Association between leukoreduced red blood cell transfusions and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

BACKGROUND AND OBJECTIVES: Hospital-acquired infections (HAIs) are an important problem in critically ill children. Studies show associations between the transfusion of non-leukoreduced red blood cell units (RBC) and increased HAI incidence rates (IRs). We hypothesize that transfusing pre-storage leukoreduced RBC is also associated with increased HAI IR. We aim to evaluate the associations between (1) a leukoreduced RBC restrictive transfusion strategy and HAI IR, (2) leukoreduced RBC transfusions and HAI IR, and (3) the number or volume of leukoreduced RBC transfusions and HAI IR in critically ill children. MATERIALS AND METHODS: This post hoc secondary analysis of the "Transfusion Requirement in Paediatric Intensive Care Units" (TRIPICU) randomized controlled trial (637 patients) used quasi-Poisson multivariable regression models to estimate HAI incidence rate ratios (IRRs) and 95% confidence intervals (CI). RESULTS: A restrictive transfusion strategy yielded an IRR of 0.88 (95% CI 0.67, 1.16). The association between transfusing leukoreduced RBCs (IRR 1.25; 95% CI 0.73, 2.13) and HAI IR was not statistically significant. However, we observed significant associations between patients who received >20 cc/kg volume of leukoreduced RBC transfusions (IRR 2.14; 95% CI 1.15, 3.99) and ≥3 leukoreduced RBC transfusions (IRR 2.40; 95% CI 1.15, 4.99) and HAI IR. CONCLUSION: Exposing critically ill children to >20 cc/kg or ≥3 leukoreduced RBC transfusions were associated with higher HAI IR, suggesting dose-response patterns.

Association between the length of storage of transfused leukoreduced red blood cell units and hospital-acquired infections in critically ill children: A secondary analysis of the TRIPICU study.

OBJECTIVE: Evaluate the association between leukoreduced red blood cell (RBC) storage length and hospital-acquired infection (HAI) incidence rate in critically ill children. BACKGROUND: RBC transfusions are common in critically ill children. Despite their benefits, observational studies suggest an association between them and HAIs. One possible mechanism for increased HAI is transfusion-related immunomodulation due to bioactive substances' release as transfused blood ages. METHODS: In this secondary analysis of the 'Transfusion Requirement in Paediatric Intensive Care Units' (TRIPICU) study, we analysed a subset of 257 participants that received only one pre-storage leukoreduced RBC transfusion. RBC storage length was classified as 1) transfusion of 'fresh' RBCs (≤10 days), 2) transfusion of 'stored' RBCs (21-34 days), and 3) transfusion of 'long-stored' RBCs (≥35 days). All were compared to a 'golden' period (11-20 days), representing the time between 'fresh' and 'stored'. We used quasi-Poisson multivariable regression models to estimate the HAI incidence rate ratio (IRR) and corresponding 95% confidence interval (CI). RESULTS: We found that the association between the length of storage time of leukoreduced RBCs and HAIs was not significant in the 'fresh' group (IRR 1.23; 95% CI 0.55, 2.78) and the 'stored' group (IRR 1.61; 95% CI 0.63, 4.13) when compared to the 'golden' period. However, we observed a statistically significant association between the 'long-stored' group and an increase in the HAI incidence rate (IRR 3.66; 95% CI 1.22, 10.98). CONCLUSION: Transfusion of leukoreduced RBC units stored for ≥35 days is associated with increased HAI incidence rate in haemodynamically stable, critically ill children.

Long noncoding miRNA gene represses wheat ß-diketone waxes.

The cuticle of terrestrial plants functions as a protective barrier against many biotic and abiotic stresses. In wheat and other Triticeae, ß-diketone waxes are major components of the epicuticular layer leading to the bluish-white glaucous trait in reproductive-age plants. Glaucousness in durum wheat is controlled by a metabolic gene cluster at the WAX1 (W1) locus and a dominant suppressor INHIBITOR of WAX1 (Iw1) on chromosome 2B. The wheat D subgenome from progenitor Aegilops tauschii contains W2 and Iw2 paralogs on chromosome 2D. Here we identify the Iw1 gene from durum wheat and demonstrate the unique regulatory mechanism by which Iw1 acts to suppress a carboxylesterase-like protein gene, W1-COE, within the W1 multigene locus. Iw1 is a long noncoding RNA (lncRNA) containing an inverted repeat (IR) with >80% identity to W1-COE The Iw1 transcript forms a miRNA precursor-like long hairpin producing a 21-nt predominant miRNA, miRW1, and smaller numbers of related sRNAs associated with the nonglaucous phenotype. When Iw1 was introduced into glaucous bread wheat, miRW1 accumulated, W1-COE and its paralog W2-COE were down-regulated, and the phenotype was nonglaucous and ß-diketone-depleted. The IR region of Iw1 has >94% identity to an IR region on chromosome 2 in Ae. tauschii that also produces miRW1 and lies within the marker-based location of Iw2 We propose the Iw loci arose from an inverted duplication of W1-COE and/or W2-COE in ancestral wheat to form evolutionarily young miRNA genes that act to repress the glaucous trait.