• A prospective analysis of circulating saturated and monounsaturated fatty acids and risk of non-Hodgkin lymphoma

      Chiu, Yu-Han; Bertrand, Kimberly A.; Zhang, Shumin; Laden, Francine; Epstein, Mara M.; Rosner, Bernard A.; Chiuve, Stephanie; Campos, Hannia; Giovannucci, Edward L.; Chavarro, Jorge E.; et al. (2018-05-14)
      Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T-NHL), B cell NHL (B-NHL) and three individual B-NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B-NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0, and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T-NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B-NHLs other than CLL/SLL and for VLCSFA and MUFA with T-NHL suggest an influence of fatty acid metabolism on lymphomagenesis.
    • Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia

      Shmukler, Boris E.; Huston, Nicholas C.; Thon, Jonathan N.; Ni, Chih-Wen; Kourkoulis, George; Lawson, Nathan D.; Paw, Barry H.; Alper, Seth L. (2015-12-01)
      We have now examined the erythroid phenotype in this zebrafish strain carrying a ZFN genomic knockout of piezo1. Genotyping was performed as previously described. In contrast to the anemic phenotype observed in zebrafish subjected to morpholino knockdown of piezo, the genomic ZFN knockout of piezo1 did not segregate either with anemia in the 3-dpf embryo or with dysmorphic erythrocyte morphology in the adult fish.
    • Recommendations on RBC Transfusion in General Critically Ill Children Based on Hemoglobin and/or Physiologic Thresholds From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative

      Doctor, Allan; Cholette, Jill M.; Remy, Kenneth E.; Argent, Andrew; Carson, Jeffrey L.; Valentine, Stacey L.; Bateman, Scot T.; Lacroix, Jacques (2018-09-01)
      OBJECTIVES: To present the consensus recommendations and supporting literature for RBC transfusions in general critically ill children from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children. METHODS: The panel of 38 experts developed evidence-based and, when evidence was lacking, expert-based recommendations and research priorities regarding RBC transfusions in critically ill children. The subgroup on RBC transfusion in general critically ill children included six experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 30, 2017, using a combination of keywords to define concepts of RBC transfusion and critically ill children. Recommendation consensus was obtained using the Research and Development/UCLA Appropriateness Method. The results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. RESULTS: Three adjudicators reviewed 4,399 abstracts; 71 papers were read, and 17 were retained. Three papers were added manually. The general Transfusion and Anemia Expertise Initiative subgroup developed, and all Transfusion and Anemia Expertise Initiative members voted on two good practice statements, six recommendations, and 11 research questions; in all instances, agreement was reached ( > 80%). The good practice statements suggest a framework for RBC transfusion in PICU patients. The good practice statements and recommendations focus on hemoglobin as a threshold and/or target. The research questions focus on hemoglobin and physiologic thresholds for RBC transfusion, alternatives, and risk/benefit ratio of transfusion. CONCLUSIONS: Transfusion and Anemia Expertise Initiative developed pediatric-specific good practice statements and recommendations regarding RBC transfusion management in the general PICU population, as well as recommendations to guide future research priorities. Clinical recommendations emphasized relevant hemoglobin thresholds, and research recommendations emphasized a need for further understanding of physiologic thresholds, alternatives to RBC transfusion, and hemoglobin thresholds in populations with limited pediatric literature.