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1.
Eur J Pediatr ; 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38678161

Neonatal herpes simplex virus (HSV) infection (HSV infection in infants less than 6 weeks of age) is rare but mortality and morbidity rates are high after disseminated disease and encephalitis. In France, the epidemiology is poorly described, and two decades ago, incidence was estimated to be 3 per 100,000 live births a year. We describe determinants, epidemiologic and clinical characteristics of neonatal HSV infection in a managed-care population attending in two major obstetric and paediatric centres, Paris, France, over a 10-year period. This retrospective case series study was conducted from 2013 to 2023, in infants less than 42 days of age who had virologically confirmed HSV infection. We report an overall rate of neonatal herpes of 5.5 per 100,000 live births a year and an incidence of symptomatic cases of 1.2 per 100,000 live births a year. HSV-1 was the major serotype involved (84.2%) and post-natal acquisition through the orolabial route reached 63.2%. All neonates who had neonatal HSV PCR screening (owing to clinical signs in parents) and who received prompt acyclovir treatment remained asymptomatic. Symptomatic forms accounted for 21.1% cases of the total and mortality was high (62.5% of symptomatic forms).   Conclusion: This case series confirms that neonates at risk for HSV disease and poor outcome are those born to HSV-seronegative mothers, preterm infants, and those who received acyclovir after onset of symptoms (mainly because mothers did not present evidence of acute HSV infection). Our study confirms the major role of HSV-1 and the frequency of its early post-natal acquisition. What is known: • Neonatal herpes simplex virus infection is rare but motality and morbidity rates are high after disseminted disease and encephalitis. National recommendations exist worldwide but mangement of this disease is not always easy. What is new: • As in France epidemiology of neonatal herpes is poorly described, our report is potentially an important addition to the existing literature. Moreover, we describe local practice that may be useful to physicians.

2.
Clin Infect Dis ; 2024 Mar 21.
Article En | MEDLINE | ID: mdl-38513236

A case of a male with human immunodeficiency virus with plasma genotyping detecting no resistance and a CRF02_AG subtype had a controlled HIV RNA on antiretroviral therapy since 2010. We introduced intramuscular therapy with cabotegravir and rilpivirine. One month later, his HIV RNA was 1500 copies/mL; genotyping found a subtype B with many mutations.

3.
J Gynecol Obstet Hum Reprod ; 53(6): 102764, 2024 Jun.
Article En | MEDLINE | ID: mdl-38492667

BACKGROUND: SARS-CoV-2 infection on pregnant women was the subject of many questions since the COVID-19 pandemic. METHODS: We aim to assess maternal and neonatal outcomes of SARS-CoV-2 infection contracted during 2nd and 3rd trimesters of pregnancy during the first two COVID-19 waves across a prospective French multicenter cohort study. Patients were included between April 2020 and January 2021 in 10 maternity hospitals in Paris area with two groups (i) pregnant women with a positive SARS-CoV-2 nasopharyngeal RT-PCR between [14WG; 37WG[(symptomatic infection), (ii) pregnant women with a negative serology (or equivocal) at delivery and without a positive SARS-CoV-2 nasopharyngeal RT-PCR at any time during pregnancy (G2 group) MAIN FINDINGS: 2410 pregnant women were included, of whom 310 had a positive SARS-CoV-2 nasopharyngeal RT-PCR and 217 between [14WG; 37WG[. Most infections occurred between 28 and 37 weeks of gestation (56 %). Most patients could be managed as outpatients, while 23 % had to be hospitalized. Among women with a positive RT-PCR, multiparous women were over-represented (OR = 2.45[1.52;3.87]); were more likely to deliver before 37 weeks of gestation (OR = 2.19[1.44;3.24]) and overall cesarean deliveries were significantly increased (OR = 1.53[1.09;2.13]). CONCLUSIONS: This study highlights the maternal, obstetrical, and neonatal burden associated with SARS-CoV-2 infections during the first two pandemic waves before availability of vaccines. TRIAL REGISTRATION: NCT04355234 (registration date: 21/04/2020).


COVID-19 , Pregnancy Complications, Infectious , Pregnancy Outcome , SARS-CoV-2 , Humans , Female , COVID-19/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Adult , Prospective Studies , Infant, Newborn , France/epidemiology , Pregnancy Outcome/epidemiology , Cohort Studies , COVID-19 Nucleic Acid Testing/statistics & numerical data , Infectious Disease Transmission, Vertical/statistics & numerical data , Infectious Disease Transmission, Vertical/prevention & control , Cesarean Section/statistics & numerical data
4.
Trauma Violence Abuse ; : 15248380241229745, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38407100

Healing after gender-based violence (GBV) is multidimensional, with varying instruments used in the scientific literature to capture this phenomenon quantitively in survivor populations. The purpose of this scoping review was to (a) describe quantitative measures used to evaluate recovery after GBV, (b) compare these findings with domains uncovered in a qualitative metasynthesis about survivors' perspectives about healing after GBV, and (c) summarize recovery relationships found. We searched Pubmed, PsycInfo, and Violence/Criminology/Family Studies Abstracts. Studies were included for review if they (a) used quantitative methods, (b) evaluated healing or recovery in survivors of GBV, (c) were available in English, and (d) were empirical articles in peer-reviewed journals. Two thousand nine hundred thirty-five articles were reviewed by title and abstract, and 92 articles were reviewed by full text. Twenty-six articles were included in this review. Eight studies used an alleviation of adverse symptomology as a proxy for recovery, eight used growth-related outcomes, and ten used a combination of both types of measures. While the quantitative instruments synthesized in this review seemed to map onto some of the recovery domains identified through qualitative metasynthesis, no study synthesized measured all domains simultaneously. Studies synthesized identified that recovery-related outcomes may be influenced by social support, symptom burden, disclosure, and various therapeutic intervention programs tested in the literature to date. Synthesizing research on recovery after GBV is an essential step to understand gaps in measurement and understanding. Streamlining and using holistic recovery outcome measurement can aid in the development of evidence-based interventions to promote healing in survivor populations.

5.
Viruses ; 15(4)2023 03 23.
Article En | MEDLINE | ID: mdl-37112800

Cytomegalovirus infection is the most common congenital infection, affecting about 1% of births worldwide. Several primary, secondary, and tertiary prevention strategies are already available during the prenatal period to help mitigate the immediate and long-term consequences of this infection. In this review, we aim to present and assess the efficacy of these strategies, including educating pregnant women and women of childbearing age on their knowledge of hygiene measures, development of vaccines, screening for cytomegalovirus infection during pregnancy (systematic versus targeted), prenatal diagnosis and prognostic assessments, and preventive and curative treatments in utero.


Cytomegalovirus Infections , Fetal Diseases , Pregnancy Complications, Infectious , Pregnancy , Female , Humans , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/prevention & control , Tertiary Prevention , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/prevention & control , Prenatal Diagnosis , Infectious Disease Transmission, Vertical/prevention & control
6.
Gynecol Obstet Fertil Senol ; 51(6): 337-341, 2023 06.
Article Fr | MEDLINE | ID: mdl-37080295

OBJECTIVE: In France, C-sections are classified through a color code according to their degree of urgency. A red-classified C-section is triggered when life of mother or fetus is immediately threatened These cases happen very rarely and represent less than 1% of total deliveries. Many French maternity hospitals are above this rate. This risky procedure should remain an exception. The main purpose of this study is to develop a new tool enabling to determine the relevance of red C-sections in order to improve obstetrical practices. METHODS: Eleven national obstetrical experts were submitted with relevant-estimated indications of red C-sections. A two-round Delphi methodology was then used to reach a consensus on a new table of relevance. RESULTS: Five different groups of indications were proposed to the panel of experts. After two rounds, four groups achieved a consensus by being qualified "very relevant" or "relevant" by more than 80% of the 11 experts. CONCLUSION: The aim of this new consensual table of relevance is to improve quality of care. It allows to evaluate the relevance of red C-sections and determine when red C-sections are non-relevant but it particularly helps teams to identify ways of improvements. Finally, this tool enables a reproductible analysis that can be further intra- or inter-hospitals developed towards harmonization of practices.


Cesarean Section , Obstetrics , Pregnancy , Humans , Female , Delphi Technique , France , Hospitals, Maternity
7.
Neuro Oncol ; 25(9): 1605-1616, 2023 09 05.
Article En | MEDLINE | ID: mdl-36821432

BACKGROUND: High-grade gliomas (HGG) are aggressive brain tumors associated with short median patient survival and limited response to therapies, driving the need to develop tools to improve patient outcomes. Patient-derived xenograft (PDX) models, such as mouse PDX, have emerged as potential Avatar platforms for personalized oncology approaches, but the difficulty for some human grafts to grow successfully and the long time required for mice to develop tumors preclude their use for HGG. METHODS: We used a rapid and efficient ex-ovo chicken embryo chorioallantoic membrane (CAM) culture system to evaluate the efficacy of oncologic drug options for HGG patients. RESULTS: Implantation of fresh glioma tissue fragments from 59 of 60 patients, that include difficult-to-grow IDH-mutated samples, successfully established CAM tumor xenografts within 7 days, with a tumor take rate of 98.3%. These xenografts faithfully recapitulate the histological and molecular characteristics of the primary tumor, and the ability of individual fragments to form tumors was predictive of poor patient prognosis. Treatment of drug-sensitive or drug-resistant xenografts indicates that the CAM-glioma assay enables testing tumor sensitivity to temozolomide and carboplatin at doses consistent with those administered to patients. In a proof-of-concept study involving 14 HGG patients, we observed a correlation of 100% between the CAM xenograft response to temozolomide or carboplatin and the clinical response of patients. CONCLUSION: The CAM-glioma model is a fast and reliable assay that has the potential to serve as a complementary model to drug discovery and a real-time Avatar platform to predict the best treatment for HGG patients.


Brain Neoplasms , Glioma , Humans , Chick Embryo , Mice , Animals , Temozolomide/pharmacology , Heterografts , Carboplatin , Glioma/drug therapy , Brain Neoplasms/drug therapy , Disease Models, Animal , Xenograft Model Antitumor Assays
8.
Viruses ; 14(11)2022 10 31.
Article En | MEDLINE | ID: mdl-36366523

(1) Background: In a period where systematic screening of CMV during pregnancy is still debated, diagnosis of non primary infection (NPI) remains challenging and an obstacle to systematic screening. Our aim is to report kinetics of serological and molecular CMV markers of NPI. (2) Methods: We identified immunocompetent pregnant women with CMV NPI as women known to be seropositive for CMV before pregnancy who gave birth to cCMV infected infants. We performed CMV-IgG, CMV-IgM, CMV-IgG avidity and CMV PCR retrospectively on sequential serum samples collected during pregnancy. (3) Results: We collected 195 serum samples from 53 pregnant women with NPI during pregnancy. For 29/53 (55%) patients, no markers of active infection were observed (stable IgG titers, negative IgM and negative PCR). CMV PCR was positive in at least one serum for 18/53 (34%) patients and median viral load was 46 copies/mL, IQR (21-65). (4) Conclusions: For more than half of patients with confirmed CMV NPI during pregnancy, available diagnostic tools are liable to fail in detecting an active infection. These should therefore not be used and universal neonatal screening for CMV remains the only way to detect all cCMV infections.


Cytomegalovirus Infections , Pregnancy Complications, Infectious , Infant, Newborn , Infant , Female , Humans , Pregnancy , Cytomegalovirus/genetics , Pregnant Women , Retrospective Studies , Immunoglobulin M , Antibodies, Viral , Immunoglobulin G , Biomarkers
9.
Front Med (Lausanne) ; 9: 1003914, 2022.
Article En | MEDLINE | ID: mdl-36275794

Clear cell renal cell carcinoma (ccRCC) is an aggressive subtype of renal cell carcinoma accounting for the majority of deaths in kidney cancer patients. Advanced ccRCC has a high mortality rate as most patients progress and develop resistance to currently approved targeted therapies, highlighting the ongoing need for adequate drug testing models to develop novel therapies. Current animal models are expensive and time-consuming. In this study, we investigated the use of the chick chorioallantoic membrane (CAM), a rapid and cost-effective model, as a complementary drug testing model for ccRCC. Our results indicated that tumor samples from ccRCC patients can be successfully cultivated on the chick chorioallantoic membrane (CAM) within 7 days while retaining their histopathological characteristics. Furthermore, treatment of ccRCC xenografts with sunitinib, a tyrosine kinase inhibitor used for the treatment of metastatic RCC, allowed us to evaluate differential responses of individual patients. Our results indicate that the CAM model is a complementary in vivo model that allows for rapid and cost-effective evaluation of ccRCC patient response to drug therapy. Therefore, this model has the potential to become a useful platform for preclinical evaluation of new targeted therapies for the treatment of ccRCC.

10.
Viruses ; 14(10)2022 09 28.
Article En | MEDLINE | ID: mdl-36298692

(1) Background: What is the role of serum CMV PCR in the diagnosis of recent primary infection (PI) in pregnant women when IgG avidity is uninformative? (2) Methods: Retrospective cohort study to compare serum versus whole blood CMV PCR. (a) Qualitative assessment: CMV PCR was performed on 123 serum samples and 74 whole blood samples collected from 132 pregnant women with recent CMV PI. PCR positivity rate was used to calculate sensitivity in serum and whole blood. (b) Quantitative assessment: CMV PCR was performed on 72 paired samples of serum and whole blood collected on the same day from 57 patients. (3) Results: In pregnant women, PCR positivity rate was 89% for serum samples versus 100% in whole blood in the case of very recent PI (<15 days), but only 27% in serum versus 68% in whole blood for PI occurring from 6 weeks to 3 months before. Comparing CMV viral loads between serum and whole blood, we determined the limit of CMV DNA detection in serum as 3 log copies/mL (whole blood equivalent). (4) Conclusions: Serum CMV PCR is reliable in confirming PI in cases when only IgM is detected. It is therefore a valuable tool in introducing valaciclovir treatment as early as possible to prevent mother-to-child CMV transmission.


Cytomegalovirus Infections , Pregnancy Complications, Infectious , Female , Humans , Pregnancy , Cytomegalovirus/genetics , Pregnant Women , Valacyclovir , Retrospective Studies , Immunoglobulin M , Antibodies, Viral , Immunoglobulin G , Pregnancy Complications, Infectious/diagnosis , Infectious Disease Transmission, Vertical , Polymerase Chain Reaction
11.
Ann Biol Clin (Paris) ; 80(4): 385-388, 2022 07 01.
Article Fr | MEDLINE | ID: mdl-36099348

A 14-year-old patient underwent liver transplant. Three months after transplantation, EBV associated lymphoma was suspected. EBV serologies before and after transplantation were particularly discrepant. Eighteen months before transplantation, the serological profile suggested a recent EBV primary-infection, four months before transplantation, we had isolated anti-EBNA IgG and five days after transplantation, the serological profile suggested a past infection. All EBV PCR performed on whole blood were negative. Retrospectively, immunoblots anti-EBV IgG were performed. Blots showed no anti-EBV IgG before and until the day of liver transplantation. Five days after transplantation, slight bands of both IgG anti-p18 (VCA) and anti-EBNA-1 were found, without any other serological marker. These were probably due to passive transfers of IgG during surgery. There was therefore no argument for an immunization against EBV before or after liver transplant for this patient.


Un patient de 14 ans a subi une transplantation hépatique. Trois mois après la transplantation, un lymphome associé à l'EBV a été suspecté. Les sérologies anti-EBV (IgG anti-VCA et anti-EBNA, IgM anti-VCA) montraient des résultats particulièrement discordants et ininterprétables : profil de primo-infection EBV récente 18 mois avant la greffe, IgG anti-EBNA isolées 4 mois avant la greffe et profil d'infection ancienne 5 jours après la greffe. Les PCR EBV réalisées sur sang total étaient toujours indétectables. Rétrospectivement, des immunoblots IgG anti-EBV ont été réalisés. Les blots ne montraient pas d'IgG anti-EBV en pré-greffe jusqu'au jour de la transplantation. Cinq jours après la greffe, le blot montrait la présence d'anti-p18 (VCA) et anti-EBNA-1 présents sous forme de traces, sans autre marqueur sérologique d'infection EBV, très probablement dues à des transferts passifs d'anticorps pendant la transplantation. Aucun argument sérologique ni moléculaire n'a été retenu pour une immunisation anti-EBV avant ou après la transplantation hépatique pour ce patient.


Epstein-Barr Virus Infections , Herpesvirus 4, Human , Adolescent , Antibodies, Viral , Antigens, Viral , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Humans , Immunoglobulin G , Immunoglobulin M , Retrospective Studies
12.
Viruses ; 14(7)2022 07 13.
Article En | MEDLINE | ID: mdl-35891509

The SARS-CoV-2 variant of concern, α, spread worldwide at the beginning of 2021. It was suggested that this variant was associated with a higher risk of mortality than other variants. We aimed to characterize the genetic diversity of SARS-CoV-2 variants isolated from patients with severe COVID-19 and unravel the relationships between specific viral mutations/mutational patterns and clinical outcomes. This is a prospective multicenter observational cohort study. Patients aged ≥18 years admitted to 11 intensive care units (ICUs) in hospitals in the Greater Paris area for SARS-CoV-2 infection and acute respiratory failure between 1 October 2020 and 30 May 2021 were included. The primary clinical endpoint was day-28 mortality. Full-length SARS-CoV-2 genomes were sequenced by means of next-generation sequencing (Illumina COVIDSeq). In total, 413 patients were included, 183 (44.3%) were infected with pre-existing variants, 197 (47.7%) were infected with variant α, and 33 (8.0%) were infected with other variants. The patients infected with pre-existing variants were significantly older (64.9 ± 11.9 vs. 60.5 ± 11.8 years; p = 0.0005) and had more frequent COPD (11.5% vs. 4.1%; p = 0.009) and higher SOFA scores (4 [3-8] vs. 3 [2-4]; 0.0002). The day-28 mortality was no different between the patients infected with pre-existing, α, or other variants (31.1% vs. 26.2% vs. 30.3%; p = 0.550). There was no association between day-28 mortality and specific variants or the presence of specific mutations. At ICU admission, the patients infected with pre-existing variants had a different clinical presentation from those infected with variant α, but mortality did not differ between these groups. There was no association between specific variants or SARS-CoV-2 genome mutational pattern and day-28 mortality.


COVID-19 , SARS-CoV-2 , Adolescent , Adult , Critical Illness , Genomics , Humans , Prospective Studies , SARS-CoV-2/genetics
13.
Cancers (Basel) ; 14(11)2022 Jun 01.
Article En | MEDLINE | ID: mdl-35681731

Transforming growth factor ß (TGFß) plays a paradoxical role in cancer, first inhibiting then promoting its progression, a duality that poses a real challenge for the development of effective TGFß-targeted therapies. The major TGFß downstream effectors, SMAD2 and SMAD3, display both distinct and overlapping functions and accumulating evidence suggests that their activation ratio may contribute to the dual effect of TGFß. However, the mechanisms responsible for their selective activation remain poorly understood. Here, we provide experimental evidence that hypoxia induces the pro-invasive arm of TGFß signaling through a selective increase in SMAD3 interaction with SMAD-Anchor for Receptor Activation (SARA). This event relies on HDAC6-dependent SMAD3 bioavailability, as well as increased SARA recruitment to EEA1+ endosomes. A motility gene expression study indicated that SMAD3 selectively increased the expression of ITGB2 and VIM, two genes that were found to be implicated in hypoxia-induced cell invasion and associated with tumor progression and metastasis in cohorts of cancer patients. Furthermore, CAM xenograft assays show the significant benefit of selective inhibition of the SMAD3 signaling pathway as opposed to global TGFß inhibition in preventing tumor progression. Overall, these results suggest that fine-tuning of the pro-invasive HDAC6-SARA-SMAD3 axis could be a better strategy towards effective cancer treatments.

14.
Am J Respir Cell Mol Biol ; 67(2): 164-172, 2022 08.
Article En | MEDLINE | ID: mdl-35612953

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with no curative pharmacological treatment. Current preclinical models fail to accurately reproduce human pathophysiology and are therefore poor predictors of clinical outcomes. Here, we investigated whether the chick embryo chorioallantoic membrane (CAM) assay supports the implantation of xenografts derived from IPF lung tissue and primary IPF lung fibroblasts and can be used to evaluate the efficacy of antifibrotic drugs. We demonstrate that IPF xenografts maintain their integrity and are perfused with chick embryo blood. Size measurements indicate that the xenografts amplify on the CAM, and Ki67 and pro-collagen type I immunohistochemical staining highlight the presence of proliferative and functional cells in the xenografts. Moreover, the IPF phenotype and immune microenvironment of lung tissues are retained when cultivated on the CAM and the fibroblast xenografts mimic invasive IPF fibroblastic foci. Daily treatments of the xenografts with nintedanib and PBI-4050 significantly reduce their size, fibrosis-associated gene expression, and collagen deposition. Similar effects are found with GLPG1205 and fenofibric acid, two drugs that target the immune microenvironment. Our CAM-IPF model represents the first in vivo model of IPF that uses human lung tissue. This rapid and cost-effective assay could become a valuable tool for predicting the efficacy of antifibrotic drug candidates for IPF.


Idiopathic Pulmonary Fibrosis , Animals , Chick Embryo , Chorioallantoic Membrane/metabolism , Fibroblasts/metabolism , Fibrosis , Humans , Idiopathic Pulmonary Fibrosis/metabolism , Lung/pathology
15.
Int J Mol Sci ; 24(1)2022 Dec 28.
Article En | MEDLINE | ID: mdl-36613948

Idiopathic pulmonary fibrosis (IPF) is characterized by abnormal fibroblast accumulation in the lung leading to extracellular matrix deposition and remodeling that compromise lung function. However, the mechanisms of interstitial invasion and remodeling by lung fibroblasts remain poorly understood. The invadosomes, initially described in cancer cells, consist of actin-based adhesive structures that coordinate with numerous other proteins to form a membrane protrusion capable of degrading the extracellular matrix to promote their invasive phenotype. In this regard, we hypothesized that invadosome formation may be increased in lung fibroblasts from patients with IPF. Public RNAseq datasets from control and IPF lung tissues were used to identify differentially expressed genes associated with invadosomes. Lung fibroblasts isolated from bleomycin-exposed mice and IPF patients were seeded with and without the two approved drugs for treating IPF, nintedanib or pirfenidone on fluorescent gelatin-coated coverslips for invadosome assays. Several matrix and invadosome-associated genes were increased in IPF tissues and in IPF fibroblastic foci. Invadosome formation was significantly increased in lung fibroblasts isolated from bleomycin-exposed mice and IPF patients. The degree of lung fibrosis found in IPF tissues correlated strongly with invadosome production by neighboring cells. Nintedanib suppressed IPF and PDGF-activated lung fibroblast invadosome formation, an event associated with inhibition of the PDGFR/PI3K/Akt pathway and TKS5 expression. Fibroblasts derived from IPF lung tissues express a pro-invadosomal phenotype, which correlates with the severity of fibrosis and is responsive to antifibrotic treatment.


Idiopathic Pulmonary Fibrosis , Podosomes , Mice , Animals , Podosomes/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Lung/pathology , Idiopathic Pulmonary Fibrosis/metabolism , Fibroblasts/metabolism , Fibrosis , Bleomycin/therapeutic use
16.
Cells ; 12(1)2022 12 29.
Article En | MEDLINE | ID: mdl-36611930

Neutrophils influence innate and adaptive immunity by releasing various cytokines and chemokines, by generating neutrophil extracellular traps (NETs), and by modulating their own survival. Neutrophils also produce extracellular vesicles (EVs) termed ectosomes, which influence the function of other immune cells. Here, we studied neutrophil-derived ectosomes (NDEs) and whether they can modulate autologous neutrophil responses. We first characterized EV production by neutrophils, following MISEV 2018 guidelines to facilitate comparisons with other studies. We found that such EVs are principally NDEs, that they are rapidly released in response to several (but not all) physiological stimuli, and that a number of signaling pathways are involved in the induction of this response. When co-incubated with autologous neutrophils, NDE constituents were rapidly incorporated into recipient cells and this triggered and/or modulated neutrophil responses. The pro-survival effect of GM-CSF, G-CSF, IFNγ, and dexamethasone was reversed; CXCL8 and NET formation were induced in otherwise unstimulated neutrophils; the induction of inflammatory chemokines by TNFα was modulated depending on the activation state of the NDEs' parent cells; and inducible NET generation was attenuated. Our data show that NDE generation modulates neutrophil responses in an autocrine and paracrine manner, and indicate that this probably represents an important aspect of how neutrophils shape their environment and cellular interactions.


Extracellular Traps , Extracellular Vesicles , Humans , Neutrophils/metabolism , Extracellular Traps/metabolism , Cytokines/metabolism , Chemokines/metabolism , Extracellular Vesicles/metabolism
17.
PLoS One ; 16(12): e0261011, 2021.
Article En | MEDLINE | ID: mdl-34860861

INTRODUCTION: Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in many countries. OBJECTIVES: This systematic review aims to provide the state of the art on current practices concerning management of maternal and congenital CMV infection during pregnancy, after maternal primary infection (PI) in first trimester of pregnancy. DATA SOURCES: Electronically searches on databases and hand searches in grey literature. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Primary outcome was listing biological, imaging, and therapeutic management interventions in two distinct populations: population 1 are pregnant women with PI, before or without amniocentesis; population 2 are pregnant women with congenitally infected fetuses (after positive amniocentesis). Secondary outcome was pregnancy outcome in population 2. RESULTS: Out of 4,134 studies identified, a total of 31 studies were analyzed, with 3,325 pregnant women in population 1 and 1,021 pregnant women in population 2, from 7 countries (Belgium, France, Germany, Israel, Italy, Spain and USA). In population 1, ultrasound (US) examination frequency was 0.75/month, amniocentesis in 82% cases, maternal viremia in 14% and preventive treatment with hyperimmune globulins (HIG) or valaciclovir in respectively 14% and 4% women. In population 2, US examination frequency was 1.5/month, magnetic resonance imaging (MRI) in 44% cases at 32 weeks gestation (WG), fetal blood sampling (FBS) in 24% at 28 WG, and curative treatment with HIG or valaciclovir in respectively 9% and 8% patients. CONCLUSIONS: This systematic review illustrates management of maternal and congenital CMV during pregnancy in published and non-published literature, in absence of international consensus. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019124342.


Cytomegalovirus Infections/therapy , Cytomegalovirus/isolation & purification , Fetal Diseases/therapy , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Amniocentesis/methods , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/microbiology , Disease Management , Female , Fetal Diseases/diagnosis , Fetal Diseases/microbiology , Humans , Infant, Newborn , Pregnancy , Pregnancy Complications, Infectious/microbiology , Pregnancy Outcome , Prenatal Diagnosis/methods
18.
Cancers (Basel) ; 13(5)2021 Mar 04.
Article En | MEDLINE | ID: mdl-33806378

Hypoxia in the tumor microenvironment is a negative prognostic factor associated with tumor progression and metastasis, and therefore represents an attractive therapeutic target for anti-tumor therapy. To test the effectiveness of novel hypoxia-targeting drugs, appropriate preclinical models that recreate tumor hypoxia are essential. The chicken ChorioAllantoic Membrane (CAM) assay is increasingly used as a rapid cost-effective in vivo drug-testing platform that recapitulates many aspects of human cancers. However, it remains to be determined whether this model recreates the hypoxic microenvironment of solid tumors. To detect hypoxia in the CAM model, the hypoxic marker pimonidazole was injected into the vasculature of tumor-bearing CAM, and hypoxia-dependent gene expression was analyzed. We observed that the CAM model effectively supports the development of hypoxic zones in a variety of human tumor cell line-derived and patient's tumor fragment-derived xenografts. The treatment of both patient and cell line-derived CAM xenografts with modulators of angiogenesis significantly altered the formation of hypoxic zones within the xenografts. Furthermore, the changes in hypoxia translated into modulated levels of chick liver metastasis as measured by Alu-based assay. These findings demonstrate that the CAM xenograft model is a valuable in vivo platform for studying hypoxia that could facilitate the identification and testing of drugs targeting this tumor microenvironment.

19.
J Clin Virol ; 138: 104793, 2021 05.
Article En | MEDLINE | ID: mdl-33770656

OBJECTIVES Congenital cytomegalovirus infection (cCMV) affects around 3400 newborns each year in France, of whom 700 will develop sequelae, primarily sensorineural hearing loss. Our objectives were (1) to evaluate incidence of cCMV in two French departments located in the Indian Ocean: Mayotte and La Reunion, and (2) evaluate interest and feasibility/acceptability of universal screening of cCMV at birth. MATERIAL AND METHODS We implemented a universal neonatal CMV screening in Mayotte during 7 months in 2019 and in La Reunion during one month in March 2020. Saliva swabs were collected in the first three days of life, and tested for CMV DNA by PCR. A short survey allowed evaluating whether this screening is acceptable and feasible. RESULTS: A total of 1026 newborns were screened: 854 in Mayotte and 172 in La Reunion. In Mayotte, cCMV incidence was evaluated at a minimum of 1.6 % (95 % CI 0.94-2.81). In La Reunion, cCMV incidence was evaluated at a minimum of 1.2 % (95 % CI -0.20-4.57). All cCMV infants were born to mothers with non-primary CMV infection. Only 0.7 % parents refused the screening. CONCLUSIONS cCMV incidence in Mayotte and La Reunion is higher than in metropolitan France. This diagnosis should not be overlooked, especially since the time dedicated to screening and its feeling by the parents seem to be acceptable.


Cytomegalovirus Infections , Cytomegalovirus , Comoros/epidemiology , Cytomegalovirus/genetics , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , DNA, Viral , Humans , Infant , Infant, Newborn , Neonatal Screening , Prospective Studies , Reunion/epidemiology
20.
Eur J Clin Microbiol Infect Dis ; 40(10): 2235-2241, 2021 Oct.
Article En | MEDLINE | ID: mdl-33782783

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.


Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/blood , Immunoassay/methods , SARS-CoV-2/immunology , COVID-19/virology , Humans , Immunoassay/economics , Immunoglobulin M/blood , Reagent Kits, Diagnostic , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity
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