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1.	Maier, Hannes, et al. (författare) Consensus Statement on Bone Conduction Devices and Active Middle Ear Implants in Conductive and Mixed Hearing Loss 2022 Ingår i: Otology and Neurotology. - : Lippincott, Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 43:5, s. 513-529 Tidskriftsartikel (refereegranskat)abstract Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.
2.	Erlinge, D., et al. (författare) Bivalirudin versus Heparin Monotherapy in Myocardial Infarction 2017 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 377:12, s. 1132-1142 Tidskriftsartikel (refereegranskat)abstract Background The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. Methods In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. Results A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). Conclusions Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).
3.	Linder, Stefan, et al. (författare) Treatment of de Garengeot's hernia : a meta-analysis 2019 Ingår i: Hernia. - : Springer. - 1265-4906 .- 1248-9204. ; 23:1, s. 131-141 Forskningsöversikt (refereegranskat)abstract Purposede Garengeot's hernia is a rare entity in which the appendix is located within a femoral hernia and is almost invariably encountered incarcerated in an emergency setting with concomitant appendicitis. In the literature, there are mostly single-case reports. The purpose of the present study was to perform a review of the literature to study the incidence, pathogenesis, demographics, clinical presentation, laboratory and radiological investigations, differential diagnosis, delay in diagnosis and treatment, operative findings, surgical technique, histological findings, the postoperative course, use of antibiotics, and complications regarding de Garengeot's hernia.MethodsA literature search was performed through PubMed with the following search terms, single or in combination: Garengeot, femoral hernia, and appendicitis. Additional references were also found within the articles, and two patients from Uppsala University Hospital were added.ResultsBetween 1981 and 2016, 70 publications were identified, and with the additional two patients, the present series comprised 90 patients There were 75 women (median age 73.0years) and 15 men (median age 78.0years). On examination, an inguinal mass was found in 87 patients (97%), which was painful and the cause of primary complaint in 67 patients (74%): the median duration of symptoms was 3days. Radiological investigations or ultrasound were performed in 67 patients (74%); computed tomography was the most accurate with a positive diagnosis in 23/34 patients. Appendicitis was found in 76 patients, gangrenous in 23, and perforated in 9. The surgical approach was inguinal in 76 patients, including 15 with concomitant laparotomy. The preperitoneal route was chosen in six patients, and laparoscopy alone in four patients. A mesh/plug was used in 22 patients (7/22 normal appendix) and suture repair in 59 (4/59 normal appendix: p<0.01). Complications were analysed in 79 patients and occurred in 11%. There was no mortality.Conclusionsde Garengeot's hernia is rare, being indistinguishable from an incarcerated femoral hernia in general. A delay in surgery should be avoided but if needed, computed tomography may be used for differential diagnosis. Although there is no standard treatment, mesh material does not appear advisable in the presence of a perforation, and it is beneficial for the surgeons to perform their routine method rather than a specific technique.
4.	Bohm, Felix, et al. (författare) FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction 2024 Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. Tidskriftsartikel (refereegranskat)abstract Background The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear.Methods In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization.Results A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P=0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes.Conclusions Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.) In a registry-based trial, FFR-guided PCI of nonculprit lesions did not result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI.
5.	Böhm, Felix, et al. (författare) FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction 2024 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 390:16, s. 1481-1492 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).
6.	Carlsson, Anna K, 1966, et al. (författare) Dynamic Responses of Female Volunteers in Rear Impact Sled Tests at Two Head Restraint Distances 2021 Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 9 Tidskriftsartikel (refereegranskat)abstract The objective of this study was to assess the biomechanical and kinematic responses of female volunteers with two different head restraint (HR) configurations when exposed to a low-speed rear loading environment. A series of rear impact sled tests comprising eight belted, near 50th percentile female volunteers, seated on a simplified laboratory seat, was performed with a mean sled acceleration of 2.1 g and a velocity change of 6.8 km/h. Each volunteer underwent two tests; the first test configuration, HR10, was performed at the initial HR distance ∼10 cm and the second test configuration, HR15, was performed at ∼15 cm. Time histories, peak values and their timing were derived from accelerometer data and video analysis, and response corridors were also generated. The results were separated into three different categories, HR10C (N = 8), HR15C (N = 6), and HR15NC (N= 2), based on: (1) the targeted initial HR distance [10 cm or 15 cm] and (2) whether the volunteers’ head had made contact with the HR [Contact (C) or No Contact (NC)] during the test event. The results in the three categories deviated significantly. The greatest differences were found for the average peak head angular displacements, ranging from 10° to 64°. Furthermore, the average neck injury criteria (NIC) value was 22% lower in HR10C (3.9 m2/s2), and 49% greater in HR15NC (7.4 m2/s2) in comparison to HR15C (5.0 m2/s2). This study supplies new data suitable for validation of mechanical or mathematical models of a 50th percentile female. A model of a 50th percentile female remains to be developed and is urgently required to complement the average male models to enhance equality in safety assessments. Hence, it is important that future protection systems are developed and evaluated with female properties taken into consideration too. It is likely that the HR15 test configuration is close to the limit for avoiding HR contact for this specific seat setup. Using both datasets (HR15C and HR15NC), each with its corresponding HR contact condition, will be possible in future dummy or model evaluation.
7.	Carlsson, Anna K, 1966, et al. (författare) Female volunteer motion in rear impact sled tests in comparison to results from earlier male volunteer tests 2008 Ingår i: 2008 INTERNATIONAL IRCOBI CONFERENCEONTHE BIOMECHANICS OF INJURY17. – 19. September 2008– BERN (Switzerland)PROCEEDINGS. ; , s. 461-464, s. 461-464 Konferensbidrag (refereegranskat)abstract Vehicle related crashes causing neck injuries (whiplash) are costly and common, and injury statistic data shows a larger risk of neck injuries for females than for males. This study aims at investigating differences between female and male dynamic response in rear impacts. Rear impact sled tests with female volunteers were carried out and the results were compared with previously performed tests with males in matching test conditions. The volunteer tests were performed at a change of velocity of 7 km/h. The comparison of the average response of the males and the females and their response corridors showed several differences. The horizontal head acceleration peak value was on average 40% higher and occurred on average 18% earlier for the female volunteers compared to the male volunteers. The NIC value was 45% lower and 30% earlier for the females, probably due to a 27% smaller initial head-to-head restraint distance and thereby a 24% earlier head restraint contact. The results provide characteristic differences between dynamic responses of females and males in low speed rear impacts. These results contribute to the understanding of human dynamic response in rear impacts. In addition, they can be used in the process of future development if numerical and/or mechanical human models for crash testing.
8.	Cheng, Qing, et al. (författare) Preclinical PET imaging of EGFR levels : pairing a targeting with a non-targeting Sel-tagged Affibody-based tracer to estimate the specific uptake 2016 Ingår i: EJNMMI Research. - : Springer. - 2191-219X. ; 6 Tidskriftsartikel (refereegranskat)abstract Background: Though overexpression of epidermal growth factor receptor (EGFR) in several forms of cancer is considered to be an important prognostic biomarker related to poor prognosis, clear correlations between biomarker assays and patient management have been difficult to establish. Here, we utilize a targeting directly followed by a non-targeting tracer-based positron emission tomography (PET) method to examine some of the aspects of determining specific EGFR binding in tumors. Methods: The EGFR-binding Affibody molecule Z(EGFR:2377) and its size-matched non-binding control Z(Taq:3638) were recombinantly fused with a C-terminal selenocysteine-containing Sel-tag (Z(EGFR:2377)-ST and Z(Taq:3638)-ST). The proteins were site-specifically labeled with DyLight488 for flow cytometry and ex vivo tissue analyses or with C-11 for in vivo PET studies. Kinetic scans with the C-11-labeled proteins were performed in healthy mice and in mice bearing xenografts from human FaDu (squamous cell carcinoma) and A431 (epidermoid carcinoma) cell lines. Changes in tracer uptake in A431 xenografts over time were also monitored, followed by ex vivo proximity ligation assays (PLA) of EGFR expressions. Results: Flow cytometry and ex vivo tissue analyses confirmed EGFR targeting by ZE(GFR:2377)-ST-DyLight488. [Methyl-C-11]-labeled Z(EGFR:2377)-ST-CH3 and Z(Taq:3638)-ST-CH3 showed similar distributions in vivo, except for notably higher concentrations of the former in particularly the liver and the blood. [Methyl-C-11]-Z(EGFR:2377)-ST-CH3 successfully visualized FaDu and A431 xenografts with moderate and high EGFR expression levels, respectively. However, in FaDu tumors, the non-specific uptake was large and sometimes equally large, illustrating the importance of proper controls. In the A431 group observed longitudinally, non-specific uptake remained at same level over the observation period. Specific uptake increased with tumor size, but changes varied widely over time in individual tumors. Total (membranous and cytoplasmic) EGFR in excised sections increased with tumor growth. There was no positive correlation between total EGFR and specific tracer uptake, which, since Z(EGFR:2377) binds extracellularly and is slowly internalized, indicates a discordance between available membranous and total EGFR expression levels. Conclusions: Same-day in vivo dual tracer imaging enabled by the Sel-tag technology and C-11-labeling provides a method to non-invasively monitor membrane-localized EGFR as well as factors affecting non-specific uptake of the PET ligand.
9.	Chew, Michelle, et al. (författare) Increased plasma levels of heparin-binding protein in patients with shock: a prospective, cohort study. 2012 Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 61:4, s. 375-379 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Heparin-binding protein (HBP) is a potent inducer of increased vascular permeability. The purpose of this study was to examine plasma levels of HBP in patients with shock. DESIGN: Fifty-three consecutive patients with septic and non-septic shock at a mixed-bed intensive care unit were included, as well as 20 age-matched controls. Patients with local infections but without signs of shock served as infectious controls. Enzyme-linked immunosorbent assay was used to determine plasma levels of HBP. RESULTS: There were no differences in serum HBP levels between healthy controls and those with local infections, including urinary tract infections, pneumonia and gastroenteritis, without shock. Levels of HBP were higher in patients with non-septic shock and septic shock than healthy controls. However, there was no difference in serum HBP levels between patients with septic shock and those with non-septic shock. Moreover, HBP levels were not different between patients with low and high APACHE II scores. Plasma levels of HBP were similar in surviving and non-surviving patients with shock. CONCLUSIONS: HBP is elevated in patients with shock from septic and non-septic etiologies. Future investigations are required to define the functional role of HBP in patients with shock.
10.	Demidova, Marina M., et al. (författare) Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention : A substudy of VALIDATE-SWEDEHEART trial 2023 Ingår i: Heart rhythm O2. - : Elsevier. - 2666-5018. ; 4:3, s. 200-206 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia.OBJECTIVE: We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing.METHODS: The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry.RESULTS: Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality.CONCLUSION: VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance.
11.	Dworeck, Christian, et al. (författare) Radial artery access is associated with lower mortality in patients undergoing primary PCI : a report from the SWEDEHEART registry 2020 Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 9:4, s. 323-332 Tidskriftsartikel (refereegranskat)abstract Objectives: The purpose of this observational study was to evaluate the effects of radial artery access versus femoral artery access on the risk of 30-day mortality, inhospital bleeding and cardiogenic shock in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Methods: We used data from the SWEDEHEART registry and included all patients who were treated with primary percutaneous coronary intervention in Sweden between 2005 and 2016. We compared patients who had percutaneous coronary intervention by radial access versus femoral access with regard to the primary endpoint of all-cause death within 30 days, using a multilevel propensity score adjusted logistic regression which included hospital as a random effect.Results: During the study period, 44,804 patients underwent primary percutaneous coronary intervention of whom 24,299 (54.2%) had radial access and 20,505 (45.8%) femoral access. There were 2487 (5.5%) deaths within 30 days, of which 920 (3.8%) occurred in the radial access and 1567 (7.6%) in the femoral access group. After propensity score adjustment, radial access was associated with a lower risk of death (adjusted odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.88,P = 0.025). We found no interaction between access site and age, gender and cardiogenic shock regarding 30-day mortality. Radial access was also associated with a lower adjusted risk of bleeding (adjusted OR 0.45, 95% CI 0.25-0.79,P = 0.006) and cardiogenic shock (adjusted OR 0.41, 95% CI 0.24-0.73,P = 0.002).Conclusions: In patients with ST-elevation myocardial infarction, primary percutaneous coronary intervention by radial access rather than femoral access was associated with an adjusted lower risk of death, bleeding and cardiogenic shock. Our findings are consistent with, and add external validity to, recent randomised trials.
12.	Erlinge, David, et al. (författare) Bivalirudin versus heparin in non-ST and ST-segment elevation myocardial infarction-a registry-based randomized clinical trial in the SWEDEHEART registry (the VALIDATE-SWEDEHEART trial). 2016 Ingår i: American heart journal. - New York, USA : Elsevier BV. - 1097-6744 .- 0002-8703. ; 175, s. 36-46 Tidskriftsartikel (refereegranskat)abstract The optimal anticoagulant for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) has not been validated in current practice of radial approach and pretreatment with potent P2Y12 inhibitors. Several studies have indicated increased bleeding rate and, in some instances, even increased mortality by the routine use of heparin and glycoprotein IIb/IIIa inhibitors compared to bivalirudin. Direct comparison of bivalirudin versus heparin alone has yielded contradictory results depending on study designs.
13.	Erlinge, David, et al. (författare) Bivalirudin versus heparin monotherapy in non-ST-segment elevation myocardial infarction 2019 Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:6, s. 492-501 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use.METHODS: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days.RESULTS: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78-1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68-1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58-1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77-1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30-5.93, p=0.82).CONCLUSION: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.
14.	Farnocchia, Davide, et al. (författare) The Second International Asteroid Warning Network Timing Campaign: 2005 LW3 2023 Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11 Tidskriftsartikel (refereegranskat)abstract The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
15.	Flanagan, John N., et al. (författare) Role of follistatin in promoting adipogenesis in women 2009 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:8, s. 3003-9 Tidskriftsartikel (refereegranskat)abstract CONTEXT: Follistatin is a glycoprotein that binds and neutralizes biological activities of TGFbeta superfamily members including activin and myostatin. We previously identified by expression profiling that follistatin levels in white adipose tissue (WAT) were regulated by obesity. OBJECTIVE: The objective of the study was to elucidate the role of follistatin in human WAT and obesity. DESIGN: We measured secreted follistatin protein from WAT biopsies and fat cells in vitro. We also quantified follistatin mRNA expression in sc and visceral WAT and in WAT-fractionated cells and related it to obesity status, body region, and cellular origin. We investigated the effects of follistatin on adipocyte differentiation of progenitor cells in vitro. PARTICIPANTS: Women (n = 66) with a wide variation in body mass index were recruited by advertisement and from a clinic for weight-reduction therapy. RESULTS: WAT secreted follistatin in vitro. Follistatin mRNA levels in sc but not visceral WAT were decreased in obesity and restored to nonobese levels after weight reduction. Follistatin mRNA levels were high in the stroma-vascular fraction of WAT and low in adipocytes. Recombinant follistatin treatment promoted adipogenic differentiation of progenitor cells and neutralized the inhibitory action of myostatin on differentiation in vitro. Moreover, activin and myostatin signaling receptors were detected in WAT and adipocytes. CONCLUSION: Follistatin is a new adipokine important for adipogenesis. Down-regulated WAT expression of follistatin in obesity may counteract adiposity but could, by inhibiting adipogenesis, contribute to hypertrophic obesity (large fat cells) and insulin resistance.
16.	Heinze, Karolin, et al. (författare) Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas. 2021 Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401 Tidskriftsartikel (refereegranskat)abstract ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
17.	Hofmann, Robin, et al. (författare) Oxygen therapy in ST-elevation myocardial infarction. 2018 Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:29, s. 2730-2739 Tidskriftsartikel (refereegranskat)abstract Aims: To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes.Methods and results: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days.Conclusions: Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.
18.	Hofmann, Robin, et al. (författare) Oxygen therapy in suspected acute myocardial infarction 2017 Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 377:13, s. 1240-1249 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS: In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS: A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P=0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P=0.33). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality. (Funded by the Swedish Heart–Lung Foundation and others; DETO2X-AMI ClinicalTrials.gov number, NCT01787110.)
19.	James, Stefan, 1964-, et al. (författare) Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction 2021 Ingår i: Circulation. Cardiovascular Interventions. - : Lippincott Williams & Wilkins. - 1941-7640 .- 1941-7632. ; 14:12 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry).METHODS: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days.RESULTS: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04).CONCLUSIONS: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.
20.	Khatri, C, et al. (författare) Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study 2021 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830- Tidskriftsartikel (refereegranskat)abstract Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
21.	Kullman, Eric, et al. (författare) Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study 2010 Ingår i: GASTROINTESTINAL ENDOSCOPY. - : Elsevier Science B. V., Amsterdam. - 0016-5107 .- 1097-6779. ; 72:5, s. 915-923 Tidskriftsartikel (refereegranskat)abstract Background: Covered biliary metal stents have been developed to prevent tumor ingrowth. Previous comparative studies are limited and often include few patients. Objective: To compare differences in stent patency, patient survival, and complication rates between covered and uncovered nitinol stents in patients with malignant biliary obstruction. Design: Randomized, multicenter trial conducted between January 2006 and October 2008. Setting: Ten sites serving a total catchment area of approximately 2.8 million inhabitants. Patients: A total of 400 patients with unresectable distal malignant biliary obstruction. Interventions: ERCP with insertion of covered or uncovered metal stent. Follow-up conducted monthly for symptoms indicating stent obstruction. Main Outcome Measurements: Time to stent failure, survival time, and complication rate. Results: The patient survival times were 116 days (interquartile range 242 days) and 174 days (interquartile range 284 days) in the covered and uncovered stent groups, respectively (P = .320). The first quartile stent patency time was 154 days in the covered stent group and 199 days in the uncovered stent group (P = .326). There was no difference in the incidence of pancreatitis or cholecystitis between the 2 groups. Stent migration occurred in 6 patients (3%) in the covered group and in no patients in the uncovered group (P = .030). Limitations: Randomization was not blinded. Conclusions: There were no significant differences in stent patency time, patient survival time, or complication rates between covered and uncovered nitinol metal stents in the palliative treatment of malignant distal biliary obstruction. However, covered stents migrated significantly more often compared with uncovered stents, and tumor ingrowth was more frequent in uncovered stents.
22.	Lagerqvist, Bo, et al. (författare) Outcomes 1 year after thrombus aspiration for myocardial infarction. 2014 Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 371:12, s. 1111-1120 Tidskriftsartikel (refereegranskat)abstract Routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) has not been proved to reduce short-term mortality. We evaluated clinical outcomes at 1 year after thrombus aspiration.
23.	Langerth, Ann, et al. (författare) ERCP‑related perforations : a population‑based study of incidence,mortality, and risk factors 2020 Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 34, s. 1939-1947 Tidskriftsartikel (refereegranskat)abstract Background: Perforations related to endoscopic retrograde cholangiopancreatography (ERCP) are rare but feared adverse events with highly reported morbidity and mortality rates. The aim was to evaluate the incidence and outcome of ERCP-related perforations and to identify risk factors for death due to perforations in a population-based study.Methods: Between May 2005 and December 2013, a total of 52,140 ERCPs were registered in GallRiks, a Swedish nationwide, population-based registry. A total of 376 (0.72%) were registered as perforations or extravasation of contrast during ERCP or as perforation in the 30-day follow-up. The patients with perforation were divided into fatal and non-fatal groups and analyzed for mortality risk factors. The case volume of centers and endoscopists were divided into the upper quartile (Q4) and the lower three quartile (Q1-3) groups. Furthermore, fatal group patients' records were reviewed.Results: Death within 90 days after ERCP-related perforations or at the index hospitalization occurred in 20% (75 out of 376) for all perforations and 0.1% (75 out of 52,140) for all ERCPs. The independent risk factors for death after perforation were malignancy (OR 11.2, 95% CI 5.8-21.6), age over 80 years (OR 3.8, 95% CI 2.0-7.4), and sphincterotomy in the pancreatic duct (OR 2.8, 95% CI 1.1-7.5). In Q4 centers, the mortality was similar with or without pancreatic duct sphincterotomy (14% vs. 13%, p = 1.0), but in Q1-3 centers mortality was higher (45% vs. 21%, p = 0.024).Conclusions: ERCP-related perforations are severe adverse events with low incidence (0.7%) and high mortality rate up to 20%. Malignancy, age over 80 years, and sphincterotomy in the pancreatic duct increase the risk to die after a perforation. The risk of a fatal outcome in perforations after pancreatic duct sphincterotomy was reduced when occurred at a Q4-center. In the case of a complicated perforation a transfer to a Q4-center may be considered.
24.	Lill, Christina M., et al. (författare) The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease 2015 Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416 Tidskriftsartikel (refereegranskat)abstract A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
25.	Linder, Astrid, et al. (författare) Influence of gender, height, weight, age, seated position and collision site related to neck pain symptoms in rear end impacts 2012 Ingår i: 2012 IRCOBI Conference Proceedings. ; , s. 235-248 Konferensbidrag (refereegranskat)abstract Rear end vehicle collisions can result in occupants suffering neck pain symptoms of varying degree and duration. These injuries are generally called whiplash injuries and they are common and costly. This study analyses the occurance and duration of neck pain symptoms of one particular vehicle make with focus on the influence of occupant specific information. Data collected from a Swedish vehicle make, model year 1993 up to model year 2007 at a maximum of three years old, were analysed. The results from this study show that passengers are more likely than drivers to suffer neck pain symptoms, in crashes that occurred in that particular make of car. No significant differences in risk related to age, gender weight, and height could be identified, except for: Females aged 35-44 had higher risk to have long and medium term neck pain symptoms than males in the same group of age. Males aged >=65 had higher risk to have long and medium term neck pain symptoms than males aged 35-44. Females in group "Braking" had higher risk of any type of neck pain symptoms than males. Where the occupant was seated in the front seat of the carinfluenced the occurance of neck pain symptoms and their duration for both males and females, with passengers posing a higher risk of suffering neck pain symptoms compared to drivers. Of the drivers, 17 percent reported neck pain symptoms compared to 44 percent of the passengers. When grouped into the categories males and females, 15 percent of the male and 19 percent of the female drivers reported neck pain symptoms compared to 44 percent of the male and 43 percent of the female passengers. With respect to the different collision sites, rear end collisions at traffic lights most often resulted in occupants reporting neck pain symptoms. Collisions in roundabouts most often resulted in different impact scenarios and occupants reported suffering neck pain symptoms of mid and long term duration. The result of this study indicates the need for improved understanding of the differences between driver and passenger response in different driving scenarios. In addition, occupant charactersisics should also be studied.
26.	Linder, Stefan (författare) Assessment of diagnostic and prognostic factors in pancreatic duct carcinoma 1997 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The diagnosis pancreatic carcinoma is suggested by a combination of clinical and radiological signs. The differential diagnosis vs. chronic pancreatitis may, however, be difficult. Morphological verification of malignancy is therefore necessary before initiating non-surgical therapy. The present study is focused on the use of cytological material in the diagnosis of pancreatic carcinoma and some tumour biological properties that may have a prognostic impact in patients with pancreatic carcinoma. A series of 334 patients with suspected pancreatic carcinoma underwent percutaneous fine-needle aspiration biopsy (FNAB). A malignant diagnosis was clenched in 270 and cytology was positive in 187. There were no false positive interpretations in 64 patients without a carcinoma. Thus, the sensitivity, specificity and overall accuracy were 69%, 100% and 75%, respectively. There were no complications or cutaneous metastases. FNAB can therefore be considered a safe and reliable procedure for confirming pretreatment diagnoses of pancreatic carcinoma. Morphometry was studied as an aid to conventional morphology in cytological material from 100 patients with pancreatic carcinoma and 15 with chronic pancreatitis. There were pronounced differences between the two patient groups and interobserver reproducibility was demonstrated. The results therefore indicate that morphometry may be used as an adjunct to conventional cytology in the diagnosis of pancreatic carcinoma. DNA ploidy was assessed by performing image cytometry (ICM) on cytological samples from 128 patients with pancreatic carcinoma. There were 39 (30%) DNA diploid, 21 (17%) tetraploid and 68 (53%) aneuploid tumours. Among patients who had undergone resection, the DNA pattern was diploid to a greater extent than among those who received non-surgical treatment. Prognostic information was obtained by DNA ploidy and morphometric variables alone, and in combination. The proliferating antigen Ki-67 and p53 protein expression were analysed by immunohistochemistry (IHC) performed on formalin-fixed paraffin-embedded tumour material. The p53 protein was expressed in 22 tumours (46%) while 26 (54%) were negative. Immunoreactivity of the Ki-67 antigen was evaluated by scoring and interactive image analyses (the proliferating cell index, PCI, and proliferating cell area, PCA, were calculated). All three variables correlated with survival time but only PCA and p53 protein expression had independent prognostic value. The expression of extracellular matrix (ECM) proteins and adhesion molecules was studied by IHC performed on frozen sections from 10 pancreatic carcinomas. Normal pancreas tissue served as control material. In contrast to the normal pancreas, the basement membrane in carcinomas was discontinuous as demonstrated by type IV collagen and laminin. These two ECM proteins, together with tenascin and vitronectin, were present in cancer cell areas of the stroma. Corresponding integrin receptors (a2, a3, a~) were expressed on cancer cells, thus providing possibilities for interactions and increased capacity for local invasiveness.
27.	Linder, Tomas (författare) Light Scattering in Fiber-based Materials : a foundation for characterization of structural properties 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Deeper knowledge of light propagation in fiber-based materials is fundamental in order to understand their optical appearance as well as for industrial applications. Light scattering measurements are appropriate in handling dynamic industrial environments and can provide information regarding structural properties. In general, on-line property measurements are best utilized by establishing an understanding of the underlying physics and using that knowledge in an optimal way to determine the parameters or properties sought after. Light scattering is affected by numerous parameters such as size, shape, concentration and refractive index of the scattering particles as well as the waveleng th of the incident source. In addition, anisotropic light diffusion in media which have a directional-dependency, such as structured fiber-based materials, are neither well understood nor well investigated.By approximating cellulose fibers as infinitely long, straigth cylinders it is possible to use an analytical solution to Maxwell’s equations to describe the scattering characteristics such as phase functions and scattering efficiency. This makes it possible to utilize both the wave nature of light and structural properties of the fiber network when modelling multiple light scattering. The developed model solves the radiative transfer equation numerically using theMonte Carlo method resulting in a description of multiple scattering in a sphere-cylinder media.The results show that scattering media consisting of infinite long, straigth, homogeneous or hollow cylinders scatter light very differently as compared with a media consisting of spherical particles. Both scattered intensity and the degree of depolarization are affected by a strong forward scattering behavior observed for cylindrical particles. This strong forward scattering behavior was also found to enhance lateral scattering in paper, and therefore predicts a larger extent of lateral light scattering than models using rotationally invariant single scattering phase functions. A strong relationship between anisotropic diffusion and to degree of in-plane fiber orientation was also observed using both measurements and simulations. In conclusion, it was found that the approximation of cellulose fibers as infinitely long, straigth cylinders is reasonable when modelling scattering in paper. The findings indicate that parameters such as geometrical properties, particle composition, fiber orientation and fiber orientation variations can be measured by monitoring scattered light intensity. The obtained knowledge provides a base for further development of on-line sensing techniques that meet industrial requirements. Since the theory is general, it is likewise relevant and applicable to other areas of material science where imaging or remote sensing techniques are of interest.
28.	Omerovic, Elmir, et al. (författare) Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years 2024 Ingår i: Cardiovascular Revascularization Medicine. - : Elsevier. - 1553-8389 .- 1878-0938. Tidskriftsartikel (refereegranskat)abstract BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years.METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here.RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups.CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin.REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.
29.	Reizenstein, Johan A., et al. (författare) Impact of age at diagnosis on prognosis and treatment in laryngeal cancer 2010 Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 32:8, s. 1062-1068 Tidskriftsartikel (refereegranskat)abstract BACKGROUND.: The aims of this study were to analyze how age affects treatment and treatment outcome, and to determine whether tumor characteristics differ between different age groups with laryngeal cancer. METHODS.: Patients with laryngeal cancer during 1978-2004 in the Uppsala-Orebro region in Sweden were retrospectively studied. RESULTS.: There were no significant differences in the 945 cases between age groups concerning major patient and tumor characteristics, such as male/female ratio, distribution of glottic/supraglottic tumors, stage, or site of recurrence. Overall survival (OS) and disease-specific survival (DSS) were worse among the oldest, although a significant proportion was cured. Relapse risk was lower among the oldest (12%) compared with the youngest (23%). The risk of never becoming tumor-free was 25% among the oldest and 7% in the youngest. Among the most elderly, only 1 late recurrence occurred. CONCLUSION.: Elderly patients with laryngeal carcinoma cope well with treatment. Undertreatment may determine outcome more than age. The oldest group should be followed for a minimum of 2 years.
30.	Reizenstein, Johan A, et al. (författare) Time trends in T3 to T4 laryngeal cancer : a population-based long-term analysis. 2014 Ingår i: Head and Neck. - : Wiley. - 1043-3074 .- 1097-0347. ; 36:12 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: A decline in laryngectomies and survival in laryngeal cancer has been reported, especially among patients with advanced tumors.METHODS: Of 1058 patients with laryngeal cancer diagnosed from 1978 to 2007 in the Uppsala-Örebro region in Sweden, 263 T3 to T4 tumors treated with curative intent were studied retrospectively. Two time periods were defined, 1978 to 1992 and 1993 to 2007.RESULTS: Glottic tumors decreased constituting 68.6% of cases in 1978 to 1992 and 47.9% in 1993 to 2007. Laryngectomies were performed in 38.8% and 34.5% in the corresponding time periods. The use of laryngectomy was not strongly prognostic. A decline in overall survival (OS) over time could only be identified for the first year of follow-up. Chemotherapy was only used in a minority of cases.CONCLUSION: The marked decrease of glottic site may mark a shift in etiology. Laryngectomy was not strongly associated with improved survival. The absence of improved survival calls for intensified research.
31.	Soderlund, Claes, et al. (författare) Nitinol versus steel partially covered self-expandable metal stent for malignant distal biliary obstruction: a randomized trial. 2014 Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 46:11, s. 941-948 Tidskriftsartikel (refereegranskat)abstract Covered nitinol alloy self-expandable metal stents (SEMSs) have been developed to overcome the shortcomings of steel SEMS in patients with malignant biliary obstruction. In a randomized, multicenter trial, we compared stent patency, patient survival, and adverse events in patients with partly covered stents made from steel or nitinol.
32.	Sparv, David, et al. (författare) The Analgesic Effect of Oxygen in Suspected Acute Myocardial Infarction : A Substudy of the DETO2X-AMI Trial 2018 Ingår i: JACC: Cardiovascular Interventions. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 39, s. 546-546 Tidskriftsartikel (refereegranskat)abstract Objectives: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI. Background: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain. Methods: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported. Results: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74). Conclusions: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose.
33.	Stone, Vicki, et al. (författare) The Essential Elements of a Risk Governance Framework for Current and Future Nanotechnologies 2018 Ingår i: Risk Analysis. - : Wiley. - 0272-4332 .- 1539-6924. ; 38:7, s. 1321-1331 Tidskriftsartikel (refereegranskat)abstract Societies worldwide are investing considerable resources into the safe development and use of nanomaterials. Although each of these protective efforts is crucial for governing the risks of nanomaterials, they are insufficient in isolation. What is missing is a more integrative governance approach that goes beyond legislation. Development of this approach must be evidence based and involve key stakeholders to ensure acceptance by end users. The challenge is to develop a framework that coordinates the variety of actors involved in nanotechnology and civil society to facilitate consideration of the complex issues that occur in this rapidly evolving research and development area. Here, we propose three sets of essential elements required to generate an effective risk governance framework for nanomaterials. (1) Advanced tools to facilitate risk-based decision making, including an assessment of the needs of users regarding risk assessment, mitigation, and transfer. (2) An integrated model of predicted human behavior and decision making concerning nanomaterial risks. (3) Legal and other (nano-specific and general) regulatory requirements to ensure compliance and to stimulate proactive approaches to safety. The implementation of such an approach should facilitate and motivate good practice for the various stakeholders to allow the safe and sustainable future development of nanotechnology.
34.	Sundelin, Håkan, et al. (författare) Business case for electric road 2018 Konferensbidrag (refereegranskat)abstract Electrified roads have the potential to reduce carbon dioxide emissions from the transport sector. Where long-distance heavy traffic is concerned, there is actually no cheaper alternative which is equally energy-efficient, has such low carbon dioxide emissions and for which the energy supply is assured in Sweden and the rest of Europe. Many questions nevertheless remain.In this preliminary study we have focussed on the business ecosystem likely to be built up alongside an electrified road. This has been done by means of interviewing interested parties and a thorough review of previous publications. On the basis of this background information, a computation model has been developed to be able to analyse the influence of various parameters. The stretch of 120 kilometre long road between Gävle and Borlänge has been used as a case study but an attempt to find other applicable stretches has also been undertaken. The model has a solid footing with the parties involved in the project and with people who have good insight into financial computations previously undertaken in relation to electrified roads.The computation model that has been developed is primarily thought of as a model for overall surpluses or deficits for all stakeholders in the business ecosystem. It is not, therefore, a complete socio-economic model, which would include considerably more consequences for society at large, such as the influence on local and national businesses, increased employment and so forth. The model has been developed on the assumption that all prices and values are given for a point in time when the solution is in an ’early commercialisation phase’.In comparison with diesel routes, it generally applies for electrified roads that every kilometre of road and every vehicle adds extra costs and that every kilometre driven creates savings. Thus for an electrified road system to be profitable, the stretch of electrified road must comprise a significant percentage of the overall distance driven by a truck. Nor must the stretch of road be too short, for then too much time is spent loading/unloading and too few kilometres (where the savings occur) are driven. Following familiarisation with various scenarios, a coherent, highly qualitative judgment, based on the electrified road computation model, would suggest that the suitable characteristics for such roads would be:A distance of at least twenty kilometresAnnual average daily traffic (AADT) for electrified road trucks should be around two times as many as the number of electrified kilometresThe electrified stretch should comprise 60% percent or more of the trucks’ overall distance driven each year.For the case of Gävle-Borlänge (120 km), it appears that the stretch will be able to pay for itself, for example, when 190 electrified trucks complete the stretch an average of 4 times per day throughout the year (back and forth twice a day 365 days a year), amounting to 92% of the vehicles’ overall distance being driven on electrified road.
35.	Sundelin, Håkan, et al. (författare) Förstudie av affärsekosystem för elvägar 2017 Rapport (övrigt vetenskapligt/konstnärligt)abstract Elvägar har potential att minska koldioxidutsläppen från transportsektorn. För långväga tungtrafik finns egentligen inga rimliga alternativ som både är energieffektiva, har lågtkoldioxidutsläpp och där energiförsörjningen är säkrad såväl i Sverige som i övriga Europa,men det återstår ännu många frågor.I denna förstudie har vi fokuserat på det affärsekosystem som kommer att byggas upp kringen elväg. Detta har gjorts genom intressentintervjuer och en grundlig genomgång av tidigarepublikationer. Utifrån denna bakgrundsinformation har en kalkyl skapats för att kunnaanalysera olika parametrars påverkan. Sträckan Gävle-Borlänge har använts som fallstudie,men ett första försök att finna andra lämpliga sträckor har även genomförts. Kalkylen harförankrats med projektets parter och personer med god insikt i tidigare genomfördaekonomiska kalkyler av elvägar.För att undersöka förutsättningar för ett framtida samarbete har projektet fört dialog medEU projektet FABRIC, organisationerna CEDR och ERTRAC, samt även amerikanskaintressenter. I de fall då det inneburit deltagande på konferenser så har kunskapen från dessaförmedlats genom nyhetsbrevet OMEV.Den kalkyl som skapats är i första hand tänkt som en kalkyl över totalt över- eller underskottför alla inblandade aktörer i affärsekosystemet. Det är alltså inte en komplettsamhällsekonomisk kalkyl som skulle inkludera betydligt fler konsekvenser för samhället istort, såsom påverkan på lokalt och nationellt näringsliv, ökad sysselsättning etc. Kalkylen ärgjord med antagandet att alla priser och värden anges för en punkt i tiden då lösningenbefinner sig i en ”tidig kommersialiseringsfas”.För elvägar i jämförelse med dieselvägar gäller generellt att varje vägkilometer och varjefordon skapar extra kostnader, och varje körd kilometer skapar besparingar. Därför vill manför lönsamma elvägssystem att sträckan på elväg utgör en avsevärd andel av lastbilarnastotala körda distans. Dock får sträckan inte vara för kort för då ägnas för mycket tid åtlastning och för få kilometrar (där besparingen sker) blir körda. En samlad och i hög gradkvalitativ bedömning efter att ha bekantat sig med olika scenarier, baserade påelvägskalkylen, är att lämpliga egenskaper för öppna vägsträckor är:• Minst ett par mils distans,• Årsdygnstrafik (ÅDT) för elvägslastbilar bör, i bägge riktningarna, vara ungefärdubbelt så många som sträckans antal kilometer i en riktning.• Elsträckan utgör en avsevärd andel av lastbilarnas totala körda distans varje år,åtminstone 40 %, och gärna en bit över 60 %.Ingående värden i kalkylen baseras på en kartläggning av tidigare genomfördakostnadsanalyser. Med hjälp av experter har vi sedan valt en sannolik nivå. Andelen (60 %)av den totala sträckan som elektrifieras baseras på preliminära resultat av en analys avsträckan Gävle-Borlänge från forskningsprojektet ERSET.Slutna elvägsystem har en del fördelar i termer av att de har förmodat färrediffusionsbarriärer. Det krävs dock stora volymer för att nå lönsamhet. För områden som har stora volymer kan det dock fungera enligt den här modellen. Tänkbara fall skulle kunna varahamnar, gruvor och andra typer av storskaliga industriskyttlar.I ett slutet system längs en 30 km lång sträcka med 50 lastbilar behöver varje lastbil körafram och tillbaka 8 gånger per dag 365 dagar om året för att nå break-even. Vidmedelhastigheten 50 km/h blir det 9,6 timmar – exklusive på och avlastning. Om vi antar attvarje på- respektive avlastning tar 15 minuter tillkommer 4 timmar. En framtida fråga är dåvilka produktionsanläggningar som kan sysselsätta 50 lastbilar 13,5 timmar om dagen 365dagar om året.För fallet Gävle-Borlänge framgår det att sträckan kan betala sig exempelvis då 190elvägslastbilar passerar sträckan i snitt 4 gånger varje dag hela året (t.ex. två gånger fram ochtillbaka 365 gånger per år), vilket utgör 92 % elvägsandel av fordonets totala distans.Sträckan Göteborg – Stockholm har diskuterats i flertalet rapporter och analysen visar attden kan bli lönsam. Det krävs dock en avsevärd investering, men en storskalig utbyggnad ärsamtidigt det scenario som kräver lägst andel elvägsfordon. ÅDT för tunga lastbilar påsträckan varierar längs sträckan mellan 1000 och 2000. Analysen visar att elvägssystemetskulle betala av sig om 700 elvägslastbilar trafikerade sträckan en gång varje dag året omvilket ger en elvägslastbils-ÅDT på 854, d.v.s. mellan 43 % och 86 % av totala flödet.
36.	Triebel, Rudolph, et al. (författare) SPENCER : A Socially Aware Service Robot for Passenger Guidance and Help in Busy Airports 2016 Ingår i: Field and Service Robotics. - Cham : Springer. - 9783319277028 - 9783319277004 ; , s. 607-622 Konferensbidrag (refereegranskat)abstract We present an ample description of a socially compliant mobile robotic platform, which is developed in the EU-funded project SPENCER. The purpose of this robot is to assist, inform and guide passengers in large and busy airports. One particular aim is to bring travellers of connecting flights conveniently and efficiently from their arrival gate to the passport control. The uniqueness of the project stems from the strong demand of service robots for this application with a large potential impact for the aviation industry on one side, and on the other side from the scientific advancements in social robotics, brought forward and achieved in SPENCER. The main contributions of SPENCER are novel methods to perceive, learn, and model human social behavior and to use this knowledge to plan appropriate actions in real-time for mobile platforms. In this paper, we describe how the project advances the fields of detection and tracking of individuals and groups, recognition of human social relations and activities, normative human behavior learning, socially-aware task and motion planning, learning socially annotated maps, and conducting empirical experiments to assess socio-psychological effects of normative robot behaviors.
37.	Venetsanos, Dimitrios, et al. (författare) Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention : A subgroup analysis of the VALIDATE-SWEDEHEART trial 2019 Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:6, s. 502-509 Tidskriftsartikel (refereegranskat)abstract AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.
38.	Völz, Sebastian, et al. (författare) Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management : A prespecified subgroup analysis from VALIDATE-SWEDEHEART 2019 Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:6, s. 510-519 Tidskriftsartikel (refereegranskat)abstract Aims: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin.Methods and results: A total of 6006 patients with acute coronary syndrome planned for percutaneous coronary intervention were randomised to either bivalirudin or unfractionated heparin. Arterial access was left to the operator discretion. Overall, 90.5% of patients underwent transradial access and 9.5% transfemoral access. Baseline risk was higher in transfemoral access. The unadjusted hazard ratio for the primary outcome was lower with transradial access (hazard ratio 0.53, 95% confidence interval 0.43-0.67, p<0.001) and remained lower after multivariable adjustment (hazard ratio 0.56, 95% confidence interval 0.52-0.84, p<0.001). Transradial access was associated with lower risk of death (hazard ratio 0.41, 95% confidence interval 0.28-0.60, p<0.001) and major bleeding (hazard ratio 0.57, 95% confidence interval 0.44-0.75, p<0.001). There was no interaction between treatment with bivalirudin and access site for the primary endpoint (p=0.976) or major bleeding (p=0.801).Conclusions: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.
39.	Völz, Sebastian, et al. (författare) Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance 2020 Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 75:22, s. 2785-2799 Tidskriftsartikel (refereegranskat)abstract Background: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris. Objectives: The purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI. Methods: Data was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching. Results: In total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697). Conclusions: In this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris.
40.	Wang, Xin, et al. (författare) The proteasome deubiquitinase inhibitor VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells 2016 Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6, s. 1-14 Tidskriftsartikel (refereegranskat)abstract Inhibition of deubiquitinase (DUB) activity is a promising strategy for cancer therapy. VLX1570 is an inhibitor of proteasome DUB activity currently in clinical trials for relapsed multiple myeloma. Here we show that VLX1570 binds to and inhibits the activity of ubiquitin-specific protease-14 (USP14) in vitro, with comparatively weaker inhibitory activity towards UCHL5 (ubiquitin-C-terminal hydrolase-5). Exposure of multiple myeloma cells to VLX1570 resulted in thermostabilization of USP14 at therapeutically relevant concentrations. Transient knockdown of USP14 or UCHL5 expression by electroporation of siRNA reduced the viability of multiple myeloma cells. Treatment of multiple myeloma cells with VLX1570 induced the accumulation of proteasome-bound high molecular weight polyubiquitin conjugates and an apoptotic response. Sensitivity to VLX1570 was moderately affected by altered drug uptake, but was unaffected by overexpression of BCL2-family proteins or inhibitors of caspase activity. Finally, treatment with VLX1570 was found to lead to extended survival in xenograft models of multiple myeloma. Our findings demonstrate promising antiproliferative activity of VLX1570 in multiple myeloma, primarily associated with inhibition of USP14 activity.
41.	Bravo, L, et al. (författare) 2021 swepub:Mat__t
42.	Tabiri, S, et al. (författare) 2021 swepub:Mat__t

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