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Background Prophylactic administration of tranexamic acid has been associated with reduced postpartum blood loss after cesarean delivery in several small trials, but evidence of its benefit in this clinical context remains inconclusive.Methods In a multicenter, double-blind, randomized, controlled trial, we assigned women undergoing cesarean delivery before or during labor at 34 or more gestational weeks to receive an intravenously administered prophylactic uterotonic agent and either tranexamic acid (1 g) or placebo. The primary outcome was postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1000 ml or receipt of a red-cell transfusion within 2 days after delivery. Secondary outcomes included gravimetrically estimated blood loss, provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, and postpartum blood transfusion.Results Of the 4551 women who underwent randomization, 4431 underwent cesarean delivery, 4153 (93.7%) of whom had primary outcome data available. The primary outcome occurred in 556 of 2086 women (26.7%) in the tranexamic acid group and in 653 of 2067 (31.6%) in the placebo group (adjusted risk ratio, 0.84; 95% confidence interval [CI], 0.75 to 0.94; P=0.003). There were no significant between-group differences in mean gravimetrically estimated blood loss or in the percentage of women with provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, or postpartum blood transfusion. Thromboembolic events in the 3 months after delivery occurred in 0.4% of women (8 of 2049) who received tranexamic acid and in 0.1% of women (2 of 2056) who received placebo (adjusted risk ratio, 4.01; 95% CI, 0.85 to 18.92; P=0.08).Conclusions Among women who underwent cesarean delivery and received prophylactic uterotonic agents, tranexamic acid treatment resulted in a significantly lower incidence of calculated estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not result in a lower incidence of hemorrhage-related secondary clinical outcomes. (Funded by the French Ministry of Health; TRAAP2 ClinicalTrials.gov number, NCT03431805.)Blood-Loss Prevention after Cesarean Delivery In this trial involving women undergoing cesarean delivery (all of whom received prophylactic uterotonic medication), tranexamic acid treatment resulted in a significantly lower incidence of estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not reduce the risk of hemorrhage-related secondary clinical outcomes.

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS. Patients received LEN alone, 10 mg per day, 21 days per 4 weeks (L arm) or LEN (same schedule) + erythropoietin (EPO) beta, 60,000 U per week (LE arm). In an intent-to-treat (ITT) analysis, erythroid response (HI-E, IWG 2006 criteria) after four treatment cycles (primary end point) was 23.1% (95% CI 13.5-35.2) in the L arm and 39.4% (95% CI 27.6-52.2) in the LE arm (P=0.044), while RBC-TI was reached in 13.8 and 24.2% of the patients in the L and LE arms, respectively (P=0.13). Median response duration was 18.1 and 15.1 months in the L and LE arms, respectively (P=0.47). Side effects were moderate and similar in the two arms. Low baseline serum EPO level and a G polymorphism of CRBN gene predicted HI-E. Combining LEN and EPO significantly improves erythroid response over LEN alone in lower-risk non-del5q MDS patients with anemia resistant to ESA

Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis.

Osteoporosis is a skeletal disorder characterized by abnormal bone microarchitecture and low bone mineral density (BMD), responsible for an increased risk of fractures and skeletal fragility. It is a common pathology of the aging population. However, when osteoporosis occurs in children or young adults, it strongly suggests an underlying genetic etiology. Over the past two decades, several genes have been identified as responsible for this particular kind of considered monogenic early-onset osteoporosis (EOOP) or juvenile osteoporosis, the main ones being COL1A1, COL1A2, LRP5, LRP6, WNT1, and more recently PLS3. In this study, the objective was to characterize a large cohort of patients diagnosed with primary osteoporosis and to establish its diagnosis yield. The study included 577 patients diagnosed with primary osteoporosis and its diagnosis yield was established. To this end, next-generation sequencing (NGS) of a panel of 21 genes known to play a role in bone fragility was carried out. A genetic etiology was explained in about 18% of cases, while the others remain unexplained. The most frequently identified gene associated with EOOP is LRP5, which was responsible for 8.2% of the positive results (47 patients). As unexpected, 17 patients (2.9%) had a variant in PLS3 which encodes plastin 3. Alterations of PLS3 are associated with dominant X-linked osteoporosis, an extremely rare disease. Given the rarity of this disease, we focused on it. It was observed that males were more affected than females, but it is noteworthy that three females with a particularly severe phenotype were identified. Of these three, two had a variant in an additional gene involved in EOP, illustrating the probable existence of digenism. We significantly increase the number of variants potentially associated with EOOP, especially in PLS3. The results of our study demonstrate that molecular analysis in EOOP is beneficial and useful.

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) as conditioning regimen prior to autologous stem-cell transplantation (ASCT) remains the standard of care for patients with mantle cell lymphoma (MCL) who are eligible for transplantation. The replacement of carmustine with bendamustine (BeEAM) was described as a promising alternative in non-Hodgkin lymphoma. The aim of this retrospective study was to compare the BeEAM with the BEAM regimen in MCL patients in the frontline setting. Sixty and 108 patients were included in the BeEAM and the BEAM groups, respectively. At 3 years, progression-free survival (PFS) was significantly higher in the BeEAM than in the BEAM group (84% [73–96] vs. 63% [51–79], p = 0.03). The overall survival was not statistically different between the two groups (p = 0.2). In multivariable analysis, BeEAM regimen remained associated with higher PFS (HR = 0.377, 95% CI, 0.146–0.970; p = 0.043). Subgroup analyses in patients treated with prior rituximab–aracytine induction alone showed that BeEAM improved the PFS compared with BEAM regimen (p = 0.04). Despite the high rate of acute renal failure KDIGO III (32%), treatment-related mortality was not increased with the BeEAM regimen. A prospective randomized trial will be necessary to confirm the beneficial effect of the BeEAM regimen in MCL patients undergoing ASCT.

BACKGROUND: Ruptured middle cerebral artery aneurysm (MCAa) can lead to intracerebral hematoma, and surgical evacuation can be performed in these cases. MCAa can be treated by clipping or before by endovascular therapy (EVT). Our objective was to compare the impact on the functional outcome of MCAa in patients with intracerebral hematoma requiring evacuation. METHODS: This is a multicenter, retrospective, cohort study with nine French neurosurgical units from January 1, 2013, to December 31, 2020. All participants were adult patients who required evacuation of an intracerebral hematoma. We looked for risk factors for poor outcomes by comparing the baseline characteristics and treatments performed by using the 6-month modified Rankin scale score. Poor outcomes were defined by an modified Rankin scale score of 3-6. RESULTS: A total of 162 patients were included. A total of 129 (79.6%) patients were treated by microsurgery, and 33 (20.4%) patients were treated by EVT. In multivariate analysis, factors associated with poor outcomes included hematoma volume, realization of a decompressive craniectomy, occurrence of procedure-related symptomatic cerebral ischemia, occurrence of delayed cerebral ischemia, and EVT. In the propensity score matching analysis (n = 33 per group), poor outcomes were observed in 30% of the patients in the clipping group versus 76% in the EVT group (P \\textless 0.001). These differences may have been related to a longer delay between hospital admission and hematoma evacuation in the EVT group. CONCLUSIONS: In the specific subgroup of ruptured MCAa with intracerebral hematoma that requires surgical evacuation, clipping with concomitant hematoma evacuation could provide better functional outcomes than EVT followed by surgical evacuation.

Zoonotic species of Capnocytophaga genus belong to the oral microbiota of dogs and cats. They may be responsible for serious human infections, mainly after animal bites, with a high mortality rate. In France, only few cases have been reported and no multicenter study has been conducted. Our aim was to describe the French epidemiology of Capnocytophaga zoonosis. We conducted a multicenter (21 centers) retrospective non-interventional, observational study in France describing the epidemiology of Capnocytophaga zoonosis (C. canimorsus, C. cynodegmi, C. canis) over 10 years with regard to clinical and bacteriological data. From 2009 to 2018, 44 cases of Capnocytophaga zoonotic infections were described (C. canimorsus, n = 41; C. cynodegmi, n = 3). We observed an increase (2.5 times) in the number of cases over the study period (from the first to the last 5 years of the study). The most frequent clinical presentations were sepsis (n = 37), skin and soft tissue infections (n = 12), meningitis (n = 8), osteoarticular infections (n = 6), and endocarditis (n = 2). About one-third of patients with sepsis went into septic shock. Mortality rate was 11%. Mortality and meningitis rates were significantly higher for alcoholic patients (p = 0.044 and p = 0.006, respectively). Other comorbidities included smoking, splenectomy, diabetes mellitus, and immunosuppressive therapy are associated to zoonotic Capnocytophaga infection. Eighty-two percent of cases involved contact with dogs, mostly included bites (63%). Despite all isolates were susceptible to the amoxicillin-clavulanic acid combination, three of them were resistant to amoxicillin.

Although central venous catheter (CVC)-related thrombosis (CRT) is a severe complication of home parenteral nutrition (HPN), the amount and quality of data in the diagnosis and management of CRT remain low. We aimed to describe current practices regarding CVC management in French adult and pediatric HPN centers, with a focus on CVC obstruction and CRT. Current practices regarding CVC management in patients on HPN were collected by an online-based cross-sectional survey sent to expert physicians of French HPN centers. We compared these practices to published guidelines and searched for differences between pediatric and adult HPN centers’ practices. Finally, we examined the heterogeneity of practices in both pediatric and adult HPN centers. The survey was completed by 34 centers, including 21 pediatric and 13 adult centers. We found a considerable heterogeneity, especially in the responses of pediatric centers. On some points, the centers’ responses differed from the current guidelines. We also found significant differences between practices in adult and pediatric centers. We conclude that the management of CVC and CRT in patients on HPN is a serious and complex situation for which there is significant heterogeneity between HPN centers. These findings highlight the need for more well-designed clinical trials in this field.

Background:Pneumococcal vaccination is recommended for patients with chronic inflammatory rheumatism treated with immunosuppressants. Methotrexate (MTX) is the first-line treatment used in rheumatoid arthritis (RA), but can decrease the immune response of anti-pneumococcal vaccination in RA patients. It is recommended to vaccine before initiation of MTX but it is also recommended to start MTX as soon as the diagnosis of RA is made.Objectives:The main objective of VACIMRA study was then to compare, in the context of a prospective, randomized, multicenter, open trial, the rate of immunological response in RA patients receiving the pneumococcal 13 -valent conjugate vaccine (PCV13) either 1 month before MTX initiation (group DELAY: GD) or simultaneously with MTX (group IMMEDIATE: GI).Methods:RA patients (ACR/EULAR 2010 criteria) were vaccinated with PCV13 at randomization and two months later with 23-valent pneumococcal polysaccharide vaccine (PPV23). Ig G concentrations of the 13 serotypes contained in PCV13 were measured at baseline and during follow-up at 1, 3, 6 and 12 months. After randomization 1:1, MTX was initiated immediately in GI or at one month in GD. Oral steroids were allowed but less than 10mg/day. Disease activity, infections and side effects were collected throughout the study. Outcomes were serotype-specific IgG concentrations of the 13 pneumococcal serotypes contained in PCV13 using ELISA and functional antibody activity using an opsonophagocytic killing assay (OPA), reported as the opsonisation indices (OIs). Positive antibody response was defined as ≥ 2-fold increase in the IgG concentration by ELISA. For OI, response was defined as a value ≥ to the serotype threshold provided by the laboratory. Main outcome was the responder rates at one month after PCV13, defined by at least 3 positives antibody responses out of 5 of the target serotypes (1, 3, 5, 7F, 19A) by ELISA or OPA. The main analysis was performed in the full analysis set (FAS) with a logistic mixed model.Results:276 RA patients were randomized: 188 in GI and 188 in GD. For the primary end point, data of 249 patients were analyzed in FAS and 224 for per protocol (PP). Characteristics of the RA patients at baseline were similar between the two groups: 70% female, mean age 55.6 years, RA duration 2 months, 69% ACPA+, 21% erosive, DAS28-CRP 4.6. Compared to GI, the rates of responders were significantly higher in GD: 88% versus 75% (p<0.01) and 96% versus 88% (p=0.02) by ELISA and OPA respectively, in FAS. These differences were also observed without imputation of missing values in FAS and PP analysis. The proportions of responders at 12 months were still higher in GD with ELISA or OPA tests. Evolution of geometric mean concentrations during the year of follow-up were higher for most of the 13 serotypes in GD compared to GI. The cumulative doses of steroids were similar between GI and GD during the follow-up. As expected, cumulative dose of MTX was higher in GI than in GD during follow-up. However, the weekly mean doses of MTX were similar at 3, 6 and 12 months between the two groups. The use of targeted DMARDs at 1 year was comparable between the two groups. There was no difference in terms of serious adverse events between groups with one pneumococcal infection in the GD during follow-up. There were no unexpected side effects observed with PCV13 and PPV23. At 1 month, DAS28 scores were higher in GD than in GI: 3.95 vs 3.38 for DAS28-ESR and 3.54 vs 3.01 for DAS28-CRP (p<0.01). Beyond the 1st month, DAS28 scores were similar between the two groups.Conclusion:This study clearly demonstrates that in RA, PCV13 vaccine administered 1 month prior starting MTX, allows a significantly higher immunological response at 1 month, in comparison to patients vaccinated simultaneously with MTX. The proportions of responders were also significantly higher in GD at 1 year with no differences on disease control and treatments used for RA such as glucocorticoids or targeted DMARDs. These results strongly support to vaccinate patients before MTX initiationREFERENCES:NIL.Acknowledgements:F-CRIN networks: i REIVAC and CRI-IMMIDIATE.Disclosure of Interests:Jacques Morel Abbvie,, Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, Glaxo Smith Kline, Lilly, Médac, Nordic-Pharma, Novartis, Pfizer, Sandoz, Sanofi, Abbvie, Bristol Myers Squibb, Boerhinger Ingelheim, Fresenius Kabi, Galapagos, Glaxo Smith Kline, Lilly, Novartis, Sanofi, Abbvie, Biogen, Bristol Myers Squibb, Fresenius Kabi, Lilly, Novartis, Pfizer, Sanofi, Servier, Emmanuelle Dernis: None declared, Christian Roux: None declared, Christophe Richez: None declared, Olilvier Brocq: None declared, Bruno Fautrel: None declared, Carine Salliot: None declared, Olivier Vittecoq: None declared, Xavier Mariette: None declared, Frederic Lioté: None declared, Slim Lassoued: None declared, Cécile Gaujoux-Viala: None declared, Arnaud Constantin: None declared, Martin Soubrier: None declared, Valerie Devauchelle-Pensec: None declared, Vincent Goeb: None declared, Jacques-Eric Gottenberg: None declared, Hubert Marotte: None declared, Anouck Remy Moulard: None declared, Claire Daien: None declared, Gael Mouterde: None declared, helena Huguet: None declared, Odile Launay: None declared, Florence Galtier: None declared, Marie Christine Picot: None declared.