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Artikel ; Online: Clonal Hematopoiesis and Epigenetic Age Acceleration in Elderly Danish Twins.

Soerensen, Mette / Tulstrup, Morten / Hansen, Jakob Werner / Weischenfeldt, Joachim / Grønbæk, Kirsten / Christensen, Kaare

HemaSphere

2022 Band 6, Heft 9, Seite(n) e768

Abstract: Clonal hematopoiesis of indeterminate potential (CHIP) is common in the elderly and has been reported to associate with accelerated epigenetic age (AgeAccel), especially intrinsic (ie, cell-type independent) AgeAccel and to a lesser degree extrinsic ... ...

Abstract	Clonal hematopoiesis of indeterminate potential (CHIP) is common in the elderly and has been reported to associate with accelerated epigenetic age (AgeAccel), especially intrinsic (ie, cell-type independent) AgeAccel and to a lesser degree extrinsic AgeAccel, which reflects the immune-cell composition of the peripheral blood. We investigated the association between CHIP occurrence and AgeAccel in 154 Danish twin pairs aged 73-90 years (mean 79), using both individual-level and intrapair analyses, the latter to control for shared genetic and environmental factors. Of 308 individuals, 116 carried a CHIP mutation. CHIP carriers had non-significantly increased AgeAccel compared with non-carriers; the strongest association was for the Intrinsic Epigenetic Age Acceleration (IEAA) estimator (CHIP carriers 1.4 years older,
Sprache	Englisch
Erscheinungsdatum	2022-08-26
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000768
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: ProGraME: A novel flow cytometry algorithm for the diagnosis of low-risk myelodysplastic syndromes in patients with cytopenia.

Therkelsen, Jesper / Traeden, Dicte Wilhjelm / Schjødt, Ida / Andersen, Mette Klarskov / Sjö, Lene Dissing / Hansen, Jakob Werner / Grønbaek, Kirsten / Dimopoulos, Konstantinos

European journal of haematology

2023 Band 111, Heft 6, Seite(n) 851–862

Abstract: Objectives: Flow cytometry (FC) is, together with morphology, genetics, and cytogenetics, used in the diagnostic assessment of cytopenia, as its value in evaluating bone marrow dysplasia been highlighted by several studies. However, despite the ... ...

Abstract	Objectives: Flow cytometry (FC) is, together with morphology, genetics, and cytogenetics, used in the diagnostic assessment of cytopenia, as its value in evaluating bone marrow dysplasia been highlighted by several studies. However, despite the development of algorithms and guidelines, there is still a lack of standardization of the FC assessment of bone marrow dysplasia. Methods: By combining FC, together with morphological analysis and cytogenetic/molecular assessment in a training cohort of 209 patients, we created a novel score, ProGraME, which includes four parameters, each from a different cell lineage (Progenitor cells, Granulocytes, Monocytes, Erythroid precursors), solely based on relevant population gating. Points for ProGraME were attained for: lymphoid precursors ≤5% of all CD34+ cells (1.5 point); a granulocyte-to-lymphocyte side-scatter ratio ≤6 (1 point); a monocyte CD33-CV% ≥ 63 (2 points), and an erythroid precursor CD36-CV% ≥ 65 (2 points). Results: Using a cutoff of ≥2 as suggestive of dysplasia, ProGraME showed a sensitivity of 91% and a specificity of 81% in the training cohort and 95% and 75%, respectively, in an independent validation cohort of 159 patients. In addition, ProGraME had a very high negative predictive value of 97.1% and 97.8% in the training and validation cohorts, respectively, offering a useful tool for excluding bone marrow dysplasia. Finally, among the 23 CCUS patients that scored positive for dysplasia with ProGraME in the training cohort, 16 of them (69%) carried high-risk mutations, suggesting that FC might help identify early changes of dysplasia. Conclusions: ProGraME can potentially optimize the FC diagnosis of low-risk myelodysplasia without minimal requirements of flow analysis other than accurate population gating.
Mesh-Begriff(e)	Humans ; Flow Cytometry ; Myelodysplastic Syndromes/diagnosis ; Leukopenia ; Predictive Value of Tests ; Lymphocytes
Sprache	Englisch
Erscheinungsdatum	2023-08-23
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.14086
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Inflammatory Cytokine Profiles Do Not Differ Between Patients With Idiopathic Cytopenias of Undetermined Significance and Myelodysplastic Syndromes.

Nielsen, Amalie Bach / Hansen, Jakob Werner / Ørskov, Andreas Due / Dimopoulos, Konstantinos / Salem, Mohammad / Grigorian, Mariam / Bruunsgaard, Helle / Grønbæk, Kirsten

HemaSphere

2022 Band 6, Heft 5, Seite(n) e0713

Abstract: Immune dysregulation has been highlighted as a key player in the pathogenesis of myelodysplastic syndromes (MDS), but little is known about cytokine profiles in patients with unexplained cytopenia with or without mutations in MDS-associated genes (clonal ...

Abstract	Immune dysregulation has been highlighted as a key player in the pathogenesis of myelodysplastic syndromes (MDS), but little is known about cytokine profiles in patients with unexplained cytopenia with or without mutations in MDS-associated genes (clonal cytopenias of undetermined significance [CCUS] and idiopathic cytopenias of undetermined significance [ICUS], respectively), which often precede MDS. Here, we study the cytokine profiles in 111 patients with ICUS (N = 41), CCUS (
Sprache	Englisch
Erscheinungsdatum	2022-04-22
Erscheinungsland	United States
Dokumenttyp	Journal Article
ISSN	2572-9241
ISSN (online)	2572-9241
DOI	10.1097/HS9.0000000000000713
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: A predictive model for bone marrow disease in cytopenia based on noninvasive procedures.

Træden, Dicte / Tulstrup, Morten / Cowland, Jack Bernard / Sjö, Lene Dissing / Bøgsted, Martin / Grønbæk, Kirsten / Andersen, Mette Klarskov / Hansen, Jakob Werner

Blood advances

2022 Band 6, Heft 11, Seite(n) 3541–3550

Abstract: Bone marrow specimens are the core of the diagnostic workup of patients with cytopenia. To explore whether next-generation sequencing (NGS) could be used to rule out malignancy without bone marrow specimens, we incorporated NGS in a model to predict ... ...

Abstract	Bone marrow specimens are the core of the diagnostic workup of patients with cytopenia. To explore whether next-generation sequencing (NGS) could be used to rule out malignancy without bone marrow specimens, we incorporated NGS in a model to predict presence of disease in the bone marrow of patients with unexplained cytopenia. We analyzed the occurrence of mutations in 508 patients with cytopenia, referred for primary workup of a suspected hematologic malignancy from 2015 to 2020. We divided patients into a discovery (n = 340) and validation (n = 168) cohort. Targeted sequencing, bone marrow biopsy, and complete blood count were performed in all patients. Mutations were identified in 267 (53%) and abnormal bone marrow morphology in 188 (37%) patients. Patients with isolated neutropenia had the lowest frequency of both mutations (21%) and abnormal bone marrow morphology (5%). The median number of mutations per patient was 2 in patients with abnormal bone marrow morphology compared with 0 in patients with a nondiagnostic bone marrow morphology (P < .001). In a multivariable logistic regression, mutations in TET2, SF3B1, U2AF1, TP53, and RUNX1 were significantly associated with abnormal bone marrow morphology. In the validation cohort, a model combining mutational status and clinical data identified 34 patients (20%) without abnormal bone marrow morphology with a sensitivity of 100% (95% confidence interval: 93%-100%). Overall, we show that NGS combined with clinical data can predict the presence of abnormal bone marrow morphology in patients with unexplained cytopenia and thus can be used to assess the need of a bone marrow biopsy.
Mesh-Begriff(e)	Anemia/pathology ; Bone Marrow/pathology ; Bone Marrow Diseases/pathology ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Myelodysplastic Syndromes/genetics
Sprache	Englisch
Erscheinungsdatum	2022-04-15
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006649
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Modifiable and nonmodifiable risk factors for non-ventilator-associated hospital-acquired pneumonia identified in a retrospective cohort study.

Kachalov, Viacheslav N / Kuster, Stefan P / Balakrishna, Suraj / Schreiber, Peter W / Jakob, Werner / Sax, Hugo / Kouyos, Roger D / Wolfensberger, Aline

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2022 Band 28, Heft 11, Seite(n) 1451–1457

Abstract: Objectives: Hospital-acquired pneumonia in nonventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on ... ...

Abstract	Objectives: Hospital-acquired pneumonia in nonventilated patients (nvHAP) belongs to the most common healthcare-associated infections. This study aimed to investigate risk factors for nvHAP in patients outside the intensive care unit, focusing on modifiable risk factors. Methods: All inpatients admitted to an academic teaching hospital in Switzerland between 2017 and 2018 were included. nvHAP was defined according to European Centre for Disease Prevention and Control criteria. Patient days during and after ICU stay were excluded. Candidate risk factors-both constant and time varying-were included in uni- and multivariable Cox proportional hazards models. The decay ratio and the characteristic time of influence of hazard ratios (HRs) was estimated by adopting a linear decay in the Cox model. Results: A total of 66 001 hospitalizations with 314 (0.48%) nvHAP and 471 401 patient days were included. Median age was 57 years (interquartile range: 38 to 71 years) and 32 253 (48.9%) patients were male. Among nonmodifiable risk factors, age (adjusted HR (aHR) 2.66 for age ≥60 years, 95% CI 1.59 to 4.45) and male sex (aHR 1.71, 95% CI 1.34 to 2.18) were independently associated with nvHAP. Time-varying exposures showing strongest independent association with nvHAP were tube feeding (aHR 3.24, 95% CI 2.17 to 4.83), impaired consciousness (aHR 2.32, 95% CI 1.63 to 3.31), and severely impaired activity and mobility (aHR 2.06, 95% CI 1.50 to 2.84). The association with nvHAP decayed within 7.1 to 13.2 days after these exposures ended. Discussion: The risk for nvHAP varies with time, depending on the patient's medical condition and medical interventions. Several risk factors for nvHAP represent potential targets for specific prevention measures.
Mesh-Begriff(e)	Humans ; Male ; Middle Aged ; Female ; Retrospective Studies ; Healthcare-Associated Pneumonia/epidemiology ; Healthcare-Associated Pneumonia/prevention & control ; Cross Infection/microbiology ; Intensive Care Units ; Risk Factors ; Hospitals, Teaching
Sprache	Englisch
Erscheinungsdatum	2022-05-18
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2022.05.011
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: [The cause of cytopenia of undetermined significance can often be found by using next generation sequencing].

Hansen, Jakob Werner / Husby, Simon / Grønbæk, Kirsten

Ugeskrift for laeger

2017 Band 179, Heft 25

Abstract: Patients with persistent cytopenia are frequently referred to the haematological departments , and a diagnosis of myelodysplastic syndrome is often suspected. After routine assessment including a broad range of blood tests, bone marrow biopsy, and ... ...

Abstract	Patients with persistent cytopenia are frequently referred to the haematological departments , and a diagnosis of myelodysplastic syndrome is often suspected. After routine assessment including a broad range of blood tests, bone marrow biopsy, and cytogenetics, a definite diagnosis can still not be found for some patients, although they have symptomatic cytopenia. In these cases, next generation sequencing is a valuable supplement in identifying patients with early stages of myeloid cancer.
Mesh-Begriff(e)	Clone Cells ; DNA Mutational Analysis ; Hematopoiesis/genetics ; Humans ; Leukemia, Myeloid, Acute/blood ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/genetics ; Mutation ; Myelodysplastic Syndromes/blood ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Pancytopenia/blood ; Pancytopenia/diagnosis ; Pancytopenia/genetics ; Risk Factors
Sprache	Dänisch
Erscheinungsdatum	2017-07-18
Erscheinungsland	Denmark
Dokumenttyp	Journal Article ; Review
ZDB-ID	124102-3
ISSN	1603-6824 ; 0041-5782
ISSN (online)	1603-6824
ISSN	0041-5782
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Buch: Handbuch ausgewählter Klimastationen der Erde

Müller, Manfred J.

1272 Stationen

(Forschungsstelle Bodenerosion der Universität Trier, Mertesdorf (Ruwertal) ; 5)

1996

Verfasserangabe	von Manfred J. Müller. Mitarb.: Karlheinz Baltes und Dietmar Werle. Kartographie: Erwin Lutz und Christoph Renschler. Hrsg.: Gerold Richter
Serientitel	Forschungsstelle Bodenerosion der Universität Trier, Mertesdorf (Ruwertal) ; 5 Forschungsstelle Bodenerosion der Universität Trier
Überordnung	Forschungsstelle Bodenerosion der Universität Trier
Schlagwörter	Klimastation ; Klima
Sprache	Deutsch
Umfang	400 S. : graph. Darst., Kt.
Ausgabenhinweis	5., erg. und verb. Aufl.
Erscheinungsort	Trier
Erscheinungsland	Deutschland
Dokumenttyp	Buch
Anmerkung	Literaturverz. S. 21 - 24
HBZ-ID	HT007611808
Datenquelle	Katalog ZB MED Ernährung, Umwelt, Agrar

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Artikel ; Online: Long-term clinical outcomes of patients with hematologically unexplained cytopenia after routine assessment: A single center study.

Johansen, Morten Munk / Andersen, Michael Asger / Grønbaek, Kirsten / Hansen, Jakob Werner

European journal of haematology

2018

Abstract: Objective: We investigated mortality and long-term development of malignant hematological disease, cancer, liver-, renal-, and rheumatic disease in patients with unexplained cytopenia (UC).: Methods: We screened all patients referred to the ... ...

Abstract	Objective: We investigated mortality and long-term development of malignant hematological disease, cancer, liver-, renal-, and rheumatic disease in patients with unexplained cytopenia (UC). Methods: We screened all patients referred to the outpatient clinic at the Department of Hematology, Rigshospitalet, Copenhagen, with a suspected myeloid neoplasm from June 2009 to the end of 2012. Through registry linkage, we obtained information on hospital-based ICD-10 diagnoses and survival. We estimated cumulative incidences of disease and hazard ratios of all-cause mortality using the Aalen-Johansen estimator and Cox regression. We compared incidences and mortality with a control cohort. Results: Among 1820 referrals, 221 had UC. The UC group had a 5-year cumulative incidence of malignant hematological disease of 8.91% (CI 95%: 4.98-12.84) compared to 0.93(CI 95%: 0.32-1.55) in the matched controls. In addition, UC patients had higher incidences of cancer, liver, and rheumatic disease. Mortality was higher in UC patients compared to the matched controls with a HR of 1.43 [P = 0.038, CI 95%: 1.02-2.00] adjusted for comorbidity, sex, and age. Most of the mortality and morbidity were ascribed to patients 50 years or older. Conclusions: Unexplained cytopenia patients had a higher incidence of malignant hematological-, cancer-, liver-, and rheumatic disease and increased mortality compared to the general population.
Sprache	Englisch
Erscheinungsdatum	2018-07-20
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.13146
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: TET2 mutations are associated with hypermethylation at key regulatory enhancers in normal and malignant hematopoiesis

Morten Tulstrup / Mette Soerensen / Jakob Werner Hansen / Linn Gillberg / Maria Needhamsen / Katja Kaastrup / Kristian Helin / Kaare Christensen / Joachim Weischenfeldt / Kirsten Grønbæk

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Band 10

Abstract: TET2 mutations are frequent in myeloid malignancies and in elderly individuals with or without cytopenia. Here, the authors analyse the association between TET2 mutations and methylation changes in healthy elderly twins and patients with cytopenia and ... ...

Abstract	TET2 mutations are frequent in myeloid malignancies and in elderly individuals with or without cytopenia. Here, the authors analyse the association between TET2 mutations and methylation changes in healthy elderly twins and patients with cytopenia and compare them to those from leukemia.
Schlagwörter	Science ; Q
Sprache	Englisch
Erscheinungsdatum	2021-10-01T00:00:00Z
Verlag	Nature Portfolio
Dokumenttyp	Artikel ; Online
Datenquelle	BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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Buch ; Konferenzbeitrag: Wasser und Boden im Lichte neuer geowissenschaftlicher Forschung

Müller, Manfred J.

Vorträge im Rahmen des Flensburger Geographischen Umweltkolloquiums

(Flensburger regionale Studien ; 5)

1991

Körperschaft	Pädagogische Hochschule Flensburg / Forschungsstelle für Regionale Landeskunde
Veranstaltung/Kongress	Flensburger Geographisches Umweltkolloquium (1989, Flensburg)
Verfasserangabe	Forschungsstelle für Regionale Landeskunde an der Pädagogischen Hochschule Flensburg ... M. J. Müller (Hrsg.)
Serientitel	Flensburger regionale Studien ; 5
Überordnung
Schlagwörter	Deutschland ; Bodenschutz
Schlagwörter	Bodenerhaltung
Sprache	Deutsch
Umfang	132 S. : Ill., graph. Darst., Kt.
Erscheinungsort	Flensburg
Erscheinungsland	Deutschland
Dokumenttyp	Buch ; Konferenzbeitrag
HBZ-ID	HT004835200
ISBN	3-923444-42-7 ; 978-3-923444-42-7
Datenquelle	Katalog ZB MED Ernährung, Umwelt, Agrar

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