Tackling the unknowns in understanding and management of hospital acquired anemia.

Hospital acquired anemia (HAA) has been a recognized entity for nearly 50 years. Despite multiple hypotheses, a mechanistic understanding is lacking, and targeted interventions have not yet yielded significantly impactful results. Known risk factors include advanced age, multiple co-morbidities, low bone marrow reserve, admission to the intensive care unit, and frequent phlebotomy. However, confounding variables in many studies continues to complicate the identification of additional risk factors. Improved understanding of iron metabolism, erythropoiesis, and the erythroid iron restriction response in the last few decades, as well as the recent demonstration of poor outcomes correlating with increased transfusion have refocused attention on HAA. While retrospective database studies provide ample correlative data between 1) HAA and poor outcomes; 2) reduction of phlebotomy volume and decrease in transfusion requirement; and 3) over-transfusion and increased mortality, no causal link between reduced phlebotomy volume, decreased rates of HAA, and improved mortality or other relevant outcomes have been definitely established. Here, we review the current state of knowledge and provide a summary of potential directions to understand and mitigate HAA. There are at present no clear guidelines on whether and when to evaluate hospitalized patients for underlying causes of anemia. We thus provide a guide for clinicians in general practice toward identifying patients at the highest risk for HAA, decreasing blood loss through phlebotomy to the greatest degree feasible, and evaluating and treating reversible causes of anemia in a targeted population.

Clinical trials for pathogen reduction in transfusion medicine: a review.

Despite the implementation of highly sensitive methods for the detection of pathogens in donor blood products, the risk of transmission of infectious disease to transfusion recipients remains. Of greatest concern, and accounting for most of the risk, are newly-emerging pathogens for which screening assays do not yet exist or well-known pathogens for which testing regimens are not routinely employed. Furthermore, passive donor screening programs are unlikely to capture all potentially infective donors. A promising strategy to overcome these limitations is the proactive incapacitation of pathogens residing in donor units. Several unique pathogen reduction/inactivation (PR/PI) platforms have been developed and implemented in clinical settings. The aims of this article are to review: (1) the basic methodology underlying PR/PI platforms, (2) the potential toxicities associated with PR/PI treatment of blood products, and (3) the data and outcomes from clinical trials involving currently available PR/PI platforms.

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient-months of remission and treatment failure showed that the remission rate in the study sample statistically exceeds the rate in historical controls (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal deficiencies were statistically similar between study patients (29%) and those in a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These preliminary findings reflect the promising potential of tissue-based ACTH-antibody-guided assay for improving the cure rates of Cushing disease patients undergoing TSR. Further studies with larger sample sizes, further refinements of assay interpretation, and longer-term follow-ups are needed.

Homogeneous amplification nucleobase quenching assay to detect the E474Q LCHAD deficiency mutation.

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare and potentially fatal autosomal recessive disorder of fatty acid metabolism. Early institution of dietary therapy is essential and places a premium on rapid diagnosis. Pregnancy with an LCHAD-deficient fetus is often complicated in the third trimester by liver disease, particularly acute fatty liver of pregnancy. All cases of isolated LCHAD deficiency have at least one copy of the E474Q mutation in the gene encoding the alpha-subunit of the mitochondrial trifunctional protein. Previously published methods for detecting this mutation are based upon allele-specific restriction enzyme digestion of a DNA fragment generated by PCR, followed by gel electrophoresis to resolve the products. We have developed a faster and less expensive assay for the E474Q mutation using PCR followed directly by differential melting of a fluorescently labeled oligodeoxyribonucleotide probe, using nucleobase quenching to detect probe hybridization.