Immunomodulatory Properties of Packed Red Blood Cells during Storage.

Introduction: Red blood cell (RBC) transfusion may affect the recipient immune system. During RBC storage in an unphysiological environment, RBC quality and function are impaired, the cells bleb extracellular vesicles (EVs), and other bioactive substances accumulate in the storage medium. EVs can carry reactive biomolecules and mediate cell-cell interactions. Thus, EVs could explain RBC transfusion related immunomodulation, particularly after prolonged storage. Methods: We exposed peripheral blood mononuclear cells (PBMCs) to allogeneic RBC supernatant (SN) and EVs from fresh and longer-stored RBC units, diluted plasma, and storage solution SAGM, and studied activation and proliferation of T-cells by flow cytometry, and cytokine secretion of LPS-stimulated PBMCs by enzyme-linked immunosorbent assay (ELISA). Results: Both fresh and longer-stored RBC SN but not EVs induced immunomodulation in recipient cells. RBC SN and diluted plasma augmented the proliferation of particularly CD8+ T-cells in a 4-day proliferation assay. T-cell activation by SN was evident already after 5 h as shown by upregulation of CD69. SN suppressed monocyte TNF-α and increased IL-10 secretion while diluted plasma increased secretion of both cytokines. Conclusion: This in vitro study demonstrates that stored RBC SN will have mixed immunomodulatory effects depending on responder cells and conditions, independent of RBC storage age. Fresh RBCs containing relatively few EVs can induce immune responses. Residual plasma in the products may contribute to these effects.

Storage time of red blood cells among ICU patients with septic shock.

BACKGROUND: We aimed to describe the exposure to blood transfusions and mortality among patients with septic shock. METHODS: We did a retrospective cohort study of two cohorts-patients with septic shock registered in a Danish ICU database (2008-2010) and patients from the Transfusion Requirements in Septic Shock (TRISS) trial (2011-2013). We extracted information on blood transfusions issued to all patients. We investigated the number of patients receiving very fresh blood (less than 7 days), very old blood (more than 24 days) and blood with a mixture of storage time. RESULTS: In the Danish cohort, 1637 patients were included of whom 1394 (85%) received 20,239 blood units from 14 days prior the ICU admission to 90 days after; 33% were transfused before, 77% in the ICU and 36% after ICU. The exposure to exclusively very fresh or very old blood was 3% and 4%, respectively. In the TRISS cohort, 77% of the 937 patients received 5047 RBC units; 3% received exclusively very fresh and 13% very old blood. The point estimate of mortality was higher among patients receiving large amounts of exclusively very fresh and very old blood, but the number of patients were very small. CONCLUSIONS: Patients with septic shock were transfused both before and after ICU. Exposure to blood of less than 7 days or more than 24 days old were limited. We were not able to detect higher mortality among the limited number of patients with septic shock transfused with very fresh or very old blood.

Phospholipid composition of packed red blood cells and that of extracellular vesicles show a high resemblance and stability during storage.

Red blood cells (RBCs) are stored up to 35-42days at 2-6°C in blood banks. During storage, the RBC membrane is challenged by energy depletion, decreasing pH, altered cation homeostasis, and oxidative stress, leading to several biochemical and morphological changes in RBCs and to shedding of extracellular vesicles (EVs) into the storage medium. These changes are collectively known as RBC storage lesions. EVs accumulate in stored RBC concentrates and are, thus, transfused into patients. The potency of EVs as bioactive effectors is largely acknowledged, and EVs in RBC concentrates are suspected to mediate some adverse effects of transfusion. Several studies have shown accumulation of lipid raft-associated proteins in RBC EVs during storage, whereas a comprehensive phospholipidomic study on RBCs and corresponding EVs during the clinical storage period is lacking. Our mass spectrometric and chromatographic study shows that RBCs maintain their major phospholipid (PL) content well during storage despite abundant vesiculation. The phospholipidomes were largely similar between RBCs and EVs. No accumulation of raft lipids in EVs was seen, suggesting that the primary mechanism of RBC vesiculation during storage might not be raft -based. Nonetheless, a slight tendency of EV PLs for shorter acyl chains was observed.

Preventing sexual abusers of children from reoffending: systematic review of medical and psychological interventions.

OBJECTIVE: To evaluate the effectiveness of current medical and psychological interventions for individuals at risk of sexually abusing children, both in known abusers and those at risk of abusing. DESIGN: Systematic review of interventions designed to prevent reoffending among known abusers and prevention for individuals at risk of sexually abusing children. Randomised controlled trials and prospective observational studies were eligible. Primary outcomes were arrests, convictions, breaches of conditions, and self reported sexual abuse of children after one year or more. RESULTS: After review of 1447 abstracts, we retrieved 167 full text studies, and finally included eight studies with low to moderate risk of bias. We found weak evidence for interventions aimed at reducing reoffending in identified sexual abusers of children. For adults, evidence from five trials was insufficient regarding both benefits and risks with psychological treatment and pharmacotherapy. For adolescents, limited evidence from one trial suggested that multisystemic therapy prevented reoffence (relative risk 0.18, 95% confidence interval 0.04 to 0.73); lack of adequate research prevented conclusions about effects of other treatments. Evidence was also inadequate regarding effectiveness of treatment for children with sexual behavioural problems in the one trial identified. Finally, we found no eligible research on preventive methods for adults and adolescents who had not sexually abused children but were at higher risk of doing so (such as those with paedophilic sexual preference). CONCLUSION: There are major weaknesses in the scientific evidence, particularly regarding adult men, the main category of sexual abusers of children. Better coordinated and funded high quality studies including several countries are urgently needed. Until conclusive evidence is available, realistic clinical strategies might involve reduction of specific risk factors for sex crimes, such as sexual preoccupation, in abusers at risk of reoffending.