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      Older Age and High Serum Ferritin Levels Associated With the Risk of Chronic Cytopenia in Hemodialysis Patients

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          Abstract

          Leukopenia or thrombocytopenia is sometimes observed in end-stage renal disease (ESRD) patients, but the association between chronic leukopenia or thrombocytopenia and hemodialysis (HD) is still unclear. We aimed to investigate the incidence of chronic leukopenia or thrombocytopenia in patients with ESRD who received HD and to determine the risk factors of this complication. We retrospectively analyzed ESRD patients treated with HD at Ditmanson Medical Foundation Chia-Yi Christian Hospital in 2018. The risk factors for the occurrence of chronic leukopenia and thrombocytopenia were analyzed by Cox regression models. Of the 473 patients in our study cohort, 46 (9.7%) patients had a hematologic abnormality, including 18 patients with chronic leukopenia, 18 with chronic thrombocytopenia, and 10 with pancytopenia. Multivariate analysis revealed that patient age ≥60 years at the initiation of dialysis was a significant predictor for both chronic leukopenia [adjusted hazard ratio (aHR), 2.71; 95% confidence interval (CI), 1.06-6.89] and chronic thrombocytopenia (aHR, 2.83; 95% CI, 1.08–7.35). Chronic liver disease (aHR, 3.31; 95% CI, 1.27–8.61) and serum ferritin levels >800 mg/dl (aHR, 3.29; 95% CI, 1.29–8.39) were risk factors for chronic thrombocytopenia. A trend showed that vitamin D from intravenous supplementation (aHR, 0.13; 95% CI, 0.01–1.16, P = 0.066) and serum phosphorous level (aHR, 0.73; 95% CI, 0.53–1.02, P = 0.068) may be associated with chronic thrombocytopenia. Our study demonstrated that hematological abnormality was a long-term complication of HD. These results reveal that older patients with HD and high serum ferritin levels are at an elevated risk for chronic cytopenia. Healthcare professionals should be aware of this risk when treating HD patients in order to improve their prognosis.

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          Most cited references 49

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          The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

          Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.
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            Epidemiological features of CKD in Taiwan.

            The incidence of end-stage renal disease (ESRD) in Taiwan is the highest in the world. However, epidemiological features of earlier chronic kidney disease (CKD) have not been investigated. Since implementation of the National Health Insurance Program in 1995, more than 96% of the population in Taiwan has been enrolled. A nationally representative cohort of 200,000 individuals randomly sampled from the National Health Insurance enrollees was followed up from 1996 to 2003. Clinical conditions were defined by using diagnostic codes. The prevalence and incidence of clinically recognized CKD were assessed. We also identified risk factors associated with the development of CKD. The prevalence of clinically recognized CKD increased from 1.99% in 1996 to 9.83% in 2003. The overall incidence rate during 1997 to 2003 was 1.35/100 person-years. The multivariate model indicates that age is a key predictor of CKD, with an odds ratio of 13.95 for the group aged 75-plus years compared with the group younger than 20 years. Other factors associated with increased risk for the development of CKD include diabetes, hypertension, hyperlipidemia, and female sex. The prevalence and incidence of CKD in Taiwan are relatively high compared with other countries. Our finding provides a reasonable explanation for the subsequent epidemic of ESRD in Taiwan. Further study is needed to identify the entire burden of CKD and the effectiveness of risk-factor modification.
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              Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence.

              Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow-biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers. (Funded by the National Human Genome Research Institute and others.).
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                29 October 2020
                2020
                : 7
                Affiliations
                1Division of Hematology and Oncology, Department of Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital , Chiayi, Taiwan
                2Min-Hwei Junior College of Health Care Management , Tainan, Taiwan
                3Division of Nephrology, Department of Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital , Chiayi, Taiwan
                4Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science , Tainan, Taiwan
                5Department of Applied Life Science and Health, Chia Nan University of Pharmacy and Science , Tainan, Taiwan
                Author notes

                Edited by: Natalia Lopez-Andres, NavarraBiomed, Spain

                Reviewed by: Maria-Eleni Roumelioti, University of New Mexico, United States; Ashish K. Solanki, Medical University of South Carolina, United States

                *Correspondence: Peir-Haur Hung dtmedg3@ 123456yahoo.com.tw

                This article was submitted to Nephrology, a section of the journal Frontiers in Medicine

                †These authors have contributed equally to this work

                Article
                10.3389/fmed.2020.568350
                7662880
                33195315
                Copyright © 2020 Lee, Wang, Kuo, Lee, Lu, Hsiao, Hsu and Hung.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 49, Pages: 9, Words: 5167
                Categories
                Medicine
                Original Research

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