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In the original article, the affiliation of co-author Cecilia Beatrice Chighizola should have read: “Experimental Laboratory of Immunological and Rheumatologic Researches, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, Milan, Italy”. These details have been corrected only in this corrigendum to preserve the published version of record.

Objectives To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Coronavirus disease-2019 (COVID-19) related to Coronavirus-2 (SARS-CoV-2) is a worldwide health concern. Despite the majority of patients will evolve asymptomatic or mild-moderate upper respiratory tract infections, 20% will develop severe disease. Based on current pathogenetic knowledge, a severe COVID-19 form is mainly a hyperinflammatory, immune-mediated disorder, triggered by a viral infection. Due to their particular immunological features, pregnant women are supposed to be particularly susceptible to complicate by intracellular infections as well as immunological disturbances. As an example, immune-thrombosis has been identified as a common immune-mediated and pathogenic phenomenon both in COVID-19, in obstetric diseases and in COVID-19 pregnant women. According to extensive published clinical data, is rationale to expect an interference with the normal development of pregnancy in selected SARS-CoV-2-infected cases, mainly during third trimester. This manuscript provides insights of research to elucidate the potential harmful responses to SARS-CoV-2 and /or other coronavirus infections, as well as bidirectional interactions between COVID-19 and pregnancy to improve their respective management.

Objectives. To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods. This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results. A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion. Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment approximate to 12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein (r=0.341; P=0.006), and negatively with global longitudinal strain (r=-0.581; P

Background: No absolute data on the treatment of antiphospholipid antibodies (aPL) related to refractory obstetric complications exist to date. TNF-alpha play a major role in this disorder. Objective: To assess the effectiveness of TNF-alpha blockers in 18 aPL-positive women with recurrent infertility after therapy with low-molecular-weight heparin (LMWH) plus aspirin (LDA) plus hydroxychloroquine (HCQ). Methods: Prospective case-series of 12 women fulfilling Sydney criteria for obstetric antiphospholipid syndrome (OAPS) and 6 with incomplete forms (OMAPS). All women tested positive for aPL at least twice. Non criteria aPL were tested in 15/18. Complement, TNF-alpha and IL-10 were also evaluated. Women were closely monitored for fetal well-being and possible malformations throughout gestation and the postpartum period. Results: Sixteen patients were started on adalimumab and 2 on certolizumab. Twelve women completed gestation: 9 at term and 3 pre-term. Differences in laboratory categories and outcomes were observed when OAPS and OMAPS were compared. First trimester miscarriage or implantation failure recurred in 6 cases, all of the OAPS group. Malformations were not seen in the newborns. Conclusions: Overall, good obstetric results were obtained in 70% of previous LMWH-LDA+HCQ refractory cases. TNF-alpha blockers were well tolerated without adverse effects. The combination of LMWH plus LDA plus TNF-alpha blockers appears to be a promising treatment for refractory obstetric complaints related to aPL; nevertheless, outcome differences between OAPS and OMAPS do exist. (C) 2019 Published by Elsevier Inc.

Aim: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). Methods: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. Results: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). Conclusion: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.

Aim: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). Methods: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. Results: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in Era, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). Conclusion: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.

Background: Obstetric morbidity (OM) is a common feature of antiphospholipid syndrome (OAPS). Women having OAPS-only and women with OM related to antiphospholipid antibodies (aPL) but not fulfilling APS classification criteria (OMAPS), may show similar patterns. Aim: The aim of this research was to collect records of OAPS and OMAPS cases in order to have valuable information about their clinical features, laboratory, treatment, pregnancy outcomes and long-term follow-up. Methods: EUROAPS/EUROMAPS is a registry in the frame of the European Forum on Antiphospholipid Antibody projects. Its own website has been available since June 2010: www.euroaps.org. Results: This registry comprises 211 women including 304 pre-enrolment pregnancies, and 226 prospective cases, 194 of OAPS and 32 of OMAPS. OM was more frequent in OAPS than in OMAPS, independent of treatment. In the prospective cohort, standard aPL data was available in 202 cases and treatment data in all 226 cases. Good fetal outcomes were obtained when low dose aspirin plus low molecular weight heparin were administered. Prevalence of thrombotic events and/or cases evolving into full-blown systemic lupus erythematosus (SLE) was low. Conclusions: OAPS could be a different form of APS. OMAPS/OMAPS fetal outcomes were better when treated. The prevalence of thrombosis and progression to SLE were lower than in ‘classical’ APS. Lupus (2012) 21, 766–768.

To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population.This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications.In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)).Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John WileySons Ltd.

The co-existence of inherited thrombophilia with antiphospholipid antibody (aPL) positivity is not uncommon. This association does not overrule the diagnosis of antiphospholipid syndrome. Infection may present together with transient aPL positivity, usually aCL-IgM isotype. Thus certain infections, virus particularly, may increase “per se” thrombotic risk. Herein, we communicate the case of a 29-year-old man who sought medical attention because of a ten days course left-side abdominal pain, cough, fever, fatigue, arthralgia and mild dyspnoea. The patient was diagnosed of multiple pulmonary and splenic infarcts. Interestingly, laboratory results showed the presence of JAK2- V617F mutation, positive CMV serology, first IgM and IgG further, as well as LA test and aCL-IgM transiently but recurrently positive. The role played by these aPL transiently positive antibodies – laboratory category I – as a trigger in the development of this thrombotic diathesis is being discussed.

Background:. An increasing number of persons seek medical solutions for esthetic indications and for diverse pathological conditions, such as malformations, trauma, or cancer. Despite manufacturers' and different authors' claims that fillers are non-immunogenic or that complications are uncommon, unwanted adverse reactions do occur. Objectives: To review the literature regarding the multiple types of immune-mediated adverse reactions related to medical dermal filler injections/prosthesis. Methods: A comprehensive MEDLINE, PubMed, and Google Scholar electronic database search was performed (2000-January 2012). Selected articles published before 2000 referring to general concerns regarding the studied topic were also included. The search provided almost 300 articles. Finally, 235 studies were selected and included. Results: All known fillers present in the market have been shown to be able to provoke early- and late-onset inflammatory adverse reactions. Their true prevalence is unknown but appears to be significant. The majority of the late-onset adverse effects are inflammatory and immune-mediated in nature. Edema, granulomas, sarcoid-like disorders, and panniculitis are the findings most commonly seen. Rarely, systemic granulomatous and autoimmune diseases, and to lesser extent acute hypersensitivity reactions can be seen. Conclusions: All implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions that may appear early or late and range from local to systemic. Most fillers act more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies. Management of both acute and systemic reactions is often difficult and requires anti-inflammatory and occasionally immunosuppressive therapy. (C) 2013 Elsevier Inc. All rights reserved.

An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.