| 1. |
- Bjurman, Christian, 1983, et al.
(författare)
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Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
- 2017
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Ingår i: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
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Tidskriftsartikel (refereegranskat)abstract
- Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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| 2. |
- Carlsson, Axel C., et al.
(författare)
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High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction
- 2017
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 228, s. 253-259
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Tidskriftsartikel (refereegranskat)abstract
- Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.
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| 3. |
- Elmroth, Kerstin, 1970, et al.
(författare)
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Cleavage of cellular DNA by calicheamicin γ1
- 2003
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Ingår i: DNA Repair. - 1568-7864 .- 1568-7856. ; 2:4, s. 363-374
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Tidskriftsartikel (refereegranskat)abstract
- It is assumed that the efficient antitumor activity of calicheamicin γ1 is mediated by its ability to introduce DNA double-strand breaks in cellular DNA. To test this assumption we have compared calicheamicin γ1-mediated cleavage of cellular DNA and purified plasmid DNA. Cleavage of purified plasmid DNA was not inhibited by excess tRNA or protein indicating that calicheamicin γ1 specifically targets DNA. Cleavage of plasmid DNA was not affected by incubation temperature. In contrast, cleavage of cellular DNA was 45-fold less efficient at 0°C as compared to 37° due to poor cell permeability at low temperatures. The ratio of DNA double-strand breaks (DSB) to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when calicheamicin γ1 cleaved purified plasmid DNA. DNA strand breaks introduced by calicheamicin γ1 were evenly distributed in the cell population as measured by the comet assay. Calicheamicin γ1-induced DSBs were repaired slowly but completely and resulted in high levels of H2AX phosphorylation and efficient cell cycle arrest. In addition, the DSB-repair deficient cell line Mo59J was hyper sensitive to calicheamicin γ. The data indicate that DSBs is the crucial damage after calicheamicin γ1 and that calicheamicin γ1-induced DSBs are recognized normally. The high DSB:SSB ratio, specificity for DNA and the even damage distribution makes calicheamicin γ1 a superior drug for studies of the DSB-response and emphasizes its usefulness in treatment of malignant disease.
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| 4. |
- Erlandsson, A C, et al.
(författare)
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Herpes simplex virus type 1 infection and glucocorticoid treatment regulate viral yield, glucocorticoid receptor and NF-kappaB levels.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:1, s. 165-76
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between the endocrine and immune systems has come into focus in recent years with the insight that endocrine parameters may affect susceptibility to both auto-immune and infectious diseases. Our interest in immunoendocrine regulation led us to investigate the effects of glucocorticoids on Herpes simplex virus type 1 (HSV-1) infections. Glucocorticoids used to treat inflammatory conditions are not yet recommended for HSV-1 therapy, since they have been reported to prolong viral shedding both in vivo and in vitro. Here we report that glucocorticoids did not alter the viral yield in human gingival fibroblast (HGF) cell culture when glucocorticoid treatment and viral infection occured simultaneously, but the viral yield increased when cells were treated with the glucocorticoid dexamethasone (dex) prior to viral infection. We found that viral infection in our primary cell system increased NF-kappaB levels and DNA binding. In addition, the amount of glucocorticoid receptor (GR) increased following viral infection, and HSV-1 infection as such could induce glucocorticoid-driven transcription of a reporter gene in human embryo kidney (HEK) 293 cells stably transfected with GR. Dex treatment did not affect HSV-1-induced binding of p65 to an NF-kappaB element in an electrophoretic mobility shift assay, and acyclovir was still efficient as an anti-viral drug in the presence of dex. Further studies of the observed effects of HSV-1 infection and glucocorticoid treatment on GR and NF-kappaB regulation could give insights into the immunoendocrine mechanisms important for defence and therapy against viral infections.
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| 5. |
- Hammarsten, Ola, et al.
(författare)
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Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
- 2022
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the gamma-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results: Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing gamma-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of gamma-H2AX in response to radiation. Conclusions: The combination of the CDA and the gamma-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.
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| 6. |
- Ognissanti, Damiano, et al.
(författare)
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Cardiac troponin T concentrations and patient-specific risk of myocardial infarction using the novel PALfx parameter
- 2019
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 1873-2933 .- 0009-9120. ; 66, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial infarction (MI) is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample from a patient with chest pain. There is no conventional method to estimate the risk of MI at a specific cTnT concentration. The purpose of this study was to evaluate the performance of a novel method that converts cTnT concentrations to patient-specific risks of MI. Methods: Admission cTnT measurements in 15,425 ED patients from three hospitals with a primary complaint of chest pain, with or without a clinical diagnosis of MI, were Box-Cox-transformed to normality density functions to calculate the percentage with MI among patients with a given cTnT concentration, the parametric predictive value among lookalikes (PALfx). The ability of the PALfx to generate stable risk estimates of MI was examined by bootstrapping and expressed as the coefficient of variation (CV). Results: Four age and sex-specific subgroups above or below 60 years of age with distinct cTnT distributions were identified among patients without MI. The cTnT distributions across subgroups with MI were similar, allowing us to use all admissions with MI to calculate the PALfx in the four subgroups. For instance, at a baseline cTnT concentration of 7 ng/L, a female patient < 60 years would have a 0.5% risk of MI whereas a male patient > 60 years would have a 1.9% risk of MI. To assess the stability of the PALfx method we bootstrapped smaller and smaller subsets of the 15,422 ED visits. We found that 1950 patients without MI and 50 patients with MI were sufficient to limit the variation of the PALfx with a CV of 0.8–5.4%, close to the CV using the entire dataset. The MI risk estimates were similar when data from the three hospitals were used separately to derive the PALfx equations. Conclusions: The PALfx can be used to estimate the risk of MI at patient-specific cTnT concentrations with acceptable margins of error. The patient-specific risk of disease using the PALfx could complement decision limits.
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| 7. |
- Roos, A., et al.
(författare)
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Investigations, findings, and follow-up in patients with chest pain and elevated high-sensitivity cardiac troponin T levels but no myocardial infarction
- 2017
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 232, s. 111-116
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated troponin levels, in patients without myocardial infarction (MI), are associated with increased mortality. In an observational cohort study we aimed to assess how patients with elevated high-sensitivity cardiac troponin T (hs-cTnT) levels, and no MI are investigated and followed up, compared to patients with MI. Methods: During January 1, 2011 to December 31, 2012, all patients > 25 years of age, with chest pain and elevated hs-cTnT levels or MI, at the Karolinska University Hospital were included. We calculated risk ratios (RR) with 95% confidence intervals (CI) for echocardiographies, stress tests, and follow-up, and compared medication in patients with and without MI. Results: 1848 patients with elevated hs-cTnT levels but no MI, of whom 871 (47%) had no prior heart disease, and 667 patients with MI were included. Echocardiography was performed in 609 patients (33%) without MI and 580 (87%) with MI (adjusted RR 0.42; 95% CI, 0.37-0.48). Follow-up was planned for 856 (46%) patients without MI and 611 (92%) with MI (adjusted RR 0.54; 95% CI, 0.48-0.60). Among patients without MI and no heart disease who underwent echocardiography 46 (14%) had a left ventricular ejection fraction of <= 40%, and on stress tests 27 (37%) had findings associated with ischemia. Platelet inhibitors and statins were started in 266 (25%) and 199 (17%) patients without MI, respectively, compared with 424 (93%), and 416 (86%) patients with MI. Conclusions: Patients with elevated hs-cTnT levels and no MI are rarely investigated for detection of cardiac disease or followed up, or started on cardiovascular medication that potentially could prevent future cardiovascular events and death. (C) 2017 Elsevier Ireland Ltd. All rights reserved.
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| 8. |
- Roos, A., et al.
(författare)
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Stable High-Sensitivity Cardiac Troponin T Levels and Outcomes in Patients With Chest Pain
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 70:18, s. 2226-2236
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND There is a paucity of data on the association between high-sensitivity cardiac troponin (hs-cTn) levels and outcomes in patients with chest pain but no myocardial infarction (MI), or any other condition that may lead to acutely elevated troponin levels. OBJECTIVES The authors hypothesized that any detectable high-sensitivity cardiac troponin T (hs-cTnT) level is associated with adverse outcomes. METHODS All patients (N = 22,589)> 25 years of age with chest pain and hs-cTnT analyzed concurrently in the emergency department of Karolinska University Hospital, Stockholm, Sweden from 2011 to 2014 were eligible for inclusion. After excluding all patients with acute conditions that may have affected hs-cTnT, or MI associated with the visit, or insufficient information to determine whether troponin levels were stable, Cox regression was used to estimate risks for all-cause, cardiovascular, and noncardiovascular mortality, MI, and heart failure at different levels of troponins. RESULTS A total of 19,460 patients with a mean age of 54 +/- 17 years were included. During a mean follow-up of 3.3 +/- 1.2 years, 1,349 (6.9%) patients died. Adjusted hazard ratios (with 95% confidence intervals) for all-cause mortality were 2.00 (1.66 to 2.42), 2.92 (2.38 to 3.59), 4.07 (3.28 to 5.05), 6.77 (5.22 to 8.78), and 9.68 (7.18 to 13.00) in patients with hs-cTnT levels of 5 to 9, 10 to 14, 15 to 29, 30 to 49, and >= 50 ng/l, respectively, compared with patients with hs-cTnT levels < 5 ng/l. There was a strong and graded association between all detectable levels of hs-cTnT and risk for MI, heart failure, and cardiovascular and noncardiovascular mortality. CONCLUSIONS Among patients with chest pain and stable troponin levels, any detectable level of hs-cTnT is associated with an increased risk of death and cardiovascular outcomes and should merit further attention. (C) 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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| 9. |
- von Otter, Malin, 1978, et al.
(författare)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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