| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 7. |
- Mohammad, M. A., et al.
(författare)
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Intravenous beta-blocker therapy in ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention is not associated with benefit regarding short-term mortality: a Swedish nationwide observational study
- 2017
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Ingår i: Eurointervention. - : Europa Digital & Publishing. - 1774-024X .- 1969-6213. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Our aim was to investigate the impact of intravenous (IV) beta-blocker therapy on short-term mortality and other in-hospital events in patients with ST-segment elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PCI). Methods and results: Using the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we identified all patients with STEMI undergoing PCI between 2006 and 2013. Patients with cardiogenic shock and cardiac arrest at presentation were excluded. The primary endpoint was mortality within 30 days. Secondary endpoints were in-hospital events (mortality, cardiogenic shock and left ventricular ejection fraction [LVEF] <40% at discharge). We adjusted for confounders with a multivariable model and propensity score matching. Out of 16,909 patients, 2,876 (17.0%) were treated with an IV beta-blocker. After adjusting for confounders, the IV beta-blocker group had higher 30-day all-cause mortality (HR: 1.44, 95% CI: 1.14-1.83), more in-hospital cardiogenic shock (OR: 1.53, 95% CI: 1.09-2.16) and were more often discharged with an LVEF <40% (OR: 1.70, 95% CI: 1.51-1.92). Conclusions: In this large nationwide observational study, the use of IV beta-blockers in patients with STEMI treated with primary PCI was associated with higher short-term mortality, lower LVEF at discharge, as well as a higher risk of in-hospital cardiogenic shock.
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| 13. |
- Boldrup, Linda, et al.
(författare)
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Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:12, s. 19389-19402
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Tidskriftsartikel (refereegranskat)abstract
- Due to the high frequency of loco-regional recurrences, which could be explained by changes in the field surrounding the tumor, patients with squamous cell carcinoma of head and neck show poor survival. Here we identified a total of 554 genes as dysregulated in clinically tumor free tongue tissue in patients with tongue tumors when compared to healthy control tongue tissue. Among the top dysregulated genes when comparing control and tumor free tissue were those involved in apoptosis (CIDEC, MUC1, ZBTB16, PRNP, ECT2), immune response (IFI27) and differentiation (KRT36). Data suggest that these are important findings which can aid in earlier diagnosis of tumor development, a relapse or a novel squamous cell carcinoma of the tongue, in the absence of histological signs of a tumor.
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| 15. |
- Daniel, M., et al.
(författare)
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Prevalence of Anxiety and Depression Symptoms in Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries
- 2018
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 131:9, s. 1118-1124
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial infarction with non-obstructive coronary arteries is a working diagnosis for several heart disorders. Previous studies on anxiety and depression in patients with myocardial infarction with non-obstructive coronary arteries are lacking. Our aim was to investigate the prevalence of anxiety and depression among patients with myocardial infarction with non-obstructive coronary arteries. METHODS: We included 99 patients with myocardial infarction with non-obstructive coronary arteries together with age- and sex-matched control groups who completed the Beck Depression Inventory and the Hospital Anxiety and Depression Scale (HADS) 3 months after the acute event. RESULTS: Using the Beck Depression Inventory, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (35%) was higher than in healthy controls (9%; P = .006) and similar to that of patients with coronary heart disease (30%; P = .954). Using the HADS anxiety subscale, we found that the prevalence of anxiety in patients with myocardial infarction with non-obstructive coronary arteries (27%) was higher than in healthy controls (9%; P = .002) and similar to that of patients with coronary heart disease (21%; P = .409). Using the HADS depression subscale, we found that the prevalence of depression in patients with myocardial infarction with non-obstructive coronary arteries (17%) was higher than in healthy controls (4%; P = .003) and similar to that of patients with coronary heart disease (13%; P = .466). Patients with myocardial infarction with non-obstructive coronary arteries and takotsubo syndrome scored higher on the HADS anxiety subscale than those without (P = .028). CONCLUSIONS: This is the first study on the mental health of patients with myocardial infarction with non obstructive coronary arteries to show that prevalence rates of anxiety and depression are similar to those in patients with coronary heart disease. (C) 2018 Elsevier Inc. All rights reserved.
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| 24. |
- Ekenbäck, C, et al.
(författare)
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Takotsubo twins
- 2019
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Ingår i: BMJ case reports. - : BMJ. - 1757-790X. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Takotsubo syndrome is an intriguing condition of often stress induced reversible cardiac dysfunction mimicking myocardial infarction, but without explanatory coronary obstructions. The pathogenesis of the syndrome is not yet fully understood, though altered sympathetic regulation or response to cardiac sympathetic stimuli is likely to be involved. We present a unique and clinically detailed report of identical twin sisters, who both developed Takotsubo syndrome in association to mental stress shortly after menopause, also covering a potential relapse of disease in one of the twins, supporting the theory of a genetic contribution to the development of the syndrome proposed by previous case reports and small genetic studies.
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| 26. |
- Gu, Xiaolian, 1976-, et al.
(författare)
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Copy number variation : A prognostic marker for young patients with squamous cell carcinoma of the oral tongue
- 2019
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 48:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Background The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment. Materials and methods To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (<= 40 years) and five elderly patients (>= 50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes. Results In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044). Conclusions Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.
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| 27. |
- Gu, Xiaolian, et al.
(författare)
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Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.
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| 28. |
- Gu, Xiaolian, 1976-, et al.
(författare)
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High immune cytolytic activity in tumor-free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue
- 2019
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Ingår i: The journal of pathology. Clinical research. - : John Wiley & Sons. - 2056-4538. ; 5:4, s. 240-247
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Tidskriftsartikel (refereegranskat)abstract
- Immune cells and cytolytic activity within the tumor microenvironment are being intensively studied. Through transcriptome profiling, immune cell enumeration using the xCell tool and cytolytic activity quantification according to granzyme A (GZMA) and perforin (PRF1) mRNA levels, we investigated immunoreactivity in tumor and/or tumor‐free tongue tissue samples from 31 patients with squamous cell carcinoma of the oral tongue and 14 healthy individuals (control tongue tissues). We found significantly altered immune cell compositions (p < 0.001) and elevated cytolytic activity (p < 0.001) in tumor compared to tumor‐free samples, and altered infiltration of a subset of immune cells (e.g. CD8+ T cells, p < 0.01) as well as increased cytolytic activity (p < 0.001) in tumor‐free compared to control samples. Controlling for patient age at diagnosis and tumor stage, Cox regression analysis showed that high cytolytic activity in tumor‐free samples associated with improved disease‐free survival (hazard ratio= 4.20, 95% CI = 1.09–16.20, p = 0.037). However, the degree of cytolytic activity in tumor samples did not provide prognostic information. Taken together, our results show the presence of cancer‐related immune responses in clinically tumor‐free tongue in patients with squamous cell carcinoma of the oral tongue. Measuring cytolytic activity in tumor‐free tongue samples contralateral to tumor might thus be an effective approach to predict clinical outcome.
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| 33. |
- Lundwall, K, et al.
(författare)
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Paricalcitol, Microvascular and Endothelial Function in Non-Diabetic Chronic Kidney Disease: A Randomized Trial
- 2015
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 42:4, s. 265-273
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Vitamin D deficiency, sympathetic activation and endothelial dysfunction are associated with increased cardiovascular risk in patients with chronic kidney disease (CKD). Studies have so far failed to establish the role of vitamin D and vitamin D receptor activator (VDRA) treatment in moderate CKD. This trial was designed to assess whether VDRA treatment can ameliorate sympathetic activation and macro- and microvascular dysfunction in non-diabetic patients with moderate CKD. <b><i>Methods:</i></b> We conducted a randomized controlled double-blind trial using placebo, 1 or 2 μg of paricalcitol, a VDRA, for 3 months. We assessed muscle sympathetic nerve activity (MSNA) by microneurography, pulse wave velocity (PWV) by tonometry, flow mediated vasodilatation (FMD) by brachial ultrasound, skin microcirculation assessed by iontophoresis and capillary blood velocity (CBV) by videophotometric capillaroscopy. <b><i>Results:</i></b> Thirty-six patients with a mean age of 65 years and mean estimated glomerular filtration rate of 40 ml/min/1.73 m<sup>2</sup> were included. We found a significant decline in endothelial function after 3 months, except in the group receiving 2 μg of paricalcitol. The higher dose (2 μg) seemed to attenuate the decline in microvascular endothelial function, assessed by iontophoresis of acetylcholine (p = 0.06 for all groups, p = 0.65 for the 2 μg group) and for FMD (p = 0.006 for all groups, p = 0.54 for the 2 μg group). We found a borderline significance (p = 0.05) for improved CBV in the treated groups. We found no significant changes between treatments in MSNA, PWV or albuminuria. <b><i>Conclusions:</i></b> Endothelial function declined significantly over 3 months in patients with moderate CKD, and this decline could be ameliorated by VDRA treatment (NCT01204528).
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| 37. |
- Petchey, Owen L., et al.
(författare)
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The ecological forecast horizon, and examples of its uses and determinants
- 2015
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 18:7, s. 597-611
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Tidskriftsartikel (refereegranskat)abstract
- Forecasts of ecological dynamics in changing environments are increasingly important, and are available for a plethora of variables, such as species abundance and distribution, community structure and ecosystem processes. There is, however, a general absence of knowledge about how far into the future, or other dimensions (space, temperature, phylogenetic distance), useful ecological forecasts can be made, and about how features of ecological systems relate to these distances. The ecological forecast horizon is the dimensional distance for which useful forecasts can be made. Five case studies illustrate the influence of various sources of uncertainty (e.g. parameter uncertainty, environmental variation, demographic stochasticity and evolution), level of ecological organisation (e.g. population or community), and organismal properties (e.g. body size or number of trophic links) on temporal, spatial and phylogenetic forecast horizons. Insights from these case studies demonstrate that the ecological forecast horizon is a flexible and powerful tool for researching and communicating ecological predictability. It also has potential for motivating and guiding agenda setting for ecological forecasting research and development.
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| 39. |
- Sgaramella, Nicola, et al.
(författare)
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Ethnicity based variation in expression of E-cadherin in patients with squamous cell carcinoma of the oral tongue
- 2018
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 16:5, s. 6603-6607
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Tidskriftsartikel (refereegranskat)abstract
- The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, -catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.
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| 40. |
- Sgaramella, Nicola, et al.
(författare)
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Searching for new targets and treatments in the battle against squamous cell carcinoma of the head and neck, with specific focus on tumours of the tongue
- 2018
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Ingår i: Current Topics in Medicinal Chemistry. - : Bentham Science Publishers. - 1568-0266 .- 1873-4294. ; 18:3, s. 214-218
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Forskningsöversikt (refereegranskat)abstract
- Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of tumours not only concerning the site of origin but also regarding aetiology. The 5-year survival for the whole group of SCCHN tumours has not significantly improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N status, gains and losses of specific chromosomes are the only factors shown to be independent prognostic markers for these tumours. Worldwide, an increasing number of people ≤ 40 years are seen being affected by tongue SCC, the most common tumour within the SCCHN group. Even without any clinical signs of metastasis, up to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In this mini review, field cancerization, tumour microenvironment, the so called EMT (epithelial mesenchymal transition) process and the role of viruses in development of SCCHN are discussed as well as potential new therapeutic targets. For the group of tongue SCC, with the increasing incidence seen in young patients and particularly women, new data with impact on prognosis and treatment are urgently needed. But as long as data from the analyses of several sub sites are presented as valid for the whole group of tumours, this vital point is missed.
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| 42. |
- Strindlund, Klas, et al.
(författare)
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Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours
- 2017
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Ingår i: Journal of Oral Pathology & Medicine. - : John Wiley & Sons. - 0904-2512 .- 1600-0714. ; 46:10, s. 967-971
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Tidskriftsartikel (refereegranskat)abstract
- Backgroundc-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. MethodsImmunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. ResultsAll 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. ConclusionsThe present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.
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| 44. |
- Volz, S, et al.
(författare)
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Reply
- 2019
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Ingår i: Journal of hypertension. - 1473-5598. ; 37:2, s. 449-451
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 45. |
- Wilms, Torben, et al.
(författare)
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No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue
- 2017
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.
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