Emmanuel Curis

• PhD, Pharm D
• Université Paris Cité

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on splenomegaly and constitutional symptoms, but it does not rever...

BACKGROUND Donor cell engraftment is a prerequisite of successful allogeneic hematopoietic stem cell transplantation. Based on peripheral blood analyses, it is characterized by early myeloid recovery and T and B cell lymphopenia. However, cellular networks associated with bone marrow engraftment of allogeneic human cells have been poorly described....

La connaissance de la capacité d’une méthode à détecter le composant à doser fait partie intégrante de la validation d’une méthode de dosage, lorsque cela est pertinent pour l’interprétation des résultats. Cette capacité se traduit, dans les documents réglementaires, par les notions de limite de détection (plus petite quantité détectable) et de qua...

Background Innovative tools to reliably identify patients with acute stroke are needed. Peripheral monocyte subsets, i.e. classical‐Mon1, intermediate‐Mon2, and non‐classical‐Mon3, with their activation marker expression analyzed using flow‐cytometry (FCM) could be interesting cell biomarker candidates. Aim to assess the inter‐operator variability...

Introduction: The knowledge of dabigatran levels is helpful for decision-making in specific situations such as urgent surgery or when the question of reversal arises (uncontrolled bleeding, eligibility for thrombolysis). However, a limited number of observational studies are available regarding comparisons between quantification methods. The objec...

Objectives: The performance of non-invasive prenatal screening using cell-free DNA testing in maternal blood in twin pregnancies is still under-evaluated, while serum marker-based strategies yield poor results. This study aims at assessing the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancies as a first-tier test. T...

Background The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels. Objectives To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (...

Introduction: Chylous abdominal effusions are serious complications that can be triggered by various aetiologies. The biochemical diagnosis of chyle leakage in ascites or in peritoneal fluid capsules relies on the detection of chylomicrons. Assaying the fluid's concentration of triglycerides is still the first-line tool. Given that only one compar...

Drug-metabolizing enzymes and drug transporters are key determinants of drug pharmacokinetics and response. The cocktail-based cytochrome P450 (CYP) and drug transporter phenotyping approach consists in the administration of multiple CYP or transporter-specific probe drugs to determine their activities simultaneously. Several drug cocktails have be...

Background and purpose: In patients with acute ischemic stroke (AIS) using a direct oral factor-Xa anticoagulant (DOAC) during the last 48 hours, a fixed plasma heparin-calibrated anti-Xa activity (0.5 IU/mL) was proposed as a threshold below which patients could be eligible for thrombolysis and/or thrombectomy. Besides, specific DOAC-calibrated a...

Background Chylous effusions such as chylothorax, chylopericardium and chylous ascites are marked by the abnormal presence of chylomicrons in serous membranes. These relatively rare situations are associated with high morbidity and mortality rates. Given that a macroscopic assessment of the fluid is insufficient, the current gold standard method fo...

Background: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions and polypharmacy, receive direct oral anticoagulants (DOAC), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. Aims: To investigate: i/DOAC concentration-time prof...

Les techniques de pharmacotechnie actuelles permettent d'améliorer la biodisponibilité, stabilité et efficacité des molécules et par extension innover en termes de stratégies thérapeutiques. Elles peuvent, à titre d'exemple, permettre l'optimisation des doses de substances actives et d'excipients au regard de l'efficacité thérapeutique du produit f...

Background: Substance use disorder emerges in a small proportion of drug users and has the characteristics of a chronic relapsing pathology. Aims: Our study aimed to demonstrate and characterize the variability in the expression of the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. Methods: A cocaine-CPP paradigm i...

(Abstracted from Am J Obstet Gynecol 2021;225:403.e1–403.e22) The most common tumors of the reproductive tract are uterine myomas (leiomyomata, fibroids). These benign tumors are often symptomatic in women of reproductive age and can affect fertility, pregnancy, and childbirth.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity. Methods Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and t...

Resumen Objectifs: Si l’on considère le vaste périmètre que couvre la rhumatologie et la prévalence de la douleur au cœur de cette spécialité, il nous a semblé nécessaire de mener une étude sur les habitudes de prescription dans le contexte de l’épidémie internationale des opioïdes et compte tenu de l’efficacité modérée des opioïdes forts dans le t...

BACKGROUND Uterine artery embolization is an effective and safe technique for the treatment of uterine fibroids, but its use remains controversial for women who wish to procreate. OBJECTIVE To study the clinical, anatomical and obstetrical results of uterine artery embolization in patients of childbearing age not eligible for myomectomy. STUDY DE...

The inducible p25 overexpression mouse model recapitulate many hallmark features of Alzheimer's disase including progressive neuronal loss, elevated Aβ, tau pathology, cognitive dysfunction, and impaired synaptic plasticity. We chose p25 mice to evaluate the physical and functional integrity of the blood-brain barrier (BBB) in a context of Tau path...

Bipolar disorder (BD) is a chronic and burdensome psychiatric disease, characterized by variations in mood and energy. The literature has consistently demonstrated an association between BD and childhood maltreatment (CM), and genetic variants of circadian genes have been associated with an increased vulnerability to develop BD. In this context, en...

Background Cerebral amyloid angiopathy (CAA) is a frequent cause of both intracerebral hemorrhage (ICH) and cognitive impairment in the elderly. Diagnosis rely on the Boston criteria, which use MRI markers including ≥2 exclusively lobar cerebral microbleeds (lCMBs). Although amyloid PET may provide molecular diagnosis, its specificity relative to A...

Introduction ST Genesia is a new automated system enabling quantitative standardized evaluation of thrombin generation (TG), for example, in patients receiving anti‐Xa direct inhibitors (xabans). Data on its analytical performances are scarce. Methods Over an 18‐month period, repeatability, reproducibility, and accuracy were assessed using STG‐Thr...

Eftrenonacog-alfa is a recombinant factor IX-Fc fusion protein increasingly prescribed in hemophilia B patients. We aimed to assess its pharmacodynamics (PD) in real-life setting via FIX activity measurement and thrombin generation assay (TGA). Sixty samples from 15 severe hemophilia B treated patients were collected at different time points. FIX a...

Introduction Pregnant women with sickle cell disease (SCD) are at high risk for sickle cell-related complications, obstetrical complications, and perinatal morbidity. Chronic inflammation and the proangiogenic environment associated with SCD have been associated with endothelial damage. It is unknown whether SCD complications could be associated wi...

Cluster analysis, commonly used to explore large biomedical datasets, can be challenging, notably due to missing data or left‐censored data induced by the sensitivity limits of the biochemical measurement method. Usually, complete‐case analysis, simple imputation, or stochastic simple imputation are applied before clustering. More recently, consens...

Objectives: Given the scope of rheumatology and it’s prevalence of pain it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists’ opioid prescribing patterns in non-cancer pa...

One of the greatest benefits of synchrotron radiation is the ability to perform chemical speciation analysis through X-ray absorption spectroscopies (XAS). XAS imaging of large sample areas can be performed with either full-field or raster-scanning modalities. A common practice to reduce acquisition time while decreasing dose and/or increasing spat...

Introduction Bipolar disorder (BD) is highly associated with childhood maltreatment (CM), the exposure to such early adversity being suggested to disrupt the expression of several biological pathways. This study aims at exploring associations between the mRNA levels of 9 HPA axis genes in lymphoblastoid cell lines from patients with BD according to...

Background: Cancer and aging are both frequently associated with malnutrition, a factor of poor prognosis. In adult cancer patients, this may be related in part to impaired energy metabolism, with higher than predicted resting energy expenditure (REE) in about 50% of patients. We hypothesized that frequently impaired energy metabolism in elderly p...

Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment...

Because quantitative reverse transcription PCR (RT-qPCR) gene expression data are compositional, amounts of quantified RNAs must be normalized using reference genes. However, the two most used methods to select reference genes (NormFinder and geNorm) ignore the compositional nature of RT-qPCR data, and often lead to different results making reliabl...

Introduction: Lupus Anticoagulant testing using dilute Russell Viper Venom Time (dRVVT) is challenging in patients receiving Direct Oral AntiCoagulants (DOAC) due to potential false positive results. In a multicenter study, we evaluated the in vitro removal of DOAC by activated charcoal (DOAC remove®), allowing reliable dRVVT testing. Materials a...

High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine that emerges as a promising peripheral marker of inflammation. HMGB1 and C-reactive protein levels were assessed in plasma of control subjects and remitted patients with bipolar disorder (BD). HMGB1 levels were significantly higher in patients with BD as compared to control subjects w...

Although bone marrow aspiration (BMA) is still considered a painful procedure, pain level remains poorly documented. We therefore conducted a prospective study intended to evaluate pain level in adult patients undergoing BMA at the sternal or iliac crest site to identify factors associated with pain. We enrolled a total of 448 patients who underwen...

Background: Rivaroxaban is a direct factor Xa inhibitor with substantial inter-individual pharmacokinetic (PK) variability. Pharmacodynamic (PD) variability, especially assessed with thrombin generation (TG), has been less documented. Objectives: i/to assess TG parameter time-profiles in healthy volunteers, TG being studied under different condi...

Objectif Étudier l’influence du profil d’expression et de méthylation du gène CHRONO, un nouveau gène circadien, sur le profil chronobiologique des patients bipolaires normothymiques et confirmer que CHRONO est intégré au sein du réseau de co-expression des gènes circadiens. Méthodes Le niveau de transcription de CHRONO a été mesuré par qPCR à par...

Aims Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this in...

Background/objectives: Sickle cell disease (SCD) complications mostly result from vascular dysfunction, concerning systemic microvasculature and cerebral large vessels. The aim of this cohort study was to identify potential circulating biomarkers predictive for further vascular event occurrence in pediatric SCD. Methods: We consecutively enrolle...

Background: Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blo...

Background: Multiple imputation by chained equations (MICE) requires specifying a suitable conditional imputation model for each incomplete variable and then iteratively imputes the missing values. In the presence of missing not at random (MNAR) outcomes, valid statistical inference often requires joint models for missing observations and their in...

Brain mural cells form a heterogeneous family which significantly contributes to the maintenance of the blood-brain barrier and regulation of the cerebral blood flow. Current procedures to isolate them cannot specifically separate their distinct subtypes, in particular vascular smooth muscle cells (VSMCs) and mid-capillary pericytes (mcPCs), which...

Motivation RNA quantification experiments result in compositional data, however usual methods for compositional data analysis (additive log ratio [alr], centered log ratio [clr], isometric log ratio [ilr]) do not apply easily and give results difficult to interpret.To handle this,a method based on disjoint subgraphs in a graph whose nodes are the qua...

Introduction Le trouble bipolaire est un trouble de l’humeur caractérisé par l’alternance d’épisodes maniaques ou dépressifs. Quoique le lithium soit le traitement de première ligne pour prévenir les rechutes d’épisodes thymiques, aucun consensus n’existe dans la littérature sur les critères utilisés pour définir et prédire cette réponse. L’échelle...

Objectives: Genome-wide association studies (GWAS) have become increasingly popular to identify associations between single nucleotide polymorphisms (SNPs) and phenotypic traits. The GWAS method is commonly applied within the social sciences. However, statistical analyses will need to be carefully conducted and the use of dedicated genetics softwa...

Background This study aims at characterizing French psychiatrists’ opinions regarding definition criteria and factors associated with lithium prophylactic response in patients with bipolar disorders. Methods After a literature review, an online survey targeted French psychiatrists in 2016. Results Literature review showed inconsistencies in reporte...

Vitamin K antagonist rodenticide pharmacodynamics (PD) is studied in rodents with traditional laboratory tests. We wondered if thrombin generation test (TGT) could add value.Difethialone (10 mg/kg) was administered per os to 97 OFA-Sprague Dawley rats. PD was studied over a 72 h-period using the Calibrated Automated Thrombogram on platelet poor pla...

Contexte : La maladie d'Alzheimer est la première cause de démence au monde du fait d'une population vieillissante. Afin de mieux comprendre les mécanismes moléculaires de la neuroinflammation dans cette maladie, nous avons étudié les effets de la neuroinflammation, induite artificiellement chez le rat, sur le métabolisme lipidique cérébral. Méthod...

Ornithine δ-aminotransferase (OAT, E.C. 2.6.1.13) catalyzes the transfer of the δ-amino group from ornithine (Orn) to α-ketoglutarate (aKG), yielding glutamate-5-semialdehyde and glutamate (Glu), and vice versa. In mammals, OAT is a mitochondrial enzyme, mainly located in the liver, intestine, brain, and kidney. In general, OAT serves to form gluta...

Previous association studies have shown mixed results between glutamic acid decarboxylase like-1 (GADL1) gene polymorphism and prophylactic lithium response in bipolar disorder (BD) patients. In the present study, GADL1 gene expression was investigated in regard to lithium response, using Alda scale, in lymphoblastoid cells (LCLs) of 36 Caucasian B...

Objectives: We examine if the lithium response is associated with changes in core clock genes expressions. Methods: The effect of a therapeutic concentration of lithium (1mM) on the expression levels of 17 circadian genes, was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of BD patients, defined as lithi...

Citrulline has anti-inflammatory properties and exerts beneficial effects on various impaired functions in aging. However, there are few data on citrulline action on immune function in aged populations. The objective of the study was to evaluate citrulline ability, after in vivo and in vitro administration, to modulate macrophage functions in aged...

Gaussian mixture analysis is frequently used to model the age-at-onset (AAO) in bipolar I disorder and identify homogeneous subsets of patients. This study aimed to examine whether, using admixture analysis of AAO, cross-sectional designs (which cause right truncation), unreliable diagnosis for individuals younger than 10 years old (which causes le...

La neurofibromatose de type 1 (NF1 ; numéro OMIM 162200), ou maladie de Von Recklinghausen, est l'une des maladies génétiques rares les plus fréquentes. Elle a une répartition mondiale homogène et une incidence estimée à 1 cas pour 2500 naissances. Il s'agit d'une maladie à transmission autosomique dominante dont la pénétrance est quasi-complète à...

Parmi les mécanismes physiopathologiques du traumatisme crânien figure notamment la voie du monoxyde d'azote (NO), principalement produit par les NO-synthases de type 1 (NOS1) et 2 (NOS2). Le monoxyde d'azote forme des peroxynitrites, qui entraînent diverses altérations fonctionnelles au niveau cérébral. Alors qu'il n'existe aucun traitement préven...

Context: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR). Objective: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome Methods: We performed a retro...

Background: Lithium (Li) is the first-line treatment for bipolar disorder (BD), but its mechanisms of action remain unknown. Although the chronobiological action of Li is well documented in animals, its effects on sleep and chronotypes in remitted BD patients have never been investigated. Methods: OPTHYMUM is a multicenter, cross-sectional, observ...

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or wh...

Background Opioid analgesic prescription represents a growing problem in many countries with increased opioid-related overdoses and deaths being reported. In rheumatology setting, strong opioids are considered poorly effective and not recommended as first line treatment in pain management. Objectives The aim of this study was to investigate rheuma...

Introduction Le trouble bipolaire de type I (TBI) est un trouble de l’humeur caractérisé par un ou plusieurs épisodes maniaques ou mixtes pouvant être accompagnés d’épisodes dépressifs majeurs. Les profils évolutifs de la maladie et de réponse au traitement sont très hétérogènes d’un patient à l’autre. L’identification de sous-groupes homogènes de...

L’ensemble des laboratoires de biologie médicale a l’obligation, pour chaque analyse, de s’engager dans une démarched’accréditation selon les référentiels du Comité français d’accréditation (COFRAC) et la norme européenne EN ISO15189. Le service d’hématologie de l’hôpital Lariboisière a souhaité étendre sa portée d’accréditation début 2015 àl’hémos...

Determine accuracy and precision of an unknown concentration obtained from calibration line in laboratory This article presents a practical example of how to couple analytical chemistry and statistics laboratory works to show to the students how the determination of the calibration line conditions influences the accuracy and the precision of the re...

The role of vasopressin (AVP) in the pathophysiology of primary aldosteronism (PA) remains unclear. 1) Primary: To investigate AVP secretion in PA by measuring the plasma concentration of copeptin (PCop), the C-terminal portion of provasopressin; 2) secondary: to assess renal sensitivity to AVP. Cross-sectional study Setting: Tertiary-care hospital...

To evaluate the diagnostic accuracy of CT in postoperative colorectal anastomotic leakage (AL). Two independent blinded radiologists reviewed 153 CTs performed for suspected AL within 60 days after surgery in 131 consecutive patients, with (n = 58) or without (n = 95) retrograde contrast enema (RCE). Results were compared to original interpretation...

Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the dete...

Despite improvements in patient management and extensive use of therapeutic drug monitoring (TDM), the rate of acute cellular rejection (ACR) remains high in patients treated with tacrolimus (TAC). Moreover, some patients experienced ACR while their whole-blood (WB) concentrations were maintained within the therapeutic range meaning that TDM in WB...

Our objective was to evaluate the contribution of monitoring B cell subset depletion after rituximab in patients with rheumatoid arthritis (RA) in order to guide reintroduction to forestall relapse. This prospective, monocentre study included all RA patients receiving two 1‐g rituximab infusions at a 15‐day interval. The patients were followed clin...

The expression of aryl hydrocarbon receptor (AhR) transcription factor was detected at transcript level in freshly isolated human brain microvessels and in the hCMEC /D3 human cerebral microvascular endothelial cell line. Recent studies have demonstrated that AhR pathway is able to crosstalk with other pathways such as hypoxia signaling pathway. Th...

Incidence of poisonings with serotonin reuptake inhibitors (SRIs) is growing. SRI toxicity is considered low but its actual impact in multidrug poisonings remains unclear. Our objective was to evaluate the consequences of SRI exposure in patients referred to the emergency department (ED) for deliberate multidrug exposure. Patients admitted for mult...

L’interprétation de l’état acidobasique peut se faire par deux approches : classique, centrée sur le bicarbonate, ou moderne ou approche de Stewart, dans laquelle le bicarbonate est considéré comme une variable dépendante. L’analyse classique repose sur l’interprétation simultanée de la bicarbonatémie et de la PCO2. Le base excess (BE) permet de qu...

Background Major Depressive Disorder (MDD) is the 3rd source for burden worldwide according to the World Health Organization (WHO). This comes partly from unsatisfactory response rates after usual treatment, highlighting the need for early indicators such as early improvement of depressive symptoms to adapt treatment strategies, especially for seve...

To classify the renal artery (RA) anatomy based on specific requirements for endovascular renal artery denervation (RDN) in patients with drug-resistant hypertension (RH). The RA anatomy of 122 consecutive RH patients was evaluated by computed tomography angiography and classified as two types: A (main RA ≥20 mm in length and ≥4.0 mm in diameter) o...

A soluble (pro)renin receptor (sPRR) circulates in plasma and is able to bind renin and prorenin. It is not known whether plasma sPRR concentrations vary with the activity of the renin-angiotensin system. We measured plasma sPRR, renin, prorenin, and aldosterone concentrations in 121 white and 9 black healthy subjects, 40 patients with diabetes mel...

Aging is associated with a blunted anabolic response to dietary intake, possibly related to a decrease in systemically available amino acids (AAs), which in turn may stem from increased splanchnic AA metabolism. Splanchnic sequestration can be saturated by pulse feeding (80% of daily protein intake in a single meal), enabling increased protein synt...