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1.
  • Löfvenberg, Christian, 1978-, et al. (författare)
  • Prevalence of severe-to-Profound hearing loss in the adult Swedish population and comparison with cochlear implantation rate
  • 2022
  • Ingår i: Acta Oto-Laryngologica. - : Taylor & Francis. - 0001-6489 .- 1651-2251. ; 142:5, s. 410-414
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The prevalence of disabling hearing loss is increasing worldwide. However, previous studies on hearing loss prevalence have enrolled small populations or only provided estimates.Aim: To establish the prevalence of severe-to-profound hearing loss (STPHL) in the adult Swedish population and compare it with the cochlear implantation rate in Sweden.Material and methods: We established a database containing over 15 million audiograms obtained from regions covering > 99% of the Swedish population by extracting audiogram data from the computer software application, Auditbase. We used this database to calculate the percentage of adult patients with bilateral hearing levels >= 70 dB. We collected data regarding cochlear implantations in Sweden from the National Board of Welfare and Health.Results: The prevalence of STPHL in the adult Swedish population was 0.28%. There were regional variations in the prevalence and rate of cochlear implantation; however, there was no association between both parameters.Conclusions: This study presents an updated and reliable prevalence figure for STPHL in Sweden.Significance: Patients with STPHL have extensive rehabilitation requirements; accordingly, it is important to determine the accurate prevalence of STPHL to inform the allocation of adequate resources.
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2.
  • Beaulieu, Luc, et al. (författare)
  • AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy
  • 2023
  • Ingår i: Medical physics (Lancaster). - : WILEY. - 0094-2405. ; 50:8, s. E946-E960
  • Tidskriftsartikel (refereegranskat)abstract
    • The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for Ir-192-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.
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3.
  • Bergtagen
  • 2020. - 200
  • Samlingsverk (redaktörskap) (populärvet., debatt m.m.)
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4.
  • Brady, Lauren, et al. (författare)
  • Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer
  • 2021
  • Ingår i: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 29
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Prostate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy.METHODS: Tissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups - Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared.RESULTS: Pathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066).CONCLUSION: In this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.
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5.
  • Carlsson, Jessica, 1984-, et al. (författare)
  • PD-L1 Expression is Associated With Poor Prognosis in Renal Cell Carcinoma
  • 2020
  • Ingår i: Applied immunohistochemistry & molecular morphology (Print). - : Lippincott Williams & Wilkins. - 1541-2016 .- 1533-4058. ; 28:3, s. 213-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Programmed death ligand 1 (PD-L1) is a protein which, when interacting with its receptor programmed death 1, acts as a negative regulator of the antitumor T-cell-mediated immune response. The prognostic value of PD-L1 expression in renal cell carcinoma (RCC) has been controversial. In this study, the prognostic value of PD-L1 expression in RCC was evaluated by analyzing PD-L1 immunoreactivity in tumor cells and tumor-infiltrating immune cells (TIICs) in 346 RCC patients with long-term follow-up. PD-L1 positivity in tumor cells was associated with higher World Health Organization nucleolar grade (P<0.001), recurrence (P=0.011), and death due to RCC (P=0.031). PD-L1 positivity in TIICs was associated with higher nucleolar grade (P<0.001), higher T-stage (P=0.031), higher N-stage (P=0.01), recurrence (P=0.007), and death due to RCC (P=0.001). A significant positive association of time to cancer-specific death with both PD-L1-positive tumor cells and TIICs were also found. The data indicate that RCC patients with PD-L1-positive tumor cells and TIICs are at significant risk for cancer progression and the expression may be used as a complementary prognostic factor in the management of RCC patients.
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6.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer
  • 2021
  • Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p ,0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression. 
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7.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
  • 2020
  • Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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8.
  • Davidsson, Sabina, 1972-, et al. (författare)
  • Soluble Levels of CD163, PD-L1, and IL-10 in Renal Cell Carcinoma Patients
  • 2022
  • Ingår i: Diagnostics. - : MDPI. - 2075-4418. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • CD163+ M2 macrophages have been suggested to counteract tumor immunity by increasing immunosuppressive mechanisms including PD-L1 and IL-10 expression. Soluble levels of PD-L1, IL-10, and CD163 have been reported as potential biomarkers in various cancers, although the prognostic value in renal cell carcinoma (RCC) has to be further elucidated. In the present study, we measured the levels of sPD-L1, sIL-10, and sCD163 in 144 blood samples from patients with RCC. The levels were determined by using enzyme linked immunosorbent assays. Soluble PD-L1 and CD163 were detectable in 100% of the serum samples, and sCD163 in 22% of the urine samples, while only a minority of the samples had detectable sIL-10. Significantly higher serum levels of sPD-L1 and sCD163 were observed in patients with metastatic disease (p < 0.05). The results also showed that patients with high levels of sPD-L1 in serum had shorter cancer-specific survival compared with patients with low levels (p = 0.002). The results indicate that sPD-L1 most significantly reflects tumor progression in RCC.
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9.
  • Dorofte, Luiza, 1982-, et al. (författare)
  • Low level of interobserver concordance in assessing histological subtype and tumor grade in patients with penile cancer may impair patient care
  • 2022
  • Ingår i: Virchows Archiv. - : Springer. - 0945-6317 .- 1432-2307. ; 480:4, s. 879-886
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation between penile squamous cell carcinoma patients who can benefit from limited organ-sparing surgery and those at significant risk of lymph node metastasis is based on histopathological prognostic factors including histological grade and tumor histological subtype. We examined levels of interobserver and intraobserver agreement in assessment of histological subtype and grade in 207 patients with penile squamous cell carcinoma. The cases were assessed by seven pathologists from three hospitals located in Sweden and Italy. There was poor to moderate concordance in assessing both histological subtype and grade, with Fleiss kappas of 0.25 (range: 0.02-0.48) and 0.23 (range: 0.07-0.55), respectively. When choosing HPV-associated and non-HPV-associated subtypes, interobserver concordance ranged from poor to good, with a Fleiss kappa value of 0.36 (range: 0.02-0.79). A re-review of the slides by two of the pathologists showed very good intraobserver concordance in assessing histological grade and subtype, with Cohen's kappa values of 0.94 and 0.91 for grade and 0.95 and 0.84 for subtype. Low interobserver concordance could lead to undertreatment and overtreatment of many patients with penile cancer, and brings into question the utility of tumor histological subtype and tumor grade in determining patient treatment in pT1 tumors. 
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10.
  • Edstorp, Jessica, et al. (författare)
  • Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
  • 2024
  • Ingår i: Diabetes/Metabolism Research and Reviews. - 1520-7552. ; 40:3, s. e3758-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods: We used data from a population-based Swedish case-control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results: Individuals who developed LADA did not have a higher prevalence of infectious disease 1–10 years before diabetes diagnosis. For example, OR was estimated at 0.87 (0.66, 1.14) for any versus no respiratory infectious disease within 1–3 years. Similar results were seen for LADA with high-risk HLA genotypes (OR 0.95 [0.64, 1.42]) or high GADA levels (OR 1.10 [0.79, 1.55]), ≥2 episodes (OR 0.89 [0.56, 1.40]), and in infections treated using antibiotics (OR 1.03 [0.73, 1.45]). The only significant association was observed with lower respiratory disease the year preceding LADA diagnosis (OR 1.67 [1.06, 2.64]). Conclusions: Our findings do not support the idea that exposure to infections increases the risk of LADA. A higher prevalence of respiratory infection in the year before LADA diagnosis could reflect increased susceptibility to infections due to hyperglycemia.
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11.
  • Edstorp, Jessica, et al. (författare)
  • Incidence of lada and type 2 diabetes in relation to tobacco use and genetic susceptibility to type 2 diabetes and related traits : Findings from a swedish case-control study and the norwegian hunt study
  • 2023
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 46:5, s. 1028-1036
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. RESEARCH DESIGN AND METHODS We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS. RESULTS The RR of LADA was elevated in high IR-GRS heavy smokers (‡15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (‡15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D. CONCLUSIONS Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use.
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12.
  • Edstorp, Jessica, et al. (författare)
  • Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
  • 2023
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 66, s. 70-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypotheses: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. Methods: Analyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. Results: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. Conclusions/interpretation: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. Data availability: Analysis codes are shared through GitHub (https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA). Graphical abstract: [Figure not available: see fulltext.]
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13.
  • Glombik, Dominik, 1988-, et al. (författare)
  • Penile cancer : long-term infectious and thromboembolic complications following lymph node dissection - a population-based study (Sweden)
  • 2023
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:5, s. 458-464
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To assess the long-term risks of infectious and thromboembolic events following inguinal (ILND) and pelvic (PLND) lymph node dissection in men with penile cancer.MATERIAL AND METHODS: A total of 364 men subjected to ILND with or without PLND for penile cancer between 2000 and 2012 were identified in the Swedish National Penile Cancer Register. Each patient was matched based on age and county of residence with six penile cancer-free men. The Swedish Cancer Register and other population-based registers were used to retrieve information on treatment and hospitalisation for selected infectious and thromboembolic events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models with multiple imputation.RESULTS: The risk of infectious events remained increased for more than five years postoperatively in men with penile cancer compared with matched controls. The palpable nodal disease was the only predictor of these events, with risk increasing with the cN stage. The HR at one, three and five years and six months postoperatively was 8.60 (95% CI 5.16-14.34), 4.02 (95% CI 2.65-6.09) and 1.93 (95% CI 1.11-3.38), respectively. An increased risk of thromboembolic events persisted for three years postoperatively. The HR at one and three years postoperatively was 13.51 (95% CI 6.53-27.93) and 2.12 (95% CI 1.07-4.20). The results correspond well with the over-prescription of anticoagulants observed during this period. An association with bulky disease (cN3) was observed.CONCLUSIONS: Lymph node dissection for penile cancer is associated with an increased risk of infectious and thromboembolic events. The findings of this population-based study show that the risks of these events remain increased more than five years for infectious and three years for thromboembolic events. Improved awareness of long-term complications following ILND is of importance both among patients and care givers to ensure early detection and treatment.
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14.
  • Glombik, Dominik, 1988-, et al. (författare)
  • Risk of second HPV-associated cancers in men with penile cancer
  • 2021
  • Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 60:5, s. 667-671
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of this study was to examine the risk of HPV-associated oral cavity, oropharyngeal or anal cancer in men with penile cancer to test the hypothesis of an increased risk to develop a second HPV-associated cancer later in life.MATERIAL AND METHODS: We conducted a population-based register study including all men in Sweden diagnosed with penile cancer between 2000 and 2012. For each patient, six men without penile cancer were matched based on age and county of residence. Data were retrieved from Swedish cancer and population registers, to assess the risk of oral cavity, oropharyngeal or anal cancer in patients with penile cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Risks in men with penile cancer were also compared with the background Swedish male population by use of standardized incidence ratios.RESULTS: In total, 1634 men with and 9804 without penile cancer were included in the study. Among men with penile cancer, four men were subsequently diagnosed with oral cavity cancer, one with oropharyngeal cancer and one with anal cancer. Corresponding numbers among the penile cancer-free men were ten, two and three, respectively. There was evidence of an increased risks of all three cancers under study with an HR of 2.84 (95% CI 0.89-9.06) for oral cavity cancer, 3.66 (95% CI 0.33-40.39) for oropharyngeal cancer and 2.34 (95% CI 0.24-22.47) for anal cancer. When comparing the incidence of these malignancies between penile cancer patients and the background population, the patterns of association were similar.CONCLUSIONS: Our findings indicate that men with penile cancer are at an increased risk of a second HPV-associated cancer of the oral cavity, oropharynx and anal canal. Considering that our study was based on small numbers reflecting the rarity of these cancers, larger studies are needed to confirm our findings.
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15.
  • Hussain, Alia Arif, et al. (författare)
  • A naturalistic study of plasma lipid alterations in female patients with anorexia nervosa before and after weight restoration treatment
  • 2024
  • Ingår i: Journal of Eating Disorders. - : BioMed Central (BMC). - 2050-2974. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plasma lipid concentrations in patients with anorexia nervosa (AN) seem to be altered.Methods: We conducted a naturalistic study with 75 adult female patients with AN and 26 healthy female controls (HC). We measured plasma lipid profile, sex hormones and used self-report questionnaires at admission and discharge.Results: Total cholesterol (median (IQR): 4.9 (1.2)) and triglycerides (TG) (1.2 (0.8)) were elevated in AN at admission (BMI 15.3 (3.4)) compared with HC (4.3 (0.7), p = 0.003 and 0.9 (0.3), p = 0.006) and remained elevated at discharge (BMI 18.9 (2.9)) after weight restoration treatment. Estradiol (0.05 (0.1)) and testosterone (0.5 (0.7)) were lower in AN compared with HC (0.3 (0.3), p = < 0.001 and 0.8 (0.5), p = 0.03) and remained low at discharge. There was no change in eating disorder symptoms. Depression symptoms decreased (33 (17) to 30.5 (19), (p = 0.007)). Regression analyses showed that illness duration was a predictor of TG, age was a predictor of total cholesterol and LDL, while educational attainment predicted LDL and TG.Conclusion: Lipid concentrations remained elevated following weight restoration treatment, suggesting an underlying, premorbid dysregulation in the lipid metabolism in AN that persists following weight restoration. Elevated lipid concentrations may be present prior to illness onset in AN.Level of evidence: III: Evidence obtained from well-designed cohort or case–control analytic studies.
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16.
  • Hussain, Alia Arif, et al. (författare)
  • Elevated lipid class concentrations in females with anorexia nervosa before and after intensive weight restoration treatment : a lipidomics study
  • 2023
  • Ingår i: International Journal of Eating Disorders. - : John Wiley & Sons. - 0276-3478 .- 1098-108X. ; 56:12, s. 2260-2272
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To study the plasma lipidome of patients with anorexia nervosa (AN) before and after weight restoration treatment and report associations with AN subtypes and oral contraceptive pill (OCP) usage.Methods: Quantitative shotgun lipidomics analysis was used to study plasma lipids of 50 female patients with AN before and after weight restoration treatment and 50 healthy female controls (HC). The AN group was assessed with blood samples and questionnaires before and after weight restoration. Results: In total we quantified 260 lipid species representing 26 lipid classes of which13 lipid class concentrations were elevated in patients with AN at admission compared with HC. Lipid classes remained elevated after weight restoration treatment of 84 days (median; interquartile range 28), and only the concentration of the ceramide lipid class increased between pre- and post-treatment (p =.03), whereas lysophosphatidylcholine (LPC, p =.02), ether-linked Phosphatidylcholine (LPCO, p =.02), and lysophosphatidylethanolamine (LPE, p =.009) decreased.Conclusion: In AN, 13 out of 26 lipid class concentrations were elevated at admission and remained elevated post-treatment. Ceramides increased further between pre- and post-weight restoration treatment, which could be related to the rapid weight gain during re-nutrition. Further research is needed to elucidate the effects of weight restoration treatment on short- and long-term lipid profiles in individuals with AN.Public Significance Statement: Lipidomics research can increase the understanding of AN, a complex and potentially life-threatening eating disorder. By analyzing lipids, or fats, in the body, we can identify biological markers that may inform diagnosis and develop more effective treatments. This research can also shed light on the underlying mechanisms of the disorder, leading to a better understanding of the processes involved in eating behavior.
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17.
  • Häggström, Margaretha, 1962, et al. (författare)
  • Att undervisa i hållbar utveckling - Relationellt perspektiv
  • 2022
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Hur kan lärare arbeta med hållbar utveckling i en tid då globala kriser och klimatförändringar väcker både rädsla och oro? Och hur kan elever samtidigt känna hopp inför sin framtid och sitt vuxna liv? Dessa frågor är utgångspunkt för det utvecklings- och forskningsprojekt som utgör basen i denna bok. Du får följa med i berättelser som lärare och elever skapat tillsammans för att utveckla kunskap om social, ekologisk och ekonomisk hållbarhet. Boken redogör för de pedagogiska utgångspunkterna, men ger också rikligt med praktiska exempel på metoder och former för undervisning i och genom demokratiska och relationella förhållningssätt. Du får konkreta tips på hur du kan integrera hållbar utveckling i undervisningen. Såväl kritiska aspekter som lärdomar och möjligheter lyfts fram. I centrum står eleven och läraren utifrån det relationspedagogiska perspektivet. Att undervisa i hållbar utveckling: Relationellt perspektiv vänder sig till lärarstudenter och verksamma lärare i årskurs F-6. Bokens syfte är att inspirera, stödja och utgöra diskussionsunderlag i skolans arbete med miljöperspektivet och hållbar utveckling.
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18.
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19.
  • Nilsson, Maria, et al. (författare)
  • Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder : A Clinical Study
  • 2020
  • Ingår i: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 46:1, s. 121-129
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: There are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum. METHODS: All participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: A total of 51 participants (As/ASD, n = 22; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups. CONCLUSION: Our results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.
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20.
  • Qvick, Alvida, 1990-, et al. (författare)
  • Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer
  • 2021
  • Ingår i: Molecular Medicine. - : Springer. - 1076-1551 .- 1528-3658. ; 27:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data.Methods: Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics.Results: There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb-IV disease compared to patients with stage I-IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37-9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb-IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I-IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples.Conclusion: This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group.
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21.
  • Rodriguez-Espigares, Ismael, et al. (författare)
  • GPCRmd uncovers the dynamics of the 3D-GPCRome
  • 2020
  • Ingår i: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 17:8, s. 777-787
  • Tidskriftsartikel (refereegranskat)abstract
    • G-protein-coupled receptors (GPCRs) are involved in numerous physiological processes and are the most frequent targets of approved drugs. The explosion in the number of new three-dimensional (3D) molecular structures of GPCRs (3D-GPCRome) over the last decade has greatly advanced the mechanistic understanding and drug design opportunities for this protein family. Molecular dynamics (MD) simulations have become a widely established technique for exploring the conformational landscape of proteins at an atomic level. However, the analysis and visualization of MD simulations require efficient storage resources and specialized software. Here we present GPCRmd (http://gpcrmd.org/), an online platform that incorporates web-based visualization capabilities as well as a comprehensive and user-friendly analysis toolbox that allows scientists from different disciplines to visualize, analyze and share GPCR MD data. GPCRmd originates from a community-driven effort to create an open, interactive and standardized database of GPCR MD simulations.
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22.
  • Rohrer, Julia M., et al. (författare)
  • Putting the Self in Self-Correction : Findings From the Loss-of-Confidence Project
  • 2021
  • Ingår i: Perspectives on Psychological Science. - : Sage Publications. - 1745-6916 .- 1745-6924. ; 16:6, s. 1255-1269
  • Tidskriftsartikel (refereegranskat)abstract
    • Science is often perceived to be a self-correcting enterprise. In principle, the assessment of scientific claims is supposed to proceed in a cumulative fashion, with the reigning theories of the day progressively approximating truth more accurately over time. In practice, however, cumulative self-correction tends to proceed less efficiently than one might naively suppose. Far from evaluating new evidence dispassionately and infallibly, individual scientists often cling stubbornly to prior findings. Here we explore the dynamics of scientific self-correction at an individual rather than collective level. In 13 written statements, researchers from diverse branches of psychology share why and how they have lost confidence in one of their own published findings. We qualitatively characterize these disclosures and explore their implications. A cross-disciplinary survey suggests that such loss-of-confidence sentiments are surprisingly common among members of the broader scientific population yet rarely become part of the public record. We argue that removing barriers to self-correction at the individual level is imperative if the scientific community as a whole is to achieve the ideal of efficient self-correction.
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23.
  • Torbrand, Christian, et al. (författare)
  • Sentinel Node Identification with Hybrid Tracer-guided and Conventional Dynamic Sentinel Node Biopsy in Penile Cancer : A Prospective Study in 130 Patients from the Two National Referral Centres in Sweden
  • 2022
  • Ingår i: European Urology Oncology. - : European Association of Urology. - 2588-9311. ; 5:6, s. 704-711
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Studies suggest that a hybrid indocyanine green (ICG)-99mTc-nanocolloid tracer improves sentinel node (SN) identification compared to conventional dynamic sentinel node biopsy (DSNB).OBJECTIVE: To investigate hybrid tracer-guided SN identification in a multicentre setting and determine false-negative (FN) and complication rates.DESIGN, SETTING, AND PARTICIPANTS: A total of 130 patients with penile cancer scheduled for DSNB were prospectively included between February 2016 and December 2017 at two national Swedish referral centres. ICG-99mTc-nanocolloid hybrid tracer was used in the standard DSNB protocol.INTERVENTION: SNs were identified intraoperatively using radioguidance, fluorescence imaging, and blue dye.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of SNs identified by each tracer and the rates of complications and nodal recurrence during median follow-up of 34 mo were recorded. Differences in proportions between groups were compared using χ2 and McNemar's tests.RESULTS AND LIMITATIONS: Overall, 453 SNs were identified preoperatively via single-photon emission computed tomography/computed tomography. Among the 425 SNs excised, radioguidance, fluorescence, and blue dye identified 414 (97%), 363 (85%), and 349 (82%), respectively. Fluorescence imaging helped to detect six SNs that were negative using the other tracers, two of which were from the same patient and contained metastases. Histopathological examination detected 33 metastatic SNs in 20/130 patients (15%). The FN rate was 12% per groin (95% confidence interval 8-16%).CONCLUSIONS: Identification of SNs in patients with penile cancer relies mainly on radioguidance, while fluorescence (ICG) and blue dye methods for optical SN identification are comparable. However, the value of fluorescence imaging should be further evaluated in studies with long-term follow-up.PATIENT SUMMARY: In this study, we investigated addition of a dye called indocyanine green (ICG) for assessment of lymph nodes in patients with cancer of the penis. ICG did not improve the rate of detection of nodes most likely to harbour cancer because of their location in the drainage pathway for lymphatic fluid, but did help in identifying additional metastases.
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24.
  • Vikerfors, Anders, 1984-, et al. (författare)
  • Plasma Levels of Pentraxin 3 : A Potential Prognostic Biomarker in Urinary Bladder Cancer Patients
  • 2024
  • Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Urinary bladder cancer (BC) represents a major health issue, and identifying novel biomarkers for early disease detection and outcome prediction is paramount. It has already been established that the immune system plays a role in tumour initiation and progression in which the inflammatory marker pentraxin 3 (PTX3) might be involved, presenting a variety of functions in different cancers. The aim of this study was to investigate whether plasma levels of PTX3 could be used as a biomarker for patients with BC. Plasma levels of PTX3 were determined in 118 BC patients and 50 controls by ELISA. Patients with BC had significantly higher PTX3 levels compared to controls. The value as a diagnostic biomarker is probably limited, however, since no significant difference in PTX3 levels was seen between patients with non-muscle-invasive BC and controls; they were seen only between patients with muscle-invasive disease and controls. However, the potential value of PTX3 as a prognostic biomarker was indicated by significantly higher PTX3 levels in patients who developed metastatic disease during follow-up compared to patients who did not develop metastatic disease. The conclusions from this study are that plasma levels of PTX3 have limited value as a diagnostic biomarker, although they have potential as a prognostic biomarker for patients with BC.
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25.
  • Vikerfors, Anders, 1984-, et al. (författare)
  • Soluble PD-L1 in Serum and Urine in Urinary Bladder Cancer Patients
  • 2021
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Soluble PD-L1 (sPD-L1) levels have been identified as a potential biomarker for various cancers, but its diagnostic and prognostic value in urinary bladder cancer (BC) remains to be fully elucidated. In this study, we investigated sPD-L1 levels in serum and urine samples from 132 patients with BC and compared them to 51 patients with hematuria (controls). The levels of sPD-L1 in serum and urine were determined using ELISA. Soluble PD-L1 could be detected in 99.5% of the serum samples and 34.4% of the urine samples. Patients diagnosed with BC had significantly higher urinary levels of sPD-L1, compared to controls, however no difference were found in serum sPD-L1 levels (p = 0.038 and p = 0.61, respectively). Significantly higher serum sPD-L1 levels were found in patients with muscle invasive disease and metastatic disease, compared to patients with non-muscle invasive BC and non-metastatic disease (p < 0.05). There was also a trend for higher urine sPD-L1 levels in patients with metastatic disease, compared to patients with non-metastatic disease (p = 0.05). The results from this study suggest that sPD-L1 in serum, but not in urine, could be a potential prognostic biomarker for patients with BC.
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26.
  • Wihl, Jessica, et al. (författare)
  • Medical and nonmedical information during multidisciplinary team meetings in cancer care
  • 2021
  • Ingår i: Current Oncology. - : MDPI AG. - 1718-7729. ; 28:1, s. 1008-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Multidisciplinary team (MDT) meetings provide treatment recommendations based on available information and collective decision-making in teams with complementary professions, disciplines and skills. We aimed to map ancillary medical and nonmedical patient information during case presentations and case discussions in MDT meetings in cancer care. Methods: Through a nonparticipant, observational approach, we mapped verbal information on medical, nonmedical and patient-related characteristics and classified these based on content. Data were collected from 336 case discussions in three MDTs for neuro-oncology, sarcoma and hepato-biliary cancer. Results: Information on physical status was presented in 48.2% of the case discussions, psychological status in 8.9% and comorbidity in 48.5% of the cases. Nonmedical factors, such as family relations, occupation, country of origin and abode were referred to in 3.6–7.7% of the cases, and patient preferences were reported in 4.2%. Conclusions: Provision of information on comorbidities in half of the cases and on patient characteristics and treatment preferences in <10% of case discussions suggest a need to define data elements and develop reporting standards to support robust MDT decision-making.
  •  
27.
  • Zelic, Renata, et al. (författare)
  • Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer
  • 2021
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Virtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998-2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen's kappa and Bland and Altman's limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.
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28.
  • Zelic, Renata, et al. (författare)
  • Prognostic Utility of the Gleason Grading System Revisions and Histopathological Factors Beyond Gleason Grade.
  • 2022
  • Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 14, s. 59-70
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear.Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction.Patients and Methods: We conducted a case-control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998-2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC).Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ≥50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS.Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ≥50% cancer further improve PCa death discrimination slightly.
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29.
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