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We propose a method for recruiting asymptomatic Amyloid positive individuals in clinical trials, using a two-step process. We first select during a pre-screening phase a subset of individuals which are more likely to be amyloid positive based on the automatic analysis of data acquired during routine clinical practice, before doing a confirmatory PET-scan to these selected individuals only. This method leads to an increased number of recruitments and to a reduced number of PET-scans, resulting in a decrease in overall recruitment costs. We validate our method on three different cohorts, and consider five different classification algorithms for the pre-screening phase. We show that the best results are obtained using solely cognitive, genetic and socio-demographic features, as the slight increased performance when using MRI or longitudinal data is balanced by the cost increase they induce. We show that the proposed method generalizes well when tested on an independent cohort, and that the characteristics of the selected set of individuals are identical to the characteristics of a population selected in a standard way. The proposed approach shows how Machine Learning can be used effectively in practice to optimize recruitment costs in clinical trials.

Importance: Prognostic factors are lacking in neurosarcoidosis (NS), and the association of immunosuppressive treatments with outcomes are unclear., Objectives: To identify prognostic factors of and analyze the association of immunosuppressive treatment with relapse of NS., Design, Setting, and Participants: In this retrospective study, a cohort of 234 patients fulfilled the diagnostic criteria for NS in a tertiary referral center in Paris, France, from January 1, 1990, through December 31, 2015. The median follow-up was 8 years (range, 2 months to 23 years)., Main Outcomes and Measures: All neurologic and extraneurologic data and treatments were analyzed. Functional outcomes measured by the absolute value and the variation from baseline of the Expanded Disability Status Scale (EDSS) score at 60 months after the diagnosis, overall survival, and relapse-free survival (RFS) were assessed. Analyses were stratified by the period of NS diagnosis (1990-1999 vs 2000-2015)., Results: The 234 patients undergoing assessment included 117 women (50.0%) and 117 men (50.0%); median age was 42 years (interquartile range, 32-53 years). The probable 10-year survival rate was 89% (95% CI, 84%-94%). Older age (hazard ratio [HR] per 10 years, 1.64; 95% CI, 1.19-2.27; P = .003), peripheral nervous system involvement (HR, 6.75; 95% CI, 2.31-19.7; P < .001), and higher baseline EDSS score (HR per point, 1.21; 95% CI, 1.06-1.39; P = .005) were associated with mortality. The estimated 10-year RFS rate was 14% (95% CI, 9%-22%) for all relapses and 28% (95% CI, 20%-38%) for neurologic relapses. Encephalic involvement was associated with shorter neurologic RFS (HR, 2.35; 95% CI, 1.44-3.83; P < .001). A lower risk for relapse was associated with cyclophosphamide (HR, 0.26; 95% CI, 0.11-0.59; P = .001), methotrexate sodium (HR, 0.47; 95% CI, 0.25-0.87; P = .02), and infliximab (HR, 0.16; 95% CI, 0.02-1.24; P = .08) treatments. Follow-up was greater than 60 months in 160 patients (68.4%). An elevated baseline EDSS score (odds ratio [OR] per point, 1.92; 95% CI, 1.55-2.37; P < .001), tobacco use (OR, 3.64; 95% CI, 1.36-9.73; P = .01), encephalic symptoms (OR, 3.04; 95% CI, 1.11-8.38; P = .03), and less than 4 extraneurologic sarcoidosis localizations (OR, 3.06; 95% CI, 1.04-8.98; P = .04) were associated with an EDSS value of at least 2.5 at 60 months. Encephalic involvement (16 of 17 patients [94.1%]; P = .008) and peripheral nervous system involvement (5 of 17 patients [29.4%]; P = .03) were associated with worsening of the EDSS score at 60 months., Conclusions and Relevance: This study identifies putative factors affecting morbidity and mortality in patients with NS. Immunosuppressive therapies (ie, intravenous cyclophosphamide, methotrexate, and infliximab) in these patients may be associated with lower relapse rates.

Purpose: To compare perfusion-weighted (PW) imaging and apparent diffusion coefficient (ADC) maps in prediction of infarct size and growth in patients with acute middle cerebral artery infarct., Materials and Methods: This study was approved by the local institutional review board. Written informed consent was obtained from all 80 patients. Subsequent infarct volume and growth on follow-up magnetic resonance (MR) images obtained within 6 days were compared with the predictions based on PW images by using a time-to-peak threshold greater than 4 seconds and ADC maps obtained less than 12 hours after middle cerebral artery infarct. ADC- and PW imaging-predicted infarct growth areas and infarct volumes were correlated with subsequent infarct growth and follow-up diffusion-weighted (DW) imaging volumes. The impact of MR imaging time delay on the correlation coefficient between the predicted and subsequent infarct volumes and individual predictions of infarct growth by using receiver operating characteristic curves were assessed., Results: The infarct volume measurements were highly reproducible (concordance correlation coefficient [CCC] of 0.965 and 95% confidence interval [CI]: 0.949, 0.976 for acute DW imaging; CCC of 0.995 and 95% CI: 0.993, 0.997 for subacute DW imaging). The subsequent infarct volume correlated (P<.0001) with ADC- (ρ=0.853) and PW imaging- (ρ=0.669) predicted volumes. The correlation was higher for ADC-predicted volume than for PW imaging-predicted volume (P<.005), but not when the analysis was restricted to patients without recanalization (P=.07). The infarct growth correlated (P<.0001) with PW imaging-DW imaging mismatch (ρ=0.470) and ADC-DW imaging mismatch (ρ=0.438), without significant differences between both methods (P=.71). The correlations were similar among time delays with ADC-predicted volumes but decreased with PW imaging-based volumes beyond the therapeutic window. Accuracies of ADC- and PW imaging-based predictions of infarct growth in an individual prediction were similar (area under the receiver operating characteristic curve [AUC] of 0.698 and 95% CI: 0.585, 0.796 vs AUC of 0.749 and 95% CI: 0.640, 0.839; P=.48)., Conclusion: The ADC-based method was as accurate as the PW imaging-based method for evaluating infarct growth and size in the subacute phase., (© RSNA, 2012)

Objectives: To determine the feasibility, toxicity and efficacy of a first-line combination of intraperitoneal (i.p.) paclitaxel and cisplatin and intravenous (i.v.) ifosfamide in untreated patients with Stage IIIc ovarian cancer after cytoreduction or biopsies only., Methods: Twenty-six patients entered the trial from 1995 to 1999. Twenty underwent initial cytoreduction which was complete, with residual nodules < 0.5 cm or = 0.5 cm in six, five and nine patients, respectively. Six patients underwent biopsies only at initial surgery. Ten cycles of chemotherapy were planned by both routes. Second-look surgery was planned for all patients., Results: Twenty-one (81%) of the 26 patients were in complete clinical remission (CCR) at the time of second-look surgery. Of the 15 patients who underwent second-look surgery, ten were in CCR including seven in complete remission (CR) confirmed pathologically. Median overall-survival had not been reached at 53 months (range 16-87), and median disease-free survival was 40 months (range 8-85), for a median follow-up of 53 months (range 16-87). Local toxicity consisted mainly of mild abdominal pain. Systemic toxicity was essentially haematological, with eight (31%) grade 3-4 leukopenia., Conclusion: This study has demonstrated the feasibility, moderate toxicity and efficacy of first-line intraperitoneal paclitaxel-cisplatin chemotherapy.

Non-B HIV-1 samples collected in France between 1999 and 2001 were sequenced in the env, reverse transcriptase (RT), and protease genes (1) to characterize further the non-B strains circulating in the country, (2) to assess the importance of recombination, and (3) to describe the polymorphism of RT and protease genes and appreciate a possible impact on susceptibility to antiretroviral (ARV) drugs. The results show that, within a background of CRF02&#95;AG predominance, there is a high genetic diversity of non-B isolates, including intersubtype recombinants. There is an extensive polymorphism of protease and RT genes compared with B consensus sequences; we have so far no data indicating that these non-B isolates may have reduced sensitivity to ARV drugs.

Multiple imaging techniques are available to diagnose cervical arterial dissections. It may be possible to image the vessel wall hematoma (US, MRI, 2D or 3D MRA source images, CTA source images), the narrowed arterial lumen (MRA, CTA, catheter angiography), or the hemodynamic impact of the affected vessel. There is no available guideline in the literature regarding the imaging work-up at diagnosis or follow-up. The Société Française Neurovasculaire and the Société Française de Neuroradiologie have sponsored a multi-center study to evaluate current imaging strategies. Results from several centers, while being variable, do share some similarities: the preferred use of non-invasive or minimally invasive techniques to evaluate the vessel wall and the vascular lumen and/or hemodynamic impact, the use of fat suppressed sequences at MRI, the use of Gadolinium enhanced MRA, the limited interest for CT techniques, and the still important use of catheter angiography in selected cases.

We assess the genetic relationships between 49 HIV-1 group O strains from 24 and 25 patients living in Cameroon and France, respectively. Strains were sequenced in four genomic regions: gag (p24) and three env regions (C2-V3, gp41, and for 22 C2-gp41). In each of the genomic regions analyzed, the genetic diversity among the group O strains was higher than that exhibited by group M. We characterize three major group O phylogenetic clusters (O:A, O:B, and O:C) that comprised the same virus strains in each of the genomic regions analyzed. The majority of strains cluster in O:A, a cluster previously identified by analysis of pol and env sequences. Group O recombinants were also identified. Importantly, the distinction between these three major group O clades was weak compared to the strong clustering apparent in the global group M phylogenetic tree that led to the identification of subtypes. Thus, these clusters of group O viruses should not be considered as equivalent to the group M subtypes. This difference between the pattern of group O and the global group M diversity, both taking into account the pandemic status of the group M subtypes and the comparatively small number of group O-infected individuals (the majority being from Cameroon), indicates that the group O phylogeny primarily represents viral divergence in the Cameroon region, analogous to group M viral diversity present in the Democratic Republic of Congo.

Objectives: To determine the contribution of methionine/valine (Met/Val) polymorphism at codon 129 of the prion protein (PrP) gene in the neuropathologic pattern and mechanisms of lesion development in sporadic Creutzfeldt-Jakob disease., Background: Creutzfeldt-Jakob disease is a transmissible spongiform encephalopathy characterized by a conformational change of PrP and a variety of PrP deposits in the brain, some of which aggregate into amyloid plaques., Methods: The authors semiquantitatively assessed neuropathologic lesions and performed PrP immunolabeling in 70 patients (39 Met/Met, 11 Met/Val, 20 Val/Val) who had died in France between 1994 and 1998., Results: Met/Met cases (mild lesions mostly involving the occipital areas, low PrP load, few focal PrP nonamyloid deposits, no amyloid plaques) contrasted with Met/Val cases (marked lesions especially in the parahippocampal gyrus, high PrP load, numerous amyloid plaques) and with Val/Val cases (younger patients, longer course of disease: 11.5 +/- 3 months, and distinct neuropathology: severe lesions heavily involving the hippocampal formation and basal ganglia, high PrP load, numerous focal nonamyloid deposits, rare amyloid plaques). The course of Val/Val patients younger than age 55 was particularly long (19.9 +/- 7 months), and the isocortex bore the brunt of the pathology, suggesting a distinct variety., Conclusions: Polymorphism at codon 129 modulates the phenotype of sporadic Creutzfeldt-Jakob disease. The Val genotype enhances the production of proteinase-resistant PrP, and the Met/Val genotype facilitates its aggregation into amyloid plaques.

Objective: To estimate the statistical distribution of the incubation period of Creutzfeldt-Jakob disease (CJD) in human growth hormone (hGH) recipients in France., Background: Published papers suggest that the median incubation period of hGH-related CJD is approximately 15 years, but there are as yet no statistical data that support this assertion., Methods: Of the 1,361 hGH recipients who were included in this study, 55 had developed CJD at the time of the study. Individual data on hGH treatment history were available. Different mathematical models were used to estimate the statistical distribution of the incubation period. One main feature of the models was to take into account the occurrence of future CJD cases., Results: Models showed that the mean incubation period was 9 to 10 years, and the 95th percentile of the distribution was 15 to 16 years. Data and models indicated that the incubation period was significantly shorter in homozygotes at codon 129 of the prion protein gene than in heterozygotes., Conclusions: The short mean incubation period of CJD in French hGH recipients may be due to high infectivity in hormone lots. Estimates of the 95th percentile indicate that the number of hGH-related CJD cases may continue to increase in the coming years.

Background: Recent developments in animal and humans transmissible spongiform encephalopathies have motivated a study on incidence and risk factors of Creutzfeldt-Jakob disease (CJD) in France and 4 other European countries., Methods: CJD cases were ascertained through a national network including 250 neurological departments or neuropathological laboratories. CJD cases were classified as definite, probable or possible. Overall incidence rate and age-standardized incidence rates by department were computed. Standardized incidence ratios and their 95% confidence intervals were computed for comparing observed and expected number of CJD cases in each department., Results: Between 1992 and 1995, 216 CJD cases were registered (mean incidence rate: 0.87 per million inhabitants). The distribution of CJD cases was heterogeneous (p < 0.007). Nevertheless, the distribution of standardized incidence ratios fitted quite well a Poisson distribution. The observed number of CJD cases was significantly higher than expected in 4 departments and lower in 1 department., Conclusion: Incidence of CJD in France is similar to that observed in other European countries. Analysis of distribution of CJD cases by department showed a few significant differences which can be due to random fluctuations.

We diagnosed Cruetzfeldt-Jakob disease in 34 patients (16 definite, 18 probable) who had received human growth hormone extract for various period of time (mean +/- SD, 2.9 years), but particularly during the period between January 1984 and July 1985, a potential high-risk factor. Disease duration for deceased patients (n = 30) was 17 +/- 9 months. The clinical picture was homogeneous, starting with cerebellar ataxia and ocular motor disorders in about 90% of the patients. Neurologic deterioration, including dementia and myoclonic jerks, occurred within months. The high number of cases (1.5% of those treated between 1959 and 1988, 3% of those treated during the putative high-risk period) is still unexplained. We discuss the possibility that new cases will be detected,the risk of contaminating the general public, and the sanitary measures undertaken to prevent this.

Transmissible spongiform encephalopathies (TSE) are rare lethal diseases induced in humans and animals by unconventional agents (TSA) named also prions or virinos. TSA/prions have unconventional properties; in particular, they resist to almost all the chemical and physical processes which inactivate conventional viruses. Natural history of TSE indicates that organs are infectious a long time before the appearance of the clinical symptoms. The only specific marker of the TSA infections is the post-translational accumulation of the host encoded protein PrP (Prion Protein). Iatrogenic Creutzfeldt-Jakob disease (CJD) cases have been described after neurosurgery, treatment with pituitary derived hormones, and cornea and dura mater grafting. TSA associated infectivity is depending upon the nature of the organ in a given infected individual: central nervous system has the highest infectivity, spleen and lymph nodes a medium infectivity, and organs like bone or skin do not harbor any detectable infectious particle. Therefore, donors with neurologic history must be excluded and treatment with pituitary derived hormones should be considered as potentially infected with TSA, and excluded.