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- Kjellman, M., et al.
(författare)
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A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
- 2021
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Ingår i: Neuroendocrinology. - : S. Karger AG. - 0028-3835 .- 1423-0194. ; 111:9, s. 840-849
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
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| 4. |
- Haagenrud, Svein, et al.
(författare)
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Environmental Characterisation and Mapping with respect to Durability
- 2005
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Ingår i: 10th International conference on durability of building materials and components.
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Konferensbidrag (refereegranskat)abstract
- Service life planning calls for characterisation and classification of the exposure environment for the constructed asset(s) in question. Lack of knowledge of environmental exposure data and models among the building sector players is an important barrier for further progress towards service life prediction. The ever more evident climate change highlights even more the need for data and models on the exposure, when it comes to address its impact on the built environment. In general, requirements for establishing and implementing systems for quantitative characterisation and classification of durability of materials and components are: 1) well defined, and relatively simple damage functions for the materials in question, 2) availability of environmental exposure data/loads, including methods and models for assessing their geographical distribution, and 3) user friendly IT systems for storage, processing and modelling the environmental loads onto structures. Service life functions related to environmental degradation are today available for a range of building materials and components. As for availability of environmental data and models, as well as proper IT systems, it is shown that for most European countries, such data and models are available from meteorological offices and the environmental research area, and that these data and the work performed are directly applicable for service life planning and life cycle management of constructed assets. A short review of some of the most applicable models for environmental exposure and for degradation and damage of building materials and structures is included. The global climate system is likely to undergo changes, regardless of the implementation of abatement policies under the Kyoto Protocol or other regimes. Both the functionality of the existing built environment and the design of future buildings are likely to be altered by climate change impacts, and the expected implications of these new conditions are now investigated. The data and models are often directly exhibited in computer-based systems, often on GIS based platforms. With the rapid development of IFC based standards for digital object oriented models of building products there is a huge need for property sets, such as durability and service life data, linked directly to the building elements. The significant drive within the AEC/IFC community to provide for relevant location based data (GIS) via IFC format will be a major facilitator for access to site specific durability data, described by degradation models containing environmental (and other) degradation factors.
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| 5. |
- Haagenrud, Svein, et al.
(författare)
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Environmental Characterisation and Mapping with respect to Durability : LYON [France] 17-20 April 2005
- 2005
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Ingår i: 10th International Conference on Durability of Building Materials and Components.
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Konferensbidrag (refereegranskat)abstract
- Service life planning calls for characterisation and classification of the exposure environment for theconstructed asset(s) in question. Lack of knowledge of environmental exposure data and modelsamong the building sector players is an important barrier for further progress towards service lifeprediction. The ever more evident climate change highlights even more the need for data and modelson the exposure, when it comes to address its impact on the built environment.In general, requirements for establishing and implementing systems for quantitative characterisationand classification of durability of materials and components are: 1) well defined, and relatively simpledamage functions for the materials in question, 2) availability of environmental exposure data/loads,including methods and models for assessing their geographical distribution, and 3) user friendly ITsystems for storage, processing and modelling the environmental loads onto structures.Service life functions related to environmental degradation are today available for a range of buildingmaterials and components. As for availability of environmental data and models, as well as proper ITsystems, it is shown that for most European countries, such data and models are available frommeteorological offices and the environmental research area, and that these data and the workperformed are directly applicable for service life planning and life cycle management of constructedassets. A short review of some of the most applicable models for environmental exposure and fordegradation and damage of building materials and structures is included. The global climate system is likely to undergo changes, regardless of the implementation of abatementpolicies under the Kyoto Protocol or other regimes. Both the functionality of the existing builtenvironment and the design of future buildings are likely to be altered by climate change impacts, andthe expected implications of these new conditions are now investigated. The data and models are often directly exhibited in computer-based systems, often on GIS basedplatforms. With the rapid development of IFC based standards for digital object oriented models ofbuilding products there is a huge need for property sets, such as durability and service life data, linkeddirectly to the building elements. The significant drive within the AEC/IFC community to provide forrelevant location based data (GIS) via IFC format will be a major facilitator for access to site specificdurability data, described by degradation models containing environmental (and other) degradationfactors.
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| 7. |
- Nesti, Cedric, et al.
(författare)
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Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size : a retrospective, Europe-wide, pooled cohort study
- 2023
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 24:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAwareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1–2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1–2 cm in size in patients with or without right-sided hemicolectomy.MethodsIn this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1–2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693.Findings282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1–2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0–15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 –21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36–2·17]; p=0·71).InterpretationThis study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1–2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort.
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| 8. |
- Olbjern, Christine, et al.
(författare)
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Fecal microbiota profiles in treatment-naive pediatric inflammatory bowel disease : associations with disease phenotype, treatment, and outcome
- 2019
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Ingår i: Clinical and Experimental Gastroenterology. - Macclesfield, United Kingdom : DOVE MEDICAL PRESS LTD. - 1178-7023. ; 12, s. 37-49
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Imbalance in the microbiota, dysbiosis, has been identified in inflammatory bowel disease (IBD). We explored the fecal microbiota in pediatric patients with treatment-naive IBD, non-IBD patients with gastrointestinal symptoms and healthy children, its relation to IBD subgroups, and treatment outcomes. Patients and methods: Fecal samples were collected from 235 children below 18 years of age. Eighty children had Crohns disease (CD), 27 ulcerative colitis (UC), 3 IBD unclassified, 50 were non-IBD symptomatic patients, and 75 were healthy. The bacterial abundance of 54 predefined DNA markers was measured with a 16S rRNA DNA-based test using GA-Map (TM) technology at diagnosis and after therapy in IBD patients. Results: Bacterial abundance was similarly reduced in IBD and non-IBD patients in 51 of 54 markers compared to healthy patients (Pamp;lt;0.001). Only Prevotella was more abundant in patients (Pamp;lt;0.01). IBD patients with ileocolitis or total colitis had more Ruminococcus gnavus (P=0.02) than patients with colonic CD or left-sided UC. CD patients with upper gastrointestinal manifestations had higher Veillonella abundance (Pamp;lt;0.01). IBD patients (58%) who received biologic therapy had lower baseline Firmicutes and Mycoplasma hominis abundance (Pamp;lt;0.01) than conventionally treated. High Proteobacteria abundance was associated with stricturing/penetrating CD, surgery (Pamp;lt;0.01), and nonmucosal healing (Pamp;lt;0.03). Low Faecalibacterium prausnitzii abundance was associated with prior antibiotic therapy (P=0.001), surgery (P=0.02), and nonmucosal healing (Pamp;lt;0.03). After therapy, IBD patients had unchanged dysbiosis. Conclusion: Fecal microbiota profiles differentiated IBD and non-IBD symptomatic children from healthy children, but displayed similar dysbiosis in IBD and non-IBD symptomatic patients. Pretreatment fecal microbiota profiles may be of prognostic value and aid in treatment individualization in pediatric IBD as severe dysbiosis was associated with an extensive, complicated phenotype, biologic therapy, and nonmucosal healing. The dysbiosis persisted after therapy, regardless of treatments and mucosal healing.
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