Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study.

OBJECTIVES: To determine clinical and ultrasonographic predictors of joint replacement surgery across Europe in primary osteoarthritis (OA) of the knee. METHODS: This was a 3-year prospective study of a painful OA knee cohort (from a EULAR-sponsored, multicentre study). All subjects had clinical evaluation, radiographs and ultrasonography (US) at study entry. The rate of knee replacement surgery over the 3-year follow-up period was determined using Kaplan-Meier survival data analyses. Predictive factors for joint replacement were identified by univariate log-rank test then multivariate analysis using a Cox proportional-hazards regression model. Potential baseline predictors included demographic, clinical, radiographic and US features. RESULTS: Of the 600 original patients, 531 (88.5%), mean age 67+/-10 years, mean disease duration 6.1+/-6.9 years, had follow-up data and were analysed. During follow-up (median 3 years; range 0-4 years), knee replacement was done or required for 94 patients (estimated event rate of 17.7%). In the multivariate analysis, predictors of joint replacement were as follows: Kellgren and Lawrence radiographic grade (grade > or =III vs <III, hazards ratio (HR) = 4.08 (95% CI 2.34 to 7.12), p<0.0001); ultrasonographic knee effusion (> or =4 mm vs <4 mm) (HR = 2.63 (95% CI 1.70 to 4.06), p<0.0001); knee pain intensity on a 0-100 mm visual analogue scale (> or =60 vs <60) (HR = 1.81 (95% CI 1.15 to 2.83), p=0.01) and disease duration (> or =5 years vs <5 years) (HR=1.63 (95% CI 1.08 to 2.47), p=0.02). Clinically detected effusion and US synovitis were not associated with joint replacement in the univariate analysis. CONCLUSION: Longitudinal evaluation of this OA cohort demonstrated significant progression to joint replacement. In addition to severity of radiographic damage and pain, US-detected effusion was a predictor of subsequent joint replacement.

Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals--the Swiss HIV Cohort Study.

BACKGROUND: Replicative phenotypic HIV resistance testing (rPRT) uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT) compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. METHODS: Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS). We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA <50 copies/mL or ≥1.5 log reduction). RESULTS: Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR) for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09). Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15). CONCLUSIONS: In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

The magmatic to hydrothermal evolution of the intrusive Mont Saint-Hilaire Complex: Insights into the late-stage evolution of peralkaline rocks

The Cretaceous Mont Saint-Hilaire complex (Quebec, Canada) comprises three major rock units that were emplaced in the following sequence: (I) gabbros; (II) diorites; (III) diverse partly agpaitic foid syenites. The major element compositions of the rock-forming minerals, age-corrected Nd and oxygen isotope data for mineral separates and trace element data of Fe-Mg silicates from the various lithologies imply a common source for all units. The distribution of the rare earth elements in clinopyroxene from the gabbros indicates an ocean island basalt type composition for the parental magma. Gabbros record temperatures of 1200 to 800 degrees C, variable silica activities between 0 center dot 7 and 0 center dot 3, and f(O2) values between -0 center dot 5 and +0 center dot 7 (log delta FMQ, where FMQ is fayalite-magnetite-quartz). The diorites crystallized under uniform a(SiO2) (a(SiO2) = 0 center dot 4-0 center dot 5) and more reduced f(O2) conditions (log delta FMQ similar to-1) between similar to 1100 and similar to 800 degrees C. Phase equilibria in various foid syenites indicate that silica activities decrease from 0 center dot 6-0 center dot 3 at similar to 1000 degrees C to < 0 center dot 3 at similar to 550 degrees C. Release of an aqueous fluid during the transition to the hydrothermal stage caused a(SiO2) to drop to very low values, which results from reduced SiO(2) solubilities in aqueous fluids compared with silicate melts. During the hydrothermal stage, high water activities stabilized zeolite-group minerals. Fluid inclusions record a complex post-magmatic history, which includes trapping of an aqueous fluid that unmixed from the restitic foid syenitic magma. Cogenetic aqueous and carbonic fluid inclusions reflect heterogeneous trapping of coexisting immiscible external fluids in the latest evolutionary stage. The O and C isotope characteristics of fluid-inclusion hosted CO(2) and late-stage carbonates imply that the surrounding limestones were the source of the external fluids. The mineral-rich syenitic rocks at Mont Saint-Hilaire evolved as follows: first, alkalis, high field strength and large ion lithophile elements were pre-enriched in the (late) magmatic and subsequent hydrothermal stages; second, percolation of external fluids in equilibrium with the carbonate host-rocks and mixing processes with internal fluids as well as fluid-rock interaction governed dissolution of pre-existing minerals, element transport and precipitation of mineral assemblages determined by locally variable parameters. It is this hydrothermal interplay between internal and external fluids that is responsible for the mineral wealth found at Mont Saint-Hilaire.

Early Stage Primary Bone Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study

Purpose/Objective(s): Primary bone lymphoma (PBL) represents less than 1% of all malignant lymphomas, and 4-5% of all extranodal lymphomas. In this study, we assessed the disease profile, outcome, and prognostic factors in patients with stage I and II PBL.Materials/Methods: Between 1987 and 2008, 116 consecutive patients with PBL treated in 13 RCNinstitutions were included in this study. Inclusion criteriawere: age.17 yrs, PBLin stage I and II, andminimum6months follow-up. The median agewas 51 yrs (range: 17-93).Diagnosticwork-up included plain boneXray (74%of patients), scintigraphy (62%), CT-scan (65%),MRI (58%), PET (18%), and bone-marrow biopsy (84%).All patients had biopsy-proven confirmation of non-Hodgkin's lymphoma (NHL). The histopathological type was predominantly diffuse large B-cell lymphoma (78%) and follicular lymphoma (6%), according to theWHOclassification. One hundred patients had a high-grade, 7 intermediate and 9 low-gradeNHL. Ninety-three patients had anAnn-Arbor stage I, and 23 had a stage II. Seventy-seven patients underwent chemoradiotherapy (CXRT), 12 radiotherapy (RT) alone, 10 chemotherapy alone (CXT), 9 surgery followed by CXRT, 5 surgery followed by CXT, and 2 surgery followed by RT. One patient died before treatment.Median RT dosewas 40Gy (range: 4-60).Themedian number ofCXTcycleswas 6 (range, : 2-8).Median follow-upwas 41months (range: 6-242).Results: Following treatment, the overall response rate was 91% (CR 74%, PR 17%). Local recurrence was observed in 12 (10%) patients, and systemic recurrence in 17 (15%) patients. Causes of death included disease progression in 16, unrelated disease in 6, CXT-related toxicity in 1, and secondary cancer in 2 patients. The 5-yr overall survival (OS), disease-free survival (DFS), lymphoma- specific survival (LSS), and local control (LC) were 76%, 69%, 78%, and 92%, respectively. In univariate analyses (log-rank test), favorable prognostic factors for survival were: age\50 years (p = 0.008), IPI score #1 (p = 0.009), complete response (p\0.001), CXT (p = 0.008), number of CXT cycles $6 (p = 0.007), and RT dose . 40 Gy (p = 0.005). In multivariate analysis age, RT dose, complete response, and absence of B symptoms were independent factors influencing the outcome. There were 3 patients developing grade 3 or more (CTCAE.V3.0) toxicities.Conclusions: This large multicenter study, confirms the relatively good prognosis of early stage PBL, treated with combined CXRT. Local control was excellent, and systemic failure occurred infrequently. A sufficient dose of RT (. 40 Gy) and completeCXT regime (. 6 cycles) were associated with a better outcome. Combined modality appears to be the treatment of choice.Author Disclosure: L. Cai, None; M.C. Stauder, None; Y.J. Zhang, None; P. Poortmans, None; Y.X. Li, None; N. Constantinou, None; J. Thariat, None; S. Kadish, None; M. Ozsahin, None; R.O. Mirimanoff, None.

Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir.

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.

Integration of high-resolution geophysical data for the characterization of alluvial aquifers : new approaches and implications for hydrological predictions

Abstract Accurate characterization of the spatial distribution of hydrological properties in heterogeneous aquifers at a range of scales is a key prerequisite for reliable modeling of subsurface contaminant transport, and is essential for designing effective and cost-efficient groundwater management and remediation strategies. To this end, high-resolution geophysical methods have shown significant potential to bridge a critical gap in subsurface resolution and coverage between traditional hydrological measurement techniques such as borehole log/core analyses and tracer or pumping tests. An important and still largely unresolved issue, however, is how to best quantitatively integrate geophysical data into a characterization study in order to estimate the spatial distribution of one or more pertinent hydrological parameters, thus improving hydrological predictions. Recognizing the importance of this issue, the aim of the research presented in this thesis was to first develop a strategy for the assimilation of several types of hydrogeophysical data having varying degrees of resolution, subsurface coverage, and sensitivity to the hydrologic parameter of interest. In this regard a novel simulated annealing (SA)-based conditional simulation approach was developed and then tested in its ability to generate realizations of porosity given crosshole ground-penetrating radar (GPR) and neutron porosity log data. This was done successfully for both synthetic and field data sets. A subsequent issue that needed to be addressed involved assessing the potential benefits and implications of the resulting porosity realizations in terms of groundwater flow and contaminant transport. This was investigated synthetically assuming first that the relationship between porosity and hydraulic conductivity was well-defined. Then, the relationship was itself investigated in the context of a calibration procedure using hypothetical tracer test data. Essentially, the relationship best predicting the observed tracer test measurements was determined given the geophysically derived porosity structure. Both of these investigations showed that the SA-based approach, in general, allows much more reliable hydrological predictions than other more elementary techniques considered. Further, the developed calibration procedure was seen to be very effective, even at the scale of tomographic resolution, for predictions of transport. This also held true at locations within the aquifer where only geophysical data were available. This is significant because the acquisition of hydrological tracer test measurements is clearly more complicated and expensive than the acquisition of geophysical measurements. Although the above methodologies were tested using porosity logs and GPR data, the findings are expected to remain valid for a large number of pertinent combinations of geophysical and borehole log data of comparable resolution and sensitivity to the hydrological target parameter. Moreover, the obtained results allow us to have confidence for future developments in integration methodologies for geophysical and hydrological data to improve the 3-D estimation of hydrological properties.

Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach.

BACKGROUND: HIV-1 RNA viral load is a key parameter for reliable treatment monitoring of HIV-1 infection. Accurate HIV-1 RNA quantitation can be impaired by primer and probe sequence polymorphisms as a result of tremendous genetic diversity and ongoing evolution of HIV-1. A novel dual HIV-1 target amplification approach was realized in the quantitative COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 (HIV-1 TaqMan test v2.0) to cope with the high genetic diversity of the virus. OBJECTIVES AND STUDY DESIGN: The performance of the new assay was evaluated for sensitivity, dynamic range, precision, subtype inclusivity, diagnostic and analytical specificity, interfering substances, and correlation with the COBAS AmpliPrep/COBAS TaqMan HIV-1 (HIV-1 TaqMan test v1.0) predecessor test in patients specimens. RESULTS: The new assay demonstrated a sensitivity of 20 copies/mL, a linear measuring range of 20-10,000,000 copies/mL, with a lower limit of quantitation of 20 copies/mL. HIV-1 Group M subtypes and HIV-1 Group O were quantified within +/-0.3 log(10) of the assigned titers. Specificity was 100% in 660 tested specimens, no cross reactivity was found for 15 pathogens nor any interference for endogenous substances or 29 drugs. Good comparability with the predecessor assay was demonstrated in 82 positive patient samples. In selected clinical samples 35/66 specimens were found underquantitated in the predecessor assay; all were quantitated correctly in the new assay. CONCLUSIONS: The dual-target approach for the HIV-1 TaqMan test v2.0 enables superior HIV-1 Group M subtype coverage including HIV-1 Group O detection. Correct quantitation of specimens underquantitated in the HIV-1 TaqMan test v1.0 test was demonstrated.

iLOGP: A Simple, Robust, and Efficient Description of n-Octanol/Water Partition Coefficient for Drug Design Using the GB/SA Approach.

The n-octanol/water partition coefficient (log Po/w) is a key physicochemical parameter for drug discovery, design, and development. Here, we present a physics-based approach that shows a strong linear correlation between the computed solvation free energy in implicit solvents and the experimental log Po/w on a cleansed data set of more than 17,500 molecules. After internal validation by five-fold cross-validation and data randomization, the predictive power of the most interesting multiple linear model, based on two GB/SA parameters solely, was tested on two different external sets of molecules. On the Martel druglike test set, the predictive power of the best model (N = 706, r = 0.64, MAE = 1.18, and RMSE = 1.40) is similar to six well-established empirical methods. On the 17-drug test set, our model outperformed all compared empirical methodologies (N = 17, r = 0.94, MAE = 0.38, and RMSE = 0.52). The physical basis of our original GB/SA approach together with its predictive capacity, computational efficiency (1 to 2 s per molecule), and tridimensional molecular graphics capability lay the foundations for a promising predictor, the implicit log P method (iLOGP), to complement the portfolio of drug design tools developed and provided by the SIB Swiss Institute of Bioinformatics.

The IFNL3/4 ΔG variant increases susceptibility to cytomegalovirus retinitis among HIV-infected patients.

BACKGROUND: Cytomegalovirus (CMV) retinitis is a major cause of visual impairment and blindness among patients with uncontrolled HIV infections. Whereas polymorphisms in interferon-lambda 3 (IFNL3, previously named IL28B) strongly influence the clinical course of hepatitis C, few studies examined the role of such polymorphisms in infections due to viruses other than hepatitis C virus. OBJECTIVES: To analyze the association of newly identified IFNL3/4 variant rs368234815 with susceptibility to CMV-associated retinitis in a cohort of HIV-infected patients. DESIGN AND METHODS: This retrospective longitudinal study included 4884 white patients from the Swiss HIV Cohort Study, among whom 1134 were at risk to develop CMV retinitis (CD4 nadir <100 /μl and positive CMV serology). The association of CMV-associated retinitis with rs368234815 was assessed by cumulative incidence curves and multivariate Cox regression models, using the estimated date of HIV infection as a starting point, with censoring at death and/or lost follow-up. RESULTS: A total of 40 individuals among 1134 patients at risk developed CMV retinitis. The minor allele of rs368234815 was associated with a higher risk of CMV retinitis (log-rank test P = 0.007, recessive mode of inheritance). The association was still significant in a multivariate Cox regression model (hazard ratio 2.31, 95% confidence interval 1.09-4.92, P = 0.03), after adjustment for CD4 nadir and slope, HAART and HIV-risk groups. CONCLUSION: We reported for the first time an association between an IFNL3/4 polymorphism and susceptibility to AIDS-related CMV retinitis. IFNL3/4 may influence immunity against viruses other than HCV.

Effect of early antiretroviral therapy during primary HIV-1 infection on cell-associated HIV-1 DNA and plasma HIV-1 RNA.

Background: Early initiation of combination antiretroviral therapy (ART) during primary HIV-1 infection may prevent the establishment of large viral reservoirs, possibly resulting in improved control of plasma viraemia rebound after ART cessation.Methods: Levels of cell-associated HIV-1 DNA and plasma HIV-1 RNA were measured longitudinally in 32 acutely and recently infected patients, who started ART <= 120 days after the estimated date of infection, and interrupted ART after 18 months (median) of continuous therapy. Averages of HIV-1 DNA and RNA concentrations present in blood 30-365 days after therapy interruption (median duration 300 days, range 195-358) were compared between patients who started ART <= 60 days after the estimated date of infection (early starters), those who started between 61 and 120 days (later starters), and, for HIV-1 RNA only, with 89 untreated participants of the Swiss HIV Cohort Study with documented sero-conversion and longitudinal measurements collected 90-455 days after the first positive HIV test.Results: In early ART starters, average levels of plasma HIV-1 RNA and cell-associated HIV-1 DNA after treatment interruption were 1 log(10) (P=0.008) and 0.4 log(10) (P=0.03) lower compared with later starters. Average post-treatment plasma HIV-1 RNA levels in early starters were significantly lower, respectively, compared with untreated controls (-1.2 log(10); P<0.0004).Conclusions: Early treatment initiation within 2 months after HIV infection compared with later therapy initiation resulted in reduced levels of plasma viraemia and proviral HIV-1 DNA for >= 1 year after subsequent ART cessation. Plasma HIV-1 RNA levels in early starters were also significantly lower than in untreated controls.

Intravitreal ranibizumab (Lucentis) for the treatment of myopic choroidal neovascularization.

BACKGROUND: Macular choroidal neovascularization (CNV) is one of the most vision-threatening complications of myopia, which can lead to severe vision loss. The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab in the treatment of myopic CNV. METHODS: We conducted a prospective, consecutive, interventional study of patients with subfoveal or juxtafoveal CNV secondary to pathologic myopia (PM) treated with intravitreal injection of ranibizumab in the Jules Gonin University Eye Hospital from June 2006 to February 2008. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT), and fluorescein angiography (FA) were performed at baseline and monthly for all patients. Indications for retreatment were loss in BCVA associated either with persistent leakage from CNV shown on FA, and/or evidence of CNV activity on OCT. RESULTS: The study included 14 eyes of 14 patients. The mean spherical equivalent refractive error was -12.5 (range, -8.0 D to -16.0 D). Mean time of follow-up was 8.4 months (range from 3 to 16 months, SD: 3). The mean number of intravitreal injections administered for each patient was 2.36 (SD 1.5). The mean initial visual acuity (VA) was 0.19 decimal equivalent (log-MAR: 0.71, SD: 0.3). A statistically significant improvement to a mean VA of 0.48 decimal equivalent (log-MAR:0.32, SD: 0.25) was demonstrated at the final follow-up. VA improved by a mean of 3.86 (SD 2.74) lines. Nine patients (64%) demonstrated a gain of 3 or more lines. Mean central macular thickness (CMT) measured with OCT was 304 microm (SD: 39) at the baseline, and was reduced significantly at the final follow-up to 153 microm (SD: 23). Average CMT reduction was 170 microm (SD: 57). No injection complications or drug-related side effects were noted during the follow-up period. CONCLUSIONS: In this small series of eyes with limited follow-up, intravitreal ranibizumab was a safe and effective treatment for CNV secondary to PM, resulting in functional and anatomic improvements.

Efficacy of daptomycin in implant-associated infection due to methicillin-resistant Staphylococcus aureus: importance of combination with rifampin.

Limited treatment options are available for implant-associated infections caused by methicillin (meticillin)-resistant Staphylococcus aureus (MRSA). We compared the activity of daptomycin (alone and with rifampin [rifampicin]) with the activities of other antimicrobial regimens against MRSA ATCC 43300 in the guinea pig foreign-body infection model. The daptomycin MIC and the minimum bactericidal concentration in logarithmic phase and stationary growth phase of MRSA were 0.625, 0.625, and 20 microg/ml, respectively. In time-kill studies, daptomycin showed rapid and concentration-dependent killing of MRSA in stationary growth phase. At concentrations above 20 microg/ml, daptomycin reduced the counts by >3 log(10) CFU/ml in 2 to 4 h. In sterile cage fluid, daptomycin peak concentrations of 23.1, 46.3, and 53.7 microg/ml were reached 4 to 6 h after the administration of single intraperitoneal doses of 20, 30, and 40 mg/kg of body weight, respectively. In treatment studies, daptomycin alone reduced the planktonic MRSA counts by 0.3 log(10) CFU/ml, whereas in combination with rifampin, a reduction in the counts of >6 log(10) CFU/ml was observed. Vancomycin and daptomycin (at both doses) were unable to cure any cage-associated infection when they were given as monotherapy, whereas rifampin alone cured the infections in 33% of the cages. In combination with rifampin, daptomycin showed cure rates of 25% (at 20 mg/kg) and 67% (at 30 mg/kg), vancomycin showed a cure rate of 8%, linezolid showed a cure rate of 0%, and levofloxacin showed a cure rate of 58%. In addition, daptomycin at a high dose (30 mg/kg) completely prevented the emergence of rifampin resistance in planktonic and adherent MRSA cells. Daptomycin at a high dose, corresponding to 6 mg/kg in humans, in combination with rifampin showed the highest activity against planktonic and adherent MRSA. Daptomycin plus rifampin is a promising treatment option for implant-associated MRSA infections.

Estimation of percentage body fat in 6- to 13-year-old children by skinfold thickness, body mass index and waist circumference.

We evaluated the accuracy of skinfold thicknesses, BMI and waist circumference for the prediction of percentage body fat (PBF) in a representative sample of 372 Swiss children aged 6-13 years. PBF was measured using dual-energy X-ray absorptiometry. On the basis of a preliminary bootstrap selection of predictors, seven regression models were evaluated. All models included sex, age and pubertal stage plus one of the following predictors: (1) log-transformed triceps skinfold (logTSF); (2) logTSF and waist circumference; (3) log-transformed sum of triceps and subscapular skinfolds (logSF2); (4) log-transformed sum of triceps, biceps, subscapular and supra-iliac skinfolds (logSF4); (5) BMI; (6) waist circumference; (7) BMI and waist circumference. The adjusted determination coefficient (R² adj) and the root mean squared error (RMSE; kg) were calculated for each model. LogSF4 (R² adj 0.85; RMSE 2.35) and logSF2 (R² adj 0.82; RMSE 2.54) were similarly accurate at predicting PBF and superior to logTSF (R² adj 0.75; RMSE 3.02), logTSF combined with waist circumference (R² adj 0.78; RMSE 2.85), BMI (R² adj 0.62; RMSE 3.73), waist circumference (R² adj 0.58; RMSE 3.89), and BMI combined with waist circumference (R² adj 0.63; RMSE 3.66) (P < 0.001 for all values of R² adj). The finding that logSF4 was only modestly superior to logSF2 and that logTSF was better than BMI and waist circumference at predicting PBF has important implications for paediatric epidemiological studies aimed at disentangling the effect of body fat on health outcomes.

Incidence et pronostic des métastases ganglionnaires dans les sarcomes des membres

Introduction : Bien que rares chez l'adulte, les sarcomes des tissus mous restent une maladie au pronostic très sombre. En effet, leur survie globale à 5 ans est de 50 % chez la femme et de 41 % chez l'homme. De plus, ils sont particulièrement difficiles à traiter, en raison de leur agressivité, de leur résistance face aux chimiothérapies et à la radiothérapie et d'autre part leur localisation conduit souvent à des opérations mutilantes. Pour les sarcomes des membres, il existe une opération appelée perfusion isolée du membre (ILP). Cela consiste à réaliser une chimiothérapie par voie intra-artérielle, en isolant le membre qui est perfusé par une solution Melphalan et de Tumor Necrosis Factor α à l'aide d'une circulation extra-corporelle pour son oxygénation. Ce type de traitement est à visée palliative, évitant une amputation du membre atteint. Pour accéder aux vaisseaux permettant la canulation de la pompe, un curage ganglionnaire est généralement effectué. Patients et méthode : Pour cette étude rétrospective, nous avons analysé la base de données des 278 ILP réalisées au Centre Hospitalier Universitaire Vaudois (CHUV) à Lausanne depuis mai 1988. Nous avons extrait et analysé de cette étude rétrospective 57 ILP réalisées pour des sarcomes. L'étude porte sur 52 patients traités entre le 19 février 1992 et le 14 décembre 2011, après avoir exclu les patients n'ayant pas bénéficié d'un curage ganglionnaire et la seconde ILP pour 4 patients qui en ont eu 2. Pour chacun de ces patients, les protocoles opératoires, les rapports d'examens radiologiques ainsi que les rapports de pathologies ont été revus et analysés. Nous avons également effectué une revue de la littérature sur PubMed. Résultats : Il y avait 28 hommes (53.8%) et 24 femmes (46.2 %). L'âge moyen au moment de l'ILP était de 56,7 ans (écart-type 16,8). Seul 3 patients sur les 52 avaient des métastases à distance au moment du diagnostic. Le curage ganglionnaire radical a montré que 13 patients (25 %) avaient une atteinte des ganglions lymphatiques (N+). Parmi les types histologiques qui ont présenté au moins une métastase ganglionnaire, on retrouve 2 léomyosarcomes, 2 sarcomes indifférenciés (anciennement MFH), 3 sarcomes épithélioïdes, 4 angiosarcomes et 2 synoviosarcomes. Pour les patients N0, la survie globale moyenne estimée par la méthode de Kaplan et Meier a été de 95,98 mois (CI 95% 66,72-125,23 mois). Pour les patients N1 la survie globale moyenne a chuté à 28,72 mois (CI 95% 6,48-50,97). Le test du Log Rank donne un Chi2 de 9,659 (P=0,002). La moyenne de survie sans maladie a été de 38,03 mois pour le groupe (N0) et de 10,87 mois pour le groupe N1, (CI 95 % 25,75-50,3 et 1,87-19,88 respectivement) et une valeur de P= 0.006. Nous n'avons pas mis en évidence de différence de survie statistiquement significative (P=0.946) entre les types ou les grades histologiques, en raison de la taille du collectif. Conclusion : Bien que rares, les métastases ganglionnaires des sarcomes des membres ont un impact négatif sur la survie à long terme du patient. Les résultats obtenus montrent qu'un curage peut participer au traitement régional et confirme la nécessité de pratiquer systématiquement une lymphadénectomie radicale en vue d'offrir les meilleures chances de survie au patient. Il faudrait donc se poser la question si la présence de métastases ganglionnaires ne devrait pas modifier la prise en charge pour tendre vers un traitement plus agressif chez de tels patients. Ce qui n'est pas le cas à l'heure actuelle.

Patient- and therapy-related factors on the wear of denture teeth : results of a clinical trial

OBJECTIVE: When we examined a previously published prospective multi-center clinical trial in which complete denture-wearers were followed over a period of 2 years, we found that about 30% of the variability in the clinical wear data of denture teeth was due to unknown characteristics of the subjects. In the second part of the study, we try to identify which patient- and therapy-related factors may explain some of this variability. METHODS: The clinical wear data of denture teeth at different recall times (6, 12, 18, 24 months) in 89 subjects (at baseline) were correlated with the following parameters, which may all have an influence on the wear of denture teeth: age, gender, bruxism as reported by the subjects, number of prostheses used so far, time since last extraction, smoking, fit of dentures as judged by the subject and the clinician, average denture wearing time and wearing of denture during the night. To evaluate the influence of the different patient- and therapy-related variables, both a univariate analysis (one extra factor to the model) and a multivariate analysis were carried out using linear mixed models with the variable Log mean as the outcome. RESULTS: None of the patient- and therapy-related parameters showed a statistically significant effect on the wear of denture teeth. There was, however, a trend for women to show less wear compared to men and a trend of decreasing wear with increasing age. SIGNIFICANCE: Further research is required to identify the factors which are responsible for the high variability observed between the subjects regarding clinical wear data.