19 research outputs found

    Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer

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    BACKGROUND: The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence. METHODS: Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed. RESULTS: Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence. CONCLUSION: Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.</p

    Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania

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    The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replicable associations with genome-wide levels of evidence including a newly implicated variant on chromosome 6. Jointly, these variants account for around one-tenth of the heritability of severe malaria, which we estimate as -23% using genome-wide genotypes. We interrogate available functional data and discover an erythroid-specific transcription start site underlying the known association in ATP2B4, but are unable to identify a likely causal mechanism at the chromosome 6 locus. Previously reported HLA associations do not replicate in these samples. This large dataset will provide a foundation for further research on thegenetic determinants of malaria resistance in diverse populations.Peer reviewe

    Psychosocial development in survivors of childhood differentiated thyroid carcinoma: A cross-sectional study

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    Objective: The impact of childhood differentiated thyroid carcinoma (DTC) on psychosocial development has not yet been studied. The aim of this study was to evaluate the achievement of psychosocial developmental milestones in long-term survivors of childhood DTC. Design and methods: Survivors of childhood DTC diagnosed between 1970 and 2013 were included. Reasons for exclusion were age 35 years at follow-up, a follow-up period <5 years or diagnosis with DTC as a second malignant neoplasm. Survivors gathered peer controls of similar age and sex (n=30

    A tribute to Jonathan Borwein (Part 2) Preface

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    A field trial to assess a blood-Stage malaria vaccine

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    BACKGROUND--Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS--In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS--The cumulative incidence of the primary end point was 48.4% in the malariavaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS--On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine

    Lactimicrobium massiliense gen. nov., sp. nov.; Anaerolactibacter massiliensis gen. nov., sp. nov.; Galactobacillus timonensis gen. nov., sp. nov. and Acidipropionibacterium timonense sp. nov. isolated from breast milk from healthy breastfeeding African women

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    Four strains isolated by microbial culturomics from breast milk of healthy mothers from Mali were not identified and characterized by taxono-genomics. This led us to propose the new genera and species Lactimicrobium massiliense, Anaerolactibacter massiliensis and Galactobacillus timonensis containing type strain Marseille-P4301T (CSUR P4301T), Marseille-P4302T (CSUR P4302T) and Marseille-P4641T (CSUR P4641T), respectively. The strain Marseille-P4482 represents a novel species, Acidipropionibacterium timonense, in a previously known genus with type strain being Marseille-P4482T (CSUR P4482T). Keywords: Culturomics, human breast milk, microbiome, microbiota, taxono-genomic
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