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- Gerdtsson, Axel, et al.
(författare)
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Validation of a prediction model for post-chemotherapy fibrosis in nonseminoma patients
- 2023
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Ingår i: Bju International. - 1464-4096 .- 1464-410X. ; 132:3, s. 329-336
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Tidskriftsartikel (refereegranskat)abstract
- Objective To validate Vergouwe's prediction model using the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) RETROP database and to define its clinical utility. Materials and methods Vergouwe's prediction model for benign histopathology in post-chemotherapy retroperitoneal lymph node dissection (PCRPLND) uses the following variables: presence of teratoma in orchiectomy specimen; pre-chemotherapy level of alphafetoprotein; b-Human chorionic gonadotropin and lactate dehydrogenase; and lymph node size pre- and postchemotherapy. Our validation cohort consisted of patients included in RETROP, a prospective population-based database of patients in Sweden and Norway with metastatic nonseminoma, who underwent PC-RPLND in the period 2007-2014. Discrimination and calibration analyses were used to validate Vergouwe's prediction model results. Calibration plots were created and a Hosmer-Lemeshow test was calculated. Clinical utility, expressed as opt-out net benefit (NBopt-out), was analysed using decision curve analysis. Results Overall, 284 patients were included in the analysis, of whom 130 (46%) had benign histology after PC-RPLND. Discrimination analysis showed good reproducibility, with an area under the receiver-operating characteristic curve (AUC) of 0.82 (95% confidence interval 0.77-0.87) compared to Vergouwe's prediction model (AUC between 0.77 and 0.84). Calibration was acceptable with no recalibration. Using a prediction threshold of 70% for benign histopathology, NBopt-out was 0.098. Using the model and this threshold, 61 patients would have been spared surgery. However, only 51 of 61 were correctly classified as benign. Conclusions The model was externally validated with good reproducibility. In a clinical setting, the model may identify patients with a high chance of benign histopathology, thereby sparing patients of surgery. However, meticulous follow-up is required.
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- Gerdtsson, Anna S, et al.
(författare)
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Evaluation of Solid Supports for Slide- and Well-Based Recombinant Antibody Microarrays
- 2016
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Ingår i: Microarrays. - : MDPI AG. - 2076-3905. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Antibody microarrays have emerged as an important tool within proteomics, enabling multiplexed protein expression profiling in both health and disease. The design and performance of antibody microarrays and how they are processed are dependent on several factors, of which the interplay between the antibodies and the solid surfaces plays a central role. In this study, we have taken on the first comprehensive view and evaluated the overall impact of solid surfaces on the recombinant antibody microarray design. The results clearly demonstrated the importance of the surface-antibody interaction and showed the effect of the solid supports on the printing process, the array format of planar arrays (slide- and well-based), the assay performance (spot features, reproducibility, specificity and sensitivity) and assay processing (degree of automation). In the end, two high-end recombinant antibody microarray technology platforms were designed, based on slide-based (black polymer) and well-based (clear polymer) arrays, paving the way for future large-scale protein expression profiling efforts.
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- Gerdtsson, Anna Sandström, et al.
(författare)
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Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis
- 2016
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 10:8, s. 1305-1316
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.
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- Malm, Johan, et al.
(författare)
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Long-term prediction of prostate cancer diagnosis and death using PSA and obesity related anthropometrics at early middle age: Data from the malmö preventive project
- 2018
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 9:5, s. 5778-5785
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate whether anthropometric parameters add to PSA measurements in middle-aged men for risk assessment of prostate cancer (PCa) diagnosis and death. Results: After adjusting for PSA, both BMI and weight were significantly associated with an increased risk of PCa death with the odds of a death corresponding to a 10 kg/m2 or 10 kg increase being 1.58 (95% CI 1.10, 2.28; p = 0.013) and 1.14 (95% CI 1.02, 1.26; p = 0.016) times greater, respectively. AUCs did not meaningfully increase with the addition of weight or BMI to prediction models including PSA. Materials and Methods: In 1974 to 1986, 22,444 Swedish men aged 44 to 50 enrolled in Malmö Preventive Project, Sweden, and provided blood samples and anthropometric data. Rates of PSA screening in the cohort were very low. Documentation of PCa diagnosis and disease-specific death up to 2014 was retrieved through national registries. Among men with anthropometric measurements available at baseline, a total of 1692 men diagnosed with PCa were matched to 4190 controls, and 464 men who died of disease were matched to 1390 controls. Multivariable conditional logistic regression was used to determine whether diagnosis or death from PCa were associated with weight and body mass index (BMI) at adulthood after adjusting for PSA. Conclusions: Men with higher BMI and weight at early middle age have an increased risk of PCa diagnosis and death after adjusting for PSA. However, in a multivariable numerical statistical model, BMI and weight do not importantly improve the predictive accuracy of PSA. Risk-stratification of screening should be based on PSA without reference to anthropometrics. © Assel et al.
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- Romantsik, Olga, et al.
(författare)
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Severe intraventricular hemorrhage causes long-lasting structural damage in a preterm rabbit pup model
- 2022
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 92:2, s. 403-414
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Tidskriftsartikel (refereegranskat)abstract
- Background Intraventricular hemorrhage causes significant lifelong mortality and morbidity, especially in preterm born infants. Progress in finding an effective therapy is stymied by a lack of preterm animal models with long-term follow-up. This study addresses this unmet need, using an established model of preterm rabbit IVH and analyzing outcomes out to 1 month of age. Methods Rabbit pups were delivered preterm and administered intraperitoneal injection of glycerol at 3 h of life and approximately 58% developed IVH. Neurobehavioral assessment was performed at 1 month of age followed by immunohistochemical labeling of epitopes for neurons, synapses, myelination, and interneurons, analyzed by means of digital quantitation and assessed via two-way ANOVA or Student's t test. Results IVH pups had globally reduced myelin content, an aberrant cortical myelination microstructure, and thinner upper cortical layers (I-III). We also observed a lower number of parvalbumin (PV)-positive interneurons in deeper cortical layers (IV-VI) in IVH animals and reduced numbers of neurons, synapses, and microglia. However, there were no discernable changes in behaviors. Conclusions We have established in this preterm pup model that long-term changes after IVH include significant wide-ranging alterations to cortical organization and microstructure. Further work to improve the sensitivity of neurocognitive testing in this species at this age may be required. Impact This study uses an established animal model of preterm birth, in which the rabbit pups are truly born preterm, with reduced organ maturation and deprivation of maternally supplied trophic factors. This is the first study in preterm rabbits that explores the impacts of severe intraventricular hemorrhage beyond 14 days, out to 1 month of age. Our finding of persisting but subtle global changes including brain white and gray matter will have impact on our understanding of the best path for therapy design and interventions.
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