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1.	Moberg, Christina, et al. (författare) De unga gör helt rätt när de stämmer staten 2022 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)abstract 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
2.	Ahlsson, Anders, et al. (författare) Is There a Weekend Effect in Surgery for Type A Dissection? : Results From the Nordic Consortium for Acute Type A Aortic Dissection Database 2019 Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 108:3, s. 770-776 Tidskriftsartikel (refereegranskat)abstract Background: Aortic dissection type A requires immediate surgery. In general surgery populations, patients operated on during weekends have higher mortality rates compared with patients whose operations occur on weekdays. The weekend effect in aortic dissection type A has not been studied in detail.Methods: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) registry includes data for 1,159 patients who underwent type A dissection surgery at 8 Nordic centers during 2005 to 2014. This study is based on data relating to surgery conducted during weekdays versus weekends and starting between 8:00 AM and 8:00 Pm ("daytime") versus from 8:00 Pm to 8:00 AM ("nighttime"), as well as time from symptoms, admittance, and diagnosis to surgery. The influence of timing of surgery on the 30-day mortality rate was assessed using logistic regression analysis.Results: The 30-day mortality was 18% (204 of 1,159), with no difference in mortality between surgery performed on weekdays (17% [150 of 889]) and on weekends (20% [54 of 270], p = 0.45), or during nighttime (19% [87 of 467]) versus daytime (17% [117 of 680], p = 0.54). Time from symptoms to surgery (median 7.0 hours vs 6.5 hours, p = 0.31) did not differ between patients who survived and those who died at 30 days. Multivariable regression analysis of risk factors for 30-day mortality showed no weekend effect (odds ratio, 1.04; 95% confidence interval, 60.67 to 1.60; p = 0.875), but nighttime surgery was a risk factor (odds ratio, 2.43; 95% confidence interval, 1.29 to 4.56; p = 0.006).Conclusions: The 30-day mortality in surgical repair of aortic dissection type A was not significantly affected by timing of surgery during weekends versus weekdays. Nighttime surgery seems to predict increased 30-day mortality, after correction for other risk factors.
3.	Ahlsson, Anders, et al. (författare) Is there a weekend effect in surgery for type A dissection? - Results from the NORCAAD database 2019 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 108:3, s. 770-776 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Aortic dissection type A requires immediate surgery. In general surgery populations, patients operated during weekends have higher mortality rates compared to patients operated on weekdays. The weekend effect in aortic dissection type A has not been studied in detail.METHODS: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) registry includes patients (N=1,159) who underwent type A dissection surgery at eight Nordic centers during 2005-2014. This study is based on data relating to surgery conducted during weekdays vs. weekends, and starting between 8 am and 8 pm ("daytime") vs. from 8 pm to 8 am ("nighttime"), as well as time from symptoms/admittance/diagnosis to surgery. The influence of timing of surgery on 30-day mortality was assessed using logistic regression analysis.RESULTS: The 30-day mortality was 18% (204/1,159), with no difference in mortality between surgery performed on weekdays (17%, 150/889) and on weekends (20%, 54/270, p=0.45), or during nighttime (19%, 87/467) vs. daytime (17%, 117/680, p=0.54). Time from symptoms to surgery (median 7.0 hours vs. 6.5 hours, p=0.31) did not differ between patients who survived and those dead at 30 days. Multivariable regression analysis of risk factors for 30-day mortality showed no weekend effect (OR 1.04 [0.67-1.60], p=0.875), but nighttime surgery was a risk factor (OR 2.43 [1.29-4.56], p=0.006).CONCLUSIONS: Thirty-day mortality in surgical repair of aortic dissection type A was not significantly affected by timing of surgery during weekends vs. weekdays. Nighttime surgery seems to predict increased 30-day mortality, after correction for other risk factors.
4.	Geirsson, Arnar, et al. (författare) Hospital volumes and later year of operation correlates with better outcomes in acute Type A aortic dissection 2018 Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press. - 1010-7940 .- 1873-734X. ; 53:1, s. 276-281 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Acute Type A aortic dissection remains a life-threatening disease, but there are indications that its surgical mortality is decreasing. The aim of this report was to study how surgical mortality has changed and what influences those changes.METHODS: Nordic Consortium for Acute Type A Aortic Dissection is a retrospective database comprising 1159 patients (mean age 61.6 ± 12.2 years, 68% male) treated for acute Type A aortic dissection at 8 centres in Denmark, Finland, Iceland and Sweden from 2005 to 2014. Data gathered included demographics, symptoms, type of procedure, complications and 30-day mortality.RESULTS: The annual number of operations increased significantly from 85 in 2005 to 150 in 2014 (P < 0.001). Chest pain was present in 85% of patients, 24% were hypotensive on presentation and 28% had malperfusion syndrome. Open distal anastomosis technique under hypothermic circulatory arrest was used in 85% of cases and its use increased significantly throughout the study. The 30-day mortality decreased from 24% in 2005 to 13% in 2014 (P = 0.003). Independent predictors for 30-day mortality were preoperative cardiac arrest, malperfusion syndrome, Penn Class C, Penn Class B and C and cardiopulmonary bypass time, whereas later calendar year and higher hospital operative volumes predicted improved survival.CONCLUSIONS: Surgical mortality for acute Type A aortic dissection remains high but has decreased significantly over the last decade. This correlated with later year of operation and increased the number of operations performed per year, indicating that cumulative surgical experience contributes significantly to improved surgical outcomes.
5.	Geirsson, Arnar, et al. (författare) The Nordic Consortium for Acute type A Aortic Dissection (NORCAAD) : objectives and design 2016 Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 50:5-6, s. 334-340 Tidskriftsartikel (refereegranskat)abstract Objectives: The Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) is a collaborative effort of Nordic cardiac surgery centers to study acute type A aortic dissection (ATAAD). Here, we outline the overall objectives and the design of NORCAAD.Design: NORCAAD currently consists of eight centers in Denmark, Finland, Iceland and Sweden. Data was collected for patients undergoing surgery for ATAAD from 2005 to 2014. A total of 194 variables were retrospectively collected including demographics, past medical history, preoperative medications, symptoms at presentation, operative variables, complications, bleeding and blood transfusions, need for late reoperations, 30-day mortality and long-term survival.Results: Information was gathered in the database for 1159 patients, of which 67.6% were male. The mean age was 61.5 +/- 12.1 years. The mean follow-up was 3.1 +/- 2.9 years with a total of 3535 patient years.Conclusions: NORCAAD provides a foundation for close collaboration between cardiac surgery centers in the Nordic countries. Substudies in progress include: short-term outcomes, long-term survival, time interval from diagnosis until operation, effects of surgical techniques, malperfusion syndrome, renal failure, bleeding and neurological complications on outcomes and the rate of late reoperations.
6.	Munch, Marie W., et al. (författare) Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia The COVID STEROID 2 Randomized Trial 2021 Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 326:18, s. 1807-1817 Tidskriftsartikel (refereegranskat)abstract Question What is the effect of 12 mg vs 6 mg of dexamethasone on the number of days alive without life support at 28 days in patients with COVID-19 and severe hypoxemia? Findings In this randomized trial that included 1000 patients with COVID-19 and severe hypoxemia, treatment with 12 mg/d of dexamethasone resulted in 22.0 days alive without life support at 28 days compared with 20.5 days in those receiving 6 mg/d of dexamethasone. This difference was not statistically significant. Meaning Compared with 6 mg of dexamethasone, 12 mg of dexamethasone did not statistically significantly reduce the number of days alive without life support at 28 days. This multicenter randomized clinical trial compares the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. IMPORTANCE A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. OBJECTIVE To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. INTERVENTIONS Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and >= 1 serious adverse reactions at 28 days). RESULTS Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). CONCLUSIONS AND RELEVANCE Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference.
7.	Peden, John F., et al. (författare) A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease 2011 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344 Tidskriftsartikel (refereegranskat)abstract Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
8.	2019 Tidskriftsartikel (refereegranskat)
9.	Allentoft, Morten E., et al. (författare) Population genomics of post-glacial western Eurasia 2024 Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 301-311 Tidskriftsartikel (refereegranskat)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.
10.	Bjurbom, Markus, et al. (författare) Type A Aortic Dissection Repair in Patients With Prior Cardiac Surgery 2023 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 115:3, s. 591-598 Tidskriftsartikel (refereegranskat)abstract Background: Emergency surgery for acute type A aortic dissection in patients with previous cardiac surgery is controversial. This study aimed to evaluate the association between previous cardiac surgery and outcomes after surgery for acute type A aortic dissection, to appreciate whether emergency surgery can be offered with acceptable risks. Methods: All patients operated on for acute type A aortic dissection between 2005 and 2014 from the Nordic Consortium for Acute Type A Aortic Dissection database were eligible. Patients with previous cardiac surgery were compared with patients without previous cardiac surgery. Univariable and multivariable statistical analyses were performed to identify predictors of 30-day mortality and early major adverse events (a secondary composite endpoint comprising 30-day mortality, perioperative stroke, postoperative cardiac arrest, or de novo dialysis). Results: In all, 1159 patients were included, 40 (3.5%) with previous cardiac surgery. Patients with previous cardiac surgery had higher 30-day mortality (30% vs 17.8%, P = .049), worse medium-term survival (51.7% vs 71.2% at 5 years, log rank P = .020), and higher unadjusted prevalence of major adverse events (52.5% vs 35.7%, P = .030). In multivariable analysis, previous cardiac surgery was not associated with 30-day mortality (odds ratio 0.78; 95% CI, 0.30-2.07; P = .624) or major adverse events (odds ratio 1.07; 95% CI, 0.45-2.55, P = .879). Conclusions: Major adverse events after surgery for acute type A aortic dissection were more frequent in patients with previous cardiac surgery. Previous cardiac surgery itself was not an independent predictor for adverse events, although the small sample size precludes definite conclusions. Previous cardiac surgery should not deter from emergency surgery.
11.	Bjursten, Henrik, et al. (författare) Once after a full moon : acute type A aortic dissection and lunar phases 2022 Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press. - 1569-9293 .- 1569-9285. ; 34:1, s. 105-110 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD.METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period).RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated.CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.
12.	Chemtob, Raphaelle A., et al. (författare) Stroke in acute type A aortic dissection : the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) 2020 Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1010-7940 .- 1873-734X. ; 58:5, s. 1027-1034 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients. METHODS: The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014. RESULTS: Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P < 0.001), syncope (30.6% vs 17.6%, P < 0.001), cardiogenic shock (33.1% vs 20.7%, P < 0.001) and pericardial tamponade (25.9% vs 14.7%, P < 0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P = 0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P < 0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P < 0.001). CONCLUSIONS: Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
13.	Chemtob, Raphaelle A, et al. (författare) Stroke in acute type A aortic dissection: the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD). 2020 Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - 1873-734X. ; 58:5, s. 1027-1034 Tidskriftsartikel (refereegranskat)abstract Stroke is a serious complication in patients with acute type A aortic dissection (ATAAD). Previous studies investigating stroke in ATAAD patients have been limited by small cohorts and have shown diverging results. We sought to identify risk factors for stroke and to evaluate the effect of stroke on outcomes in surgical ATAAD patients.The Nordic Consortium for Acute Type A Aortic Dissection database included patients operated for ATAAD at 8 Scandinavian Hospitals between 2005 and 2014.Stroke occurred in 177 (15.7%) out of 1128 patients. Patients with stroke presented more frequently with cerebral malperfusion (20.6% vs 6.3%, P<0.001), syncope (30.6% vs 17.6%, P<0.001), cardiogenic shock (33.1% vs 20.7%, P<0.001) and pericardial tamponade (25.9% vs 14.7%, P<0.001) and more often underwent total aortic arch replacement (10.7% vs 4.7%, P=0.016), compared to patients without stroke. In the 86 patients presenting with cerebral malperfusion, 38.4% developed stroke. Thirty-day and 5-year mortality in patients with and without stroke were 27.1% vs 13.6% and 42.9% vs 25.6%, respectively. Stroke was an independent predictor of early- [odds ratio 2.02, 95% confidence interval (CI) 1.34-3.05; P<0.001] and midterm mortality (hazard ratio 1.68, 95% CI 1.27-2.23; P<0.001).Stroke in ATAAD patients is associated with increased early- and midterm mortality. Preoperative cerebral malperfusion and impaired haemodynamics, as well as total aortic arch replacement, were more frequent among patients who developed stroke. Importantly, a large proportion of patients presenting with cerebral malperfusion did not develop a permanent stroke, indicating that signs of cerebral malperfusion should not be considered a contraindication for surgery.
14.	Geirsson, Arnar, et al. (författare) Differential outcomes of open and clamp-on distal anastomosis techniques in acute type A aortic dissection 2019 Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:5, s. 1750-1758 Tidskriftsartikel (refereegranskat)abstract Objectives: Open-distal anastomosis is the preferred technique over clamp-on technique for surgical repair of acute type A aortic dissection (ATAAD). The aim of this study was to define how outcomes of ATAAD were affected by the use of either technique.Methods: Nordic Consortium for Acute Type A Aortic Dissection includes 8 academic cardiothoracic hospitals in 4 Nordic countries. The cohort consisted of 1134 patients, 153 clamp-on and 981 open-distal, from 2005 to 2014.Results: Patients who underwent operation with the clamp-on were younger, more frequently had coronary artery disease, bicuspid aortic valve, hypotension/shock or syncope, and a greater PennClass than open-distal patients. Postoperative cerebral vascular accident occurred less frequently in clamp-on (14/153, 10%) compared with the open-distal group (190/981, 20%). Clamp-on had greater 30-day mortality (39/153, 25%) than the open-distal group (158/981, 16%), and 5-year survival was also worse in clamp-on (61.8% +/- 4.4%) compared with the open-distal group (73.0% +/- 1.6%). The open-distal technique was used more frequently in greater-volume hospitals but was not independently associated with 30-day mortality. Preoperative condition was an independent risk factor whereas hospital volume and later year of operation were beneficial in regard to short-term outcome. Open-distal was independently associated with improved mid-term survival.Conclusions: Patients who underwent operation with the clamp-on were sicker on presentation and had worse short-and mid-term survival compared with the open-distal group. Patients in the open-distal group had greater rates of cerebrovascular complications. The results support the routine use of open-distal anastomosis as the primary operative strategy for ATAAD, although clamp-on can be performed successfully in select cases.
15.	Hansson, Lars-Anders, et al. (författare) Food-chain length alters community responses to global change in aquatic systems 2013 Ingår i: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 3, s. 228-233 Tidskriftsartikel (refereegranskat)abstract Synergies between large-scale environmental changes, such as climate change1 and increased humic content (brownification)2, will have a considerable impact on future aquatic ecosystems. On the basis of modelling, monitoring and experimental data, we demonstrate that community responses to global change are determined by food-chain length and that the top trophic level, and every second level below, will benefit from climate change, whereas the levels in between will suffer. Hence, phytoplankton, and thereby algal blooms, will benefit from climate change in three-, but not in two-trophic-level systems. Moreover, we show that both phytoplankton (resource) and zooplankton (consumer) advance their spring peak abundances similarly in response to a 3 °C temperature increase; that is, there is no support for a consumer/resource mismatch in a future climate scenario. However, in contrast to other taxa, cyanobacteria—known as toxin-producing nuisance phytoplankton3—benefit from a higher temperature and humic content irrespective of the food-chain composition. Our results are mirrored in natural ecosystems. By mechanistically merging present food-chain theory with large-scale environmental and climate changes, we provide a powerful framework for predicting and understanding future aquatic ecosystems and their provision of ecosystem services and water resources.
16.	Hansson, Lars-Anders, et al. (författare) Food-chain length alters community responses to global change in aquatic systems 2013 Ingår i: Nature Climate Change. - 1758-6798. ; 3:3, s. 228-233 Tidskriftsartikel (refereegranskat)abstract Synergies between large-scale environmental changes, such as climate change(1) and increased humic content (brownification)(2), will have a considerable impact on future aquatic ecosystems. On the basis of modelling, monitoring and experimental data, we demonstrate that community responses to global change are determined by food-chain length and that the top trophic level, and every second level below, will benefit from climate change, whereas the levels in between will suffer. Hence, phytoplankton, and thereby algal blooms, will benefit from climate change in three-, but not in two-trophic-level systems. Moreover, we show that both phytoplankton (resource) and zooplankton (consumer) advance their spring peak abundances similarly in response to a 3 degrees C temperature increase; that is, there is no support for a consumer/resource mismatch in a future climate scenario. However, in contrast to other taxa, cyanobacteria-known as toxin-producing nuisance phytoplankton(3)-benefit from a higher temperature and humic content irrespective of the food-chain composition. Our results are mirrored in natural ecosystems. By mechanistically merging present food-chain theory with large-scale environmental and climate changes, we provide a powerful framework for predicting and understanding future aquatic ecosystems and their provision of ecosystem services and water resources.
17.	Olsson, Christian, et al. (författare) Medium-term survival after surgery for acute Type A aortic dissection is improving 2017 Ingår i: European Journal of Cardio-Thoracic Surgery. - : Oxford University Press. - 1010-7940 .- 1873-734X. ; 52:5, s. 852-857 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: To report long-term survival and predictors of mortality in patients included in a large, contemporary, multicentre, multinational database: Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD), which consists of 8 centres in 4 Nordic countries.METHODS: Currently, NORCAAD includes 1159 patients operated between 2005 and 2014. In 30-day survivors (n = 955, 82%), the Kaplan-Meier and Cox proportional hazard methods were used to analyse medium-term (up to 8 years) survival and relative survival versus a matched normal population. Pre- and intraoperative predictors were expressed as hazard ratio (HR) with 95% confidence interval (95% CI).RESULTS: Cumulative follow-up was 3514 patient-years with a median of 3.2 years (range 0-10.2 years). Survival was 95% (95% CI 93-96) at 1 year, 86% (95% CI 83-88) at 5 years and 76% (95% CI 72-81) at 8 years. Relative survival versus a matched normal population was 95% (95% CI 94-97) at 1 year, 90% (95% CI 87-93) at 5 years and 85% (95% CI 80-90) at 8 years. In multivariable analysis, increased age (HR 1.05 per year, 95% CI 1.04-1.07), previous abdominal or thoracic aortic repair (HR 3.2, 95% CI 1.6-6.4) and chronic renal disease (HR 2.7, 95% CI 1.2-6.2) were associated with increased medium-term mortality. Open distal anastomosis (HR 0.55, 95% CI 0.35-0.87) and operation in the 2010-2014 period (HR 0.90, 95% CI 0.83-0.97) were associated with decreased medium-term mortality.CONCLUSIONS: Medium-term survival after acute Type A aortic dissection in the NORCAAD registry is satisfactory, close to a matched normal population and improved in the later part of the study period. The use of open distal anastomosis was associated with decreased medium-term mortality.
18.	Oudin, Anna, et al. (författare) Impact of national holidays and weekends on incidence of acute type A aortic dissection repair 2022 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.
19.	Pan, Emily, et al. (författare) Outcome after type A aortic dissection repair in patients with preoperative cardiac arrest 2019 Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 144, s. 1-5 Tidskriftsartikel (refereegranskat)abstract AIM OF THE STUDY: Patients presenting with acute type A aortic dissection (ATAAD) and cardiac arrest before surgery are considered to have very poor prognosis, but limited data is available. We used a large database to evaluate the outcome of ATAAD patients with a cardiac arrest before surgery.METHODS: We evaluated 1154 surgically treated ATAAD patients from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database between 2005 and 2014. Patients with (n = 44, 3.8%) and without preoperative cardiac arrest were compared and variables univariably associated with mortality in the cardiac arrest group were identified. Median follow-up time was 2.7 years (interquartile range 0.5-5.5).RESULTS: Thirty-day mortality in the arrest and non-arrest group was 43.2% and 16.6%, respectively (odds ratio [OR] 3.83, CI 2.06-7.09; P < 0.001). In the nine patients with ongoing cardiopulmonary resuscitation when cardiopulmonary bypass was initiated, five died intraoperatively and one died after 65 days. In patients surviving the operation, stroke was significantly more common in the arrest group (48.4% vs 18.2%; OR 4.21, CI 2.05-8.67; P < 0.001). In total, 50.0% (22/44) of the arrest patients survived to the end of follow-up. Non-survivors in the arrest group more often had DeBakey type I dissection, cardiac tamponade, cardiac malperfusion and higher preoperative serum lactate (all P < 0.05).CONCLUSIONS: Early mortality and complications after ATAAD surgery in patients with a preoperative cardiac arrest are high, but mid-term outcome after surviving the initial period is acceptable. Preoperative cardiac arrest should not be considered an absolute contraindication for a surgical ATAAD repair.
20.	Reckermann, M., et al. (författare) Human impacts and their interactions in the Baltic Sea region 2022 Ingår i: Earth Syst. Dynam.. - : Copernicus GmbH. - 2190-4987 .- 2190-4979. ; 13:1, s. 1-80 Forskningsöversikt (refereegranskat)abstract Coastal environments, in particular heavily populated semi-enclosed marginal seas and coasts like the Baltic Sea region, are strongly affected by human activities. A multitude of human impacts, including climate change, affect the different compartments of the environment, and these effects interact with each other. As part of the Baltic Earth Assessment Reports (BEAR), we present an inventory and discussion of different human-induced factors and processes affecting the environment of the Baltic Sea region, and their interrelations. Some are naturally occurring and modified by human activities (i.e. climate change, coastal processes, hypoxia, acidification, submarine groundwater discharges, marine ecosystems, non-indigenous species, land use and land cover), some are completely human-induced (i.e. agriculture, aquaculture, fisheries, river regulations, offshore wind farms, shipping, chemical contamination, dumped warfare agents, marine litter and microplastics, tourism, and coastal management), and they are all interrelated to different degrees. We present a general description and analysis of the state of knowledge on these interrelations. Our main insight is that climate change has an overarching, integrating impact on all of the other factors and can be interpreted as a background effect, which has different implications for the other factors. Impacts on the environment and the human sphere can be roughly allocated to anthropogenic drivers such as food production, energy production, transport, industry and economy. The findings from this inventory of available information and analysis of the different factors and their interactions in the Baltic Sea region can largely be transferred to other comparable marginal and coastal seas in the world.
21.	Skelton, Alasdair, et al. (författare) Sveriges utsläpp måste minska nu, regeringen : 531 forskare: Annars är sveket monumentalt – ni kan inte säga att ni inte visste 2023 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)
22.	Uimonen, Mikko, et al. (författare) Outcome After Surgery for Acute Type A Aortic Dissection With or Without Primary Tear Resection 2022 Ingår i: Annals of Thoracic Surgery. - : Elsevier. - 0003-4975 .- 1552-6259. ; 114:2, s. 492-501 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The outcome in patients after surgery for acute type A aortic dissection without replacement of the part of the aorta containing the primary tear is undefined.METHODS: Data of 1122 patients who underwent surgery for acute type A aortic dissection in 8 Nordic centers from January 2005 to December 2014 were retrospectively analyzed. The patients with primary tear location unfound, un-known, not confirmed, or not recorded (n = 243, 21.7%) were excluded from the analysis. The patients were divided into 2 groups according to whether the aortic reconstruction encompassed the portion of the primary tear (tear resected [TR] group, n = 730) or not (tear not resected [TNR] group, n = 149). The restricted mean survival time ratios adjusted for patient characteristics and surgical details between the groups were calculated for all-cause mortality and aortic reoperation-free survival. The median follow-up time was 2.57 (interquartile range, 0.53-5.30) years.RESULTS: For the majority of the patients in the TR group, the primary tear was located in the ascending aorta (83.6%). The reconstruction encompassed both the aortic root and the aortic arch in 7.4% in the TR group as compared with 0.7% in the TNR patients (P < .001). There were no significant differences in all-cause mortality (adjusted restricted mean survival time ratio, 1.01; 95% confidence interval, 0.92-1.12; P = .799) or reoperation-free survival (adjusted restricted mean survival time ratio, 0.98; 95% confidence interval, 0.95-1.02; P = .436) between the TR and TNR groups.CONCLUSIONS: Primary tear resection alone does not determine the midterm outcome after surgery for acute type A aortic dissection. (Ann Thorac Surg 2022;114:492-501) (c) 2022 by The Society of Thoracic Surgeons.
23.	Zindovic, Igor, et al. (författare) Malperfusion in acute type A aortic dissection : An update from the Nordic Consortium for Acute Type A Aortic Dissection 2019 Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier. - 0022-5223 .- 1097-685X. ; 157:4, s. 1324-1333 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate the effect of preoperative malperfusion on 30-day and late mortality and postoperative complications using data from the Nordic Consortium for Acute Type A Aortic Dissection (ATAAD) registry.Methods: We studied 1159 patients who underwent ATAAD surgery between January 2005 and December 2014 at 8 Nordic centers. Multivariable logistic and Cox regression analyses were performed to identify independent predictors of 30-day and late mortality.Results: Preoperative malperfusion was identified in 381 of 1159 patients (33%) who underwent ATAAD surgery. Thirty-day mortality was 28.9% in patients with preoperative malperfusion and 12.1% in those without. Independent predictors of 30-day mortality included any malperfusion (odds ratio, 2.76; 95% confidence interval [CI], 1.94-3.93), cardiac malperfusion (odds ratio, 2.37; 95% CI, 1.34-4.17), renal malperfusion (odds ratio, 2.38; 95% CI, 1.23-4.61) and peripheral malperfusion (odds ratio, 1.95; 95% CI, 1.26-3.01). Any malperfusion (hazard ratio, 1.72; 95% CI, 1.21-2.43), cardiac malperfusion (hazard ratio, 1.89; 95% CI, 1.24-2.87) and gastrointestinal malperfusion (hazard ratio, 2.25; 95% CI, 1.18-4.26) were predictors of late mortality. Malperfusion was associated with significantly poorer survival at 1, 3, and 5 years (95.0% +/-0.9% vs 88.7% +/-1.9%, 90.1% +/-1.3% vs 84.0% +/-2.4%, and 85.4% +/-1.7% vs 80.8% +/-2.7%; log rank P = .009).Conclusions: Malperfusion has a significant influence on early and late outcomes in ATAAD surgery. Management of preoperative malperfusion remains a major challenge in reducing mortality associated with surgical treatment of ATAAD.
24.	Aad, G., et al. (författare) A search for t (t)over-bar resonances with the ATLAS detector in 2.05 fb(-1) of proton-proton collisions at root s=7 TeV 2012 Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 72:7 Tidskriftsartikel (refereegranskat)
25.	Adams, Emma Catherine, et al. (författare) The structure-function relationship for alumina supported platinum during the formation of ammonia from nitrogen oxide and hydrogen in the presence of oxygen 2016 Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 18:16, s. 10850-10855 Tidskriftsartikel (refereegranskat)abstract We study the structure-function relationship of alumina supported platinum during the formation of ammonia from nitrogen oxide and dihydrogen by employing in situ X-ray absorption and Fourier transform infrared spectroscopy. Particular focus has been directed towards the effect of oxygen on the reaction as a model system for emerging technologies for passive selective catalytic reduction of nitrogen oxides. The suppressed formation of ammonia observed as the feed becomes net-oxidizing is accompanied by a considerable increase in the oxidation state of platinum as well as the formation of surface nitrates and the loss of NH-containing surface species. In the presence of (excess) oxygen, the ammonia formation is proposed to be limited by weak interaction between nitrogen oxide and the oxidized platinum surface. This leads to a slow dissociation rate of nitrogen oxide and thus low abundance of the atomic nitrogen surface species that can react with the adsorbed hydrogen species. In this case the consumption of hydrogen through the competing water formation reaction and decomposition/oxidation of ammonia are of less importance for the net ammonia formation.
26.	Adams, Emma, 1989, et al. (författare) Structure-function relationship for alumina supported platinum during formation of ammonia from nitrogen oxide and hydrogen in presence of oxygen 2016 Ingår i: Physical Chemistry Chemical Physics. - 1463-9084 .- 1463-9076. ; 18:16, s. 10850-10855 Tidskriftsartikel (refereegranskat)abstract We study the structure-function relationship of alumina supported platinum during forma- tion of ammonia from nitrogen oxide and dihydrogen by employing in situ X-ray absorption and Fourier transformed infrared spectroscopy. Particular focus is directed towards the effect of increased levels of oxygen on the reaction as a model system for emerging technologies for passive selective catalytic reduction of nitrogen oxides. The suppressed formation of ammo- nia observed as the feed becomes net-oxidizing is accompanied by a considerable increase in the oxidation state of platinum as well as enhanced formation of surface nitrates and loss of NH-containing surface species. In the presence of (excess) oxygen, the ammonia formation is proposed to be limited by the weak interaction between nitrogen oxide and the oxidized platinum surface. This leads to slow dissociation rate of nitrogen oxide and thus low abun- dance of atomic nitrogen surface species that can react with adsorbed hydrogen atoms. In this case the consumption of hydrogen through the competing water formation reaction and decomposition/oxidation of ammonia are of less importance for the net ammonia formation.
27.	Akerstrom, Finn, et al. (författare) Association between catheter ablation of atrial fibrillation and mortality or stroke 2024 Ingår i: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 110, s. 163-169 Tidskriftsartikel (refereegranskat)abstract Objective Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. Methods We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. Results Patients who underwent catheter ablation were healthier (mean CHA(2)DS(2)-VASc score 1.4 +/- 1.4 vs 1.6 +/- 1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5 +/- 2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). Conclusions Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.
28.	Berger, Karoline, 1991, et al. (författare) Interleukin-6 Induces Stem Cell Propagation through Liaison with the Sortilin-Progranulin Axis in Breast Cancer. 2023 Ingår i: Cancers. - 2072-6694. ; 15:24 Tidskriftsartikel (refereegranskat)abstract Unraveling the complex network between cancer cells and their tumor microenvironment is of clinical importance, as it might allow for the identification of new targets for cancer treatment. Cytokines and growth factors secreted by various cell types present in the tumor microenvironment have the potential to affect the challenging subpopulation of cancer stem cells showing treatment-resistant properties as well as aggressive features. By using various model systems, we investigated how the breast cancer stem cell-initiating growth factor progranulin influenced the secretion of cancer-associated proteins. In monolayer cultures, progranulin induced secretion of several inflammatory-related cytokines, such as interleukin (IL)-6 and -8, in a sortilin-dependent manner. Further, IL-6 increased the cancer stem fraction similarly to progranulin in the breast cancer cell lines MCF7 and MDA-MB-231 monitored by the surrogate mammosphere-forming assay. In a cohort of 63 patient-derived scaffold cultures cultured with breast cancer cells, we observed significant correlations between IL-6 and progranulin secretion, clearly validating the association between IL-6 and progranulin also in human-based microenvironments. In conclusion, the interplay between progranulin and IL-6 highlights a dual breast cancer stem cell-promoting function via sortilin, further supporting sortilin as a highly relevant therapeutic target for aggressive breast cancer.
29.	Björnerås, Caroline, et al. (författare) Inland blue holes of The Bahamas - chemistry and biology in a unique aquatic environment 2020 Ingår i: Fundamental and Applied Limnology. - : Schweizerbart science publishers. - 1863-9135. ; 194:2, s. 95-106 Tidskriftsartikel (refereegranskat)abstract While lake systems in temperate regions have been extensively studied, tropical and subtropical systems have received less attention. Here, we describe the water chemistry and biota of ten inland blue holes on Andros Island, The Bahamas, representative of the morphological, abiotic, and biotic variation among Androsian inland blue holes. The majority of the studied blue holes were vertically stratified with oxic freshwater overlying anoxic saline groundwater of marine origin. Water chemistry (e.g. total phosphorus and nitrogen) in shallow waters was similar among blue holes, while turbidity and water color varied. Presence of hydrogen sulfide and reduced iron in and below the halocline indicate reducing conditions in all stratified blue holes. The biota above the halocline was also similar among blue holes with a few taxa dominating the phytoplankton community, and the zooplankton community consisting of copepods and rotifers. The Bahamas mosquitofish (Gambusia hubbsi) was present in all investigated blue holes, often accompanied by other small planktivorous fish, while the piscivorous bigmouth sleeper (Gobiomorus donnitor) was only present in some of the blue holes. Our field study reinforces that inland blue holes are highly interesting for biogeochemical research, and provide naturally replicated systems for evolutionary studies.
30.	Bovinder Ylitalo, Erik, et al. (författare) A novel DNA methylation signature is associated with androgen receptor activity and patient prognosis in bone metastatic prostate cancer 2021 Ingår i: Clinical Epigenetics. - : BioMed Central. - 1868-7083 .- 1868-7075. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Background: Patients with metastatic prostate cancer (PC) are treated with androgen deprivation therapy (ADT) that initially reduces metastasis growth, but after some time lethal castration-resistant PC (CRPC) develops. A better understanding of the tumor biology in bone metastases is needed to guide further treatment developments. Subgroups of PC bone metastases based on transcriptome profiling have been previously identified by our research team, and specifically, heterogeneities related to androgen receptor (AR) activity have been described. Epigenetic alterations during PC progression remain elusive and this study aims to explore promoter gene methylation signatures in relation to gene expression and tumor AR activity.Materials and methods: Genome-wide promoter-associated CpG methylation signatures of a total of 94 tumor samples, including paired non-malignant and malignant primary tumor areas originating from radical prostatectomy samples (n = 12), and bone metastasis samples of separate patients with hormone-naive (n = 14), short-term castrated (n = 4) or CRPC (n = 52) disease were analyzed using the Infinium Methylation EPIC arrays, along with gene expression analysis by Illumina Bead Chip arrays (n = 90). AR activity was defined from expression levels of genes associated with canonical AR activity.Results: Integrated epigenome and transcriptome analysis identified pronounced hypermethylation in malignant compared to non-malignant areas of localized prostate tumors. Metastases showed an overall hypomethylation in relation to primary PC, including CpGs in the AR promoter accompanied with induction of AR mRNA levels. We identified a Methylation Classifier for Androgen receptor activity (MCA) signature, which separated metastases into two clusters (MCA positive/negative) related to tumor characteristics and patient prognosis. The MCA positive metastases showed low methylation levels of genes associated with canonical AR signaling and patients had a more favorable prognosis after ADT. In contrast, MCA negative patients had low AR activity associated with hypermethylation of AR-associated genes, and a worse prognosis after ADT.Conclusions: A promoter methylation signature classifies PC bone metastases into two groups and predicts tumor AR activity and patient prognosis after ADT. The explanation for the methylation diversities observed during PC progression and their biological and clinical relevance need further exploration.
31.	Bovinder Ylitalo, Erik, et al. (författare) Bone remodeling in relation to androgen receptor activity in prostate cancer bone metastases 2018 Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 78:16, s. 50-50 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
32.	Bovinder Ylitalo, Erik, et al. (författare) Integrated DNA methylation and gene expression analysis of molecular heterogeneity in prostate cancer bone metastasis Annan publikation (övrigt vetenskapligt/konstnärligt)
33.	Bovinder Ylitalo, Erik, et al. (författare) Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response 2017 Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 71:5, s. 776-787 Tidskriftsartikel (refereegranskat)abstract Background: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. Objectives: To identify molecular subgroups of PC bone metastases of relevance for therapy.Design, setting, and participants: Fresh-frozen bone metastasis samples from men with CRPC (n = 40), treatment-naïve PC (n = 8), or other malignancies (n = 12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription–polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n = 77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n = 12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n = 284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.Results and limitations: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non–AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non–AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.Conclusions: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored. Patient summary: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.
34.	Chemtob, Raphaelle A., et al. (författare) Effects of Sex on Early Outcome following Repair of Acute Type A Aortic Dissection : Results from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) 2019 Ingår i: AORTA. - : Georg Thieme Verlag KG. - 2325-4637. ; 7:1, s. 7-14 Tidskriftsartikel (refereegranskat)abstract Background Female sex is known to have increased perioperative mortality in cardiac surgery. Studies reporting effects of sex on outcome following surgical repair for acute Type A aortic dissection (ATAAD) have been limited by small cohorts of heterogeneous patient populations and have shown diverging results. This study aimed to compare perioperative characteristics, operative management, and postoperative outcome between sexes in a large and well-defined cohort of patients operated for ATAAD. Methods The Nordic Consortium for Acute Type A Aortic Dissection study included patients with surgical repair of ATAAD at eight Nordic centers between January 2005 and December 2014. Independent predictors of 30-day mortality were identified using multivariable logistic regression. Results Females represented 373 (32%) out of 1,154 patients and were significantly older (65 ± 11 vs. 60 ± 12 years, p < 0.001), had lower body mass index (25.8 ± 5.4 vs. 27.2 ± 4.3 kg/m 2, p < 0.001), and had more often a history of hypertension (59% vs. 48%, p = 0.001) and chronic obstructive pulmonary disease (8% vs. 4%, p = 0.033) compared with males. More females presented with DeBakey class II as compared with males with dissection of the ascending aorta alone (33.4% vs. 23.1%, p = 0.003). Hypothermic cardiac arrest time (28 ± 16 vs. 31 ± 19 minutes, p = 0.026) and operation time (345 ± 133 vs. 374 ± 135 minutes, p < 0.001) were shorter among females. There was no difference between the sexes in unadjusted intraoperative death (9.1% vs. 6.7%, p = 0.17) or 30-day mortality (17.7% vs. 17.4%, p = 0.99). In a multivariable analysis including perioperative factors influencing mortality, no difference was found between females and males in 30-day mortality (odds ratio: 0.92, 95% confidence interval: 0.62-1.38, p = 0.69). Conclusions This study found no association between sex and early mortality following surgery for ATAAD, despite females being older and having more comorbidities, yet also presenting with a less widespread dissection than males.
35.	Crnalic, Sead, et al. (författare) Nuclear androgen receptor staining in bone metastases is related to a poor outcome in prostate cancer patients 2010 Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 17:4, s. 885-895 Tidskriftsartikel (refereegranskat)abstract Androgen receptors (ARs) are probably of importance during all phases of prostate cancer (PC) growth, but their role in bone metastases is largely unexplored. Bone metastases were therefore collected from hormone-naive (n=11), short-term castrated (n=7) and castration-resistant PC (CRPC, n=44) patients by biopsy (n=4) or at surgery to alleviate symptoms from metastases complications (metastasis surgery, n=58), and immunostained for nuclear ARs, Ki67, active caspase-3, prostate-specific antigen (PSA) and chromogranin A, and results were related to serum PSA, treatments and outcome. Nuclear AR immunostaining was decreased and apoptosis was increased, but cell proliferation remained largely unaffected in metastases within a few days after surgical castration. In CRPC patients, nuclear AR staining of metastases was increased when compared to short-term castrated patients. The nuclear AR staining score was related to tumour cell proliferation, but it was not associated with other downstream effects of AR activation such as apoptosis and PSA staining, and it was only marginally related to the presence of neuroendocrine tumour cells. Serum PSA at metastasis surgery, although related to outcome, was not associated with AR staining, markers of metastasis growth or PSA staining in metastases. High nuclear AR immunostaining was associated with a particularly poor prognosis after metastasis surgery in CRPC patients, suggesting that such men may benefit from the potent AR blockers now tested in clinical trials.
36.	Djusberg, Erik, et al. (författare) High Levels of the AR-V7 Splice Variant and Co-Amplification of the Golgi Protein Coding YIPF6 in AR Amplified Prostate Cancer Bone Metastases 2017 Ingår i: The Prostate. - : Wiley-Blackwell Publishing Inc.. - 0270-4137 .- 1097-0045. ; 77:6, s. 625-638 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The relation between androgen receptor (AR) gene amplification and other mechanisms behind castration-resistant prostate cancer (CRPC), such as expression of constitutively active AR variants and steroid-converting enzymes has been poorly examined. Specific aim was to examine AR amplification in PC bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying novel molecular targets for treatment. METHODS: Gene amplification was assessed by fluorescence in situ hybridization in cryo-sections of clinical PC bone metastases (n = 40) and by PCR-based copy number variation analysis. Whole genome mRNA expression was analyzed using H12 Illumina Beadchip arrays and specific transcript levels were quantified by qRT-PCR. Protein localization was analyzed using immunohistochemistry and confocal microscopy. The YIPF6 mRNA expression was transiently knocked down and stably overexpressed in the 22Rv1 cell line as representative for CRPC, and effects on cell proliferation, colony formation, migration, and invasion were determined in vitro. Extracellular vesicles (EVs) were isolated from cell cultures using size-exclusion chromatography and enumerated by nanoparticle tracking analysis. Protein content was identified by LC-MS/MS analysis. Blood coagulation was measured as activated partial thromboplastin time (APTT). Functional enrichment analysis was performed using the MetaCore software. RESULTS: AR amplification was detected in 16 (53%) of the bone metastases examined from CRPC patients (n = 30), and in none from the untreated patients (n = 10). Metastases with AR amplification showed high AR and AR-V7 mRNA levels, increased nuclear AR immunostaining, and co-amplification of genes such as YIPF6 in the AR proximity at Xq12. The YIPF6 protein was localized to the Golgi apparatus. YIPF6 overexpression in 22Rv1 cells resulted in reduced cell proliferation and colony formation, and in enhanced EV secretion. EVs from YIPF6 overproducing 22Rv1 cells were enriched for proteins involved in blood coagulation and, accordingly, decreased the APTT in a dose-dependent fashion. CONCLUSIONS: AR amplified CRPC bone metastases show high AR-V7 expression that probably gives resistance to AR-targeting drugs. Co-amplification of the Golgi protein coding YIPF6 gene with the AR may enhance the secretion of pro-coagulative EVs from cancer cells and thereby stimulate tumor progression and increase the coagulopathy risk in CRPC patients.
37.	Drake, Isabel, et al. (författare) The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease: evidence from cross-sectional, longitudinal and Mendelian randomisation analyses 2022 Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65, s. 128-139 Tidskriftsartikel (refereegranskat)abstract Aims/hypothesis Galectin-1 modulates inflammation and angiogenesis, and cross-sectional studies indicate that galectin-1 may be a uniting factor between obesity, type 2 diabetes and kidney function. We examined whether circulating galectin-1 can predict incidence of chronic kidney disease (CKD) and type 2 diabetes in a middle-aged population, and if Mendelian randomisation (MR) can provide evidence for causal direction of effects. Methods Participants (n = 4022; 58.6% women) in the Malmo Diet and Cancer Study-Cardiovascular Cohort enrolled between 1991 and 1994 (mean age 57.6 years) were examined. eGFR was calculated at baseline and after a mean follow-up of 16.6 +/- 1.5 years. Diabetes status was ascertained through registry linkage (mean follow-up of 18.4 +/- 6.1 years). The associations of baseline galectin-1 with incident CKD and type 2 diabetes were assessed with Cox regression, adjusting for established risk factors. In addition, a genome-wide association study on galectin-1 was performed to identify genetic instruments for two-sample MR analyses utilising the genetic associations obtained from the Chronic Kidney Disease Genetics (CKDGen) Consortium (41,395 cases and 439,303 controls) and the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (74,124 cases and 824,006 controls). One genome-wide significant locus in the galectin-1 gene region was identified (sentinel SNP rs7285699; p = 2.4 x 10(-11)). The association between galectin-1 and eGFR was also examined in individuals with newly diagnosed diabetes from the All New Diabetics In Scania (ANDIS) cohort. Results Galectin-1 was strongly associated with lower eGFR at baseline (p = 2.3 x 10(-89)) but not with incident CKD. However, galectin-1 was associated with increased risk of type 2 diabetes (per SD increase, HR 1.12; 95% CI 1.02, 1.24). Two-sample MR analyses could not ascertain a causal effect of galectin-1 on CKD (OR 0.92; 95% CI 0.82, 1.02) or type 2 diabetes (OR 1.05; 95% CI 0.98, 1.14) in a general population. However, in individuals with type 2 diabetes from ANDIS who belonged to the severe insulin-resistant diabetes subgroup and were at high risk of diabetic nephropathy, genetically elevated galectin-1 was significantly associated with higher eGFR (p = 5.7 x 10(-3)). Conclusions/interpretation Galectin-1 is strongly associated with lower kidney function in cross-sectional analyses, and two-sample MR analyses suggest a causal protective effect on kidney function among individuals with type 2 diabetes at high risk of diabetic nephropathy. Future studies are needed to explore the mechanisms by which galectin-1 affects kidney function and whether it could be a useful target among individuals with type 2 diabetes for renal improvement.
38.	Glynn, Anders, et al. (författare) Declining levels of PCB, HCB and p,p'-DDE in adipose tissue from food producing bovines and swine in Sweden 1991-2004 2009 Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 74:11, s. 1457-1462 Tidskriftsartikel (refereegranskat)abstract The official control programme for organochlorine (OC) contaminants in food producing animals in Sweden was used to study temporal and spatial trends of the polychlorinated biphenyl CB 153, hexachlorobenzene (HCB) and p,p'-DDE in adipose tissue from bovines and swine 1991-2004. Our results show that efforts to decrease OC contamination of animal feed and the environment have had a positive impact on the contamination of the animal production. OC concentrations declined significantly in almost all studied regions of Sweden. OC temporal trends were slower in bovines (6-8% per year) than in swine (10-12%). Power analyses showed that data from more than 10 years of sampling were needed for a detection of an annual OC level change of 5% in both species in the control programme, due to large within- and between-year variation in OC levels. CB 153 and p,p'-DDE levels were higher in southern than in northern Sweden. Levels decreased with age in milk cows, but not in young nulliparous cows (heifers) and bulls. Moreover, milk cows and bulls had significantly lower OC levels than heifers. Levels were not age-dependent among swine, but castrated male swine (barrows) had significantly lower OC levels than young female swine (gilts). Levels of the studied OCs are now in many cases below the LOQ of the analytical method used. Future time trend studies of these OCs thus depend on lowered LOQs in the control programme.
39.	Glynn, Anders, et al. (författare) Reply to comments of Jose G. Dorea on "Declining levels of PCB, HCB and p,p '-DDE in adipose tissue from food producing bovines and swine in Sweden 1991-2004" by Glynn et al. [Chemosphere 74(11)(2009)1457-1462] 2009 Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 76:6, s. 868-868 Tidskriftsartikel (refereegranskat)
40.	Günther, Torsten, et al. (författare) Population genomics of Mesolithic Scandinavia : Investigating early postglacial migration routes and high-latitude adaptation 2018 Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 16:1 Tidskriftsartikel (refereegranskat)abstract Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the Last Glacial Maximum (LGM). However, the routes and genetic composition of these postglacial migrants remain unclear. We sequenced the genomes, up to 57x coverage, of seven hunter-gatherers excavated across Scandinavia and dated from 9,500-6,000 years before present (BP). Surprisingly, among the Scandinavian Mesolithic individuals, the genetic data display an east-west genetic gradient that opposes the pattern seen in other parts of Mesolithic Europe. Our results suggest two different early postglacial migrations into Scandinavia: initially from the south, and later, from the northeast. The latter followed the ice-free Norwegian north Atlantic coast, along which novel and advanced pressure-blade stone-tool techniques may have spread. These two groups met and mixed in Scandinavia, creating a genetically diverse population, which shows patterns of genetic adaptation to high latitude environments. These potential adaptations include high frequencies of low pigmentation variants and a gene region associated with physical performance, which shows strong continuity into modern-day northern Europeans.
41.	Hajdu, Flora, et al. (författare) Sveriges utsläpp måste minska nu, regeringen 2023 Ingår i: Aftonbladet. - 1103-9000. Tidskriftsartikel (populärvet., debatt m.m.)
42.	Halin Bergström, Sofia, et al. (författare) Extratumoral Heme Oxygenase-1 (HO-1) Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth. 2016 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:6 Tidskriftsartikel (refereegranskat)abstract Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1). To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer.
43.	Hansson, Emma C., 1985, et al. (författare) Coronary artery bypass grafting-related bleeding complications in patients treated with ticagrelor or clopidogrel : a nationwide study 2016 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 37:2, s. 189-197 Tidskriftsartikel (refereegranskat)abstract AIMS:Excessive bleeding impairs outcome after coronary artery bypass grafting (CABG). Current guidelines recommend withdrawal of clopidogrel and ticagrelor 5 days (120 h) before elective surgery. Shorter discontinuation would reduce the risk of thrombotic events and save hospital resources, but may increase the risk of bleeding. We investigated whether a shorter discontinuation time before surgery increased the incidence of CABG-related major bleeding complications and compared ticagrelor- and clopidogrel-treated patients.METHODS AND RESULTS:All acute coronary syndrome patients in Sweden on dual antiplatelet therapy with aspirin and ticagrelor (n = 1266) or clopidogrel (n = 978) who underwent CABG during 2012-13 were included in a retrospective observational study. The incidence of major bleeding complications according to the Bleeding Academic Research Consortium-CABG definition was 38 and 31%, respectively, when ticagrelor/clopidogrel was discontinued <24 h before surgery. Within the ticagrelor group, there was no significant difference between discontinuation 72-120 or >120 h before surgery [odds ratio (OR) 0.93 (95% confidence interval, CI, 0.53-1.64), P = 0.80]. In contrast, clopidogrel-treated patients had a higher incidence when discontinued 72-120 vs. >120 h before surgery (OR 1.71 (95% CI 1.04-2.79), P = 0.033). The overall incidence of major bleeding complications was lower with ticagrelor [12.9 vs. 17.6%, adjusted OR 0.72 (95% CI 0.56-0.92), P = 0.012].CONCLUSION:The incidence of CABG-related major bleeding was high when ticagrelor/clopidogrel was discontinued <24 h before surgery. Discontinuation 3 days before surgery, as opposed to 5 days, did not increase the incidence of major bleeding complications with ticagrelor, but increased the risk with clopidogrel. The overall risk of major CABG-related bleeding complications was lower with ticagrelor than with clopidogrel.
44.	Hansson, Emma C., 1985, et al. (författare) Preoperative dual antiplatelet therapy increases bleeding and transfusions but not mortality in acute aortic dissection type A repair. 2019 Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X .- 1010-7940. ; 56:1, s. 182-188 Tidskriftsartikel (refereegranskat)abstract Acute aortic dissection type A is a life-threatening condition, warranting immediate surgery. Presentation with sudden chest pain confers a risk of misdiagnosis as acute coronary syndrome resulting in subsequent potent antiplatelet treatment. We investigated the impact of dual antiplatelet therapy (DAPT) on bleeding and mortality using the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database.The NORCAAD database is a retrospective multicentre database where 119 of 1141 patients (10.4%) had DAPT with ASA+clopidogrel (n=108) or ASA+ticagrelor (n=11) before surgery. The incidence of major bleeding and 30-day mortality was compared between DAPT and non-DAPT patients with logistic regression models before and after propensity score matching.Before matching, 51.3% of DAPT patients had major bleeding when compared to 37.7% of non-DAPT patients (P=0.0049). DAPT patients received more transfusions of red blood cells [median 8U (Q1-Q3 4-15) vs 5.5U (2-11), P<0.0001] and platelets [4U (2-8) vs 2U (1-4), P=0.0001]. Crude 30-day mortality was 19.3% vs 17.0% (P=0.60). After matching, major bleeding remained significantly more common in DAPT patients, 51.3% vs 39.3% [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.05-2.51; P=0.028], but mortality did not significantly differ (OR 0.88, 95% CI 0.51-1.50; P=0.63). Major bleeding was associated with increased 30-day mortality (adjusted OR 2.44, 95% CI 1.72-3.46; P<0.0001).DAPT prior to acute aortic dissection repair was associated with increased bleeding and transfusions but not with mortality. Major bleeding per se was associated with a significantly increased mortality. Correct diagnosis is important to avoid DAPT and thereby reduce bleeding risk, but ongoing DAPT should not delay surgery.
45.	Helgason, Dadi, et al. (författare) Acute Kidney Injury After Acute Repair of Type A Aortic Dissection 2021 Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 111:4, s. 1292-1298 Tidskriftsartikel (refereegranskat)abstract Background: The aim of this study was to examine the incidence, risk factors, and outcomes of patients with acute kidney injury (AKI) after surgery for acute type A aortic dissection (ATAAD) using the Nordic Consortium for Acute Type A Aortic Dissection registry. Methods: Patients who underwent ATAAD surgery at 8 Nordic centers from 2005 to 2014 were analyzed for AKI according to the RIFLE criteria. Patients who died intraoperatively, those who had missing baseline or postoperative serum creatinine, and patients on preoperative renal replacement therapy were excluded. Results: AKI occurred in 382 of 941 patients (40.6%), and postoperative dialysis was required for 105 patients (11.0%). Renal malperfusion was present preoperatively in 42 patients (5.1%), of whom 69.0% developed postoperative AKI. In multivariable analysis patient-related predictors of AKI included age (per 10 years; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.15-1.48), body mass index >30 kg/m2 (OR, 2.16; 95% CI, 1.51-3.09), renal malperfusion (OR, 4.39; 95% CI, 2.23-9.07), and other malperfusion (OR, 2.10; 95% CI, 1.55-2.86). Perioperative predictors were cardiopulmonary bypass time (per 10 minutes; OR, 1.04; 95% CI, 1.02-1.07) and red blood cell transfusion (OR per transfused unit, 1.08; 95% CI, 1.06-1.10). Rates of 30-day mortality were 17.0% in the AKI group compared with 6.6% in the non-AKI group (P < .001). In 30-day survivors AKI was an independent predictor of long-term mortality (hazard ratio, 1.86; 95% CI; 1.24-2.79). Conclusions: AKI is a common complication after surgery for ATAAD and independently predicts adverse long-term outcome. Of note one-third of patients presenting with renal malperfusion did not develop postoperative AKI, possibly because of restoration of renal blood flow with surgical repair. Mortality risk persists beyond the perioperative period, indicating that close clinical follow-up of these patients is required.
46.	Helgason, Dadi, et al. (författare) Acute Kidney Injury Following Acute Repair of Type A Aortic Dissection. 2021 Ingår i: The Annals of thoracic surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 111:4, s. 1292-1298 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to examine the incidence, risk factors and outcomes of patients with acute kidney injury (AKI) following surgery for acute type A aortic dissection (ATAAD) using the NORCAAD registry.Patients that underwent ATAAD surgery at eight Nordic centers from 2005-2014 were analyzed for AKI according to the RIFLE-criteria. Patients who died intraoperatively, those who had missing baseline or postoperative serum creatinine (SCr), and patients on preoperative RRT, were excluded.AKI occurred in 382/941 (40.6%) patients and postoperative dialysis was required for 105 (11.0%) patients. Renal malperfusion was present preoperatively in 42 (5.1%) patients, of whom 69.0% developed postoperative AKI.In multivariable analysis, patient-related predictors of AKI included age (per 10 years, OR=1.30, 95% CI:1.15-1.48), body mass index>30 kg/m2 (OR=2.16, 95% CI:1.51-3.09), renal malperfusion (OR=4.39, 95% CI:2.23-9.07) and other malperfusion (OR:2.10, 95% CI:1.55-2.86). Perioperative predictors were cardiopulmonary bypass time (per 10 minutes, OR=1.04, 95% CI:1.02-1.07) and red blood cell transfusion (OR=1.08, 95% CI:1.06-1.10). Rates of 30-day mortality were 17.0% in the AKI group compared with 6.6% in the non-AKI group (p<0.001). In 30-day survivors, AKI was an independent predictor of long-term mortality (HR=1.86, 95% CI:1.24-2.79).AKI is a common complication following surgery for ATAAD and independently predicts adverse long-term outcome. Of note, one-third of patients presenting with renal malperfusion did not develop postoperative AKI, possibly due to restoration of renal blood flow with surgical repair. Mortality risk persists beyond the perioperative period, indicating that close clinical follow-up of these patients is required.
47.	Hibar, Derrek P., et al. (författare) Novel genetic loci associated with hippocampal volume 2017 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Tidskriftsartikel (refereegranskat)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
48.	Hörnberg, Emma, et al. (författare) Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival 2011 Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4, s. e19059- Tidskriftsartikel (refereegranskat)abstract Background: Constitutively active androgen receptor variants (AR-V) lacking the ligand binding domain (LBD) may promote the development of castration-resistant prostate cancer (CRPC). The expression of AR-Vs in the clinically most important metastatic site, the bone, has, however, not been well documented. Our aim was therefore to compare levels of AR-Vs in hormone-naive (HN) and CRPC bone metastases in comparison to primary PC and non-malignant prostate tissue, as well as in relation to AR protein expression, whole-genome transcription profiles and patient survival.Methodology/Principal Findings: Hormone-naı¨ve (n = 10) and CRPC bone metastases samples (n = 30) were obtained from 40 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13 prostatectomized men. Levels of full length AR (ARfl) and AR-Vs termed AR-V1, AR-V7, and AR-V567es mRNA were measured with RT-PCR and whole-genome transcription profiles with an Illumina Beadchip array. Protein levels were examined by Western blotting and immunohistochemistry. Transcripts for ARfl, AR-V1, and AR-V7 were detected in most primary tumors and metastases, and levels were significantly increased in CRPC bone metastases. The AR-V567es transcript was detected in 23% of the CRPC bone metastases only. A sub-group of CRPC bone metastases expressed LBD-truncated AR proteins at levels comparable to the ARfl. Detectable AR-V567es and/or AR-V7 mRNA in the upper quartile, seen in 1/3 of all CRPC bone metastases, was associated with a high nuclear AR immunostaining score, disturbed cell cycle regulation and short survival.Conclusions/Significance: Expression of AR-Vs is increased in CRPC compared to HN bone metastases and associated with a particularly poor prognosis. Further studies are needed to test if patients expressing such AR-Vs in their bone metastases benefit more from drugs acting on or down-stream of these AR-Vs than from therapies inhibiting androgen synthesis.
49.	Jernberg, Emma, et al. (författare) Characterization of prostate cancer bone metastases according to expression levels of steroidogenic enzymes and androgen receptor splice variants 2013 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:11, s. e77407- Tidskriftsartikel (refereegranskat)abstract Background: Intra-tumoral steroidogenesis and constitutive androgen receptor (AR) activity have been associated withcastration-resistant prostate cancer (CRPC). This study aimed to examine if CRPC bone metastases expressed higher levels ofsteroid-converting enzymes than untreated bone metastases. Steroidogenic enzyme levels were also analyzed in relation toexpression of constitutively active AR variants (AR-Vs) and to clinical and pathological variables.Methodology/Principal Findings: Untreated, hormone-naıve (HN, n = 9) and CRPC bone metastases samples (n = 45) wereobtained from 54 patients at metastasis surgery. Non-malignant and malignant prostate samples were acquired from 13prostatectomy specimens. Transcript and protein levels were analyzed by real-time RT-PCR, immunohistochemistry andimmunoblotting. No differences in steroidogenic enzyme levels were detected between CRPC and HN bone metastases.Significantly higher levels of SRD5A1, AKR1C2, AKR1C3, and HSD17B10 mRNA were however found in bone metastases thanin non-malignant and/or malignant prostate tissue, while the CYP11A1, CYP17A1, HSD3B2, SRD5A2, and HSD17B6 mRNAlevels in metastases were significantly lower. A sub-group of metastases expressed very high levels of AKR1C3, which wasnot due to gene amplification as examined by copy number variation assay. No association was found between AKR1C3expression and nuclear AR staining, tumor cell proliferation or patient outcome after metastases surgery. With only oneexception, high AR-V protein levels were found in bone metastases with low AKR1C3 levels, while metastases with highAKR1C3 levels primarily contained low AR-V levels, indicating distinct mechanisms behind castration-resistance in individualbone metastases.Conclusions/Significance: Induced capacity of converting adrenal-gland derived steroids into more potent androgens wasindicated in a sub-group of PC bone metastases. This was not associated with CRPC but merely with the advanced stage ofmetastasis. Sub-groups of bone metastases could be identified according to their expression levels of AKR1C3 and AR-Vs,which might be of relevance for patient response to 2nd line androgen-deprivation therapy.
50.	Jernberg, Emma, et al. (författare) Molecular features of prostate cancer bone metastases harboring androgen receptor gene amplification Annan publikation (övrigt vetenskapligt/konstnärligt)abstract The relation between AR amplification and other mechanisms behind castration-resistance in prostate cancer, such as increased expression of AR splice variants and steroid-converting enzymes in CRPC metastases, has been poorly examined. Specific aims of this study were therefore to examine AR amplification in hormone-naïve and castration-resistant prostate cancer (CRPC) bone metastases and to explore molecular and functional consequences of this, with the long-term goal of identifying molecular targets for treatment of CRPC bone metastases. AR amplification was assessed by fluorescence in situ hybridization and verified in 16 (53 %) of the CRPC bone metastases (n=30), and in none of the untreated bone metastases (n=10). AR amplification was associated with increased expression of AR and its constitutively active AR-V7 splice variant as well as with co-amplification of genes in the AR proximity at Xq12, such as of YIPF6. Furthermore, gene expression pattern pointed at decreased osteoclast activity, and consequently decreased bone resorption and increased bone mineral density in AR amplified metastases. In conclusion, our results indicated a sclerotic phenotype in CRPC bone metastases with AR amplification that may be of both biological and clinical relevance. This is a novel hypothesis that requires to be thoroughly examined.

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