory factor analysis of the VEINES-QOL/Sym suggested three underlying dimensions: limitations in daily activities, DVT-related symptoms, and psychological impact. CONCLUSIONS The VEINES-QOL/Sym questionnaire is a practical, reliable, valid, and responsive instrument to measure quality of life and symptoms in elderly patients with DVT and can be used with confidence in prospective studies to measure outcomes in such patients.

Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism.

OBJECTIVE To determine the prognostic accuracy of cardiac biomarkers alone and in combination with clinical scores in elderly patients with non-high-risk pulmonary embolism (PE). DESIGN Ancillary analysis of a Swiss multicentre prospective cohort study. SUBJECTS A total of 230 patients aged ≥65 years with non-high-risk PE. MAIN OUTCOME MEASURES The study end-point was a composite of PE-related complications, defined as PE-related death, recurrent venous thromboembolism or major bleeding during a follow-up of 30 days. The prognostic accuracy of the Pulmonary Embolism Severity Index (PESI), the Geneva Prognostic Score (GPS), the precursor of brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) was determined using sensitivity, specificity, predictive values, receiver operating characteristic (ROC) curve analysis, logistic regression and reclassification statistics. RESULTS The overall complication rate during follow-up was 8.7%. hs-cTnT achieved the highest prognostic accuracy [area under the ROC curve: 0.75, 95% confidence interval (CI): 0.63-0.86, P < 0.001). At the predefined cut-off values, the negative predictive values of the biomarkers were above 95%. For levels above the cut-off, the risk of complications increased fivefold for hs-cTnT [odds ratio (OR): 5.22, 95% CI: 1.49-18.25] and 14-fold for NT-proBNP (OR: 14.21, 95% CI: 1.73-116.93) after adjustment for both clinical scores and renal function. Reclassification statistics indicated that adding hs-cTnT to the GPS or the PESI significantly improved the prognostic accuracy of both clinical scores. CONCLUSION In elderly patients with nonmassive PE, NT-proBNP or hs-cTnT could be an adequate alternative to clinical scores for identifying low-risk individuals suitable for outpatient management.

Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study.

BACKGROUND In patients with acute pulmonary embolism (PE), rapid and accurate risk assessment is paramount in selecting the appropriate treatment strategy. The prognostic value of right ventricular dysfunction (RVD) assessed by multidetector CT (MDCT) in normotensive patients with PE has lacked adequate validation. METHODS The study defined MDCT-assessed RVD as a ratio of the RV to the left ventricle short axis diameter greater than 0.9. Outcomes assessed through 30 days after the diagnosis of PE included all-cause mortality and 'complicated course', which consisted of death from any cause, haemodynamic collapse or recurrent PE. RESULTS MDCT detected RVD in 533 (63%) of the 848 enrolled patients. Those with RVD on MDCT more frequently had echocardiographic RVD (31%) than those without RVD on MDCT (9.2%) (p<0.001). Patients with RVD on MDCT had significantly higher brain natriuretic peptide (269±447 vs 180±457 pg/ml, p<0.001) and troponin (0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001) levels in comparison with those without RVD on MDCT. During follow-up, death occurred in 25 patients with and in 13 patients without RVD on MDCT (4.7% vs 4.3%; p=0.93). Those with and those without RVD on MDCT had a similar frequency of complicated course (3.9% vs 2.3%; p=0.30). CONCLUSIONS The PROgnosTic valuE of CT study showed a relationship between RVD assessed by MDCT and other markers of cardiac dysfunction around the time of PE diagnosis, but did not demonstrate an association between MDCT-RVD and prognosis.

Derivation and validation of multimarker prognostication for normotensive patients with acute symptomatic pulmonary embolism.

RATIONALE Not all patients with acute pulmonary embolism (PE) have a high risk of an adverse short-term outcome. OBJECTIVES This prospective cohort study aimed to develop a multimarker prognostic model that accurately classifies normotensive patients with PE into low and high categories of risk of adverse medical outcomes. METHODS The study enrolled 848 outpatients from the PROTECT (PROgnosTic valuE of Computed Tomography) study (derivation cohort) and 529 patients from the Prognostic Factors for Pulmonary Embolism (PREP) study (validation cohort). Investigators assessed study participants for a 30-day complicated course, defined as death from any cause, hemodynamic collapse, and/or adjudicated recurrent PE. MEASUREMENTS AND MAIN RESULTS A complicated course occurred in 63 (7.4%) of the 848 normotensive patients with acute symptomatic PE in the derivation cohort and in 24 patients (4.5%) in the validation cohort. The final model included the simplified Pulmonary Embolism Severity Index, cardiac troponin I, brain natriuretic peptide, and lower limb ultrasound testing. The model performed similarly in the derivation (c-index of 0.75) and validation (c-index of 0.85) cohorts. The combination of the simplified Pulmonary Embolism Severity Index and brain natriuretic peptide testing showed a negative predictive value for a complicated course of 99.1 and 100% in the derivation and validation cohorts, respectively. The combination of all modalities had a positive predictive value for the prediction of a complicated course of 25.8% in the derivation cohort and 21.2% in the validation cohort. CONCLUSIONS For normotensive patients who have acute PE, we derived and validated a multimarker model that predicts all-cause mortality, hemodynamic collapse, and/or recurrent PE within the following 30 days.

Quality of life after pulmonary embolism: validation of the French version of the PEmb-QoL questionnaire.

BackgroundThe PEmb-QoL is a validated 40-item questionnaire to quantify health-related quality of life in patients having experienced pulmonary embolism (PE). It covers six health dimensions: frequency of complaints, activities of daily living limitations, work-related problems, social limitations, intensity of complaints, and emotional complaints. Originally developed in Dutch and English, we sought to prospectively validate the psychometric properties of a French version of the PEmb-QoL.MethodsWe performed a forward and backward translation of the English version of the PEmb-QoL into French. French-speaking consecutive adult patients with an acute, objectively confirmed PE admitted to the emergency department of a Swiss university hospital between 08/2009 and 09/2011 were recruited telephonically. We used standard psychometric tests and criteria to evaluate the acceptability, reliability, and validity of the French version of the PEmb-QoL. We also performed an exploratory factor analysis.ResultsOverall, 102 patients were enrolled in the study. The French version of the PEmb-QoL showed good reliability (internal consistency, item¿total and inter-item correlations), reproducibility (test-retest reliability), and validity (convergent, discriminant) in French-speaking patients with PE. The exploratory factor analysis suggested three underlying dimensions: limitations in daily activity (items 4b-m, 5a-d), symptoms (items 1a-h and 7), and emotional complaints (items 9a-f and j).ConclusionWe successfully validated the French version of the PEmb-QoL questionnaire in patients with PE. Our results show that the PEmb-QoL is a valuable tool for assessing health-related quality of life after PE in French-speaking patients.

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis

BACKGROUND For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis. METHODS AND RESULTS In a controlled clinical trial, 48 patients (mean age 50±21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N=24) or conventional catheter-directed thrombolysis (N=24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55%±27% in the ultrasound-assisted catheter-directed thrombolysis group and 54%±27% in the conventional catheter-directed thrombolysis group (P=0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively (P>0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively (P>0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group (P=0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0±3.9 [range 0-15] versus 1.9±1.9 [range 0-7]; P=0.21), respectively. CONCLUSIONS In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01482273.