Dual MPO/PR3 ANCA positivity and vasculitis: insights from a 7-cases study and an AI-powered literature review.

OBJECTIVES: Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles, and outcomes of patients with DP-ANCA. METHODS: A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analyzing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an AI-based search using BIBOT software with a manual PUBMED database search. RESULTS: The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%), (ii) drug-induced AAV (∼25%), (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%), and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%). CONCLUSION: This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases.

Venous thromboembolism and amyotrophic lateral sclerosis: the Venous Thrombo-Embolism and Sclerosis Lateral Amyotrophic study.

Background: Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease. Given the inflammatory nature of ALS and the high number of ALS-related clinical circumstances (eg, prolonged immobilization and infections), patients with ALS may have a high risk of venous thromboembolism (VTE). Objectives: To determine the annual incidence rate of VTE and the predictors of VTE in patients with ALS. Methods: We analyzed a prospective cohort of patients with ALS diagnosed between 2009 and 2019 followed in the Brest University Hospital ALS Centre. Results: Among 227 patients with ALS, VTE occurred in 19 patients during a median follow-up period of 717 days (IQR, 488-1308), yielding an annual incidence rate of 2.93% (95% CI, 1.88%-4.53%). Predictors for VTE were a family history of VTE (hazard ratio [HR], 15.24; 95% CI, 1.72-134.84; P = .01), the presence of noninvasive ventilation at ALS diagnosis (HR, 6.98; 95% CI, 1.09-44.59; P = .04) and a short time (ie, <213 days) between first symptoms and ALS diagnosis (HR, 5.48; 95% CI, 1.57-19.11; P = .01). Recurrent VTE occurred within 3 months after stopping anticoagulation in 5 patients (26.3%). Conclusion: The annual incidence of VTE in patients with ALS is high. Predictive factors of VTE were a VTE history, noninvasive ventilation, and a short time between first symptoms of ALS and ALS diagnosis.

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. METHODS: This observational multicentre case-control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire. RESULTS: 378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype. CONCLUSIONS: In women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype.

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

Women with severe postpartum hemorrhage have a decreased endogenous thrombin potential before delivery.

BACKGROUND: Severe postpartum hemorrhage (PPH), defined as a blood loss ≥1000 mL, is associated with maternal morbidity and mortality. OBJECTIVES: We aimed at characterizing coagulation properties of predelivery plasmas from pregnant women with thrombin generation assay and hemostatic biomarkers (plasminogen activator inhibitor-1, tissue factor [TF], and thrombomodulin). METHODS: A nested case-control study was conducted within the "Study of Biological Determinants of Bleeding Postpartum," a French prospective cohort study, in order to compare women with severe PPH (cases) and controls matched for age, body mass index, term, and mode of delivery. Plasma was collected at entry in the delivery room, and blood loss was measured objectively. The predelivery endogenous thrombin generation potential (ETP) was measured in plasma using calibrated automated thrombinography and low TF concentration. Hemostatic biomarkers were measured using ELISA kits. RESULTS: A total of 142 women (71 cases and 71 controls) were investigated. There was no difference in the median lag phase, thrombin peak, and time to peak between cases and controls. However, median predelivery ETP was lower in cases than in controls (2170 vs 2408 nM.min, P < .0001), independently of mode of delivery and PPH etiology. Median plasminogen activator inhibitor-1 and TF levels were higher in cases compared with controls (107.4 vs 68.1 ng/mL, P = .0003; 34.4 vs 27.4 pg/mL, P = .007), whereas thrombomodulin levels did not differ between the 2 groups. CONCLUSION: Among thrombin generation assay parameters, predelivery ETP levels may have a predictive value for severe PPH.

Hemostatic biomarkers associated with postpartum hemorrhage: a systematic review and meta-analysis.

Postpartum hemorrhage (PPH) is a leading cause of maternal morbi-mortality. Although obstetric risk factors are well described, the impact of predelivery hematologic and hemostatic biomarkers remains incompletely understood. In this systematic review, we aimed to summarize the available literature on the association between predelivery hemostatic biomarkers and PPH/severe PPH. Searching MEDLINE, EMBASE, and CENTRAL databases from inception to October 2022, we included observational studies on unselected pregnant women without bleeding disorder reporting on PPH and on predelivery hemostatic biomarkers. Two review authors independently performed title, abstract and full-text screening, upon which quantitative syntheses of studies reporting on the same hemostatic biomarker were conducted, calculating the mean difference (MD) between women with PPH/severe PPH and controls. A search on 18 October 2022 yielded 81 articles fitting our inclusion criteria. The heterogeneity between studies was considerable. With regard to PPH, the estimated average MD in the investigated biomarkers (platelets, fibrinogen, hemoglobin, Ddimer, activated partial thromboplastin time, and prothrombin time) were not statistically significant. Women who developed severe PPH had lower predelivery platelets than controls (MD = -26.0 109/L; 95% confidence interval, -35.8 to -16.1), whereas differences in predelivery fibrinogen concentration (MD = -0.31 g/L; 95% confidence interval, -0.75 to 0.13) and levels of factor XIII or hemoglobin were not statistically significant in women with and without severe PPH. Predelivery platelet counts were, on average, lower in women with severe PPH compared with controls, suggesting the potential usefulness of this biomarker for predicting severe PPH. This trial was registered at the International Prospective Register of Systematic Reviews as CRD42022368075.

Family history of postpartum hemorrhage is a risk factor for postpartum hemorrhage after vaginal delivery: results from the French prospective multicenter Haemorrhages and Thromboembolic Venous Disease of the Postpartum cohort study.

BACKGROUND: Postpartum hemorrhage is a major component of perinatal morbidity and mortality that affects young women worldwide and is still often unpredictable. Reducing the incidence of postpartum hemorrhage is a major health issue and identifying women at risk for postpartum hemorrhage is a key element in preventing this complication. OBJECTIVE: This study aimed to estimate postpartum hemorrhage prevalence after vaginal delivery and to identify postpartum hemorrhage risk factors. STUDY DESIGN: Unselected pregnant women ≥16 years of age admitted to 1 of 6 maternity wards in Brittany (France) for vaginal birth after 15 weeks of gestation were recruited in this prospective, multicenter cohort study between June 1, 2015, and January 31, 2019. Postpartum hemorrhage was defined as blood loss ≥500 mL in the 24 hours following delivery. Independent risk factors for postpartum hemorrhage were determined using logistic regression. Missing data were imputed using the Multivariate Imputation by Chained Equations method. RESULTS: Among 16,382 included women, the postpartum hemorrhage prevalence was 5.37%. A first-degree family history of postpartum hemorrhage (adjusted odds ratio, 1.63; 95% confidence interval, 1.24-2.14) and a personal transfusion history (adjusted odds ratio, 1.90; 95% confidence interval, 1.23-2.92) were significantly associated with postpartum hemorrhage. The use of oxytocin during labor was also a risk factor for postpartum hemorrhage (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.44). Inversely, smoking during pregnancy and intrauterine growth restriction were associated with a reduced risk for postpartum hemorrhage (adjusted odds ratio, 0.76; 95% confidence interval, 0.63-0.91, and 0.34; 95% confidence interval, 0.13-0.87, respectively). CONCLUSION: In addition to classical risk factors, this study identified a family history of postpartum hemorrhage and personal transfusion history as new characteristics associated with postpartum hemorrhage after vaginal delivery. The association of postpartum hemorrhage with a family history of postpartum hemorrhage suggests a hereditary hemorrhagic phenotype and calls for genetic studies. Identifying women at risk for postpartum hemorrhage is a key element of being prepared for this complication.

Triple positive profile in antiphospholipid syndrome: prognosis, relapse and management from a retrospective multicentre study.

OBJECTIVE: Antiphospholipid syndrome (APS) is defined by the association of thromboembolic and/or obstetrical clinical manifestations and the presence of antiphospholipid antibodies. The objective of our study was to evaluate the impact of the triple-positive profile in a cohort of 204 APS patients. METHODS: We conducted a retrospective study, including patients with primary or secondary APS, meeting the Sydney criteria with at least one thrombotic and/or obstetrical complication. Clinical characteristics and the risk of relapse (defined by the occurrence of a new thrombotic event and/or a new adverse obstetrical event) between triple-positive and non-triple-positive APS patients were compared. RESULTS: 204 patients were included in our study, 68 were triple-positive and 136 were single or double positive. 122 patients (59.8%) had primary APS. 67 patients (32.8%) had obstetrical APS, with a higher rate among triple-positive patients (45.6% vs 26.5%, p=0.010), and 170 patients (83.3%) had thrombotic APS, without difference between triple-positive and others. Thrombotic events were more often venous (56.4%) than arterial (37.7%). Triple-positive patients had more placental complications than others (17.6% vs 2.9%, p=0.001) and more non-criteria events (48.5% vs 25.7%, p=0.002). Among non-criteria events, there was a higher frequency of Sneddon syndrome in triple-positive patients (7.4% vs 0.7%, p=0.028). The relapse rate was higher in triple-positive patients than in others (63.2% vs 39,7%, p=0002). In multivariate analysis, the triple-positive profile was associated with a higher risk of relapse (HR 1.63; 95% CI 1.04 to 2.55; p=0.031). CONCLUSION: The triple-positivity is associated with a higher risk of relapse and obstetrical complications.

Identifying high-risk profile in primary antiphospholipid syndrome through cluster analysis: French multicentric cohort study.

INTRODUCTION: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by thrombosis (arterial, venous or small vessel) or obstetrical events and persistent antiphospholipid antibodies (aPL), according to the Sydney classification criteria. Many studies have performed cluster analyses among patients with primary APS and associated autoimmune disease, but none has focused solely on primary APS. We aimed to perform a cluster analysis among patients with primary APS and asymptomatic aPL carriers without any autoimmune disease, to assess prognostic value. METHODS: In this multicentre French cohort study, we included all patients with persistent APS antibodies (Sydney criteria) measured between January 2012 and January 2019. We excluded all patients with systemic lupus erythematosus or other systemic autoimmune diseases. We performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with baseline patient characteristics to generate clusters. RESULTS: We identified four clusters: cluster 1, comprising 'asymptomatic aPL carriers', with low risk of events during follow-up; cluster 2, the 'male thrombotic phenotype', with older patients and more venous thromboembolic events; cluster 3, the 'female obstetrical phenotype', with obstetrical and thrombotic events; and cluster 4, 'high-risk APS', which included younger patients with more frequent triple positivity, antinuclear antibodies, non-criteria manifestations and arterial events. Regarding survival analyses, asymptomatic aPL carriers relapsed less frequently than the others, but no other differences in terms of relapse rates or deaths were found between clusters. CONCLUSIONS: We identified four clusters among patients with primary APS, one of which was 'high-risk APS'. Clustering-based treatment strategies should be explored in future prospective studies.

The Histopathological "Placentitis Triad" Is Specific for SARS-CoV-2 Infection, and Its Acute Presentation Can Be Associated with Poor Fetal Outcome.

(1) Background: Placental histological lesions reported in relation with SARS-CoV-2 infection are various, with potential consequences such as fetal growth retardation, prematurity or stillbirth/neonatal death. We report here on a placental pathological association which could be specific for SARS-CoV-2 infection and associated with poor fetal outcome; (2) Methods: We collected all the placental pathological examinations performed in Brest University Hospital (France) since the beginning of COVID-19 pandemic with a known maternal SARS-CoV-2 infection and a poor pregnancy outcome. In these cases, we described the pathological lesions and we searched for these lesions in a large series of placentas collected and examined in the same institution before the SARS-CoV-2 pandemic; (3) Results: Three cases with severe fetal outcome (tardive abortion, prematurity, neonatal death), from the first to the third trimesters of pregnancy, were included. The three cases showed features of massive and acute "placentitis triad" consisting in massive perivillous fibrin deposition, sub-acute intervillositis and trophoblastic necrosis. This association was not encountered in any of 8857 placentas analyzed during the period between 2002 and 2012 in our institution; (4) Conclusions: The "placentitis triad" appears to be specific for SARS-CoV-2 infection and, in case of massive and acute presentation, could result in poor fetal outcome.

Venous Thromboembolism Associated with Assisted Reproductive Technology: A Systematic Review and Meta-analysis.

BACKGROUND: Hormonal exposure leads to an increased risk of venous thromboembolism (VTE) but the risk of VTE associated with assisted reproductive technology (ART) is not clearly determined. METHODS: We searched in PubMed, EMBASE, Web of Science, and the Cochrane Library databases and identified all relevant articles published up to February 1, 2021. The primary objective was to determine the frequency of VTE associated with ART. Secondary objectives were to determine (1) the risk of VTE associated with ART as compared to pregnancy without ART; (2) the risk of VTE associated with ovarian hyperstimulation syndrome (OHSS); and (3) to determine potential risk factors of VTE related to ART. RESULTS: Fourteen studies were included. The overall frequency of VTE associated with ART was 0.23% (95% confidence interval [CI]: 0.07-0.46). Women undergoing ART had a two- to threefold increased risk of VTE as compared to spontaneous pregnancy (relative risk [RR]: 2.66; 95% CI: 1.60-4.43). The overall frequency of VTE specifically related to OHSS was <0.001%. The risk of VTE after ART complicated by OHSS, as compared to ART without OHSS, was higher but not statistically significant (RR: 14.83; 95% CI: 0.86-255.62). Risk factors of VTE associated with ART were in vitro fertilization procedure (RR, odds ratio [OR], and hazard ratio varying from 1.77, 95% CI: 1.41-2.23 to 4.99, 95% CI: 1.24-20.05), hyperhomocysteinemia (OR: 15.2; 95% CI: 2.0-115.0), polycystic ovarian syndrome (PCOS) (RR: 4.8; 95% CI: 1.7-13.4), successful ART leading to pregnancy (OR: 13.94; 95% CI: 1.41-137.45). CONCLUSION: Further large prospective studies on risk factors of VTE in women undergoing ART are needed in order to optimize thromboprophylaxis in this context.

Clinical risk factors for vasculo-placental disorders: results from a prospective case-control study nested in HEMOTHEPP French cohort study.

OBJECTIVE: Determine clinical risk factors for vasculo-placental disorders in singleton pregnancies. DESIGN: Prospective case-control study nested in HEMOTHEPP French cohort. SETTING: Women delivered between June, 2015 and January, 2019 in any maternity ward of Finistère. POPULATION: Cases were women with vasculo-placental disorders (pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption or stillbirth). Controls were women matched for age at delivery and parity. METHODS: Clinical data were collected by obstetricians or midwives during antenatal care visits and delivery, and recorded by trained research assistants. MAIN OUTCOME MEASURES: Occurrence of a vasculo-placental disorder. RESULTS: 505 women with vasculo-placental disorder (299 pre-eclampsia, 253 IUGR, 44 placental abruptions, 11 stillbirths) and 1515 matched controls were selected out of 20,075 participants. In multivariable analysis, four clinical parameters were associated with pre-eclampsia: obesity (Odd ratio (OR) = 3.11, 95%CI 2.11-4.58), French overseas origin (OR = 4.41, 95%CI 1.87-10.42), previous vasculo-placental disorder (OR = 5.14, 95%CI 2.72-9.70), aspirin during pregnancy (OR = 10.10, 95%CI 1.99-51.08). Three clinical parameters were associated with IUGR: auto-immune/inflammatory disorder (OR = 3.75, 95%CI 1.83-7.68), previous vasculo-placental disorder (OR = 3.63, 95%CI 2.06-6.41), smoking during pregnancy (OR = 2.66, 95%CI 1.91- 3.71). A previous venous thromboembolism (VTE) was associated with IUGR in univariable but not in multivariable analysis (OR = 3.72, 95%CI 0.82-17.00, p = 0.09). CONCLUSIONS: Clinical risk factors differ between IUGR and pre-eclampsia, the later, but not the former, being associated with cardiovascular risk factors.

Comparison between idiopathic and VEXAS-relapsing polychondritis: analysis of a French case series of 95 patients.

OBJECTIVE: A new adult-onset autoinflammatory syndrome has been described, named VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic). We aimed to compare the clinical characteristics, the laboratory features and the outcomes between idiopathic-relapsing polychondritis (I-RP) and VEXAS-relapsing polychondritis (VEXAS-RP). METHODS: Patients from French retrospective multicentre cohort of RP were separated into two groups: a VEXAS-RP and an I-RP. RESULTS: Compared with patients with I-RP (n=40), patients with VEXAS-RP (n=55) were men (96% vs 30%, p<0.001) and were older at diagnosis (66 vs 44 years, p<0.001). They had a greater prevalence of fever (60% vs 10%, p<0.001), of skin lesions (82% vs 20%, p<0.001), of ocular involvement (57% vs 28%, p=0.01), of pulmonary infiltrates (46% vs 0%, p<0.001), of heart involvement (11% vs 0%, p=0.0336) and with higher median C-reactive protein levels (64 mg/L vs 10 mg/L, p<0.001). Seventy-five per cent of the patients with VEXAS-RP had myelodysplastic syndrome (MDS) versus none in I-RP group. The glucocorticoids use, and the number of steroid sparing agents were similar in both groups, but patients with VEXAS-RP had more frequent refractory disease (remission obtained in 27% vs 90%, p<0001). VEXAS-RP was associated with higher risk of death: six patients (11%) died in the VEXAS-RP group after a median follow-up of 37 months and none in the I-RP group after a median follow-up of 92 months (p<0.05). CONCLUSION: We report the largest cohort of VEXAS-RP, characterised by high prevalence of male sex, fever, skin lesion, ocular involvement, pulmonary infiltration, heart involvement, older age and MDS association.

Long-term prophylaxis in hereditary angioedema management: Current practices in France and unmet needs.

Background: Hereditary angioedema (HAE) is characterized by unpredictable and potentially life-threatening attacks of cutaneous and submucosal swelling. Over the past decade, new agents, based on a better understanding of the underlying biologic mechanisms of HAE, have changed the face of long-term prophylaxis (LTP). Objective: The objective was to describe current practices and unmet needs with regard to LTP for HAE in expert centers in France. Methods: The study was conducted in France in 2020. Based on their experience with patients with HAE who had visited their center at least once in the past 3 years, physicians from 25 centers who are expert in the management of HAE were requested to fill in a questionnaire that encapsulated their active patient list, criteria for prescribing LTP, and medications used. They were asked about potential unmet needs with currently available therapies. They were asked to express their expectations with regard to the future of HAE management. Results: Analysis was restricted to 20 centers that had an active patient file and agreed to participate. There were 714 patients with C1 inhibitor (C1-INH) deficiency, of whom 423 (59.2%) were treated with LTP. Altered quality of life triggered the decision to start LTP, as did the frequency and severity of attacks. Ongoing LTP included androgens (28.4%), progestins (25.8%), lanadelumab (25.3%), tranexamic acid (14.2%), intravenous C1-INHs (5.6%), and recombinant C1-INH (0.7%). Twenty-nine percent of the patents with LTP were considered to still have unmet needs. Physicians' concerns varied among therapies: poor tolerability for androgens and progestins, a lack of efficacy for tranexamic acid and progestins, dosage form, and high costs for C1-INHs and lanadelumab. Physicians' expectations encompassed more-efficacious and better-tolerated medications, easier treatment administration for the sake of improved quality of life of patients, and less-expensive therapies. Conclusion: Despite the recent enrichment of the therapeutic armamentarium for LTP, physicians still expressed unmet needs with currently available therapies.

Use of biologics to treat relapsing and/or refractory polyarteritis nodosa: data from a European collaborative study.

OBJECTIVES: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN). METHODS: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease. RESULTS: Forty-two patients with PAN received a total of 53 biologic courses, including TNF-α blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases and other biologics in 10 cases. TNF-α blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission, partial response, treatment failure and treatment discontinuation due to severe adverse events occurred in, respectively, 40%, 13%, 40% and 7% of patients receiving TNF-α blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the three biologics, leading to early biologics discontinuation in only three cases. CONCLUSION: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.

Excessive gestational weight gain is an independent risk factor for gestational diabetes mellitus in singleton pregnancies: Results from a French cohort study.

OBJECTIVE: Increase in prevalence of maternal obesity worldwide raises concern among health professionals. Our purpose was to evaluate the impact of maternal obesity and of excessive gestational weight gain (GWG) on the course of singleton pregnancies in a French maternity ward. STUDY DESIGN: 3599 consecutive women who delivered from April 2013 to May 2015 at Brest University Hospital were included in HPP-IPF cohort study, a study designed to evaluate clinical and biological determinants of postpartum hemorrhage (PPH). Maternal obesity was defined by a pre-pregnancy Body Mass Index (BMI) ≥ 30 kg/m2 and excessive GWG was defined according to the Institute of Medicine 2009 guidelines. Obstetric complications(including gestational diabetes mellitus (GDM), gestational hypertension, pre-eclampsia, venous thromboembolism, PPH, cesarean section (C-section) and macrosomia) were collected prospectively in a standardized case report form. For each complication, Odd Ratios (OR) according to pre-pregnancy BMI and GWG were calculated in univariable and multivariable analyses. RESULTS: Out of the 3162 women analyzed for this report, 583 (18.4%) were overweight, 400 (12.7%) were obese and 36.6% had excessive GWG. In multivariable analysis, after adjustment for confounding factors, obese women were at increased risk of GDM (OR 5.83, 95%CI 4.37-7.79), PPH (OR 1.69, 95%CI 1.19-2.41), C-section (OR 2.50, 95%CI 1.92-3.26) and macrosomia (OR 1.90, 95%CI 1.31-2.76). Similarly, women with excessive GWG were at increased risk of GDM (OR 1.55, 95%CI 1.17-2.06), C-section (OR 1.46, 95%CI 1.16-1.83) and macrosomia (OR 2.09, 95%CI 1.50-2.91). CONCLUSIONS: Maternal obesity and excessive GWG are independent risk factors for GDM, C-section and macrosomia in singleton pregnancies. Further studies are needed to evaluate if a lifestyle intervention aiming at avoiding excessive GWG could improve clinical outcomes in pregnant women.

Anticoagulation for VTE: Impact on the Risk of Major Adverse Cardiovascular Events.

BACKGROUND: It was recently established that patients who developed VTE are at increased risk of major adverse cardiovascular events (MACE) compared with the general population. However, whether the anticoagulation used for VTE influences the risk of MACE remains undescribed. RESEARCH QUESTION: Does the anticoagulant treatment for VTE affect the risk of subsequent MACE? STUDY DESIGN AND METHODS: This study included patients from a large prospective cohort who received only one family of anticoagulant treatment after the acute phase of VTE, including vitamin K antagonist (VKAs) and direct oral anticoagulants (DOACs). MACE included nonfatal acute coronary syndrome, nonfatal stroke, and all-cause death. The secondary outcome, MACE-2, included cardiovascular death instead of all-cause death. Cox proportional and Fine-Gray models served to study the relationship between anticoagulation characteristics and the risk of outcomes. RESULTS: A total of 3,790 patients (47.2% male; mean age, 60.48 years) were included. A total of 1,228 patients (32.4%) were treated for 0 to 3 months (median in overall population, 6 months). Compared with these patients, those treated for 3 to 12 months (hazard ratio [HR], 0.64; 95% CI, 0.54-0.76) or > 12 months (HR, 0.47, 95% CI, 0.39-0.56) had a significant reduced risk of MACE following adjustment for confounders. Findings were similar for MACE-2 (sub-HR for 3-12 months, 0.61 [95% CI, 0.47-0.79]; sub-HR > 12 months, 0.52 [95% CI, 0.39-0.68]). After adjustment for confounders, there was a reduced risk of MACE (HR, 0.53; 95% CI, 0.39-0.71) and MACE-2 (sub-HR, 0.48; 95% CI, 0.29-0.77) in patients treated with DOACs (vs VKAs). INTERPRETATION: Treatment of VTE for > 3 months is associated with a reduced risk of MACE, as is treatment with DOACs vs VKAs. These findings, which may influence the choice of anticoagulation strategies for VTE, need confirmation by randomized clinical trials.

Validation of the French translation of a self-administered questionnaire looking for a history of pre-eclampsia.

We evaluated the diagnostic performances of the French translation of a self-administered questionnaire designed by Diehl et al. looking for a history of pre-eclampsia. After a phone call, 206 women who gave birth at Brest University Hospital responded to the questionnaire online. Then, their responses were compared to their medical files. The sensitivity of the questionnaire was 95.2% and its specificity was 98.0%. This French questionnaire has then demonstrated its validity. It can now be used to explore the role of a pre-eclampsia history on various pathologies and, by this mean, to improve knowledge about women's health.