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- Koelmel, Jeremy P., et al.
(författare)
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An actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry
- 2022
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Ingår i: Exposome. - : Oxford University Press. - 2635-2265 .- 2635-2265. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Omics-based technologies have enabled comprehensive characterization of our exposure to environmental chemicals (chemical exposome) as well as assessment of the corresponding biological responses at the molecular level (eg, metabolome, lipidome, proteome, and genome). By systematically measuring personal exposures and linking these stimuli to biological perturbations, researchers can determine specific chemical exposures of concern, identify mechanisms and biomarkers of toxicity, and design interventions to reduce exposures. However, further advancement of metabolomics and exposomics approaches is limited by a lack of standardization and approaches for assigning confidence to chemical annotations. While a wealth of chemical data is generated by gas chromatography high-resolution mass spectrometry (GC-HRMS), incorporating GC-HRMS data into an annotation framework and communicating confidence in these assignments is challenging. It is essential to be able to compare chemical data for exposomics studies across platforms to build upon prior knowledge and advance the technology. Here, we discuss the major pieces of evidence provided by common GC-HRMS workflows, including retention time and retention index, electron ionization, positive chemical ionization, electron capture negative ionization, and atmospheric pressure chemical ionization spectral matching, molecular ion, accurate mass, isotopic patterns, database occurrence, and occurrence in blanks. We then provide a qualitative framework for incorporating these various lines of evidence for communicating confidence in GC-HRMS data by adapting the Schymanski scoring schema developed for reporting confidence levels by liquid chromatography HRMS (LC-HRMS). Validation of our framework is presented using standards spiked in plasma, and confident annotations in outdoor and indoor air samples, showing a false-positive rate of 12% for suspect screening for chemical identifications assigned as Level 2 (when structurally similar isomers are not considered false positives). This framework is easily adaptable to various workflows and provides a concise means to communicate confidence in annotations. Further validation, refinements, and adoption of this framework will ideally lead to harmonization across the field, helping to improve the quality and interpretability of compound annotations obtained in GC-HRMS.
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| 2. |
- Korrel, Maarten, et al.
(författare)
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Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial
- 2023
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Ingår i: The Lancet Regional Health. - : ELSEVIER. - 2666-7762. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Background The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, & GE;1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society. Copyright & COPY; 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 3. |
- Leu Agelii, Monica, 1977, et al.
(författare)
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Disease activity trajectories in rheumatoid arthritis: a tool for prediction of outcome
- 2021
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 501:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.
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