Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling

Abstract Background In randomized clinical trials or observational studies, it is common to collect biomarker values longitudinally on a cohort of individuals. The investigators may be interested in grouping individuals that share similar changes of biomarker values and use these groups for diagnosis or therapeutic purposes. However, most classical model-based classification methods rely mainly on empirical models such as splines or polynomials and do not reflect the physiological processes. Methods A model-based classification method was developed for longitudinal biomarker measurements through a pharmacokinetic model that describes biomarker changes over time. The method is illustrated using data on human Chorionic Gonadotrophic Hormone measurements after curettage of hydatidiform moles. Results The resulting classification was linked to the evolution toward gestational trophoblastic neoplasia and may be used as a tool for early diagnosis. The diagnostic accuracy of the pharmacokinetic model was more reproducible than the one of a purely mathematical model that did not take into account the biological processes. Conclusion The use of pharmacokinetic models in model-based classification approaches can lead to clinically useful classifications

Occupational Trichloroethylene Exposure and Cervical Pathology: A Case-Control Study

Trichloroethylene (TCE) is suspected of association with elevated risk of cervical cancer. A case-control study was performed in a geographical area in which occupational TCE exposure is high. The study objective was to analyze the correlation between occupational TCE exposure and cervical cancer (including precancerous conditions).Case and control subjects were recruited by gynecologists. General and occupational data were collected by telephonic interviews. An industrial hygienist assessed occupational TCE exposure on a task-exposure matrix. Analysis focused on occupational TCE exposure at various levels and on cumulative dose. Multivariate analysis was performed to take account of the various risk factors.In total, 67 case and 67 age-matched control subjects were included. Mean age was 36 years in both groups. Five of the possible general risk factors correlated significantly with cervical dysplasia or cancer: number of partners, history of genital or anal wart, interval between first period and first sexual relation, parity, and body mass index, the last three showing inverse correlation. Elevated risk was found in women who had had jobs as manual workers according to the PCS French classification (professions and socioprofessional categories), and production and related workers according to ISCO classification (International Standard Classification of Occupations), with odds ratios (ORs), adjusted on general and medical risk factors, of 7.68 [95% confidence interval (CI): 1.39-42.54] and 7.48 (1.30-43.24), respectively, among skilled service sector workers; the adjusted OR was close to significance, at 4.67 (95% CI: 0.92-23.67). No occupational sectors were significantly associated with elevated risk. In all, 17 (25.4%) case and 15 (22.4%) control subjects were exposed to TCE: raw OR = 1.17 (95% CI: 0.54-2.52), adjusted OR = 1.51 (95% CI: 0.42-5.41). There was no significant correlation between cumulative dose and exposure time.The study found no significantly increased risk of cervical dysplasia or cancer associated with occupational TCE exposure

Additional file 1: of Early diagnosis of gestational trophoblastic neoplasia based on trajectory classification with compartment modeling

Simulation design and results. (PDF 101 kb

Imaging Characteristics of Venous Parenchymal Abnormalities

International audienceBackground and Purpose-There are few published data on the patterns of parenchymal imaging abnormalities in a context of cerebral venous thrombosis (CVT). The objectives of the present study were to describe the patterns of parenchymal lesions associated with CVT and to determine the lesion sites. Methods-We included 44 consecutively hospitalized patients with CVT and parenchymal lesions on magnetic resonance imaging. The diagnosis of CVT had been confirmed by magnetic resonance imaging/magnetic resonance venography. Magnetic resonance imaging patterns for CVT were retrospectively analyzed with regard to the lesion's type, shape, and site. Results-The most frequent stroke subtype was hemorrhagic ischemia (in 56.8% of cases), followed by intracerebral hematoma (in 22.72% of cases) and nonhemorrhagic ischemia (in 20.45% of cases). Although there were no significant differences between these 3 groups with regard to the clinical and radiological characteristics, we observed a nonsignificant trend (P=0.08) toward a shorter time interval between hospital admission and magnetic resonance imaging for nonhemorrhagic stroke. The CVT parenchymal abnormalities were centered on 6 main foci and were related to the site of venous occlusion: (1) the inferior parietal lobule (n=20; 44.5%), associated mainly with occlusion of the transverse sinus (n=10) or pure cortical veins (n=10); (2) the inferior and posterior temporal regions (n=10; 22.75%), associated mainly with occlusion of the transverse sinus (n=9); (3) the parasagittal frontal region (n=6; 13.6%), associated mainly with occlusion of the superior sagittal sinus (n=4) or the transverse sinus (n=4); (4) the thalamus (n=5; 11.3%) associated with occlusion of the straight sinus (n=5); (5) the cerebellar hemisphere (n=2; 4.5%), associated in both cases with occlusion of the transverse sinus; and (6) the deep hemispheric regions (n=3; 6.8%), associated with occlusion of the superior sagittal sinus in all cases. Conclusions-Parenchymal lesions caused by CVT display specific anatomic patterns, which is mainly determined by the site of venous occlusion

Imaging Characteristics of Venous Parenchymal Abnormalities

International audienceBackground and Purpose-There are few published data on the patterns of parenchymal imaging abnormalities in a context of cerebral venous thrombosis (CVT). The objectives of the present study were to describe the patterns of parenchymal lesions associated with CVT and to determine the lesion sites. Methods-We included 44 consecutively hospitalized patients with CVT and parenchymal lesions on magnetic resonance imaging. The diagnosis of CVT had been confirmed by magnetic resonance imaging/magnetic resonance venography. Magnetic resonance imaging patterns for CVT were retrospectively analyzed with regard to the lesion's type, shape, and site. Results-The most frequent stroke subtype was hemorrhagic ischemia (in 56.8% of cases), followed by intracerebral hematoma (in 22.72% of cases) and nonhemorrhagic ischemia (in 20.45% of cases). Although there were no significant differences between these 3 groups with regard to the clinical and radiological characteristics, we observed a nonsignificant trend (P=0.08) toward a shorter time interval between hospital admission and magnetic resonance imaging for nonhemorrhagic stroke. The CVT parenchymal abnormalities were centered on 6 main foci and were related to the site of venous occlusion: (1) the inferior parietal lobule (n=20; 44.5%), associated mainly with occlusion of the transverse sinus (n=10) or pure cortical veins (n=10); (2) the inferior and posterior temporal regions (n=10; 22.75%), associated mainly with occlusion of the transverse sinus (n=9); (3) the parasagittal frontal region (n=6; 13.6%), associated mainly with occlusion of the superior sagittal sinus (n=4) or the transverse sinus (n=4); (4) the thalamus (n=5; 11.3%) associated with occlusion of the straight sinus (n=5); (5) the cerebellar hemisphere (n=2; 4.5%), associated in both cases with occlusion of the transverse sinus; and (6) the deep hemispheric regions (n=3; 6.8%), associated with occlusion of the superior sagittal sinus in all cases. Conclusions-Parenchymal lesions caused by CVT display specific anatomic patterns, which is mainly determined by the site of venous occlusion

Pregnancy after oocyte donation in a patient with NLRP7 gene mutations and recurrent molar hydatidiform pregnancies

International audienceMolar pregnancies are benign trophoblastic diseases associated with a risk of malignant transformation. If aetiology remains mostly unknown, the risk of recurrent molar pregnancy is around 1.5% after one molar pregnancy and around 25% after 2 molar pregnancies. In the later situation, genetic mutations have been described, increasing hugely this risk. In case of mutations, probability to obtain a normal pregnancy is estimated around 1.8%. We report the case of a Caucasian 30-year-old woman whose previous five spontaneous pregnancies had a negative outcome: a spontaneous miscarriage and then 4 complete hydatidiform moles. Genetic testing revealed that the patient carried two heterozygous mutations in theNLRP7gene (c.2982-2A > G and Y318CfsX7). According to this, counselling was conducted to advocate for oocyte donation in order to obtain a normal pregnancy. This technique enabled a complication-free, singleton pregnancy that resulted in a healthy term live birth of a 2900 g female. Few months after delivery, the patient presented a new complete hydatidiform mole. Women presented with mutations in theNLRP7, KHDC3LorPADI6genes are unlikely to obtain normal pregnancies, with a major risk of reproductive failure. In such a context, oocyte donation may be the best option. Only 4 normal pregnancies and deliveries have been published in this situation through this technique to our knowledge

Patience, prudence et petits pas, A la recherche du sens du travail social et médico-social.: L'exemple des Maisons de la métropole du territoire de Vénissieux - Saint-Fons

International audienceCet ouvrage de "sociologie dessinée" est le fruit d'une recherche-action mené par le Collectif Métis qui a rassemblé et fait dialoguer pendant deux ans une équipe de sociologues, un illustrateur, des praticiens du travail social et des agents d'encadrement

Terminal 6q deletions cause brain malformations, a phenotype mimicking heterozygous DLL1 pathogenic variants : A multicenter retrospective case series

International audienceTerminal 6q deletion is a rare genetic condition associated with a neurodevelopmental disorder characterized by intellectual disability and structural brain anomalies. Interestingly, a similar phenotype is observed in patients harboring pathogenic variants in the DLL1 gene. Our study aimed to further characterize the prenatal phenotype of this syndrome as well as to attempt to establish phenotype-genotype correlations. We collected ultrasound findings from 22 fetuses diagnosed with a pure 6qter deletion. We reviewed the literature and compared our 22 cases with 14 fetuses previously reported as well as with patients with heterozygous DLL1 pathogenic variants. Brain structural alterations were observed in all fetuses. The most common findings (>70%) were cerebellar hypoplasia, ventriculomegaly, and corpus callosum abnormalities. Gyration abnormalities were observed in 46% of cases. Occasional findings included cerebral heterotopia, aqueductal stenosis, vertebral malformations, dysmorphic features, and kidney abnormalities. This is the first series of fetuses diagnosed with pure terminal 6q deletion. Based on our findings, we emphasize the prenatal sonographic anomalies, which may suggest the syndrome. Furthermore, this study highlights the importance of chromosomal microarray analysis to search for submicroscopic deletions of the 6q27 region involving the DLL1 gene in fetuses with these malformations