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We summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as “high-risk” or B3 lesions). Finally, seven frequently asked questions are answered.

Radioprotection issues about breast exposure to ionizing radiation (IR) for women with hereditary predisposition for breast cancer (BC) should be considered with modern perspectives including epidemiology and radiobiology. Consistent epidemiological data are only available for the BRCA1 or BRCA2 mutation carriers. Radiobiology investigates the repair function in both proven mutation carriers and high family risk women with no identified mutation. Some specific assays help to quantify undeniable differences according to the dose and the genetic status. Specific low-dose effects are clearly identified. A lack of control in deoxyribonucleic acid recombination called hyper-recombination is a well-identified cause of misrepaired double-strand breaks (DSBs), genomic instability, and cellular transformation. While radio-induced BC risk obviously depends on age at exposure, it appears that the genetic status of women may also constitute another main parameter. Convergent epidemiological and biological data lead to be highly cautious considering the potential effects of breast radiation exposure in BRCA1/2 mutation carriers. More generally, differences in individual response to IR are now well-established with cumulative evidence for a population more susceptible to radiation exposure even if all inherent molecular and cellular mechanisms are not fully elucidated. Indications for any kind of IR exposure involving breast, chest, or shoulders should be systematically justified in these women, including screening mammographic exposures.

Surgical incision with drainage remains the first-line therapy recommendation for breast abscesses greater than 5 cm. To determine recovery with ultrasound guided (US-guided) procedures for treatment of lactational breast abscesses without surgical incision for drainage. Institutional review board approval and written informed patient consent were obtained for this retrospective study. From May 1, 2009, to June 1, 2018, 92 consecutive women (mean age 30 years, range 18–45) with 105 abscesses were treated with oral antibiotics and US-guided percutaneous drainage under local anesthesia. A total number of 202 US-guided procedures were performed. Three techniques were used: needle aspiration (diameter 18 to 14G), pigtail catheter insertion (diameter 5 to 7F), and/or vacuum-assisted biopsy/aspiration (diameter 10G). When using needle aspiration or pigtail catheter, a saline irrigation of the cavity was performed according to pus viscosity. The median diameter of abscesses was 4.5 cm (range 1–15), 82/105 (78%) were larger than 3 cm and 40/105 (38%) larger than 5 cm. US-guided management was successful for 101/105 (96%; 95% CI, (91–99%)) abscesses regardless the size. After the first round of procedures, 49/105 (47%) abscesses were recovered, 56/105 (53%) needed more than one drainage with a median number drainages of 2.6 (2–6). In 4/105 cases (4%), women underwent additional surgery under general anesthesia. By excluding abscesses which occurred in the weaning phase (n = 17), breastfeeding carried on for 68/75 (91%) women. Unlike previous studies, US percutaneous guided management of lactational abscesses is effective even for abscesses greater than 5 cm and allows continued breastfeeding.

International audience; Down syndrome is characterized by premature aging and dementia with neurological features that mimic those found in Alzheimer's disease. This pathology in Down syndrome could be related to inflammation, which plays a role in other neurodegenerative diseases. We previously found a link between the NFkB pathway, long considered a prototypical proinflammatory signaling pathway, and the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). DYRK1A is associated with early onset of Alzheimer's disease in Down syndrome patients. Here, we sought to determine the role of DYRK1A on regulation of the NFkB pathway in the mouse brain. We found that over-expression of Dyrk1A (on a C57BL/6J background) stabilizes IB protein levels by inhibition of calpain activity and increases cytoplasmic p65 sequestration in the mouse brain. In contrast, Dyrk1A-deficient mice (on a CD1 background) have decreased IB protein levels with an increased calpain activity and decreased cytoplasmic p65 sequestration in the brain. Taken together, our results demonstrate a role of DYRK1A in regulation of the NFkB pathway. However, decreased IB and DYRK1A protein levels associated with an increased calpain activity were found in the brains of mice over-expressing Dyrk1A after lipopolysaccharide treatment. Although inflammation induced by lipopolysaccharide treatment has a positive effect on calpastatin and a negative effect on DYRK1A protein level, a positive effect on microglial activation is maintained in the brains of mice over-expressing Dyrk1A.

This article summarises the information that should be provided to women and referring physicians about breast ultrasound (US). After explaining the physical principles, technical procedure and safety of US, information is given about its ability to make a correct diagnosis, depending on the setting in which it is applied. The following definite indications for breast US in female subjects are proposed: palpable lump; axillary adenopathy; first diagnostic approach for clinical abnormalities under 40 and in pregnant or lactating women; suspicious abnormalities at mammography or magnetic resonance imaging (MRI); suspicious nipple discharge; recent nipple inversion; skin retraction; breast inflammation; abnormalities in the area of the surgical scar after breast conserving surgery or mastectomy; abnormalities in the presence of breast implants; screening high-risk women, especially when MRI is not performed; loco-regional staging of a known breast cancer, when MRI is not performed; guidance for percutaneous interventions (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring patients with breast cancer receiving neo-adjuvant therapy, when MRI is not performed. Possible indications such as supplemental screening after mammography for women aged 40–74 with dense breasts are also listed. Moreover, inappropriate indications include screening for breast cancer as a stand-alone alternative to mammography. The structure and organisation of the breast US report and of classification systems such as the BI-RADS and consequent management recommendations are illustrated. Information about additional or new US technologies (colour-Doppler, elastography, and automated whole breast US) is also provided. Finally, five frequently asked questions are answered. • US is an established tool for suspected cancers at all ages and also the method of choice under 40. • For US-visible suspicious lesions, US-guided biopsy is preferred, even for palpable findings. • High-risk women can be screened with US, especially when MRI cannot be performed. • Supplemental US increases cancer detection but also false positives, biopsy rate and follow-up exams. • Breast US is inappropriate as a stand-alone screening method.

We have generated a Xenopus laevis transgenic line, MBP-GFP-NTR, allowing conditional ablation of myelin-forming oligodendrocytes. In this transgenic line the transgene is driven by the proximal portion of the myelin basic protein regulatory sequence, specific to mature oligodendrocytes. The transgene protein is formed by the green fluorescent protein reporter fused to the Escherichia coli nitroreductase (NTR) selection enzyme. The NTR enzyme converts the innocuous prodrug metronidazole (MTZ) to a cytotoxin. Ablation of oligodendrocytes by MTZ treatment of the tadpole induced demyelination, and here we show that myelin debris are subsequently eliminated by microglial cells. After cessation of MTZ treatment, remyelination proceeded spontaneously. We questioned the origin of remyelinating cells. Our data suggest that Sox10+ oligodendrocyte precursor cells (OPCs), which are already present in the optic nerve prior to the experimentally induced demyelination, are responsible for remyelination, and this required only minimal (if any) cell division of OPCs.

Contains fulltext : 177890.pdf (Publisher’s version ) (Open Access) EUSOBI and 30 national breast radiology bodies support mammography for population-based screening, demonstrated to reduce breast cancer (BC) mortality and treatment impact. According to the International Agency for Research on Cancer, the reduction in mortality is 40 % for women aged 50-69 years taking up the invitation while the probability of false-positive needle biopsy is

The phagocyte NADPH oxidase Nox2 generates superoxide ions implicated in the elimination of microorganisms and the redox control of inflammatory signaling. However, the role of Nox2 in phagocyte functions unrelated to immunity or pathologies is unknown. During development, oriented cell migrations insure the timely recruitment and function of phagocytes in developing tissues. Here, we have addressed the role of Nox2 in the directional migration of microglial cells during development. We show that microglial Nox2 regulates the chemotaxis of purified microglia mediated by the colony stimulating factor-1 receptor (CSF-1R) and the vascular endothelial growth factor receptor-1 (VEGFR1). Stimulation of these receptors triggers activation of Nox2 at the leading edge of polarized cells. In the early postnatal stages of mouse brain development, Nox2 is activated in macrophages / microglial cells in the lateral ventricle or the adjacent subventricular zone (SVZ). Fluorescent microglia injected into the lateral ventricle infiltrate the dorso-caudal SVZ through a mechanism that is blocked by pretreatment of the injected cells with an irreversible Nox inhibitor. Infiltration of endogenous microglia into the caudal SVZ of the cerebral cortex is prevented by (1) Nox2 gene deficiency, (2) treatment with a Nox2 inhibitor (apocynin), and (3) invalidation of the VEGFR1 kinase. We conclude that phagocytes move out of the lateral ventricle soon after birth and infiltrate the cortical SVZ through a mechanism requiring microglial Nox2 and VEGFR1 activation. Nox2 therefore modulates the migration of microglia and their development.

The time has come to individualize radiation prescriptions on the basis of individual response rather than on population averages of organ tolerance.

Mammographic density assessed at full-field digital mammography by using Breast Imaging Reporting and Data Systems (BI-RADS) classification and semiautomatic and fully automatic computer-assisted methods was significantly associated with breast cancer risk; radiologist-assigned BI-RADS density categorization was as accurate as computer-assisted methods for discrimination of patients with breast cancer from control subjects.

Mobile phone communications are conveyed by radiofrequency (RF) electromagnetic fields, including pulse-modulated global system for mobile communications (GSM)-1800 MHz, whose effects on the CNS affected by pathological states remain to be specified. Here, we investigated whether a 2-h head-only exposure to GSM-1800 MHz could impact on a neuroinflammatory reaction triggered by lipopolysaccharide (LPS) in 2-week-old or adult rats. We focused on the cerebral cortex in which the specific absorption rate (SAR) of RF averaged 2.9 W/kg. In developing rats, 24 h after GSM exposure, the levels of cortical interleukin-1s (IL1s) or NOX2 NADPH oxidase transcripts were reduced by 50 to 60%, in comparison with sham-exposed animals (SAR = 0), as assessed by RT-qPCR. Adult rats exposed to GSM also showed a 50% reduction in the level of IL1s mRNA, but they differed from developing rats by the lack of NOX2 gene suppression and by displaying a significant growth response of microglial cell processes imaged in anti-Iba1-stained cortical sections. As neuroinflammation is often associated with changes in excitatory neurotransmission, we evaluated changes in expression and phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the adult cerebral cortex by Western blot analyses. We found that GSM exposure decreased phosphorylation at two residues on the GluA1 AMPAR subunit (serine 831 and 845). The GSM-induced changes in gene expressions, microglia, and GluA1 phosphorylation did not persist 72 h after RF exposure and were not observed in the absence of LPS pretreatment. Together, our data provide evidence that GSM-1800 MHz can modulate CNS cell responses triggered by an acute neuroinflammatory state.

Background In the United States, the Agency for Healthcare Research and Quality (AHRQ) has developed 20 Patient Safety Indicators (PSIs) to measure the occurrence of hospital adverse events from medico-administrative data coded according to the ninth revision of the international classification of disease (ICD-9-CM). The adaptation of these PSIs to the WHO version of ICD-10 was carried out by an international consortium. Methods Two independent teams transcoded ICD-9-CM diagnosis codes proposed by the AHRQ into ICD-10-WHO. Using a Delphi process, experts from six countries evaluated each code independently, stating whether it was “included”, “excluded” or “uncertain”. During a two-day meeting, the experts then discussed the codes that had not obtained a consensus, and the additional codes proposed. Results Fifteen PSIs were adapted. Among the 2569 proposed diagnosis codes, 1775 were unanimously adopted straightaway. The 794 remaining codes and 2541 additional codes were discussed. Three documents were prepared: (1) a list of ICD-10-WHO codes for the 15 adapted PSIs; (2) recommendations to the AHRQ for the improvement of the nosological frame and the coding of PSI with ICD-9-CM; (3) recommendations to the WHO to improve ICD-10. Conclusions This work allows international comparisons of PSIs among the countries using ICD-10. Nevertheless, these PSIs must still be evaluated further before being broadly used.

Individual response to ionizing radiation is an important information required to apply an efficient radiotherapy treatment against tumour and to avoid any adverse effects in normal tissues. In 1981, Fertil and Malaise have demonstrated that the post-irradiation local tumor control determined in vivo is correlated with clonogenic cell survival assessed in vitro. Furthermore, these authors have reminded the relevance of the concept of intrinsic radiosensitivity that is specific to each individual organ (Fertil and Malaise, 1981) [1]. To date, since clonogenicity assays are too time-consuming and do not provide any other molecular information, a plethora of research groups have attempted to determine the molecular bases of intrinsic radiosensitivity in order to propose reliable and faster predictive assays. To this aim, several approaches have been developed. Notably, the recent revolution in genomic and proteomic technologies is providing a considerable number of data but their link with radiosensitivity still remains to be elucidated. On another hand, the systematic screening of some candidate genes potentially involved in the radiation response is highlighting the complexity of the molecular and cellular mechanisms of DNA damage sensoring and signalling and shows that an abnormal radiation response is not necessarily due to the impairment of one single protein. Finally, more modest approaches consisting in focusing some specific functions of DNA repair seem to provide more reliable clues to predict over-acute reactions caused by radiotherapy. In this review, we endeavoured to analyse the contributions of these major approaches to predict human radiosensitivity.

Background Since July 1, 2006 bone mineral density (BMD) testing has been reimbursed for osteoporosis screening under specific clinical conditions in France. Concurrently, drug coverage has been extended to all anti-osteoporotic treatments in women with low BMD. It was thus expected that the utilisation of BMD testing and subsequent treatment would increase significantly. Objective To examine the pattern of use of BMD testing following reimbursement by the French National Health Insurance and subsequent prescriptions reimbursed for anti-osteoporotic treatment in the general population of the Rhone-Alpes area, France. Methods Time trends, age and sex distribution of the population, and specialty of the physicians who performed the test were examined from all physicians’ claims for BMD testing between 2006 and 2009 in Rhone-Alpes. A prospective inception cohort of all women aged 50 years and older, without prior reimbursement for anti-osteoporotic treatment and who had a BMD test between January 1, 2007 and March 31, 2007, was then created. Women were followed for 1 year for their reimbursements of estrogen or other anti-osteoporotic treatment (bisphosphonates, raloxifene, teriparatide and strontium ranelate) after their initial BMD test. Results Between July 2006 and August 2009, 140,038 BMD tests were reimbursed in Rhone-Alpes, France, among which 94.8% were performed in women aged 50 years and older. In women, the number of BMD tests tended to significantly decrease during the study period ( p for trend = 0.047). The inception cohort was composed of 9635 women without prior anti-osteoporotic treatment. Among women without prior estrogen treatment, 27.3% ( n = 2339) initiated an anti-osteoporotic treatment within 4 months after a BMD test, mostly with bisphosphonates (16.8% n = 1441), followed by strontium ranelate (5.8% n = 498) and raloxifene (3.4% n = 290). At 1 year 1702 women (71.7%) were still on treatment. Conclusion Following the decision by the French National Health Insurance of repayment of BMD measurement, the proportion of women who had BMD testing tended to decrease instead of increase over the time period. Although BMD screening is focused in France on high risk women, only 25% of those who had an initial BMD test were subsequently treated with an anti-osteoporotic medication.

Advanced glycation end products (AGEs) are thought to play a central role in the pathogenesis of diabetes complications. For this reason, a non-invasive tool using skin autofluorescence (AF) quantification that correlates with levels of tissue AGEs has been developed. The present study aimed to assess whether or not skin AF is associated with microvascular complications in patients with type 1 diabetes (T1D).All consecutive patients with T1D (n=133) had three AF measures taken on the forearm, using illumination with a fluorescent tube, all on the same day after breakfast or lunch. Potential associations between skin AF levels and microvascular complications, age, diabetes duration and health status were then assessed using a multivariate linear-regression model.On age-adjusted analyses, diabetes duration, retinopathy, nephropathy and neuropathy were significantly associated with skin AF levels (all P0.001). AF levels increased significantly with severity in both retinopathy and nephropathy (P0.001). After adjusting for age, diabetes duration, HbA(1c), smoking, retinopathy, nephropathy and neuropathy, the association of AF levels remained significant with nephropathy and neuropathy, but not with retinopathy and diabetes duration.This study suggests an independent association between skin AF levels and diabetic nephropathy and neuropathy, but not retinopathy, in T1D patients. Prospective studies are needed to confirm the ability of skin AF levels to predict microangiopathy.

We estimated the excess hospital expenditure attributable to osteoporotic hip fracture (HF) within a population of 6,019 patients. Post-fracture excess of hospital days was 23.1, including 22.7 days in rehabilitation care. HF might result from a patient's pre-fracture poor health status rather than predispose to a worsening of such pre-existing conditions.Hip fracture represents a large burden on hospital services. It is unclear whether the post-fracture expenditure is linked to a worsening of pre-fracture comorbid conditions. We estimated the excess hospital expenditure attributable to osteoporotic HF following the initial hospitalization for acute care (index stay).We identified 6,019 patients (or = 50 years) who experienced HF in 2005 and compared their hospitalizations 1 year before and 1 year after the index stay. Excess expenditure was estimated by subtracting the utilization of hospital days or costs (Euros 2005) before the index stay from those after the index stay. Factors associated with hospitalization during the pre-fracture and post-fracture years were identified using multivariate logistic regressions.Beside the index stay, post-fracture excess of hospital days was 23.1 (95% Confidence Interval (CI) [21.8-24.3]), including 22.7 days (95% CI [21.7-23.7]) in rehabilitation care and 0.3 days (95% CI [0-0.9]) in acute care. Estimated excess cost per patient waseuro5,986 (95% CI [5,638-6,335]) after the index stay, includingeuro5,673 (95% CI [5,419-5,928]) in rehabilitation care. Male and elderly patients were at higher risk to be hospitalized in acute care during the year preceding and succeeding HF.Osteoporotic HF represents a pronounced excess expenditure in hospital, which is mostly linked to rehabilitation care. Considering that utilization of inpatient acute care was quite similar before and after the index stay, HF might result from a patient's pre-fracture poor health status, rather than predispose to a worsening of such pre-existing conditions.

Background A control chart can help to interpret and reduce sources of variability in patient safety by continuously monitoring indicators. The aim of this study was to monitor the outcome of thyroid surgery using control charts. Methods Patients who had thyroid surgery during 2006–2007 were included in the study. Safety was monitored based on postoperative complications of recurrent laryngeal nerve palsy and hypocalcaemia. Indicators were extracted prospectively from the hospital information system and plotted each month on a P-control chart. Performance of the surgical team was also measured retrospectively for 2004–2005 (baseline period) to compare surgical outcomes before and after control chart implementation. Electromyographic monitoring of recurrent laryngeal nerves was not used, nor was calcium or vitamin D given routinely. Results The outcomes of 1114 thyroid procedures were monitored. Although the proportion of patients with recurrent laryngeal nerve palsy was similar for baseline and monitored periods (6·4 and 7·2 per cent respectively), there was a 35·3 per cent decrease in hypocalcaemia after implementation of control charts (P < 0·001). Complications almost doubled during a period when one surgeon was away and operating room renovations took place. Conclusion Outcome monitoring in thyroid surgery using control charts is useful for identifying potential issues in patient safety.

There was 75% variation in the trend in hip fracture incidence with age in women aged 50 to 85 in France. In southwest France, the women are at higher risk of hip fracture at younger ages. This finding should be taken into account when examining risk factors. Few studies have analysed the geographical variations in the relationship between age and hip fracture incidence. Our goal was to assess these variations among women under 85 within the same country. The study population included women aged 50 to 85 who were living in France in 2004. Hip fracture cases were identified in the French Diagnosis Related Groups (DRG)-like database using the diagnosis code for closed hip fractures and procedural codes for treatment. The Moran index and a spatial model using latitude and longitude were used to assess the geographical heterogeneities of cumulative incidence risk (CIR) and age effect. A total of 29,218 hip fracture cases were identified. A south-to-north CIR gradient ranging from 7 to 16% was observed. The variation in the number of years until double hip fracture incidence was 75% (i.e. 1.49 to 2.57 years). In the south, and more markedly in southwest France, the women are at higher risk of hip fracture at a younger age. The risk of fracture may be different between women of the same age. This may be hidden in a comparison of standardised ratios. This finding should be considered when examining risk factors and implementing public health interventions.

BACKGROUND The conditions of use and access to medical records have become an important source of interest in the last decade. In this context, our main objective was to assess the impact of a paper patient-held records, shared with healthcare professionals. METHODS In the particular case of breast cancer management, we identified the expectations of practitioners and patients. Secondly and according to a Delphi method, we defined the content and size of a medical record, which could be held by the patient. Following these preliminary studies, we conducted a randomized controlled trial, comparing patients with usual follow-up to others holding the new record containing essential information for coordination of care. RESULTS The patient-held record favoured membership and satisfaction of both patients and health professionals. It was used as a communication tool between physicians and patients, but could also cause anxiety to some patients. Patient quality of life, data confidentiality and costs of care remained identical in the two arms. With its benefits for both patients and healthcare professionals, a new concept of medical records was revealed by this study. CONCLUSION New models for healthcare organization deeply modify the roles and relationships of all the actors in the healthcare system. Further research on patient-held records is needed to evaluate the full range of its benefits and limits.

To assess the prescription patterns of anti-osteoporosis medications, three cross-sectional analyses were performed between 2004 and 2006. Women aged 50 and older were identified from the health insurance claims database of the Rhone-Alpes area. HRT prescriptions decreased while bisphosphonates and raloxifene prescriptions increased, respectively, in different age groups. The objective of this study was to assess the prescription patterns of hormone replacement therapy (HRT) and anti-osteoporosis medications (AOM) in post-menopausal French women since the WHI and the revision of the French clinical practice guidelines in 2004. Three cross-sectional analyses were performed between 2004 and 2006. Women aged 50 and older who had at least one claim for a prescription for HRT, bisphosphonates or raloxifene were identified from health insurance claims database of the Rhone-Alpes area. A 39% decrease in the number of women who had HRT was observed (67,241 to 41,024). Twenty-one percent and 18% increases were observed, respectively, for bisphosphonates (39,192 to 47,395) and raloxifene (10,263 to 12,060). HRT and raloxifene were mainly prescribed to women aged 55 to 64 (58% and 39%, respectively), bisphosphonates to women aged 65 to 84 (70%). Ninety-eight percent of women had HRT prescribed by a gynaecologist or a general practitioner (GP). Most AOM were prescribed by a GP; 13% of women had AOM prescribed by a rheumatologist. Prescriptions for HRT in post-menopausal French women have significantly decreased while bisphosphonates and raloxifene prescriptions have increased, respectively, in different age groups but to a lesser extent than the HRT decrease.

Backgrounds Since 2001, the French national case mix program is allowed by law to use an enciphering algorithm named “FOIN” to produce a unique anonymous identifier in order to crosslink, within and across hospitals, discharge abstracts from a given patient. This algorithm “thrashes” the person's health insurance number, date of birth and gender. Before using information produced by the case mix program, either for case mix payment or for epidemiology research or for assessing care approaches, the quality of linkage must be evaluated. Methods Foin error flags were first assessed in the 2002 Rhone-Alpes regional case mix database. Second, for the two university hospitals of Lyon and Saint-Etienne, double identifiers (two or more Foin identifiers for the same patient) and collisions (a single Foin identifier for at least two patients) were compared with others identifiers: administrative identifier and an anonymous identifier produced by Anonymat® software from name, forename and date of birth. Third, Foin error flags are crossed with Foin double identifier or collision mistakes. Results First, among 1 668 971 hospital discharge abstracts from the regional case mix database, 206 710 (12.4%) had at least one Foin error flag. The most frequent error flag (93 026 [5.5%] stays) was due to the lack of the three identifying variables. The greatest number for error flags concerned the stays of newborns (38.5%) and those of public hospitals (17.3%). Second, Foin created a few double identifiers: 1.2% among 137 236 patients from university hospital of Lyon and 0.3% among 39 512 patients from university hospital of Saint-Etienne. The collisions concerned 7776 (5.7%) patients from Lyon and 460 (1.2%) from Saint-Etienne. The identifier produced by Anonymat performed better than the one produced by Foin: 99.6% from the two university hospitals. Third, less than 3% of stays without Foin error flag nevertheless had mistakes on Foin when compared with others identifiers. Conclusion The overall assessment is not in favour of a quality threshold using the Foin identifier on a routine basis except in some areas and if certain activities like neonatology are excluded. There are several ways to improve the linkage of health data.

Because senile plaques in Alzheimer's disease (AD) contain reactive microglia in addition to potentially neurotoxic aggregates of amyloid-β (Aβ), we examined the influence of microglia on the viability of rodent neurons in culture exposed to aggregated Aβ 1–40. Microglia enhanced the toxicity of Aβ by releasing glutamate through the cystine-glutamate antiporter system Xc−. This may be relevant to Aβ toxicity in AD, because the system Xc−-specific xCT gene is expressed not only in cultured microglia but also in reactive microglia within or surrounding amyloid plaques in transgenic mice expressing mutant human amyloid precursor protein or in wild-type mice injected with Aβ. Inhibition of NMDA receptors or system Xc−prevented the microglia-enhanced neurotoxicity of Aβ but also unmasked a neuroprotective effect of microglia mediated by microglial secretion of apolipoprotein E (apoE) in the culture medium. Immunodepletion of apoE or targeted inactivation of the apoE gene in microglia abrogated neuroprotection by microglial conditioned medium, whereas supplementation by human apoE isoforms restored protection, which was potentiated by the presence of microglia-derived cofactors. These results suggest that inhibition of microglial system Xc−might be of therapeutic value in the treatment of AD. Its inhibition not only prevents glutamate excitotoxicity but also facilitates neuroprotection by apoE.

Objectives. To assess the accuracy and interobserver variability of T 2 -weighted (T 2 W) and contrast-enhanced dynamic (CE-Dyn) magnetic resonance imaging (MRI) in predicting the results of transrectal biopsy in patients with suspected recurrent prostate cancer after external beam radiotherapy. Methods. A total of 22 patients with increasing prostate-specific antigen levels after external beam radiotherapy for prostate cancer underwent T 2 W and CE-Dyn MRI of the prostate. The CE-Dyn sequence (acquisition time 30 seconds) was repeated three times after the injection of gadolinium. All patients underwent subsequent transrectal biopsy. Three independent readers interpreted the MRI scans. The MRI and biopsy results were correlated in 10 prostate sectors (the sextants of the peripheral zone, the two transitional zones, and the two seminal vesicles). Results. Biopsy cores were obtained in 147 prostate sectors. Of these, 63 were positive for cancer in 19 patients. On the T 2 W images, the three readers interpreted as positive for cancer 15, 15, and 13 of the 19 patients showing cancer at biopsy. They interpreted as negative 3, 0, and 1 of the 3 patients showing no cancer at biopsy. On CE-Dyn images, the three readers correctly classified all the patients as positive or negative for cancer. The T 2 W and CE-Dyn MRI findings were concordant with biopsy results in, respectively, 81 to 95 and 107 to 117 prostate sectors (P

The loss of neuronal cells, a prominent event in the development of the nervous system, involves regulated triggering of programmed cell death, followed by efficient removal of cell corpses. Professional phagocytes, such as microglia, contribute to the elimination of dead cells. Here we provide evidence that, in addition to their phagocytic activity, microglia promote the death of developing neurons engaged in synaptogenesis. In the developing mouse cerebellum, Purkinje cells die, and 60% of these neurons that already expressed activated caspase-3 were engulfed or contacted by spreading processes emitted by microglial cells. Apoptosis of Purkinje cells in cerebellar slices was strongly reduced by selective elimination of microglia. Superoxide ions produced by microglial respiratory bursts played a major role in this Purkinje cell death. Our study illustrates a mammalian form of engulfment-promoted cell death that links the execution of neuron death to the scavenging of dead cells.

La radiosensibilite individuelle est un phenomene, decouvert il y a un siecle, que des methodes modernes d’investigation par immunofluorescence de cibles de la signalisation et de la reparation des lesions de l’ADN permettent d’evaluer et de quantifier. Parce que la radiosensibilite peut varier d’un facteur 1 a 10 selon les individus, et que 5 a 15 % de la population serait plus radiosensible, ce phenomene pose une question de sante publique et devrait etre pris en compte par le systeme de radioprotection.

Difficulties and disagreements in pathologic interpretation and classification of intraductal proliferative lesions, as well as in diagnosing microinvasion, should be considered as potential sources of overdiagnosis.

The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.

In the central nervous system (CNS), nitric oxide (NO) is thought to be involved in a variety of functions including synaptic plasticity, long term potentiation, and neurotoxicity. The aim of the present study was to investigate the expression of nitric oxide synthase (NOS) in the mouse CNS, following surgical injury to the hippocampus. NOS expression was assessed by histochemical detection of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-diaphorase) activity and immunohistochemistry of the inducible NOS (iNOS). Two days after injury to the CA1 hippocampal field, NADPH-diaphorase activity was detected in pyramidal and granular neurons and also in glial cells in the hippocampus, in contrast to the non-injured one where NADPH-diaphorase staining was observed only in a few interneurons. NADPH-diaphorase histochemistry combined with immunolabelling for GFAP and F4/80 demonstrated that these glial cells were astrocytes and microglia. This pattern of NOS expression is induced specifically after a hippocampal injury since lesion to the prefrontal or cerebellar cortex leads to NOS activity only in monocytes/macrophages like cells. Despite the large expression of NOS detected by NADPH-diaphorase histochemistry after lesioning the hippocampus, immunostaining for iNOS was confined to microglia. The fact that induction of high levels of NOS activity are detected in glial cells after a lesion to the hippocampus could be accounted for by the sensitivity of this structure to a high release of glutamate.

International audience; Because patients with Hodgkin disease are also candidates for repeat scanning with body CT and/or PET/CT, the importance of optimizing acquisition parameters by using all breast irradiation imaging technologies must be highly considered.

Women with high risk of breast or ovarian cancers might be more susceptible to radiation-induced cancer because most of tumor suppressor genes are also implicated in the radio-induced DNA damage repair and signaling. Recent radiobiological advances may help to re-consider the potential cellular and molecular consequences of the standard two-view mammographic screening. A major radiobiological effect exacerbated in high family risk women caused by mammographic repeated doses was pointed out on relevant cellular model (untransformed and non tumoral human breast epithelial cells): the Low and Repeated Dose (LORD) effect. In parallel, while magnetic resonance imaging (MRI) is reported to be less sensitive than mammography for detection of ductal carcinoma in situ, a recent study highlighted the increased ability of MRI to detect them related to the experience both of radiologists and MRI centers. Hence, along with studies confirming improvement of the sensitivity of MRI to detect ductal carcinoma in situ, the supra-additivity effect induced by the two-view mammographic screening in high family risk patients suggests that mammographic exposures can be limited seriously. Consequently, a single view (oblique) per breast in association with annual MRI, with the sole aim to detect calcifications reflecting carcinoma in situ non detectable by MRI, might represent currently a compromise.

International audience; Purpose: To assess in vitro mammographic radiation-induced DNA damage in mammary epithelial cells from 30 patients with low (LR) or high (HR) family risk of breast cancer. Materials and methods: Spontaneous and radiation-induced DNA double-strand breaks (DSB) were quantifi ed by using immunofl uorescence of the phosphorylated H2AX histone ( γ H2AX) in diff erent conditions of mammography irradiation (2, 4, 2 2 mGy). Results: HR patients showed signifi cantly more spontaneous γ H2AX foci than LR patients ( p 0.014). A signifi cant dose-eff ect was observed, with an exacerbation in HR patients ( p 0.01). The dose repetition (2 2 mGy) provided more induced and more unrepaired DSB than 2 mGy and 4 mGy, and was exacerbated in HR ( p 0.006). Conclusions: This study highlights the existence of DSB induced by mammography and revealed by γ H2AX assay with two major radiobiological eff ects occurring: A low-dose eff ect, and a LOw and Repeated Dose (LORD) eff ect. All these eff ects were exacerbated in HR patients. These fi ndings may lead us to reevaluate the number of views performed in screening using a single view (oblique) in women whose mammographic benefi t has not properly been proved such as HR patients.

Background Many authors advocate total or near-total thyroidectomy for thyroid carcinoma. This study examined the relationship between hospital volume of thyroidectomies and choice of bilateral thyroidectomy for thyroid carcinoma. Methods Data were extracted from the administrative databases of all hospital discharge abstracts in the Rhône-Alpes area of France. The study population included inpatient stays from 1999 to 2004 with a diagnosis of thyroid disease (benign or malignant) and a procedural code for thyroid surgery. Multivariable logistic regression analyses were performed to determine factors associated with the extent of surgery (unilateral versus bilateral) for thyroid carcinoma. Results A total of 20 140 thyroidectomies were identified, including 4006 procedures for cancer. Compared with hospitals performing a high volume of procedures for all thyroid diseases (at least 100 annually), the risk of a unilateral procedure for thyroid cancer increased by 2·46 (95 per cent confidence interval 1·63 to 3·71) in low-volume hospitals (fewer than ten operations per year) and by 1·56 (1·27 to 1·92) in medium-volume centres (ten to 99 per year). Conclusion There is a significant relationship between hospital volume and the decision to perform bilateral surgery for thyroid carcinoma. Thyroid cancer surgery should be performed by experienced surgical teams in high-volume centres.

Before electronic records become operational, patient-held records provide an opportunity to improve communication between patients and healthcare professionals. Our aim was to design the appropriate organization, layout and content for such a shared record for breast cancer management, based on a consensus between the various stakeholders. We therefore conducted a Delphi study within a working group of 48 members, including patients, oncologists, general practitioners, nurses and other professionals. The procedure featured three rounds during which participants' judgements were collected via mailed questionnaires and quantitative and qualitative feedback was provided on a regular basis. These three rounds were followed by an evaluation phase. Forty members (83%) participated in the three rounds. According to the agreement reached, the shared record was expected to include a front summary card, four sections for groups of users authorized to write down or insert information in the record (patient, physicians, medical auxiliaries and other healthcare professionals), and one section for medical imaging files. In addition, the record was to include specific categories of information as subsections within each of the various user sections. The participant satisfaction rate was over 90% for all aspects of the procedure, with the exception of interaction within the working group (79%).

Reactive oxygen species (ROS) modulate intracellular signaling but are also responsible for neuronal damage in pathological states. Microglia, the resident CNS macrophages, are prominent sources of ROS through expression of the phagocyte oxidase which catalytic subunit Nox2 generates superoxide ion (O2·−). Here we show that microglia also express Nox1 and other components of nonphagocyte NADPH oxidases, including p22phox, NOXO1, NOXA1, and Rac1/2. The subcellular distribution and functions of Nox1 were determined by blocking Nox activity with diphenylene iodonium or apocynin, and by silencing theNox1gene in microglia purified from wild-type (WT) or Nox2-KO mice. [Nox1-p22phox] dimers localized in intracellular compartments are recruited to phagosome membranes during microglial phagocytosis of zymosan, and Nox1 produces O2·−in zymosan-loaded phagosomes. In microglia activated with lipopolysaccharide (LPS), Nox1 produces O2·−, which enhances cell expression of inducible nitric oxide synthase and secretion of interleukin-1β. Comparisons of microglia purified from WT, Nox2-KO, or Nox1-KO mice indicate that both Nox1 and Nox2 are required to optimize microglial production of nitric oxide. By injecting LPS in the striatum of WT and Nox1-KO mice, we show that Nox1 also enhances microglial production of cytotoxic nitrite species and promotes loss of presynaptic proteins in striatal neurons. These results demonstrate the functional expression of Nox1 in resident CNS phagocytes, which can promote production of neurotoxic compounds during neuroinflammation. Our study also shows that Nox1- and Nox2-dependent oxidases play distinct roles in microglial activation and that Nox1 is a possible target for the treatment of neuroinflammatory states.

Resume L’identification des femmes porteuses d’une mutation genetique ou d’une predisposition genetique suffisamment elevee pour etre assimilee a la premiere categorie, est determinante pour pouvoir induire une modification de la strategie de depistage. Compte tenu du risque cumule de cancer du sein et du vecu tres anxiogene des investigations chez ces patientes, le radiologue se doit d’optimiser le choix des technologies a disposition, le rythme des examens proposes et l’ordre chronologique de leur realisation. Les particularites tumorales et de croissance cellulaire connues chez les patientes mutees vont contribuer a elaborer ces modalites. Au travers des dernieres recommandations nationales publiees, d’une analyse critique de la litterature, de la revue des technologies recentes et des pratiques, les modalites de depistage sont exposees et commentees.

Hip fractures are responsible for excessive mortality, decreasing the 5-year survival rate by about 20%. From an economic perspective, they represent a major source of expense, with direct costs in hospitalization, rehabilitation, and institutionalization. The incidence rate sharply increases after the age of 70, but it can be reduced in women aged 70-80 years by therapeutic interventions. Recent analyses suggest that the most efficient strategy is to implement such interventions in women at the age of 70 years. As several guidelines recommend bone mineral density (BMD) screening of postmenopausal women with clinical risk factors, our objective was to assess the cost-effectiveness of two screening strategies applied to elderly women aged 70 years and older.A cost-effectiveness analysis was performed using decision-tree analysis and a Markov model. Two alternative strategies, one measuring BMD of all women, and one measuring BMD only of those having at least one risk factor, were compared with the reference strategy "no screening". Cost-effectiveness ratios were measured as cost per year gained without hip fracture. Most probabilities were based on data observed in EPIDOS, SEMOF and OFELY cohorts.In this model, which is mostly based on observed data, the strategy "screen all" was more cost effective than "screen women at risk." For one woman screened at the age of 70 and followed for 10 years, the incremental (additional) cost-effectiveness ratio of these two strategies compared with the reference was 4,235 euros and 8,290 euros, respectively.The results of this model, under the assumptions described in the paper, suggest that in women aged 70-80 years, screening all women with dual-energy X-ray absorptiometry (DXA) would be more effective than no screening or screening only women with at least one risk factor. Cost-effectiveness studies based on decision-analysis trees maybe useful tools for helping decision makers, and further models based on different assumptions should be performed to improve the level of evidence on cost-effectiveness ratios of the usual screening strategies for osteoporosis.

Summary Objective: In French national claims databases, claims are currently anonymous i.e. not linked to individual patients. In order to improve our estimate of the medical activity related to cancer in one French region, a statistical method was developed to use claims data to assess the number of cancer patients hospitalized in acute care. Methods: This method used the medical and administrative information available in the claims (i.e. age, primary site, length of stay) to predict an average number of stays per patient, followed by a number of patients. It was based on a two-phase study design using an internal dataset which contained personal identifiers to estimate the model parameters. Results: The predicted number of acute care patients hospitalized in one or several health care centers in one French region was 38,109 with a 95% predictive interval (37,990; 38,228) for the first six months of 2002. A prediction error of 24% was found. Conclusion: We provide a good estimate of the morbidity in acute care hospitals using claims data that is not linked to individual patients. This estimate reflects the medical activity and can be used to anticipate acute care needs.

This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy-naïve hormone-refractory prostate cancer.Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation.Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (or =50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent-to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patientsor =5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The impact of combined chemotherapy on the quality-of-life (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period.This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study.

Our objectives were to determine time-enhancement curves of prostate cancer, peripheral zone, and adenoma at gadolinium-enhanced MR imaging, and to determine if a high-spatial/low-temporal dynamic imaging could be accurate in depicting prostate cancer, or if a higher temporal resolution (and a lower spatial resolution) should be favored. Thirty-nine patients with prostate cancer underwent MR imaging before radical prostatectomy by using T1- and T2-weighted axial images and a single-slice dynamic gadolinium-enhanced sequence (40 images; one image per 6 s; injection of 20 ml at 2 ml/s). After analysis of the pathologic specimens, four region-of-interest (ROI) cursors (cancer, peripheral zone, adenoma, and muscle) were retrospectively placed on dynamic images. Time-enhancement curves of the ROIs were obtained. The theoretical accuracy of a 30-s dynamic multislice MR sequence in depicting cancer within peripheral zone and adenoma (ROC curves) was calculated from these curves. On average, prostate cancer enhanced more and earlier than peripheral zone and adenoma, but there were great interindividual variations. For start delays ranging from 12 to 84 s, the areas under the ROC curves ranged from 0.602 to 0.698 for the depiction of cancer within adenoma and from 0.614 to 0.827 for the depiction of cancer within peripheral zone. The best results were obtained with a 36-s start delay. In conclusion, we found a 30-s scanning window which seems to allow a good depiction of cancer within peripheral zone. Because of largely overlapping enhancement patterns, cancer will probably not be depicted within adenoma by dynamic imaging, at least by using low temporal resolution.

Estimations of the number of hospitalized incident cancer cases show biases when claims databases are used. This is due to false reports of incident cancer because of a lack of specificity, and because of unrecorded cancers resulting from a lack of sensitivity. We present a statistical method to provide corrected estimations. This method is based on a two-phase study design using an external data set for sensitivity and specificity estimates. Inaccuracy of the corrected number of hospitalized incident cancer cases was assessed by a credibility interval determined by a Bayesian approach using a Monte Carlo method. Based on the population hospitalized in a large group of French University hospitals, 334 women were identified in the French claims database as having potential incident cases of breast cancer in 1997. According to our method, the corrected number was 565 (550-580). In absence of hospital-based cancer registries, our approach provides estimates and credibility intervals, and has many potential applications in defining hospital policies with its applicability to other diseases.

To evaluate the accuracy of gadolinium-enhanced MRI in gauging the extent of the tissue damage induced by transrectal high intensity focused ultrasound (HIFU) therapy and to assess how well the results obtained with this modality correlate with histological findings (control biopsies).Twenty-one patients with biopsy-proven prostate cancer (T1-T2-T3a, Nx, M0) who gave informed consent were included in the protocol. They underwent pre- and postoperative (2-5 days after HIFU treatment) MR examinations. Fifteen patients also underwent a follow-up MR examination 1-5 months postoperatively. MR findings were compared with the results of postoperative transrectal biopsy examinations.The prostate volume increased after the HIFU session from 43.9+/-18.6 to 52.1+/-21 cm(3) by day 2 (p0.001). On fat-saturated gadolinium-enhanced T1-weighted images, the treated area appeared as a hypointense zone surrounded by a peripheral rim of enhancement in all patients. A positive correlation (r = 0.75) was found between the volume of the hypointense zone measured at days 2-5 (30+/-11 cm(3), 67% of the posttreatment prostate volume) and the theoretical target volume (22+/-5 cm(3), 61% of the initial prostate volume). MRI showed that the anterior part of the base was not reached by the ultrasound beam. The mean volume of the untreated zone (prostate without any MRI modifications) was 8 cm(3) (range, 0.4-36). No correlation was found between the MRI appearance of the treated area and the intensity of the necrosis or the presence of foci of residual, viable cancer.Gadolinium-enhanced MRI is an accurate way of determining the extent of tissue damage induced in HIFU ablative therapy, but cannot predict histological results.

Immunofluorescence that permits the detection of nuclear targets specific to DNA damage signalling and repair have completely renewed the approach of individual radiosensitivity. It is a concern in radiotherapy in which radiosensitivity is responsible for the development of adverse side-effects in normal tissues in absence of any mistake in the dose delivery. Furthermore, individual radiosensitivity at low-dose has been recently demonstrated in human mammary epithelium exposed ex vivo in the conditions of mammographic screening. Although these results do not demonstrate directly the existence of mutagenesis, they indicate a possible link between cancer proneness and radiosensitivity. Hence, individual radiosensitivity is a real concern for public health since 5-15% of the population may be concerned and radiosensitive individuals generally show higher cancer risk than the rest of the population. Thus, individual radiosensitivity is a key issue to be addressed in future recommendations of the radioprotection system.

The influence of an early chronic phenobarbital (PhB) exposure on local cerebral glucose utilization (LCGU) and on behavior was studied in the rat. The animals were treated from Postnatal Day 2 to Postnatal Day 35 by a daily injection of 50 mg/kg PhB or by saline and tested between 10 and 35 days for short-term effects of the drug on LCGU and between 70 and 90 days for long-term effects of PhB on LCGU and behavior. PhB induced short- and long-lasting reductions in the overall rates of LCGU in hippocampal and cerebellar areas, but no significant changes in LCGU in the different cell layers of these two cerebral areas. PhB also changed the pattern of maturation of the rates of LCGU as compared to control subjects. The barbiturate treatment induced a decrease in the exploratory behavior of PhB- as compared to saline-treated rats in the open field, as well as a significant 25% decrease in the rate of spontaneous alternation with delay. In addition, PhB-treated rats needed significantly more time than control animals to perform their trials in the nonrewarded T maze testing. However, the neonatal barbiturate exposure did not induce changes in performances of adult rats in the rewarded eight arm maze. The results of the present study show that there is no apparent correlation between the rates of energy metabolism in the hippocampus and the impairment of learning abilities of adult rats in behavioral tests related to the hippocampus.