62 research outputs found

    Tumor Heterogeneity of Fibroblast Growth Factor Receptor 3 (FGFR3) Mutations in Invasive Bladder Cancer: Implications for Peri-Operative anti-FGFR3 Treatment

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    Background: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. Patients: and methods We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201).Results: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type.Conclusions: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting

    Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma.

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    Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA

    Burden of community-acquired and nosocomial rotavirus gastroenteritis in the pediatric population of Western Europe: a scoping review

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    <p>Abstract</p> <p>Background</p> <p>Rotavirus affects 95% of children worldwide by age 5 years and is the leading cause of severe dehydrating diarrhea. The objective of this review was to estimate the burden of rotavirus gastroenteritis (RVGE) in the Western European pediatric population.</p> <p>Methods</p> <p>A comprehensive literature search (1999-2010) was conducted in PubMed and other sources (CDC; WHO, others). Data on the epidemiology and burden of RVGE among children < 5 years-old in Western Europe --including hospital-acquired disease--were extracted.</p> <p>Results</p> <p>76 studies from 16 countries were identified. The mean percentage of acute gastroenteritis (AGE) cases caused by rotavirus ranged from 25.3%-63.5% in children < 5 years of age, peaking during winter. Incidence rates of RVGE ranged from 1.33-4.96 cases/100 person- years. Hospitalization rates for RVGE ranged from 7% to 81% among infected children, depending on the country. Nosocomial RVGE accounted for 47%-69% of all hospital-acquired AGE and prolonged hospital stays by 4-12 days. Each year, RVGE incurred 0.540.54- 53.6 million in direct medical costs and 1.71.7-22.4 million in indirect costs in the 16 countries studied. Full serotyping data was available for 8 countries. G1P[8], G2P[4], G9P[8], and G3P[8] were the most prevalent serotypes (cumulative frequency: 57.2%- 98.7%). Serotype distribution in nosocomial RVGE was similar.</p> <p>Conclusions</p> <p>This review confirms that RVGE is a common disease associated with significant morbidity and costs across Western Europe. A vaccine protecting against multiple serotypes may decrease the epidemiological and cost burden of RVGE in Western Europe.</p

    Simulation des effets de la variabilité atmosphérique sur les grands feux en France

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    International audienceLarge wildfires across parts of France can cause devastating damage which puts lives, infrastructure, and the natural ecosystem at risk. In the climate change context, it is essential to better understand how these large wildfires relate to weather and climate and how they might change in a warmer world. Such projections rely on the development of a robust modelling framework linking large wildfires to present-day atmospheric variability. Drawing from a MODIS product and a gridded meteorological dataset, we derived a suite of biophysical and fire danger indices and developed generalized linear models simulating the probability of large wildfires ( > 100 ha) at 8 km spatial and daily temporal resolutions across the entire country over the last two decades. The models were able to reproduce large-wildfire activity across a range of spatial and temporal scales. Different sensitivities to weather and climate were detected across different environmental regions. Long-term drought was found to be a significant predictor of large wildfires in flammability-limited systems such as the Alpine and south-western regions. In the Mediterranean, large wildfires were found to be associated with both short-term fire weather conditions and longer-term soil moisture deficits, collectively facilitating the occurrence of large wildfires. Simulated probabilities on days with large wildfires were on average 2-3 times higher than normal with respect to the mean seasonal cycle, highlighting the key role of atmospheric variability in wildfire spread. The model has wide applications, including improving our understanding of the drivers of large wildfires over the historical period and providing a basis on which to estimate future changes to large wildfires from climate scenarios

    Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up

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    Methods: Seventy four children referred because of insufficient control of persistent asthma were randomly allocated to 1 year follow up by a paediatrician or asthma nurse. The main outcome measure was the percentage of symptom-free days. Additional outcome measures were airway hyperresponsiveness, lung function, daily dose of inhaled corticosteroids (ICS), number of exacerbations, number of additional visits to the general practitioner, absence from school, functional health status, and disease specific quality of life. Results: There were no significant differences at the end of the 1 year study period between the two treatment groups in percentage of symptom-free days (mean difference 2.5%; 95% CI -8.8 to 13.8), airway hyperresponsiveness (log(10) PD(20) 0.06; -0.19 to 0.32), functional health status (10.1; -0.3 to 19.8), disease specific quality of life of patients (0.08; -0.9 to 0.7), and disease specific quality of life of caregivers (0.09; -0.2 to 0.3), nor in any other outcome parameters. Most outcome parameters improved considerably over the 1 year study period. These improvements were achieved although the daily dose of ICS was reduced by a mean of 26% compared with the dose received by children at referral. All parents were satisfied with the asthma care received. Conclusions: After initial assessment in a multidisciplinary clinic, childhood asthma can be successfully managed by an asthma nurse in close cooperation with a paediatrician. During close follow up by paediatrician or asthma nurse, asthma control improved despite a reduction in ICS dose

    Multiple types of dieting prospectively predict weight gain during the freshman year of college.

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    The freshman year of college is a period of heightened risk for weight gain. This study examined measures of restrained eating, disinhibition, and emotional eating as predictors of weight gain during the freshman year. Using Lowe\u27s multi-factorial model of dieting, it also examined three different types of dieting as predictors of weight gain. Sixty-nine females were assessed at three points during the school year. Weight gain during the freshman year averaged 2.1 kg. None of the traditional self-report measures of restraint, disinhibition, or emotional eating were predictive of weight gain. However, both a history of weight loss dieting and weight suppression (discrepancy between highest weight ever and current weight) predicted greater weight gain, and these effects appeared to be largely independent of one another. Individuals who said they were currently dieting to lose weight gained twice as much (5.0 kg) as former dieters (2.5 kg) and three times as much as never dieters (1.6 kg), but the import of this finding was unclear because there was only a small number of current dieters (N=7). Overall the results indicate that specific subtypes of dieting predicts weight gain during the freshman year better than more global measures of restraint or overeating.<br /
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