History of pre-eclampsia does not appear to be a risk factor for vascular phenotype in women with systemic sclerosis.

Background: Vascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection.

Objectives: To explore risk factors for a vascular phenotype of SSc, among them a history of pre-eclampsia.

Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study.

Background: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome.

Methods: This multicentre, prospective, observational study was done at 76 centres in France.

Hydroxychloroquine may be beneficial in preeclampsia and recurrent miscarriage.

Recurrent miscarriage (RM) and vasculoplacental disorders, such as preeclampsia (PE), affect women of childbearing age worldwide. Vascular endothelial dysfunction and immunological impairment are associated with both RM and PE. To date, there is no effective or optimal therapeutic approach for these conditions.

Blood anti-Müllerian hormone is a possible determinant of recurrent early miscarriage, yet not conclusive in predicting a further miscarriage.

Research Question: Is blood anti-Müllerian hormone (AMH) concentration a strong determinant of unexplained recurrent early miscarriage (REM)?

Design: In the first part of the study, AMH concentrations measured using an Immunotech ELISA Kit were compared between 188 unselected (mostly fertile) women consecutively referred for three or more miscarriages in the first trimester of pregnancy and 376 age-matched parous women without pregnancy loss. Cases and controls were previously enrolled in an incident case-control study on thrombophilic mutations. Blood samples were collected >2 months after any recognized obstetric event or hormonal treatment.

Hydroxychloroquine for prevention of recurrent miscarriage: study protocol for a multicentre randomised placebo-controlled trial BBQ study.

Introduction: Recurrent miscarriage (RM), defined by three or more consecutive losses during the first trimester of pregnancy, affects 1%-2% of fertile couples. Standard investigations fail to reveal any apparent cause in ~50% of couples. However, on the basis of animal models and clinical studies, several hypotheses have been put forward concerning underlying mechanisms of RM: altered ovarian reserve, progesterone defect, thrombotic and/or endothelial dysfunction and immunological disturbances.

Minisci-Photoredox-Mediated α-Heteroarylation of N-Protected Secondary Amines: Remarkable Selectivity of Azetidines.

The development of a general, mild, and functional-group-tolerant direct functionalization of N-heteroarenes by C-H functionalization with N-protected amines, including azetidines under Minisci-mediated photoredox conditions, is reported. A broad scope of substituted azetidines, including spirocyclic derivatives, and heterocycles were explored. This reaction enables the production of sp3-rich complex druglike structures in one step from unactivated feedstock amines and heterocycles.

Thrombotic risk assessment and analytical performance of the chemiluminescent analyzer IDS-iSYS for the detection of anti-cardiolipin and anti-beta 2 glycoprotein I autoantibodies.

Patients with antiphospholipid antibodies (APLA) are predisposed to develop thrombosis, however the standardization of anti-cardiolipin (aCL) and anti-beta 2 glycoprotein I (β2-GPI) Ab assays are challenging. Therefore we decided to test the performance of a new chemiluminescent assay (CLIA), and assayed aCL and aβ2-GPI IgG/M in serum from 120 healthy individuals, 108 patients with idiopathic venous thrombosis, 78 patients with antiphospholipid syndrome (APS), and 64 non-thrombotic APLA-carriers using CLIA IDS-iSYS. Very good (aCL/aβ2-GPI IgG) to moderate (aCL/aβ2-GPI IgM) agreement with a commercial and an in house ELISA assay were observed and, in particular, CLIA demonstrated the highest sensitivity in aβ2-GPI IgG detection.

Clinical Characteristics of Pruritus in Systemic Sclerosis Vary According to the Autoimmune Subtype.

Pruritus is a frequent symptom in systemic sclerosis (SSc), with a prevalence of 40-65%, but its pathophysiology is poorly understood. This study investigated the immunological component of pruritus. Fifty-six patients with SSc responded to a standardized questionnaire regarding both SSc disease and pruritus characteristics.

Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up.

Among patients with venous thromboembolism (VTE), the persistent detection of antiphospholipid (aPL) antibodies (Ab) represents an independent high risk factor for recurrence. However, oral anticoagulation vitamin K antagonist therapy, frequently used in these patients, is problematic in assessing and/or confirming a diagnosis of primary aPL syndrome (pAPS), suggesting use of alternative strategies. For this reason, and by analogy with other autoimmune diseases, a flow cytometer approach testing peripheral T cell subsets (CD3, CD4, and CD8), B cell subsets (B1, transitional, naive, and memory), and NK cells can be proposed.

Enoxaparin for prevention of unexplained recurrent miscarriage: a multicenter randomized double-blind placebo-controlled trial.

It is common practice in many centers to offer antithrombotic medications to women with unexplained recurrent miscarriage, in the presence or absence of inherited thrombophilia. Although no benefit of aspirin vs placebo has been clearly demonstrated, a double-blind placebo-controlled trial on the effect of low-molecular-weight heparin is lacking. We enrolled 258 pregnant women with a history of unexplained recurrent miscarriage (≥2 consecutive miscarriages before 15 weeks' gestation) and a negative thrombophilia workup.

Unexplained pregnancy loss: a marker of basal endothelial dysfunction?

Objective: To compare the microparticle levels of women referred for unexplained pregnancy loss with those of parous controls.

Design: Incident case-control study.

Setting: University medical center.

Increased thrombin generation measured in the presence of thrombomodulin in women with early pregnancy loss.

Compared with 537 parous controls with no history of pregnancy loss, a lower thrombomodulin-related inhibition of the endogenous thrombin potential was measured in 264 cases with previous unexplained pregnancy loss, especially when losses occurred between 9 and 12 weeks of gestation. Adjusting age, protein S, factor VIII, factor V Leiden, and prothrombin G20210A did not change the results.

Impact of atazanavir-based HAART regimen on the carotid intima-media thickness of HIV-infected persons: a comparative prospective cohort.

Objective: With the advent of highly active antiretroviral therapy regimens, it is crucial to consider their long-term benefits to risk ratios among HIV-infected persons. The impact of protease inhibitors on the cardiovascular risk is controversial.

Design: This observational cohort was designed to investigate the cardiovascular impact of boosted atazanavir (ATV/r), a protease inhibitor that does not provide major dyslipidemia or insulin resistance.

Statin use does not affect the outcome of acute infection: a prospective cohort study.

Unlabelled: Statins are used to prevent atherosclerosis because of their hypolipemic effects. In vitro testing and murine models suggest that statins may affect outcome in sepsis. Our meta-analysis of epidemiological studies in humans confirms that previous statin use appears to have a protective effect on infection rates and outcomes.

Metabolic syndrome: a major risk factor for atherosclerosis in HIV-infected patients (SHIVA study).

Objective: Metabolic syndrome (MetS) is directly related to a high incidence of cardiovascular disease in the general population. The association is more doubtful among HIV-infected patients, although MetS has an elevated prevalence in this population. We explored the impact of MetS on early atherosclerosis markers.

Correlations between carotid IMT, factor VIII activity level and metabolic disturbances: a cardio-vascular risk factor in the HIV positive persons.

In the HIV infection, the short time-scale between the HIV-induced cardiovascular events and the onset of antiretroviral therapy elicits a thrombophilic co-factor that worsens the induced atherosclerosis. We compared the factor VIII plasma activity, previously implicated in arterial and venous thrombosis, with a surrogate marker of atherosclerosis, the carotid intima-media thickness, and with the usual atherosclerosis risk factors in 154 HIV infected outpatients. The FVIII plasma activity is significantly associated with the carotid intima-media thickness and, strongly, with blood glucose and triglycerides levels.

Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.

Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of TMC278 displaying high potency against wild-type and mutant viruses compared to nevirapine and efavirenz. The pharmacokinetic profile of the best newly synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical trials.

Structure-activity relationship in the 3-iodo-4-phenoxypyridinone (IOPY) series: The nature of the C-3 substituent on anti-HIV activity.

As part of a systematic SAR study on the 3-iodo-4-phenoxypyridinone 3 (IOPY) type non-nucleoside reverse transcriptase inhibitors, the analogues 4a-4z bearing different C-3 substituents were synthesized and evaluated for their anti-HIV activity against wild-type HIV-1 and four of the principal HIV mutant strains (K103N, Y181C, Y188L, and I100L). The results show that the 3-vinyl analogue 4j is the only compound which displays anti-HIV activity comparable to IOPY 3, and in this respect represents a possible back-up to this lead molecule.