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Ståhle, Elisabeth
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Publications (10 of 82) Show all publications
Grinberg, M., Djureinovic, D., Brunnström, H. R., Mattsson, J. S., Edlund, K., Hengstler, J. G., . . . Micke, P. (2017). Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters.. Modern Pathology, 30(7), 964-977.
Open this publication in new window or tab >>Reaching the limits of prognostication in non-small cell lung cancer: an optimized biomarker panel fails to outperform clinical parameters.
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2017 (English)In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 30, no 7, 964-977 p.Article in journal (Refereed) Published
Abstract [en]

Numerous protein biomarkers have been analyzed to improve prognostication in non-small cell lung cancer, but have not yet demonstrated sufficient value to be introduced into clinical practice. Here, we aimed to develop and validate a prognostic model for surgically resected non-small cell lung cancer. A biomarker panel was selected based on (1) prognostic association in published literature, (2) prognostic association in gene expression data sets, (3) availability of reliable antibodies, and (4) representation of diverse biological processes. The five selected proteins (MKI67, EZH2, SLC2A1, CADM1, and NKX2-1 alias TTF1) were analyzed by immunohistochemistry on tissue microarrays including tissue from 326 non-small cell lung cancer patients. One score was obtained for each tumor and each protein. The scores were combined, with or without the inclusion of clinical parameters, and the best prognostic model was defined according to the corresponding concordance index (C-index). The best-performing model was subsequently validated in an independent cohort consisting of tissue from 345 non-small cell lung cancer patients. The model based only on protein expression did not perform better compared to clinicopathological parameters, whereas combining protein expression with clinicopathological data resulted in a slightly better prognostic performance (C-index: all non-small cell lung cancer 0.63 vs 0.64; adenocarcinoma: 0.66 vs 0.70, squamous cell carcinoma: 0.57 vs 0.56). However, this modest effect did not translate into a significantly improved accuracy of survival prediction. The combination of a prognostic biomarker panel with clinicopathological parameters did not improve survival prediction in non-small cell lung cancer, questioning the potential of immunohistochemistry-based assessment of protein biomarkers for prognostication in clinical practice.Modern Pathology advance online publication, 10 March 2017; doi:10.1038/modpathol.2017.14.

National Category
Cancer and Oncology Medical Genetics
Identifiers
urn:nbn:se:uu:diva-318128 (URN)10.1038/modpathol.2017.14 (DOI)000404718100006 ()28281552 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2018-01-13Bibliographically approved
Baron, T., Orndahl, L. H., Kero, T., Sörensen, J., Bjerner, T., Hedin, E.-M., . . . Flachskampf, F. (2017). Volumetric quantification of regurgitant volume in asymptomatic severe degenerative mitral regurgitation by echocardiography and cardiac mri with independent validation of forward stroke volume by positron emission tomography. Paper presented at 66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 17-19, 2017, Washington, DC. Journal of the American College of Cardiology, 69(11 Suppl), 1973-1973.
Open this publication in new window or tab >>Volumetric quantification of regurgitant volume in asymptomatic severe degenerative mitral regurgitation by echocardiography and cardiac mri with independent validation of forward stroke volume by positron emission tomography
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2017 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 11 Suppl, 1973-1973 p.Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-321054 (URN)10.1016/S0735-1097(17)35362-7 (DOI)000397342302695 ()
Conference
66th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 17-19, 2017, Washington, DC
Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2017-05-05Bibliographically approved
Milojevic, M., Head, S. J., Parasca, C. A., Serruys, P. W., Mohr, F. W., Morice, M.-C., . . . Holmes, D. R. . (2016). Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX. Journal of the American College of Cardiology, 67(1), 42-55.
Open this publication in new window or tab >>Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX
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2016 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 1, 42-55 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI). OBJECTIVES The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients. METHODS An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths. RESULTS In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores. CONCLUSIONS During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Keyword
cardiac death, cause of death, coronary artery bypass grafting, heart failure, myocardial infarction, percutaneous coronary intervention, stroke, sudden death, SYNTAX
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-275548 (URN)10.1016/j.jacc.2015.10.043 (DOI)000367520500007 ()26764065 (PubMedID)
Available from: 2016-02-04 Created: 2016-02-04 Last updated: 2017-11-30Bibliographically approved
Baron, T., Örndahl, L. H., Kero, T., Sörensen, J., Bjerner, T., Hedin, E.-M., . . . Flachskampf, F. A. (2016). Comparison of left ventricular volumes and regurgitant volumes by echocardiography and magnetic resonance in patients with severe degenerative mitral regurgitation. Paper presented at Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY. European Heart Journal, 37, 1239-1239.
Open this publication in new window or tab >>Comparison of left ventricular volumes and regurgitant volumes by echocardiography and magnetic resonance in patients with severe degenerative mitral regurgitation
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2016 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, 1239-1239 p.Article in journal, Meeting abstract (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-313883 (URN)000383869506148 ()
Conference
Congress of the European-Society-of-Cardiology (ESC), AUG 27-31, 2016, Rome, ITALY
Available from: 2017-01-25 Created: 2017-01-25 Last updated: 2017-11-29Bibliographically approved
Thorén, E., Hellgren, L. & Ståhle, E. (2016). High incidence of atrial fibrillation after coronary surgery.. Interactive Cardiovascular and Thoracic Surgery, 22(2), 176-180.
Open this publication in new window or tab >>High incidence of atrial fibrillation after coronary surgery.
2016 (English)In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 22, no 2, 176-180 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Postoperative atrial fibrillation (POAF) affects a third of all patients after coronary artery bypass surgery (CABG), but short-term follow-up of heart rhythm after discharge has been sporadic and shown varied results. The aim of this study was to examine the incidence of post-discharge atrial fibrillation (AF) for 30 days following hospital discharge after CABG.

METHODS: A total of 67 patients, 19 (28%) with POAF during the initial hospitalization and 48 (72%) without POAF were included. Patients recorded intermittent electrocardiogram registrations three times daily, and additionally in case of arrhythmia symptoms. Presence of post-discharge AF was compared between the groups. All patients were in sinus rhythm at discharge.

RESULTS: Twenty of 67 patients (30%) were diagnosed with post-discharge AF. Overall, 35% of them were entirely asymptomatic. POAF patients had a higher incidence of post-discharge AF (11 of 19, 58%) than non-POAF patients (9 of 48, 19%), with six times the odds of developing post-discharge AF compared with non-POAF patients [odds ratio (OR) 6.0; 95% CI 1.9-19, P = 0.002]. Patients with POAF registered episodes of post-discharge AF earlier during the follow-up period (mean Day 3 after discharge, range 1-9 days) than non-POAF patients (Day 10, range 7-14 days, P < 0.001).

CONCLUSIONS: A high incidence of both symptomatic and asymptomatic AF was recorded during 30 days following hospital discharge after CABG. The incidence was highest among patients with POAF, of whom more than half experienced post-discharge AF.

Keyword
Parastomal hernia, Mesh, Surgery, Rectal cancer, Colostomy
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-269580 (URN)10.1093/icvts/ivv326 (DOI)000372420100010 ()26598007 (PubMedID)
Available from: 2015-12-17 Created: 2015-12-17 Last updated: 2017-12-01Bibliographically approved
Djureinovic, D., Hallström, B. M., Horie, M., Mattsson, J. S., La Fleur, L., Fagerberg, L., . . . Micke, P. (2016). Profiling cancer testis antigens in non-small-cell lung cancer. JCI INSIGHT, 1(10), Article ID e86837.
Open this publication in new window or tab >>Profiling cancer testis antigens in non-small-cell lung cancer
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2016 (English)In: JCI INSIGHT, ISSN 2379-3708, Vol. 1, no 10, e86837Article in journal (Refereed) Published
Abstract [en]

Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-310039 (URN)10.1172/jci.insight.86837 (DOI)000387113300012 ()27699219 (PubMedID)
Available from: 2016-12-09 Created: 2016-12-09 Last updated: 2016-12-09Bibliographically approved
Milojevic, M., Head, S. J., Parasca, C. A., Serruys, P. W., Mohr, F.-W., Morice, M.-C., . . . Holmes, D. R. (2015). Causes of Death after Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Complex Coronary Artery Disease: 5-Year follow-up of the SYNTAX trial. Paper presented at 27th Annual Symposium on Transcatheter Cardiovascular Therapeutics (TCT), OCT 11-15, 2015, San Francisco, CA. Journal of the American College of Cardiology, 66(15), B60-B60.
Open this publication in new window or tab >>Causes of Death after Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in Complex Coronary Artery Disease: 5-Year follow-up of the SYNTAX trial
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2015 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 15, B60-B60 p.Article in journal, Meeting abstract (Other academic) Published
Keyword
Coronary artery bypass grafting, DES, Survival
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-269134 (URN)000363329000128 ()
Conference
27th Annual Symposium on Transcatheter Cardiovascular Therapeutics (TCT), OCT 11-15, 2015, San Francisco, CA
Note

Meeting Abstract: TCT-164

Available from: 2015-12-28 Created: 2015-12-14 Last updated: 2017-12-01Bibliographically approved
Iqbal, J., Zhang, Y.-J., Holmes, D. R., Morice, M.-C., Mack, M. J., Kappetein, A. P., . . . Serruys, P. W. (2015). Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Follow-Up. Circulation, 131(14), 1269-1277.
Open this publication in new window or tab >>Optimal Medical Therapy Improves Clinical Outcomes in Patients Undergoing Revascularization With Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting Insights From the Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial at the 5-Year Follow-Up
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2015 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 14, 1269-1277 p.Article in journal (Refereed) Published
Abstract [en]

Background-There is a paucity of data on the use of optimal medical therapy (OMT) in patients with complex coronary artery disease undergoing revascularization with percutaneous coronary intervention or coronary artery bypass grafting (CABG) and its long-term prognostic significance. Methods and Results-The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) trial is a multicenter, randomized, clinical trial of patients (n=1800) with complex coronary disease randomized to revascularization with percutaneous coronary intervention or CABG. Detailed drug history was collected for all patients at discharge and at the 1-month, 6-month, 1-year, 3-year, and 5-year follow-ups. OMT was defined as the combination of at least 1 antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Five-year clinical outcomes were stratified by OMT and non-OMT. OMT was underused in patients treated with coronary revascularization, especially CABG. OMT was an independent predictor of survival. OMT was associated with a significant reduction in mortality (hazard ratio, 0.64; 95% confidence interval, 0.48-0.85; P=0.002) and composite end point of death/myocardial infarction/stroke (hazard ratio, 0.73; 95% confidence interval, 0.58-0.92; P=0.007) at the 5-year follow-up. The treatment effect with OMT (36% relative reduction in mortality over 5 years) was greater than the treatment effect of revascularization strategy (26% relative reduction in mortality with CABG versus percutaneous coronary intervention over 5 years). On stratified analysis, all the components of OMT were important for reducing adverse outcomes regardless of revascularization strategy. Conclusions-The use of OMT remains low in patients with complex coronary disease requiring coronary intervention with percutaneous coronary intervention and even lower in patients treated with CABG. Lack of OMT is associated with adverse clinical outcomes. Targeted strategies to improve OMT use in postrevascularization patients are warranted.

Keyword
coronary artery bypass, coronary artery disease, stents
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-252171 (URN)10.1161/CIRCULATIONAHA.114.013042 (DOI)000352275300012 ()25847979 (PubMedID)
Available from: 2015-05-06 Created: 2015-05-04 Last updated: 2017-12-04Bibliographically approved
Bourantas, C. V., Zhang, Y.-J., Garg, S., Mack, M., Dawkins, K. D., Kappetein, A. P., . . . Serruys, P. W. (2015). Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery: An Analysis of the SYNTAX Study. Catheterization and cardiovascular interventions, 85(2), 199-206.
Open this publication in new window or tab >>Prognostic Implications of Severe Coronary Calcification in Patients Undergoing Coronary Artery Bypass Surgery: An Analysis of the SYNTAX Study
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2015 (English)In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 85, no 2, 199-206 p.Article in journal (Refereed) Published
Abstract [en]

ObjectivesTo investigate the prognostic implications of the presence of severe lesion calcification in patients undergoing coronary artery bypass graft (CABG) operation. BackgroundThere is robust evidence that lesion calcification is a predictor of worse prognosis in patients undergoing percutaneous coronary intervention; however, there is limited data about the prognostic implication of lesion calcium in patients treated with CABG. MethodsWe retrospectively analyzed data from 1,545 patients who underwent CABG and were recruited in the SYNTAX study and CABG registry. Two experts reviewed the angiographic data and classified patients in two groups: those with severely calcified coronary arteries and those without severe lesion calcification. Clinical outcomes at 5-year follow-up were collected and compared in the two groups. ResultsOne out of three patients exhibited severe lesion calcification (n=588). Patients with calcified coronaries had an increased mortality at 5-year follow-up (17.1% vs. 9.9%, P<0.001) and a higher event rate of death-myocardial infarction (MI) compared with those without (19.4% vs. 13.2%, P=0.003), but there was no statistical significant difference between the two groups for major adverse cardiovascular events (MACE, 26.8% vs. 21.8%, P=0.057). In multivariate Cox regression analysis severe lesion calcification was an independent predictor of an increased all-cause mortality (hazard ratio: 1.39, 95% confidence interval: 1.02-1.89; P=0.037) but it was not an independent predictor of the combined end-points death-MI or MACE. ConclusionsSevere lesion calcification is associated with an increased mortality in patients undergoing CABG, but it is not an independent predictor of death-MI or MACE. This paradox can be attributed to the fact that CABG allows perfusion of the healthy coronaries bypassing the diseased arteries and thus it minimizes the risk of coronary events due to progressive atherosclerosis. (c) 2014 Wiley Periodicals, Inc.

Keyword
clinical outcomes, revascularization, coronary artery disease
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-246348 (URN)10.1002/ccd.25545 (DOI)000348505000007 ()24824456 (PubMedID)
Available from: 2015-03-10 Created: 2015-03-05 Last updated: 2017-12-04Bibliographically approved
Djureinovic, D., Hallström, B., Mattsson, J. S., La Fleur, L., Botling, J., Fagerberg, L., . . . Micke, P. (2015). The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens. Journal of Thoracic Oncology, 10(9), S256-S256.
Open this publication in new window or tab >>The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens
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2015 (English)In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, S256-S256 p.Article in journal, Meeting abstract (Other academic) Published
Keyword
Cancer testis antigens, lung cancer, RNA sequencing, immunohistochemistry
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-298969 (URN)000370365100450 ()
Available from: 2016-07-13 Created: 2016-07-12 Last updated: 2017-11-28Bibliographically approved
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