Case 1: A 40-year-old woman with myocardial infarction A 40-year-old female was diagnosed with systemic lupus erythematosus (SLE) at the age of 30 based on malar rash, arthritis, positive antinuclear ...antibodies, anti-double-stranded DNA antibodies, hypocomplementaemia, and biopsy-proven Class IV lupus nephritis. She was treated with glucocorticoids (GC), hydroxychloroquine (HCQ), and intravenous pulses of cyclophosphamide followed by mycophenolate mofetil (MMF) achieving complete remission 6 months later. Four years later, she suffered from a second SLE flare in the form of Class IV lupus nephritis as well as arthritis, receiving induction treatment with GC and MMF and achieving complete renal response 8 months later. She remained in lupus low disease activity for the next 5 years with prednisone 2.5 mg/day, HCQ 300 mg/day, and MMF 500 mg/12h. She was a current smoker, and her previous history included arterial hypertension and dyslipidaemia treated with enalapril 10 mg/day and atorvastatin 20 mg/day. At the current admission, she presented at Emergency Department with thoracic pain and shortness of breath. She was diagnosed with myocardial infarction. Coronary angiography showed an atherosclerotic plaque in anterior descending coronary artery that required percutaneous coronary intervention and stenting. The patient was discharged without acute complications under treatment with dual platelet anti-aggregation. What could we have done to avoid this outcome? Learning Objectives Discuss the general management of cardiovascular risk factors in patients with SLE Discuss the usefulness of different scoring tools to assess the atherosclerotic cardiovascular disease in SLE patients and the potential utility of imaging Discuss the objectives of treatment (primary prevention) of the different cardiovascular risk factors (hypertension, dyslipidaemia, tobacco) in SLE patients and the indications of aspirin in primary prevention
For patients with antiphospholipid syndrome (APS), the consensus is to treat those who develop thrombosis with long-term oral anticoagulation therapy and to prevent obstetric manifestations by use of ...aspirin and heparin. These recommendations are based on data from randomized controlled trials and observational studies. Despite this body of knowledge, areas of uncertainty regarding the management of APS exist where evidence is scarce or nonexistent. In other words, for a subset of patients the course of management is unclear. Some examples are patients with 'seronegative' APS, those who do not fulfil the formal (clinical or serological) classification criteria for definite APS, and those with recurrent thrombotic events despite optimal anticoagulation. Other challenges include the treatment of clinical manifestations not included in the classification criteria, such as haematologic manifestations (thrombocytopenia and haemolytic anaemia), neurologic manifestations (chorea, myelitis and multiple sclerosis-like lesions), and nephropathy and heart valve disease associated with antiphospholipid antibodies (aPL), as well as the possible withdrawal of anticoagulation treatment in selected cases of thrombotic APS in which assays for aPL become persistently negative. This Review focuses on the current recommendations for thrombotic and obstetric manifestations of APS, as well as the management of difficult cases. Some aspects of treatment, such as secondary prophylaxis of venous thrombosis, are based on strong evidence--the 'lights' of APS treatment. Conversely, other areas, such as the treatment of non-criteria manifestations of APS, are based only on expert consensus or common sense and remain the 'shadows' of APS therapy.
This study investigates the effect of violent crime on school district–level achievement in English language arts (ELA) and mathematics. The research design exploits variation in achievement and ...violent crime across 813 school districts in the United States and seven birth cohorts of children born between 1996 and 2002. The identification strategy leverages exogenous shocks to crime rates arising from the availability of federal funds to hire police officers in the local police departments where the school districts operate. Results show that children who entered the school system when the violent crime rate in their school districts was lower score higher in ELA by the end of eighth grade, relative to children attending schools in the same district but who entered the school system when the violent crime rate was higher. A 10% decline in the violent crime rate experienced at ages 0–6 raises eighth-grade ELA achievement in the district by 0.03 standard deviations. Models that estimate effects by race and gender show larger impacts among Black children and boys. The district-wide effect on mathematics achievement is smaller and statistically nonsignificant. These findings extend our understanding of the geography of educational opportunity in the United States and reinforce the idea that understanding inequalities in academic achievement requires evidence on what happens inside as well as outside schools.
The catastrophic antiphospholipid syndrome (CAPS) is a life-threating variant of the antiphospholipid syndrome characterized by the development of multiple thrombosis in a short period of time, ...usually ending up in the failure of function of several vital organs. Most CAPS episodes are related to a prothrombotic situation or precipitating factor such as infections, surgical procedures or malignant diseases. In patients with CAPS, the development of multiple thrombosis leads to an important cytokine release that worsens the already critical patient's situation. The disease usually involves the kidneys, the lungs and the heart, although any organ system can be affected. Although occasionally the disease affects large vessels, in the majority of cases it affects small vessels, leading to a disseminated microangiopathic syndrome resembling thrombotic thrombocytopenic purpura. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in those CAPS cases associated to systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Mortality is still around 30% despite current treatment.
•CAPS is characterized by the development of multiple thrombosis in a short period of time, mainly affecting small vessels.•Most CAPS episodes are related to a precipitating factor such as infections, surgical procedures or malignant diseases.•The disease usually involves the kidneys, the lungs and the heart, although any organ system can be affected.•Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins.•Rituximab and eculizumab have also been used in refractory cases. However, mortality is still around 30% despite treatment.
The data combine objectively measured sleep and thrice‐daily salivary cortisol collected from a 4‐day diary study in a large Midwestern city with location data on all violent crimes recorded during ...the same time period for N = 82 children (Mage = 14.90, range = 11.27–18.11). The primary empirical strategy uses a within‐person design to measure the change in sleep and cortisol from the person's typical pattern on the night/day immediately following a local violent crime. On the night following a violent crime, children have later bedtimes. Children also have disrupted cortisol patterns the following morning. Supplementary analyses using varying distances of the crime to the child's home address confirm more proximate crimes correspond to later bedtimes.
Abstract Objective To analyze the clinical and immunologic manifestations of patients with catastrophic antiphospholipid syndrome (CAPS) from the “CAPS Registry”. Methods The demographic, clinical ...and serological features of 500 patients included in the website-based “CAPS Registry” were analyzed. Frequency distribution and measures of central tendency were used to describe the cohort. Comparison between groups regarding qualitative variables was undertaken by chi-square or Fisher exact test while T-test for independent variables was used to compare groups regarding continuous variables. Results 500 patients (female: 343 69%; mean age 38 ± 17) accounting for 522 episodes of CAPS where included in the analysis. Forty percent of patients had an associated autoimmune disease, mainly systemic lupus erythematosus (SLE) (75%). The majority of CAPS episodes were triggered by a precipitating factor (65%), mostly infections (49%). Clinically, CAPS was characterized by several organ involvement affecting kidneys (73%), lungs (60%), brain (56%), heart (50%), and skin (47%). Lupus anticoagulant, IgG anticardiolipin and IgG anti-β2-glycprotein antibodies were the most often implicated antiphospholipid antibodies (83%, 81% and 78% respectively). Mortality accounted for 37% of episodes of CAPS. Several clinical differences could be observed based on the age of presentation and its association to SLE. Those cases triggered by a malignancy tended to occur in older patients, while CAPS episodes in young patients were associated with an infectious trigger and peripheral vessels involvement. Additionally, CAPS associated with SLE were more likely to have severe cardiac and brain involvement leading to a higher mortality (48%). Conclusion Although the presentation of CAPS is characterized by multiorgan thrombosis and failure, clinical differences among patients exist based on age and underlying chronic diseases, e.g. malignancy, SLE.
High prevalence of both criteria and extra-criteria antiphospholipid antibodies (aPL) has been reported in COVID-19 patients. However, the differences in aPL prevalence decreased when an age-matched ...control group was included. The association of aPL with thrombotic events in COVID-19 is very heterogeneous. This could be influenced by the fact that most of the studies carried out were conducted on small populations enriched with elderly patients in which aPL was measured only at a single point and they were performed with non-standardized assays. The few studies that confirmed aPL in a second measurement showed that aPL levels hardly changed, with the exception of the lupus anticoagulant that commonly reduced. COVID-19 coagulopathy is an aPL-independent phenomenon closely associated with the onset of the disease. Thrombosis occurs later in patients with aPL presence, which is likely an additional prothrombotic factor. B2-glycoprotein deficiency (mainly aPL antigen caused both by low production and consumption) is very common during the SARS-CoV2 infection and has been associated with a greater predisposition to COVID-19 complications. This could be a new prothrombotic mechanism that may be caused by the blockage of its physiological functions, the anticoagulant state being the most important.
To describe the real-world experience of eculizumab use in patients with catastrophic antiphospholipid syndrome (CAPS) according to the information provided by the “CAPS Registry”.
We analyzed the ...demographic, clinical and immunological data from all the patients included in the “CAPS Registry” treated with eculizumab and described the indications for eculizumab administration, dose, outcome, use of prophylactic vaccines and adverse effects.
The “CAPS Registry” currently includes 584 patients from whom 39 (6.7%) were treated with eculizumab (it was used as a rescue therapy in 30 cases while in 6 cases it was used as first line therapy). Mean age of eculizumab treated patients was 39 years (SD = 14.6), 72% were female, 77% had a primary APS and 79% had a precipitating factor before the CAPS event. Thrombocytopenia was present in 28 (72%) cases and features of microangiopathic hemolytic anemia were present in 15 (38.5%). Twenty-nine (74.4%) patients recovered from the episode of CAPS (four showed only partial remission). Symptoms worsened in 9 patients, from whom 5 finally died despite the treatment. There was only one relapse after a median follow up of 10.7 months. The most common treatment regimen was 900 mg weekly for four weeks and 1200 mg fortnightly.
According to the real-world experience provided by the “CAPS Registry”, eculizumab can be considered in some patients with CAPS refractory to previous therapies, especially if they present with features of complement-mediated thrombotic microangiopathy.
•Complement pathway has been identified as a critical mechanism in the development of CAPS.•Eculizumab is a humanized monoclonal antibody that binds to the C5 complementprotein.•74.4% of CAPS patients treated with eculizumab recovered without recurrence of thrombosis.•We suggest considering eculizumab in CAPS patients who present with complement mediated thrombotic microangiopathy.
Abstract The catastrophic antiphospholipid syndrome (APS) is the most severe form of APS with acute multiple organ involvement and small vessel thrombosis. During the 13th International Congress on ...Antiphospholipid Antibodies (aPL) a “Catastrophic APS Task Force” was developed to discuss the challenges in the diagnosis and management of catastrophic APS. The purpose of this paper is to summarize the diagnostic challenges (false-positive/negative aPL results and overlap with other thrombotic microangiopathies) and propose updated diagnostic algorithms for catastrophic APS. Important steps of the diagnostic algorithms include: a) history of APS or persistent aPL-positivity; b) three or more organ new thrombosis developing in less than a week; c) biopsy diagnosis of microthrombosis; and d) other explanations for multiple organ thromboses and/or microthrombosis.
Abstract The catastrophic variant of the antiphospholipid syndrome (APS) is characterized by thrombosis in multiple organs developing over a short period of time. First-line treatment for the ...catastrophic APS is the combination of anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulin. Despite this regimen, the mortality remains high and new treatment options are needed. By a systematic review of the Catastrophic APS Registry (CAPS Registry), we identified 20 patients treated with rituximab. The purpose of this study is to describe the clinical manifestations, laboratory features, and outcomes of rituximab-treated CAPS patients. In addition, the rationale for using rituximab in catastrophic APS is discussed.
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