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- Appelgren, Daniel, et al.
(författare)
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Active NET formation in Libman–Sacks endocarditis without antiphospholipid antibodies : A dramatic onset of systemic lupus erythematosus
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:6, s. 310-318
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Tidskriftsartikel (refereegranskat)abstract
- Although neutrophil extracellular traps (NETs) have been highlighted in several systemic inflammatory diseases, their clinical correlates and potential pathological role remain obscure. Herein, we describe a dramatic onset of systemic lupus erythematosus (SLE) with clear-cut pathogenic implications for neutrophils and NET formation in a young woman with cardiac (Libman–Sacks endocarditis) and central nervous system (psychosis and seizures) involvement. Despite extensive search, circulating antiphospholipid autoantibodies, a hallmark of Libman–Sacks endocarditis, could not be detected. Instead, we observed active NET formation in the tissue of the mitral valve, as well as in the circulation. Levels of NET remnants were significantly higher in serially obtained sera from the patient compared with sex-matched blood donors (p =.0011), and showed a non-significant but substantial correlation with blood neutrophil counts (r = 0.65, p =.16). The specific neutrophil elastase activity measured in serum seemed to be modulated by the provided immunosuppressive treatment. In addition, we found anti-Ro60/SSA antibodies in the cerebrospinal fluid of the patient but not NET remnants or increased elastase activity. This case illustrates that different disease mechanisms mediated via autoantibodies can occur simultaneously in SLE. NET formation with release of cytotoxic NET remnants is a candidate player in the pathogenesis of this non-canonical form of Libman–Sacks endocarditis occurring in the absence of traditional antiphospholipid autoantibodies. The case description includes longitudinal results with clinical follow-up data and a discussion of the potential roles of NETs in SLE.
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| 2. |
- Bengtsson, Johan, et al.
(författare)
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Correlation between ADC, ADC ratio, and Gleason Grade group in prostate cancer patients undergoing radical prostatectomy : Retrospective multicenter study with different MRI scanners
- 2023
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Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: MRI is an important tool in the prostate cancer work-up, with special emphasis on the ADC sequence. This study aimed to investigate the correlation between ADC and ADC ratio compared to tumor aggressiveness determined by a histopathological examination after radical prostatectomy.Methods: Ninety-eight patients with prostate cancer underwent MRI at five different hospitals prior to radical prostatectomy. Images were retrospectively analyzed individually by two radiologists. The ADC of the index lesion and reference tissues (contralateral normal prostatic, normal peripheral zone, and urine) was recorded. Absolute ADC and different ADC ratios were compared to tumor aggressivity according to the ISUP Gleason Grade Groups extracted from the pathology report using Spearman’s rank correlation coefficient (ρ). ROC curves were used to evaluate the ability to discriminate between ISUP 1-2 and ISUP 3-5 and intra class correlation and Bland-Altman plots for interrater reliability.Results: All patients had prostate cancer classified as ISUP grade ≥ 2. No correlation was found between ADC and ISUP grade. We found no benefit of using the ADC ratio over absolute ADC. The AUC for all metrics was close to 0.5, and no threshold could be extracted for prediction of tumor aggressivity. The interrater reliability was substantial to almost perfect for all variables analyzed.Conclusions: ADC and ADC ratio did not correlate with tumor aggressiveness defined by ISUP grade in this multicenter MRI study. The result of this study is opposite to previous research in the field.
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| 3. |
- Indira Chandran, Vineesh, et al.
(författare)
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Ultrasensitive Immunoprofiling of Plasma Extracellular Vesicles Identifies Syndecan-1 as a Potential Tool for Minimally Invasive Diagnosis of Glioma
- 2019
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 25:10, s. 3115-3127
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Liquid biopsy has great potential to improve the management of brain tumor patients at high risk of surgery-associated complications. Here, the aim was to explore plasma extracellular vesicle (plEV) immunoprofiling as a tool for noninvasive diagnosis of glioma.Experimental Design: PlEV isolation and analysis were optimized using advanced mass spectrometry, nanoparticle tracking analysis, and electron microscopy. We then established a new procedure that combines size exclusion chromatography isolation and proximity extension assay-based ultrasensitive immunoprofiling of plEV proteins that was applied on a well-defined glioma study cohort (n = 82).Results: Among potential candidates, we for the first time identify syndecan-1 (SDC1) as a plEV constituent that can discriminate between high-grade glioblastoma multiforme (GBM, WHO grade IV) and low-grade glioma [LGG, WHO grade II; area under the ROC curve (AUC): 0.81; sensitivity: 71%; specificity: 91%]. These findings were independently validated by ELISA. Tumor SDC1 mRNA expression similarly discriminated between GBM and LGG in an independent glioma patient population from The Cancer Genome Atlas cohort (AUC: 0.91; sensitivity: 79%; specificity: 91%). In experimental studies with GBM cells, we show that SDC1 is efficiently sorted to secreted EVs. Importantly, we found strong support of plEVSDC1 originating from GBM tumors, as plEVSDC1 correlated with SDC1 protein expression in matched patient tumors, and plEVSDC1 was decreased postoperatively depending on the extent of surgery.Conclusions: Our studies support the concept of circulating plEVs as a tool for noninvasive diagnosis and monitoring of gliomas and should move this field closer to the goal of improving the management of cancer patients.
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