Eleftherios C. Vamvakas

BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.

Allogeneic blood transfusion (ABT)-related immunomodulation (TRIM) encompasses the laboratory immune aberrations that occur after ABT and their established or purported clinical effects. TRIM is a real biologic phenomenon resulting in at least one established beneficial clinical effect in humans, but the existence of deleterious clinical TRIM effects has not yet been confirmed. Initially, TRIM encompassed effects attributable to ABT by immunomodulatory mechanisms (e.g., cancer recurrence, postoperative infection, or virus activation). More recently, TRIM has also included effects attributable to ABT by pro-inflammatory mechanisms (e.g., multiple-organ failure or mortality). TRIM effects may be mediated by: (1) allogeneic mononuclear cells; (2) white-blood-cell (WBC)-derived soluble mediators; and/or (3) soluble HLA peptides circulating in allogeneic plasma. This review categorizes the available randomized controlled trials based on the inference(s) that they permit about possible mediator(s) of TRIM, and examines the strength of the evidence available for relying on WBC reduction or autologous transfusion to prevent TRIM effects.

As the risks of allogeneic blood transfusion (ABT)-transmitted viruses were reduced to exceedingly low levels in the US, transfusion-related acute lung injury (TRALI), hemolytic transfusion reactions (HTRs), and transfusion-associated sepsis (TAS) emerged as the leading causes of ABT-related deaths. Since 2004, preventive measures for TRALI and TAS have been implemented, but their implementation remains incomplete. Infectious causes of ABT-related deaths currently account for less than 15% of all transfusion-related mortality, but the possibility remains that a new transfusion-transmitted agent causing a fatal infectious disease may emerge in the future. Aside from these established complications of ABT, randomized controlled trials comparing recipients of non-white blood cell (WBC)-reduced versus WBC-reduced blood components in cardiac surgery have documented increased mortality in association with the use of non-WBC-reduced ABT. ABT-related mortality can thus be further reduced by universally applying the policies of avoiding prospective donors alloimmunized to WBC antigens from donating plasma products, adopting strategies to prevent HTRs, WBC-reducing components transfused to patients undergoing cardiac surgery, reducing exposure to allogeneic donors through conservative transfusion guidelines and avoidance of product pooling, and implementing pathogen-reduction technologies to address the residual risk of TAS as well as the potential risk of the next transfusion-transmitted agent to emerge in the foreseeable future.

Allogeneic blood transfusion results in the infusion into the recipient of large amounts of foreign antigens in both soluble and cell-associated forms. The persistence of these antigens in the circulation of the recipient may create conditions that allow the development of immune down-regulation.

BACKGROUND: Various bioactive substances are released from white cell (WBC) granules into red cell (RBC) components in a time-dependent manner during blood storage. Some of these substances may have immunosuppressive effects and may contribute to transfusion-induced immunomodulation. RBCs transfused after prolonged storage may be associated with a higher incidence of postoperative infections than fresh RBCs. This hypothesis does not seem to have been investigated in a clinical study. STUDY DESIGN AND METHODS: The records of 416 consecutive patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. The association between the length of storage of the transfused RBCs, as well as the number of units of non-WBC-reduced allogeneic RBCs and/or platelets transfused, and the occurrence of postoperative pneumonia was calculated by logistic regression analyses adjusting for the effects of confounding factors. Among these were the numbers of days of intubation, days of impaired consciousness, and units of RBCs transfused. RESULTS: By Centers for Disease Control and Prevention criteria, pneumonia developed in 54 patients (13.0%). Among 269 patients given RBCs, the risk of pneumonia increased by 1 percent per day of increase in the mean storage time of the transfused RBCs (p<0.005). In an analysis of all patients, the risk of pneumonia increased by 5 percent per unit of non-WBC-reduced allogeneic RBCs and/or platelets received (p = 0.0584). CONCLUSION: After adjustment for the effects of the risk factors for pneumonia and the number of transfused RBCs, an association was observed between the length of storage of transfused RBCs and the development of postoperative pneumonia. This association should be investigated further in future studies of the outcomes of blood transfusion.