12 research outputs found
Caspofungin Increases Fungal Chitin and Eosinophil and γΎ T Cell-Dependent Pathology in Invasive Aspergillosis
The polysaccharide-rich fungal cell wall provides pathogen-specific targets for antifungal therapy and distinct molecular patterns that stimulate protective or detrimental host immunity. The echinocandin antifungal caspofungin inhibits synthesis of cell wall ÎČ-1,3-glucan and is used for prophylactic therapy in immune-suppressed individuals. However, breakthrough infections with fungal pathogen Aspergillus fumigatus are associated with caspofungin prophylaxis. In this study, we report in vitro and in vivo increases in fungal surface chitin in A. fumigatus induced by caspofungin that was associated with airway eosinophil recruitment in neutropenic mice with invasive pulmonary aspergillosis (IA). More importantly, caspofungin treatment of mice with IA resulted in a pattern of increased fungal burden and severity of disease that was reversed in eosinophil-deficient mice. Additionally, the eosinophil granule proteins major basic protein and eosinophil peroxidase were more frequently detected in the bronchoalveolar lavage fluid of lung transplant patients diagnosed with IA that received caspofungin therapy when compared with azole-treated patients. Eosinophil recruitment and inhibition of fungal clearance in caspofungin-treated mice with IA required RAG1 expression and γΎ T cells. These results identify an eosinophil-mediated mechanism for paradoxical caspofungin activity and support the future investigation of the potential of eosinophil or fungal chitin-targeted inhibition in the treatment of IA
Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000â14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries
Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed
data for children (aged 0â14 years) and adults (aged 15â99 years) diagnosed with a haematological malignancy
during 2000â14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and
morphology, in young patients (aged 0â24 years).
Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3
that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0â14 years),
adolescents (15â19 years), and young adults (20â24 years). We categorised leukaemia subtypes according to the
International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases
for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs,
using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by
country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age
survival estimates were standardised to the marginal distribution of young people with leukaemia included in the
analysis.
Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and
20272 (12·3%) young adults. In 2010â14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients)
and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and
young adults for all leukaemias combined during 2010â14 varied widely, ranging from 46% in Mexico to more than
85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better
age-standardised survival (from 43% in Ecuador to â„80% in parts of Europe, North America, Oceania, and Asia) than
those with acute myeloid leukaemia (from 32% in Peru to â„70% in most high-income countries in Europe,
North America, and Oceania). Throughout 2000â14, survival from all leukaemias combined remained consistently
higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young
adults in most countries.
Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children,
adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower
survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators
of the quality of cancer management in this age group.peer-reviewe
Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000â2014 (CONCORD-3)
Background:
Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology.
Methods:
We analyzed individual data for adults (15â99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000â2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator.
Results:
The study included 556,237 adults. In 2010â2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%â38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000â2004 and 2005â2009. These improvements were more noticeable among adults diagnosed aged 40â70 years than among younger adults.
Conclusions:
To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines
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Investigating reindeer pastoralism and exploitation of high mountain zones in northern Mongolia through ice patch archaeology
In interior Eurasia, high mountain zones are crucial to pastoral subsistence, providing seasonally productive pastures and abundant wild resources. In some areas of northern Mongolia, mountainous tundra zones also support a low-latitude population of domestic reindeer herdersâa lifestyle whose origins are poorly characterized in the archaeological record of early Mongolia. Traditionally, reindeer pastoralists make significant seasonal use of munkh mus (eternal ice) for their domestic herds, using these features to cool heat-stressed animals and provide respite from insect harassment. In recent years, many of these features have begun to melt entirely for the first time, producing urgent threats to traditional management techniques, the viability of summer pastures, and reindeer health. The melting ice is also exposing fragile organic archaeological materials that had previously been contained in the patch. We present the results of horseback survey of ice patches in Baruun Taiga special protected area, providing the first archaeological insights from the region. Results reveal new evidence of historic tool production and wild resource use for fishing or other activities, and indicate that ice patches are likely to contain one of the few material records of premodern domestic reindeer use in Mongolia and lower Central Asia. The areaâs ancient ice appears to be rapidly melting due to changing climate and warming summer temperatures, putting both cultural heritage and traditional reindeer herding at extreme risk in the years to come
Caspofungin Increases Fungal Chitin and Eosinophil and γΎ T CellâDependent Pathology in Invasive Aspergillosis
Modulation of the IL-6 Receptor α Underlies GLI2-Mediated Regulation of Ig Secretion in Waldenström Macroglobulinemia Cells
30-Day Mortality in Acute Pulmonary Embolism: Prognostic Value of Clinical Scores and Anamnestic Features
Investigating reindeer pastoralism and exploitation of high mountain zones in northern Mongolia through ice patch archaeology
Isolate-Dependent Growth, Virulence, and Cell Wall Composition in the Human Pathogen Aspergillus fumigatus
Global survival trends for brain tumors, by histology: Analysis of individual records for 67,776 children diagnosed in 61 countries during 2000â2014 (CONCORD-3): ntroduction: Tumors of the central nervous system are among the leading causes of cancer-related death in children. Population-based cancer survival reflects the overall effectiveness of a health care system in managing cancer. Inequity in access to care world-wide may result in survival disparities.Methods: We considered children (0-14 years) diagnosed with a brain tumor during 2000-2014, regardless of tumor behavior. Data underwent a rigorous, three-phase quality control as part of CONCORD-3. We implemented a revised version of the International Classification of Childhood Cancer (third edition) to control for under-registration of non-malignant astrocytic tumors. We estimated net survival using the unbiased nonparametric Pohar Perme estimator.Results: The study included 67,776 children. We estimated survival for 12 histology groups, each based on relevant ICD-O-3 codes. Age-standardized 5-year net survival for low-grade astrocytoma ranged between 84% and 100% world-wide during 2000-2014. In most countries, 5-year survival was 90% or more during 2000-2004, 2005-2009, and 2010-2014. Global variation in survival for medulloblastoma was much wider, with age-standardized 5-year net survival between 47% and 86% for children diagnosed during 2010-2014.Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors in children, by histology. We devised an enhanced version of ICCC-3 to account for differences in cancer registration practices world-wide. Our findings may have public health implications, because low-grade glioma is 1 of the 6 index childhood cancers included by WHO in the Global Initiative for Childhood Cancer.
Abstract Introduction Tumors of the central nervous system are among the leading causes of cancer-related death in children. Population-based cancer survival reflects the overall effectiveness of a health care system in managing cancer. Inequity in access to care world-wide may result in survival disparities. Methods We considered children (0â14 years) diagnosed with a brain tumor during 2000â2014, regardless of tumor behavior. Data underwent a rigorous, three-phase quality control as part of CONCORD-3. We implemented a revised version of the International Classification of Childhood Cancer (third edition) to control for under-registration of non-malignant astrocytic tumors. We estimated net survival using the unbiased nonparametric Pohar Perme estimator. Results The study included 67,776 children. We estimated survival for 12 histology groups, each based on relevant ICD-O-3 codes. Age-standardized 5-year net survival for low-grade astrocytoma ranged between 84% and 100% world-wide during 2000â2014. In most countries, 5-year survival was 90% or more during 2000â2004, 2005â2009, and 2010â2014. Global variation in survival for medulloblastoma was much wider, with age-standardized 5-year net survival between 47% and 86% for children diagnosed during 2010â2014. Conclusions To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors in children, by histology. We devised an enhanced version of ICCC-3 to account for differences in cancer registration practices world-wide. Our findings may have public health implications, because low-grade glioma is 1 of the 6 index childhood cancers included by WHO in the Global Initiative for Childhood Cancer