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  • 1
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2003-2003
    Abstract: Abstract 2003 The prognosis of patients suffering from AML with manifestations of accompanying extramedullary leukemia (EML) including myeloid sarcoma (MS) compared to that of AML patients not exhibiting EML manifestations is still an open question as results from previous studies have been contradictory most likely due to selection bias. Here we present an analysis performed in a cohort of 2261 patients representing 〉 90% of all AML patients diagnosed and treated in Denmark during the eleven-year period January 2000 through December 2010. The goal was to investigate the prognostic impact of presence of EML at time of AML diagnosis by a retrospective population- and registry-based analysis Of these patients, 219 (9.7%) showed signs of EML at time of AML presentation. Anatomic sites of EML were: lymph nodes (3.0%), skin (2.7%), spleen (1.7%), oral (1.3%), CNS (0.4%), testes (0.2%), other sites (1.1%), and two or more anatomical sites (0.5%). In 27 cases myeloid sarcoma was not accompanied by AML in the bone marrow and, thus, presented as isolated MS. In total, 1168 of the 2261 (52 %) patients were treated with curative intention. Allogeneic stem cell transplantation (Standard allo in 105 cases, and reduced intensity conditioning (RIC) transplant in 90 cases) was conducted in a total of 195 patients (118 in CR1, 65 in CR2, and 12 during other disease stages). Overall the frequencies of allogeneic transplantations in curatively treated patients were 13.7% in patients with EML and 8.5% in patients without EML. The presence of EML at time of leukemia diagnosis had no statistical significance to probability of obtaining complete remission (CR), nor to duration of overall survival (OS) (Table 1. and Fig. 1). By contrast, well-established prognostic parameters such as presenting cytogenetic abnormalities (categorized according to revised MRC-criteria, D. Grimwade et al. Blood, 2010), age, leukocyte count, and type of leukemia (secondary vs de novo) were all found to be statistically significant to probability of attainment of (CR) and to duration of OS in uni- as well as multivariate analyses. Gender was of borderline statistical significance with respect to probability of attainment of CR and to OS (Table 1).Figure 1Years from AML diagnosisPatients with EML(n = 132)Patients without EML(n = 1007)p-value (log-rank test) = 0.51Figure 1. Years from AML diagnosis. / Patients with EML. / (n = 132). / Patients without EML. / (n = 1007). / p-value (log-rank test) = 0.51Table 1.Factors of significance to probability of attainment of CR and to overall survival (OS)Probability of CR (Logistic regression, nevaluable = 927)Probability of overall survival (Cox regression, nevaluable = 958)VariableOdds ratio (OR)95% CI of ORP valueHazard ratio95% CI of HRP valueEML––0.82––0.54Age1.061.04–1.08 〈 10−41.041.03–1.04 〈 10−4Cytogenetics2.291.63–3.21 〈 10−41.931.65–2.25 〈 10−4Male gender1.481.03–2.070.03––0.06    WBC1.0051.002–1.007 〈 10−41.0011.000–1.0020.02    Secondary2.151.47–3.14 〈 10−41.391.15–1.680.001 Additionally, patients with EML at leukemia presentation who were subjected to an allogeneic stem cell transplantation had a prognosis no different from that of AML patients not exhibiting signs of EML (Fig.2). Analyses of progression free survival are ongoing and will be presented at the meeting.Figure 2Years from AML diagnosisPatients without EML(n = 165)Patients with EML(n = 30)p-value (log-rank test) = 0.75Figure 2. Years from AML diagnosis. / Patients without EML. / (n = 165). / Patients with EML. / (n = 30). / p-value (log-rank test) = 0.75 From this analysis we conclude that presence of EML does not predict for an inferior CR-rate or for shorter survival in AML. We find no clear justification for a more aggressive therapeutic approach or performance of allogeneic stem cell transplantation in AML patients with EML. Therapeutic decisions should be guided by other prognostic parameters, e.g., age and cytogenetic aberrations which are of far greater importance than the presence of EML. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. LB-61-LB-61
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. LB-61-LB-61
    Abstract: Background: Breast cancer is the most frequently diagnosed malignancy among women and is the leading cause of cancer related death worldwide. Molecular genetic studies have revealed many subgroups of breast cancer within which the genomic alterations affecting chromosome arm 1q are considered to be an early event in breast carcinogenesis and are correlated with favorable prognosis for the patients. We have found a high percentage of concordance between the AI and MLPA assays pointing towards gain of the 1q25.3 region in breast cancer. Aims: Our main objective was to compare the sensitivity and specificity of AI and synthetic probe-based MLPA with other cytogenetic method (FISH) in breast cancer patients with or without previously confirmed alterations within 1q25.3. Methods: FISH was performed on formalin-fixed paraffin-embedded tumor material in order to verify previous findings and assess the level of genetic alterations of 1q25.3 in breast cancer. The 1q25.3 test and 1p35 reference probes labeled with different fluorochromes were utilized for analysis. Results: A total of 70 nuclei from each breast cancer case were examined and scored for the percentage of 1q25.3 alterations. The non-tumorigenic nuclei obtained from healthy individuals served as adequate cut-off for the 1q25.3-specific changes. The overall FISH results are consistent with results obtained from previous analysis in the majority of analysed cases. Furthermore, FISH resolved the level of 1q25.3 alterations in few cases that were uncertain by AI and MLPA analysis. Conclusion: This study shows that both AI and MLPA assays are able to map regions of copy number changes in the cancer genome and are in concordance with molecular cytogenetics. These three techniques proved to be an efficient tool for diagnosis of 1q25.3 alterations, however, confusing results in AI and MLPA analysis might be obtained while using non-microdissected tumor DNA as a template. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-61.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 3
    Online Resource
    Online Resource
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 4855-4855
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4855-4855
    Abstract: Myelodysplastic syndrome (MDS) is a highly heterogeneous disease. The etiology involves both environmental and genetic factors. Identification of new pathogenetic mechanisms may have important impact on the choice of treatment as well as the development of new treatment options. Familial disease gives a unique opportunity to study those mechanisms. Familial occurrence of MDS is rare and mainly associated with autosomal recessive genetic syndromes such as Fanconi anaemia, Bloom syndrome, Diamond-Blackfan syndrome and megakaryocytic thrombocytopenia. Cytogenetic abnormalities are in general seen in 50% of MDS cases. Most frequently, abnormalities involving chromosome 5 or 7 are observed, which has also been described in rare cases of familial MDS. We here present a unique family in which a father and two of his three children were diagnosed with refractory anemia (RA) with cytogenetic aberrations resulting in three different translocations involving chromosome 1q and resulting in trisomy of 1q. Trisomy 1q is often seen in sporadic MDS, but the unbalanced translocations observed in this family may originate from inherited centromere instability of chromosome 1. The genetic background for the observed centromere instability could be a DNA methylation deficiency, which we plan to investigate further.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
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  • 4
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 63, No. 6 ( 2014-06), p. 1319-1325
    Abstract: Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure–lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center’s criteria was 42.5% (95% confidence interval, 38.0%–47.0%) and 39.7% (36.2%–43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
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  • 5
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3542-3542
    Abstract: Abstract 3542 The prognosis of acute promyelocytic leukemia (APL) has improved markedly over the last two decades. Clinical trials have demonstrated excellent survival of patients receiving anthracycline-based chemotherapy in combination with all-trans-retinoid acid (ATRA). It is not clear whether the excellent survival results demonstrated in clinical trials during recent years, also do apply to unselected patients including elderly and frail patients for whom a clinical trial may not be available. In order to investigate survival and death rates in APL over the course of treatment, we conducted a retrospective analysis of survival in 105 consecutive APL-patients diagnosed in Denmark January 2000 through June 2012. Data were retrieved from the Danish National Acute Leukemia Registry which covers 95 – 100 % of all acute leukemia cases diagnosed in Denmark since January 2000 (not including children). A diagnosis of APL was confirmed in 105 (3.9 %) of 2726 adult patients (age ≥ 15 years) with acute myeloid leukemia (AML) diagnosed in Denmark during the 12½ year period. This corresponds to an incidence rate of 1.53 APL cases per million inhabitants per year. The diagnosis of APL was based upon cytogenetic analysis (performed in 96 (91 %) of cases), and/or interphase FISH (iFISH), and/or RT-PCR in a total of 100 cases. In 5 cases clinical signs and morphological changes in bone marrow were highly suggestive of APL and these cases were, thus, deemed to have APL. Median age at diagnosis of APL was 50 years (range 15 to 83 years) and median leukocyte count was 2.65 (range 0.2 to 99.0 × 109/L). In 104 patients with data available for analysis, very early death (VED, within the first week from the date of diagnostic bone marrow) occurred in 10 cases (9.6 %), and early death (ED, death within 30 day from diagnosis) occurred in 22 (21 %) cases. Death between day 30 and 5 years from diagnosis occurred in 11 cases. No deaths were seen after 5 years from diagnosis. For all patients, estimated overall survival at 10 years was 65 % (Figure 1). Patients surviving beyond day 30 from day of diagnosis (82 cases) had an excellent overall survival of greater than 80 % at 10 years (Figure 2). Survival of patients were strongly correlated with WHO-performance status whereas age over 50 years and presenting leukocyte count greater than 10 × 109/L could not be definitely associated with inferior survival (Table 1 and Figure 3). Table 1. Factors of importance to survival in unselected APL-patients Probability of overall survival (Univariate Cox Regression, nevaluable= 104) Probability of overall survival (multivariate Cox Regression, nevaluable= 101) Variable Hazard ratio 95% CI of HR P value Hazard ratio 95% CI of HR P value Age (≤50 vs. 〉 50 years) 2.17 1.07–4.42 0.03 1.44 0.67–3.09 NS WHO performance status (0–1 vs. ≥2) 5.20 2.57–10.5 〈 10−4 4.06 1.88–8.78 〈 10−4 WBC (≤10 × vs. 〉 10 × 109/L) 1.76 0.86–3.61 NS 1.62 0.79–3.33 NS From this population-based analysis we conclude that early death continues to be the predominant hazard to patients with APL. Two thirds of deaths in APL-patients do occur during the first month from diagnosis. Patients with a poor performance status at disease presentation carry a particularly dismal prognosis. For all APL-patients, every possible effort should be made to facilitate prompt diagnosis and speedy initiation of treatment with ATRA and anthracycline-based chemotherapy. When timely applied, currently available treatments are highly effective and result in cure in a high proportion of patients including elderly patients and patients with high leukocyte count at time of disease presentation. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 6
    In: Gene, Elsevier BV, Vol. 656 ( 2018-05), p. 86-94
    Type of Medium: Online Resource
    ISSN: 0378-1119
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1999
    In:  Hypertension Vol. 33, No. 3 ( 1999-03), p. 781-786
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 3 ( 1999-03), p. 781-786
    Abstract: Abstract —Insulin resistance is related to physical inactivity, which is a risk factor for cardiovascular disease and death. Moreover, blood pressure responses during the first 6 minutes of an exercise test (600 kilo/pound/meter [kpm] per min) are more predictive for cardiovascular morbidity and mortality than blood pressure at rest, which could reflect that exercise blood pressure correlates more closely to peripheral structural vascular changes than casual blood pressure. We have recently shown a correlation between insulin resistance and minimal forearm vascular resistance (MFVR) in young men recruited from the highest blood pressure percentiles during a military draft session. In the present study, we tested the hypotheses that insulin sensitivity relates to physical fitness and that blood pressure responses during an exercise test relate to peripheral structural vascular changes in these men; we also tested whether these findings were interrelated. We assessed insulin sensitivity and physical fitness in 27 young men randomly selected from the cohort having a blood pressure of 140/90 mm Hg or higher during the compulsory military draft session in Oslo. Insulin sensitivity correlated with physical fitness ( r =0.58, P =0.002). Systolic blood pressure after 6 minutes of exercise (600 kpm/min) correlated with MFVR ( r =0.46, P =0.015). MFVR and physical fitness independently explained 60% of the variation in insulin sensitivity, and MFVR independently explained 19% of the variation of systolic blood pressure after 6 minutes of exercise. In conclusion, insulin sensitivity is related to physical fitness and exercise blood pressure to structural vascular properties in these young men.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1999
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 1998
    In:  Hypertension Vol. 32, No. 5 ( 1998-11), p. 838-843
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 5 ( 1998-11), p. 838-843
    Abstract: Abstract —Insulin resistance is a part of the metabolic cardiovascular syndrome. We aimed to test the hemodynamic hypothesis of insulin resistance, which suggests that a decreased skeletal muscle blood supply with subsequent reduced nutritional flow causes insulin resistance in skeletal muscle. We assessed determinants of peripheral blood flow such as maximal forearm blood flow (MFBF), minimal forearm vascular resistance (MFVR), and whole blood viscosity (WBV) in 27 young men with borderline elevation of blood pressure. Insulin sensitivity measured as glucose disposal rate (GDR) correlated with MFBF ( r =0.55, P =0.003), MFVR ( r =−0.58, P =0.002), and WBV ( r =−0.39, P =0.046 at shear rate 201 s −1 ). There was no correlation between GDR and myocardial thickness or left ventricular mass. In a stepwise multiple regression analysis, MFVR and WBV explained 54% of the variation in GDR. The relative increase in mean arterial blood pressure during a mental stress test, as a marker of reactivity or an alert reaction, was correlated with MFVR ( r =0.56, P =0.002) and inversely with GDR ( r =−0.45, P =0.018) and MFBF ( r =−0.49, P =0.01) but not with cardiac dimensions. In a stepwise multiple regression analysis, 48% of the increase in blood pressure during a mental stress test was explained by MFVR and WBV. Fasting insulin correlated with MFVR ( r =0.41, P =0.036) and GDR ( r =−0.62, P =0.001). These data show a positive association between the appearance of peripheral structural vascular changes as quantified through a hemodynamic technique and insulin resistance in young men with borderline elevation of blood pressure. The cause-effect relationship of this finding needs further evaluations.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 1998
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  • 9
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. 3 ( 2013-09), p. 526-532
    Abstract: It is unknown whether the decline in blood pressure (BP) after renal denervation (RDN) is caused by denervation itself or concomitantly improved drug adherence. We aimed to investigate the BP lowering effect of RDN in true treatment-resistant hypertension by excluding patients with poor drug adherence. Patients with resistant hypertension (n=18) were referred for a thorough clinical and laboratory work-up. Treatment-resistant hypertension was defined as office systolic BP 〉 140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs, including a diuretic. In addition, ambulatory daytime systolic BP 〉 135 mm Hg was required after witnessed intake of antihypertensive drugs to qualify. RDN (n=6) was performed with Symplicity Catheter System. The mean office and ambulatory BPs remained unchanged at 1, 3, and 6 months in the 6 patients, whereas there was no known change in antihypertensive medication. Two patients, however, had a fall in both office and ambulatory BPs. Our findings question whether BP falls in response to RDN in patients with true treatment-resistant hypertension. Additional research must aim to verify potential BP lowering effect and identify a priori responders to RDN before this invasive method can routinely be applied to patients with drug-resistant hypertension. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01673516.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
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  • 10
    Online Resource
    Online Resource
    Informa UK Limited ; 2015
    In:  Leukemia & Lymphoma Vol. 56, No. 11 ( 2015-11-02), p. 3219-3221
    In: Leukemia & Lymphoma, Informa UK Limited, Vol. 56, No. 11 ( 2015-11-02), p. 3219-3221
    Type of Medium: Online Resource
    ISSN: 1042-8194 , 1029-2403
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2030637-4
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