Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial.

Background: Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.

2023 ACR/EULAR antiphospholipid syndrome classification criteria.

Objective: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR.

Methods: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard.

Results: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-β-glycoprotein I antibodies).

Neuropsychiatric Manifestations of Antiphospholipid Syndrome-A Narrative Review.

Antiphospholipid syndrome (APS) is a common autoimmune pro-thrombotic condition characterised by thrombosis and pregnancy morbidity. There are a broad range of neuropsychiatric manifestations associated with APS, from focal symptoms to more global dysfunction. Patients commonly present with transient ischaemic attacks and ischaemic strokes, with identifiable lesions on brain imaging.

Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial.

Background: The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2-3 years of letrozole in postmenopausal patients with breast cancer who have already received 2-3 years of tamoxifen.

Methods: This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy.

Recent advances in the management of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies.

Clinical utility of the global anti-phospholipid syndrome score for risk stratification: a pooled analysis.

Objective: Recently, our group conceived a risk score for clinical manifestations of APS (the global APS score, or GAPSS) that takes into account the combination of independent cardiovascular risk factors and the aPL positivity profile. These include hyperlipidaemia, arterial hypertension, aCL, anti-β2 glycoprotein-I, aPS-PT and the LA. A complementary version, the adjusted GAPSS (aGAPSS), which excludes aPS-PT, was also designed.

The Clinical Relevance of Noncriteria Antiphospholipid Antibodies.

While lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β glycoprotein I (anti-βGPI) antibodies represent the best available and the most widely used tests in the investigation for antiphospholipid syndrome (APS), evidence gathered in recent years indicates that other antiphospholipid antibodies (aPL) specificities may also play a role in the syndrome. Several autoantibodies have been shown to be complexed with phospholipids other than cardiolipin, or to some domains of βGPI, or else directed to other proteins of the coagulation cascade, and these have also been proposed to be of relevance to APS, and their diagnostic value and clinical utility are the focus of current research.

Recent advances in understanding antiphospholipid syndrome.

Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient's plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.

Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study.

Background: Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population.

Methods: A total of 1284 Sardinian patients with histologically-proven diagnosis of colorectal carcinoma (CRC) and presenting with metastatic disease were included into the study.

Prognostic role of mutations in Sardinian patients with colorectal carcinoma.

The presence of mutations in the KRAS gene is a predictor of a poor clinical response to EGFR-targeted agents in patients affected by colorectal cancer (CRC), but its significance as a global prognostic factor remains unclear. The aim of the present study was to evaluate the impact of the KRAS mutational status on time to first metastasis (TTM) and overall survival (OS) in a cohort of Sardinian CRC patients. A total of 551 patients with metastatic CRC at the time of enrolment were included.

Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses.

Twenty-year brain magnetic resonance imaging follow-up study in Systemic Lupus Erythematosus: Factors associated with accrual of damage and central nervous system involvement.

To evaluate the long-term progression of cerebral MRI abnormalities in patients with longstanding SLE, 30 patients (age 53.5 ± 11.3) underwent brain MRI at baseline (b-MRI) and after 19.

Association between SREBP-1 gene expression in mammary gland and milk fat yield in Sarda breed sheep.

The aim of this study was to examine the expression patterns of SREBP-1 gene in milk somatic cells and its association with milk fat yield during early lactation in Sarda breed sheep. A sample of 20 Sarda ewes, aged between 4 and 5 years, in their third to fourth lactation were chosen. From each ewe 28 days after lambing milk yield was measured, and a 160 ml milk sample for the RNA extraction and to test somatic cells count and lactose, fat and protein contents were collected.

The global anti-phospholipid syndrome score in primary APS.

Objective: The aim of this study was to evaluate the clinical relevance of the global APS score (GAPSS) in a cohort of primary APS patients.

Methods: This study included 62 consecutive patients with primary APS. Data on clinical manifestations, conventional cardiovascular risk factors and aPL profile were collected.

Thrombotic risk assessment in systemic lupus erythematosus: validation of the global antiphospholipid syndrome score in a prospective cohort.

Objective: This study was performed to prospectively and independently validate the Global Antiphospholipid Syndrome Score (GAPSS), a system derived from the combination of independent risk factors for thrombosis, including antiphospholipid antibodies (aPL) and conventional cardiovascular risk factors.

Methods: The GAPSS was applied to 51 consecutive systemic lupus erythematosus patients, all positive for aPL and prospectively followed up for mean ± SD 32.94 ± 12.

Autoantibodies involved in neuropsychiatric manifestations associated with systemic lupus erythematosus: a systematic review.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most important manifestations of SLE, and includes a variety of clinical manifestations, classified by the American College of Rheumatology in 19 different neuropsychiatric syndromes. To date, more than 116 antibodies have been reported in SLE and at least 20 of them, including 11 brain-specific and 9 systemic antibodies, have been controversially associated with NPSLE. To systematically review the available evidence, to define the association between the above antibodies and NPSLE as a whole and with the 19 neuropsychiatric syndromes associated with SLE, by strictly applying the American College Rheumatology case definitions.

The estimated frequency of antiphospholipid antibodies in young adults with cerebrovascular events: a systematic review.

Background: Around 10% of all thrombotic cerebrovascular events (CVE) occur in young population and in a large proportion of those the trigger remains undetermined. Antiphospholipid antibodies (aPL) are recognised risk factors for ischaemic stroke and recurrent thrombotic events; however, the frequency of aPL in young people with CVE is still an unresolved issue.

Objectives: To estimate the frequency of aPL in young adults with CVE and to determine whether aPL-positive young individuals are at greater risk of CVE when compared with individuals without aPL by systematically reviewing the literature.

Validation of a commercially available kit to detect anti-phosphatidylserine/prothrombin antibodies in a cohort of systemic lupus erythematosus patients.

Background: Antiprothrombin antibodies detection comprises two different ELISAs: prothrombin coated on irradiated plates (aPT) or phosphatidylserine/prothrombin (aPS/PT) as the antigen. While several commercial kits are available for the detection of aPT, aPS/PT are usually detected by in-house assays. Recently, a new commercially available kit was launched and, therefore, we decided to test its efficiency by comparing it to our in-house assay.

Anti-prothrombin (aPT) and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies and the risk of thrombosis in the antiphospholipid syndrome. A systematic review.

Antibodies to prothrombin are detected by directly coating prothrombin on irradiated ELISA plates (aPT) or by using the phosphatidylserine/prothrombin complex as antigen (aPS/PT). Although these antibodies have both been associated with antiphospholipid syndrome (APS) and a correlation between the two assays have been reported, it seems that aPT and aPS/PT belong to different populations of autoantibodies. It was our objective to systematically review the available evidence on aPT and aPS/PT antibodies and the risk of thrombosis in APS.