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Background: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028). Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours.

Objectives: In cerebral small vessel disease, white-matter hyperintensities (WMH) and lacunes are both related to cognition. Still, their respective contribution in older people remains unclear. The purpose of this study is to assess the topographic distribution of lacunes and determine whether it has an impact on cognitive functions in a sample of non-disabled patients with age-related white-matter changes. Methods: Data were drawn from the baseline evaluation of the LADIS (Leucoaraioisis and Disability study) cohort of non-disabled subjects beyond 65 years of age. The neuropsychological evaluation was based on the Mini Mental Status Examination (MMSE), a modified Alzheimer Diseases Assessment Scale for global cognitive functions, and compound Z scores for memory, executive functions, speed and motor control. WMH were rated according to the Fazekas scale; the number of lacunes was assessed in the following areas: lobar white matter, putamen/pallidum, thalamus, caudate nucleus, internal/external capsule, infratentorial areas. An analysis of covariance was performed after adjustment for possible confounders. Results: Among 633 subjects, 47% had at least one lacune (31% at least one within basal ganglia). The presence of lacunes in the thalamus was associated with lower scores of MMSE (β = −0.61; p = 0.043), and worse compound scores for speed and motor control (β = −0.25; p = 0.006), executive functions (β = −0.19; p = 0.022) independently of the cognitive impact of WMH. There was also a significant negative association between the presence of lacunes in putamen/pallidum and the memory compound Z score (β = −0.13; p = 0.038). By contrast, no significant negative association was found between cognitive parameters and the presence of lacunes in internal capsule, lobar white matter and caudate nucleus. Conclusion: In non-disabled elderly subjects with leucoaraisosis, the location of lacunes within subcortical grey matter is a determinant of cognitive impairment, independently of the extent of WMH.

The aim of the study was to demonstrate the noninferiority of polyacrylamide hydrogel (PH) vs. polylactic acid (PLA) for the treatment of facial lipoatrophy in HIV-infected adults.A randomized, blinded, multicentre, noninferiority 96-week study was carried out. Patients with facial lipoatrophy were randomly assigned to receive intradermal injections with PH or PLA, and were blinded to the filler. The primary efficacy endpoint was patient satisfaction at week 48 assessed using a visual analogue scale score (VAS). Secondary efficacy end-points included cheek thickness and skin-fold, lipoatrophy grading and quality of life. Safety was assessed by the reporting of adverse events.A total of 148 patients were included in the study; 93% were men, the median age was 47 years, the median CD4 count was 528 cells/μL, and the median duration of antiretroviral therapy was 12 years. Mean VAS increased from 2.8 at baseline to 7.1 and 7.5 in the PLA and PH arms, respectively, at week 48 (P=0.0002 for noninferiority) and was sustained at week 96 (6.7 and 7.9 in the PLA and PH arms, respectively; P=0.003 for noninferiority). Cheek thickness and skin-fold increases and lipoatrophy improvement were similar in the two arms. Quality of life remained unchanged or improved depending on the questionnaire used. In injected patients, subcutaneous nodules emerged in 28 (41%) and 26 (37%) patients in the PLA and PH arms, respectively (P=0.73). Four patients in the PH arm developed severe inflammatory nodules, a median of 17 months after the last injection.PH and PLA have similar efficacies in the treatment of facial lipoatrophy, but PH may be associated with more delayed inflammatory nodules.

Previous studies have recommended that several repeat measurements of nuchal translucency (NT) be obtained to optimize sensitivity of the screening process. However, truncation is applied within the risk calculation for small NT measurements; therefore, repeating NT measurements in the lower range may be unnecessary. The aim of this study was to determine the optimal number of NT measurements and whether this is dependent on the initial value obtained.We simulated the expected distribution of sets of five repeat NT measurements and their corresponding likelihood ratios (LR) for a variety of crown-rump length (CRL) values at 11-14 weeks' gestation, based on the published mixture model for first-trimester NT measurements and on published data regarding NT measurement variability. The ratio between LR obtained from the highest and the initial measurement in each set were computed, with a ratio of 1 indicating that repeat measurements would have no effect on risk estimation. We calculated NT cut-offs below which a change in estimated LR would occur in fewer than 10% of cases if repeat measurements were obtained, and we tested this approach on a real first-trimester screening dataset.The simulations performed indicated that repeating NT measurements when the first NT obtained ranged between ≤ 0.9 and ≤ 1.6 mm at CRLs of 45 and 84 mm, respectively, is not useful. When applied to a real dataset, our approach allowed avoiding repetition of measurements in 47/165 cases (28%).Although there is some variability in NT measurements, repeat assessment is not useful to optimize screening performance for the smallest NT measurements due to lower truncation limits that are applied in risk calculation. Our study provides NT cut-off values, in relation to CRL, below which it appears that there is no need to repeat measurements once a good quality image has been obtained.

The recommended duration of pulmonary tuberculosis therapy is 6 months. For extrapulmonary tuberculosis, treatment duration depends on tuberculosis involvement and HIV status. The objective of this study was to describe the main characteristics of a cohort of extrapulmonary tuberculosis patients, to compare patients with a 6-month treatment to those with more than a 6-month treatment, and to analyze the compliance of medical centres with recommended duration of treatment.A retrospective cohort study of 210 patients with extrapulmonary tuberculosis was carried from January 1999 to December 2006 in two hospitals in the north-east of Paris. These patients were treated with quadruple therapy during two months, followed by dual therapy during 4 months (n=77) or more (n=66). The characteristics of each group were compared by uni- and multivariate analysis. The primary endpoint was the rate of relapse or treatment failure at 24-month follow-up after treatment completion.No relapse was observed after 24 months of follow-up after the end of treatment in the two groups. In univariate analysis, patients with lymph node tuberculosis were more often treated for 6 months than at other sites of tuberculosis (respectively 61% versus 40.9%; P=0.02); the decision of treatment duration was related to medical practices (79.2% treated 6 months in one hospital versus 20.7% in the other, P0.001); patients living in private residence were more often treated during 6 months than patients living in residence (24.2% versus 10.3%, P=0.042). In multivariate analysis, only hospital (P=0.046), sex (P=0.007) and private residence were significantly different in each group.A period of 6 months seems to be sufficient to treat extrapulmonary tuberculosis (except for neuromeningeal localization).

A case-control study was conducted to identify risk factors for Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients. Eleven cases of PCP were matched with 22 controls. Cases occurred a median of 18 months after transplantation, and none of the recipients was receiving prophylaxis. Univariate analysis showed that graft rejection, duration of steroid use, use of mammalian target of rapamycin (mTOR) inhibitors and lymphocytopenia at the time of prophylaxis discontinuation were risk factors for PCP. In the multivariate model, only graft rejection (OR 8.66, p 0.017) remained significantly associated with PCP. In patients with a history of graft rejection, PCP prophylaxis should be maintained, especially among those with lymphocytopenia.

Numerous studies investigating the efficacy of TNF-alpha antagonists in moderate-to-severe plaque-type psoriasis have been published. We present a graphic synthesis of efficacy data based on a systematic review of the published studies.The Medline, Embase and Cochrane Library bibliographic databases were searched for studies based on the following selection criteria: 1. Original studies, 2. Using infliximab, etanercept or adalimumab as the sole systemic treatment for plaque-type cutaneous psoriasis, 3. Minimum follow-up of 10 weeks, 4. Use of the PASI75 index (improvement of at least 75% from baseline PASI score) as an endpoint. Twenty-one articles were selected and PASI75 scores and corresponding 95% confidence intervals were calculated at three, six and 12 months.At M3, success rates were about 80% with infliximab and adalimumab once-weekly, around 50% with etanercept 50mg twice-weekly and adalimumab fortnightly; and 30% with etanercept 25mg twice-weekly. Maintenance regimens after three months ensured success rates above 50% with all three treatments, although the long-term results were based on fewer studies.Our graphic synthesis and tolerance data for the three drugs should guide clinicians in their therapeutic choices in moderate-to-severe plaque-type psoriasis. Additional studies with better reporting of loss to follow-up are needed to better assess the long-term efficacy of these drugs.

Thresholds of sperm parameters associated with intrauterine insemination (IUI) success are controversial. This entails heterogeneous practices and leads to low success rate (approximately 8% per attempt). The aim of this study was to evaluate the influence of sperm parameters on the outcome of IUI.This study included 248 cycles of IUI. Parameters of the raw and selected sperm, as well as the main female characteristics, have been prospectively tabulated and compared, according to the presence or not of a clinical pregnancy.In all, 28 clinical pregnancies were obtained (11.3% per cycle). Thresholds of 10% for the forward motility "a" in the whole sperm and of 20% for the percentage of typical spermatozoa in the selected sperm were related to the success of IUI. The number of motile inseminated spermatozoa, concentration and overall motility of sperm, determined before or after selection, did not have any significant influence on the outcome of IUI.Thresholds determined in our study should help to optimize the use of IUI.

Study A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON ® TB Gold In-tube, QF–TB–IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital. Patients Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry. Results Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case. Conclusion This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.

Multiple embryo transfer is responsible for a high rate of multiple pregnancies (ICSI), with subsequent risks of premature birth and perinatal death. This prospective non randomized study aimed to assess the ability of an elective single-embryo transfer (eSET) policy to reduce the twin pregnancy rate, compared to a double embryo transfer (DET) approach.Between March 2005 and May 2006, 180 eligible women were proposed to benefit from an eSET transfer rather than a DET. Inclusion criteria were (i) age less than 37 years old; (ii) at least two good quality embryos available (three to five cells at day 2 or six to nine cells at day 3; less than 20% fragmentation and the absence of multinucleates blastomeres), after IVF or ICSI and (iii) no more than one previous failed treatment cycle. Outcome analysis included cycles with frozen-thawed embryo transfer (FET).According to patients' decision, 107 and 73 women had an eSET (59.4%) and a DET (40.6%) respectively. No differences were found between eSET and DET groups regarding demographics and biologicals parameters. The clinical pregnancy rate (PR) per transfer was 43.9% in eSET group and 57.5% in DET group (p=0.07). The twin pregnancy rates were 0 and 14.3%, in eSET and DET groups, respectively (p=0.007). The cumulative PR per patient, including the outcome of performed FET cycles, was 63.6% in eSET group and 61.6% in DET group. In this case, the cumulative twin pregnancy rates were 2.9 and 15.6% in eSET and DET groups, respectively (p=0.02).Our data show that in a selected population of women, transferring one fresh embryo and then, if required, one or two frozen-thawed embryos significantly reduces the twin pregnancy rate without decreasing the overall pregnancy rate. This study supports the policy of eSET in this subgroup of patients.

Tuberculosis (TB) is a persistent public health problem in European cities. France has been unable to report on treatment outcomes until now, and it is not known whether the World Health Organization (WHO) target cure rate of 85% has been met.All patients placed under treatment in four hospitals and five out-patient Social Medical Centres in Paris were followed up between 1996 and 2005. Patient monitoring and evaluation were performed using a new software programme, TB-INFO.In a cohort of 1127 patients, 76% had pulmonary TB, of whom 39% were smear-positive, 81% were foreign-born and 9.3% were human immunodeficiency virus positive. At the end of the follow-up, 16% were cured and 54% had completed treatment. Among the 1118 non-multidrug-resistant patients, these percentages were 17% and 46%, respectively, for smear-positive pulmonary patients. Some patients died (1.9%) or failed treatment (0.1%), but many more defaulted (20.5%) as they interrupted treatment (1.5%), were lost to follow-up (19.5%) or were transferred out (7.9%).This 10-year follow-up of TB patients, managed with TB-INFO software, shows that a patient monitoring system can be implemented in France, providing essential information. Treatment success in this cohort of patients was far below the WHO target.

To describe management of vaginal mesh erosion following transvaginal repair of acystocele by placement of a polypropylene mesh.Retrospective analysis of 34 consecutive cases of vaginal mesh erosion following transvaginal repair of cystocele using synthetic mesh (Gynemesh or Gynemesh-Soft). We have analyzed the results of both medical and surgical management of this complication. Furthermore, we also assessed sexual and urinary morbidity in women with mesh erosion (n = 34) and in women who had undergone the same procedure but without mesh erosion (n = 111).Among the 34 patients with vaginal mesh erosion, 23 (68%) have undergone local therapy using Colposeptine (Chlorquinaldol + Promestriène). In 12 (52%) cases no modification of the surface of the erosion was observed. In 6 (26%) cases, a decrease of the surface of the mesh erosion was observed. In 5 (22%) cases the mesh erosion had completely disappeared, with a follow-up of 2 to 9 months. Nineteen symptomatic patients (19/32, 59%) required partial (n = 18) or complete (n = 1) excision of the mesh, associated with vaginal mucosal closure, under general anaesthesia. Duration of operation ranged from 15 to 40 minutes for partial excision of the mesh. This procedure was successful in 14 cases (77%). Four women required repeated resection of the mesh because of recurrence. The incidence of de novo dyspareunia was 12% in patients with vaginal mesh erosion, and 11% in patients without mesh erosion (p = 0.81). The incidence of urge urinary symptoms and voiding dysfunction symptoms was respectively 8% versus 9% (p = 0.95), and 8% versus 10% (p = 0.81) in the 2 groups.Management of vaginal mesh erosion is simple and is associated with a low rate of morbidity. However, patients should be informed that vaginal erosion of the mesh can occur.

Five years after introducing the Permanent Access to Healthcare activity (PASS), it became necessary to analyse how it works.A computerized data collection and assessment system intended to evaluate the PASS health activities has been set up in 11 University Hospitals and ten General Hospitals. From January 1st to June, 30th 2003 data was captured in a computer.The patients requiring medical advice are young (with an average age of 35 years) and present several signs of poverty in terms of accommodation, social relationships and financial means. Besides, almost all of them are uninsured. The PASS public corresponds completely to the created system. Poverty risk factors vary according to the geographic origin. Indeed, French people often suffer from isolation, whereas foreign patients present financial problems. The major part of patients are foreigners and more than a third of them do not speak French, which is an additional obstacle to care. Most of the time, the PASS patients present digestive disorders, nevertheless there are some differences between French and foreign patients. Indeed, foreigners very frequently have digestive and osteoarticluar problems, whereas French patients suffer from psychic disorders and present addictive behaviours. Some patients are sent to physicians downtown (9%) and to external medicosocial assistance centres (39.5%).This study (first one in France) provides us with homogenous data regarding the activities of PASS centres nationwide. The usefulness of computers and its acceptability facilitate data diffusion, with possibilities of adapting to each centre while preserving a common basis.

To incorporate quality-of-life considerations in assessing high dose therapy (HDT) for patients with Multiple Myeloma (MM).A quality-adjusted survival analysis. using the quality-adjusted time without symptoms or toxicity (Q-TWiST) method, was applied to two randomized clinical trials conducted in patients with MM which compared randomized assignment to HDT vs. conventional chemotherapy (CCT) alone (MAG91) or followed by HDT (MAG90). Treatment benefit in terms of mean Q-TWiST was assessed through threshold utility analyses, i.e., sensitivity analyses of the choice of the utility coefficients over all possible values of utility weights.In both trials, results slightly favored the first-line HDT group over the first-line CCT group, with an average gain in TWiST of about 5.5 months over the 58 month-median follow-up period (27.8 vs. 22.3 months, respectively) in the MAG90 trial and 5.8 months over the 56 month-median follow-up period (19.1 vs. 13.3 months, respectively) in the MAG91 trial. The utility threshold analyses revealed that the first-line HDT group had a statistically increased mean quality-of-life adjusted time compared to the other group for a broad range of utility coefficient values.The development of such understandable and intuitive measures of expressing the relative benefit of complex treatment strategies is expected to be used in clinical decision making in the near future.

Immune recovery after cord blood transplantation (CBT) is of concern owing to the low number of lymphocytes transferred with the graft and their immaturity. Risk factors influencing lymphocyte subset reconstitution related to disease, patient, donor and transplant were studied in 63 children (16 years), given either related (n = 14) or unrelated (n = 49) CBT for malignant (n = 33) or non-malignant diseases (n = 30). Only children with sustained myeloid engraftment were analysed. Absolute numbers of T (CD3(+), CD4(+), CD8(+)), B and natural killer (NK) cells were reported 2--3, 6, 9, 12 and 12--24 months after CBT. Median patient age was 4.0 years (0--15) and median follow-up was 23 months (1.7--61.0). Twenty-six patients received human leucocyte antigen (HLA)-matched CBT and 37 received HLA-mismatched CBT. The median number of nucleated cells (NCs) collected/recipient weight was 6.1 x 10(7)/kg. In this selected population, the estimate 2 year survival was 85%. Lymphocyte reconstitution (defined as the median time to reach the normal value of age-matched healthy children) was 3, 6 and 8 months for NK, B and CD8(+) cells, while it was 11.7 months for both CD3(+) and CD4(+) lymphocytes. In the multivariate analysis, factors favouring T-cell recovery were: related donor (P = 0.002); higher NCs/kg (P = 0.005) and recipient cytomegalovirus (CMV)-positive serology (P = 0.04). Presence of acute graft-versus-host disease (GVHD) delayed T-cell recovery (P = 0.04). To summarize, in children with sustained myeloid engraftment the concern that lymphocyte recovery after CBT could be delayed does not appear to be substantiated by our results.

When intramedullary pinning is used to treat metacarpal fractures, as recently described by Förstner (1994) and Foucher (1995), the closed reduction technique developed by Jahss (1938) is applied in the same way as for conservative fracture treatment. It is not always possible to achieve complete anatomical reduction using this closed technique. The intramedullary pinning technique, that we have applied since 1989, involves a Kirschner wire which is bent at one end. Apart from reducing the fracture, the pre-set Kirschner wire serves as a butressing internal fixator. The elastic clamping of the wire acts as an internal wire spring splint, permitting early mobilisation. We have operated on 62 metacarpal fractures using the above-mentioned technique over a period of 6 years until 1995. Anatomic reduction was realized in 50 of 62 fractures. In the follow-up of 32 fractures, we noticed four complications: one infection, two paraesthesias, and one non-union.