| 1. |
- Allentoft, Morten E., et al.
(author)
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Population genomics of post-glacial western Eurasia
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311
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Journal article (peer-reviewed)abstract
- Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.
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| 2. |
- Adams, Yvonne, et al.
(author)
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3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
- 2023
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In: ISCIENCE. - : CELL PRESS. - 2589-0042. ; 26:1
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Journal article (peer-reviewed)abstract
- Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
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| 3. |
- Allentoft, Morten E., et al.
(author)
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100 ancient genomes show repeated population turnovers in Neolithic Denmark
- 2024
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In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 329-337
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Journal article (peer-reviewed)abstract
- Major migration events in Holocene Eurasia have been characterized genetically at broad regional scales1–4. However, insights into the population dynamics in the contact zones are hampered by a lack of ancient genomic data sampled at high spatiotemporal resolution5–7. Here, to address this, we analysed shotgun-sequenced genomes from 100 skeletons spanning 7,300 years of the Mesolithic period, Neolithic period and Early Bronze Age in Denmark and integrated these with proxies for diet (13C and 15N content), mobility (87Sr/86Sr ratio) and vegetation cover (pollen). We observe that Danish Mesolithic individuals of the Maglemose, Kongemose and Ertebølle cultures form a distinct genetic cluster related to other Western European hunter-gatherers. Despite shifts in material culture they displayed genetic homogeneity from around 10,500 to 5,900 calibrated years before present, when Neolithic farmers with Anatolian-derived ancestry arrived. Although the Neolithic transition was delayed by more than a millennium relative to Central Europe, it was very abrupt and resulted in a population turnover with limited genetic contribution from local hunter-gatherers. The succeeding Neolithic population, associated with the Funnel Beaker culture, persisted for only about 1,000 years before immigrants with eastern Steppe-derived ancestry arrived. This second and equally rapid population replacement gave rise to the Single Grave culture with an ancestry profile more similar to present-day Danes. In our multiproxy dataset, these major demographic events are manifested as parallel shifts in genotype, phenotype, diet and land use.
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| 4. |
- Capo, Eric, et al.
(author)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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In: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Research review (peer-reviewed)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 5. |
- Kjær, Lene Jung, et al.
(author)
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Potential drivers of human tick-borne encephalitis in the Örebro region of Sweden, 2010-2021
- 2023
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
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Journal article (peer-reviewed)abstract
- Incidence of tick-borne encephalitis (TBE) has increased during the last years in Scandinavia, but the underlying mechanism is not understood. TBE human case data reported between 2010 and 2021 were aggregated into postal codes within Örebro County, south-central Sweden, along with tick abundance and environmental data to analyse spatial patterns and identify drivers of TBE. We identified a substantial and continuing increase of TBE incidence in Örebro County during the study period. Spatial cluster analyses showed significant hotspots (higher number of cases than expected) in the southern and northern parts of Örebro County, whereas a cold spot (lower number of cases than expected) was found in the central part comprising Örebro municipality. Generalised linear models showed that the risk of acquiring TBE increased by 12.5% and 72.3% for every percent increase in relative humidity and proportion of wetland forest, respectively, whereas the risk decreased by 52.8% for every degree Celsius increase in annual temperature range. However, models had relatively low goodness of fit (R2 < 0.27). Results suggest that TBE in Örebro County is spatially clustered, however variables used in this study, i.e., climatic variables, forest cover, water, tick abundance, sheep as indicator species, alone do not explain this pattern.
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| 6. |
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| 7. |
- Ahlgren, Madeleine, 1976-, et al.
(author)
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Self-reported symptoms of low energy availability among female elite athletes and controls
- 2023
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Conference paper (peer-reviewed)abstract
- AimWe aimed to investigate symptoms of low energy availability (LEA) among athletes and recreational active people, and the associations with EDs, excessive exercise, and motivation for training and dietary behavioural changes. MethodsSwedish female national team athletes (n=150) from 26 sports, and recreational active women (n=108), 18-39 years were recruited via sport organizations and social media. Participants filled out an anonymous on-line survey comprising the LEA in Females Questionnaire (LEAF-Q), the Eating Disorder Examination Questionnaire (EDE-Q), the Major Depression Index (MDI), the Exercise Addiction Inventory (EAI), and the Motivation to Change Questionnaire (MCQ). LEAF-Q total score >8 and EDE-Q Global score >2.3 were used to classify participants as having symptoms of LEA and eating disorders (EDs), respectively.ResultsOf all participants, 47% had symptoms of LEA with no difference between elite athletes (47%) and controls (48%). Participants with LEA had lower body mass and BMI compared to those with no symptoms, while no differences were found in age or training load. Most of the participants with LEA (69%) did not have symptoms of EDs. However, when excluding all participants with ED symptoms (n=65), participants with LEA had higher EDE-Q sub scale scores, MDI and EAI scores, and they reported poorer health status and reduced ability to increase energy intake and to lower the training load compared to participants with no LEA symptoms. ConclusionOur findings confirm earlier indications that symptoms of LEA is frequent among elite athletes as well as sedentary people, and that most LEA cases do not have EDs. However, our findings suggest that symptoms of LEA may still be associated with poor well-being, restricted eating and excessive training behaviour and negative focus on body shape and weight. Reversing LEA by increased energy intake and/or reduced training load is the only treatment to prevent REDs health and performance implications. Our findings therefore emphasize the need for multidisciplinary prevention strategies to ensure necessary dietary and training behavioural changes.
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| 8. |
- Ambrosini, Valentina, et al.
(author)
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Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
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In: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
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Journal article (peer-reviewed)abstract
- Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research.
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| 9. |
- Bolin, Kristian, et al.
(author)
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Characteristics of finasteride users in comparison with non-users: a Nordic nationwide study based on individual-level data from Denmark, Finland, and Sweden
- 2020
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In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 29:4, s. 453-460
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Journal article (peer-reviewed)abstract
- Purpose: Published epidemiological studies on the association between finasterideuse and the risk of male breast cancer have been inconclusive due to methodologicallimitations including a few male breast cancer cases included. Determinants of malebreast cancer have been studied, but it remains unexplored whether these are alsorelated to finasteride use and thereby constitute potential confounders. This studyaimed to assess whether there are differences between finasteride users andnonusers with regard to numerous potential confounders.Methods: In total, 246 508 finasteride users (≥35 years) were identified in the pre-scription registries of Denmark (1995-2014), Finland (1997-2013), and Sweden(2005-2014). An equal number of nonusers were sampled. The directed acyclic graph(DAG) methodology was used to identify potential confounders for the associationbetween finasteride and male breast cancer. A logistic regression model comparedfinasteride users and nonusers with regard to potential confounders that were mea-surable in registries and population surveys.Results: Finasteride users had higher odds of testicular abnormalities (odds ratio[OR] 1.40; 95% confidence interval [CI] 1.36-1.44), obesity (1.31; 1.23-1.39), exoge-nous testosterone (1.61; 1.48-1.74), radiation exposure (1.22; 1.18-1.27), and diabe-tes (1.07; 1.04-1.10) and lower odds of occupational exposure in perfume industry orin high temperature environments (0.93; 0.87-0.99), living alone (0.89; 0.88-0.91), liv-ing in urban/suburban areas (0.97; 0.95-0.99), and physical inactivity (0.70;0.50-0.99) compared to nonusers.Conclusions: Systematic differences between finasteride users and nonusers werefound emphasizing the importance of confounder adjustment of associationsbetween finasteride and male breast cancer.
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| 10. |
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| 11. |
- Ekbäck, Peter, 1961-, et al.
(author)
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Road Management in Denmark and Sweden : A Comparison and Analysis of Institutional Designs
- 2020
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In: Nordic Journal of Surveying and Real Estate Research. - : Nordic Journal of Surveying and Real Estate Research. - 1459-5877 .- 2341-6599. ; 15:1, s. 38-55
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Journal article (peer-reviewed)abstract
- Management of roads and the institutional solution chosen is dependent on a number of factors such as, regulatory tradition, and roadnetwork scale. It is likely that some solutions are more efficient than others,and this article compares and analyses Danish and Swedish institutional solutions regarding road management. The aim is to explore and briefly evaluate the systems in terms of institutional efficiency. The hypothesis is that, efficient institutions have a better ability for survival in the politicalprocesses. It is observed that the chosen solutions on national and municipallevel are much alike, and therefore appear efficient. However, for common private roads, the institutional designs are very different, and seem to bebased on two diametrically contrasting views on how to govern this kind of roads.
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| 12. |
- Elam, Cecilia, et al.
(author)
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Effects of age on muscle power, postural control and functional capacity after short-term immobilization and retraining.
- 2022
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In: Journal of musculoskeletal & neuronal interactions. - 1108-7161. ; 22:4, s. 486-497
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Journal article (peer-reviewed)abstract
- This study investigated the effect of lower limb immobilization and retraining on postural control and muscle power in healthy old and young men.Twenty men, nine old (OM:67.3±4.4 years) and eleven young (YM:24.4±1.6 years) underwent 2 weeks of unilateral whole-leg casting, followed by 4 weeks of retraining. Measures included center of pressure (CoP) sway length and area during single- and double-leg stance, maximal leg extensor muscle power, habitual and maximal 10-m gait speed, sit-to-stand performance, and 2-min step test.After immobilization, leg extension muscle power decreased by 15% in OM (from 2.68±0.60 to 2.29±0.63 W/kg, p<0.05) and 17% in YM (4.37±0.76 to 3.63±0.69 W/kg, p<0.05). Double-leg CoP sway area increased by 45% in OM (218±82 to 317±145 mm2; p<0.05), with no change in YM (p=0.43). Physical function did not change after immobilization but sit-to-stand performance (+20%, p<0.05) and 2-min step test (+28%, p<0.05) increased in OM following retraining. In both groups, all parameters returned to baseline levels after retraining.Two weeks of lower limb immobilization led to decreases in maximal muscle power in both young and old, whereas postural control was impaired selectively in old men. All parameters were restored in both groups after 4 weeks of resistance-based retraining.
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| 13. |
- Gronbaek, Jonathan Kjaer, et al.
(author)
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Left-handedness should not be overrated as a risk factor for postoperative speech impairment in children after posterior fossa tumour surgery : a prospective European multicentre study
- 2022
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In: Child's Nervous System. - : Springer Nature. - 0256-7040 .- 1433-0350. ; 38:8, s. 1479-1485
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Journal article (peer-reviewed)abstract
- Purpose Cerebellar mutism syndrome (CMS) is a severe neurological complication of posterior fossa tumour surgery in children, and postoperative speech impairment (POSI) is the main component. Left-handedness was previously suggested as a strong risk factor for POSI. The aim of this study was to investigate the relationship between handedness and the risk of POSI. Methods We prospectively included children (aged < 18 years) undergoing surgery for posterior fossa tumours in 26 European centres. Handedness was assessed pre-operatively and postoperative speech status was categorised as either POSI (mutism or reduced speech) or habitual speech, based on the postoperative clinical assessment. Logistic regression was used in the risk factor analysis of POSI as a dichotomous outcome. Results Of the 500 children included, 37 (7%) were excluded from the present analysis due to enrolment at a reoperation; another 213 (43%) due to missing data about surgery (n = 37) and/or handedness (n = 146) and/or postoperative speech status (n = 53). Out of the remaining 250 (50%) patients, 20 (8%) were left-handed and 230 (92%) were right-handed. POSI was observed equally frequently regardless of handedness (5/20 [25%] in left-handed, 61/230 [27%] in right-handed, OR: 1.08 [95% CI: 0.40-3.44], p = 0.882), also when adjusted for tumour histology, location and age. Conclusion We found no difference in the risk of POSI associated with handedness. Our data do not support the hypothesis that handedness should be of clinical relevance in the risk assessment of CMS.
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| 14. |
- Herchenhan, Andreas, et al.
(author)
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Early Growth Response Genes Increases Rapidly After Mechanical Overloading and Unloading in Tendon Constructs
- 2020
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In: Journal of Orthopaedic Research. - : WILEY. - 0736-0266 .- 1554-527X. ; 38:1, s. 173-181
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Journal article (peer-reviewed)abstract
- Tendon cells exist in a dense extracellular matrix and mechanical loading is important for the strength development of this matrix. We therefore use a three-dimensional (3D) culture system for tendon formation in vitro. The objectives of this study were to elucidate the temporal expression of tendon-related genes during the formation of artificial tendons in vitro and to investigate if early growth response-1 (EGR1), EGR2, FOS, and cyclooxygenase-1 and -2 (PTGS1 and PTGS2) are sensitive to mechanical loading. First, we studied messenger RNA (mRNA) levels of several tendon-related genes during formation of tendon constructs. Second, we studied the mRNA levels of, for example, EGR1 and EGR2 after different degrees of loading; dynamic physiologic-range loading (2.5% strain), dynamic overloading (approximately 10% strain), or tension release. The gene expression for tendon-related genes (i.e., EGR2, MKX, TNMD, COL3A1) increased with time after seeding into this 3D model. EGR1, EGR2, FOS, PTGS1, and PTGS2 did not respond to physiologic-range loading. But overloading (and tension release) lead to elevated levels of EGR1 and EGR2 (p amp;lt;= 0.006). FOS and PTGS2 were increased after overloading (both p amp;lt; 0.007) but not after tension release (p = 0.06 and 0.08). In conclusion, the expression of tendon-related genes increases during the formation of artificial tendons in vitro, including EGR2. Furthermore, the gene expression of EGR1 and EGR2 in human tendon cells appear to be sensitive to overloading and unloading but did not respond to the single episode of physiologic-range loading. These findings could be helpful for the understanding of tendon tensional homeostasis. (c) 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
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| 15. |
- Hoeffner, Rikke, et al.
(author)
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Muscle fascicle and sarcomere adaptation in response to Achilles tendon elongation in an animal model
- 2023
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In: Journal of applied physiology. - : AMER PHYSIOLOGICAL SOC. - 8750-7587 .- 1522-1601. ; 135:2, s. 326-333
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Journal article (peer-reviewed)abstract
- Permanent loss of muscle function seen after an Achilles tendon rupture may partly be explained by tendon elongation and accompanying shortening of the muscle. Muscle fascicle length shortens, serial sarcomere number is reduced, and the sarcomere length is unchanged after Achilles tendon transection (ATT), and these changes are mitigated with suturing. The method involved in this study was a controlled laboratory study. Two groups of rats underwent ATT on one side with a contralateral control (CTRL): A) ATT with 3 mm removal of the Achilles tendon and no suturing (substantial tendon elongation), and B) ATT with suture repair (minimal tendon elongation). The operated limb was immobilized for 2 wk to reduce load. Four weeks after surgery the rats were euthanized, and hindlimbs were analyzed for tendon length, gastrocnemius medialis (GM) muscle mass, length, fascicle length, sarcomere number and length. No differences were observed between the groups, and in both groups the Achilles tendon length was longer (15.2%, P < 0.001), GM muscle mass was smaller (17.5%, P < 0.001), and muscle length was shorter (8.2%, P < 0.001) on the ATT compared with CTRL side. GM fascicle length was shorter (11.2%, P < 0.001), and sarcomere number was lower (13.8%, P < 0.001) on the ATT side in all regions. Sarcomere length was greater in the proximal (5.8%, P < 0.001) and mid (4.2%, P 1/4 0.003), but not distal region on the ATT side. In this animal model, regardless of suturing, ATT resulted in tendon elongation, loss of muscle mass and length, and reduced serial sarcomere number, which resulted in an "overshoot" lengthening of the sarcomeres.
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| 16. |
- Hoff Rudhult, Maria
(author)
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SIDA VID SIDA? : Svenska företag i biståndsverksamheten, 1946–2013
- 2023
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Doctoral thesis (other academic/artistic)abstract
- This thesis studies how the way private businesses were viewed came to affect their participation, and thus role, in Swedish development aid activities in the 1946-2013 period. The role is here viewed in terms of the relationship between “the public” and “the private”. The relationship between public and private activities, as well as the distinction between them, is mutable, and needs to be understood within the framework of a specific context. This, in turn, means that these relationships between the state, in the form of public activity, and the businesses, in the form of private activity, constitute the more comprehensive research problem of the thesis. The analytical strategy of the thesis is based on a discourse theoretical approach, discursive institutionalism, to study how development aid, based on the ideal of “solidarity”, was formulated, established and upheld as an area of policy, focusing especially on the role that was concurrently created for Swedish private businesses. The application of a genealogical approach in the reading of political texts as well as archival material, reports and evaluations, makes visible how the businesses have been part of the Swedish developmental aid activities during practically the entirety of the time period studied, and that this has not been openly accounted for in the public political material. The study shows that upholding the ideal of the “solidarity-based” politics regarding development aid was enabled by applying different logics of action to different parts of the development aid activity. This is made clear by the political ability to involve businesses in development aid activities without having to expressly renounce the position of solidarity. The result of the thesis also shows that the ideal of “solidarity” influenced both the preconditions for distinctions between public and private, and how views of businesses as illegitimate or legitimate actors in development aid activity changed over time.
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| 17. |
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| 18. |
- Kjaer, Josefin, et al.
(author)
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Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors : A Propensity-Score Matched Cohort Study
- 2022
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In: Annals of Surgery Open. - : Wolters Kluwer. - 2691-3593. ; 3:1
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Journal article (peer-reviewed)abstract
- Objective: To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study.Background: Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results.Methods: Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women’s Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000–2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival.Results: Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043).Conclusions: Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.
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| 19. |
- Kjaer, Josefin, et al.
(author)
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Long-term outcome after resection and thermal hepatic ablation of pancreatic neuroendocrine tumour liver metastases
- 2021
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In: BJS open. - : Oxford University Press (OUP). - 2474-9842. ; 5:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: Pancreatic neuroendocrine tumours (Pan-NETs) are rare tumours that often present with or develop liver metastases. The aim of this retrospective study was to evaluate liver surgery and thermal hepatic ablation (THA) of Pan-NET liver metastases and to compare the outcomes with those of a control group. METHOD: Patients with Pan-NET treated in Uppsala University Hospital and Sahlgrenska University Hospital from 1995-2018 were included. Patient records were scrutinized for baseline parameters, survival, treatment and complications. RESULTS: Some 108 patients met the criteria for inclusion; 57 patients underwent treatment with liver surgery or THA and 51 constitute the control group. Median follow-up was 3.93years. Five-year survival in the liver surgery/THA group was 70.6 (95 per cent c.i. 0.57 to 0.84) per cent versus 42.4 (95 per cent c.i. 40.7 to 59.1) per cent in the control group (P=0.016) and median survival was 9.1 (95 per cent c.i. 6.5 to 11.7) versus 4.3 (95 per cent c.i. 3.4-5.2) years. In a multivariable analysis, surgery or THA was associated with a decreased death-years rate (hazard ratio 0.403 (95 per cent c.i. 0.208 to 0.782, P=0.007). CONCLUSION: Liver surgery and/or THA was associated with longer overall survival in Pan-NET with acceptable mortality and morbidity rates. These treatments should thus be considered in Pan-NET patients with reasonable tumour burden in an intent to alleviate symptoms and to improve survival.
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| 20. |
- Kjaer, Josefine, et al.
(author)
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Overall Survival in Patients with Stage IV Pan-NET Eligible for Liver Transplantation
- 2023
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In: World Journal of Surgery. - : Springer Nature. - 0364-2313 .- 1432-2323. ; 47, s. 340-347
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Journal article (peer-reviewed)abstract
- BACKGROUND: The use of liver transplantation (LT) in patients with stage IV neuroendocrine pancreatic tumors (pan-NET) is under debate. Previous studies report a 5-year survival of 27-53% after LT in pan-NET and up to 92.7% in patients with mixed NETs. This study aimed to determine survival rates of patients with stage IV pan-NET meeting criteria for LT while only subjected to multimodal treatment.METHODS: Medical records of patients with pan-NET diagnosed from 2000 to 2021 at a tertiary referral center were evaluated for eligibility. Patients without liver metastases, who did not undergo primary tumor surgery, age > 75 years and with grade 3 tumors were excluded. The patients were divided into groups; all included patients, patients meeting the Milan, the United Network for Organ Sharing (UNOS) or the European Neuroendocrine Tumor Society (ENETS) criteria for LT. Kaplan-Meier survival analysis was used to calculate overall survival.RESULTS: Out of 519 patients with pan-NET, 41 patients were included. Mean follow-up time was 5.4 years. Overall survival was 9.3 years (95% Cl 6.8-11.7), and 5-year survival was 64.7% (95% CI 48.2-81.2). Patients meeting the Milan, ENETS and UNOS criteria for LT had a 5-year survival of 64.9% (95% CI 32.2-97.6), 85.7% (95% CI 59.8-100.0) and 55.4% (95% CI 26.0-84.8), respectively.CONCLUSIONS: In patients with stage IV pan-NET, grade 1 and 2, with no extra abdominal disease, 5-year survival was 64.7% (95% CI 48.2-81.2). As these survival rates exceed previously published series of LT for pan-NET, the evidence base for this treatment is very weak.
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| 21. |
- Magnusson, S. Peter, et al.
(author)
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Heterotopic Ossification After an Achilles Tendon Rupture Cannot Be Prevented by Early Functional Rehabilitation: A Cohort Study
- 2020
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In: Clinical Orthopaedics and Related Research. - : LIPPINCOTT WILLIAMS & WILKINS. - 0009-921X .- 1528-1132. ; 478:5, s. 1101-1108
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Journal article (peer-reviewed)abstract
- Background Tendon loading might play a role in the development of heterotopic ossification after Achilles tendon ruptures. Early heavy loading on a healing tendon in animals has been shown to prolong the proinflammatory response, and inflammatory cells are thought to drive heterotopic ossification formation. Taken together, this suggests that early rehabilitation might influence heterotopic ossification development. Questions/purposes The purposes of this study were to investigate (1) whether the presence of heterotopic ossification after Achilles tendon ruptures influences clinical outcome and (2) whether early mobilization or weightbearing prevents the development of heterotopic ossification. Methods This was a retrospective analysis of 69 patients from a previous clinical trial. All patients were treated surgically, but with three different early rehabilitation protocols after surgery: late weightbearing and ankle immobilization, late weightbearing and ankle mobilization, and early weightbearing and ankle mobilization. Plain radiographs taken 2, 6, 12, 26, and 52 weeks postoperatively were analyzed for heterotopic ossification, which was detected in 19% of patients (13 of 69) at 52 weeks. Heterotopic ossification was measured, scored, and correlated to clinical outcomes; heel-raise index (HRI), ankle joint ROM, tendon strain, Achilles tendon rupture score (ATRS), and Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire scores at 26 and 52 weeks postoperatively. Results Heterotopic ossification had no adverse effects on patient-reported outcomes (ATRS or VISA-A), tendon strain, or ROM. In fact, patients with heterotopic ossification tended to have a better HRI at 52 weeks compared with patients without (mean difference 14% [95% CI -0.2 to 27]; p = 0.053). Neither the occurrence (heterotopic ossification/no heterotopic ossification) nor the heterotopic ossification severity (ossification score) differed between the three rehabilitation groups. Seventeen percent of the patients (four of 24) with early functional rehabilitation (early weightbearing and ankle joint mobilization exercise) had heterotopic ossification (score, 2-3) while late weightbearing and immobilization resulted in heterotopic ossification in 13% of the patients (score, 3-4). Conclusions Heterotopic ossification occurs relatively frequently after Achilles tendon ruptures but appears to have no adverse effects on functional outcomes. Furthermore, heterotopic ossification develops during the first 6 weeks after rupture, and weightbearing or ankle-joint mobilization does not prevent this from occurring.
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| 22. |
- Schaltz-Buchholzer, Frederik, et al.
(author)
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BCG skin reactions by 2 months of age are associated with better survival in infancy : A prospective observational study from Guinea-Bissau
- 2020
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In: BMJ Global Health. - : BMJ. - 2059-7908. ; 5:9
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Journal article (peer-reviewed)abstract
- Introduction Receiving Bacille Calmette-Guérin (BCG)-Denmark vaccine at birth has been associated with ∼40% reductions in all-cause neonatal mortality. We evaluated determinants of BCG skin reaction characteristics by age 2 months and tested the association with subsequent mortality. Methods Prospective observational study amalgamating five trials providing BCG-at-birth that were conducted between 2002 and 2018 in Guinea-Bissau. The reaction status and size were evaluated at home-visits by 2 months of age among 6012 neonates; mortality from 2 to 12 months was assessed at subsequent visits. Reaction determinants were evaluated by binomial regression providing risk ratios (RRs). In Cox-models providing adjusted mortality rate ratios (aMRRs), we assessed the association between (1) having a 2-month reaction (yes/no) and (2) reaction size tertiles and subsequent all-cause mortality risk. A subgroup had their BCG reaction evaluated and were bled at age 4 weeks; their samples underwent in vitro analysis for specific and non-specific cytokine responses. Results The BCG strain was the main determinant for developing a 2-month reaction and the reaction size: the BCG-Russia/BCG-Denmark RR for large-reaction was 0.38 (0.30-0.47) and the BCG-Russia/BCG-Japan RR was 0.61 (0.51-0.72). 5804 infants (96.5%) were reactors by age 2 months; 208 (3.5%) were non-reactors. The 2-12 months mortality risk was 4.8% (10/208) for non-reactors, 2.9% (64/2213) for small reactors, 1.8% (30/1710) for medium reactors and 0.8% (15/1881) for large reactors. The reactor/non-reactor aMRR was 0.49 (0.26-0.95) and there was a linear trend of decreasing mortality with increasing reaction size (p for trend <0.001). BCG reactors had higher 4-week specific and non-specific cytokine responses, responses that were highest among those with large reactions. Conclusion Among BCG-vaccinated infants, having a BCG skin reaction by age 2 months was associated with markedly better survival, as was the reaction size. Our findings thus support that BCG has substantial effects on all-cause mortality. Emphasising at-birth vaccination with immunogenic BCG strains and revaccinating non-reactors and small reactors could have major public health benefits.
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| 23. |
- Tatsuno, Hideyuki, et al.
(author)
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Hot Branching Dynamics in a Light-Harvesting Iron Carbene Complex Revealed by Ultrafast X-ray Emission Spectroscopy
- 2020
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In: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:1, s. 364-372
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Journal article (peer-reviewed)abstract
- Iron N-heterocyclic carbene (NHC) complexes have received a great deal of attention recently because of their growing potential as light sensitizers or photocatalysts. We present a sub-ps X-ray spectroscopy study of an FeIINHC complex that identifies and quantifies the states involved in the deactivation cascade after light absorption. Excited molecules relax back to the ground state along two pathways: After population of a hot 3MLCT state, from the initially excited 1MLCT state, 30 % of the molecules undergo ultrafast (150 fs) relaxation to the 3MC state, in competition with vibrational relaxation and cooling to the relaxed 3MLCT state. The relaxed 3MLCT state then decays much more slowly (7.6 ps) to the 3MC state. The 3MC state is rapidly (2.2 ps) deactivated to the ground state. The 5MC state is not involved in the deactivation pathway. The ultrafast partial deactivation of the 3MLCT state constitutes a loss channel from the point of view of photochemical efficiency and highlights the necessity to screen transition-metal complexes for similar ultrafast decays to optimize photochemical performance.
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| 24. |
- Tiensuu Janson, Eva, et al.
(author)
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Nordic guidelines 2021 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms
- 2021
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:7, s. 931-941
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Journal article (peer-reviewed)abstract
- Background: The diagnostic work-up and treatment of patients with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) has undergone major advances and new methods are introduced. Furthermore, an update of the WHO classification has resulted in a new nomenclature for GEP-NEN that is implemented in the clinic.Aim: These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat GEP-NEN patients and aims to be useful in the daily practice for clinicians.
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| 25. |
- Vester, Peter, et al.
(author)
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Tracking structural solvent reorganization and recombination dynamics following e-photoabstraction from aqueous I-with femtosecond x-ray spectroscopy and scattering
- 2022
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In: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 157:22
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Journal article (peer-reviewed)abstract
- We present a sub-picosecond resolved investigation of the structural solvent reorganization and geminate recombination dynamics following 400 nm two-photon excitation and photodetachment of a valence p electron from the aqueous atomic solute, I-(aq). The measurements utilized time-resolved X-ray Absorption Near Edge Structure (TR-XANES) spectroscopy and X-ray Solution Scattering (TR-XSS) at the Linac Coherent Light Source x-ray free electron laser in a laser pump/x-ray probe experiment. The XANES measurements around the L1-edge of the generated nascent iodine atoms (I0) yield an average electron ejection distance from the iodine parent of 7.4 ± 1.5 Å with an excitation yield of about 1/3 of the 0.1M NaI aqueous solution. The kinetic traces of the XANES measurement are in agreement with a purely diffusion-driven geminate iodine-electron recombination model without the need for a long-lived (I0:e-) contact pair. Nonequilibrium classical molecular dynamics simulations indicate a delayed response of the caging H2O solvent shell and this is supported by the structural analysis of the XSS data: We identify a two-step process exhibiting a 0.1 ps delayed solvent shell reorganization time within the tight H-bond network and a 0.3 ps time constant for the mean iodine-oxygen distance changes. The results indicate that most of the reorganization can be explained classically by a transition from a hydrophilic cavity with a well-ordered first solvation shell (hydrogens pointing toward I-) to an expanded cavity around I0 with a more random orientation of the H2O molecules in a broadened first solvation shell.
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