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Background The worldwide incidence of invasive breast cancer in women is increasing according to several studies. This increase in incidence seems to be higher in young women ( Methods We collected data from the Isere cancer registry in France of all invasive breast cancers from January 1990 to December 2018. The standardized incidence rate was calculated for four age groups ( Results A total of 23,703 cases were selected, including 1343 young women ( Conclusion Our study confirms the current trend of increasing the incidence of breast cancer in young women, associated with improved survival very likely attributable to earlier diagnosis due to increased awareness, and improvements in treatment. A better individualized risk-based screening strategy is needed for these patients. Additional studies will be needed to more accurately assess the risk of developing breast cancer and improve diagnostic performance.

The heat shock factor 1 (HSF1)-dependent transcriptional activation of human pericentric heterochromatin in heat-shocked cells is the most striking example of transcriptional activation of heterochromatin. Until now, pericentric heterochromatin of chromosome 9 has been identified as the primary target of HSF1, in both normal and tumor heat-shocked cells. Transcriptional awakening of this large genomic region results in the nuclear accumulation of satellite III (SATIII) noncoding RNAs (ncRNAs) and the formation in cis of specific structures known as nuclear stress bodies (nSBs). Here, we show that, in four different male cell lines, including primary human fibroblasts and amniocytes, pericentric heterochromatin of chromosome Y can also serve as a unique primary site of HSF1-dependent heterochromatin transcriptional activation, production of SATIII ncRNA, and nucleation of nuclear stress bodies (nSBs) upon heat shock. Our observation suggests that the chromosomal origin of SATIII transcripts in cells submitted to heat shock is not a determinant factor as such, but that transcription of SATIII repetitive units or the SATIII ncRNA molecules is the critical element of HSF1-dependent transcription activation of constitutive heterochromatin.

Meta-analyses of randomized controlled trials that started from 1963 to 1991 reported a decrease of breast cancer mortality, associated with mammography screening. However, the effectiveness of population-based screening programs conducted currently might have changed due to the higher effectiveness of treatments for late-stage cancers and the better diagnostic performance of mammography. The main objective of this study was to predict the reduction of breast cancer mortality associated with mammography screening in the current French setting. We compared breast cancer mortality in 2 simulated cohorts of women, which differed from each other solely in a 70% biennial participation in screening from 50 to 74 years old. The microsimulation model used for predictions was calibrated with incidence rates of breast cancer according to stage that were observed in Isère and Loire-Atlantique departments, France, in 2007–2013. The model predicted a decrease of breast cancer mortality associated with mammography screening of 18% (95% CI: 5, 31) and 17% (95% CI: 3, 29) for models calibrated with data from Isère and Loire-Atlantique departments, respectively. Our results highlight the interest in biennial mammography screening from ages 50 to 74 years old to decrease breast cancer mortality in the current setting, despite improvements in treatment effectiveness.

BACKGROUND Liver cancer is the fifth most common cancer and the second cause of cancer-related deaths worldwide. Transarterial chemoembolization (TACE) is the best treatment of intermediate hepatocellular carcinoma (HCC). Doxorubicin is the most commonly used drug despite a low level of evidence. AIM To compare the objective response rate of idarubicin-based TACE (Ida-TACE) against doxorubicin-based TACE (Dox-TACE) in intermediate stage HCC. METHODS Between January 2012 and December 2014, all patients treated with TACE at our academic hospital were screened. Inclusion criteria were patients with Child-Pugh score A or B, a performance status below or equal to 1, and no prior TACE. Either lipiodol TACE or drug-eluting beads TACE could be performed with 10 mg of idarubicin or 50 mg of doxorubicin. Each patient treated with idarubicin was matched with two doxorubicin-treated patients. The TACE response was assessed by independent radiologists according to the mRECIST criteria. RESULTS Sixty patients were treated with doxorubicin and thirty with idarubicin. There were 93% and 87% of cirrhotic patients and 87% and 70% of Child-Pugh A in the doxorubicin and idarubicin groups, respectively. The median number of HCC per patient was two in both groups with 31% and 26% of single nodules in doxorubicin and idarubicin groups, respectively. Objective response rate after first TACE was 76.7% and 73.3% (P = 0.797) with 41.7% and 40.0% complete response in doxorubicin and idarubicin groups, respectively. Progression-free survival was 7.7 mo in both groups, and liver transplant-free survival was 24.9 mo and 21.9 mo in doxorubicin and idarubicin groups, respectively. Safety profiles were similar in both groups, with grade 3-4 adverse events in 35% of Dox-TACE and 43% of Ida-TACEs. CONCLUSION Ida-TACE and Dox-TACE showed comparable results in terms of efficacy and safety. Ida-TACE may represent an interesting alternative to Dox-TACE in the management of patients with intermediate stage HCC.

The need for semen preservation in domestic birds is a result of the reduction in genetic variability of domestic bird livestock and of the increasing risk of line extinction for health and safety reasons. Cryopreservation of embryos and primordial germ cells (PGC) is not routinely feasible in birds. The project therefore involved semen frozen in optimal safety and traceable conditions. Whole blood samples were also frozen to provide samples of analyses of genomes and health status. The feasibility of using ex situ conservation, i.e., collecting biological material to be stored outside the usual production area of the species (ex situ genetic stock), to preserve and manage rare breeds was tested with 4 subfertile populations: 3 rare experimental lines used for research into energy metabolism (R+), growth (Y33), and immunity (B4/B4), reared under known health status and the oldest endangered patrimonial French breed, the Gauloise dorée with an unknown health status. A general infrastructure was set up for the health screening and remediation of diseases, collection and storage of frozen cells and 2 sites were created for the storage of frozen samples. The screening and remediation of diseases of the Gauloise dorée, which was contaminated with various Salmonella and Mycoplasma strains, was achieved by successive treatment of parents, incubated eggs and young chicks with Baytril followed by Tiamulin. For each line, 474 to 994 semen straws have been frozen, thawed, and the semen evaluated. Insemination of frozen-thawed semen into females of the same genetic origin or of an egg-type commercial breed produced chicks in every case. For the most subfertile lines, insemination with egg-type females significantly increased the reproductive success. In conclusion, we report on the benefits of a semen and blood cryobanking complex for the management of endangered lines and strains of domestic birds. Current stocks made possible the restoration of more than 96% of the initial genome. This project also provided technical solutions to resolve some of the health problems frequently encountered for gene preservation in poultry.

The somatic BRAFMulticentric retrospective observational study including patients18 years treated with VMF alone for refractory BRAFFifty-seven patients: 56% female, median age 2.1 years (0.2-14.6), median treatment duration 4.1 months (1.4-29.7). Forty-one patients (72%) had at least one CAE: photosensitivity (40%), keratosis pilaris (32%), rash (26%), xerosis (21%), and neutrophilic panniculitis (16%). No skin tumor was observed. Five percent of CAEs were grade 3. None were grade 4 or led to permanent VMF discontinuation. Dose reduction was necessary for 12% of patients, temporary treatment discontinuation for 16%, none leading to loss of efficacy. VMF dose, median RPL, and efficacy were not correlated with CAE occurrence.At doses used for pediatric LCH, CAEs are frequent but rarely severe and have little impact on the continuation of treatment when managed appropriately. Regular dermatological follow-up is essential to manage CAEs and screen for possible induced skin tumors.

Objective To assess the variability of safety culture dimension scores and their associated rankings depending on three different scoring strategies using the Hospital Survey On Patient Safety Culture (HSOPS). Design Cross-sectional study using a self-administered questionnaire. Setting The study was conducted in an 1836-bed acute-care French university hospital with an annual volume of 135 999 stays, between April 2013 and November 2014. Participants All caregivers and technical-administrative staff with at least 6 months of employment, spending at least half of their working time in the hospital, were asked to participate. Intervention None. Main outcome measure The variability of the HSOPS results using three different scoring methods: the percentage of positive responses recommended by the Agency for Healthcare Research and Quality, the averaged individual means and the averaged individual sums. Results The response rate was 78.6% (n = 3978). The percentage of positive responses resulted in lower scores compared to averaged individual means and averaged individual sums in the six least developed dimensions, and gave more widely spread scores and greater 95CIs in the six most developed dimensions. Department rankings also varied greatly depending on the scoring methods. Conclusion The values of the HSOPS scores and their corresponding rankings greatly depended on the computation method. This finding shows how important it is to agree on the use of the same scoring strategies, before broadly comparing results within and across organizations.

In France, guidelines for cervical cancer screening recommend that women between the ages of 25-65 have a smear test performed once every three years. However, some women are screened significantly more frequently. In this study, we used a data-driven approach as opposed to a traditional hypothesis-driven approach to characterise the population of women who are screened more frequently than advised.Data came from an organised cervical cancer screening programme of a French department in the Alps (Isère). We retrospectively selected women aged between 25 to 65 years old who had at least two smear tests during the follow up period (2011-2015). We used a data-driven clustering approach to compare the population of over-screened women with other populations. We then performed a descriptive analysis of the over-screened population using univariate (ChiA total of 10,000 patients were randomly chosen from a population of 54,073. In our univariate analysis, women in the over-screened population were significantly younger, participated less in organised screening, were more likely to be followed by a gynaecologist and had more smear test results showing inflammation than the other populations. Patient location (urban v.s. rural area) was not significant for this population. The multivariate analysis confirmed these results.This data-driven approach based on an unsupervised learning method enables us to more accurately characterise the over-screened population. These data invite to improve communication with the youngest women and the gynecologists to recall the benefit of an interval between two normal smears complying with the recommendations. This approach could help to improve the prevention and have a real impact on this Public Health issue.

Summary Introduction The objective of our study was to describe and analyse the Post-Colonoscopy Colorectal Cancers (PCCRCs) and endoscopist performance-related risk factors in the Isere regional screening programme. Method This was a population-based retrospective cohort study between 2002–2013, where Post-Colonoscopy Colorectal Cancers (PCCRCs) were defined as colorectal adenocarcinoma diagnosed between six and sixty months post-colonoscopy following a positive gFOBT. We analysed the endoscopist performance-related risk factors of the 62 gastroenterologists who had carried out at least 30 colonoscopies during this period. Results During the period reviewed, there were 10,557 negative colonoscopies performed. Fifteen post-colonoscopy colorectal cancers were diagnosed from 2002–2013 with an average patient age of 67.1 years. Men comprised 73% of the cases and 53% of all the cases were found in the distal colon. These 15 cases comprised 1.1% of all Colorectal Cancers (CRCs) diagnosed in the screening programme, with an incidence rate of 0.42 (0.21–0.77) per 1,000 person-years. The aetiological breakdown was as follows: 47% related to missed cancers, 27% were new cancers, 20% were failed biopsy detection, and 6% related to incomplete removal. The Adenoma Detection Rate (ADR) among gastroenterologists was an average of 30%, but large heterogeneity was present within this number, ranging from 11% to 49%. Conclusion The post-colonoscopy colorectal cancer prevalence and incident rate were low relative to the literature. However, significant heterogeneity was present in the adenoma detection rate. Decreasing this heterogeneity by establishing a national benchmark, regular performance feedback and training modules should homogenise adenoma detection rates and decrease the number of interval cancers in the region.

International audience; For the past 50 yr, practices for ex situ preservation of endangered breeds have been extended. Semen and primordial germ cells, gonadic tissues have been frozen to create genetic stocks of chicken genetic diversity in cryobanks. Semen cryopreservation stays the preferred method since it is not invasive. Many protocols have been developed to cryopreserve chicken semen, but they give highly variable success rate. The aim of the present study was to standardize and prove the effectiveness of semen long-term storage for the restitution of lost families. We showed that semen straws stored for 18 yr in liquid nitrogen did not lose their fertilizing ability. We demonstrated the usefulness of cryopreserved semen stored in the French National Cryobank for the recovery of families of a subfertile experimental chicken line. In order to highlight the standardization of the cryopreserved method, different cryoprotectant protocols were also tested on a rare breed, freezing/thawing and insemination conditions were controlled. The best results were obtained using glycerol protocol, a sperm dilution of 1:4 (semen:extender). The insemination dose of 200 million sperm/female was as efficient as 400 million of sperm. Altogether, these results demonstrated the effectiveness of chicken semen long-term storage for the restoration of lost genetic resources and highlighted the importance of standardized chicken semen cryopreservation using procedures combining biophysical (cryoprotectants, freezing/thawing conditions) and zootechnical (artificial insemination) features.

International audience; BACKGROUND:Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type.METHODS:A cohort study was conducted using randomly selected cases from 10 French cancer registries. Net survival rates were computed using the Pohar-Perme estimator of the net cumulative rate. Three Cox models were independently built for adenocarcinomas, squamous cell and small cell cancers to estimate prognostic factors including CCI grade.RESULTS:A total of 646 adenocarcinomas, 524 squamous cell and 233 small cell cancers were included in the analysis. The net 8-year survival rate ranged from 12.6% (95% CI: 9.8-15.4%) for adenocarcinomas and 13.4% (95% CI: 10.1-16.7%) for squamous cell carcinomas, to 3.7% (95% CI: 1.1-6.3%) for small cell cancers. Observed and net survival rates decreased for CCI grades ≥3 for all histological group considered. After adjustment for sex, age group, stage and diagnostic mode, CCI grades 1 (HR = 1.6 [95% CI: 1.1-2.3]), 2 (HR = 1.7 [95% CI: 1.1-2.7]) and ≥ 3 (HR = 2.7 [95% CI: 1.7-4.4]) were associated with lower survival rates only for small cell cancers.CONCLUSION:After adjustment for age, sex, stage and diagnostic mode, the presence of comorbidity based on CCI grades 1-2 and ≥ 3 was associated with lower survival rates for small cell cancers whereas no differences were observed for adenocarcinomas and squamous cell cancers.

Background According to rare studies, the age at EBV primary infection (PI) has recently risen in some developed countries. A later age at infection is generally considered a risk factor for severe EBV PI, although few studies exist on this subject. Our investigation aimed to determine whether EBV seroprevalence and EBV PI epidemiology have evolved in France, and to what extent age and infection intensity (regarding biological parameters) are correlated. Methods and findings We conducted a retrospective study of the following EBV serological tests databases: tests carried out at Grenoble University Hospital (2000–2016) (n = 53,553); and tests carried out by a network of city laboratories in Grenoble area (2008–2015) (n = 27,485). The hospital population showed a continuous, significant decrease in EBV seroprevalence over the studied period for patients aged 20 and over (p

Purpose – Medical record represents the main information support used by healthcare providers. The purpose of this paper is to examine whether patient perception of hospital care quality related to compliance with medical-record keeping. Design/methodology/approach – The authors merged the original data collected as part of a nationwide audit of medical records with overall and subscale perception scores (range 0-100, with higher scores denoting better rating) computed for 191 respondents to a cross-sectional survey of patients discharged from a university hospital. Findings – The median overall patient perception score was 77 (25th-75th percentiles, 68-87) and differed according to the presence of discharge summary completed within eight days of discharge (81 v. 75, p=0.03 after adjusting for baseline patient and hospital stay characteristics). No independent associations were found between patient perception scores and the documentation of pain assessment and nutritional disorder screening. Yet, medical record-keeping quality was independently associated with higher patient perception scores for the nurses’ interpersonal and technical skills component. Research limitations/implications – First, this was a single-center study conducted in a large full-teaching hospital and the findings may not apply to other facilities. Second, the analysis might be underpowered to detect small but clinically significant differences in patient perception scores according to compliance with recording standards. Third, the authors could not investigate whether electronic medical record contributed to better compliance with recording standards and eventually higher patient perception scores. Practical implications – Because of the potential consequences of poor recording for patient safety, further efforts are warranted to improve the accuracy and completeness of documentation in medical records. Originality/value – A modest relationship exists between the quality of medical-record keeping and patient perception of hospital care.

Purpose – The purpose of this paper is to investigate trends in patient hospital quality perceptions between 1999 and 2010. Design/methodology/approach – Original data from 11 cross-sectional surveys carried out in a French single university hospital were analyzed. Based on responses to a 29-item survey instrument, overall and subscale perception scores (range 0-10) were computed covering six key hospital care quality dimensions. Findings – Of 16,516 surveyed patients, 10,704 (64.8 percent) participated in the study. The median overall patient perception score decreased from 7.86 (25th-75th percentiles, 6.67-8.85) in 1999 to 7.82 (25th-75th percentiles, 6.67-8.74) in 2010 (p for trend p for trend Practical implications – Patient perception scores may disguise divergent judgments on different care aspect while individual items highlight specific areas with room for improvement. Originality/value – Despite growing pressure on healthcare expenditure, this single-center study showed only modest reduction in patients’ hospital-care perceptions in the 2000s.

International audience; Herpes simplex virus (HSV) encephalitis is associated with a high risk of mortality and sequelae, and early diagnosis and treatment in the emergency department are necessary. However, most patients present with non-specific febrile, acute neurologic impairment; this may lead clinicians to overlook the diagnosis of HSV encephalitis. We aimed to identify which data collected in the first hours in a medical setting were associated with the diagnosis of HSV encephalitis. We conducted a multicenter retrospective case-control study in four French public hospitals from 2007 to 2013. The cases were the adult patients who received a confirmed diagnosis of HSV encephalitis. The controls were all the patients who attended the emergency department of Grenoble hospital with a febrile acute neurologic impairment, without HSV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF), in 2012 and 2013. A multivariable logistic model was elaborated to estimate factors significantly associated with HSV encephalitis. Finally, an HSV probability score was derived from the logistic model. We identified 36 cases and 103 controls. Factors independently associated with HSV encephalitis were the absence of past neurological history (odds ratio [OR] 6.25 [95 % confidence interval (CI): 2.22-16.7]), the occurrence of seizure (OR 8.09 [95 % CI: 2.73-23.94]), a systolic blood pressure ≥140 mmHg (OR 5.11 [95 % CI: 1.77-14.77]), and a C-reactive protein

International audience; The magnitude of overdiagnosis of breast cancer associated with mammography screening remains controversial because of methodological issues. The objective of this study was to quantify overdiagnosis and overtreatment associated with a population-based screening programme, taking into account lead time and uncertainty concerning baseline incidence of breast cancers.; A simulation model was developed to replicate incidence and detection rates of breast cancer observed in the Isère Département, France. The parameters of the model were estimated using an approximate Bayesian computation method.; For women aged 50-74 years during the 2007-2010 period, overdiagnosis of non-progressive breast cancers accounted for 17.0% (95% credibility interval (CI): 2.5%-35.5%) of all in situ cancers diagnosed, 5.5% (95% CI: 0.8%-9.8%) of all invasive cancers diagnosed, and 20.3% (95% CI: 3.0%-38.9%) of in situ and 13.0% (95% CI: 2.2%-23.3%) of invasive screen detected breast cancers. The estimates of overdiagnosis due to competitive causes of death were 1.0% (95% CI: 0.2%-%1.7) and 1.1% (95% CI: 0.6%-1.7%) for all in situ and invasive cancers diagnosed, respectively, and 1.3% (95% CI: 0.2%-2.0%) and 2.6% (95% CI: 1.4%-4.0%) of all in situ and invasive screen detected breast cancers, respectively. Among 1000 screen-detected cancers in 2010, 155 (95% CI: 27-284), 134 (95% CI: 10-242) and 140 (95% CI: 25-254) women underwent breast conserving surgery, lymph node dissection and radiation therapy for overdiagnosed cancers, respectively.; Our estimates of overdiagnosis should be balanced against the reduction of breast cancer mortality to assess the value of breast cancer screening programme.

This study evaluated the performance of two automated Vidas (V) and Liaison (L) immunoassays for Epstein-Barr virus (EBV) serology. The detection of the viral capsid antigen (VCA) IgM, the VCA/early antigen (VCA/EA) IgG, and the Epstein-Barr nuclear antigen (EBNA) IgG was assessed on 526 sera collected for routine EBV testing in immunocompetent subjects. The determination of expected EBV status (186 EBV primary infections, 183 past EBV infections, and 157 EBV-seronegative individuals) was based on results of routine laboratory enzyme immunoassays (EIAs) together with clinical data. The sensitivity and specificity of each individual marker were determined in comparison to the expected EBV status. The agreement between the V and L profiles and the expected EBV status was established through the interpretation of combinations of the different EBV markers. Statistically significant differences between the two tests were found for the specificity of the VCA IgM marker (96.2% for V versus 93.2% for L), the sensitivity of the VCA/EA IgG marker (89% for V versus 94% for L), and the specificity of the EBNA IgG marker (96.5% for V versus 74.2% for L). The results determined for the two assays with respect to overall agreement with the established expected EBV status were not significantly different (89.7% for V versus 88.2% for L), with discrepancies mainly observed in sera referenced as primary infections. These findings demonstrated the similar performances of the Vidas and the Liaison assays for the establishment of an EBV serological status using the VCA, EA, and EBNA markers.

Objective Estimating overdiagnosis associated with breast cancer screening may use annual incidence rates of cancer. We simulated populations invited to screening programmes to assess two lead-time adjustment methods. Methods Overdiagnosis estimates were computed using the compensatory drop method, which considered the decrease in incidence of cancers among older age groups no longer offered screening, and the method based on the decrease in incidence of late-stage cancers. Results The true value of overdiagnosis was 0% in all the data sets simulated. The compensatory drop method yielded an overdiagnosis estimate of −0.1% (95% credibility interval −0.5% to 0.5%) when participation rates among the population and risk of cancers were constant. However, if participation rates increased with calendar year as well as risk of cancer with birth cohorts, the overdiagnosis estimated was 11.0% (10.5–11.6%). Using the method based on the incidence of early- and late-stage cancers, overdiagnosis estimates were 8.9% (8.5–9.3%) and 17.6% (17.4–17.9%) when participation rates and risks of cancer were constant or increased with time, respectively. Conclusion Adjustment for lead time based on the compensatory drop method is accurate only when participation rates and risks of cancer remain constant, whereas the adjustment method based on the incidence of early- and late-stage cancers results in overestimating overdiagnosis regardless of stability of participation rates and breast cancer risk.

Summary Background Studies assessing the risk of cytomegalovirus (CMV), parvovirus B19 (B19V), rubella and varicella infections in female child-care personnel may help define appropriate preventive strategies during pregnancy. Methods Serologic testing for all four viruses and a self-administered questionnaire to identify risk factors were conducted on child-care staff aged 20–50 years old and on a reference group of women. Results In 395 exposed and 382 reference women, CMV, B19V, rubella and varicella seroprevalence were 69.4, 79.4, 98.7, 100% for exposed women, and 41.1, 68.0, 98.2, 99.7% for reference women, respectively. For CMV, the adjusted seroprevalence ratio (PR) of exposed versus reference workers, (PR, 1.43 [95% IC, 1.22–1.69]) was observed as of the first year of exposure. The risk attributed to occupation was 30.1%. Identified risk factors included exposure duration, past employment in maternity hospital, and participation in cleaning tasks. The risk attributable to personal factors ranged from 14.5% to 32.4%. The adjusted B19V PR was not significant (PR, 1.05 [95% IC, 0.94–1.16]). Conclusions French female child-care staff runs an occupational risk for CMV infection, but not for B19V infection. The fraction attributable to this CMV occupational risk was not higher than the risk associated with personal factors.

Because nasopharyngeal carcinoma (NPC) has a close association with Epstein-Barr virus (EBV), measuring serum EBV DNA and anti-EBV serum marker concentrations could be a feasible method for NPC diagnosis, monitoring and probably screening especially in a community at risk. The aim of this study was to determine the EBV pattern in sporadic NPC and in high risk NPC Tunisian families in order to evaluate their risk factors and help for NPC screening. The rates of anti-EBV antibodies and EBV DNA were determined in the serum of 47 healthy members randomly selected from 23 NPC multiplex families with two or more affected members, 93 healthy Tunisian community controls chosen with the same age, sex and geographic origin as unaffected individuals and 66 EBV positive sporadic NPC patients whose serum was available before and after treatment. Unexpectedly, significant lower concentrations of anti-EA (Early Antigen) IgG and anti-VCA (Viral Capsid Antigen) IgG were found in unaffected members from NPC families than in healthy controls while viral loads were negative in all the tested sera. For sporadic NPC patients, anti-EA IgG and anti-VCA IgA concentrations were significantly higher than in healthy controls and these rates decreased after treatment. The level of EBV DNA load varied according to the condition of the tumour. This study suggests that in the Tunisian NPC families, screening for malignancy is based on serum concentrations but not on EBV DNA load while in the sporadic NPC group, serologic markers and EBV DNA load are complementary for diagnosis and follow-up.

Objective: The objectives of this study were to determine whether peripheral blood mononuclear cell (PBMC)-associated HIV-1 DNA level in patients on long-term suppressive antiretroviral therapy (ART) was associated with plasma HIV-1 RNA level, CD4 cell count, and therapeutic factors throughout patient history. Design: Patients receiving triple or dual therapy with plasma HIV-1 RNA below detection limit for more than 3 years were recruited in a multicentric, cross-sectional study within the eight virology laboratories of the Agence Nationale de Recherche sur le SIDA et les Hepatites virales HIV quantification working group, each one in relation with a clinical center. Methods: PBMC-associated HIV-1 DNA was quantified using a standardized real-time PCR method in all laboratories. Results: A total of 236 patients was included. Median HIV-1 DNA was 2.8 log 10 copies/ 10 6 PBMCs (interquartile range 2.4-3.0). Univariate analysis showed PBMC HIV-1 DNA level to be related to pre-ART immuno-virologic status (plasma HIV-1 RNA zenith and CD4 cell count nadir) and to current CD4 + T-cell count. HIV-1 DNA was lower in patients receiving ART with inferior virologic efficacy, as they also had a higher CD4 nadir and a lower HIV-1 RNA zenith than other patients. PBMC HIV-1 DNA level was not related to therapy duration, to time spent with undetectable HIV-1 RNA or to occurrence of a blip. Plasma HIV-1 RNA zenith and CD4 cell count nadir remained predictive of HIV-1 DNA level in the multivariate model which was associated with 22% of its variability. Conclusion: Whatever the duration of treatment, HIV-1 DNA level during ART gives a picture of the intensity of viral replication and immune deficiency reached before starting therapy.

International audience; The objective was to discuss the evolution of the real incidence of breast cancer. Observed incidence as calculated by cancer registries differs from the real incidence because of the artifacts brought by diagnostic procedures and case collection. Age-period-cohort models were applied to nearly 11,200 incident breast cancers collected by the Cancer Registry of Is? from 1983 to 2002 in women aged 30-84. We took into account prior knowledge and assumptions concerning the evolution of real incidence, diagnostic procedures, and collection of cases. In the age group 30-49, no real incidence increase was seen if we assume that diagnostic procedures and collection of cases were not impaired. In women aged 50-69, an increase of real incidence and intensive screening could explain the increase of observed incidence but exact quantifications are difficult. At most, the increase due to screening would reach 50%. In women aged 70-84, no real incidence increase was suspected if we assume that changes in clinical practices and screening led to more breast cancer cases collected.

The use of streptomycin in the PrP sc detection procedures represents a new and attractive way to detect more PrP sc , the best marker for the transmissible spongiform encephalopathies (TSEs). Actually, the streptomycin PrP sc aggregating property reported recently was established as beneficial in PrP sc detection using immunohistochemistry in diagnostic as well as in experimental conditions. The present study reports in details how to use advantageously this original streptomycin property in PrP res biochemical extraction and detection. Using TSE diagnostic brain material, specificity and increased sensitivity using streptomycin-treated samples were substantiated. Then an early sequential brain and spleen sampling (from 7 to 49 days post-inoculation) from C57Bl/6 mice inoculated intra-cerebrally or intra-peritoneally with C506M3 scrapie strain was analysed using streptomycin versus ultracentrifugation PrP res extraction. Whatever the inoculation route, streptomycin allowed earlier PrP res detection in spleen (7 d.p.i.), then in brain suggesting a stronger affinity of the infectious agent for the lymphoid compartment.

The aim of this study was to describe implementation of professional practice assessment (PPA) programmes and participation of physicians and pharmacists in these programmes in a French university hospital.We conducted an observational study based on PPA programmes validated in Grenoble university hospital continuing education board between 2007 and 2011. Data were extracted from individual commitment forms filled in by professionals and programme validation forms. The main outcome was the proportion of full-time hospital practitioners who validated at least one PPA programme.Over a 5-year period, 64 PPA programmes and 509 individual commitments involving 366 professionals were validated. At study endpoint, 264 (47%) permanent professionals had validated their mandatory PPA programme. The main methods used in PPA programmes included mortality and morbidity reviews (23), multidisciplinary meetings (23), staff PPA (8) and experience feedback committees (6). The most commonly reported strengths of these programmes included team work (49%) and improvement of patient care (30%). The most commonly reported drawbacks were organizational issues (27%) and unavailability to participate (23%).Hospital practitioners and pharmacists adhered to team-based PPA programmes. Implementation of team-base continuing development programmes was the preferred modality during the study period. Implementation of continuing professional development should help support this dynamic.

To monitor multiple Epstein-Barr virus (EBV) infections during the early and convalescent stages of infectious mononucleosis (IM), a cloning and sequencing study of the LMP1 gene was conducted in saliva and peripheral blood mononuclear cells (PBMCs) from 23 patients with IM at day 0 (D0) and day 180 (D180) after the onset of the disease. Multiple EBV strains were detected in 9 (39%) of the patients during follow-up, with 7 of 9 cases detected as early as D0. Six of the nine patients harbored the same dominant strain in saliva and PBMCs during follow-up, with a trend toward a restriction of the number of EBV strains in saliva but not in PBMCs at D180. Furthermore, transmission of a minor strain was observed between partners in a heterosexual couple. There was no correlation between multiple infections and EBV DNA load in either compartment.

The knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross-sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25-65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2-3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a kappa-value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low-resource settings.

The expression of plasminogen- and colony-stimulating factor-1-associated markers was first investigated in seven bladder carcinoma cell lines and in 15 primary bladder tumors using RT-PCR (mRNAs), zymography (protein activity), ELISA and immunocytochemistry analysis (ICC) (protein levels). The mRNAs expression, the activity and the levels of the secreted proteins were not informative. Only urokinase plasminogen activator receptor (uPA-R/CD87) and possibly plasminogen activator inhibitor type-2 (PAI2) antigen expression at the cellular levels seem to be useful markers. uPA-R antigen expression correlated with the secretion of hepatocyte growth factor (HGF) ( P=0.016) and the motility of the bladder tumor cells ( P=0.014), two markers associated with a poor prognosis in bladder carcinoma. To validate our technique and confirm these preliminary results, uPA-R and PAI2 antigen expression was determined in the imprints from 129 resected bladder carcinoma fragments. uPA-R correlated with the grade ( P=0.002), tumor invasion ( P=0.003) and the ploidy ( P=0.05) of the bladder carcinomas and with the low overall survival ( P=0.045) of the patients. PAI2 correlated only with the stage ( P=0.02) and low overall survival ( P=0.038). We conclude that in bladder carcinomas, studying the transcripts of PAs, PAIs, CSF-1 and its receptor, as well as measuring their concentration or activity in culture supernatants was of no clinical interest in terms of diagnostic or prognostic value. Only the ICC of uPA-R, which correlated with the major histopathological parameters of tumors and the low overall survival, proved to be a diagnostic and prognostic marker.

Immortalization of B cells by Epstein-Barr virus (EBV) and their subsequent proliferation leads to B-cell non-Hodgkin's lymphoma in immunocompromised patients. The role of hepatitis C virus (HCV) in B-cell non-Hodgkin's lymphoma has recently been raised, and an interaction between HCV and EBV is supported by recent in vitro experiments. The aim of this study was to investigate in vivo interactions between HCV and EBV in patients with AIDS, i.e., patients exposed to the risk of EBV-related B-cell non-Hodgkin's lymphoma. A total of 135 patients were prospectively studied. Serological and molecular markers of HCV, EBV, and human immunodeficiency virus (HIV) infection were sought. All the patients harbored latent EBV infection, and 20% had detectable HCV RNA in serum. No significant relationship was found between HIV, HCV, and EBV viral load in peripheral blood mononuclear cells or plasma. There was no difference between anti-HCV-positive and -negative patients or between HCV RNA-positive and -negative patients with regard to the prevalence of EBV markers, especially EBV replication markers. The presence of EBV replication markers was not related to HCV RNA seropositivity or to HCV viral load. Five patients subsequently developed B-cell non-Hodgkin's lymphoma, none of whom had markers of EBV or HCV replication. These results argue against an in vivo interaction between HCV and EBV in patients with AIDS, and against a role of HCV infection in the occurrence of B-cell non-Hodgkin's lymphoma in these patients. J. Med. Virol. 67:510–515, 2002. © 2002 Wiley-Liss, Inc.

This study aimed to evaluate an intervention to improve blood culture practices. A cluster randomised trial in two parallel groups was performed at the Grenoble University Hospital, France. In October 2009, the results of a practices audit and the guidelines for the optimal use of blood cultures were disseminated to clinical departments. We compared two types of information dissemination: simple presentation or presentation associated with an infectious diseases (ID) specialist intervention. The principal endpoint was blood culture performance measured by the rate of patients having one positive blood culture and the rate of positive blood cultures. The cases of 130 patients in the “ID” group and 119 patients in the “simple presentation” group were audited during the second audit in April 2010. The rate of patients with one positive blood culture increased in both groups (13.62 % vs 9.89 % for the ID group, p = 0.002, 15.90 % vs 13.47 % for the simple presentation group, p = 0.009). The rate of positive blood cultures improved in both groups (6.68 % vs 5.96 % for the ID group, p = 0.003, 6.52 % vs 6.21 % for the simple presentation group, p = 0.017). The blood culture indication was significantly less often specified in the request form in the simple presentation group, while it remained stable in the ID group (p = 0.04). The rate of positive blood cultures and the rate of patients having one positive blood culture improved in both groups. The ID specialist intervention did not have more of an impact on practices than a simple presentation of audit feedback and guidelines.

Background: the reference method to study the HCV complexity was cloning and sequence analysis of a sufficient number of clones. The evolution of the viral complexity in chronic non responder patients during treatment with standard doses of interferon was not very well investigate because this method was expensive and labour intensive when large series of patients were concerned. Meanwhile, with the alternative Single-Strand Conformation Polymorphism (SSCP) method, a rough estimation of the quasispecies present in a given sample could be obtained. Objectives: the aim of the study was to analyse the evolution of HCV heterogeneity, investigated by SSCP analysis targeted to the HVR-1, in 30 nonresponders chronic hepatitis C patients treated by Interferon-α 3MUI. Results: genotype 1 was the main HCV type found in this population (77% of non responder patients). Before treatment, the SSCP assay revealed a high complexity pattern: the median of SSCP band number was 9. During IFN-α treatment, SSCP band number didn't change. However a significant decrease of the viral load was observed (P

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

Since the few data exploring a possible association between Epstein–Barr virus (EBV) and breast cancer are conflicting, we investigated this association together with the influences of geographical areas. 509 breast cancers were sampled from areas with varying risks of nasopharynx carcinoma (NPC) such as North Africa (Algeria and Tunisia, high-risk area); southern France (Marseille, intermediate-risk area); and northern Europe (northern France, the Netherlands and Denmark; low-risk areas). Polymerase chain reaction (PCR) of a subregion of EBV BamHIC encoding the EBERs demonstrated that 31.8% of the tumours contained the viral genome. No significant differences were observed among the geographical areas. However, positive samples showed higher loads of the EBV genome in the NPC high- and intermediate-risk areas than in the low-risk areas. EBV type 1 was the dominant strain. In situ hybridization studies using a35S-labelled riboprobe for EBER1 and a laser capture microdissection, combined with quantitative PCR, showed that EBV localization was restricted to some tumour epithelial cell clusters. EBV could not be detected in the stroma. Considering the whole population covered, the presence of the EBV genome was not correlated with age, menopausal status, tumour, size, nodal status or histological grade. © 2001 Cancer Research Campaign http://www. bjcancer.com

The deleterious effects of three cryoprotectants, glycerol, dimethylsulfoxide (DMSO), and dimethylacetamide (DMA), were compared on fowl spermatozoa. The viability and integrity of spermatozoa were measured with eosin-nigrosin smears. Glycerol was the least deleterious cryoprotectant, followed by DMA, and DMSO was the most toxic. Methods employing either glycerol or DMA were then compared for the cryopreservation of semen in either straws or pellets. Fertility was measured following artificial insemination. The highest fertility rates were obtained with semen frozen with DMA in pellets directly plunged in liquid nitrogen, DMA being added at -6 C (92.7%) or 5 C (84.7%). When semen was frozen in straws, glycerol equilibrated for 1 or 30 min gave the highest fertility results, but the fertility rates were lower (53.7 and 63.9%) than with DMA in pellets. The lowest results (26.7%) were obtained when semen was frozen in straws with DMA. When semen was frozen in pellets at very high cooling rates, DMA was superior to glycerol as a cryoprotectant, as evidenced by fertility. In contrast, when straws and low freezing rates were used, glycerol gave better results; however these results were never as high as those obtained with DMA and pellets. In conclusion, under our experimental conditions, the highest fertility rates were achieved with DMA and pellets. However, for gene banking, which requires high levels of safety and clear identification, glycerol and straws are more convenient.

France is the only country that practices pedigree selection of guinea fowl for meat production. The increasing risk of line extinction for sanitary or breeding failure reasons makes clear the need for an efficient method of reproductive cell cryopreservation in this species. However, an efficient method of guinea fowl sperm freezing in secured packaging is still lacking. The aim of the present study was to develop such a method. Based on results previously obtained in chickens, different cryoprotectants and freezing/thawing processes were tested and then adapted to guinea fowl. Semen quality was measured by semen viability evaluation and then by fertility measured after intravaginal artificial insemination. The best results (70% fertility with frozen-thawed sperm) were obtained by the use of the permeant cryoprotectant agents dimethyl formamide combined with a freezing rate of 30°C/min. The initial insemination frequency also affected the fertility results: 2 consecutive days of inseminations were needed in the first week to ensure enough filling of the utero-vaginal glands of the guinea fowl hen and thus to get successive fertile eggs. Thereafter, a 2-wk insemination frequency was sufficient. This new method, combining biophysical (cryoprotectant agents, freeze/thaw rate) and zootechnical (artificial insemination frequency) features, is the first cryopreservation method successfully developed in secured packaging for guinea fowl sperm. This method is now available for the practice of gene bank conservation and male reproductive management.

Background: There is considerable interest in the possibility of provision of lung cancer screening services in many developed countries. There is, however, no consensus on the target population or optimal screening regimen. Methods: In this paper, we demonstrate the use of published results on lung cancer screening and natural history parameters to estimate the likely effects of annual and biennial screening programmes in different risk populations, in terms of deaths prevented and of human costs, including screening episodes, further investigation rates and overdiagnosis. Results: Annual screening with the UK Lung Screening Study eligibility criteria was estimated to result in 956 lung cancer deaths prevented and 457 overdiagnosed cancers from 330 000 screening episodes. Biennial screening would result in 802 lung cancer deaths prevented and 383 overdiagnosed cancers for 180 000 screening episodes. Interpretation/conclusion: The predictions suggest that the intervention effect could justify the human costs. The evidence base for low-dose CT screening for lung cancer pertains almost entirely to annual screening. The benefit of biennial screening is subject to additional uncertainty but the issue merits further empirical research.

Increasing prevalence of obesity particularly affects underprivileged families and children. This study aimed to estimate the efficiency of an obesity prevention program for school-aged children in deprived urban areas.This was an intervention trial with a before-and-after comparison of a cohort of school-aged children in preschool and primary school in three deprived urban areas in Grenoble, France. All school-aged children in the first and third year of preschool and the third year of primary school during the 2008-2009 and 2009-2010 school years, whose parents agreed to participate in the study, were included. Children were seen again 2 years later. The staff of the school health service measured and weighed the children during a medical check-up, thus determining their body mass index (BMI) and Z score. A school doctor suggested specific care to the parents of overweight children. A lifestyle questionnaire was completed. The primary outcome was changes in BMI and the Z score over 2 years. The secondary outcome was changes in lifestyle and eating habits.A total of 2434 children were included in the screening campaign. Of the 2434 children included in screening, 1824 children were reviewed and evaluated at 2 years. At inclusion, overweight prevalence increased with age, from 6.4% in the first year of preschool to 21.9% in the third year of primary school. More than 60% of overweight children had a high social vulnerability score. Prevalence of overweight increased from 13.8% to 21.5% in 2 years in the entire cohort (P0.001). In the 252 overweight children, the mean BMI increased from 20 kg/m(2) to 21.8 kg/m(2) (P0.001), as did the mean Z score, which increased from 2.72 to 2.9 (P0.001). There was no significant interaction depending on whether the family physician was in private practice or employed by a health center. According to their eating habits, fewer of the overweight children had a snack in the morning and more had a school lunch. More than half of the children thought they had improved their eating habits. They played more sports (30% versus 49.5%).This study failed to demonstrate that incentive for medical management of excess weight had an effect on the short-term (2 years) evolution of the children's corpulence.

Summary Background The main objective of this study was to estimate the sensitivity of a colorectal cancer-screening program based on a guaiac fecal occult blood (FOB) test. The secondary objective was to determine whether the sensitivity varied by sex and if the difference between males and females could be explained by differences in age group at the time of the test, round of screening, how the test was provided to the participant, tumor location, and the presence of theoretical screening program exclusion criteria. Methods For the 2002–2006 period, we retrospectively analyzed data from the organized colorectal screening program in Isere, France, which was designed for asymptomatic individuals aged 50–74. Sensitivity was assessed considering the number of interval cancers diagnosed in the 2 years following the test. A logistical regression analysis was done to evaluate the factors associated with the sensitivity of the screening program. Results A total of 506 participants were included in the analysis. The overall sensitivity of the screening program was 48.4%, being 58.3% for males and 32.5% for females. In multivariate analysis, sensitivity for males was still higher than for females (OR = 2.1 [95% CI, 1.4–3.4]) after adjusting for age group, presence of exclusion criteria, the way the test was given, the round of participation, and the tumor location. A total of 183 (36.2%) study subjects presented with at least one exclusion criterion for the screening program. Conclusion The sensitivity of the colorectal cancer-screening program based on a guaiac test was insufficient, being higher for males than for females. This difference in sensitivity was not entirely explained by differences in age, characteristics of screening participation, and tumor location.

Identifying prognostic markers in local regional breast carcinomas remains an important challenge today. DNA content obtained by flow cytometry, has been found to be of prognostic value; results with other methods remain less clear. This report describes DNA image cytometry patterns which are assessed with respect to disease-free survival. From June 1982 to December 1992, 415 patients under 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1 (34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28–75) and 58.8% of the patients were premenopausal; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were used in decision-making for adjuvant treatment: hormonotherapy (48%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was carried out on air dried smears to be analysed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index; DNA histogram, integrated optical density, DNA malignancy grade, ploidy balance. With a median follow-up of 36 months (0–105), proliferation index ( P = 0.0008), DNA histogram ( P = 0.0017), integrated optical density (IOD) ( P = 0.018) and DNA malignancy grade ( P = 0.017) had a significant prognostic value on disease-free survival estimated by the Kaplan-Meier method. When these parameters were included in a Cox proportional regression hazards model, PR ( P =0.01), Scarff-Bloom histological grading ( P =0.02), axillary clearance ( P = 0.04) were significant; however, in the same model, taking into account the axillary lymph node histological status, IOD was significant for pN- patients ( P = 0.03), and proliferation index ( P = 0.03) was significant for pN+. Such results need to be updated with a longer median follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), should be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance. Copyright © 1996 Elsevier Science Ltd

Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with α-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.8% of PBMC. After 3 months of treatment, HCV RNA was still present in 63.6% of plasma samples but in only 27.3% of PBMC. A good correlation was observed between serum alanine aminotransferase level normalisation and disappearance of the viral genome in plasma. Among the six responder patients, five relapsed shortly after IFN withdrawal; HCV RNA became detectable again, especially in PBMC. These results show the presence of HCV in PBMC from most patients infected chronically. IFN therapy had an inhibitory effect on viral replication in lymphoid cells, but frequent relapses observed after cessation of treatment with IFN suggested persistence Of HCV in these Cells. © 1995 Wiley-Liss, Inc.

Summary Background and aims In France, participation in organized colorectal cancer screening remains low. The objective of this study was to identify the determinants of participation in colorectal cancer screening in Isere, a French administrative entity. Methods This study examined the target population invited for screening between 2007 and 2008 in Isere. The statistical analysis method was based on a two-level logistic regression model: the first was the individual level relative to the individuals invited for screening and the second was an aggregate level corresponding to the socioeconomic level of an invited person's residence area (IRIS: “Ilot regroupe pour l’Information Statistique”; Regrouped statistical information block). The evaluation of the socioeconomic level was based on the Townsend deprivation. Results Participation varied depending on sex, age, and health insurance plan. The people residing in the least deprived IRISes participated more than individuals residing in the most deprived IRISes. The multilevel analysis showed a 24% difference in participation between the least and the most deprived IRISes. Conclusions The use of socioeconomic data on the IRIS geographical unit has identified, socially and geographically, the populations that participate the least, although this reflects “mean” behaviors. These results could be used to set up targeted actions to encourage participation in these populations.

AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the relationship between high blood EBV DNA loads and subsequent progression to ARL.We identified 43 cases of ARL diagnosed between 1988 and 2007 within two cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral blood mononuclear cell (PBMC) samples were available within 3 years before ARL diagnosis. For each case, two controls matched for the cohort and CD4 cell count in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and serum samples with a commercial kit.High levels of EBV DNA in PBMCs collected a median of 10 months before diagnosis were associated with an increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95% confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV load) but not with primary brain lymphoma.In this study, HIV-infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent progression to systemic B lymphoma. Clinicians should be aware of the increased risk of developing systemic B lymphoma in HIV-infected patients with a high blood EBV DNA load.

In some anogenital lesions the detection of certain types of human papilloma virus, especially oncogenic types, is of interest. In a first step during a prospective study, we compared two methods for the detection of human papillomavirus (HPV) DNA in clinical samples: Southern blotting followed by hybridization with a cloned radioactive genomic probe and a classical polymerase chain reaction (PCR) followed by hybridization with a 32 P-labelled oligonucleotide probe. 118 biopsies and swabs were examined for HPV 6/11, 16, 18 and 33, 67 positive reactions were found by both methods, 5 positives only by PCR and 2 positives only by Southern blot for unidentified HPV. Patients with anogenital condylomas, dysplasias and carcinomas or asymptomatic patients were studied. Most high grade (II and III) dysplasias were associated with HPV 16 and HPV 18. Condylomata lesions and low grade dysplasia (grade I) were associated mostly with HPV 6/11, mixed type of HPV, less frequently with HPV 16 or HPV 18. As a second step a nested PCR coupled to solid support detection method was used as described by Sauvaigo et al. (1990) Nucleic Acids Res. 18, 3175–3183) to study a panel of 30 previously qualified different HPV DNA extracts. In this procedure the second round of PCR amplification involves biotinylated and dinitrophenylated labelled primers allowing the capture of PCR amplified HPV DNA sequences on streptavidin coated tubes and its revelation. We describe an improvement of HPV DNA detection by means of single-step immunoenzymatic revelation involving anti-DNP monoclonal antibodies conjugated to horseradish peroxidase enzyme. A perfect correlation with the previous results was obtained. This solid support method allows a faster and easier HPV typing compared to methods using membrane transfer.

Chronic active hepatitis B (CAH-B), anti-HBe (+) has been associated with a hepatitis B virus variant carrying a stop codon at the distal pre-C region that prevents HBeAg synthesis. We analyzed the HBV DNA pre-C region in five members of a Turkish family. The mother presented an anti-HBe (+) CAH-B and the four children different hepatitis B virus serological and clinical profiles. The pre-C region was analyzed by cloning after DNA amplification in sera and peripheral blood mononuclear cells. A method for rapid screening of a large number of cloned polymerase chain reaction products was developed for the presence of the most frequent pre-C mutations (G to A substitution at nucleotide position 1896 and 1899). At least 60 independent clones were tested for each patient by selective oligonucleotide hybridization using non-mutated (M0), one (M1) and two (M2) point-mutated probes. Results were confirmed by sequencing. The mutation 1896 was present in 91% of DNA clones from the mother. The same mutation was also found in 85% of the clones in the youngest child (D), but in less than 10% of the clones from children A and C. Only the pre-C wild-type strain was observed in child B. X gene deletions (3 to 20 nt) were also present in some clones from the mother and children A, B and C. No significant difference between serum and peripheral blood mononuclear cells concerning the viral population was observed. In this study, a method for rapid screening of numerous polymerase chain reaction clones was developed to obtain the best quantitative estimation of mutated to wild-type HCV ratio present in patients. The data suggest: 1) a different selection of precore defective mutant virus between the members of the family, 2) the presence of pre-C mutant strains in an anti-HBs positive asymptomatic patient, and 3) the presence of X gene deletions associated to pre-C stop codon. Further investigation will be required to determine the influence of these genomic defects on the pathogenicity of the hepatitis B virus strains present in the patients.

International audience; OBJECTIVE: To quantify the magnitude of overdiagnosis from non-progressive disease detected by screening mammography, after adjustment for the potential for lead time bias, secular trend in the underlying risk of breast cancer, and opportunistic screening. DESIGN: Approximate bayesian computation analysis with a stochastic simulation model designed to replicate standardised incidence rates of breast cancer. The model components included the lifetime probability of breast cancer, the natural course of breast cancer, and participation in organised and opportunistic mammography screening. SETTING: Isère, a French administrative region with nearly 1.2 million inhabitants. PARTICIPANTS: All women living in Isère and aged 50-69 during 1991-2006. MAIN OUTCOME MEASURES: Overdiagnosis, defined as the proportion of non-progressive cancers among all cases of invasive cancer and carcinoma in situ detected 1991-2006. RESULTS: In 1991-2006, overdiagnosis from non-progressive disease accounted for 1.5% of all cases of invasive cancer (95% credibility interval 0.3% to 2.9%) and 28.0% of all cases of carcinoma in situ (2.2% to 59.8%) detected either clinically or by screening mammography in Isère. When analysis was restricted to the cancers detected by screening mammography only, the estimates of overdiagnosis were 3.3% (0.7% to 6.5%) and 31.9% (2.9% to 62.3%) for invasive cancer and carcinomas in situ, respectively. CONCLUSION: Overdiagnosis from the detection of non-progressive disease by screening mammography was limited in 1991-2006 in Isère. Because carcinoma in situ accounted for less than 15% of all incident breast cancer cases, its contribution to overdiagnosis was relatively limited and imprecise.

Using flow or image cytometry, we compared the DNA distribution of cells from bladder washings from 52 patients with bladder cancer. For image cytometry, urothelial nuclei (recognized visually) were analyzed for DNA content using polymorphonuclear nuclei as internal diploid reference. For flow cytometry, two methods can be used: either all cells can be analyzed, as commonly performed, or urothelial cells can be analyzed alone, after specific derection. In this flow cytometry study, cells were doubly stained for panurothelial antigen T16 and for DNA. All the cells were first analyzed using peripheral lymphocytes as an external reference; 79% of the results were similar with results obtained from image analysis. For discordant results, flow-cytometric data were reprocessed to identify immunologically stained urothelial cells; one additional case became concordant with image cytometry when only urothelial cells were analyzed, with lymphocytes as diploid reference; a better concordance (94%) was found when the nonurothelial cells of the samples served as a diploid reference instead of peripheral lymphocytes. This suggests that we achieved an improvement of the flow-cytometric evaluations for ploidy assessement, and we conclude that, on these conditions, flow or image analysis can be considered as equivalent methods for DNA content studies of tumors. © 1993 Wiley-Liss, Inc.

An easy, rapid, and reproducible test to distinguish residual cytomegalovirus (CMV) immunoglobulin M (IgM) antibodies from antibodies produced in primary infection could be useful, especially for pregnant women. The CMV avidity of IgG antibodies with the VIDAS automated enzyme-linked fluorescent assay and 6 M urea was evaluated in a multicenter study to differentiate between primary CMV infections and past infections or reactivations. A total of 416 serum specimens were tested: 159 specimens were from follow-up of primary infections, and 257 were from past infections. All of the specimens from primary infections collected within 4 months (17 weeks) after the onset of the infection had an avidity index lower than 0.8. An avidity index higher than 0.8 excludes a recent primary infection of less than 4 months. However, an avidity index higher than 0.8 cannot confirm all past infections, since 48 specimens (18%) from past infections had an avidity index lower than 0.8 (between 0.5 and 0.8). The exclusion capacity could be improved (96.9%) by using a cutoff of 0.7, but this index would decrease the specificity of the technique, since the avidity index was found to be between 0.7 and 0.8 in two patients with recent primary infection. All specimens from primary infections obtained more than 4 months after the onset of infection had an avidity index more than 0.2. In this study, an avidity index less than 0.2 confirms the presence of a recent primary infection of less than 4 months. The VIDAS CMV IgG avidity test is a rapid, reproducible test with very good performance.

The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real-time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg-IFNα and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti-HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non-responder. Furthermore, in this cohort composed of 12% anti-HBs negative/anti-HBc positive and 20% anti-HBs positive/anti-HBc positive patients, anti-HBc was not associated with pre-therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real-time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti-HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000–000, 2010. © 2010 Wiley-Liss, Inc. J. Med. Virol. 82: 747–754, 2010. © 2010 Wiley-Liss, Inc.

International audience; The objective of this study is to determine whether the likelihood of returning for routine breast cancer screening differed for false-positive cases depending on the diagnostic work-up. Using the original data from a French population-based breast cancer screening program, we compared the attendance rates at the subsequent round of screening for 16,946 and 1,127 participants who received negative (i.e., American College of Radiology, ACR, categories 1-2) and false-positive mammograms, respectively. False-positive mammograms were categorized ACR 0 (i.e., warranting additional imaging evaluation), 3 (i.e., warranting clinical and imaging follow-up), and 4-5 (i.e., warranting biopsy). We estimated the odds ratios of attendance at subsequent screening round using logistic regression, adjusting for age and history of previous mammography. The attendance rates at the subsequent screening round were 80.6% for women who received negative mammograms versus 69.6, 74.3, and 70.1% for women who received false-positive mammograms warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy, respectively. In comparison to women who received negative mammograms, the corresponding adjusted odds ratios of returning for routine screening were 0.6 [95% confidence interval (CI) 0.4-0.8], 0.8 (95% CI 0.6-0.9), and 0.6 (95% CI 0.4-0.8). No significant differences were found in odds ratios of attendance across ACR categories among women who received false-positive mammograms. Similar figures were observed for attending at least one of the two subsequent screening rounds. In conclusion, in comparison to women with normal or benign findings on index mammograms, false-positive cases warranting additional imaging evaluation, clinical and imaging follow-up, or biopsy had uniformly decreased odds of attending subsequent routine screening rounds.

We have examined serum antibodies to Epstein-Barr virus Nuclear Antigen (EBNA)-1, -2A and -2B, in addition to antibodies to viral capsid antigen and early antigen in 100 rheumatoid arthritis patients and 50 of their relatives. Using indirect immunofluorescence on transfected cells and Western-blot technique, we have found increased frequency and titres of antibodies to EBNA-2B in patients and, to a lesser degree, in their family members, whereas other anti-Epstein-Barr virus antibodies appeared to be similar to controls. Cross-inhibition experiments were carried out and show that antibodies to EBNA-2A are distinct from those to -2B, and vice versa.

International audience; OBJECTIVE: To determine whether the implementation of two-view mammography was followed by a reduction in the rates of interval cancers. MATERIAL AND METHOD: We analyzed the data concerning women aged 50-69 who attended the breast cancer screening program between January 1, 1994 and December 31, 2006 in Isère, France. We performed Poisson regressions to estimate age-adjusted rate ratios of women being recalled, cancer detection, and interval cancer for two-view compared to single-view mammography. RESULTS: After adjusting for age, two-view mammography was associated with a higher risk of cancer detection (1.37 [95% CI, 1.16-1.62]) and with a decreased risk of 12-month (0.46 [95% CI, 0.23-0.92]) and 24-month (0.64 [95% CI, 0.46-0.88]) interval cancer. CONCLUSION: Two-view mammography for first and subsequent screens is associated with lower rates of interval breast cancer. This is at the expense of an increased number of women being recalled for further assessment after subsequent screens.