Upgrading Therapy Strategy Improves Pregnancy Outcome in Antiphospholipid Syndrome: A Cohort Management Study

The current study evaluates the efficacy and safety of different treatment strategies for pregnant patients with antiphospholipid syndrome. One hundred twenty-seven consecutive pregnancies were assessed; 87 (68.5%) with a history of pregnancy morbidity alone were treated with prophylactic low molecular weight heparin (LMWH) + low-dose aspirin (LDA, 100 mg) (group I) and 40 (31.5%) with a history of thrombosis and/or severe pregnancy complications with therapeutic LMWH + LDA (group II). LMWH doses were increased throughout the pregnancies depending on the patients' weight gain, and treatment was switched to a more intensive one at the first sign of maternal/fetal complications. The study's primary outcome was live births. There were no significant differences in live birth rate between group I (95.4%) and group II (87.5%). Even fetal complication rate was similar in the two groups; group II nevertheless had a higher prevalence of maternal and neonatal complications (p = 0.0005 and p = 0.01, respectively) and registered a significantly lower gestational age at delivery and birth weight (p = 0.0001 and p = 0.0005, respectively). Two patients in group I switched to group II therapy, six patients in group II switched to a more intensive treatment strategy (weekly plasma exchange + fortnightly intravenous immunoglobulins in addition to therapeutic LMWH + LDA). The multivariate analysis uncovered that triple antiphospholipid antibodies positivity was an independent factor leading to a more intensive therapy. All eight switched patients achieved a live birth. Study results revealed that adjusted LMWH doses and switching therapy at first signs of severe pregnancy complications led to a high rate of live births in antiphospholipid syndrome patients

AB0378 UPGRADING THERAPY STRATEGY IMPROVES PREGNANCY OUTCOME IN ANTIPHOSPHOLIPID SYNDROME: A COHORT MANAGEMENT STUDY

Background:While it is generally agreed that pregnant APS patients should receive personalized treatment, evidence-based guidelines for these patients continue to be lacking.Objectives:The current study was designed as a management cohort study aiming to evaluate the efficacy and safety of different treatment strategies for pregnant APS patients in the attempt to provide some practical suggestions for attending physicians.Methods:One-hundred-twenty-seven consecutive pregnancies were assessed; 87 (68.5%) with a history of pregnancy morbidity alone were treated with prophylactic low molecular weight heparin (LMWH)+low-dose aspirin (LDA, 100 mg) [Group I] and 40 (31.5%) with a history of thrombosis and/or severe pregnancy complications with therapeutic LMWH+LDA [Group II]. LMWH doses were increased throughout the pregnancies depending on the patients' weight gain, and treatment was switched to a more intensive one at the first sign of maternal/fetal complications. The study's primary outcome was live births.Results:There were no significant differences in live birth rate between Group I (95.4%) and Group II (87.5%). Even, fetal complication rate was similar in the two groups; the Group II nevertheless had a higher prevalence of maternal and neonatal complications (p=0.0005 and p=0.01, respectively) and registered a significantly lower gestational age at delivery and birth weight (p=0.0001 and p=0.0005, respectively). Two patients in Group I switched to Group II therapy, six patients in Group II switched to a more intensive treatment strategy (weekly plasma exchange+ fortnightly intravenous immunoglobulins in addition to therapeutic LMWH+LDA). Comparison of the clinical and laboratory characteristics between patients who had shifted to a more intensive therapy and those who did not showed a significant prevalence of history of thrombosis ± pregnancy morbidity (p=0.02, OR 5.96, 95% CI 1.33-26.62) previous pregnancy complications (p=0.02, OR 8.32, 95% CI 1.67-41.3), triple aPL positivity (p <0.0001, OR 97.13, 95% CI 10.6-890) and pregnancy complications (p<0.0001, OR 197,7, 95% CI 10.57-3699) in upgrading group, instead single aPL positivity significantly prevailed (p=0.003, OR 0.06, 95% CI 0.008-0.58) in non-upgrading group. Logistic regression analysis demonstrated that triple aPL positivity was an independent factor for switching to a more effective therapy protocol (p <0.0001, OR 98, 95% CI 10.7-897.54). All eight switched patients achieved a live birth.Conclusion:Using adjusted LMWH doses and upgrading therapy at the first signs of pregnancy complications led to a high rate of live births in a relatively large group of APS patients. The study outlines the criteria for prescribing appropriate therapy for various subsets of these patients and for switching/upgrading the treatment protocol when it is no longer sufficient. Unfortunately, for the moment there are no evidence-based guidelines on the ideal additional treatment in refractory to conventional therapy APS patients. The present results will hopefully help point the direction of future clinical trials investigating the efficacy and safety of the different therapies on large numbers of APS pregnant patients in order to identify the benefits and limits of different treatment strategies administered from the beginning of pregnancy.Disclosure of Interests:Ariela Hoxha Speakers bureau: Celgene, UCB, Novartis, Sanofi, Werfen, Maria Favaro: None declared, Antonia Calligaro: None declared, Teresa Del Ross: None declared, Alessandra Teresa Ruffatti: None declared, Chiara Infantolino: None declared, Marta Tonello: None declared, Elena Mattia: None declared, Amelia Ruffatti: None declare

Confirmation of antiphospholipid antibody positivity: a year's results in a cohort of 113 patients

Objective: To evaluate the confirmation rate of antiphospholipid antibodies (aPL), to analyze their behaviour at confirmation time, and to study the clinical value of their confirmation. Methods: Blood samples from 380 subjects, enrolled in this study from June 1, 2007 to May 31, 2008, were tested for anti-cardiolipin (aCL) and anti-beta2glycoprotein (aβ2GPI) antibodies using an ELISA method and for Lupus anticoagulant (LA) using a series of clotting tests. The samples of the 113 subjects resulting positive at the first testing time were assayed again to confirm antiphospholipid positivity. Results: aPL positivity was confirmed in 67 out of the 113 subjects (59.3%). Medium-high antibody levels of all, except IgM aCL, aPL/ELISA had a significantly higher confirmation rate with respect to that in subjects with low levels. The confirmation rate in the category I antibody patients (multiple positivity) was higher than that in the category II antibody subjects (single positivity). LA positivity was confirmed only when it was associated to other aPL. The cut-off of 40 GPL produced a confirmation rate equal to that resulting from a 99th percentile cut-off. Confirmation of aPL positivity made it possible for us to confirm the diagnosis of antiphospholipid syndrome (APS) in 8 out of the 113 subjects originally resulting positive (7,1%). APS clinical features were vascular thrombosis in 4 of these and pregnancy morbidity in the other 4. Conclusions: Our data emphasize aPL positivity confirmation selectivity, and medium-high antibody levels and category I antibodies (multiple positivity) had the best confirmation rates

Spin correlations in p⃗p⃗→pnπ+\vec{p}\vec{p}\to pn\pi^{+} pion production near threshold

A first measurement of longitudinal as well as transverse spin correlation coefficients for the reaction $\vec{p}\vec{p}\to pn\pi^+$ was made using a polarized proton target and a polarized proton beam. We report kinematically complete measurements for this reaction at 325, 350, 375 and 400 MeV beam energy. The spin correlation coefficients $A_{xx}+A_{yy}, A_{xx}-A_{yy}, A_{zz}, A_{xz},$ and the analyzing power $A_{y},$ as well as angular distributions for $\sigma(\theta_{\pi})$ and the polarization observables $A_{ij}(\theta_{\pi})$ were extracted. Partial wave cross sections for dominant transition channels were obtained from a partial wave analysis that included the transitions with final state angular momenta of $l\leq 1$. The measurements of the ${\vec{p}\vec{p}\to pn\pi^{+}}$ polarization observables are compared with the predictions from the J\"ulich meson exchange model. The agreement is very good at 325 MeV, but it deteriorates increasingly for the higher energies. At all energies agreement with the model is better than for the reaction ${\vec{p}\vec{p}\to pp\pi^{0}}$.Comment: Preprint, 21 pp, submitted to Phys. Rev. C. Keywords: Mesons, Polarization, Spin Correlations, Few body system

Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Background: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. Objective: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. Patients/methods: A comparison of patients with LA without (LA+/aβ2GPI−) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. Results and conclusions: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI− patients were positive for aPS/PT antibodies. LA+/aβ2GPI− compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic event

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ABSTRACT. Objective. The effect of low-dose aspirin (LDA) on pregnancy outcome in antiphospholipid (aPL)-positive women not fulfilling the criteria for antiphospholipid antibody syndrome (APS) was evaluated retrospectively. Methods. We evaluated 139 pregnancies of 114 aPL-positive women not fulfilling the Sydney classification criteria for definite APS (104 treated with LDA, 35 untreated). Inclusion criteria consisted of (1) any titer of aPL and no previous pregnancy or no pregnancy losses (defined as aPL carriers); (2) any titer of aPL and 1 or 2 pregnancy losses before the 10th gestational week. No women had previous thrombosis. The rate of pregnancy loss, gestational age at delivery, and birth weight percentile were compared in the treated and untreated patients. Associations between clinical and laboratory characteristics and pregnancy outcomes were investigated. Results. The rate of pregnancy loss was low in both treated and untreated groups (7.7% vs 2.9%, respectively). There were no statistically significant differences in the rate of pregnancy loss, gestational age at birth, or birth weight percentile in the treated and untreated groups. There were significant associations between gestational age at birth ≤ 34th week and positivity for lupus anticoagulant (p = 0.025) and anti-ß 2 -glycoprotein I IgG antibodies at titers &gt; 99th (p = 0.016). Conclusion. LDA treatment does not appear to improve pregnancy outcome in low-risk women not fulfilling the criteria for APS. Because antibody profile seems to influence pregnancy outcome, further studies of patients stratified according to their antibody profile are warranted. (First Releas

Top-quark rare decay t→cht\to c h in R-parity-violating SUSY

The flavor-changing top-quark decay $t\to c h$, where $h$ is the lightest CP-even Higgs boson in the minimal supersymmetric standard model, is examined in the R-parity-violating supersymmetric model. Within the existing bounds on the relevant R-parity-violating couplings, the branching fraction for $t\to c h$ can be as large as about $10^{-5}$ in some part of the parameter space.Comment: version to appear in Phys. Lett.

Dynamical R-parity Breaking at the LHC

In a class of extensions of the minimal supersymmetric standard model with (B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity symmetry is an essential and dynamical requirement for successful gauge symmetry breaking. Two consequences of these models are: (i) a new kind of R-parity breaking interaction that protects proton stability but adds new contributions to neutrinoless double beta decay and (ii) an upper bound on the extra gauge and parity symmetry breaking scale which is within the large hadron collider (LHC) energy range. We point out that an important prediction of such theories is a potentially large mixing between the right-handed charged lepton ($e^c$) and the superpartner of the right-handed gauge boson ($\widetilde W_R^+$), which leads to a brand new class of R-parity violating interactions of type $\widetilde{\mu^c}^\dagger\nu_\mu^c e^c$ and \widetilde{d^c}^\dagger\u^c e^c. We analyze the relevant constraints on the sparticle mass spectrum and the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note the "smoking gun" signals for such models to be lepton flavor/number violating processes: $pp\to \mu^\pm\mu^\pm e^+e^-jj$ (or $\tau^\pm\tau^\pm e^+e^-jj$) and $pp\to\mu^\pm e^\pm b \bar{b} jj$ (or $\tau^\pm e^\pm b \bar{b} jj$) without significant missing energy. The predicted multi-lepton final states and the flavor structure make the model be distinguishable even in the early running of the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde

A new benchmark T8-9 brown dwarf and a couple of new mid-T dwarfs from the UKIDSS DR5+ LAS

Benchmark brown dwarfs are those objects for which fiducial constraints are available, including effective temperature, parallax, age, metallicity. We searched for new cool brown dwarfs in 186 sq.deg. of the new area covered by the data release DR5+ of the UKIDSS Large Area Survey. Follow-up optical and near-infrared broad-band photometry, and methane imaging of four promising candidates, revealed three objects with distinct methane absorption, typical of mid- to late-T dwarfs, and one possibly T4 dwarf. The latest-type object, classified as T8-9, shares its large proper motion with Ross 458 (BD+13o2618), an active M0.5 binary which is 102" away, forming a hierarchical low-mass star+brown dwarf system. Ross 458C has an absolute J-band magnitude of 16.4, and seems overluminous, particularly in the K band, compared to similar field brown dwarfs. We estimate the age of the system to be less than 1 Gyr, and its mass to be as low as 14 Jupiter masses for the age of 1 Gyr. At 11.4 pc, this new late T benchmark dwarf is a promising target to constrain the evolutionary and atmospheric models of very low-mass brown dwarfs. We present proper motion measurements for our targets and for 13 known brown dwarfs. Two brown dwarfs have velocities typical of the thick disk and may be old brown dwarfs.Comment: 15 pages, 10 figures and 6 tables. Accepted by MNRAS. Uses mn2e.cls and aas_macr

Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren's syndrome: a clinical study of 81 pregnancies in 41 patients

Objective: To study the incidence and the features of congenital heart block (CHB) in patients with undifferentiated connective tissue disease (UCTD) and primary Sjögren's syndrome (pSS). Methods: We studied 81 pregnancies of 41 women attending the Outpatients' Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61%) were affected with UCTD and 16 (39%) with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. Results: CHB was found in 2 out of the 46 (4,3%) pregnancies followed by our Staff and in 2 out of the 35 (5,7%) included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0,026). Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. Conclusion: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities