Microsporidiosis in patients with autoimmune diseases undergoing monoclonal antibody associated therapy

International audienceWe present Enterocytozoon bieneusi infection in four patients with autoimmune diseases undergoing prolonged monoclonal antibody therapies. Two patients suffered from inflammatory bowel disease and received anti-TNF therapies, whereas two other patients suffered from systemic lupus erythematosus with renal involvement and received anti-CD20 or anti-BLyS protein therapies. Three out of four patients consulted for diarrhea with abdominal pain without intestinal inflammation or bleeding at the time of sampling. The fourth patient did not declare intestinal troubles. Microsporidia genotype detected in this study were S9, C, Wildboard3 with one patient harboring 2 genotypes S6 and EBCMAP-038Management of microsporidia infection included albendazole and reduction of immunosuppression treatment, but no specific treatment was implemented in two other patients. In conclusion, microsporidia infection occurs in patients with autoimmune diseases undergoing prolonged monoclonal antibody therapies. Diagnosis should be carefully assessed in this population and a thorough benefit-risk analysis is essential prior to initiating therapeutic interventions

Superficial Conjunctival Cells from Dupilumab-Treated Patients with Atopic Dermatitis with Ocular Adverse Events Display a Transcriptomic Psoriasis Signature

International audienceDupilumab has demonstrated efficacy in the treatment of atopic dermatitis. However, a subset of patients experiences ocular adverse events (OAEs), including conjunctivitis and dry eye syndrome, the pathological mechanisms of which are still unknown. In a bicentric study, we used DNA microarray analysis to compare the transcriptome of conjunctival cells of patients with atopic dermatitis collected by impression cytology before (M0) and 4 months after (M4) initiating dupilumab treatment. Thirty-six patients were included and divided in 2 groups according to their ophthalmological status at M4: 12 with OAEs (OAE+) and 24 without (OAE-). The analysis revealed 52 differentially expressed genes between OAE+ and OAE-patients at M0 and 113 at M4. Ingenuity Pathway Analysis enrichment revealed a psoriasis signature in OAE+ patients, both before and after OAE outcomes. In addition, we noticed the overexpression of several genes involved in keratinocyte differentiation, particularly encoding cornified envelope components. Among the 16 differentially expressed genes selected for real-time RT-PCR validation, 9 were confirmed as upregulated at M4 in OAE+ versus OAE-patients, validating the psoriasis signature, whereas MUC7 was downregulated. In conclusion, these results suggest that a conjunctival transcriptomic profile predisposes some patients with atopic dermatitis to developing OAEs upon dupilumab treatment

Prenatal Hemoglobin Concentration and Long-Term Child Neurocognitive Development

International audienceAnemia in pregnancy, defined by a hemoglobin level (Hb) of less than 110 g/L, contributes to infant mortality and morbidity in sub-Saharan Africa. Maternal Hb changes physiologically and pathologically during pregnancy. However, the impact of these changes on long-term child neurocognitive function is unknown. This study therefore investigates the association between Hb at specific antenatal care visits and prenatal Hb trajectories during pregnancy and long-term child neurocognitive function. We analyzed data from a prospective cohort study that included 6-year-old singleton children born to women enrolled before 29 weeks of gestation into an antimalarial drug clinical trial. Hemoglobin level was analyzed from venous blood collected at least twice during pregnancy and at delivery. We used group-based trajectory modeling to identify distinct prenatal Hb trajectories. In total, 478 children (75.1% of eligible children) had assessment of cognitive and motor functions at 6 years of age. Three distinct Hb trajectories were identified: persistently anemic (Hb <110 g/L throughout the second and third trimesters), anemic to nonanemic (Hb <110 g/L at second trimester with increasing Hb toward the third trimester to Hb ≥110 g/L), and persistently nonanemic (Hb ≥110 g/L throughout the second and third trimesters). Children of women in the persistently anemic and anemic-to-nonanemic groups had significantly lower neurocognitive scores than children of women in the persistently nonanemic group (β = −6.8, 95% CI: −11.7 to −1.8; and β = −6.3, 95% CI: −10.4 to −2.2, respectively). The study shows that maintaining an elevation of Hb at or above 110 g/L from the second to third trimester of pregnancy may be associated with optimal long-term child neurocognitive function

The HCF101 protein is an important component of the cytosolic iron–sulfur synthesis pathway in Toxoplasma gondii

International audienceSeveral key cellular functions depend on proteins harboring an iron–sulfur (Fe-S) cofactor. As these Fe-S proteins localize to several subcellular compartments, they require a dedicated machinery for cofactor assembly. For instance, in plants and algae there are Fe-S cluster synthesis pathways localizing to the cytosol, but also present in the mitochondrion and in the chloroplast, 2 organelles of endosymbiotic origin. Toxoplasma gondii is a plastid-bearing parasitic protist responsible for a pathology affecting humans and other warm-blooded vertebrates. We have characterized the Toxoplasma homolog of HCF101, originally identified in plants as a protein transferring Fe-S clusters to photosystem I subunits in the chloroplast. Contrarily to plants, we have shown that HCF101 does not localize to the plastid in parasites, but instead is an important component of the cytosolic Fe-S assembly (CIA) pathway which is vital for Toxoplasma . While the CIA pathway is widely conserved in eukaryotes, it is the first time the involvement of HCF101 in this pan-eukaryotic machinery is established. Moreover, as this protein is essential for parasite viability and absent from its mammalian hosts, it constitutes a novel and promising potential drug target

Adult Internal Cerebrospinal Fluid Shunt Overall Survival: A Meta-Analysis of Restricted Mean Survival Times from Reconstructed Kaplan-Meier Data

International audienceObjective: To assess the overall survival (OS) of internal cerebrospinal fluid shunt (ICSFS) in the adult population.Methods: MEDLINE database was searched from 2000 to 2023 to identify studies reporting on ICSFS OS. Only articles reporting on adult ICSFS OS by a Kaplan-Meier (KM) OS curve were included. Numerical data were extracted from KM curves and were then reconstructed to estimate 3, 6, 9, 12, 18, 24, 36, 48, and 60 months restricted mean survival times (RMSTs). RMSTs of ICSFS and its SE at each time of interest were used as summary measure and primary outcome across studies. To account for the effect of between-study heterogeneity, RMSTs were pooled using a random effects model.Results: Out of 421 screened studies, only 6 were included in the meta-analysis. Calculated ICSFS OS at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months were 92.4% (95% CI, 89.6-95.2), 89.5% (95% CI, 86.3-92.8), 87.5% (95% CI, 83.9-91.1), 85.2% (95% CI, 80.4-90.0), 83.4% (95% CI, 79.0-87.9), 81.6% (95% CI, 76.7-86.5), 78.8% (95% CI, 72.9-84.6), 76.7% (95% CI, 70.3-83.1), and 74.5% (95% CI, 67.8-81.1), respectively. There was a significant heterogeneity as indicated by a high I2 value of 82.5% (95% CI, 63.1-91.7). Heterogeneity test of Q = 28.63 was also significant (P < 0.001).Conclusions: On contrary to what one might think, there are few available studies assessing adult ICSFS OS. We used a novel technique to meta-analyze adult ICSFS OS. ICSFS failure rate is maximal within the 3 to 6 postoperative months. Afterward, the risk slowly decreases over time. At 5 years, less than three quarters of the patients still have a naïve functional ICSFS never revised

Incidence and impact of other malignancies after immunochemotherapy by fludarabine, cyclophosphamide, and rituximab as frontline treatment for chronic lymphocytic leukemia: A single-center retrospective study.

International audienceIndividuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) have a high risk of developing other malignancies (OMs). The development of OMs may be associated with the advanced age of CLL/SLL patients, presence of a tumor-promoting microenvironment, immune alterations inherent to CLL/SLL, or chemotherapy. Importantly, the occurrence of OMs following frontline fludarabine, cyclophosphamide and rituximab (FCR) treatment is associated with a reduction in the overall survival (OS). This retrospective study included 108 CLL/SLL patients treated with FCR immunochemotherapy, as a first line treatment. With a median follow-up of 94.9 (6-222) months, 31% developed an OM or more, within a median of 61.8 months post-FCR initiation. The most common OMs were non-melanoma skin cancers (7%), Richter's syndrome (RS) (7%), myelodysplastic syndromes (6%), prostate cancer (4%), and acute myeloid leukemia (3%). Patients with OMs had shorter survival compared to those without (104.0 versus 149.0 months, P=0.02), with RS having the worst OS at 4.8 months (P<0.0001), followed by therapy-related myeloid neoplasia (t-MN) at 14.5 months. Although the onset of OMs in patients with CLL/SLL was observed after considerable delays, its impact on survival is significant in the immunochemotherapy era, necessitating a better understanding of these patterns to improve CLL/SLL management and guide future treatment strategies

Cluster globally, Reduce locally: Scalable efficient dictionary compression for magnetic resonance fingerprinting

International audienceWith the rapid advancements in medical data acquisition and production, increasingly richer representations exist to characterize medical information. However, such large-scale data do not usually meet computing resource constraints or algorithmic complexity, and can only be processed after compression or reduction, at the potential loss of information. In this work, we consider specific Gaussian mixture models (HD-GMM), tailored to deal with high dimensional data and to limit information loss by providing component-specific lower dimensional representations. We also design anincremental algorithm to compute such representations for large data sets, overcoming hardware limitations of standard methods. Our procedure is illustrated in a magnetic resonance fingerprinting study, where it achieves a $97\%$ dictionary compression for faster and more accurate map reconstructions

Prevalence of term prelabor rupture of membranes and factors associated with a longer interval of rupture: data from the 2021 French national perinatal survey

International audienceObjectives: Term prelabor rupture of membranes (term PROM) increases maternal and neonatal morbidity, but its current prevalence is unknown. This study aimed to estimate the prevalence of term PROM and to identify factors associated with a longer interval of rupture of membranes using recent national population-based data.Study design: Women with singleton pregnancies and term deliveries from the 2021 French National Perinatal Survey were selected. The prevalence of term PROM, defined as the rupture of membranes from 37 weeks before spontaneous labor, and its 95 % confidence interval (CI) were estimated. The median interval of rupture, defined as the time between the rupture of membranes and the onset of spontaneous labor, induction or prelabor caesarean (whichever occurred first) was calculated. Sociodemographic and pregnancy factors related to a longer interval of rupture of membranes were analyzed using a survival analysis, adjusting for competitive risks of a spontaneous labor: induction of labor and prelabor cesarean. Adjusted Hazard Ratios (aHR) were calculated using multivariate analysis.Results: Among 10,810 eligible women, 3,052 had a term PROM, yielding a prevalence of 28.2 % (95 %CI 27.4-29.1). The median interval of rupture was 8.3 h (Interquartile 25-75[3.5-21.3]). Within the first 24 h following PROM, 90 % of women with a spontaneous labor were in labor. Factors associated with a longer interval of rupture included maternal age ≥35 (aHR = 0.82 95 %CI 0.72-0.93), primiparity (aHR = 0.73 95 %CI 0.66-0.81), Body-mass Index ≥25 (aHR = 0.87 95 %CI 0.77-0.97) or ≥30 (aHR = 0.73 95 %CI 0.62-0.85), being single (aHR = 0.66 95 %CI 0.48-0.90) and lower education (aHR = 0.82 95 %CI 0.69-0.97).Conclusions: Term PROM affects more than one in four women. Sociodemographic factors and parity are associated with a longer interval of rupture

Artificial Intelligence Applied to ElectroEncephaloGraphy in Epilepsy

International audienceArtificial Intelligence (AI) is progressively transforming all fields of medicine, promising substantial changes in clinical practice. In the context of epilepsy, Electroencephalography (EEG), a technique used for over a century, has historically been resistant to automated analysis due to the complexity of the signals and the challenges posed by artifact management. While the human eye excels at recognizing patterns, algorithms have demonstrated superior capabilities in detecting and characterizing specific features, such as long-term dynamics and synchrony. Furthermore, the advent of wearable EEG devices has led to an exponential increase in data volume, surpassing the limits of visual interpretation. Artificial Intelligence (AI) algorithms are now being developed to address these limitations, offering enhanced efficiency in both identifying subtle signal features and managing massive datasets. This review explores the fundamental principles of AI and its transformative potential in the field of EEG. It discusses the implications and the current limits, including improvements limited to aggregation of already known knowledge, for epilepsy diagnosis, medical and surgical treatment, and innovative approaches to patient monitoring, including seizure forecasting, highlighting how AI is poised to redefine the management of epilepsy.</div

Efficacy of Irbesartan in Celiprolol-Treated Patients With Vascular Ehlers-Danlos Syndrome

International audienceBACKGROUND: Vascular Ehlers-Danlos syndrome is a rare genetic disorder characterized by defective type III collagen and a high risk of arterial morbidity and mortality. Several cardiovascular drugs are used for treatment, including celiprolol, but no controlled trial in this condition has been conducted to date. We hypothesized the benefit of the addition of an angiotensin II receptor blocker. METHODS: A multicenter, randomized, placebo-controlled trial was conducted to assess the efficacy and safety of the angiotensin II receptor blocker irbesartan in adults with vascular Ehlers-Danlos syndrome on stable background celiprolol therapy. Patients were randomized 1:1 to receive irbesartan (150 mg/day titrated to 300 mg/day) or placebo for 2 years. The composite primary outcome was defined as any vascular Ehlers-Danlos syndrome–related fatal or nonfatal arterial event or any new or worsening arterial lesions detected by systematic head-to-pelvis computed tomography angiography or peripheral arterial duplex ultrasound at different time points, using a time-to-first-event analysis. RESULTS: Twenty-nine participants (62% female; 40.3±11.3 years of age) were randomized to irbesartan, and 28 (64% female; 40.7±11.0 years of age) were randomized to placebo. The composite primary outcome occurred in 8 of 29 patients (27.6%) receiving irbesartan versus 15 of 28 patients (53.6%) receiving placebo (hazard ratio, 0.42 [95% CI, 0.17, 0.99]; P &lt;0.05). The risk of recurrent symptomatic or nonsymptomatic arterial events was lower with irbesartan than with placebo (risk ratio, 0.37 [95% CI, 0.19, 0.68]; P =0.002). A reduction of progression of arterial lesions was observed at all sites. Irbesartan significantly reduced systolic blood pressure compared with placebo (baseline-adjusted difference of 5.4 mm Hg [ P &lt;0.001]), but no relation was observed with the reduction of the primary composite outcome. Eleven episodes of irbesartan-related hypotension were recorded, leading to a downtitration in 4 patients. CONCLUSIONS: Compared with placebo, irbesartan reduced the risk of severe symptomatic and asymptomatic arterial events in patients with vascular Ehlers-Danlos syndrome on background celiprolol therapy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02597361