1. |
- Alexeyev, Oleg, et al.
(författare)
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Association between the presence of bacterial 16S RNA in prostate specimens taken during transurethral resection of prostate and subsequent risk of prostate cancer (Sweden)
- 2006
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Ingår i: Cancer Causes and Control. - Dordrecht : Kluwer Academic Publishers. - 0957-5243 .- 1573-7225. ; 17:9, s. 1127-1133
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study bacterial 16S RNA in archival prostate samples from 352 patients with benign prostate hyperplasia (BPH) and evaluate whether the presence of bacterial DNA was different in those who later developed prostate cancer (n = 171) and in the matched controls that did not progress to cancer (n = 181).Methods: 16S DNA PCR followed by cloning and sequencing the positive samples.Results: In 96/352 (27%) of the prostate tissue specimens 16S RNA were detected. Sequence analysis revealed Propionibacterium acnes as the predominant microorganism (23% of 16S RNA positive patients). The second most frequent isolate—Escherichia coli was found in 12 (12%) patients. The other isolates included Pseudomonas sp. (3 patients), Actinomyces sp. (2), Streptococcus mutans (1), Corynebacterium sp. (2),Nocardioides sp. (1), Rhodococcus sp. (1) Veillonella sp. (2). In P. acnes positive samples 62% exhibited severe histological inflammation versus 50% in the bacteria-negative group (p = 0.602). The presence of P. acnes in the prostate was associated with prostate cancer development (OR 2.17, 95% CI 0.77–6.95).Conclusions: This study has revealed P. acnes as the most common bacteria in the prostate in BPH. Further studies are needed to clarify its role in contributing to the development of prostatic inflammation and prostate cancer.
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2. |
- Bergh, Camilla, et al.
(författare)
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30-day and 1-year mortality after skeletal fractures: a register study of 295,713 fractures at different locations
- 2021
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:6, s. 739-745
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Few studies have reported the mortality rate after skeletal fractures involving different locations, within the same population. We analyzed the 30-day and 1-year mortality rates following different fractures. Patients and methods - We included 295,713 fractures encountered in patients 16-108 years of age, registered in the Swedish Fracture Register (SFR) from 2012 to 2018. Mortality rates were obtained by linkage of the SFR to the Swedish Tax Agency population register. The standardized mortality ratios (SMR) at 30 days and 1 year were calculated for fractures in any location and for each of 27 fracture locations, using age- and sex-life tables from Statistics Sweden (www.scb.se). Results - The overall SMR at 30 days was 6.8 (95% CI 6.7-7.0) and at 1 year 2.2 (CI 2.2-2.2). The SMR was > 2 for 19/27 and 13/27 of the fracture locations at 30 days and 1 year, respectively. Humerus, femur, and tibial diaphysis fractures were all associated with high SMR, at both 30 days and 1 year. Interpretation - Patients sustaining a fracture had approximately a 7-fold increased mortality at 30 days and over 2-fold increased mortality at 1 year as compared with what would be expected in the general population. High mortality rates were seen for patients with axial skeletal and proximal extremity fractures, indicating frailty in these patient groups.
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3. |
- Bergh, Camilla
(författare)
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Aspects of bone quality and risk assessments in fracture and elective orthopaedic patients
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Bone quality, bone strength, and bone remodelling are important in many orthopaedic conditions and can have an impact on fracture incidence, bone healing, implant failure, and different outcome aspects. There is relatively sparse information on fracture incidence and mortality both for all fractures compiled and for some of the individual fracture locations. In elective orthopaedic surgery, systematic screening for bone quality is rarely performed today. Aim: The aim of the constituent studies of this thesis was to investigate epidemiology and mortality in patients sustaining different types of fractures in relation to age and gender and, furthermore, to investigate preoperative bone quality in a group of elective orthopaedic patients. Methods: In studies I, III, and IV, data collected in the Swedish Fracture Register (SFR) were combined with data from Statistics Sweden (SCB) and the Swedish Tax Agency population register to calculate incidence and mortality for all fractures.locations. The SFR data were divided into 27 anatomical locations. Incidence curves based on age and gender were calculated and grouped based on visual appearance (Study I). The standardized mortality ratio (SMR) was calculated for 30-day and 1-year mortality as the ratio between observed and expected mortality, (Studies III and IV). In study I, the catchment area was Gothenburg and surrounding municipalities, included 23,917 individuals sustaining 27,169 fractures during the 2015–2018 period. Studies III and IV included data on 295,713 fractures registered during the 2012–2018 period throughout Sweden. In study II, 65 patients undergoing elective surgery for lumbar spinal stenosis (LSS) and 53 patients with hip osteoarthrosis (HOA) undergoing hip arthroplasty all underwent dual-energy X-ray absorptiometry (DXA) measurement of the femoral neck (FN) and in three projections/areas of the lumbar spine before surgery. The LSS patients also filled out the Fracture Risk Assessment Tool (FRAX) questionnaire and the results were compared with those of the DXA investigations. Results: The fracture incidence was found to be 1229 fractures/105 person year, with the highest incidences for the wrist (201/105 ), proximal femur (181/105 ), ankle (127/105 ), proximal humerus (101/105 ), and metacarpals (89/105 ) (Study I). Women sustained 64.5% of the fractures, 9.2% of which were registered as high-energy trauma and 2.3% as open fractures. Seven fracture incidence distribution groups were created (Study I). DXA measurements in LSS patients demonstrated large variations in BMD in the different projection with the lowest values for lateral projection of the vertebrae. No major differences regarding BMD were seen between the two elective patient groups (spine and hip patients). With DXA measurement of the lateral spine 71% of the spinal stenosis patients had less than -2.5 in T-score, while the FRAX questionnaire identified only 40% of these patients as high-risk patients.(Study II). The overall SMR at 30 days was found to be 6.8 (95% CI 6.7–7.0) and at one year 2.2 (95% CI 2.2–2.2) (study III). For 19/27 and 13/27 of the fracture locations at the two time points, respectively, the SMR was >2. Humerus, femur, and tibial diaphysis fractures were all associated with high SMR at both time points. For the oldest age group, 22 out of 27 fracture locations had an SMR ≥2 at 30 days (Study IV). Fractures of the femur (i.e., proximal, diaphysis, and distal) and humerus diaphysis were among the fractures associated with the highest mortality rates and SMRs within each age group. Conclusions: Overall fracture incidence varied markedly with age and gender in different locations. The incidence curves suggested that proximal tibia fractures and ankle fractures in women, in addition to established osteoporosis-related fractures, are mainly osteoporosis related. Osteoporosis/osteopenia was common in the elective spine surgery patients, however and FRAX evaluation could not replace DXA measurement of the spine. Regardless of age, any type of femur fractures and humerus diaphysis fractures were associated with increased mortality. The high mortality rates seen for elderly patients with axial skeletal and proximal extremity fractures, indicate frailty in these patient groups.
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4. |
- Bergh, Camilla, et al.
(författare)
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Fracture incidence in adults in relation to age and gender: A study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 Bergh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Studies on fracture incidence have mostly been based on retrospectively registered data from local hospital databases. The Swedish Fracture Register (SFR) is a national quality register collecting data prospectively on fractures, at the time of care-seeking. In the present study the incidence of all different fractures, regardless of location, in adults’ > 16 years treated at the only care provider for patients with fractures within a catchment area of approximately 550,000 inhabitants, during 2015–2018 are described. Age, gender, and fracture location (according to AO/OTA classification) was used for the analyses and presentation of fracture incidences. During the 4-year study period, 23,917 individuals sustained 27,169 fractures. The mean age at fracture was 57.9 years (range 16–105 years) and 64.5% of the fractures occurred in women. The five most common fractures accounted for more than 50% of all fractures: distal radius, proximal femur, ankle, proximal humerus, and metacarpal fractures. Seven fracture incidence distribution groups were created based on age- and gender-specific incidence curves, providing visual and easily accessible information on fracture distribution. This paper reports on incidence of all fracture locations based on prospectively collected data in a quality register. The knowledge on fracture incidence related to age and gender may be of importance for the planning of orthopaedic care, involving both in- and out-patients as well as allocating surgical resources. Further, this might be useful for organizing preventive measures, especially in countries with similar socioeconomic structure and fracture burden.
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5. |
- Bergh, Camilla, et al.
(författare)
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Increased risk of revision in patients with non-traumatic femoral head necrosis.
- 2014
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 85:1, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Previous studies of patients who have undergone total hip arthroplasty (THA) due to femoral head necrosis (FHN) have shown an increased risk of revision compared to cases with primary osteoarthritis (POA), but recent studies have suggested that this procedure is not associated with poor outcome. We compared the risk of revision after operation with THA due to FHN or POA in the Nordic Arthroplasty Register Association (NARA) database including Denmark, Finland, Norway, and Sweden. Patients and methods 427,806 THAs performed between 1995 and 2011 were included. The relative risk of revision for any reason, for aseptic loosening, dislocation, deep infection, and periprosthetic fracture was studied before and after adjustment for covariates using Cox regression models. Results 416,217 hips with POA (mean age 69 (SD 10), 59% females) and 11,589 with FHN (mean age 65 (SD 16), 58% females) were registered. The mean follow-up was 6.3 (SD 4.3) years. After 2 years of observation, 1.7% in the POA group and 3.0% in the FHN group had been revised. The corresponding proportions after 16 years of observation were 4.2% and 6.1%, respectively. The 16-year survival in the 2 groups was 86% (95% CI: 86-86) and 77% (CI: 74-80). After adjusting for covariates, the relative risk (RR) of revision for any reason was higher in patients with FHN for both periods studied (up to 2 years: RR = 1.44, 95% CI: 1.34-1.54; p < 0.001; and 2-16 years: RR = 1.25, 1.14-1.38; p < 0.001). Interpretation Patients with FHN had an overall increased risk of revision. This increased risk persisted over the entire period of observation and covered more or less all of the 4 most common reasons for revision.
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6. |
- Bergh, Camilla, et al.
(författare)
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Mortality after Sustaining Skeletal Fractures in Relation to Age
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Age-related mortality across fractures in different anatomical regions are sparsely described, since most studies focus on specific age groups or fracture locations. The aim here was to investigate mortality at 30 days and 1 year post-fracture within four different age groups. All patients >= 16 years registered in the Swedish Fracture Register (SFR) 2012-2018 were included (n = 262,598 patients) and divided into four age groups: 16-49, 50-64, 65-79, and >= 80 years of age. Standardized mortality ratios (SMR) at 30 days and 1 year after sustaining a fracture were calculated using age- and gender-specific life tables from Statistics Sweden for each of the 27 fracture locations in the four age groups. Absolute mortality rates for the youngest age group for all locations were below 1% and 2% at 30 days and 1 year, respectively. For the patients in the two oldest age groups (65 and older), mortality rates were as high as 5% at 30 days and up to 25% at 1 year for certain fracture locations. For younger patients a few localizations were associated with high SMRs, whereas for the oldest age group 22 out of 27 fracture locations had an SMR of >= 2 at 30 days. Fractures of the femur (proximal, diaphysis, and distal) and humerus diaphysis fractures were among the fractures associated with the highest mortality rates and SMRs within each age group. Moderately high SMRs were further seen for pelvic, acetabulum, spine, and tibia fractures within all age groups. Regardless of age, any type of femur fractures and humerus diaphysis fractures were associated with increased mortality. In the oldest age groups, about twice as many patients died within 1 year after sustaining a fracture in almost any location, as compared with the expected mortality rates, whereas in the youngest age group only fractures in a few locations were associated with a high SMR.
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7. |
- Bergh, Camilla, et al.
(författare)
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Preoperative dual-energy X-ray absorptiometry and FRAX in patients with lumbar spinal stenosis
- 2018
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOsteoporosis implies an increased risk of complications after orthopedic surgery. For the mostly elderly group of patients undergoing lumbar spinal stenosis surgery (LSS), it is important to include skeletal health evaluation in the preoperative planning. The aim of this study was to assess spine and femoral neck (FN) bone mineral density (BMD) in LSS patients and to evaluate whether the World Health Organization (WHO) fracture risk assessment tool (FRAX) can identify patients with reduced BMD levels in the spine.MethodsThe study involved 65 LSS patients and 53 patients with hip osteoarthritis (HOA) for comparison. BMD was measured with dual-energy X-ray absorptiometry (DXA) in the lumbar spine in three projections: anterior-posterior (AP), lateral and lateral-mid (the mid-portion of the vertebrae), and FN. The LSS patients filled out the FRAX questionnaire.ResultsIn the LSS group, 43% of the women and 8% of the men were classified as being osteoporotic/osteopenic by AP spine measurement. The corresponding proportions using the lateral spine T-score -2.5 were 87% and 57%, respectively, and 82% and 53%, respectively, for the FN. The FN BMD T-score was significantly lower in the LSS group compared with the HOA group. The FRAX questionnaire identified 40% of the LSS patients with a moderate/high risk of sustaining an osteoporotic fracture within 10years, with or without simultaneous FN BMD, while 71% of these patients were classified as being osteoporotic with DXA lateral spine measurement.ConclusionIt is common with osteoporosis/osteopenia in patients undergoing spine surgery, and the identification may influence the surgical treatment why the evaluation of BMD is important preoperatively. FRAX evaluation could not replace DXA measurement of the spine regarding the identification of osteoporosis patients in the preoperative planning phase.
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10. |
- Bovinder Ylitalo, Erik, et al.
(författare)
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Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens
- 2020
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Ingår i: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 80:1, s. 214-224
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Tidskriftsartikel (refereegranskat)abstract
- Background Taxane treatment may be a suitable therapeutic option for patients with castration-resistant prostate cancer and high expression of constitutively active androgen receptor variants (AR-Vs). The aim of the study was to compare the effects of cabazitaxel and androgen deprivation treatments in a prostate tumor xenograft model expressing high levels of constitutively active AR-V7. Furthermore, mechanisms behind acquired cabazitaxel resistance were explored. Methods Mice were subcutaneously inoculated with 22Rv1 cells and treated with surgical castration (n = 7), abiraterone (n = 9), cabazitaxel (n = 6), castration plus abiraterone (n = 8), castration plus cabazitaxel (n = 11), or vehicle and/or sham operation (n = 23). Tumor growth was followed for about 2 months or to a volume of approximately 1000 mm(3). Two cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, were established from xenografts relapsing during cabazitaxel treatment. Differential gene expression between the cabazitaxel resistant and control 22Rv1 cells was examined by whole-genome expression array analysis followed by immunoblotting, immunohistochemistry, and functional pathway analysis. Results Abiraterone treatment alone or in combination with surgical castration had no major effect on 22Rv1 tumor growth, while cabazitaxel significantly delayed and in some cases totally abolished 22Rv1 tumor growth on its own and in combination with surgical castration. The cabazitaxel resistant cell lines; 22Rv1-CabR1 and 22Rv1-CabR2, both showed upregulation of the ATP-binding cassette sub-family B member 1 (ABCB1) efflux pump. Treatment with ABCB1 inhibitor elacridar completely restored susceptibility to cabazitaxel, while treatment with AR-antagonists bicalutamide and enzalutamide partly restored susceptibility to cabazitaxel in both cell lines. The cholesterol biosynthesis pathway was induced in the 22Rv1-CabR2 cell line, which was confirmed by reduced sensitivity to simvastatin treatment. Conclusions Cabazitaxel efficiently inhibits prostate cancer growth despite the high expression of constitutively active AR-V7. Acquired cabazitaxel resistance involving overexpression of efflux transporter ABCB1 can be reverted by bicalutamide or enzalutamide treatment, indicating the great clinical potential for combined treatment with cabazitaxel and anti-androgens.
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11. |
- Brisby, Helena, 1965, et al.
(författare)
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The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: A descriptive study in humans
- 2013
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:5, s. 804-814
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is common and degenerated discs are believed to be a major cause. In non-degenerated intervertebral discs(IVDs) presence of stem-/progenitor cells was recently reported in different mammals (rabbit,rat,pig). Understanding processes of disc degeneration and regenerative mechanisms within degenerated discs(DDs) is important. The aim of the study was to examine presence of local stem-/progenitor cells in human DDs and if these cell-populations could respond to paracrin stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) was collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs)(iliac crest) from two donors. Non-degenerated disc cells were collected from one donor(scoliosis) and chordoma tissue was obtained from(positive control, stem cell markers) two donors. The IVD biopsies were investigated for gene- and protein expression of: OCT3/4, CD105, CD90, STRO-1 and NOTCH1. DD cell cultures(pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples and CD90 and NOTCH1 was detected 15/15 samples. Immunohistochemistry analysis supported findings on protein level, in cells sparsely distributed in DDs tissues. DDs cell-cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1 and JAGGED1 which was observed when cultured in conditioned cell-culture media from MSC compared to cell-cultures cultured with conditioned media from non-degenerated disc cells. Expression of OCT3/4(multipotency marker) and NOTCH1(regulator of cell fate), MSC- markers CD105, CD90 and STRO-1 indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by by paracrin signalling /soluble factors from MSCs and from non-degenerated IVD cells was observed in vitro indicating that repair processes within human degenerated discs may be stimulated.
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12. |
- Chamat, J., et al.
(författare)
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Avascular necrosis in a patient diagnosed with coxartrosis : Patient med diagnosen koxartros visade sig ha avaskulär nekros. Mindre vanlig orsak till ledsmärta med hög morbiditet
- 2019
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Ingår i: Lakartidningen. - 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Coxartrosis is a common cause of hip pain among the elderly population. Avascular necrosis (AVN), also known as osteonecrosis, is a disease that most commonly affects the femoral head as a result of decreased blood supply to the bone. The etiology and pathogenesis is still unclear, but there are various traumatic and atraumatic factors that have been suggested as risk factors for AVN. However, almost half of the patients present none of these risk factors. Compared to coxartrosis, AVN typically occurs in a younger population. Initially it can be difficult to differ between these conditions. Plain film radiographic findings are absent in early stages of AVN, but magnetic resonance imaging (MRI) can provide early diagnosis. Thereby, MRI is the golden standard of noninvasive diagnostic evaluation. We present a patient with bilateral AVN that initially was diagnosed with coxartrosis.
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13. |
- Gaillard, Marie-José, et al.
(författare)
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Causes of Regional Change : Land Cover
- 2015
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Ingår i: Second Assessment of Climate Change for the Baltic Sea Basin. - Cham : Springer. - 9783319160054 - 9783319160061 ; , s. 453-477
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Bokkapitel (refereegranskat)abstract
- Anthropogenic land-cover change (ALCC) is one of the few climate forcings for which the net direction of the climate response over the last two centuries is still not known. The uncertainty is due to the often counteracting temperature responses to the many biogeophysical effects and to the biogeochemical versus biogeophysical effects. Palaeoecological studies show that the major transformation of the landscape by anthropogenic activities in the southern zone of the Baltic Sea basin occurred between 6000 and 3000/2500 cal year BP. The only modelling study of the biogeophysical effects of past ALCCs on regional climate in north-western Europe suggests that deforestation between 6000 and 200 cal year BP may have caused significant change in winter and summer temperature. There is no indication that deforestation in the Baltic Sea area since AD 1850 would have been a major cause of the recent climate warming in the region through a positive biogeochemical feedback. Several model studies suggest that boreal reforestation might not be an effective climate warming mitigation tool as it might lead to increased warming through biogeophysical processes.
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14. |
- Glimelius, Bengt, et al.
(författare)
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U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
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Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
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15. |
- Henoch, Ingela, 1956, et al.
(författare)
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The Swedish Version of the Frommelt Attitude Toward Care of the Dying Scale : Aspects of Validity and Factors Influencing Nurses' and Nursing Students' Attitudes.
- 2014
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Ingår i: Cancer Nursing. - : Lippincott Williams & Wilkins. - 0162-220X .- 1538-9804. ; 37:1, s. E1-E11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:: Nurses' attitudes toward caring for dying persons need to be explored. The Frommelt Attitude Toward Care of the Dying (FATCOD) scale has not previously been used in Swedish language. OBJECTIVES:: The objectives of this study were to compare FATCOD scores among Swedish nurses and nursing students with those from other languages, to explore the existence of 2 subscales, and to evaluate influences of experiences on attitudes toward care of dying patients. METHODS:: A descriptive, cross-sectional, and predictive design was used. The FATCOD scores of Swedish nurses from hospice, oncology, surgery clinics, and palliative home care and nursing students were compared with published scores from the United States, Israel, and Japan. Descriptive statistics, t tests, and factor and regression analyses were used. RESULTS:: The sample consisted of 213 persons: 71 registered nurses, 42 enrolled nurses, and 100 nursing students. Swedish FATCOD mean scores did not differ from published means from the United States and Israel, but were significantly more positive than Japanese means. In line with Japanese studies, factor analyses yielded a 2-factor solution. Total FATCOD and subscales had low Cronbach α's. Hospice and palliative team nurses were more positive than oncology and surgery nurses to care for dying patients. CONCLUSIONS:: Although our results suggest that the Swedish FATCOD may comprise 2 distinct scales, the total scale may be the most adequate and applicable for use in Sweden. Professional experience was associated with nurses' attitudes toward caring for dying patients. IMPLICATION FOR PRACTICE:: Care culture might influence nurses' attitudes toward caring for dying patients; the benefits of education need to be explored.
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16. |
- Henoch, Ingela, et al.
(författare)
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The Swedish version of the Frommelt Attitude Toward Care of the Dying Scale (FATCOD) : Aspects of validity and factors influencing nurses' and nursing students' attitudes
- 2014
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Ingår i: Cancer Nursing. - : Lippincott Williams & Wilkins. - 0162-220X .- 1538-9804. ; 37:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Nurses' attitudes toward caring for dying persons need to be explored. The Frommelt Attitude Toward Care of the Dying (FATCOD) scale has not previously been used in Swedish language.Objectives: The objectives of this study were to compare FATCOD scores among Swedish nurses and nursing students with those from other languages, to explore the existence of 2 subscales, and to evaluate influences of experiences on attitudes toward care of dying patients.Methods: A descriptive, cross-sectional, and predictive design was used. The FATCOD scores of Swedish nurses from hospice, oncology, surgery clinics, and palliative home care and nursing students were compared with published scores from the United States, Israel, and Japan. Descriptive statistics, t tests, and factor and regression analyses were used.Results: The sample consisted of 213 persons: 71 registered nurses, 42 enrolled nurses, and 100 nursing students. Swedish FATCOD mean scores did not differ from published means from the United States and Israel, but were significantly more positive than Japanese means. In line with Japanese studies, factor analyses yielded a 2-factor solution. Total FATCOD and subscales had low Cronbach [alpha]'s. Hospice and palliative team nurses were more positive than oncology and surgery nurses to care for dying patients.Conclusions: Although our results suggest that the Swedish FATCOD may comprise 2 distinct scales, the total scale may be the most adequate and applicable for use in Sweden. Professional experience was associated with nurses' attitudes toward caring for dying patients.Implication for Practice: Care culture might influence nurses' attitudes toward caring for dying patients; the benefits of education need to be explored.
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19. |
- Karlsson Thellenberg, Camilla, et al.
(författare)
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Risk of prostate cancer after trans urethral resection of BPH : a cohort and nested case-control study
- 2011
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 3:4, s. 4127-4138
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological and experimental evidence suggests that inflammation plays a role in both prostate cancer (PCa) and benign prostate hyperplasia (BPH). This study evaluates the risk of PC after transurethral resection (TURP) for BPH and estimates the PCa risk related to presence of inflammation in the resected material. The Pathology Department at the University Hospital of Umea (Umea, Sweden) identified BPH cases (n = 7,901) that underwent TURP between 1982 and 1997. Using these pathological specimens, we compared the incidence of PCa in the cohort to the population and calculated the standardized incidence and mortality ratios (SIR and SMR). Inflammation, the androgen receptor (AR), and p53 were evaluated in a nested case-control study of 201 cases and controls. Inflammation was graded severe or mild-moderate. In the follow-up period after TURP, cases developed prostate cancer and the controls did not. After TURP, SIR for prostate cancer increased [1.26, CI 95% (1.17–1.35)], whereas SMR decreased [0.59, CI 95% (0.47–0.73)]. Presence of inflammation at the time of TURP did not differ between cases and controls nor were there differences in p53 or AR staining. The data suggest a small increased risk of PCa after TURP and decreased PCa mortality. Inflammation at the time of TURP is not associated with PCa risk in this material. The increased PCa risk may be attributed to increased surveillance and PSA screening.
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20. |
- Klemetti, R., et al.
(författare)
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Puberty disorders among ART-conceived singletons: a Nordic register study from the CoNARTaS group
- 2022
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 37:10, s. 2402-2411
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Tidskriftsartikel (refereegranskat)abstract
- STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.
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21. |
- Nilsson, Erik, et al.
(författare)
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The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography
- 2023
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.Methods: We analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.Results: We find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.Conclusions: By co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.
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22. |
- Roberge, Jean-Michel, et al.
(författare)
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Socio-ecological implications of modifying rotation lengths in forestry
- 2016
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 45, s. 109-123
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Tidskriftsartikel (refereegranskat)abstract
- The rotation length is a key component of even-aged forest management systems. Using Fennoscandian forestry as a case, we review the socioecological implications of modifying rotation lengths relative to current practice by evaluating effects on a range of ecosystem services and on biodiversity conservation. The effects of shortening rotations on provisioning services are expected to be mostly negative to neutral (e.g. production of wood, bilberries, reindeer forage), while those of extending rotations would be more varied. Shortening rotations may help limit damage by some of today's major damaging agents (e.g. root rot, cambium-feeding insects), but may also increase other damage types (e.g. regeneration pests) and impede climate mitigation. Supporting (water, soil nutrients) and cultural (aesthetics, cultural heritage) ecosystem services would generally be affected negatively by shortened rotations and positively by extended rotations, as would most biodiversity indicators. Several effect modifiers, such as changes to thinning regimes, could alter these patterns.
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23. |
- Sandgren, Kristina, et al.
(författare)
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Histopathology-validated lesion detection rates of clinically significant prostate cancer with mpMRI, [68Ga]PSMA-11-PET and [11C]Acetate-PET
- 2023
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Ingår i: Nuclear medicine communications. - : Lippincott Williams & Wilkins. - 0143-3636 .- 1473-5628. ; 44:11, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET/CT and multiparametric MRI (mpMRI) are important diagnostic tools in clinically significant prostate cancer (csPC). The aim of this study was to compare csPC detection rates with [68Ga]PSMA-11-PET (PSMA)-PET, [11C] Acetate (ACE)-PET, and mpMRI with histopathology as reference, to identify the most suitable imaging modalities for subsequent hybrid imaging. An additional aim was to compare inter-reader variability to assess reproducibility.Methods: During 2016–2019, all study participants were examined with PSMA-PET/mpMRI and ACE-PET/CT prior to radical prostatectomy. PSMA-PET, ACE-PET and mpMRI were evaluated separately by two observers, and were compared with histopathology-defined csPC. Statistical analyses included two-sided McNemar test and index of specific agreement.Results: Fifty-five study participants were included, with 130 histopathological intraprostatic lesions >0.05 cc. Of these, 32% (42/130) were classified as csPC with ISUP grade ≥2 and volume >0.5 cc. PSMA-PET and mpMRI showed no difference in performance (P = 0.48), with mean csPC detection rate of 70% (29.5/42) and 74% (31/42), respectively, while with ACE-PET the mean csPC detection rate was 37% (15.5/42). Interobserver agreement was higher with PSMA-PET compared to mpMRI [79% (26/33) vs 67% (24/38)]. Including all detected lesions from each pair of observers, the detection rate increased to 90% (38/42) with mpMRI, and 79% (33/42) with PSMA-PET.Conclusion: PSMA-PET and mpMRI showed high csPC detection rates and superior performance compared to ACE-PET. The interobserver agreement indicates higher reproducibility with PSMA-PET. The combined result of all observers in both PSMA-PET and mpMRI showed the highest detection rate, suggesting an added value of a hybrid imaging approach.
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24. |
- Sandgren, Kristina, et al.
(författare)
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Registration of histopathology to magnetic resonance imaging of prostate cancer
- 2021
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Ingår i: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 18, s. 19-25
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The diagnostic accuracy of new imaging techniques requires validation, preferably by histopathological verification. The aim of this study was to develop and present a registration procedure between histopathology and in-vivo magnetic resonance imaging (MRI) of the prostate, to estimate its uncertainty and to evaluate the benefit of adding a contour-correcting registration.Materials and methods: For twenty-five prostate cancer patients, planned for radical prostatectomy, a 3D-printed prostate mold based on in-vivo MRI was created and an ex-vivo MRI of the specimen, placed inside the mold, was performed. Each histopathology slice was registered to its corresponding ex-vivo MRI slice using a 2D-affine registration. The ex-vivo MRI was rigidly registered to the in-vivo MRI and the resulting transform was applied to the histopathology stack. A 2D deformable registration was used to correct for specimen distortion concerning the specimen's fit inside the mold. We estimated the spatial uncertainty by comparing positions of landmarks in the in-vivo MRI and the corresponding registered histopathology stack.Results: Eighty-four landmarks were identified, located in the urethra (62%), prostatic cysts (33%), and the ejaculatory ducts (5%). The median number of landmarks was 3 per patient. We showed a median in-plane error of 1.8 mm before and 1.7 mm after the contour-correcting deformable registration. In patients with extraprostatic margins, the median in-plane error improved from 2.1 mm to 1.8 mm after the contour-correcting deformable registration.Conclusions: Our registration procedure accurately registers histopathology to in-vivo MRI, with low uncertainty. The contour-correcting registration was beneficial in patients with extraprostatic surgical margins.
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25. |
- Spyratou, Vasiliki, 1981, et al.
(författare)
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Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer
- 2023
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 62:12, s. 1698-1706
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Tidskriftsartikel (refereegranskat)abstract
- Background: For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers. Material and methods: Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio. Results: The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel. Conclusion: PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.
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26. |
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27. |
- Thellenberg Karlsson, Camilla, 1972-
(författare)
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Prostate cancer : epidemiological studies of risk factors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In spite of the fact that prostate cancer is the most common male cancer in both Sweden and many other countries in the developed world, little is known of risk factors and predisposing conditions. The only well recognized risk factors are age, race and familial aggregation. More knowledge about risk factors could lead to better preventive measures together with better treatments. One way to evaluate this is to study second primary cancers; the connection between two different cancers can give valuable insight in etiology or clues to shared risk factors. This thesis aims at evaluating risk factors for prostate cancer. We constructed a cohort of 135,713 men diagnosed with prostate cancer and reported to the Swedish Cancer Registry 1958-1996. The cohort was followed for second primary cancers and a doubled risk of male breast cancer was found. We also noted increased risks for small intestine cancers and melanoma. As a follow-up on the increased risk of male breast cancer, we performed a nested case – control study. Included cases were men with first prostate and then breast cancer (n = 41) matched to men with only prostate cancer (n =81). For these men, we collected medical records and extracted data regarding treatment. Furthermore, all men diagnosed with both prostate and breast cancer irrespective which came first (n = 83) were used as probands. To both these sets of cases with breast and prostate cancer, we identified first degree relatives and grandchildren from parish offices throughout Sweden. Linking to the Cancer Registry retrieved all cancer diagnoses amongst relatives. Results from this study show a relation between estrogen treatment of prostate cancer and the risk of developing breast cancer. We also found that a small part of the cases with both cancers appeared in families with inheritance patterns possibly attributed to BRCA2. As estrogen treatment seemed involved in increased risk of breast cancer after prostate cancer, we wanted to investigate the newly discovered Estrogen receptor β and the relation to prostate cancer risk. Previous reports have shown that ERβ acts as a negative regulator of proliferation. ERβ expression occurs mainly in prostatic epithelial cells and the expression gradually diminishes when cancer develops and aggravates. We used a single nucleotide polymorphism (SNP) association study approach to evaluate genetic variation in ERβ as a risk factor for prostate cancer. One SNP, located in the promoter region associated with a small increased risk of prostate cancer whereas variation in the rest of the gene did not. In the last paper, we investigated trans-urethral resection (TURP) of the prostate due to benign prostate hyperplasia (BPH) as a risk factor for later development of prostate cancer. Evidence has gathered that both BPH and prostate cancer are associated to inflammation. By comparing incidence and mortality in a cohort of 7,901 men with the general population there appeared to be an increased risk of prostate cancer but decreased mortality. Analyzing this increased risk further, we conducted a nested case - control study with men extracted from the cohort. Cases had a TURP and later developed prostate cancer and controls just had a TURP. We then evaluated the specimens from TURP regarding extent of inflammation, degree of androgen receptor down regulation and expression of p53, all factors previous associated with prostate cancer. None of these parameters differed between cases and controls and they can therefore not explain the increased risk. Decreased mortality but increased risk might be explained by surveillance bias, which means more medical attention to these patients, resulting in diagnosing clinically non-significant cancers. In summary, our results show a doubled risk of male breast cancer following prostate cancer. A risk that can be attributed to the use of estrogen to treat prostate cancer or to some extent a possible mutation in BRCA2. We also propose that a SNP change in the ERβ promoter confer a small increased risk of prostate cancer. A small risk elevation of prostate cancer following TURP most probable could depend on surveillance bias.
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28. |
- Thysell, Elin, et al.
(författare)
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Clinical and biological relevance of the transcriptomic-based prostate cancer metastasis subtypes MetA-C
- 2022
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 16:4, s. 846-859
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Tidskriftsartikel (refereegranskat)abstract
- To improve treatment of metastatic prostate cancer, the biology of metastases needs to be understood. We recently described three subtypes of prostate cancer bone metastases (MetA-C), based on differential gene expression. The aim of this study was to verify the clinical relevance of these subtypes and to explore their biology and relations to genetic drivers. Freshly-frozen metastasis samples were obtained as hormone-naive (n = 17), short-term castrated (n = 21), or castration-resistant (n = 65) from a total of 67 patients. Previously published sequencing data from 573 metastasis samples were also analyzed. Through transcriptome profiling and sample classification based on a set of predefined MetA-C-differentiating genes, we found that most metastases were heterogeneous for the MetA-C subtypes. Overall, MetA was the most common subtype, while MetB was significantly enriched in castration-resistant samples and in liver metastases, and consistently associated with poor prognosis. By gene set enrichment analysis, the phenotype of MetA was described by high androgen response, protein secretion and adipogenesis, MetB by high cell cycle activity and DNA repair, and MetC by epithelial-to-mesenchymal transition and inflammation. The MetB subtype demonstrated single nucleotide variants of RB transcriptional corepressor 1 (RB1) and loss of 21 genes at chromosome 13, including RB1, but provided independent prognostic value to those genetic aberrations. In conclusion, a distinct set of gene transcripts can be used to classify prostate cancer metastases into the subtypes MetA-C. The MetA-C subtypes show diverse biology, organ tropism, and prognosis. The MetA-C classification may be used independently, or in combination with genetic markers, primarily to identify MetB patients in need of complementary therapy to conventional androgen receptor-targeting treatments.
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29. |
- Wennerholm, Ulla-Britt, 1948, et al.
(författare)
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Perinatal outcome in children born after assisted reproductive technologies
- 2020
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 125:2, s. 158-166
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Forskningsöversikt (refereegranskat)abstract
- Over the past 40 years access and effectiveness of assisted reproductive technologies (ART) have increased, and to date more than 8 million children have been conceived after ART globally. Most pregnancies resulting from ART are uncomplicated and result in the birth of healthy children. Yet, it is well known that pregnancies following ART are more likely to be affected by obstetric complications such as hypertensive disorders in pregnancy, preterm birth, and low birth weight compared with spontaneously conceived pregnancies. ART children are also at increased risk of birth defects. The majority of the problems arise as a result of multiple pregnancies and can be reduced by transferring a single embryo, thereby avoiding multiple pregnancies. New ART technologies are constantly introduced, and monitoring of the health of ART children is crucial.
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30. |
- Wikström, Pernilla, et al.
(författare)
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Epithelial and stromal characteristics of primary tumors predict the bone metastatic subtype of prostate cancer and patient survival after androgen-deprivation therapy
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:21
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) bone metastases can be divided into transcriptomic subtypes, by us termed MetA-C. The MetB subtype, constituting about 20% of the cases, is characterized by high cell cycle activity, low androgen receptor (AR) activity, and a limited response to standard androgen deprivation therapy (ADT). Complementary treatments should preferably be introduced early on if the risk of developing metastases of the MetB subtype is predicted to behigh. In this study, we therefore examined if the bone metastatic subtype and patient outcome after ADT could be predicted by immunohistochemical analysis of epithelial and stromal cell markers in primary tumor biopsies obtained at diagnosis (n = 98). In this advanced patient group, primary tumor International Society of Urological Pathology (ISUP) grade was not associated with outcome or metastasis subtype. In contrast, high tumor cell Ki67 labeling (proliferation) in combination with low tumor cell immunoreactivity for PSA, and a low fraction of AR positive stroma cells in the primary tumors were prognostic for poor survival after ADT. Accordingly, the same tissue markers were associated with developing metastases enriched for the aggressive MetB subtype. The development of the contrasting MetA subtype, showing the best response to ADT, could be predicted by the opposite staining pattern. We conclude that outcome after ADT and metastasis subtype can, at least to some extent, be predicted by analysis of primary tumor characteristics, such as tumor cell proliferation and PSA expression, and AR expression in stromal cells.
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31. |
- Zarei, Maryam, et al.
(författare)
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Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
- 2024
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Ingår i: Acta Oncologica. - : MJS Publishing, Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
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32. |
- Åberg, Anna-Maja, et al.
(författare)
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High monocyte count and expression of s100a9 and s100a12 in peripheral blood mononuclear cells are associated with poor outcome in patients with metastatic prostate cancer
- 2021
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, S100A9 and S100A12, in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of S100A9 and S100A12 was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of S100A9 and S100A12 were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and S100A9 levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as S100A9 and S100A12, could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.
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