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•Neuropathic pain assessment via PROMs has improved within last years.•There is still a heterogeneous use of domains/PROMs even in higher quality studies.•Definition of a core outcome set relevant to stakeholders and patients is needed.

Byline: Sandra David, MD, PhD (Hospices Civils de Lyon, Service de Biostatistique, Lyon, France, Universite de Lyon, Pierre-Benite, France); Fatima Abbas-Chorfa, MSc (Universite de Lyon, Pierre-Benite, France); Philippe Vanhems, MD, [...]

Background and Objective: Metabolic bone disease is frequent in chronic intestinal failure. Because fluoride has a major effect on bones, the status of both fluoride and bone was studied in long-term home parenteral nutrition (HPN) patients. Design: We studied 31 adults aged ([barx] [+ or -] SD) 56.3 [+ or -] 15.1 y, mainly patients with short-bowel syndrome, who had been receiving HPN for > 1 y. Bone mineral density (BMD) was measured by absorptiometry, and serum fluoride was measured by using a fluoridesensitive electrode. All patients ate and drank ad libitum. HPN (3.4 [+ or -] 1.2 times/wk) complemented oral nutrition. Potential explicative factors were estimated by using a linear regression model (mixed-effects model). Results: Of 120 fluoride dosages (2-6/patient), 102 were above the upper normal limit (1.58 [micro]mol/L) at the laboratory. Mean ([+ or -]SD) daily fluoride supply was 8.03 [+ or -] 7.71 mg (US adequate intake: 3.1 mg/d for women and 3.8 for men; tolerable upper normal limit: 10 nag/d); intravenous fluoride varied from 0.06 to 1.45 mg, and oral fluoride varied from 0.09 to 27.8 mg. Serum fluoride concentrations were correlated with creatinine clearance and fluoride supply. BMD was significantly lower in the femoral neck than in the spinal area. After adjustment for sex and the duration of HPN, only the effect of serum fluoride on spinal BMD was significant. Two patients had symptoms of fluorosis, eg, calcaneum fissures, interosseous calcifications, or femoral neck osteoporosis. Conclusions: In chronic intestinal failure, high intakes of fluoride are frequent because of the beverages ingested to compensate for stool losses. Hyperfluoremia has an effect on bone metabolism and may increase skeletal fragility. The consumption of fluoride-rich beverages for extended periods is therefore not advisable. KEY WORDS Fluoride, bone mineral density, fluorosis, home parenteral nutrition, chronic intestinal failure

IntroductionWith advances in surgical and neonatal care, the survival of patients with oesophageal atresia (OA) has improved over time. Whereas a number of OA-related conditions (delayed primary anastomosis, anastomotic stricture and oesophageal dysmotility) may have an impact on feeding development and although children with OA experience several oral aversive events, paediatric feeding disorders (PFD) remain poorly described in this population. The primary aim of our study was to describe PFD in children born with OA, using a standardised scale. The secondary aim was to determine conditions associated with PFD.MethodsThe Feeding Disorders in Children with Oesophageal Atresia Study is a national cohort study based on the OA registry from the French National Network. Parents of children born with OA between 2013 and 2016 in one of the 22 participating centres were asked to complete the French version of the Montreal Children’s Hospital Feeding Scale.ResultsOf the 248 eligible children, 145 children, with a median age of 2.3 years (Q1–Q3 1.8–2.9, min–max 1.1–4.0 years), were included. Sixty-one children (42%) developed PFD; 13% were tube-fed (n=19). Almost 40% of children with PFD failed to thrive (n=23). The presence of chronic respiratory symptoms was associated with the development of PFD. Ten children with PFD (16%) had no other condition or OA-related complication.ConclusionPFD are common in children with OA, and there is no typical profile of patients at risk of PFD. Therefore, all children with OA require a systematic screening for PFD that could improve the care and outcomes of patients, especially in terms of growth.

Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log‐linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between‐transplant center variability (0.23 ± 0.08) was 1.8 higher than between‐dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access. Especially in elderly patients, patient case‐mix, dialysis networks, and transplant centers practices in France explain variability in kidney transplant waitlist registration at the time of or within one year of dialysis initiation.

Background and objectivesIdentifying virilisation of the genitalia in female newborns early during the neonatal period is important to diagnose pathologies. However, there is no clear threshold for clitoromegaly or for the anogenital ratio. The objective of this study was to define reference values for the external genitalia of full-term and pre-term female neonates.DesignThis was a prospective study of all females born in the study centre between May 2014 and July 2016. Clitoral length and anogenital ratio were measured in 619 newborns with a gestational age of 24+2 to 41+3 weeks during their first 3 days of life. Associations between the values at day 3 and gestational age, birth weight and other newborn characteristics were examined by linear regression.ResultsThe mean clitoral length at day 3 of life was 3.69±1.53 mm (n=551; 95th percentile, 6.5 mm; maximum, 8 mm), and the mean anogenital ratio was 0.42±0.09 (95th percentile, 0.58). There was no significant variation with gestational age or birth weight, and no significant difference between the results at day 0 and day 3.ConclusionThese results suggest that clitoromegaly can be defined as a clitoral length >6.5 mm. Values ≥8 mm should prompt further investigations. An anogenital ratio >0.6 should be considered a sign of virilisation. Since clitoral size does not vary with gestational age or birth weight, clitoromegaly should not be attributed to prematurity.

L’information préopératoire est déterminante à l’adhésion du patient au traitement mais peut être insuffisamment assimilée par le patient du fait de sa densité et de sa complexité. L’objectif de cette étude était d’évaluer la compréhension et la satisfaction des patients de l’information préopératoire de chirurgie de l’hypertrophie bénigne de prostate (HBP). Les facteurs influençant la compréhension étaient également étudiés.

Le cycle ovarien a un rythme circa-mensuel bien établi, mais les mécanismes impliqués dans sa régularité sont inconnus. La rythmicité est-elle déterminée par une horloge endogène ou par d’autres processus internes ou externes ?

Le développement de programmes d'interventions ciblées dans les pays où le paludisme est endémique nécessite des informations sur la transmission saisonnière du paludisme. Cette étude visait à déterminer les périodes épidémiques du paludisme par district sanitaire et groupe cible au Togo.

All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and HMG-CoA-reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the current risk of cardiovascular (CV) events and mortality and also to evaluate the effect of pharmacologic treatment on patient's survival, CV events, and additional vascular surgery in vascularized LE-PAD patients. This observational, cohort study analyzed prospectively collected data of 140 consecutive patients after hospitalization for LE-PAD revascularization in the vascular surgery department of our university hospital, between January 1 and June 30, 2013.

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Il n'existe que très peu de données à long terme sur la cinétique des anticorps chez les survivants de la maladie à virus Ebola (MVE). L'objectif de cette étude était de modéliser la réponse humorale en anticorps chez les survivants de la MVE en Guinée.

L'hétérogénéité des réponses du système immunitaire au sein d'une population après une infection a été observée dans plusieurs études. Cela suggère que la description d'une population à l'aide d'une seule trajectoire omet la variabilité intra- et interindividuelle complexe du contexte clinique de la vie réelle. L'objectif de cette étude était d'identifier différents profils de réponse anticorps chez les survivants de la maladie à virus Ebola (MVE) en Guinée.

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Tester la non-infériorité de la cryothérapie (Froid Sec Alkantis®, Lyon, France) seule ou en association avec un traitement antalgique vs un traitement antalgique seul de palier supérieur, pour permettre de diminuer d’un palier la puissance des antalgiques utilisés en traumatologie. Cette étude prospective randomisée de non-infériorité a inclus des patients âgés d’au moins 12 ans pour prise en charge d’un traumatisme, selon deux bras. Ils ont reçu soit un antalgique seul: palier 1 (paracétamol) si EVA<4; palier 2 (paracétamol + codéine ou paracétamol + tramadol) si 4≤EVA≤7; et palier 3 (morphine) si EVA>7; soit des antalgiques de palier inférieur systématiquement associés à la cryothérapie: cryothérapie seule si EVA<4, antalgique de palier 1 + cryothérapie si 4≤EVA≤7 et antalgique de palier 2 + cryothérapie si EVA>7. Cent soixante-dix-huit patients ont été analysés. La différence d’EVA finale entre le groupe « antalgiques seuls » et le groupe « antalgiques de palier inférieur et cryothérapie » a été estimée à 0,70 IC 95 % [0,10; 1,31]. La même analyse a été réalisée en stratifiant sur le palier d’EVA initiale, la différence d’EVA finale entre le groupe « antalgiques seuls » et le groupe « antalgiques de palier inférieur et cryothérapie » a été estimée à 0,68 IC 95 % [0,17; 1,20]. Cette étude démontre que la cryothérapie seule ou en association avec un antalgique est non inférieure mais aussi supérieure à un traitement antalgique seul de palier supérieur sur la douleur d’origine traumatique. The aim of this study was to test the non-inferiority of cryotherapy (Froid Sec Alkantis®, Lyon, France) alone or in combination with analgesia on trauma pain compared to a higher step of analgesia alone. Prospective, non-inferiority study of patients at least 12 years old admitted to the Emergency Department for treatment of trauma and randomised into two arms. The patients received either analgesic alone: step 1 (paracetamol) if VAS<4; step 2 (paracetamol + codeine or paracetamol + tramadol) if 4≤VAS≤7; and step 3 (morphine) if VAS>7 or routine lower step analgesic combined with cryotherapy: cryotherapy alone if VAS<4, step 1 analgesic + cryotherapy if 4≤VAS≤7 and step 2 analgesic + cryotherapy if VAS>7. 178 patients were analysed. The final difference in VAS between the “analgesics alone” and “lower step analgesics plus cryotherapy” was 0,70 95 % CI [0,10;1,31]. The same analysis was performed stratifying patients by initial VAS step. In this case, the difference in final VAS between the “analgesics alone” and “lower step analgesics and cryotherapy” group was 0,68 with a CI of 95 % [0,17;1,20]. This study shows that cryotherapy alone or in combination with analgesics is not inferior to a higher step analgesic treatment on trauma pain.

Contexte et objectifs :L’asthme est un enjeu majeur de santé publique en raison de la mortalité, de la morbidité, des dépenses de soins engendrées et des conséquences sur la qualité de vie des patients. Un programme éducatif a été mis en place pour apporter aux patients asthmatiques une formation complémentaire à celle reçue chez le médecin généraliste. Méthodes :Quatre séances trimestrielles sont prévues. La formation commence par un bilan initial comprenant un examen médical approfondi et un recueil d’informations (contrôle de l’asthme, qualité de vie, connaissances sur la maladie et satisfaction vis-à-vis des traitements). Au cours de ces séances, les patients voient un médecin, un kinésithérapeute et un psychologue. Ils reçoivent des informations détaillées sur la physiopathologie de l’asthme et les traitements reçus. Ils apprennent à utiliser des plans d’action en cas de crise et à tenir un carnet de bord. Un bilan final identique au bilan initial est prévu au terme de l’étude, 12 mois plus tard. Cent cinquante patients sont randomisés dans deux groupes : « éducation immédiate » (n = 75) et « éducation différée » contrôle (n = 75). Le groupe éducation immédiate bénéficie des quatre séances éducatives tandis que le groupe « éducation différée » n’a que la première séance. La survenue d’exacerbations de l’asthme pendant le suivi sera comparée entre les deux groupes, tout comme les évolutions respectives entre le bilan initial et le bilan final du contrôle de l’asthme, de la qualité de vie, de la satisfaction vis-à-vis des traitements, et du niveau de connaissance du patient. Les difficultés méthodologiques pour la mise en place et l’évaluation du projet éducatif sont évoquées dans l’article. Résultats préliminaires et discussion :A ce jour, dix patients ont été inclus dans le programme éducatif, qui a été bien accueilli par les patients. Certaines difficultés de recrutement sont analysées ; elles devront faire l’objet de mesures spécifiques.

Objective: Attention-deficit hyperactivity disorder is one of the most frequent neurodevelopmental disorders. Its diagnosis requires reference questionnaires such as the Conners’ Parent Rating Scale (CPRS). Presently, in French-speaking countries, a few translations of the revised short CPRS have been put to use without previous formal validation. We sought here for the validation of a French version (Lausanne, Switzerland) of the revised short CPRS regarding construct validity, internal consistency, and item reliability in a sample of French schoolchildren.Method: The study involved 795 children and adolescents aged 9 to 19 years from a single school. The factorial structure and item reliability were assessed with a confirmatory factor analysis for ordered categorical variables. The dimension internal consistency was assessed with Guttman’s lambda 6 coefficient.Results: The results confirmed the original and strong 3-dimensional factorial structure (Oppositional, Cognitive Problems/Inattention, and Hyperactivity), showed satisfactory item reliability, and indicated a good dimension internal consistency (Guttman’s lambda 6 coefficient: 0.87, 0.90, and 0.82, respectively, to the 3 dimensions).Conclusions: Thus, the Lausanne French version of the revised short CPRS may be considered validated regarding construct validity and item and dimension reliability; it can be now more confidently used in clinical practice.

The objective of this study was to calculate Vaccine Effectiveness (VE) in healthcare workers (HCW) and to compare VE between patients and HCW. A case-control investigation based on the prospective study was conducted between 2004 and 2009 in a teaching hospital. All HCW with influenza-like illness (ILI) from participating units (n = 24) were included, and vaccination status was characterized by interview. A total of 150 HCW presented ILI; 130 (87%) were female, 27 (18%) were positive for influenza, and 42 (28%) were vaccinated. Adjusted VE was 89% (95% CI 39 to 98). Among patients, adjusted VE was 42% (95% CI −39 to 76). The difference of VE (VEhcw- VEpat) was 46.15% (95% CI 2.41 to 144). The VE ratio (VEhcw/ VEpat) was 2.09 (95% CI −1.60 to 134.17). Influenza VE differed between HCW and patients when the flu season was taken into account. This finding confirms the major impact of host determinants on influenza VE.

In elderly hemodialysis patients, protein-energy wasting is associated with poor outcome; however, the association between body mass index (BMI) changes over time, and survival has been seldom studied in this particularly frail population.

Background:Intrauterine insemination with ovarian stimulation (IUI-OS) is a first-line treatment for couples with unexplained infertility. Individual participant data meta-analysis (IPD-MA) is the gold standard for evidence synthesis.Aim:To compare the effectiveness and safety of ovarian stimulation with gonadotrophin, Letrozole and clomiphene citrate (CC) and to explore treatment-covariate interactions for important baseline characteristics in women undergoing IUI.Method:We searched electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). We included randomised controlled trials (RCTs) comparing IUI-OS with gonadotropins, Letrozole or CC among couples with unexplained infertility. We excluded dose comparing studies of the same drug. We contacted the authors of eligible RCTs to share the IPD and established the IUI IPD-MA collaboration. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. We used a one-stage approach using a random effects model.Results:Six RCTs (n= 2299) provided IPD. Gonadotropins increased the chance of a live birth compared to both CC (5 RCTs, 1946 women, RR 1.28, 95%CI 1.10 to 1.49, I2 = 25%, moderate-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.77 95%CI 0.58 to 1.03). Gonadotropins increased the risk of a multiple pregnancy compared to both CC (4 RCTs, 1696 women, RR 2.17, 95%CI 1.33 to 3.55, I2 = 69%, low-quality evidence) whereas there was insufficient evidence of a difference between Letrozole and CC (1 RCT, 599 women, RR 0.71, 95%CI 0.33 to 1.56). No strong evidence on the treatment-covariate interactions (female age, BMI or primary versus secondary infertility) was found.Conclusion:Gonadotropins increased the chance of a live birth compared to both CC and Letrozole but also increased the chance of a multiple pregnancy. Further RCTs comparing Letrozole and other interventions in couples with unexplained infertility are needed.

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ABSTRACTInfants born to mothers who seroconverted for toxoplasmosis during pregnancy are at risk of sequelae. In the case of a negative work-up at birth, congenital infection can be ruled out only by monitoring the disappearance of maternal immunoglobulin G (IgG) transmitted through the placenta, which can be achieved by regular blood sampling during the first year. To alleviate the discomfort of this follow-up, we developed an indirect enzyme-linked immunosorbent assay to detect specific IgG diffusing passively from the blood through the gingival epithelium by collecting oral fluid on microsponges. To assess the feasibility of the test, 212 patients were first enrolled. Levels of specific IgG in oral fluid were significantly higher in seropositive (n= 195) than in seronegative (n= 17) patients (mean optical densities, 1.145 ± 0.99 versus 0.092 ± 0.127; P< 0.0001). In a population of 93 patients <15 months of age born to mothers who displayed toxoplasmic infection during pregnancy, 70 were free of congenital infection and were followed up until their serology turned negative, and 23 were congenitally infected. The same patterns of IgG were observed in the oral fluid and sera in each group. Using a cutoff of 0.04 (optical density value), the sensitivity and specificity of the test were 67.9% and 80.3%, respectively, and the probability of not having a congenital infection when the test on oral fluid was negative was 99%. Although the performance of the test needs to be improved, oral fluid sampling appears to be a promising tool for monitoring infants with suspected congenital toxoplasmosis.

Susan Watters's 'Party Politics' (November) was spot-on in its analysis of D.C.'s ailing society scene. The partisan divide will only deepen with the election results. I also think that the [...]

Des analyses longitudinales sont nécessaires pour mieux comprendre l’apparition des symptômes à long terme de la maladie à virus Ebola (MVE) chez les survivants. Les études précédentes ont rapporté des analyses transversales ponctuelles à chaque visite d’étude, ignorant l’évolution temporelle des symptômes et leur caractère intermittent entre les visites. L’objectif de cette étude était d’estimer la prévalence et d’identifier les facteurs de risque associés à l’apparition des symptômes chez les survivants de la MVE en Guinée.

Background: Beside too long delays and clinical or electrocardiographic diagnostic difficulties, one of the reasons for not having thrombolysis could be accessibility to hospital. Our objective was thus to study [...]

Background: There remains a controversy concerning the association between myocardial dysfunction diagnosed soon after acute myocardial infarction and later quality of life. We searched for correlations between criteria of myocardial [...]

In a multicenter surveillance of intensive care unit (ICU)–acquired infections, adjusted ventilator-associated pneumonia (VAP) incidence diminished by −1.0% per year (95% confidence interval [CI], −1.8 to −0.2; P= .02) in ICUs with continuous surveillance but increased by +16.1% (95% CI, 0.5%–34.1%; P= .04) in the year following surveillance disruption, suggesting a preventive effect of surveillance on VAP.Infect Control Hosp Epidemiol 2014;35(10):1290–1293

AbstractBackground:Subgroups of patients registered on a kidney transplant waiting list have higher than usual mortality levels. This study used data from the French Renal Epidemiology and Information Network (REIN) Registry to quantify the impact over time of various comorbidities on the excess risk of death among patients on the waiting list. Methods:Lexis diagrams were used to analyze time since onset of end-stage renal disease and time since registration on the waiting list. The number of excess deaths was calculated by comparison with the number of expected deaths in the general population of the same age and sex. Results:During 45,013 person-years of follow-up, 7,224 patients died, 5,956 (82) more than expected relative to the general population. There were 101 deaths among wait-listed dialysis patients, 76 more than expected. The excess risk of death increased by 45 per additional year on the waiting list (18-79, p = 0.0005). Time from end-stage renal disease onset until list registration (p = 0.004), time since registration (p < 0.001), age >65 years (p = 0.008), the presence of a primary renal disease (p = 0.028), and the number of comorbidities (p = 0.035) were independent predictors of death while on the waiting list. Conclusions:The excess risk of death while on the waiting list increased faster in patients with comorbidities. These results require consideration of ways to accelerate access to transplantation in high-risk patients.© 2013 S. Karger AG, Basel

L’objectif de cette étude a été d’évaluer l’apport de l’IRM prostatique telle qu’elle était réalisée en routine en préopératoire dans le bilan du cancer de prostate cliniquement localisé.

ABSTRACTProlonged antimicrobial therapy is recommended for methicillin-susceptible Staphylococcus aureus(MSSA) bone and joint infections (BJI), but its safety profile and risk factors for severe adverse events (SAE) in clinical practice are unknown. We addressed these issues in a retrospective cohort study (2001 to 2011) analyzing antimicrobial-related SAE (defined according to the Common Terminology Criteria for Adverse Events) in 200 patients (male, 62%; median age, 60.8 years [interquartile range {IQR}, 45.5 to 74.2 years]) with MSSA BJI admitted to a reference regional center with acute (66%) or chronic arthritis (7.5%), osteomyelitis (9.5%), spondylodiscitis (16%), or orthopedic device-related infections (67%). These patients received antistaphylococcal therapy for a median of 26.6 weeks (IQR, 16.8 to 37.8 weeks). Thirty-eight SAE occurred in 30 patients (15%), with a median time delay of 34 days (IQR, 14.75 to 60.5 days), including 10 patients with hematologic reactions, 9 with cutaneomucosal reactions, 6 with acute renal injuries, 4 with hypokalemia, and 4 with cholestatic hepatitis. The most frequently implicated antimicrobials were antistaphylococcal penicillins (ASP) (13 SAE/145 patients), fluoroquinolones (12 SAE/187 patients), glycopeptides (9 SAE/101 patients), and rifampin (7 SAE/107 patients). Kaplan-Meier curves and stepwise binary logistic regression analyses were used to determine the risk factors for the occurrence of antimicrobial-related SAE. Age (odds ratio [OR], 1.479 for 10-year increase; 95% confidence interval [CI], 1.116 to 1.960; P= 0.006) appeared to be the only independent risk factor for SAE. In patients receiving ASP or rifampin, daily dose (OR, 1.028; 95% CI, 1.006 to 1.051; P= 0.014) and obesity (OR, 8.991; 95% CI, 1.453 to 55.627; P= 0.018) were associated with the occurrence of SAE. The high rate of SAE and their determinants highlighted the importance of the management and follow-up of BJI, with particular attention to be paid to older persons, especially for ASP dosage, and to rifampin dose adjustment in obese patients.

Fluorescence imaging is nowadays a powerful tool for laboratory animal studies in oncology. This emerging technology is in full development and is becoming a complementary tool in clinics for specific cancer diagnosis. For now, it allows detection with a high spatio-temporal resolution of specific signals like tumor markers in small animals. Different ways of in vivo imaging exist: epifluorescence macroscopy, intravital imaging to visualize molecular processes combined or not with multiphoton excitation and fluorescence tomography to spatially detect deeper cellular phenomena. These techniques are impaired by the tissue optical properties: auto-fluorescence, photon scattering in tissues and by limited depth penetration of the excitation beam in tissues. To overcome these limits, scientists are developing spectral imaging, far-red imaging technologies and associated dyes to observe tumor cells biology over longer periods, on larger volumes and on a higher number of organs, thus improving the knowledge in tumor pathophysiology. A challenge in oncology is to improve early detection and prevention using novel targeted cancer diagnostics. Detection requests specific recognition. Tumor markers have to be ideally present on the surface of cancer cells. Their targeting with ligands coupled to imaging agents make them visible/detectable. In this review, after a short introduction on in vivo fluorescence imaging theories and a description of the different existing modalities, we will focus on the recent outcome of basic studies in the design of new probes and devices used to detect tumor cells.

To test the modulation of farnesoid X receptor activity on the replication of hepatitis C virus in chronically infected patients.

Gender inequity in access to renal transplantation waiting lists, in favor of men, has long since been demonstrated in a number of studies. Discrepancies between the results of the available studies might be explained by different analytical approaches or different national contexts. In this study we analyzed French end-stage renal disease registry data using a novel model to determine whether the female gender is associated with a lower probability of being listed on the transplant waiting list or with a longer time from dialysis start until registration, or both.

Simultaneous pancreas-kidney transplantation (SPKT) is a promising therapy for type 1 diabetes mellitus with chronic kidney disease. Although the long-term outcome of SPKT is extensively documented, the incidence of early complications within the first weeks after the surgery is less described. The aim of this study was to assess the incidence, causes, and risk factors of early relaparotomy after SPKT.

We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières.

Palaeogeographical reconstruction and management challenges of an archaeological site listed by UNESCO: the case of the Letoon shrine in the Xanthos Plain (Turkey)During the Hellenistic period, Xanthos and Letoon were respectively a large city and an important shrine in Lycia. Questions still remain about the geography of the Eşen Çayı delta during the first millennium BC: what were the features of the landscape surrounding the Letoon shrine? Where did the riverbed lie? Our analysis is based on a reconstruction of the geomorphological dynamics at work during the Holocene. These are then compared with historical, archaeological and literary sources. Sedimentary sampling shows that a marine bay was gradually closed during the formation of a coastline spit, which led to the development of a lagoon system. Lagoons and marshes remained predominant characteristics of the plain over a long period. A branch or a former channel of the Eşen Çayı was discovered close to the Letoon shrine. In recent decades, authorities, as well as UNESCO, are now making an effort to manage palaeoenvironmental reconstructions in their promotion of the tourist potential of archaeological sites. We propose a management project for the Letoon site.

AbstractObjective: As the prognosis for final height is unfavorable for children with idiopathic short stature (ISS), we studied the pubertal growth dynamics in these children, which is a determinant factor in final height.Subjects/methods: In a retrospective cohort study, we analyzed the pubertal period, age of puberty and peripubertal growth in 50 children with ISS.Results: The onset of puberty occurred later. Growth rate tended to become increasingly subnormal in the prepubertal period and height was –2.45 SD at puberty onset. Growth reaccelerated at this point, which tended to correct the deviation from the mean height, but it was insufficient to obtain a normal final height.Conclusions: The dynamics of growth in children with ISS showed a distinct pattern in the prepubertal and pubertal periods and puberty is significantly delayed in this population. These patterns could explain the unfavorable prognosis for children with ISS.

ABSTRACTThe HIV-1 RNA viral load is commonly used for the monitoring of disease progression and antiretroviral treatment of HIV-1-infected patients. Since the misestimating of values could lead to inappropriate therapeutical management, the comparative performances, especially the ability to span the genetic diversity of HIV-1, of available automated real-time assays need to be evaluated. We conducted a prospective study with 74 consenting patients enrolled between March 2007 and November 2008. A blood sample was obtained at the time of diagnosis of HIV seropositivity and blindly tested for HIV-1 RNA by at least 4 commercial tests: the Abbott m2000 RealTime HIV-1, bioMe´rieux NucliSens EasyQ HIV-1, version 1.2 (v1.2), and Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) v1.0 and v2.0 assays. The means of difference were null between CAP/CTM v2.0 and Abbott for CRF02_AG subtypes but positive in favor of CAP/CTM v2.0 for genotype B and negative in favor of NucliSens for all genotypes. The standard deviation (SD) of difference ranged from 0.3 to 0.59, depending on the considered couples of assays. Reliabilities of these four tests, appreciated by the standard deviation of difference between the measurement and the estimated “true” viral load and by the coefficient of reliability, were significantly different (P< 10-4) among each other. Significant differences were also observed within each group of HIV-1 genotype. The global disparity was higher for CRF02_AG than for B subtypes. This study indicates a risk of viral load misestimating or discrepancies between techniques, depending on the HIV-1 subtype, and speaks in favor of using the same assay for the monitoring of HIV-1-infected patients.

Fluorescence imaging agents in cancerologyBackground.One of the major challenges in cancer therapy is to improve early detection and prevention using novel targeted cancer diagnostics. Detection requests specific recognition. Tumor markers have to be ideally present on the surface of cancer cells. Their targeting with ligands coupled to imaging agents make them visible/detectable.Conclusions.Fluorescence imaging is a newly emerging technology which is becoming a complementary medical method for cancer diagnosis. It allows detection with a high spatio-temporal resolution of tumor markers in small animals and in clinical studies. In this review, we focus on the recent outcome of basic studies in the design of new approaches (probes and devices) used to detect tumor cells by fluorescence imaging.

This review assesses the relevance of the clinical, histological, biochemical and virological end points in the course and outcome of chronic hepatitis B. The pathway and the impact of the variation in these end points are presented, as well as their definitions. The treatment goals are discussed in terms of quality of life and survival. Prevention of the progression of the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease and hepatocellular carcinoma seems to be the best approach to improve survival. As these criteria are long-term end points, easier to use end points assessed in clinical trials as efficacy objectives were also analyzed to determine whether they can be used as accurate surrogate criteria. Results of therapy were then analyzed according to the approved end points and in terms of management of chronic hepatitis B. Finally, an attempt to define new clinical end points is discussed in view of the development of more potent antiviral strategies.

AbstractBackground/Aims:In diabetics with end-stage renal disease (ESRD), risk of death has been reported to be non-constant after the first dialysis, and different outcomes have been observed between genders. We assessed the impact of type 2 diabetes (T2DM) on mortality in dialysis regarding its differential effect by gender using time-dependent analyses. Methods:All T2DM and non-diabetic (no-DM) patients who started dialysis in two renal units in Lyon, France, between January 1, 1995, and December 31, 2007, were included. In multivariate analyses, the Cox model and Shoenfeld residual approach were used to assess the effect of T2DM on dialysis mortality by gender. Results:We included 235 T2DM (males: 57.9) and 480 no-DM (males: 65.6) patients. In males, the adjusted hazard ratio (aHR) for death in T2DM versus no-DM was 0.83 (p = 0.20) and was constant over time after the first renal replacement therapy (RRT) (p = 0.88). In females, aHR for death in T2DM versus no-DM patients was not constant over time (p = 0.002). It was 0.64 (p = 0.13) within the first year after the first RRT and 2.10 (p = 0.002) after the first year. Evolutions with time of these aHR by gender were significantly different (p = 0.009). Conclusions:T2DM was associated with death only in females. This association was not constant over time after the first dialysis.Copyright © 2009 S. Karger AG, Basel

Patients with a Klinefelter syndrome (KS), defined by a 47 XXY karyotype, were long considered infertile. Testicular sperm extraction (TESE) now allows them to access fatherhood. We will present the data of studies since first experiment of TESE. Several factors influencing TESE outcome were proposed in these different studies. Among them, clinical and hormonal parameters have reported by few studies, age has been one of the most discussed prognostic factor of positive sperm retrieval rate. Data seems to show that TESE carried out before an age greater than 30 has a poorer prognosis for positive sperm retrieval. In few studies performed in younger patient, before 20 years, SRR was closed to result for 20 to 30 year old patients. Offering a TESE before 16 years old does not improve positive sperm extraction rate. In fact, the few studies carried out before the age of 16 were of poorer prognosis, most often linked to insufficient maturation of the residual gametes. In addition, androgen therapy, frequently prescribed in case of Klinefelter syndrome, did not seem to show any effect on sperm retrieval but only few studies were interested in the possible impact of this treatment. In conclusion, further studies are necessary to determine the interest of new markers to predict the chance of sperm retrieval, taking into account age, hormonal therapy.

High-throughput single-molecule techniques are expected to challenge the demand for rapid, simple, and sensitive detection methods in health and environmental fields. Based on a single-DNA-molecule biochip for the parallelization of tethered particle motion analyses by videomicroscopy coupled to image analysis and its smart combination with aptamers, we successfully developed an aptasensor enabling the detection of single target molecules by a sandwich assay. One aptamer is grafted to the nanoparticles tethered to the surface by a long DNA molecule bearing the second aptamer in its middle. The detection and quantification of the target are direct. The recognition of the target by a pair of aptamers leads to a looped configuration of the DNA–particle complex associated with a restricted motion of the particles, which is monitored in real time. An analytical range extending over 3 orders of magnitude of target concentration with a limit of detection in the picomolar range was obtained for thrombin.

The propensity to arouse from sleep is an integrative part of the sleep structure and can have direct implications in various clinical conditions. This study was conducted to evaluate the maturation of spontaneous arousals during the first year of life in healthy infants.

We recently cloned a novel human nuclear factor (designated THAP1) from postcapillary venule endothelial cells (ECs) that contains a DNA-binding THAP domain, shared with zebrafish E2F6 and several Caenorhabditis elegans proteins interacting genetically with retinoblastoma gene product (pRB). Here, we show that THAP1 is a physiologic regulator of EC proliferation and cell-cycle progression, 2 essential processes for angiogenesis. Retroviral-mediated gene transfer of THAP1 into primary human ECs inhibited proliferation, and large-scale expression profiling with microarrays revealed that THAP1-mediated growth inhibition is due to coordinated repression of pRB/E2F cell-cycle target genes. Silencing of endogenous THAP1 through RNA interference similarly inhibited EC proliferation and G1/S cell-cycle progression, and resulted in down-regulation of several pRB/E2F cell-cycle target genes, including RRM1, a gene required for S-phase DNA synthesis. Chromatin immunoprecipitation assays in proliferating ECs showed that endogenous THAP1 associates in vivo with a consensus THAP1-binding site found in the RRM1 promoter, indicating that RRM1 is a direct transcriptional target of THAP1. The similar phenotypes observed after THAP1 overexpression and silencing suggest that an optimal range of THAP1 expression is essential for EC proliferation. Together, these data provide the first links in mammals among THAP proteins, cell proliferation, and pRB/E2F cell-cycle pathways.

To evaluate the relationship between maternal leukocytosis in women admitted after preterm premature rupture of the membranes (PPROM) and the neurodevelopmental outcomes of their infants at two years of age.