Preoperative assessment of breast cancer: Multireader comparison of contrast-enhanced MRI versus the combination of unenhanced MRI and digital breast tomosynthesis.

PURPOSE: To compare the sensitivity for breast cancer (BC) and BC size estimation of preoperative contrast-enhanced magnetic resonance imaging (CEMRI) versus combined unenhanced magnetic resonance imaging (UMRI) and digital breast tomosynthesis (DBT). PATIENTS AND METHODS: We retrospectively included 56 women who underwent DBT and preoperative 1.5 T CEMRI between January 2016-February 2017. Three readers with 2-10 years of experience in CEMRI and DBT, blinded to pathology, independently reviewed CEMRI (diffusion-weighted imaging [DWI], T2-weighted imaging, pre- and post-contrast T1-weighted imaging) and a combination of UMRI (DWI and pre-contrast T1-weighted imaging) and DBT. We calculated per-lesion sensitivity of CEMRI and UMRI + DBT, and the agreement between CEMRI, UMRI and DBT versus pathology in assessing cancer size (Bland-Altman analysis). Logistic regression was performed to assess features predictive of cancer missing. RESULTS: We included 70 lesions (64% invasive BC, 36% ductal carcinoma in situ or invasive BC with in situ component). UMRI + DBT showed lower sensitivity (86-89%) than CEMRI (94-100%), with a significant difference for the most experienced reader only (p = 0.008). False-positives were fewer with UMRI + DBT (4-5) than with CEMRI (18-25), regardless of the reader (p = 0.001-0.005). For lesion size, UMRI showed closer limits of agreement with pathology than CEMRI or DBT. Cancer size ≤1 cm was the only independent predictor for cancer missing for both imaging strategies (Odds ratio 8.62 for CEMRI and 19.16 for UMRI + DBT). CONCLUSIONS: UMRI + DBT showed comparable sensitivity and less false-positives than CEMRI in the preoperative assessment of BC. UMRI was the most accurate tool to assess cancer size.

Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS).

OBJECTIVES: The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis. METHODS: In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded. RESULTS: There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20). CONCLUSION: No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone. TRIAL REGISTRATION: ISRCTN81818945; http://isrctn.org/.

RDW in patients with systemic lupus erythematosus. Influence of anaemia and inflammatory markers.

Red blood cell distribution width (RDW) is a routine parameter that reflects size variations in erythrocytes. High RDW has been associated with cardiovascular events and inflammatory diseases. However, no studies evaluating the association of RDW with systemic lupus erythematosus (SLE) have been published. We aimed to explore the association of RDW with inflammatory markers in SLE. As SLE is often associated with anaemia, we considered this factor in order to know whether RDW is related with inflammation, anaemia or both in SLE. The study included 105 SLE patients (7 men, 98 women; aged 15-73 years) and 105 controls (9 men, 96 women; aged 18-71 years). Patients were divided according to anaemia status (26 with, 79 without). Biochemical, hematological and inflammatory parameters (C-reactive protein (CRP), fibrinogen and erythrocyte aggregation (EA1)) were analyzed. SLE patients showed increased RDW, CRP and EA1 (p < 0.001), and decreased hemoglobin levels (p < 0.001) when compared with controls. RDW was higher in SLE patients with anaemia (a-SLE) as compared with those without anaemia (na-SLE) (p < 0.01) or controls (p < 0.001). CRP in a-SLE was higher than in controls (p < 0.01) but lower than in na-SLE (p < 0.05). In na-SLE RDW correlated directly with fibrinogen and CRP (p < 0.001), but not in a-SLE. Our results indicate that SLE patients show higher RDW irrespectively of anaemia status, and that RDW is influenced by both anaemia and inflammation, but the influence of anaemia is stronger.

Rheological alterations and thrombotic events in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Nevertheless, how hemorheological alterations contribute to thrombotic risk remains a question of debate. We aimed to determine the rheological profile in 105 patients with SLE (24 with a thrombotic event) and 105 healthy controls. We determined blood viscosity and erythrocyte aggregation along with plasma lipids and fibrinogen. Although SLE patients showed lower blood viscosity at 230 s(-1) at a native hematocrit when compared with controls (p < 0.001), differences disappeared after adjusting the hematocrit to 45% (p = 0.095). When comparing SLE patients with and without thrombotic events, no differences in any rheological parameter were found (p > 0.05), except in fibrinogen which was higher in patients with thrombosis (p = 0.013). No differences in the rheological parameters were observed when venous and arterial thrombotic events were compared, although a tendency for higher fibrinogen was observed in patients with venous thrombosis (p = 0.053). Only hematocrit, fibrinogen and triglycerides were independent predictors of native blood viscosity in the multivariate regression analysis, even after adjusting for continuous variables and for tobacco and hypertension: beta coefficient: 0.727 p < 0.001; beta coefficient: 0.152 p = 0.003 and beta coefficient: 0.133 p = 0.015, respectively. The logistic regression analysis revealed that neither increased native blood viscosity (BVn > 4.33) nor increased erythrocyte aggregation (EA1 > 7.85) increased thrombotic risk: OR 0.636, CI 0.313-3.12, p = 0.578 and OR 2.01, CI 0.77-5.20, p = 0.152, respectively. However, hyperfibrinogenemia (Fbg > 342 mg/dL) increased thrombotic risk by around three times: OR 3.44 CI 1.32-8.96, p = 0.011. Our results suggest that the role of blood viscosity and erythrocyte aggregation in thrombotic risk in SLE patients fails to demonstrate any association.

Hemorheological profile in primary Sjögren's syndrome: a case-control study.

Rheological blood behavior in primary Sjögren's syndrome (SS) has been scarcely investigated. We evaluated the rheological profile (blood viscosity, plasma viscosity, erythrocyte deformability, erythrocyte aggregation, erythrocyte aggregation time and erythrocyte disaggregation threshold) along with fibrinogen, high-sensitive C reactive protein, plasma lipids, immunoglobulins, total proteins and erythrocyte sedimentation rate in 22 patients with primary SS (2 males, 20 females, aged 58 ± 9 years) and in 22 healthy volunteers (3 males, 19 females, aged 57 ± 5 years). Patients showed statistically higher plasma viscosity, erythrocyte sedimentation rate and G immunoglobulin (IgG) levels and lower total cholesterol than controls (p = 0.006, p = 0.023, p = 0.034, p = 0.036, respectively). Three patients with extraglandular involvement showed the highest plasma viscosity values: 1.98 cP, 1.70 cP and 1.65 cP, respectively. No differences were observed for the other rheological parameters analyzed. In a multivariate regression analysis, only fibrinogen, triglycerides and IgG were independent determinants for plasma viscosity values (beta coefficient: 0.335; p = 0.001; beta coefficient: 0.242; p = 0.019; beta coefficient: 0.660; p < 0.001, respectively). Our results indicate that patients with primary SS show increased plasma viscosity, mostly related with IgG levels without other alterations in the rheological profile. Further research with a larger sample size achieved by multicenter studies would be desirable.

Células endoteliales y micropartículas circulantes en pacientes portadores de anticuerpos antifosfolípidos / Circulating endothelial cells and microparticles in patients with antiphospholipid antibodies

Fundamento y objetivo: Determinar si los valores de células endoteliales circulantes (CEC), micropartículas circulantes (MP) y factor von Willebrand (FvW), marcadores establecidos de disfunción/daño endotelial, están elevados en pacientes portadores de anticuerpos antifosfolípidos (AAF) y si existe correlación con marcadores de inflamación y coagulación. Pacientes y método: Se estudian 12 pacientes portadores de AAF y 12 sujetos sanos. Se determinaron CEC, MP, FvW, proteína C reactiva (PCR), fibrinógeno (Fg), ácido siálico (AS), interleucina 6, factor tisular (FT), generación de trombina (GT) y fragmentos de protrombina (F1+2) y de fibrina (DD). Resultados: En los pacientes están significativamente elevados los valores de los marcadores de: disfunción/daño endotelial (CEC, MP y FvW), inflamación (Fg y PCR) y coagulación (FT y DD). El análisis bivariante muestra correlación significativa entre CEC y Fg, AS, PCR y DD, así como entre CEC y FvW y MP. Conclusión: Los pacientes portadores de AAF presentan una disfunción endotelial asociada a un proceso inflamatorio, que, unido a los valores elevados de Fg, FT y DD, puede inducir un estado de hipercoagulabilidad (AU)

Background and objective: To determine whether circulating endothelial cells (CECs), circulatingmicroparticles (MPs) and von Willebrand factor (vWF), established markers of endothelial dysfunction/ damage, are elevated in patients with antiphospholipid antibodies (aPL) and its possible correlation with inflammation and coagulation. Patients and methods: Twelve atients with aPL and 12 healthy subjects were studied. Levels of CECs, MPs, vWF, C reactive protein (CRP), fibrinogen (Fg), sialic acid (SA), interleukin 6 (IL-6), tissue factor (TF), thrombin generation (TG) and prothrombin (F1 + 2) and fibrin (DD) fragments were determined. Results: In patients, markers of dysfunction/damage endothelial, CECs, MPs and vWF; inflammation, Fgand CRP and coagulation, TF and DD were significantly elevated. The bivariate analysis showedsignificant correlation among CECs and Fg, AS, CRP and DD, as well as between CECs and vWF and MPs.Conclusion: Patients with aPL had endothelial dysfunction associated with an inflammatory process,which, together with high levels of Fg, TF and DD, may be responsible for the hypercoagulable state (AU)

[Circulating endothelial cells and microparticles in patients with antiphospholipid antibodies]. / Células endoteliales y micropartículas circulantes en pacientes portadores de anticuerpos antifosfolípidos.

BACKGROUND AND OBJECTIVE: To determine whether circulating endothelial cells (CECs), circulating microparticles (MPs) and von Willebrand factor (vWF), established markers of endothelial dysfunction/damage, are elevated in patients with antiphospholipid antibodies (aPL) and its possible correlation with inflammation and coagulation. PATIENTS AND METHODS: Twelve patients with aPL and 12 healthy subjects were studied. Levels of CECs, MPs, vWF, C reactive protein (CRP), fibrinogen (Fg), sialic acid (SA), interleukin 6 (IL-6), tissue factor (TF), thrombin generation (TG) and prothrombin (F1+2) and fibrin (DD) fragments were determined. RESULTS: In patients, markers of dysfunction/damage endothelial, CECs, MPs and vWF; inflammation, Fg and CRP and coagulation, TF and DD were significantly elevated. The bivariate analysis showed significant correlation among CECs and Fg, AS, CRP and DD, as well as between CECs and vWF and MPs. CONCLUSION: Patients with aPL had endothelial dysfunction associated with an inflammatory process, which, together with high levels of Fg, TF and DD, may be responsible for the hypercoagulable state.

Thrombotic events in systemic lupus erythematosus. Its association with acquired and inherited thrombophilic defects.

Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Although antiphospholipid antibodies (APAs) have been shown to be related with thrombotic tendency in these patients, in more than 40% of them, thrombosis occurs without the presence of such antibodies. We analysed the association of venous and arterial thrombotic events with acquired (anticardiolipin antibodies (ACAs) and lupus anticoagulant (LA)) and inherited (antithrombin (AT), protein C (PC), protein S (PS) deficiencies, factor V Leiden and the prothrombin G20210A mutation), thrombophilic risk factors in 86 SLE patients and 89 healthy controls. Patients showed a higher significant percentage of ACAs titres IgG>41 GPL u/ml and LA than controls (P=0.009; P<0.001, respectively), although no differences in AT, PC, PS deficiencies, factor V Leiden and prothrombin G20210A mutation was observed (P>0.05). When patients with and without thrombosis were compared, those with thrombosis showed a statistically higher percentage of ACAs IgG>41 GPL u/ml and LA (P=0.048; P=0.001, respectively), OR 4.33; 95% CI 1.01-18.50 and OR 11.57; 95% CI 3.28-40.75, respectively. When venous and arterial thrombotic events were considered separately, the presence of LA constituted a risk factor for arterial thrombosis (P=0.010), OR 11.33; 95% CI 1.86-68.89, as well as for venous thrombosis (P=0.005), OR 10.15; 95% CI 2.12-48.64, while ACAs IgG>41 GPL u/ml on their own, were not associated with arterial or venous thrombosis (P=0.142, P=0.233, respectively). In addition inherited thrombophilic risk factors AT, PC, PS deficiencies, factor V Leiden and PT G20210A mutation do not seem to increase thrombotic risk in SLE patients.

Haemorheological changes in patients with systemic lupus erythematosus do not seem to be related to thrombotic events.

Atherothrombotic events are significant factors of mortality and morbidity in patients with systemic lupus erythematosus (SLE). The extent that rheological factors may be involved in these events in these patients has not been established. We measured the following rheological parameters in 86 patients with SLE, of whom 16 had suffered venous and/or arterial thrombotic events, and in 86 healthy controls: fibrinogen (Fbg), plasma viscosity (PV), blood viscosity at 230 s(-1) both at native haematocrit (BVn 230 s(-1) and corrected to 45% (BVc 230 s(-1), erythrocyte aggregation at stasis (AE0) and at 3 s(-1) (AE1), aggregation time (Ta), aggregation index at 10 s (AI10), disaggregation threshold (gammaD), and erythrocyte deformability (ED). In addition glucose, total cholesterol (T-Chol), triglycerides (TG), haematocrit (Hct) and Body Mass Index (BMI) were determined. SLE Disease Activity Index (SLEDAI) was also assessed. The patients showed a significant increase in BMI (P=0.030), TG (P<0.001), PV (P=0.007), AE0 (P=0.005), AE1 (P=0.006), AI10 (P=0.024), gammaD (P=0.001), Fbg (P=0.050); and a significant decrease in Ta (P<0.001), Hct (P<0.001) and BVn 230 s(-1) (P=0.003). When patients with SLEDAI10 were compared, the latter had lower Hct (P=0.041) and lower BVn 230 s(-1) (P=0.017) than those with less SLEDAI. No significant differences were found in any of the parameters analysed on comparing patients who had suffered a thrombotic event with those who had not. Our results suggest that, although patients with SLE have moderate rheological changes, these do not seem to be responsible for the increase in the thrombotic tendency in these patients.

Do hemorheological alterations play any role in the development of thrombotic events in Behçet's disease?

Behçet's disease (BD) is associated with an increased thrombotic risk, although the prothrombotic mechanisms are not clearly defined. Alterations in blood rheology, specially increased erythrocyte aggregation has been suggested to play an important role in the development of thrombotic events in patients with Behçet's disease. In order to ascertain whether any rheological parameter could be involved in the pathogenesis of thrombotic events in Behçet's disease we have determined plasmatic lipids, fibrinogen, hematocrit, erythrocyte aggregation (Myrenne aggregometer), erythrocyte deformability (Rheodyn SSD), blood viscosity (Brookfield viscosimeter), plasma viscosity (Fresenius capillary viscosimeter) and erythrocyte indexes in Behçet's patients with a non-active disease when sampling, and a well matched control group. The patient group was made up of 40 Behçet's patients (20 male, 20 female aged 43+/-12 years) and the control group comprised 70 healthy volunteers (24 male, 46 female aged 45+/-13 years). Twelve of the 40 Behçet's patients have had a previous documented history of deep vein thrombosis at least six months before entering the study, and the other 28 did not. When patients and controls were compared, patients showed a statistically higher fibrinogen level (p=0.002), plasma viscosity (p=0.003), blood viscosity (p=0.021) and erythrocyte aggregation (p=0.049), the other rheological parameters not being statistically significant. No differences were observed in the rheological parameters when patients with and without a previous thrombotic episode were compared. Our results suggest that rheological alterations do not seem to play any role in the development of thrombotic events in patients with Behçet's disease.