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- Kim, Haesook T., et al.
(author)
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Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report
- 2019
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In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155
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Journal article (peer-reviewed)abstract
- Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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- Abbafati, Cristiana, et al.
(author)
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- 2020
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Journal article (peer-reviewed)
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- Berglund, Carolina, et al.
(author)
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The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus
- 2008
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In: Microbes and infection. - Paris : Elsevier. - 1286-4579 .- 1769-714X. ; 10:8, s. 878-884
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Journal article (other academic/artistic)abstract
- Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.
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- Cederholm, Tommy, et al.
(author)
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Guidance for assessment of the inflammation etiologic criterion for the GLIM diagnosis of malnutrition : A modified Delphi approach
- 2023
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In: Clinical Nutrition. - : Churchill Livingstone. - 0261-5614 .- 1532-1983. ; 43:5, s. 10
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Journal article (peer-reviewed)abstract
- BACKGROUND : The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. METHODS : A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. RESULTS : The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. Thepresence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. CONCLUSION : Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.
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- Escott-Price, Valentina, et al.
(author)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Journal article (peer-reviewed)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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