22 results on '"Vojdeman, FJ"'
Search Results
2. Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study
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Baliakas P, Hadzidimitriou A, Sutton LA, Minga E, Agathangelidis A, Nichelatti M, Tsanousa A, Scarfò L, Davis Z, Yan XJ, Shanafelt T, Plevova K, Sandberg Y, Vojdeman FJ, Boudjogra M, Tzenou T, Chatzouli M, Chu CC, Veronese S, Gardiner A, Mansouri L, Smedby KE, Bredo Pedersen L, van Lom K, Giudicelli V, Skuhrova Francova H, Nguyen Khac F, Panagiotidis P, Juliusson G, Angelis L, Anagnostopoulos A, Lefranc MP, Facco M, Trentin L, Catherwood M, Montillo M, Geisler CH, Langerak AW, Pospisilova S, Chiorazzi N, Oscier D, Jelinek DF, Darzentas N, Belessi C, Davi F, Rosenquist R, GHIA , PAOLO PROSPERO, Stamatopoulos K. Ghia P. is Co senior author, corresponding author, Baliakas, P, Hadzidimitriou, A, Sutton, La, Minga, E, Agathangelidis, A, Nichelatti, M, Tsanousa, A, Scarfò, L, Davis, Z, Yan, Xj, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, Fj, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, Cc, Veronese, S, Gardiner, A, Mansouri, L, Smedby, Ke, Bredo Pedersen, L, van Lom, K, Giudicelli, V, Skuhrova Francova, H, Nguyen Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, Mp, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, Ch, Langerak, Aw, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, Df, Darzentas, N, Belessi, C, Davi, F, Rosenquist, R, Ghia, PAOLO PROSPERO, Stamatopoulos K. Ghia P., is Co senior author, and Corresponding, Author
- Abstract
Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptorimmunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggeststhat B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never beenexplored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn.Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogeneticdata were available. These patients were followed up in 15 academic institutions throughout Europe (in CzechRepublic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collectedbetween June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptorimmunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressingunmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome ofour analysis was time to fi rst treatment, defi ned as the time between diagnosis and date of fi rst treatment.Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 majorsubsets. Stereotyped subsets showed signifi cant diff erences in terms of age, sex, disease burden at diagnosis,CD38 expression, and cytogenetic aberrations of prognostic signifi cance. Patients within a specifi c subset generallyfollowed the same clinical course, whereas patients in diff erent stereotyped subsets—despite having the sameimmunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status—showedsubstantially diff erent times to fi rst treatment. By integrating B-cell receptor immunoglobulin stereotypy (forsubsets 1, 2, and 4) into the well established Döhner cytogenetic prognostic model, we showed these, whichcollectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separateclinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2).Interpretation The molecular classifi cation of chronic lymphocytic leukaemia based on B-cell receptorimmunoglobulin stereotypy improves the Döhner hierarchical model and refi nes prognostication beyondimmunoglobulin mutational status, with potential implications for clinical decision making, especially withinprospective clinical trials.Funding European Union; General Secretariat for Research and Technology of Greece; AIRC; Italian Ministry ofHealth; AIRC Regional Project with Fondazione CARIPARO and CARIVERONA; Regione Veneto on ChronicLymphocytic Leukemia; Nordic Cancer Union; Swedish Cancer Society; Swedish Research Council; and NationalCancer Institute (NIH).
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- 2014
3. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations
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Eva Minga, Karin E. Smedby, Lesley-Ann Sutton, Nicholas Chiorazzi, Myriam Boudjogra, Kostas Stamatopoulos, Karla Plevová, Lone Bredo Pedersen, Zadie Davis, Lydia Scarfò, Andreas Agathangelidis, Monica Facco, Achilles Anagnostopoulos, Maria Chatzouli, Chrysoula Belessi, Athina Tsanousa, Panagiotis Baliakas, Kirsten van Lom, Lefteris Angelis, Yorick Sandberg, Gunnar Juliusson, Diane F. Jelinek, Fie Juhl Vojdeman, Anne Gardiner, Panagiotis Panagiotidis, Anton W. Langerak, Florence Nguyen-Khac, Hana Skuhrová Francová, Frederic Davi, Denis Moreno, Silvio Veronese, Richard Rosenquist, Marie-Paule Lefranc, Nikos Darzentas, Šárka Pospíšilová, Véronique Giudicelli, Xiao-Jie Yan, Charles C. Chu, Christian H. Geisler, Larry Mansouri, David Oscier, Mark Catherwood, Marco Montillo, Anastasia Hadzidimitriou, Livio Trentin, Paolo Ghia, Tait D. Shanafelt, Tatiana Tzenou, Baliakas, P, Agathangelidis, A, Hadzidimitriou, A, Sutton, La, Minga, E, Tsanousa, A, Scarfò, L, Davis, Z, Yan, Xj, Shanafelt, T, Plevova, K, Sandberg, Y, Vojdeman, Fj, Boudjogra, M, Tzenou, T, Chatzouli, M, Chu, Cc, Veronese, S, Gardiner, A, Mansouri, L, Smedby, Ke, Pedersen, Lb, Moreno, D, Van Lom, K, Giudicelli, V, Francova, H, Nguyen Khac, F, Panagiotidis, P, Juliusson, G, Angelis, L, Anagnostopoulos, A, Lefranc, Mp, Facco, M, Trentin, L, Catherwood, M, Montillo, M, Geisler, Ch, Langerak, Aw, Pospisilova, S, Chiorazzi, N, Oscier, D, Jelinek, Df, Darzentas, N, Belessi, C, Davi, F, Ghia, PAOLO PROSPERO, Rosenquist, R, Stamatopoulos K. Ghia P., is Co senior author, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Università Vita-Salute San Raffaele, Milan, Italy, Division of Molecular Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico, San Raffaele Scientific Institute, Milan, Italy, Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Department of Informatics, Aristotle University of Thessaloniki, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom, The Feinstein Institute for Medical Research, Mayo Clinic [Rochester], Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Hematology, Rigshospitalet, Copenhagen, Denmark, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Hematology Department, Nikea General Hospital, Piraeus, Greece, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Department of Medicine, Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lund University and Hospital Department of Hematology, Lund Stem Cell Center, Lund, Sweden, Hematology Department and Hematopoietic Cell Transplantation Unit, Georgios Papanicolaou Hospital, Thessaloniki, Greece, Universita degli Studi di Padova, Department of Hemato-Oncology, Belfast City Hospital, Belfast, United Kingdom, Immunology, and Hematology
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Male ,Oncology ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Immunology ,B-cell receptor ,Gene Rearrangement, B-Lymphocyte, Heavy Chain ,Antineoplastic Agents ,Biology ,Biochemistry ,Time-to-Treatment ,Genetic Heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,10. No inequality ,ComputingMilieux_MISCELLANEOUS ,Survival analysis ,Aged ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,B-Lymphocytes ,0303 health sciences ,Lymphoid Neoplasia ,Hematology ,Gene Expression Regulation, Leukemic ,Genetic heterogeneity ,Cell Biology ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Survival Analysis ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,Immunoglobulin heavy chain ,Female ,Somatic Hypermutation, Immunoglobulin ,Antibody ,Immunoglobulin Heavy Chains ,IGHV@ - Abstract
An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.
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- 2015
4. Levels of plasma 25-hydroxy vitamin D and risk of developing type 2 diabetes in a large Danish primary health care population.
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Rohold CK, Jørgensen HL, Vojdeman FJ, Madsen CM, Olsen A, Heegaard AM, Lind BS, Tjønneland A, Schwarz P, and Gæde PH
- Abstract
Aims: Plasma levels of Vitamin D (25(OH)D) have been suggested as a predictor for developing type 2 diabetes. The purpose of this study was therefore to investigate if a measurement of plasma 25(OH)D could predict the development of type 2 diabetes in a cohort of 222,311 individuals from primary healthcare in Denmark., Methods: The CopD-study database containing data from the Copenhagen General Practitioners Laboratory on blood tests conducted from April 2004 to January 2012 was used for identification of the study population. Incident type 2 diabetes was then defined as having at least two redeemed prescriptions of antidiabetics or at least two hospital contacts due to type 2 diabetes or one redeemed prescription and one hospital contact regarding type 2 diabetes., Results: A total of 222,311 individuals were included in the study, of whom 7652 (3.4%) developed type 2 diabetes during the follow-up period of minimum one year. Individuals who developed type 2 diabetes had a significantly lower median 25(OH)D level than persons in the non-diabetes group. The hazard ratio for development of type 2 diabetes increased by 15% per 10 n mol/L decrease in 25(OH)D level., Conclusion: In this study of 222,311 persons from primary health care in Denmark, we found a clear inverse relationship between 25(OH)D and the risk of developing type 2 diabetes. Further studies should be conducted to clarify the mechanisms behind the relationship between 25(OH)D and type 2 diabetes and the effect of oral vitamin D supplementation on the development of type 2 diabetes., (© 2024. The Author(s).)
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- 2024
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5. Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia.
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Møller HI, Persson G, Klok FB, Vojdeman FJ, Lebech M, and Hviid TVF
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- Infant, Newborn, Pregnancy, Humans, Female, C-Reactive Protein analysis, Biomarkers, Acute-Phase Proteins metabolism, Gravidity, Leukocytes, Ferritins, Transferrins, Pre-Eclampsia
- Abstract
Objectives: Preeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension., Methods: Based on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion., Results: The neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia., Conclusion: Plasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples., Competing Interests: Declaration of Competing Interest The authors declare that the study was conducted without any commercial or associative interest that could represent a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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6. Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: prevalence and correlation between DPYD -genotype variants and P-uracil concentrations.
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Paulsen NH, Qvortrup C, Vojdeman FJ, Plomgaard P, Andersen SE, Ramlov A, Bertelsen B, Rossing M, Nielsen CG, Hoffmann-Lücke E, Greibe E, Spangsberg Holm H, Nielsen HH, Lolas IBY, Madsen JS, Bergmann ML, Mørk M, Fruekilde PBN, Bøttger P, Petersen PC, Nissen PH, Feddersen S, Bergmann TK, Pfeiffer P, and Damkier P
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- Humans, Uracil, Prevalence, Genotype, Phenotype, Denmark epidemiology, Fluorouracil, Dihydrouracil Dehydrogenase (NADP) genetics, Neoplasms epidemiology, Neoplasms genetics
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- 2022
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7. Association of ferritin and transferrin saturation with all-cause mortality, and the effect of concurrent inflammation: a danish cohort study.
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Mitchell NH, Jørgensen HL, Vojdeman FJ, Sennels HP, Andersen CL, Kriegbaum M, Grand MK, Bang CW, and Lind BS
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- Male, Female, Humans, Cohort Studies, Inflammation, Hematologic Tests, Denmark, Transferrins, Transferrin analysis, Ferritins, Iron
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The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation.Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP ≥ 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP ≥ 10 mg/L. The ferritin level associated with lowest mortality was 60 µg/L for females and 125 µg/L for males with CRP < 10 mg/L. It was 52 µg/L for females and 118 µg/L for males with CRP ≥ 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP ≥ 10 mg/L.Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS.
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- 2022
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8. Chronic lymphocytic leukaemia clones are detectable decades before diagnosis.
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Vojdeman FJ, Helby J, Pedersen LB, Brieghel C, Andersen MA, Nordestgaard BG, Bojesen SE, and Niemann CU
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- Biomarkers, Tumor, DNA Mutational Analysis methods, Humans, Leukemia, Lymphocytic, Chronic, B-Cell etiology, Mutation, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, Time Factors, Clonal Evolution genetics, Early Detection of Cancer methods, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis
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- 2022
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9. Vitamin D levels and the risk of prostate cancer and prostate cancer mortality.
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Stroomberg HV, Vojdeman FJ, Madsen CM, Helgstrand JT, Schwarz P, Heegaard AM, Olsen A, Tjønneland A, Struer Lind B, Brasso K, Jørgensen HL, and Røder MA
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- Biopsy, Humans, Logistic Models, Male, Prostatic Neoplasms epidemiology, Vitamin D
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Background: Vitamin D has a role in bone turnover and potentially bone-metastatic spread of prostate cancer (PCa). The aim of this observational study was to address the association between levels of serum vitamin D, diagnosis of PCa and subsequent mortality in men who underwent a biopsy of the prostate., Methods: All men who underwent prostatic biopsy in the Danish PCa Registry (DaPCaR) and who had a serum vitamin D measurement during the period 2004 to 2010 ( n = 4,065) were identified. Men were categorized by clinical cut-offs based on seasonally adjusted serum vitamin D levels in <25 (deficient), 25-50 (insufficient), 50-75 (sufficient) and >75 nmol/L (high) serum vitamin D. Logistic regression model for association between vitamin D and risk of PCa diagnosis and multivariate survival analyses were applied., Results: No association between serum vitamin D and risk of PCa was found. Overall survival was lowest for serum vitamin D deficiency and a significantly higher PCa specific mortality (HR: 2.37, 95%CI: 1.45-3.90, p < .001) and other cause mortality (HR: 2.08, 95%CI: 1.33-3.24, p = .001) was found for PCa patients with serum vitamin D deficiency compared to serum vitamin D sufficiency., Conclusion: No association was found between serum vitamin D categories and risk of PCa in men who underwent biopsy of the prostate. Men with PCa and serum vitamin D deficiency had a higher overall and PCa specific mortality compared to men with a sufficient level of serum vitamin D.
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- 2021
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10. [The Danish screening programme for haemoglobinopathies].
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Glenthøj A, Samson M, Toft N, Diness BR, Askj R N, Vojdeman FJ, Birgens H, Sørensen MB, and Petersen J
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- Denmark epidemiology, Europe, Female, Humans, Pregnancy, Prenatal Diagnosis, Amniocentesis, Hemoglobinopathies diagnosis, Hemoglobinopathies epidemiology
- Abstract
The prevalence of people in Denmark descending from areas with a high prevalence of haemoglobinopathies is approximately one tenth and increasing. Since 1995, the Danish Health Authority has recommended haemoglobinopathy screening of pregnant women with ethnic roots outside Northern Europe. Partners of pregnant haemoglobinopathy carriers are also tested. Carrier state in both parents leads to genetic counselling, and prenatal diagnostics of the foetus (chorionic villus biopsy or amniocentesis) is offered, which can lead to abortion and/or preimplantation genetic screening for future pregnancies, as discussed in this review.
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- 2021
11. Comorbidity and mortality after hip fracture in nineteen thousand six hundred and eighty two patients aged eighteen to sixty five years in Denmark from 1996 to 2012.
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Omari A, Madsen CM, Lauritzen JB, Jørgensen HL, and Vojdeman FJ
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- Adolescent, Adult, Age Factors, Aged, Comorbidity, Denmark epidemiology, Diabetes Mellitus epidemiology, Female, Heart Diseases epidemiology, Hip Fractures epidemiology, Humans, Male, Middle Aged, Neoplasms epidemiology, Registries statistics & numerical data, Young Adult, Hip Fractures mortality
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Purpose: This nationwide study assessed associations between comorbidity and mortality after hip fracture in young and middle-aged patients., Methods: Data on 19,682 patients aged 18 to 65 years were extracted from Danish registries out of 154,047 patients who experienced a hip fracture between 1996 and 2012. Mortality and comorbidity were assessed using information on vital status, hospital admissions, and prescriptions., Results: Of the 19,682 patients 17,722 (90.0%) were middle-aged (40-65 years) and 1960 (10.0%) were young (18-39 years). The 30-day mortality rates were 3.2% (n = 570) and 1.6% (n = 32), respectively. Indicators of multi-trauma (hazard ratio (HR), 3.5 95% confidence interval (CI) [1.6-7.8], n = 2056) and having diabetes (HR, 4.4 [1.2-11.3], n = 59) and heart disease (HR, 4.4[1.3-14.8], n = 57) increased 30-day mortality in the young patients, while having cancer (HR, 5.0 [4.2-5.9], n = 1958) increased 30-day mortality in the middle-aged patients., Conclusion: Heart disease and diabetes were associated with high mortality in the young patients while having cancer was associated with high mortality in the middle-aged patients.
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- 2019
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12. Vitamin D levels and cancer incidence in 217,244 individuals from primary health care in Denmark.
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Vojdeman FJ, Madsen CM, Frederiksen K, Durup D, Olsen A, Hansen L, Heegaard AM, Lind B, Tjønneland A, Jørgensen HL, and Schwarz P
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- Adult, Denmark epidemiology, Female, Humans, Incidence, Male, Middle Aged, Neoplasms etiology, Registries, Neoplasms classification, Neoplasms epidemiology, Vitamin D blood
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Vitamin D has been linked to cancer development in both pre-clinical and epidemiological studies. Our study examines the association between serum levels of vitamin D and cancer incidence in the Capital Region of Denmark. Individuals who had vitamin D analyzed at The Copenhagen General Practitioners Laboratory between April 2004 and January 2010 were linked to Danish registries with end of follow-up date at Dec 31st 2014, excluding individuals with pre-existing cancer. Cox regression models adjusted for age in one-year intervals, sex, month of sampling, and Charlson Comorbidity Index were applied. The study population of 217,244 individuals had a median vitamin D level of 46 nmol/L (IQR 27-67 nmol/L). Non-melanoma skin cancer was the most frequent form of cancer, followed by breast-, lung-, and prostate cancers. No associations were found between increments of 10 nmol/L vitamin D and incidence of breast, colorectal, urinary, ovary or corpus uteri cancer. However, higher levels of vitamin D were associated with higher incidence of non-melanoma (HR 1.09 [1.09-1.1]) and melanoma skin cancer (HR 1.1 [1.08-1.13]) as well as prostate (HR 1.05 [1.03-1.07]) and hematological cancers (HR 1.03 [1.01-1.06]), but with lower incidence of lung cancer (HR 0.95 [0.93-0.97]). In our study, vitamin D levels are not associated with the incidence of several major cancer types, but higher levels are significantly associated with a higher incidence of skin, prostate, and hematological cancers as well as a lower incidence of lung cancer. These results do not support an overall protective effect against cancer by vitamin D., (© 2019 UICC.)
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- 2019
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13. Excess mortality following hip fracture in patients with diabetes according to age: a nationwide population-based cohort study of 154,047 hip fracture patients.
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Madsen CM, Jantzen C, Norring-Agerskov D, Vojdeman FJ, Abrahamsen B, Lauritzen JB, and Jørgensen HL
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- Age Factors, Aged, Aged, 80 and over, Denmark epidemiology, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 mortality, Female, Hip Fractures complications, Humans, Male, Middle Aged, Proportional Hazards Models, Registries, Risk Factors, Diabetes Complications mortality, Hip Fractures mortality
- Abstract
Objective: to test the hypothesis that excess mortality conferred by diabetes following hip fracture decreases with advancing age., Methods: a nationwide population-based cohort study including 154,047 patients who were admitted with a hip fracture in Denmark from 1996 to 2012. Information on hip fracture diagnosis, diabetes, other comorbidities, and the primary outcome all-cause mortality was collected using the national Danish health registries. The association between diabetes and all-cause mortality according to age was assessed using Cox proportional hazards regression in the age categories: <50, 50-59, 60-69, 70-79, 80-89 and ≥90 years., Results: during a median follow-up of 3 years (interquartile range: 1-6 years, 603,091 person-years) 114,990 died from any cause. In total, 8% (n = 12,158) of the patients had diabetes at baseline and had unadjusted, and age, sex and Charlson Comorbidity Index adjusted hazard ratios for all-cause mortality of 1.19 (95% confidence interval: 1.16-1.21) and 1.14 (1.12-1.17) as compared to patients without diabetes. The sex and Charlson Comorbidity Index adjusted hazard ratios according to age were 1.64 (1.34-2.02) for patients <50 years, 1.26 (1.12-1.40) for patients 50-59 years, 1.21 (1.13-1.29) for patients 60-69 years, 1.11 (1.07-1.16) for patients 70-79 years, 1.10 (1.07-1.14) for patients 80-89 years and 1.09 (1.02-1.16) for patients ≥90 years. There was a statistically significant interaction between diabetes and age (P < 0.001)., Conclusions: diabetes is associated with excess mortality following hip fracture across all ages, but the excess mortality decreases with advancing age., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2019
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14. [Diagnosing von Willebrand disease].
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Vojdeman FJ, Philips M, Funding E, and Gøtze JP
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- Denmark, Humans, Prevalence, von Willebrand Factor, von Willebrand Diseases diagnosis, von Willebrand Diseases epidemiology
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Von Willebrand disease (VWD) is an inherited bleeding disorder with abnormal primary haemostasis due to defects in, or decreased concentration of the glycoprotein von Willebrand factor. In Denmark, the estimated prevalence of VWD is 1% corresponding to approximately 50,000 patients, but only a few hundred have been diagnosed, mostly due to prolonged bleeding after a trauma or during surgery. Thus, VWD is underdiagnosed in the general population. Improved anamnestic screening for bleeding disorders such as VWD in certain high-risk groups can facilitate institution of prophylactic treatment.
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- 2019
15. No improvement in long-term survival over time for chronic lymphocytic leukemia patients in stereotyped subsets #1 and #2 treated with chemo(immuno)therapy.
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Baliakas P, Mattsson M, Hadzidimitriou A, Minga E, Agathangelidis A, Sutton LA, Scarfo L, Davis Z, Yan XJ, Plevova K, Sandberg Y, Vojdeman FJ, Tzenou T, Chu CC, Veronese S, Mansouri L, Smedby KE, Giudicelli V, Nguyen-Khac F, Panagiotidis P, Juliusson G, Anagnostopoulos A, Lefranc MP, Trentin L, Catherwood M, Montillo M, Niemann CU, Langerak AW, Pospisilova S, Stavroyianni N, Chiorazzi N, Oscier D, Jelinek DF, Shanafelt T, Darzentas N, Belessi C, Davi F, Ghia P, Rosenquist R, and Stamatopoulos K
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- Adult, Aged, Aged, 80 and over, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Retrospective Studies, Survival Rate, Young Adult, Drug Therapy mortality, Immunotherapy mortality, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
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- 2018
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16. Brief Report: CD52 Expression on CD4+ T Cells in HIV-Positive Individuals on cART.
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Vojdeman FJ, Gaardbo JC, Hartling HJ, Gelpi M, Hove-Skovsgaard M, Pedersen AE, and Nielsen SD
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- ADP-ribosyl Cyclase 1 analysis, Adult, CD4 Lymphocyte Count, Cohort Studies, Female, Flow Cytometry, Humans, Leukocytes, Mononuclear immunology, Male, Membrane Glycoproteins analysis, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active, CD4-Positive T-Lymphocytes chemistry, CD52 Antigen analysis, HIV Infections drug therapy, HIV Infections immunology
- Abstract
Background: HIV persists in a latent state in quiescent CD4 T cells preventing eradication of HIV. CD52 is a surface molecule modulated by HIV. We aimed at examining factors related to CD52 expression on CD4 T cells in HIV-positive individuals and the impact of initiation of combination antiretroviral therapy (cART)., Methods: Peripheral blood mononuclear cells from 18 HIV-positive individuals and 10 uninfected age- and sex-matched controls were examined by flow cytometry for CD38 and CD52 expression on CD4 T cells. Stimulation assays were performed on 8 healthy blood donors to determine a cutoff for CD52 expression., Results: All examined CD4 T cells expressed CD52. However, both CD4 T cells with higher (CD52) and with lower CD52 expression (CD52dim) were found in HIV-positive individuals compared to uninfected controls. Two % CD52dim cells defined groups of high and low CD52: the group of individuals with high CD52 had higher CD4 counts at baseline (447 vs. 54 cells/µL, P = 0.02) and higher increase in CD4 counts during follow-up compared with low CD52 (P = 0.02). After 12 months of cART, CD52 increased (median fluorescence intensity 4846 vs. 5621, P < 0.05), whereas CD38 decreased (median fluorescence intensity 1519 vs. 730, P < 0.0001)., Conclusions: All HIV-positive individuals in this cohort had CD4 T cells that expressed CD52. Higher CD4 counts were found in those with high CD52. Furthermore, an increase in CD52 was found after 12 months of cART, indicating that anti-CD52 antibodies may be more efficient for depletion of CD4 T cells in HIV-positive individuals on cART.
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- 2018
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17. Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia.
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Vojdeman FJ, Herman SEM, Kirkby N, Wiestner A, van T' Veer MB, Tjønnfjord GE, Itälä-Remes MA, Kimby E, Farooqui MZ, Polliack A, Wu KL, Doorduijn JK, Alemayehu WG, Wittebol S, Kozak T, Walewski J, Abrahamse-Testroote MCJ, van Oers MHJ, Geisler CH, and Niemann CU
- Subjects
- Adenine analogs & derivatives, Antineoplastic Agents therapeutic use, Humans, Piperidines, Prognosis, Pyrazoles therapeutic use, Pyrimidines therapeutic use, CD52 Antigen blood, Leukemia, Lymphocytic, Chronic, B-Cell blood, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell immunology
- Abstract
CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value. Following chemo-immunotherapy, sCD52 decreased in parallel with leukocytes while during ibrutinib treatment and ibrutinib-induced ymphocytosis, sCD52 decreased along with lymph node reductions. In vitro IgM stimulation of CLL cells led to increased sCD52 levels in the medium. Our findings indicate that sCD52 reflects disease activity and potentially treatment efficacy in CLL.
- Published
- 2017
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18. Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes.
- Author
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Xochelli A, Baliakas P, Kavakiotis I, Agathangelidis A, Sutton LA, Minga E, Ntoufa S, Tausch E, Yan XJ, Shanafelt T, Plevova K, Boudjogra M, Rossi D, Davis Z, Navarro A, Sandberg Y, Vojdeman FJ, Scarfo L, Stavroyianni N, Sudarikov A, Veronese S, Tzenou T, Karan-Djurasevic T, Catherwood M, Kienle D, Chatzouli M, Facco M, Bahlo J, Pott C, Pedersen LB, Mansouri L, Smedby KE, Chu CC, Giudicelli V, Lefranc MP, Panagiotidis P, Juliusson G, Anagnostopoulos A, Vlahavas I, Antic D, Trentin L, Montillo M, Niemann C, Döhner H, Langerak AW, Pospisilova S, Hallek M, Campo E, Chiorazzi N, Maglaveras N, Oscier D, Gaidano G, Jelinek DF, Stilgenbauer S, Chouvarda I, Darzentas N, Belessi C, Davi F, Hadzidimitriou A, Rosenquist R, Ghia P, and Stamatopoulos K
- Subjects
- ADP-ribosyl Cyclase 1 genetics, ADP-ribosyl Cyclase 1 immunology, Amino Acid Sequence genetics, Female, Gene Expression Regulation, Neoplastic immunology, Humans, Immunogenetics, Immunoglobulin Heavy Chains immunology, Immunoglobulin Variable Region immunology, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Male, Immunoglobulin Heavy Chains genetics, Immunoglobulin Variable Region genetics, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Somatic Hypermutation, Immunoglobulin genetics
- Abstract
Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34-expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly ( P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management. Clin Cancer Res; 23(17); 5292-301. ©2017 AACR ., (©2017 American Association for Cancer Research.)
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- 2017
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19. The HOVON68 CLL trial revisited: performance status and comorbidity affect survival in elderly patients with chronic lymphocytic leukemia.
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Vojdeman FJ, Van't Veer MB, Tjønnfjord GE, Itälä-Remes M, Kimby E, Polliack A, Wu KL, Doorduijn JK, Alemayehu WG, Wittebol S, Kozak T, Walewski J, Abrahamse-Testroote MC, van Oers MH, and Geisler CH
- Subjects
- Age Factors, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cause of Death, Clinical Trials as Topic, Combined Modality Therapy, Comorbidity, Female, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Male, Mortality, Transplantation, Homologous, Leukemia, Lymphocytic, Chronic, B-Cell epidemiology
- Abstract
In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide (FC) in contrast to younger patients. The reasons are explored in this 5-year trial update using both survival analysis and competing risk analysis on non-CLL-related mortality. Elderly FCA patients died more frequently from causes not related to CLL, and more often related to comorbidity (mostly cardiovascular) than to infection. In a Cox multivariate analysis, del(17p), performance status >0, and comorbidity were associated with a higher non-CLL-related mortality in the elderly independent of the treatment modality. Thus, while the 'fit' elderly with no comorbidity or performance status of 0 might potentially benefit from chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab treatment in elderly patients with cardiovascular comorbidity.
- Published
- 2017
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20. Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death.
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Andersen MA, Vojdeman FJ, Andersen MK, Brown Pde N, Geisler CH, Weis Bjerrum O, and Niemann CU
- Subjects
- Adult, Agammaglobulinemia diagnosis, Aged, Aged, 80 and over, Biomarkers, Cause of Death, Chromosome Aberrations, Female, Follow-Up Studies, Gene Rearrangement, B-Lymphocyte, Humans, Infections etiology, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Male, Middle Aged, Neoplasm Grading, Prognosis, Agammaglobulinemia etiology, Leukemia, Lymphocytic, Chronic, B-Cell complications, Leukemia, Lymphocytic, Chronic, B-Cell mortality
- Abstract
Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment-free survival (TFS), and overall survival (OS). A total of 159 consecutive, newly diagnosed patients were included for analysis. Twenty-five patients (16%) had a moderate or severe infection within one year of diagnosis, but no associations were found between low immunoglobulin (Ig) levels and infections. In multivariate analysis, we found age (>65), high Binet stage, high β2-microglobulin, and Ig deficiency to be associated with shorter OS. Decreased levels of IgM, deletion of chromosome 17p and unmutated IGHV status had independent negative impact on TFS. Thus, patients with hypogammaglobulinemia did not suffer more from infections early in the disease course, and decreased Ig had independent negative prognostic impact in CLL.
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- 2016
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21. Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.
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Baliakas P, Agathangelidis A, Hadzidimitriou A, Sutton LA, Minga E, Tsanousa A, Scarfò L, Davis Z, Yan XJ, Shanafelt T, Plevova K, Sandberg Y, Vojdeman FJ, Boudjogra M, Tzenou T, Chatzouli M, Chu CC, Veronese S, Gardiner A, Mansouri L, Smedby KE, Pedersen LB, Moreno D, Van Lom K, Giudicelli V, Francova HS, Nguyen-Khac F, Panagiotidis P, Juliusson G, Angelis L, Anagnostopoulos A, Lefranc MP, Facco M, Trentin L, Catherwood M, Montillo M, Geisler CH, Langerak AW, Pospisilova S, Chiorazzi N, Oscier D, Jelinek DF, Darzentas N, Belessi C, Davi F, Ghia P, Rosenquist R, and Stamatopoulos K
- Subjects
- Aged, Antineoplastic Agents therapeutic use, B-Lymphocytes drug effects, B-Lymphocytes immunology, B-Lymphocytes pathology, Female, Genetic Heterogeneity, Humans, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Male, Middle Aged, Prognosis, Somatic Hypermutation, Immunoglobulin, Survival Analysis, Time-to-Treatment, Treatment Outcome, Gene Expression Regulation, Leukemic, Gene Rearrangement, B-Lymphocyte, Heavy Chain immunology, Immunoglobulin Heavy Chains genetics, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell genetics
- Abstract
An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL., (© 2015 by The American Society of Hematology.)
- Published
- 2015
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22. Plasma alemtuzumab levels in patients with chronic lymphocytic leukemia treated with alemtuzumab combined with chemotherapy reflect the efficacy of the treatment: a hypothesis.
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Vojdeman FJ, Jurlander J, van't Veer M, Itälä-Remes M, Kimby E, Tjønnfjord GE, Walewski J, Kozák T, Polliack A, Montagna M, Regazzi M, Kirkby N, van Oers M, and Geisler CH
- Subjects
- Alemtuzumab, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized blood, Antineoplastic Combined Chemotherapy Protocols adverse effects, Humans, Induction Chemotherapy, Leukemia, Lymphocytic, Chronic, B-Cell blood, Lymphopenia chemically induced, Prognosis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
In the HOVON68 trial comparing subcutaneous low-dose alemtuzumab (LD-A) used together with fludarabine (F) and cyclophosphamide (C) with FC alone in high-risk chronic lymphocytic leukemia (CLL), LD-AFC resulted in significantly more clinical and molecular responses than FC, but also in more opportunistic infections. In a subgroup analysis of alemtuzumab trough levels during treatment by a sensitive enzyme-linked immunosorbent assay (ELISA) method, detectable levels were found in 4/6 complete and 0/3 partial responders. A relationship between alemtuzumab plasma levels, response and duration of lymphocytopenia was evident. We hypothesize that following combination therapy, the response may not be a function of the alemtuzumab levels, but the opposite, that plasma alemtuzumab levels are a function of the efficacy of the entire treatment, and the fewer leukemic target cells that are remaining, the higher are the levels of plasma alemtuzumab. This concept may well provide a guide for alemtuzumab dosage in future trials.
- Published
- 2013
- Full Text
- View/download PDF
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