Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ('Registry').

Objectives: To describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry. Methods: We identified persistently aPL-positive patients recorded as 'pregnant' during prospective follow-up, and defined 'aPL-related outcome' as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment. Results: Of the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss <10 weeks gestation. Of the remaining 40 pregnancies: (1) 26 (65%) resulted in term live delivery (TLD), 4 (10%) in PTLD between 34.0 weeks and 36.6 weeks, 5 (12.5%) in PTLD before 34th week, and 5 (12.5%) in fetal death (two associated with genetic anomalies); and (2) The aPL-related composite outcome occurred in 9 (23%). One of 26 (4%) pregnancies with TLD, 3/4 (75%) with PTLD between 34.0 weeks and 36.6 weeks, and 3/5 (60%) with PTLD before 34th week were complicated with PEC, SGA and/or PI. Fifty of 55 (91%) pregnancies were in lupus anticoagulant positive subjects, as well as all pregnancies with aPL-related composite outcome. Conclusion: In our multicentre, international, aPL-positive cohort, of 55 first pregnancies observed prospectively, 15 (27%) were complicated by early pregnancy loss. Of the remaining 40 pregnancies, composite pregnancy morbidity was observed in 9 (23%) pregnancies

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort

Objectives: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. Methods: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-β2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. Results: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ± 3.3 vs. 6 ± 3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ± 3.9; p<0.05). Conclusions: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS

Early mobilisation in critically ill COVID-19 patients: a subanalysis of the ESICM-initiated UNITE-COVID observational study

Background Early mobilisation (EM) is an intervention that may improve the outcome of critically ill patients. There is limited data on EM in COVID-19 patients and its use during the first pandemic wave. Methods This is a pre-planned subanalysis of the ESICM UNITE-COVID, an international multicenter observational study involving critically ill COVID-19 patients in the ICU between February 15th and May 15th, 2020. We analysed variables associated with the initiation of EM (within 72 h of ICU admission) and explored the impact of EM on mortality, ICU and hospital length of stay, as well as discharge location. Statistical analyses were done using (generalised) linear mixed-effect models and ANOVAs. Results Mobilisation data from 4190 patients from 280 ICUs in 45 countries were analysed. 1114 (26.6%) of these patients received mobilisation within 72 h after ICU admission; 3076 (73.4%) did not. In our analysis of factors associated with EM, mechanical ventilation at admission (OR 0.29; 95% CI 0.25, 0.35; p = 0.001), higher age (OR 0.99; 95% CI 0.98, 1.00; p ≤ 0.001), pre-existing asthma (OR 0.84; 95% CI 0.73, 0.98; p = 0.028), and pre-existing kidney disease (OR 0.84; 95% CI 0.71, 0.99; p = 0.036) were negatively associated with the initiation of EM. EM was associated with a higher chance of being discharged home (OR 1.31; 95% CI 1.08, 1.58; p = 0.007) but was not associated with length of stay in ICU (adj. difference 0.91 days; 95% CI − 0.47, 1.37, p = 0.34) and hospital (adj. difference 1.4 days; 95% CI − 0.62, 2.35, p = 0.24) or mortality (OR 0.88; 95% CI 0.7, 1.09, p = 0.24) when adjusted for covariates. Conclusions Our findings demonstrate that a quarter of COVID-19 patients received EM. There was no association found between EM in COVID-19 patients' ICU and hospital length of stay or mortality. However, EM in COVID-19 patients was associated with increased odds of being discharged home rather than to a care facility. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021)

Evaluation of angiogenic and antiangiogenic factors in patients with systemic lupus erythematosus

O lúpus eritematoso sistêmico (LES) é uma doença autoimune cuja fisiopatologia envolve mecanismos imunológicos, incluindo distúrbios nos processos de morte celular e nos mecanismos de eliminação de autoantígenos e de tolerância, acompanhados da formação de autoanticorpos patogênicos. Ele acomete principalmente mulheres jovens e a gestação nestas pacientes apresenta significativa morbimortalidade. Os achados clínicos e laboratoriais na nefrite lúpica são semelhantes àqueles encontrados em pacientes com pré-eclâmpsia (PE), especificamente hipertensão arterial, proteinúria e edema. Foi proposto o uso de fatores angiogênicos, como o fator de crescimento vascular endotelial (VEGF) e o fator de crescimento placentário (PlGF), e antiangiogênicos, como o receptor Fms-like tirosina quinase 1 solúvel (sFlt-1), para o diagnóstico diferencial entre estas duas condições, no entanto os dados disponíveis na literatura sobre estas citocinas em pacientes não gestantes com LES são inconsistentes. Este estudo foi desenhado para avaliar se existe diferença entre os níveis séricos de VEGF, PlGF e sFlt-1 em pacientes com LES com e sem atividade sistêmica da doença e se existe diferença nesses fatores quando comparamos pacientes com LES e mulheres saudáveis. Foram incluídas 54 mulheres com diagnóstico de LES em acompanhamento no ambulatório de Reumatologia do HUPE-UERJ, sem outra doença autoimune diagnosticada, e divididas de acordo com a atividade da doença. 30 pacientes tinham doença inativa (SLEDAI médio: 0,7) e 24 tinham doença ativa (SLEDAI médio: 11,6). 23 mulheres deste último grupo possuíam nefrite ativa, enquanto 20 das pacientes com doença em remissão já haviam apresentado nefrite ao longo da evolução do LES. O grupo controle foi formado por 34 mulheres hígidas atendidas no ambulatório de ginecologia da Policlínica Piquet Carneiro-UERJ. Considerando as três citocinas estudadas, as pacientes com LES apresentaram valores séricos médios superiores às mulheres do grupo controle (VEGF: 319,0 + 226,0 x 206,2 + 119,4, p=0,02; PlGF: 42,2 + 54,1 x 13,6 + 21,6, p=0,02; sFlt-1: 107,9 + 49,2 x 70,2 + 95,0, p=0,01). O grupo de pacientes com doença ativa também apresentou média superior ao controle nos três fatores (VEGF: 331,0 + 216,8 x 206,2 + 119,4, p=0,02; PlGF: 41,2 + 47,3 x 13,6 + 21,6, p=0,02; sFlt-1: 120,5 + 42,4 x 70,2 + 95,0, p=0,02), enquanto não foi encontrada diferença estatística entre o grupo de LES inativo e o controle. A média do sFlt-1 sérico foi maior nas pacientes com LES ativo do que a média das pacientes com a doença em remissão (120,5 + 54,9 x 97,8 + 42,4, p=0,02), mas não houve diferença significativa da média do VEGF e PlGF séricos entre os dois grupos. O melhor entendimento dos fatores angiogênicos e antiangiogênicos em pacientes com LES proporcionado por este estudo nos permite a análise dessas citocinas em gestantes com LES e, possivelmente, sua posterior aplicação como método diferencial entre nefrite lúpica e PE.Systemic lupus erythematosus (SLE) is an autoimmune disease which pathophysiology involves immunological mechanisms including disturbances in the processes of cell death and mechanisms of elimination of autoantigens and tolerance, accompanied by formation of pathogenic autoantibodies. It mainly affects young women and pregnancy in these patients have significant morbidity and mortality. Clinical and laboratory findings in lupus nephritis are similar to those found in patients with preeclampsia (PE), specifically hypertension, proteinuria and edema. It has been proposed the use of angiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), and antiangiogenic factors, as soluble Fms-like tyrosine kinase-1 (sFlt-1), for the differential diagnosis between these two conditions, however available data in the literature about these cytokines in non-pregnant SLE patients are inconsistent. This study was designed to evaluate whether there are differences between serum levels of VEGF, PlGF and sFlt-1 in SLE patients with and without systemic disease activity and whether there are differences in these factors when comparing SLE patients with healthy women. 54 women with SLE followed at outpatient clinic of Rheumatology HUPE - UERJ were included. They had no other autoimmune disease diagnosed and were divided according to disease activity. 30 patients had inactive disease (mean SLEDAI: 0.7), and 24 had active disease (mean SLEDAI: 11.6). 23 women in this latter group had active nephritis, while 20 patients with inactive disease had history of lupus nephritis. The control group consisted of 34 healthy women who attended the Gynecology outpatient clinic at Policlínica Piquet Carneiro - UERJ. Considering the three studied cytokines, the SLE patients had higher mean serum levels than the control group (VEGF: 319.0 + 226.0 x 206.2 + 119.4, p=0.02; PlGF: 42.2 + 54.1 x 13.6 + 21.6, p=0.02; sFlt-1: 107.9 + 49.2 x 70.2 + 95.0, p=0.01). The group of patients with active disease also had higher mean levels of all three factors than controls (VEGF: 331.0 + 216.8 x 206.2 + 119.4, p=0.02; PlGF: 41.2 + 47.3 x 13.6 + 21.6, p=0.02; sFlt-1: 120.5 + 42.4 x 70.2 + 95.0, p=0.02), whereas no statistical difference was found between the group with inactive SLE and the control group. The mean sFlt-1 levels were higher in patients with active SLE than the mean levels of patients with inactive disease (120.5 + 54.9 x 97.8 + 42.4, p=0.02), but there was no significant difference in mean serum of VEGF and PlGF levels between these two groups. A better understanding of angiogenic and antiangiogenic factors in patients with SLE provided by this study allows the analysis of these cytokines in pregnant woman with SLE and possibly their subsequent application as differential method between PE and lupus nephritis

Imunidade na gestação normal e na paciente com lúpus eritematoso sistêmico (LES)

A gravidez é uma condição fisiológica na qual ocorrem várias mudanças imunoendócrinas com a finalidade de facilitar a imunossupressão e a tolerância aos antígenos paternos e fetais. Na gravidez humana normal existe uma relativa supressão de citocinas tipo Th1 na resposta dos linfócitos, levando a uma prevalência na resposta do tipo Th2. No LES, onde prevalece a resposta imune do tipo Th2, a gravidez pode estar relacionada com a ativação da doença. Este artigo é uma revisão dessas alterações relacionadas com a resposta imune durante a gestação normal e na da paciente com LES

Challenging cases in rheumatic pregnancies

This article describes three complicated cases in rheumatology and pregnancy. The first case elucidates the challenges in treating SLE in conjunction with pulmonary arterial hypertension, while the second case features an SLE-affected pregnancy with development of portal hypertension secondary to portal vein thrombosis related to APS. The third case is a pregnant woman with stable SLE who developed thrombotic microangiopathy caused by atypical haemolytic uraemic syndrome, and failed to improve despite multiple measures including biopsy and elective preterm delivery. There are grave and unique challenges for women with autoimmune disease, but adverse outcomes can sometimes be avoided with careful and multidisciplinary medical management. Pre-conception counselling with regard to medications and disease treatment should also include discussion of the advisability of pregnancy, which may be difficult for a patient, but present the best course for optimizing health outcomes