Does a three-hour delayed pushing benefit the mode of delivery?

OBJECTIVE: The objective of this study was to compare two strategies for passive second stage management: three-hour vs two-hour delayed pushing after the diagnosis of full cervical dilation on mode of delivery and perinatal outcomes. STUDY DESIGN: This retrospective observational study included low-risk nulliparous women who reatched full cervical dilation under epidural analgesia with a single term fetus in cephalic presentation and normal fetal heart rate, between September and December 2016. Mode of delivery (spontaneous vaginal delivery versus operative delivery including cesarean section and instrumental vaginal delivery) and perinatal outcomes (post-partum hemorrhage, perineal lacerations, 5-min Apgar score, umbilical cord pH and transfer to neonatal intensive care unit) were compared between two maternity units: maternity unit A, where women could have up to a three-hour delayed pushing period after full cervical dilation diagnosis, and maternity unit B, where the delayed pushing period was a maximum of 2 h. Outcomes were compared using univariate and multivariable analyses. Adjusted odds ratios (aOR) were estimated using a logistic regression multivariable model that included potential cofounders. RESULTS: During the study period, 614 women were included, 305 in maternity unit A and 309 in maternity unit B. Women's pre-existing characteristics were comparable between the two maternity units. Women delivering in the maternity unit A had significantly lower risks of having an operative delivery compared to women delivering in the maternity unit B (respectively 18.4 vs 26.9%; aOR = 0.64; 95%CI [0.43 - 0.96]). Perinatal outcomes were comparable in the two maternity units, particularly in terms of post-partum hemorrhage rates (7.4 vs 7.8%; aOR = 1,19 [0.65 - 2.19]). CONCLUSION: Increasing the possible length of the delayed pushing period from 2 to 3 h after the diagnosis of full cervical dilation in low-risk nulliparous women appears to reduce operative deliveries without adverse effects on maternal or neonatal morbidity.

Risk factors for conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia: A retrospective case-control study.

OBJECTIVES: General anesthesia for cesarean is associated with an increased risk of maternal morbidity compared with neuraxial anesthesia. Reducing the rate of general anesthesia for urgent cesarean in women with epidural analgesia may improve maternal outcomes. Our objective was to identify the rate and factors associated with the conversion to general anesthesia for urgent cesarean among women with labor epidural analgesia. STUDY DESIGN: We performed a retrospective case-control study including singleton-laboring women with epidural analgesia who delivered after 37 gestational weeks by urgent cesarean (Port Royal Maternity unit, 2012-2017). Cases were all women who required conversion from neuraxial analgesia to general anesthesia. Controls were women just before and after each case included. Factors associated with the conversion to general anesthesia were identified using logistic regression analysis. RESULTS: Among 3,300 laboring women with an epidural analgesia who delivered by urgent cesarean during the study period, 113 (3.4%,) had a conversion to general anesthesia. Factors associated with conversion to general anesthesia were a cervical dilation ≥ 5 cm at the time of epidural placement (aOR 2.55, 95%CI 1.05-6.21), asymmetric sensory blockade (aOR 3.39, 95%CI 1.11-10.36), need for ≥2 rescue top-ups (aOR 2.88, 95%CI 1.29-6.44), and category 1 cesarean (aOR 3.61, 95%CI 1.77-7.33). CONCLUSION: Among women with labor epidural analgesia, suboptimal analgesia significantly increased the risk for conversion to general anesthesia for urgent cesarean. Epidural placement without delay during labor, regular checks of epidural analgesia efficiency, and epidural replacement in case of inadequate epidural analgesia may decrease the rate of avoidable general anesthesia for urgent cesarean.

Benefits of the «en caul¼ technique for extremely preterm breech vaginal delivery.

INTRODUCTION: The "en caul" technique, i.e. delivery with intact membranes, may reduce the risk of obstetric trauma in vaginal breech delivery of extreme preterm infants. We aimed at comparing perinatal mortality and morbidity among extremely preterm breech vaginal deliveries between infants delivered "en caul" and those with "ruptured membranes". MATERIAL AND METHODS: We performed a fourteen-year retrospective study in a tertiary university center. All vaginal deliveries of singleton breech live infants with an antenatal decision of active resuscitation between 24 weeks and 27+6 weeks were included. Perinatal outcomes were compared between the "en caul" group, with intact membranes at the onset of pushing efforts and the "ruptured membranes" group, with ruptured membranes at the onset of pushing efforts. The primary outcome was perinatal mortality defined by intrapartum or neonatal death. The secondary outcomes were fetal extraction difficulties, arterial pH and 5 min Apgar score. RESULTS: We included 52 infants in the "en caul" group and 71 in the "ruptured membranes" group. The perinatal mortality rate did not differ between the two groups (19.2% in the "en caul" group versus 28.2% in the "ruptured membranes" group, p = 0.25). The mean arterial pH at birth was higher in the « en caul ¼ group (7.32 ± 0.1 vs 7.24 ± 0.1, p = 0.001). There were no differences between the groups for fetal extraction difficulties, especially fetal head entrapment (9.6% versus 9.9%). CONCLUSION: Even though the "en caul" technique does not seem to decrease the perinatal mortality rate, it remains a simple technique, which could improve neonatal morbidity.

Evaluation of the 4 diagnosis criteria proposed by the SMFM and the AFE foundation for amniotic fluid embolism in a monocentric population.

OBJECTIVE: The Society of Maternal Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation have recently proposed four diagnostic criteria for amniotic fluid embolism (AFE): presence of (1) sudden cardiac arrest or both respiratory and hemodynamic collapse, and (2) biological disseminated intravascular coagulopathy (DIC), and (3) absence of fever, and (4) clinical onset during labor or within 30 min of delivery. The objectives of our study were to describe the clinical presentation of women with a strong suspicion of AFE and to assess the validity of the four criteria proposed for AFE definition. MATERIAL AND METHODS: We performed a retrospective study including all patients with a strong suspicion of AFE who delivered between 2006 and 2018 at the Port Royal maternity unit, Paris. Strong suspicion of AFE was defined by a clinical presentation in favor of AFE associated with a biological pattern and/or autopsy result supporting AFE. The mention of AFE in files was essential to include the patients in our study. We estimated the incidence and mortality rate of AFE. Then, the presence of each of the four diagnosis criteria of the SMFM score was described, as well as the clinical and biological patterns. RESULTS: Among the 54 140 women who delivered during the study period, 14 had a strong suspicion of AFE (0.03 %), accounting for 25.9/100 000 deliveries (95 %CI (12.3-39.5/100,000)). All women had biological tests or autopsy supporting the diagnosis of AFE. Six of 14 patients (43 %) presented with all the four diagnostic criteria of the SMFM definition. All 14 women presented a hemodynamic collapse, but respiratory symptoms were lacking in 8 patients (57 %); 71 % fulfilled the criterion of biological DIC, and all patients had a clinical coagulopathy and a massive postpartum hemorrhage. Absence of fever was lacking in three women. In addition, all patients presented premonitory symptoms such as neurological disorders or irreversible and inaugural fetal bradycardia. CONCLUSION: The four SMFM diagnostic criteria were present in less than half of the women with a strong suspicion of AFE. We propose an alternative clinical and pragmatic definition to diagnose AFE, which has to be validated in the future. Early diagnosis of AFE based solely on clinical criteria can help clinicians anticipate the severity of the situation and optimize care.

[Term Prelabor Rupture of Membranes: CNGOF Guidelines for Clinical Practice - Short Text]. / Rupture des membranes à terme avant travail. Recommandations pour la pratique clinique du CNGOF ­ Texte court.

OBJECTIVE: To determine the management of patients with term prelabor rupture of membranes. METHODS: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges. RESULTS: Term prelabor rupture of membranes is considered a physiological process up to 12hours of rupture (Professional consensus). In case of expectant management and with a low rate of antibiotic prophylaxis, home care compared to hospitalization could be associated with an increase in neonatal infections (LE3), especially in case of group B streptococcus colonization (LE3). Home care is therefore not recommended (Grade C). In the absence of spontaneous labor within 12hours of rupture, antibiotic prophylaxis could reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12hours of rupture in term prelabor rupture of the membranes is therefore recommended (Grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (Grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1) or misoprostol (LE1), is associated with shorter rupture of membranes to delivery intervals when compared to expectant management. Compared with expectant management, immediate induction of labor is not associated with lower rates of neonatal infection (LE1), even among women with a positive streptococcus B vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (Grade B). Induction of labor is not associated with an increase or decrease in the cesarean delivery rate (LE2), whatever parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (Grade B). No induction method (oxytocin, dinoprostone, misoprostol or Foley® catheter) has demonstrated superiority over another, whether to reduce rate of intrauterine or neonatal infection, rate of cesarean delivery or to shorten rupture of membranes to delivery intervals regardless of Bishop's score and parity. CONCLUSION: Term prelabor rupture of membranes is a frequent event. A 12-hour delay without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation justifying an antibiotic prophylaxis. Expectant management or induction of labor can both be proposed, even in case of positive screening for streptococcus B, depending on the patient's wishes and maternity units' organization (Professional consensus).

[Term Prelabor Rupture of Membranes: CNGOF Guidelines for Clinical Practice - Methods for Inducing Labor]. / Rupture des membranes à terme avant travail. Recommandations pour la pratique clinique du CNGOF ­ Méthodes de déclenchement.

OBJECTIVES: To assess the studies comparing induction methods in women with term prelabor rupture of the membranes and establish if one is superior to the others. METHODS: The MedLine database, the Cochrane Library and the recommendations from the French and foreign obstetrical societies or colleges have been consulted. RESULTS: The included studies compared medical induction methods: oxytocin (intravenous), dinoprostone (vaginal gel, pessary or intracervical gel), and misoprostol (oral or vaginal route); and a mechanical induction method: the Foley catheter. The primary outcome measures were: labor induction to delivery interval, number of women delivered within 12 or 24hours of initiation of induction and cesarean delivery rate. The small sample size of the included studies as well as the limited number of reported complications does not provide a reasonable basis for concluding on the secondary outcome measures: pyrexia, chorioamnionitis, uterine tachysystole, Apgar scores of<7 at 5minutes. Induction of labor with misoprostol (oral and vaginal) reduced the labor induction to delivery interval compared with dinoprostone (LE2). This interval was unchanged when comparing induction with oxytocin and Foley catheter (LE2). The data comparing this interval in women induced with dinoprostone versus oxytocin and misoprostol versus oxytocin is limited or inconsistent. The cesarean delivery rate was comparable in women induced with dinoprostone (vaginal gel) versus oxytocin (LE2), misoprostol (oral and vaginal route) versus oxytocin (LE2), Foley catheter versus oxytocin (LE2), misoprostol versus dinoprostone (LE2) and misoprostol versus Foley catheter (LE2). The number of women delivered within 24hours of initiation of induction was comparable when induced with oral misoprostol versus oxytocin (LE2) and Foley catheter versus oxytocin (LE2). There is a lack of data for this outcome when comparing dinoprostone versus oxytocin, vaginal misoprotsol versus oxytocin, and misoprostol (oral and vaginal) versus dinoprostone. No induction method is superior to another for nulliparous women or women with unfavorable cervix (LE2). CONCLUSION: The superiority of an induction method, in terms of effectiveness or safety, could not be established with the current available data for women with term prelabor rupture of the membranes. An increased risk of chorioamnionitis due to induction using Foley catheter could not be ruled out by the available data. All medical methods are suitable for inducing women with term prelabor rupture of the membranes (Grade B).

Update: Focus in-hospital maternal cardiac arrest.

The incidence of maternal cardiac arrest ranges from 1/55,000 to 1/12,000 births. It is due most frequently to cardiovascular, hemorrhagic, and anesthesia-related causes, as well as to amniotic fluid embolism. The basic principles of resuscitation remain applicable in this situation, but the physiological modifications of pregnancy must be taken into account, in particular, the aortocaval compression syndrome. After 24 weeks of gestation, a salvage cesarean delivery must be performed immediately, without transfer to the operating room, if resuscitation maneuvers have failed 4 min after arrest, because this interval conditions the mother's neurological prognosis and improves neonatal survival.

Women and academic careers in obstetrics and gynaecology: aspirations and obstacles among postgraduate trainees - a mixed-methods study.

OBJECTIVE: To examine the relationship between gender and a career in academic medicine. DESIGN: Mixed-methods study. SETTING: Obstetrics-gynaecology postgraduate training programme in Paris, France. SAMPLE: Postgraduate trainees in obstetrics-gynaecology (n = 204). METHODS: Statistical analysis of quantitative survey data, thematic analysis of qualitative interview data and integrative analysis. MAIN OUTCOME MEASURES: Women's aspirations and obstacles related to their decision about a career in academic medicine. RESULTS: A career in academic medicine was envisaged by 13% of the women residents and 27% of the men (P = 0.01). Women reported receiving advice from a mentor less often than men (38.8% versus 52.9%, P = 0.002). Overall, 40.6% of women and 2.9% of men reported experiencing gender discrimination (P < 0.001). In response to the question 'Do you have doubts about your ability to pursue or succeed at an academic career?', 62.4% of the women and only 17.7% of the men answered yes (P < 0.001). The global analysis identified the following obstacles: persistent gender stereotypes that produce everyday sexism, lack of identification with male role models, lack of mentors, perceived discrimination, an ideal of professional excellence that is difficult to attain, constraining professional organisational norms, inequality between men and women in the domestic and family spheres, and finally self-censorship and important doubts about their ability to combine a demanding career and a fulfilling personal life. CONCLUSIONS: Women reported the desire to follow a career in academic medicine half as often as men. Improving the presence and visibility of role models for residents and combating workplace discrimination will address some of the barriers to women choosing a career in academic medicine. TWEETABLE ABSTRACT: Women obstetric trainees in France are only half as likely as men to envisage following an academic path.

[Intrauterine blood transfusion: Status report of 4years of practice in France (2011-2014)]. / Transfusions fœtales érythrocytaires : état des lieux sur 4 ans en France (2011­2014).

OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's (IUT) performed in France, among the French prenatal diagnosis centers in order to study the etiology of severe anemia requiring IUT. METHODS: We conducted a national retrospective descriptive study between 2011 and 2014. The data were collected using a survey sent by email to all French prenatal diagnosis centers. RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during the study period. The geographical repartition of these centers was appropriate for the "Aquitaine Pyrénées" region. Five centers performed 68 % of the national activity and one center performed 40 % the national activity. Each year, a mean of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the etiologies) with anti-RhD being the most prevalent antibody. The second etiology was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The French IUT activity was stable in numbers and indications during the study period. A national register could be set up in order to better evaluate prospectively the number of pregnancies concerned by IUT and to study the prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.

The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca2+-activated K+ channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca2+ homeostasis in epithelial cancers.

Ophiobolin A induces paraptosis-like cell death in human glioblastoma cells by decreasing BKCa channel activity.

Glioblastoma multiforme (GBM) is the most lethal and common malignant human brain tumor. The intrinsic resistance of highly invasive GBM cells to radiation- and chemotherapy-induced apoptosis accounts for the generally dismal treatment outcomes. This study investigated ophiobolin A (OP-A), a fungal metabolite from Bipolaris species, for its promising anticancer activity against human GBM cells exhibiting varying degrees of resistance to proapoptotic stimuli. We found that OP-A induced marked changes in the dynamic organization of the F-actin cytoskeleton, and inhibited the proliferation and migration of GBM cells, likely by inhibiting big conductance Ca(2+)-activated K(+) channel (BKCa) channel activity. Moreover, our results indicated that OP-A induced paraptosis-like cell death in GBM cells, which correlated with the vacuolization, possibly brought about by the swelling and fusion of mitochondria and/or the endoplasmic reticulum (ER). In addition, the OP-A-induced cell death did not involve the activation of caspases. We also showed that the expression of BKCa channels colocalized with these two organelles (mitochondria and ER) was affected in this programmed cell death pathway. Thus, this study reveals a novel mechanism of action associated with the anticancer effects of OP-A, which involves the induction of paraptosis through the disruption of internal potassium ion homeostasis. Our findings offer a promising therapeutic strategy to overcome the intrinsic resistance of GBM cells to proapoptotic stimuli.

Targeting SKCa channels in cancer: potential new therapeutic approaches.

Many studies have reported changes in potassium channel expression in many cancers and the involvement of these channels in various stages of cancer progression. By contrast, data concerning SKCa channels (small conductance calcium-activated potassium channels) have only recently become available. This review aims i) to present the structure and physiology of SKCa channels, ii) to provide an overview of published data concerning the SKCa proteins produced in tumor cells, and, whenever possible, the biological function assigned to them and iii) to review previous and novel modulators of SKCa channels. SKCa channels are activated by low concentrations of intracellular calcium and consist of homo- or heteromeric assemblies of α-subunits named SK1, SK2 and SK3. SK2-3 channels are expressed in tumors and have been assigned a biological function in cancer cells: the enhancement of cell proliferation and cell migration by hijacking the functions of SK2 and SK3 channels, respectively. Two major classes of SKCa modulators have been described: toxins (apamin) and small synthetic molecules. Most SKCa blockers are pore blockers, but some modify the calcium sensitivity of SKCa channels without interacting with the apamin binding site. In this review, we present edelfosine and ohmline as atypical anticancer agents and novel SK3 inhibitors. Edelfosine and ohmline are synthetic alkyl-lipids with structures different from all previously described SKCa modulators. They should pave the way for the development of a new class of migration-targeted anticancer agents. We believe that such blockers have potential for use in the prevention or treatment of metastasis.

New alkyl-lipid blockers of SK3 channels reduce cancer cell migration and occurrence of metastasis.

Edelfosine is an inhibitor of SK3 channel mediated cell migration. However, this compound bears adverse in vivo side effects. Using cell SK3 dependent cell-migration assay, patch-clamp, (125)I-apamin binding, and in vivo experiments we tested the ability of 15 lipid derivatives with chemical structures inspired from edelfosine to inhibit SK3 channels. Using a structure-activity relationship approach we identified an edelfosine analog named Ohmline (1-O-hexadecyl- 2-O-methyl-sn-glycero-3-lactose) with potent inhibitory effects on the SK3 channel. Its potency was greater for SK3 channels than for SK1 channels; it did not affect IKCa channels and only slightly but not significantly affected SK2 channels. This is the first SKCa channel blocker that can be used to discriminate between SK2 and SK1/SK3 channels and represents a useful tool to investigate the functional role of SK3 channels in peripheral tissues (that do not express SK1 channels). This compound, which acts with an IC(50) of 300 nM, did not displace apamin from SKCa channels and had no effect on non-specific edelfosine targets such as protein kinase C (PKC), receptors for platelet activating factor (PAF) and lysophosphatidic acid (LPA), as well as non-cancerous cells. This is promising because the pitfalls associated with the use of edelfosine-like compounds have been that their effective and high concentrations are often cytotoxic due to their detergent-like character causing normal cell lysis. Finally, Ohmline reduced metastasis development in a mice model of tumor indicating that this compound could become a lead compound for the first class of lipid-antimetastatic agent.

The SK3/K(Ca)2.3 potassium channel is a new cellular target for edelfosine.

BACKGROUND AND PURPOSE: The 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (edelfosine) is an ether-linked phospholipid with promising anti-cancer properties but some side effects that preclude its full clinical therapeutic exploitation. We hypothesized that this lipid could interact with plasma membrane ion channels and modulate their function. EXPERIMENTAL APPROACH: Using cell migration-proliferation assays, patch clamp, spectrofluorimetry and ¹²5I-Apamin binding experiments, we studied the effects of edelfosine on the migration of breast cancer MDA-MB-435s cells, mediated by the small conductance Ca²(+) -activated K(+) channel, SK3/K(Ca)2.3. KEY RESULTS: Edelfosine (1 µM) caused plasma membrane depolarization by substantially inhibiting activity of SK3/K(Ca)2.3 channels, which we had previously demonstrated to play an important role in cancer cell migration. Edelfosine did not inhibit ¹²5I-Apamin binding to this SK(Ca) channel; rather, it reduced the calcium sensitivity of SK3/K(Ca)2.3 channel and dramatically decreased intracellular Ca²(+) concentration, probably by insertion in the plasma membrane, as suggested by proteinase K experiments. Edelfosine reduced cell migration to the same extent as known SK(Ca) channel blockers. In contrast, K+ channel openers prevented edelfosine-induced anti-migratory effects. SK3 protein knockdown decreased cell migration and totally abolished the effect of edelfosine on MDA-MB-435s cell migration. In contrast, transient expression of SK3/K(Ca)2.3 protein in a SK3/K(Ca)2.3-deficient cell line increased cell migration and made these cells responsive to edelfosine. CONCLUSIONS AND IMPLICATIONS: Our data clearly establish edelfosine as an inhibitor of cancer cell migration by acting on SK3/K(Ca)2.3 channels and provide insights into the future development of a new class of migration-targeted, anti-cancer agents.

[Diversity of hepatitis B virus and its consequences]. / Impact clinique, thérapeutique et diagnostique de la diversité génétique du virus de l'hépatite B.

The genetic diversity of hepatitis B virus (HBV) was defined on the basis of the characterisation of the major determinants in the antigenic loop of HBs antigen (Ag). Historically, nine subtypes were defined. Recently, based on sequence analysis, HBV genomes have been classified into eight genotypes (A-H) which present distinct geographical distributions. Genetic mutants may have a selective advantage in patients treated with passive or active immunization (hepatitis B immune globulin or vaccine). Anti-viral treatment can be responsible for the emergence of escape mutants with resistant mutations in the polymerase gene. These substitutions can lead to changes on HBsAg structure. The lack of detection of several envelope mutant viruses by some commercial HBsAg assays has been demonstrated. Substitutions involving precore/core region have also been found to prevent HBeAg synthesis.

[Epidemiological surveillance of blood donors and residual risk of blood-borne infections in France, 2001 to 2003]. / Surveillance épidémiologique des donneurs de sang homologues et risque résiduel en France entre 2001 et 2003.

The national surveillance of French blood donors is performed by the Institut de Veille Sanitaire and the National Reference Center for Hepatitis B and C in transfusion in collaboration with the Etablissement Français du Sang and the Army blood center. The main objectives of this surveillance are to evaluate trends in prevalence and incidence rates of blood-borne infections in the blood donor population, to identify routes of contamination and to assess residual risk. This exhaustive surveillance also contributes to evaluate the blood donor selection and the impact of measures taken to prevent infections in the general population. The analyse of the database of all blood donations obtained from 2001 to 2003 has shown that prevalence rates were stable in the study period (0.60 per 10(4) donors for HIV, 8.0 per 10(4) donors for HCV, 1.8 per 10(4) first-time donors for HBs Ag and 0.56 per 10(4) donors for HTLV), The incidence rate of HIV and HBV (1 per 10(5) person-years) was three-times higher than for HCV (0.35 per 10(5) person-years) and eleven times higher than for HTLV (0.09 per 10(5) person-years). At least, the residual risk of transfusion-transmitted viral infections is very low: 1/3,150,000 donations for HIV, 1/10,000,000 donations for HCV and 1/640,000 donations for HBV. The yield of Nucleic Acid Testing (NAT) is limited since only 2 donations for HIV and 3 for HCV which were negative for antibodies were discarded thank to the NAT.

Determination of hepatitis B virus subtypes by an enzyme immunoassay method using monoclonal antibodies to type-specific epitopes of HBsAg.

We described a Hepatitis B surface antigen (HBsAg) subtyping method based on a commercial enzyme immunoassay (EIA) for detection of HBsAg in which the procedure was modified to include the use of monoclonal antibodies with restricted anti-HBs specificities. This method, which was able to classify HBsAg as: ayw1, ayw2, ayw3, ayw3* (intermediate between ayw3 and ayw4), ayw4, ayr, adw2, adw4 and adr, was compared to counter electrophoresis procedure (CEP) by testing HBsAg positive sera from blood donors included in a prospective national epidemiological survey. Among the 256 HBsAg positive samples tested with both techniques, 111 (43.3%) could not be subtyped with CEP vs 10 (3.9%) with our modified EIA. This difference was related to the serum HBsAg concentration which must be greater than 3000 ng/mL and 100 ng/mL for CEP and EIA, respectively. The results obtained from 145 sera with both methods were concordant. Seventeen out of 18 samples partially classified as ay with CEP were completely determined with EIA. This reliable procedure, derived from commercially available reagents, can be easily used in several applications such as large epidemiologic studies and as a substitute for nucleotide sequencing genotyping which is not adapted for large-scale screening and not applicable on samples from nonviremic hepatitis B virus (HBV) carriers.

Microalbuminuria and markers of the atherosclerotic process: the D.E. S.I.R. study.

The relationship between microalbuminuria and tissue-type plasminogen activator antigen (tPA-ag) and fibrinogen was evaluated in non-diabetic subjects. Subjects were participants of the D.E.S.I. R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) Study. Analyses were carried out on 2248 women and 2402 men for fibrinogen and on 272 women and 284 men for tPA-ag. Microalbuminuria was defined as urinary albumin concentration greater than 20 mg/l. Men with microalbuminuria had a 6% higher fibrinogen concentration than those without (3.07 g/l (95% confidence interval: 2.99,3.15) vs. 2.89 g/l (2.87,2.91), adjusted for age and smoking). This relationship existed in hypertensive as well as non-hypertensive subjects. The association between microalbuminuria and tPA-ag existed only in hypertensive men, those with microalbuminuria having a 21% higher tPA-ag than those without (4.39 ng/ml (3.70,5.08) vs. 3.63 ng/ml (3.32,3.94), adjusted for age and smoking). Adjustment for other risk markers for cardiovascular disease did not change the results. There was no relationship between microalbuminuria and these haemostatic factors in women. The results of this study suggest that in non-diabetic men, microalbuminuria is associated with fibrinogen, but with tPA-ag only when concomitant with hypertension.

GB virus type C/HGV markers in HCV RNA-positive French blood donors: correlation with HCV genotypes and risk factors.

BACKGROUND: Exposure to GB virus type C/HGV (GBV-C/HGV) could be determined by detection either of RNA by RT-PCR or of antibodies of the envelope protein E2. STUDY DESIGN AND METHODS: The aim of the study was to determine the proportion of the GBV-C/HGV markers of infection in a blood donor population infected with HCV and to identify GBV-C/HGV routes of transmission that are associated with HCV genotypes and risk factors. RESULTS: Among 306 HCV RNA-positive blood donors, the proportion of GBV-C/HGV RNA-positive donors and anti-E2-positive donors was 19.3 percent (95% CI = 15.0-24.2%) and 42.1 percent (95% CI = 36.6-47.9%), respectively. Exposure to GBV-C/HGV (RNA or anti-E2) was significantly associated with the risk factor of IV drug use. There was a trend toward association with HCV subtypes 1a and 3a, probably because these HCV subtypes are the most frequent in IV drug users. No correlation was observed between ALT elevation and the presence of GBV-C/HGV RNA. CONCLUSION: In persons with HCV infection, IV drug use seems to be a major route of GBV-C/HGV transmission. Precautions taken to avoid HCV infection will probably also decrease GBV-C/HGV transmission.