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  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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  • Ovadia, C., et al. (författare)
  • Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses
  • 2019
  • Ingår i: The Lancet. - : Elsevier BV. - 0140-6736. ; 393:10174, s. 899-909
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. Methods We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. Findings We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0.83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0.32%) of 163 947 control pregnancies (odds ratio [OR] 1.46 [95% CI 0.73-2.89]; I-2 = 59.8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0.83 [95% CI 0.74-0.92]), but not alanine aminotransferase (ROC AUC 0.46 [0.35-0.57]). For singleton pregnancies, the prevalence of stillbirth was three (0.13%; 95% CI 0.02-0.38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 mu mol/L versus four (0.28%; 0.08-0.72) of 1412 cases with total bile acids of 40-99 mu mol/L (hazard ratio [HR] 2.35 [95% CI 0.52-10.50]; p=0.26), and versus 18 (3.44%; 2.05-5.37) of 524 cases for bile acids of 100 mu mol/L or more (HR 30.50 [8.83-105.30]; p<0.0001). Interpretation The risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 mu mol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery. Funding Tommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust. Copyright (c) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • van de Sande-Bruinsma, Nienke, et al. (författare)
  • Antimicrobial drug use and resistance in Europe
  • 2008
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 14:11, s. 1722-30
  • Tidskriftsartikel (refereegranskat)abstract
    • Our study confronts the use of antimicrobial agents in ambulatory care with the resistance trends of 2 major pathogens, Streptococcus pneumoniae and Escherichia coli, in 21 European countries in 2000-2005 and explores whether the notion that antimicrobial drug use determines resistance can be supported by surveillance data at national aggregation levels. The data obtained from the European Surveillance of Antimicrobial Consumption and the European Antimicrobial Resistance Surveillance System suggest that variation of consumption coincides with the occurrence of resistance at the country level. Linear regression analysis showed that the association between antimicrobial drug use and resistance was specific and robust for 2 of 3 compound pathogen combinations, stable over time, but not sensitive enough to explain all of the observed variations. Ecologic studies based on routine surveillance data indicate a relation between use and resistance and support interventions designed to reduce antimicrobial drug consumption at a national level in Europe.
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  • Kristoffersson, Anders N., 1985-, et al. (författare)
  • Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria
  • 2020
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:12, s. 1644-1650
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.
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  • Stafoggia, M., et al. (författare)
  • Joint effect of heat and air pollution on mortality in 620 cities of 36 countries
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 181
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mor-tality is still inconsistent. Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. Methods: We used daily data on all-cause mortality, air temperature, particulate matter <= 10 mu m (PM10), PM <= 2.5 mu m (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 mu g/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 mu g/ m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 mu g/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.
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  • Ben David, O., et al. (författare)
  • Evaluation of the Mechanical Properties of PMMA Reinforced with Carbon Nanotubes - Experiments and Modeling
  • 2014
  • Ingår i: Experimental Mechanics. - : Springer Science and Business Media LLC. - 1741-2765 .- 0014-4851. ; 54:2, s. 175-186
  • Tidskriftsartikel (refereegranskat)abstract
    • The effective mechanical properties of polymethyl-methacrylate (PMMA) reinforced with carbon nanotubes (CNTs) were evaluated by means of two approaches: experiments and a micromechanical model. With various concentrations of CNTs, two specimen fabrication processes were examined: hot pressing (HP) and injection molding (IM). Experiments included a series of uniaxial tensile tests guided by an ASTM standard. Using displacement control, tests were carried out while images were taken of the gage area. The in-plane displacement fields were evaluated by means of Digital Image Correlation (DIC). A MATLAB program was then used to calculate strains, create stress-strain and strain-force curves and determine Young's modulus E, Poisson's ratio , the ultimate tensile stress and the strain to failure . In addition, simulations were carried out using a micromechanical model (High-Fidelity Generalized Method of Cells or HFGMC). A Repeating Unit Cell (RUC) consisting of one CNT and PMMA surrounding it was modeled and analyzed in order to determine the effective mechanical properties of the composite. This method allows for imperfect bonding between the phases which is controlled by two parameters. These damage parameters decrease the stress-strain response of the material. However, the increase of the volume fraction increases the composite response. These two conflicting effects appear to provide the observed decrease in Young's modulus for low volume fractions as discussed. The effects of CNT concentration, geometry and orientation, as well as the interface between the phases, were examined. It was seen from the experimental results, for HP specimens, that for low concentrations of CNTs, E initially decreases and then increases significantly as the weight fraction increases. This behavior of E was quantitatively predicted by the HFGMC model. For IM specimens, Young's modulus is nearly constant for low weight fractions of CNTs and then increases with weight fraction.
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  • Cao, Junyue, et al. (författare)
  • Principles of Systems Biology, No. 21
  • 2017
  • Ingår i: CELL SYSTEMS. - : CELL PRESS. - 2405-4712. ; 5:3, s. 158-160
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • This month: relating single cells to populations (Cao/Packer, Wu/Altschuler, O'Brien, Friedman), an excess of ribosomes (Barkai), human pathology atlas (Uhlen), signatures of feedback (Rahi), and major genome redesign (Baumgart).
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  • Cao, Junyue, et al. (författare)
  • Principles of Systems Biology, No. 21 : Editorial
  • 2017
  • Ingår i: CELL SYSTEMS. - : Elsevier BV. - 2405-4712. ; 5:3, s. 158-160
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • This month: relating single cells to populations (Cao/Packer, Wu/Altschuler, O'Brien, Friedman), an excess of ribosomes (Barkai), human pathology atlas (Uhlen), signatures of feedback (Rahi), and major genome redesign (Baumgart).
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  • DeFronzo, Ralph A., et al. (författare)
  • Type 2 diabetes mellitus
  • 2015
  • Ingår i: Nature Reviews Disease Primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes mellitus (T2DM) is an expanding global health problem, closely linked to the epidemic of obesity. Individuals with T2DM are at high risk for both microvascular complications (including retinopathy, nephropathy and neuropathy) and macrovascular complications (such as cardiovascular comorbidities), owing to hyperglycaemia and individual components of the insulin resistance (metabolic) syndrome. Environmental factors (for example, obesity, an unhealthy diet and physical inactivity) and genetic factors contribute to the multiple pathophysiological disturbances that are responsible for impaired glucose homeostasis in T2DM. Insulin resistance and impaired insulin secretion remain the core defects in T2DM, but at least six other pathophysiological abnormalities contribute to the dysregulation of glucose metabolism. The multiple pathogenetic disturbances present in T2DM dictate that multiple antidiabetic agents, used in combination, will be required to maintain normoglycaemia. The treatment must not only be effective and safe but also improve the quality of life. Several novel medications are in development, but the greatest need is for agents that enhance insulin sensitivity, halt the progressive pancreatic β-cell failure that is characteristic of T2DM and prevent or reverse the microvascular complications. For an illustrated summary of this Primer, visit: http://go.nature.com/V2eGfN.
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  • Evers, AWM, et al. (författare)
  • Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus
  • 2018
  • Ingår i: Psychotherapy and psychosomatics. - : S. Karger AG. - 1423-0348 .- 0033-3190. ; 87:4, s. 204-210
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. <b><i>Methods:</i></b> A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. <b><i>Results:</i></b> There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. <b><i>Conclusions:</i></b> The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.
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  • Furtado, R. H. M., et al. (författare)
  • Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial
  • 2022
  • Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 145:21, s. 1581-1591
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Dapagliflozin improved heart failure and kidney outcomes in patients with type 2 diabetes (T2DM) with or at high risk for atherosclerotic cardiovascular disease in the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events - Thrombolysis in Myocardial Infarction 58). Here, the aim was to analyze the efficacy and safety of dapagliflozin stratified according to baseline systolic blood pressure (SBP). METHODS: The DECLARE-TIMI 58 trial randomly assigned patients with T2DM and either previous atherosclerotic cardiovascular disease or atherosclerotic cardiovascular disease risk factors to dapagliflozin or placebo. Patients were categorized by baseline SBP levels: <120, 120 to 129, 130 to 139, 140 to 159, and >= 160 mm Hg (normal, elevated, stage 1, stage 2, and severe hypertension, respectively). Efficacy outcomes of interest were hospitalization for heart failure and a renal-specific composite outcome (sustained decrease in estimated glomerular filtration rate by 40%, progression to end-stage renal disease, or renal death). Safety outcomes included symptoms of volume depletion, lower extremity amputations, and acute kidney injury. RESULTS: The trial comprised 17160 patients; mean age, 64.0 +/- 6.8 years; 37.4% women; median duration of T2DM, 11 years; 40.6% with prevalent cardiovascular disease. Overall, dapagliflozin reduced SBP by 2.4 mm Hg (95% CI, 1.9-2.9; F<0.0001) compared with placebo at 48 months. The beneficial effects of dapagliflozin on hospitalization for heart failure and renal outcomes were consistent across all baseline SBP categories, with no evidence of modification of treatment effect (P-interactions = 5 0.28 and 0.52, respectively). Among normotensive patients, the hazard ratios were 0.66 (95% CI, 0.42-1.05) and 0.39 95% CI, 0.19-0.78), respectively, for hospitalization for heart failure and the renal-specific outcome. Events of volume depletion, amputation, and acute kidney injury did not differ with dapagliflozin overall or within any baseline SBP group. CONCLUSIONS: In patients with T2DM with or at high atherosclerotic cardiovascular disease risk, dapagliflozin reduced risk for hospitalization for heart failure and renal outcomes regardless of baseline SBP, with no difference in adverse events of interest at any level of baseline SBP. These results indicate that dapagliflozin provides cardiorenal benefits in patients with T2DM at high atherosclerotic cardiovascular disease risk independent of baseline blood pressure.
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  • Jolliffe, DA, et al. (författare)
  • Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials
  • 2020
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundA 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed.MethodsSystematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633).FindingsWe identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger’s test).InterpretationVitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.FundingNone
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  • Meyer, L, et al. (författare)
  • Thrombectomy for secondary distal, medium vessel occlusions of the posterior circulation: seeking complete reperfusion
  • 2022
  • Ingår i: Journal of neurointerventional surgery. - : BMJ. - 1759-8486 .- 1759-8478. ; 14:7, s. 654-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether to approach distal occlusions endovascularly or not in medium-sized vessels secondary to proximal large vessel occlusion stroke remains unanswered.ObjectiveTo investigates the technical feasibility and safety of thrombectomy for secondary posterior circulation distal, medium vessel occlusions (DMVO).MethodsTOPMOST (Treatment fOr Primary Medium vessel Occlusion STroke) is an international, retrospective, multicenter, observational registry of patients treated for distal cerebral artery occlusions. This study subanalysis endovascularly treated occlusions of the posterior cerebral artery in the P2 and P3 segment secondary preprocedural or periprocedural thrombus migration between January 2014 and June 2020. Technical feasibility was evaluated with the modified Thrombolysis in Cerebral Infarction (mTICI) scale. Procedural safety was assessed by the occurrence of symptomatic intracranial hemorrhage (sICH) and intervention-related serious adverse events.ResultsAmong 71 patients with secondary posterior circulation DMVO who met the inclusion criteria, occlusions were present in 80.3% (57/71) located in the P2 segment and in 19.7% (14/71) in the P3 segment. Periprocedural migration occurred in 54.9% (39/71) and preprocedural migration in 45.1% (32/71) of cases. The first reperfusion attempt led in 38% (27/71) of all cases to mTICI 3. On multivariable logistic regression analysis, increased numbers of reperfusion attempts (adjusted odds ratio (aOR)=0.39, 95% CI 0.29 to 0.88, p=0.009) and preprocedural migration (aOR=4.70, 95% CI,1.35 to 16.35, p=0.015) were significantly associated with mTICI 3. sICH occurred in 2.8% (2/71).ConclusionThrombectomy for secondary posterior circulation DMVO seems to be safe and technically feasible. Even though thrombi that have migrated preprocedurally may be easier to retract, successful reperfusion can be achieved in the majority of patients with secondary DMVO of the P2 and P3 segment.
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  • Persson, Ninni, et al. (författare)
  • Regional brain shrinkage and change in cognitive performance over two years : The bidirectional influences of the brain and cognitive reserve factors
  • 2016
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 126, s. 15-26
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.
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  • Persson, Ninni, et al. (författare)
  • Regional brain shrinkage over two years : Individual differences and effects of pro-inflammatory genetic polymorphisms
  • 2014
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 103, s. 334-348
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined regional changes in brain volume in healthy adults (N = 167, age 19–79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the Hc, CbH, In, OF, and PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants modified shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1β C-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFR C677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC, thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan.
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  • Wetmore, Stephen J., et al. (författare)
  • Challenges and Opportunities in Managing the Dizzy Older Adult
  • 2011
  • Ingår i: Otolaryngology: Head and Neck Surgery. - : Wiley. - 0194-5998 .- 1097-6817. ; 144:5, s. 651-656
  • Konferensbidrag (refereegranskat)abstract
    • Balance disorders are common in elderly people, not only resulting in distressing sensations but also leading to reduced activity levels and quality of life. It has been estimated that 30% of elderly patients experience a balance disorder. Managing these disorders is a substantial challenge for patients and their caregivers and physicians. Moreover, abnormalities in balance are associated with falls, a major cause of morbidity and mortality for elderly people. Management is complicated by the inherent difficulties in assessing the generic complaint of dizziness, as well as the likelihood of multiple, often nonvestibular causes. The authors of this mini-seminar review both vestibular and nonvestibular causes of balance disorders in elderly people, emphasizing practical therapeutic maneuvers that can be used.
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