Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review.

Red cell transfusions are intended to improve oxygen delivery to tissues. Although studies comparing hemoglobin concentration triggers for transfusion have been done, the hemoglobin threshold for clinical benefit remains uncertain. Direct measurement of tissue oxygenation with non-invasive near infrared spectroscopy has been proposed as a more physiological transfusion trigger, but its clinical role remains unclear. This systematic review examined the role of near infrared spectroscopy for detection of anemia and guiding transfusion decisions. Abstracts were identified up until May 2019 through searches of PubMed, EMBASE and The Web of Science. There were 69 studies meeting the inclusion criteria, most (n = 65) of which were observational studies. Tissue oxygen saturation had been measured in a wide range of clinical settings, with neonatal intensive care (n = 26) and trauma (n = 7) being most common. Correlations with hemoglobin concentration and tissue oxygenation were noted and there were correlations between changes in red cell mass and changes in tissue oxygenation through blood loss or transfusion. The value of tissue oxygenation for predicting transfusion was determined in only four studies, all using muscle oxygen saturation in the adult trauma setting. The overall sensitivity was low at 34% (27%-42%) and while it had better specificity at 78% (74%-82%), differing and retrospective approaches create a high level of uncertainty with respect to these conclusions. There were four prospective randomized studies involving 540 patients, in cardiac and neurological surgery and in neonates that compared near infrared spectroscopy to guide transfusion decisions with standard practice. These showed a reduction in the number of red cells transfused per patient (OR: 0.44 [0.09-0.79]), but not the number of patients who received transfusion (OR: 0.71 [0.46-1.10]), and no change in clinical outcomes. Measuring tissue oxygen saturation has potential to help guide transfusion; however, there is a lack of data upon which to recommend widespread implementation into clinical practice. Standardization of measurements is required and greater research into levels at which tissue oxygenation may lead to adverse clinical outcomes would help in the design of future clinical trials.

GSTZ1 genotypes correlate with dichloroacetate pharmacokinetics and chronic side effects in multiple myeloma patients in a pilot phase 2 clinical trial.

Dichloroacetate (DCA) is an investigational drug targeting the glycolytic hallmark of cancer by inhibiting pyruvate dehydrogenase kinases (PDK). It is metabolized by GSTZ1, which has common polymorphisms altering enzyme or promoter activity. GSTZ1 is also irreversibly inactivated by DCA. In the first clinical trial of DCA in a hematological malignancy, DiCAM (DiChloroAcetate in Myeloma), we have examined the relationship between DCA concentrations, GSTZ1 genotype, side effects, and patient response. DiCAM recruited seven myeloma patients in partial remission. DCA was administered orally for 3 months with a loading dose. Pharmacokinetics were performed on day 1 and 8. Trough and peak concentrations of DCA were measured monthly. GSTZ1 genotypes were correlated with drug concentrations, tolerability, and disease outcomes. One patient responded and two patients showed a partial response after one month of DCA treatment, which included the loading dose. The initial half-life of DCA was shorter in two patients, correlating with heterozygosity for GSTZ1*A genotype, a high enzyme activity variant. Over 3 months, one patient maintained DCA trough concentrations approximately threefold higher than other patients, which correlated with a low activity promoter genotype (-1002A, rs7160195) for GSTZ1. This patient displayed the strongest response, but also the strongest neuropathy. Overall, serum concentrations of DCA were sufficient to inhibit the constitutive target PDK2, but unlikely to inhibit targets induced in cancer. Promoter GSTZ1 polymorphisms may be important determinants of DCA concentrations and neuropathy during chronic treatment. Novel dosing regimens may be necessary to achieve effective DCA concentrations in most cancer patients while avoiding neuropathy.

Comparison of the bone marrow trephine sample quality between OnControl drill system and the Jamshidi needle.

INTRODUCTION: Bone marrow biopsies are a key diagnostic and monitoring intervention in haematology with manual bone marrow techniques the established method of choice. Powered biopsy devices are now available, but are not widely used in haematology. This study compared the quality of bone marrow trephines obtained with the Jamshidi needle and OnControl powered drill system. METHODS: Retrospective analysis was undertaken on trephine samples prior to and after implementation of the OnControl drill system. Trephine size and quality were assessed independently by three pathologists and compared between techniques and operators using nonparametric tests. RESULTS: There were 164 samples assessed (Jamshidi n = 69, OnControl, same site as aspirate n = 48, OnControl, separate site from aspirate n = 47). The assessable and total length were similar between the Jamshidi and OnControl techniques, with increased crush artefact observed with the OnControl drill (P < 0.001). Using a separate puncture site for trephine collection and aspirate did not reduce the artefact seen with the OnControl system (P = 0.274). Smaller samples (P < 0.001) and an increase in crushed (P = 0.009) and connective tissue (P = 0.002) were seen in trephines obtained by nonlaboratory-based trainees, regardless of the needle used or their stage of training, compared to laboratory trainees. CONCLUSIONS: Trephines obtained by either method had similar assessable areas. The OnControl system was associated with more artefact, a finding in line with previous studies. There was no improvement by sampling the trephine from a separate site to the aspirate. Laboratory-based trainees who reviewed marrow morphology produced trephines with better assessable length than those not based in the laboratory.