| 1. |
- Lambregts, Doenja M. J., et al.
(författare)
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Current controversies in TNM for the radiological staging of rectal cancer and how to deal with them : results of a global online survey and multidisciplinary expert consensus
- 2022
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Ingår i: European Radiology. - : Springer Nature. - 0938-7994 .- 1432-1084. ; 32:7, s. 4991-5003
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To identify the main problem areas in the applicability of the current TNM staging system (8(th) ed.) for the radiological staging and reporting of rectal cancer and provide practice recommendations on how to handle them. Methods A global case-based online survey was conducted including 41 image-based rectal cancer cases focusing on various items included in the TNM system. Cases reaching < 80% agreement among survey respondents were identified as problem areas and discussed among an international expert panel, including 5 radiologists, 6 colorectal surgeons, 4 radiation oncologists, and 3 pathologists. Results Three hundred twenty-one respondents (from 32 countries) completed the survey. Sixteen problem areas were identified, related to cT staging in low-rectal cancers, definitions for cT4b and cM1a disease, definitions for mesorectal fascia (MRF) involvement, evaluation of lymph nodes versus tumor deposits, and staging of lateral lymph nodes. The expert panel recommended strategies on how to handle these, including advice on cT-stage categorization in case of involvement of different layers of the anal canal, specifications on which structures to include in the definition of cT4b disease, how to define MRF involvement by the primary tumor and other tumor-bearing structures, how to differentiate and report lymph nodes and tumor deposits on MRI, and how to anatomically localize and stage lateral lymph nodes. Conclusions The recommendations derived from this global survey and expert panel discussion may serve as a practice guide and support tool for radiologists (and other clinicians) involved in the staging of rectal cancer and may contribute to improved consistency in radiological staging and reporting.
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| 2. |
- Amkreutz, J. A. M. P., et al.
(författare)
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Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Arthritis
- 2021
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Ingår i: Arthritis and Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 73:6, s. 921-930
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Autoantibodies, such as anti–citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. Methods: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. Results: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm2 (95% confidence interval [95% CI] 0.91–0.93) versus 0.95 g/cm2 (95% CI 0.93–0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08–0.29] versus 0.48 [95% CI 0.33–0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti–carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. Conclusion: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed. © 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.
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| 3. |
- Bahadoer, Renu R., et al.
(författare)
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Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) : a randomised, open-label, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:1, s. 29-42
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Tidskriftsartikel (refereegranskat)abstract
- Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocardnoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within S weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 x 5 Gy over a maximum of 8 days) followed by six cycles of CAPDX chemotherapy (capecitabine 1000 mg/m(2) orally twice daily on days 1-14, oxaliplatin 130 mg/m(2) intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m(2) intravenously on day 1, leucovorin [folinic acid] 200 mg/m 2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m(2) intravenously and fluorouracil 600 mg/m 2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPDX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1.8 Gy up to 50.4 Gy or 25 fractions of 2.0 Gy up to 50.0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m(2) followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPDX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921, and is now complete. Findings Between June 21,2011, and June 2,2016,920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4.6 years (IQR 3.5-5.5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23.7% (95% CI 19.8-27.6) in the experimental group versus 30.4% (26.1-34.6) in the standard of care group (hazard ratio 0.75, 95% CI 0.60-0-95; p=0-019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.
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| 4. |
- Prata, Ilaria, et al.
(författare)
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Results of a diagnostic imaging audit in a randomised clinical trial in rectal cancer highlight the importance of careful planning and quality control
- 2023
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Ingår i: Insights into Imaging. - : Springer. - 1869-4101. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Background: Magnetic resonance (MR) imaging is the modality used for baseline assessment of locally advanced rectal cancer (LARC) and restaging after neoadjuvant treatment. The overall audited quality of MR imaging in large multicentre trials on rectal cancer is so far not routinely reported.Materials and methods: We collected MR images obtained within the Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation (RAPIDO) trial and performed an audit of the technical features of image acquisition. The required MR sequences and slice thickness stated in the RAPIDO protocol were used as a reference.Results: Out of 920 participants of the RAPIDO study, MR investigations of 668 and 623 patients in the baseline and restaging setting, respectively, were collected. Of these, 304/668 (45.5%) and 328/623 (52.6%) MR images, respectively, fulfilled the technical quality criteria. The main reason for non-compliance was exceeding slice thickness 238/668, 35.6% in the baseline setting and 162/623, 26.0% in the restaging setting. In 166/668, 24.9% and 168/623, 27.0% MR images in the baseline and restaging setting, respectively, one or more of the required pulse sequences were missing.Conclusion: Altogether, 49.0% of the MR images obtained within the RAPIDO trial fulfilled the image acquisition criteria required in the study protocol. High-quality MR imaging should be expected for the appropriate initial treatment and response evaluation of patients with LARC, and efforts should be made to maximise the quality of imaging in clinical trials and in clinical practice.
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| 5. |
- Kaldmäe, Margit, et al.
(författare)
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A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder
- 2022
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 30:5, s. 733-742, e1-e7
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Tidskriftsartikel (refereegranskat)abstract
- Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of “life on the edge of solubility.” Here, we investigate whether these features can be modulated by fusing the protein to a highly soluble spider silk domain (NT∗). The chimeric protein displays highly efficient translation and is fully active in human cancer cells. Biophysical characterization reveals a compact conformation, with the disordered transactivation domain of p53 wrapped around the NT∗ domain. We conclude that interactions with NT∗ help to unblock translation of the proline-rich disordered region of p53. Expression of partially disordered cancer targets is similarly enhanced by NT∗. In summary, we demonstrate that inducing co-translational folding via a molecular “spindle and thread” mechanism unblocks protein translation in vitro.
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| 6. |
- Brännström, Mats, 1958, et al.
(författare)
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Reproductive, obstetric, and long-term health outcome after uterus transplantation: results of the first clinical trial
- 2022
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 0015-0282 .- 1556-5653. ; 118:3, s. 576-585
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate reproductive, obstetric, and long-term health of the first completed study of uterus transplantation (UTx). Design: Prospective. Setting: University hospital. Patient(s): Nine live donor UTx procedures were conducted and seven were successful. Donors, recipients, and children born were observed. Intervention(s): In vitro fertilization was performed with embryo transfer (ET) of day 2 or day 5 embryos in natural cycles. Pregnancies and growth trajectory of the children born were observed. Health-related quality of life, psychosocial outcome, and medical health of donors and recipients were evaluated by questionnaires. Main Outcome Measure(s): The results of in vitro fertilization, pregnancies, growth of children, and long-term health of patients were reported. Result(s): Six women delivered nine infants, with three women giving birth twice (cumulative birth rates of 86% and 67% in surgically successful and performed transplants, respectively). The overall clinical pregnancy rate (CPR) and live birth rate (LBR) per ET were 32.6% and 19.6%, respectively. For day 2 embryos, the CPR and LBR per ET were 12.5% and 8.6%, respectively. For day 5 embryos, the CPR and LBR per ET were 81.8% and 45.4%, respectively. Fetal growth and blood flow were normal in all pregnancies. Time of delivery (median in full pregnancy weeks + days [ranges]) by cesarean section and weight deviations was 35 + 3 (31 + 6 to 38 + 0) and -1% (-13% to 23%), respectively. Three women developed preeclampsia and four neonates acquired respiratory distress syndrome. All children were healthy and followed a normal growth trajectory. Measures of long-term health in both donors and recipients were noted to be favorable. When UTx resulted in a birth, scores for anxiety, depression, and relationship satisfaction were reassuring for both the donors and recipients. Conclusion(s): The results of this first complete UTx trial show that this is an effective infertility treatment, resulting in births of healthy children and associated with only minor psychological and medical long-term effects for donors and recipients. Clinical Trial Registration Number: NCT02987023.
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| 7. |
- Cagnotto, Giovanni, et al.
(författare)
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Abatacept in rheumatoid arthritis: survival on drug, clinical outcomes, and their predictors-data from a large national quality register
- 2020
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background There are limited data regarding efficacy of abatacept treatment for rheumatoid arthritis (RA) outside clinical trials. Quality registers have been useful for observational studies on tumor necrosis factor inhibition in clinical practice. The aim of this study was to investigate clinical efficacy and tolerability of abatacept in RA, using a national register. Methods RA patients that started abatacept between 2006 and 2017 and were included in the Swedish Rheumatology Quality register (N = 2716) were investigated. Survival on drug was estimated using Kaplan-Meier analysis. The European League Against Rheumatism (EULAR) good response and Health Assessment Questionnaire (HAQ) response (improvement of >= 0.3) rates (LUNDEX corrected for drug survival) at 6 and at 12 months were assessed. Predictors of discontinuation were investigated by Cox regression analyses, and predictors of clinical response by logistic regression. Significance-based backward stepwise selection of variables was used for the final multivariate models. Results There was a significant difference in drug survival by previous biologic disease-modifying antirheumatic drug (bDMARD) exposure (p < 0.001), with longer survival in bionaive patients. Men (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.74-0.98) and methotrexate users (HR 0.85, 95% CI 0.76-0.95) were less likely to discontinue abatacept, whereas a high pain score predicted discontinuation (HR 1.14 per standard deviation, 95% CI 1.07-1.20). The absence of previous bDMARD exposure, male sex, and a low HAQ score were independently associated with LUNDEX-corrected EULAR good response. The absence of previous bDMARD exposure also predicted LUNDEX-corrected HAQ response. Conclusions In this population-based study of RA, bDMARD naive patients and male patients were more likely to remain on abatacept with a major clinical response.
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| 8. |
- Elliot, Anders H., et al.
(författare)
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Pretreatment MRI in Primary Rectal Cancer as a Predictor for Oncological Outcomes After Surgery for Local Recurrence
- 2021
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Ingår i: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 41:5, s. 2459-2465
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC). Patients andMethods: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated.Results: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found.Conclusion: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified.
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| 9. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 10. |
- Söder, Lennart, 1956-, et al.
(författare)
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Är kärnkraften nödvändig för en fossilfri, svensk, elproduktion?
- 2020
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Rapport (populärvet., debatt m.m.)abstract
- Efter flera år av stöd har sol- och vind-el blivit ekonomiskt konkurrenskraftiga och börjat konkurrera ut stora termiska anläggningar för elproduktion. Det stängs nu kol- och kärnkraftverk i flera länder i världen och förespråkare för dessa teknologier hävdar, på olika sätt, att marknaden styr fel och att dessa kraftverk ”behövs” av olika skäl.I denna rapport har vi undersökt om det finns någon grund för ett sådant ”behov” av kärnkraftverk i Sverige som motiverar att det sker nyinvesteringar trots att konkurrensen på marknaden håller på att slå ut dem.Syftet med denna rapport är inte att fastslå om man bör ha ett framtida elsystem med eller utan kärnkraft, utan att analysera grunderna, dvs kunskapsläget, för påståendet att det är nödvändigt att ha kärnkraft. Alla diskussioner om framtiden är osäkra, så vi gör heller inte anspråk på att förutse hur framtiden kommer se ut. Upplägget är att gå igenom olika frågeställningar, och koppla dessa till frågan om huruvida kärnkraften är nödvändig för framtiden, så som framförts med exempelvis följande argument:a) Kärnkraft behövs av ekonomiska skälb) Kärnkraft behövs för att vi inte ska vara importberoendec) Kärnkraft behövs eftersom det finns kapacitetsbrist i t ex Malmö och Stockholmd) Kärnkraft behövs för att klara elektrifieringen av transporterna och industrine) Kärnkraft behövs för att klara klimatmåletf) Kärnkraft behövs för att vi ska få el alla timmar, dvs klara leveranssäkerheteng) Kärnkraften behövs för att klara frekvensstabilitetenh) Kärnkraft behövs för stödtjänster till elsystemetI avsnitt 2-7 finns en genomgång av dagsläget. I avsnitt 8 finns en mer detaljerad genomgång av listan a)-h) ovan. Mer tekniska detaljer om systembalansering och effektbalansberäkningar finns i Bilaga A-C.Den slutsats vi drar är att kärnkraften inte är nödvändig för att vi ska kunna få ett stabilt, säkert och fossilfritt elsystem i Sverige i framtiden. Ett elsystem med stor mängd sol- och vindkraft ser dock annorlunda ut än ett med stor mängd kärnkraft. Frågan är då om detta system blir dyrare. Ingen vet vad olika kraftslag kommer att kosta år 2045, men under senare år har det skett en kraftig minskning av kostnaderna för sol- och vindkraft. Samtidigt har kärnkraftens kostnader istället ökat kraftigt. Den är nu betydligt dyrare än ny vindkraft.
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