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Introduction: VEXAS is a syndrome described in 2020, caused by mutations of the UBA1 gene, and displaying a large pleomorphic array of clinical and hematological features. Nevertheless, these criteria lack significance to discriminate VEXAS from other inflammatory conditions at the screening step. This work hence first focused on singling out dysplastic features indicative of the syndrome among peripheral blood (PB) polymorphonuclears (PMN). A deep learning algorithm is then proposed for automatic detection of these features., Methods: A multicentric dataset, comprising 9514 annotated PMN images was gathered, including UBA1 mutated VEXAS (n = 25), UBA1 wildtype myelodysplastic (n = 14), and UBA1 wildtype cytopenic patients (n = 25). Statistical analysis on a subset of patients was performed to screen for significant abnormalities. Detection of these features on PB was then automated with a convolutional neural network (CNN) for multilabel classification., Results: Significant differences were observed in the proportions of PMNs with pseudo-Pelger, nuclear spikes, vacuoles, and hypogranularity between patients with VEXAS and both cytopenic and myelodysplastic controls. Automatic detection of these abnormalities yielded AUCs in the range [0.85-0.97] and a F1-score of 0.70 on the test set. A VEXAS screening score was proposed, leveraging the model outputs and predicting the UBA1 mutational status with 0.82 sensitivity and 0.71 specificity on the test patients., Conclusion: This study suggests that computer-assisted analysis of PB smears, focusing on suspected VEXAS cases, can provide valuable insights for determining which patients should undergo molecular testing. The presented deep learning approach can help hematologists direct their suspicions before initiating further analyses., (© 2024 John Wiley & Sons Ltd.)

Background: Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal., Objective: To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination., Study Design: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery., Results: Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery., Conclusion: Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We report the results of the French multicentric phase II study MIITOP (NCT00960739), which evaluated tandem infusions of 131 I-metaiodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory metastatic neuroblastoma (NBL)., Methods: Patients received 131 I-mIBG on day 1, with intravenous topotecan daily on days 1-5. A second activity of 131 I-mIBG was given on day 21 to deliver a whole-body radiation dose of 4 Gy, combined with a second course of topotecan on days 21-25. Peripheral blood stem cells were infused on day 31., Results: Thirty patients were enrolled from November 2008 to June 2015. Median age at diagnosis was 5.5 years (2-20). Twenty-one had very high-risk NBL (VHR-NBL), that is, stage 4 NBL at diagnosis or at relapse, with insufficient response (i.e., less than a partial response of metastases and more than three mIBG spots) after induction chemotherapy; nine had progressive metastatic relapse. Median Curie score at inclusion was 6 (1-26). Median number of prior lines of treatment was 3 (1-7). Objective response rate was 13% (95% confidence interval [CI]: 4-31) for the whole population, 19% for VHR-NBL, and 0% for progressive relapses. Immediate tolerance was good, with nonhematologic toxicity limited to grade-2 nausea/vomiting in eight patients. Two-year event-free survival was 17% (95% CI: 6-32). Among the 16 patients with VHR-NBL who had not received prior myeloablative busulfan-melphalan consolidation, 13 had at least stable disease after MIITOP; 11 subsequently received busulfan-melphalan; four of them were alive (median follow-up: 7 years)., Conclusion: MIITOP showed acceptable tolerability in this heavily pretreated population and encouraging survival rates in VHR-NBL when followed by busulfan-melphalan., (© 2023 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Aging is associated with bone marrow (BM) inflammaging and, in some individuals, with the onset of clonal hematopoiesis (CH) of indeterminate potential. In this study conducted on 94 strictly healthy volunteers (18 to 80 yo), we measured BM and peripheral blood (PB) plasma levels of 49 hematopoietic and inflammatory cytokines. With aging, 7 cytokines increased in BM (FLT3L, CXCL9, HGF, FGF-2, CCL27, IL-16, IL-18) and 8 decreased (G-CSF, TNF, IL-2, IL-15, IL-17A, CCL7, IL-4, IL-10). In PB, 10 cytokines increased with age (CXCL9, FLT3L, CCL27, CXCL10, HGF, CCL11, IL-16, IL-6, IL-1 beta, CCL2). CH was associated with higher BM levels of MIF and IL-1 beta, lower BM levels of IL-9 and IL-5 and higher PB levels of IL-15, VEGF-A, IL-2, CXCL8, CXCL1 and G-CSF. These reference values provide a useful tool to investigate anomalies related to inflammaging and potentially leading to the onset of age-related myeloid malignancies or inflammatory conditions., Competing Interests: Declaration of Competing Interest All authors have read the journal's policy on disclosure of potential conflicts of interest and have none to declare. All authors have read the journal's authorship statement., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) has been reported as a safe and efficient therapy for treating refractory ventricular tachycardia (VT) despite optimal medical treatment and catheter ablation. However, data on the use of SBRT in patients with electrical storm (ES) is lacking. The aim of this study was to assess the clinical outcomes associated with SBRT in the context of ES., Methods: This retrospective study included patients who underwent SBRT in the context of ES from March 2020 to March 2021 in one tertiary center (CHU Lille). The target volume was delineated according to a predefined workflow. The efficacy was assessed with the following end points: sustained VT recurrence, VT reduced with antitachycardia pacing, and implantable cardioverter defibrillator shock., Results: Seventeen patients underwent SBRT to treat refractory VT in the context of ES (mean 67±12.8 age, 59% presenting ischemic heart disease, mean left ventricular ejection fraction: 33.7± 9.7%). Five patients presented with ES related to incessant VT. Among these 5 patients, the time to effectiveness ranged from 1 to 7 weeks after SBRT. In the 12 remaining patients, VT recurrences occurred in 7 patients during the first 6 weeks following SBRT. After a median 12.5 (10.5-17.8) months follow-up, a significant reduction of the VT burden was observed beyond 6 weeks (-91% [95% CI, 78-103]), P <0.0001). The incidence of implantable cardioverter defibrillator shock and antitachycardia pacing was 36% at 1 year., Conclusions: SBRT is associated with a significant reduction of the VT burden in the event of an ES; however, prospective randomized control trials are needed. In patients without incessant VT, recurrences are observed in half of patients during the first 6 weeks. VT tolerance and implantable cardioverter defibrillator programming adjustments should be integrated as part of an action plan defined before SBRT for each patient.

Ring sideroblasts are commonly seen in myelodysplastic neoplasms and are a key condition for identifying distinct entities of myelodysplastic neoplasms according to the WHO classification. However, the presence of ring sideroblasts is not exclusive to myelodysplastic neoplasms. Ring sideroblasts are as well either encountered in non-clonal secondary acquired disorders, such as exposure to toxic substances, drug/medicine, copper deficiency, zinc overload, lead poison, or hereditary sideroblastic anemias related to X-linked, autosomal, or mitochondrial mutations. This review article will discuss diseases associated with ring sideroblasts outside the context of myelodysplastic neoplasms. Knowledge of the differential diagnoses characterized by the presence of ring sideroblasts in bone marrow is essential to prevent any misdiagnosis, which leads to delayed diagnosis and subsequent management of patients that differ in the different forms of sideroblastic anemia.

Objective: We report a successful live birth after oocytes in vitro maturation (IVM) and fresh embryo transfer in a patient with autoimmune premature ovarian failure (POF) and performed a review of the literature of livebirths obtained after oocytes IVM treatment in this indication., Methods: The patient was a 24-year-old woman with autoimmune POF diagnosed post-partum, who developed autoimmune polyglandular syndrome with serum anti-ovarian and anti-21-hydroxylase antibodies. The patient had typical symptoms of POF: secondary amenorrhea with hypoestrogenism, elevated gonadotropins and infertility; however, the serum anti-Müllerian hormone level and total antral follicle count remained normal. IVM of immature oocytes was performed after the administration of 150 IU highly purified human menopausal gonadotropin for three consecutive days and an injection of 10,000 IU human chorionic gonadotropin to trigger ovulation., Results: The six oocyte-cumulus complexes collected matured in vitro . After intracytoplasmic sperm injection (ICSI), five embryos were obtained. Pregnancy was achieved after the fresh transfer of two embryos and appropriate endometrial preparation. A normal female child was delivered following a 37-weeks pregnancy characterized by the onset of adrenal insufficiency and unstable diabetes., Conclusions: We report a successful livebirth after IVM treatment in a patient with autoimmune premature ovarian failure (POF). Management of reproductive age women with autoimmune pathology requires fertility counseling. Early diagnosis of autoimmune POF is important for early conception and oocyte preservation, because the only other option at present is ovum donation.

The incidence of myelodysplastic syndrome increases with aging and the early diagnosis enables optimal care of these diseases. The DxH 800 hematology analyzer measures and calculates 126 cytological parameters, but only 23 are used for routine CBC assessment. The goal of this study was to use the 103 unexploited "research parameters" to develop an algorithm allowing for an early detection of subclinical MDS patients by triggering morphological analysis. Blood sample parameters from 101 MDS patients and 88 healthy volunteers were analyzed to identify the critical "research parameters" with: (i) the most significant differences between MDS patients and healthy volunteers, (ii) the best contributions to principal component analysis (PCA), first axis, and (iii) the best correlations with PCA, first two axes (cos 2 > 0.6). Ten critical "research parameters" of white blood cells were identified, allowing for the calculation of an MDS-likelihood score (MDS-LS), based on logistic regression. Automatic calculation of the MDS-LS is easily implementable on the middleware system of the DxH 800 to generate a flag for blood smear review, and possibly early detection of MDS patients in the general population.

Background: To evaluate if women with a history of myomectomy have a modified preterm birth risk compared to women with myomas during pregnancy., Methods: Retrospective cohort study including all women with a history of myomectomy (operated group) or uterine myomas during pregnancy (unoperated group) who delivered in a tertiary center between January, 2011 and December, 2017. The operated group included women who had a myomectomy history with or without myomas during the ongoing pregnancy. The unoperated group included women with uterine myoma(s) seen on at least one ultrasound during pregnancy without history of myomectomy. The primary outcome was preterm birth < 37 weeks, and the secondary outcome spontaneous preterm birth < 37 weeks. To control for confounding factors, a propensity score approach was used. Two sensitivity analysis were performed, one repeating the analysis using the propensity score after excluding operated women with persistent myomas and one using a classical multivariable logistic regression model., Results: The cohort included 576 women: 283 operated women and 293 unoperated women. The rate of preterm birth was similar in the two groups: 12.6% in the unoperated group and 12.0% in the operated group (p = 0.82). No difference in preterm birth risk was shown between unoperated and operated women in the cohort matched on the propensity score: OR 0.86; 95%CI [0.47-1.59]. These results were consistent for spontaneous preterm birth (OR 1.61; 95%CI [0.61-4.23]) and for the sensitivity analyses., Conclusion: In women with a leiomyomatous uterus, a history of myomectomy is not associated with a reduced preterm birth risk.

Clonal hematopoiesis (CH) of indeterminate potential has been described in blood samples from large series of patients. Its prevalence and consequences are still not well understood because sequencing methods vary and because most studies were performed in cohorts comprising individuals with nonhematologic diseases. Here, we investigated the frequency of CH in 82 paired bone marrow and blood samples from carefully selected healthy adult volunteers. Forty-one genes known to be mutated in myeloid malignancies were sequenced with a 1% threshold of detection. In bone marrow samples, clones were found in almost 40% of healthy volunteers more than 50 years old. The most frequent mutations were found in DNMT3A and TET2, with 1 individual carrying 3 variants. Variant allele frequencies were highly concordant between blood and bone marrow samples. Blood parameters were normal except for those in 2 individuals: 1 had a mild macrocytosis and 1 had a mild thrombocytosis. Furthermore, no morphologic abnormalities or dysplasia were detected when bone marrow smears were carefully evaluated. Individuals with CH differed from others by age (62.8 vs 38.6 years; P < .0001) and platelet count (294 vs 241 ×109/L; P = .0208), the latter being no more significant when removing the 2 individuals who carried the JAK2 p.V617F mutation. These results confirm that CH is a very common condition in healthy adults over 50 years old. Consequently, the detection of driver myeloid mutations should be interpreted with caution in the absence of cytologic abnormalities in the blood and/or the bone marrow., (© 2020 by The American Society of Hematology.)

Objectives: To assess the benefit of non-pharmacological intervention promoting on smoking cessation, obstetric and neonatal outcomes, to offer pregnant women who smoke (PWS) optimal care., Methods: We searched Medline Database, Cochrane Library and consulted international guidelines., Results: "Counselling" involving globally all kind of non-pharmacological interventions has a benefit on smoking cessation (NP1) and a moderate benefit on birth weight and prematurity (NP2). The brief intervention seems ineffective on smoking cessation (NP2). The effects of motivational interviewing have not been demonstrated during pregnancy (NP2). Cognitive-behavioral interventions do not show superiority (NP2). Financial incentives have a benefit for smoking cessation and possibly for neonatal outcomes (NP1). Feedback interventions (Co tester) provide heterogeneous results (NP2). Self-help interventions (NP2) and health education (NP2) seem effective on smoking cessation. Hypnotherapy and acupuncture have been little or not studied in PWS. Moderate physical activity did not show a significant effect (NP2) on smoking cessation but seem to reduce craving for tobacco (NP3)., Conclusions: We recommend asking all PWS about their smoking consumption and detailing their smoking history, offering them different types of counselling according to their preferences and involving them multidisciplinary (grade A). The systematic use of feedback is not recommended (grade C) but experience suggests that the CO tester is important in establishing a therapeutic alliance (professional consensus). The use of self-help interventions (grade C) and health education (grade B) are recommended., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: The objective of this chapter is to evaluate the risks of second-hand-smoke during pregnancy and to assess the benefits of antenatal care., Methods: Bibliographical research in French and English using the Medline and Cochrane databases and the recommendations of international societies., Results: Exposure to second-hand smoke appears to be higher at home and in the car, with potential consequences for pregnancy, especially prematurity (NP3). Complete avoidance of smoking at home significantly reduces exposure to passive smoking compared to incomplete avoidance (NP4). The more numerous the sources, the higher the intoxication is (NP4). The major risk factor associated with passive smoking is the presence of a spouse who smokes. Other associated factors are the presence of a smoker at home or in the car, young population (<25 years), low level of education, old smoking (NP4). Passive smoking is associated with an increased risk of fetal death in utero, fetal malformations, prematurity and birth weight under 2500g (NP2). No specific management is recommended for all pregnant women. Nevertheless, in a specific population of pregnant women with vulnerabilities, a behavioral approach aimed at teaching them to negotiate with their entourage may be beneficial in order to reduce the effects of passive smoking on pregnancy (NP2)., Conclusion: It is recommended to advise women and their family (especially spouses) to create a smoke-free environment, especially at home and in the car (professional consensus). It is recommended to provide a minimum amount of smoking cessation advice to pregnant women's entourage (professional consensus)., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objectives: To provide up-to-date evidence-based guidelines for the management of smoking cessation during pregnancy., Methods: Systematic review of the international literature. We identified papers published between January 2003 and April 2019 in Cochrane PubMed, and Embase databases with predefined keywords. All reports published in French and English relevant to the areas of focus were included and classified according the level of evidence ranging from 1 (highest) to 4 (lowest). The strength of the recommendations was classified according to the Haute Autorité de santé, France (ranging from A, highest to C, lowest)., Results: "Counseling", involving globally all kind of non-pharmacological interventions, has a modest benefit on smoking cessation, birth weight and prematurity. Moderate physical activity did not show a significant effect on smoking cessation. The systematic use of feedback by measuring the expired air carbon monoxide concentration do not influence smoking abstinence but it may be used in establishing a therapeutic alliance. The use of self-help interventions and health education are recommended in helping pregnant smokers quit. The prescription of nicotine replacement therapies (NRT) may be offered to any pregnant woman who has failed stopping smoking without medication This prescription can be initiated by the health care professional taking care of the pregnant woman in early pregnancy. There is no scientific evidence to propose the electronic cigarette for smoking cessation to pregnant smokers; it is recommended to provide the same advice and to use methods that have already been evaluated. The use of waterpipe (shisha/narghile) during pregnancy is associated with decreased fetal growth. It is recommended not to use waterpipe during pregnancy. Breastfeeding is possible in smokers, but less often initiated by them. Although its benefit for the child's development is not demonstrated to date, breastfeeding allows the mother to reduce or stop smoking. The risk of postpartum relapse is high (up to 82% at 1 year). The main factors associated with postpartum abstinence are breastfeeding, not having a smoker at home, and having no symptoms of postpartum depression., Conclusions: Smoking during pregnancy concerns more than hundred thousand women and their children per year in France. It is a major public health burden. Health care professionals should be mobilized for reducing or even eradicating it., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Nicotine is the main addictive substance in tobacco and its addictive effects mainly involve dopamine. Nicotine is mainly metabolized (C-oxidation) in the liver to cotinine by the cytochrome P450 enzyme system. Nicotine half-life is short being about 2hours. Nicotine metabolism appears to be increased during pregnancy, mainly due to an increased cytochrome activity and maternal cardiac output. Thus, the smoking behavior of the pregnant woman is subsequently modified with an increase in withdrawal syndromes and an increased desire to smoke. These pharmacological elements should be taken into account when prescribing nicotine replacement therapy. Regarding the markers of tobacco intoxication, there is a good correlation between the importance of smoking and the measurement of expired air carbon monoxide. Although there is no evidence of decreased obstetrical complications related to its use, it is simple and non-invasive and therefore may be useful in routine practice. It gives an instantaneous value of tobacco intoxication, and represents a starting point for dialogue and management and can help to highlight the reality of withdrawal. Regarding the evaluation of tobacco addiction, the most commonly used questionnaires are the Fagerström tests (FTCD, HSI…), which are well correlated with cotinine concentration. However, there is insufficient evidence of their usefulness in reducing tobacco consumption during pregnancy to recommend them in current practice. DSM-V diagnostic criteria for addiction should be known as they can also be used to characterize the intensity of this addiction., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)