9 research outputs found
VAV1 and BAFF, via NFÎșB pathway, are genetic risk factors for myasthenia gravis
Objective To identify novel genetic loci that predispose to earlyâonset myasthenia gravis (EOMG) applying a twoâstage association study, exploration, and replication strategy. Methods Thirtyâfour loci and one confirmation loci, human leukocyte antigen (HLA)âDRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, Bâcell activating factor (BAFF), and tumor necrosis factorâalpha (TNFâα), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLAâDRA and TNFâα loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for Tâ and Bâcell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of Bâcells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factorâkappaB (NFÎșB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG
322. Evaluation of the BioFireÂź Bone and Joint Infection (BJI) Panel for the Detection of Microorganisms and Antimicrobial Resistance Genes in Synovial Fluid Specimens
Background
Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFireÂź Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods.
Methods
Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures.
Results
A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes.
Conclusion
The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs
LA CARENCE EN FER (MISE AU POINT BIBLIOGRAPHIQUE ; ETUDE EPIDEMIOLOGIQUE ET D'IMPACT SUR LA QUALITE DE VIE)
CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF
The structure of multidimensional strained flames under transcritical conditions
International audienc
Agricultural exposure and risk of soft tissue sarcomas and gastrointestinal stromal sarcoma in the AGRIculture and CANcer (AGRICAN) cohort
BACKGROUND: Sarcomas are a heterogeneous group of tumors whose incidence is nearly 5 per 100 000 inhabitants in Europe. Their causes are poorly understood, although occupational exposures (especially farming and pesticides) are suspected. METHODS: The AGRICAN cohort is a prospective study of 181,842 individuals enrolled in 2005-2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, GIST (gastro-intestinal stromal tumors) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. RESULTS: Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (1) among cattle farmers working <â10âyears (HR(<10years) =2.45, 95%CI 1.36-4.43) and breeding â„â50 livestock (HR(â„50 animals) =3.84, 95%CI 1.60-9.22), especially if involved in animal care and building disinfection, (2) in greenhouse production (HR=1.82, 95%CI 1.01-3.30), and (3) in field-grown vegetable production (HR=1.49, 95%CI 0.96-2.32). Concerning histological subtypes, GIST were positively associated with pesticide use in vineyards (HR=2.24, 95%CI 0.95-5.30). For myomatous and fibrous sarcoma, the only increase was seen in field-grown vegetable production (HR=2.37, 95%CI 1.16-4.85). CONCLUSION: In AGRICAN, the risk of sarcomas was increased in several farming activities with differences according to histological subtype
VAV 1 and BAFF , via NF ÎșB pathway, are genetic risk factors for myasthenia gravis
International audienc
VAV1 and BAFF, via NFÎșB pathway, are genetic risk factors for myasthenia gravis
Objective To identify novel genetic loci that predispose to earlyâonset myasthenia gravis (EOMG) applying a twoâstage association study, exploration, and replication strategy. Methods Thirtyâfour loci and one confirmation loci, human leukocyte antigen (HLA)âDRA, were selected as candidate genes by team members of groups involved in different research aspects of MG. In the exploration step, these candidate genes were genotyped in 384 EOMG and 384 matched controls and significant difference in allele frequency were found in eight genes. In the replication step, eight candidate genes and one confirmation loci were genotyped in 1177 EOMG patients and 814 controls, from nine European centres. Results Allele frequency differences were found in four novel loci: CD86, AKAP12, VAV1, Bâcell activating factor (BAFF), and tumor necrosis factorâalpha (TNFâα), and these differences were consistent in all nine cohorts. Haplotype trend test supported the differences in allele frequencies between cases and controls. In addition, allele frequency difference in female versus male patients at HLAâDRA and TNFâα loci were observed. Interpretation The genetic associations to EOMG outside the HLA complex are novel and of interest as VAV1 is a key signal transducer essential for Tâ and Bâcell activation, and BAFF is a cytokine that plays important roles in the proliferation and differentiation of Bâcells. Moreover, we noted striking epistasis between the predisposing VAV1 and BAFF haplotypes; they conferred a greater risk in combination than alone. These, and CD86, share the same signaling pathway, namely nuclear factorâkappaB (NFÎșB), thus implicating dysregulation of proinflammatory signaling in predisposition to EOMG
Global Retinoblastoma Presentation and Analysis by National Income Level
This cross-sectional analysis reports the retinoblastoma stage at
diagnosis across the world during a single year, investigates
associations between clinical variables and national income level, and
investigates risk factors for advanced disease at diagnosis.
Key PointsQuestionIs the income level of a country of residence
associated with the clinical stage of presentation of patients with
retinoblastoma? FindingsIn this cross-sectional analysis that included
4351 patients with newly diagnosed retinoblastoma, approximately half of
all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from
low-income countries had extraocular tumor at time of diagnosis compared
with 1.5\% of patients from high-income countries. MeaningThe clinical
stage of presentation of retinoblastoma, which has a major influence on
survival, significantly differs among patients from low-income and
high-income countries, which may warrant intervention on national and
international levels.
ImportanceEarly diagnosis of retinoblastoma, the most common intraocular
cancer, can save both a child's life and vision. However, anecdotal
evidence suggests that many children across the world are diagnosed
late. To our knowledge, the clinical presentation of retinoblastoma has
never been assessed on a global scale. ObjectivesTo report the
retinoblastoma stage at diagnosis in patients across the world during a
single year, to investigate associations between clinical variables and
national income level, and to investigate risk factors for advanced
disease at diagnosis. Design, Setting, and ParticipantsA total of 278
retinoblastoma treatment centers were recruited from June 2017 through
December 2018 to participate in a cross-sectional analysis of
treatment-naive patients with retinoblastoma who were diagnosed in 2017.
Main Outcomes and MeasuresAge at presentation, proportion of familial
history of retinoblastoma, and tumor stage and metastasis. ResultsThe
cohort included 4351 new patients from 153 countries; the median age at
diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976
patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were
from low- and middle-income countries (LMICs). Globally, the most common
indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by
strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients
from high-income countries (HICs) were diagnosed at a median age of 14.1
months, with 656 of 666 (98.5\%) patients having intraocular
retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income
countries were diagnosed at a median age of 30.5 months, with 256 of 521
(49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having
metastasis. Lower national income level was associated with older
presentation age, higher proportion of locally advanced disease and
distant metastasis, and smaller proportion of familial history of
retinoblastoma. Advanced disease at diagnosis was more common in LMICs
even after adjusting for age (odds ratio for low-income countries vs
upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80],
and for lower-middle-income countries vs upper-middle-income countries
and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis
study is estimated to have included more than half of all new
retinoblastoma cases worldwide in 2017. Children from LMICs, where the
main global retinoblastoma burden lies, presented at an older age with
more advanced disease and demonstrated a smaller proportion of familial
history of retinoblastoma, likely because many do not reach a
childbearing age. Given that retinoblastoma is curable, these data are
concerning and mandate intervention at national and international
levels. Further studies are needed to investigate factors, other than
age at presentation, that may be associated with advanced disease in
LMICs