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- Aad, G., et al.
(författare)
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- 2010
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swepub:Mat__t
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 6. |
- Ivarsson, Ylva, et al.
(författare)
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Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:7, s. 2542-2547
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Tidskriftsartikel (refereegranskat)abstract
- The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein-protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions.
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| 7. |
- Norlén, Olov, et al.
(författare)
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Bethesda III Thyroid Nodules : The Role of Ultrasound in Clinical Decision Making
- 2014
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Ingår i: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1068-9265 .- 1534-4681. ; 21:11, s. 3528-3533
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Tidskriftsartikel (refereegranskat)abstract
- Assessment for thyroid nodules includes ultrasound (US) and cytology according to the Bethesda classification. There is no firm consensus regarding clinical management for nodules classified as Bethesda III. Our aim was investigate the value of US to predict malignancy in these nodules. Patients with Bethesda III nodules who underwent thyroid surgery from July 2011 to July 2013 were included. Inclusion criteria mandated that US were available for review by two observers blinded to each other's results and histological outcome. The nodules were scrutinized with six US criteria: hypoechoic attenuation (HA), irregular margins (IM), taller than wide, microcalcifications (MC), loss of halo, and increased central vascularity. Disagreements between observers were solved by consensus. There were 141 patients (121 women) with a mean age of 55 years. Mean nodule size was 25 mm. The malignancy rate was 13 %. Interobserver ratios were moderate to very strong for all six predictors (kappa = 0.60-0.94). However, only HA, IM, and MC were predictors of malignancy by univariate analysis (all p < 0.002). Logistic regression revealed an odds ratio of malignancy versus no malignancy for HA 4.8, IM 3.3, and MC 4.0 (all p < 0.05). The positive and negative predictive value for malignancy when having one or more of these three criteria was 22 % and 98 %, respectively. HA, IM, and MC were predictors of malignancy in Bethesda III nodules. In addition, the negative predictive value for any of these three criteria was high; a nodule that lacks all of these three criteria is thus unlikely to be malignant.
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| 8. |
- Norlén, Olov, et al.
(författare)
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Long-term outcome after parathyroidectomy for lithium-induced hyperparathyroidism
- 2014
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 101:10, s. 1252-1256
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Tidskriftsartikel (refereegranskat)abstract
- Background: The accepted management of lithium-associated hyperparathyroidism (LiHPT) is open four-gland parathyroid exploration (OPTX). This approach has recently been the subject of controversy. A recent study has shown very high long-term recurrence rates after OPTX, whereas some have promoted unilateral focused parathyroidectomy as appropriate management. The aim was to evaluate long-term outcomes after surgery for LiHPT and to assess the accuracy of preoperative imaging. Methods: This was a retrospective cohort study that comprised all patients undergoing initial surgery for LiHPT between 1990 and 2013. The cumulative recurrence rate was calculated by the Kaplan-Meier method. The sensitivity and specificity of sestamibi scintigraphy and ultrasound imaging for identification of single-gland versus multigland disease was investigated using intraoperative assessment as reference. Results: Of 48 patients, 45 had OPTX and three underwent focused parathyroidectomy. Multiglandular disease was documented in 27 patients and 21 had a single adenoma. The median follow-up was 5.9 (range 0.3-22) years and 16 patients died during follow-up. The 10-year cumulative recurrence rate was 16 (95 per cent confidence interval 2 to 29) per cent. No permanent complications occurred after primary surgery for LiHPT. Twenty-four patients had at least one preoperative ultrasound or sestamibi scan. For concordant sestamibi scintigraphy and ultrasound imaging, the sensitivity and specificity for identifying single-gland versus multigland disease was five of nine and five of eight respectively. Conclusion: Surgery provided a safe and effective management option for patients with LiHPT in this series, with a long-term cure rate of well over 80 per cent.
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