ASO Visual Abstract: Time to Surgical Treatment and Facility Characteristics as Potential Drivers of Racial Disparities in Breast Cancer Mortality: Delay,Facilities, and Breast Cancer Mortality

Annals of Surgical Oncology -     

Platelet in vitro assays: their correspondence with their in vivo hemostatic potential

Developments during the past few years have resulted in multiple kinds of platelet products for transfusion. This involves different collection methods, containers, preservative solutions, modifications of storage temperatures and durations, and additional treatments such as pathogen reduction. Much experience has been obtained testing these processes in vitro to seek indications of in vivo effectiveness. Availability of an in vitro method that correlated with in vivo effectiveness would be extremely valuable for these different kinds of platelet products and as more innovation in platelet preparation occurs in the future. This report reviews the methods for in vitro platelet testing with a view to their in vivo implications and whether such testing could be helpful in projecting the clinical effectiveness of different platelet products.     

Therapeutic efficacy and safety of platelets treated with a photochemical process for pathogen inactivation: the SPRINT Trial

We report a transfusion trial of platelets photochemically treated for pathogen inactivation using the synthetic psoralen amotosalen HCl. Patients with thrombocytopenia were randomly assigned to receive either photochemically treated (PCT) or conventional (control) platelets for up to 28 days. The primary end point was the proportion of patients with World Health Organization (WHO) grade 2 bleeding during the period of platelet support. A total of 645 patients (318 PCT and 327 control) were evaluated. The primary end point, the incidence of grade 2 bleeding (58.5% PCT versus 57.5% control), and the secondary end point, the incidence of grade 3 or 4 bleeding (4.1% PCT versus 6.1% control), were equivalent between the 2 groups (P =.001 by noninferiority). The mean 1-hour posttransfusion platelet corrected count increment (CCI) (11.1 x 10(3) PCT versus 16.0 x 10(3) control), average number of days to next platelet transfusion (1.9 PCT versus 2.4 control), and number of platelet transfusions (8.4 PCT versus 6.2 control) were different (P <.001). Transfusion reactions were fewer following PCT platelets (3.0% PCT versus 4.4% control; P =.02). The incidence of grade 2 bleeding was equivalent for PCT and conventional platelets, although posttransfusion platelet count increments and days to next transfusion were decreased for PCT compared with conventional platelets.     

Estimates of hepatic glyceroneogenesis in type 2 diabetes mellitus in humans

Glyceroneogenesis, that is, formation of triglyceride-glycerol from pyruvate, is a critical component of triglyceride fatty acid cycling in vivo. The quantitative contribution of glyceroneogenesis to triglyceride-glycerol and its hormonal regulation have not been examined in humans. We have quantified the contribution of pyruvate to very low-density lipoprotein (VLDL) triglycerides in subjects with type 2 diabetes mellitus using the deuterium labeling of body water technique. Subjects with type 2 diabetes mellitus were studied before and after a 6-month behavioral intervention therapy, during fasting and during a hyperinsulinemic normoglycemic clamp. Response to glucagon infusion was examined in 5 healthy subjects after an overnight fast. Glyceroneogenesis contributed approximately 54% to VLDL triglyceride-glycerol in type 2 diabetes mellitus as compared with approximately 12% contribution of plasma glucose. There was no effect of insulin plus glucose during hyperinsulinemic clamp on glyceroneogenesis even after clinical interventions, when insulin sensitivity had improved. In healthy subjects, the contribution of triosephosphates to plasma VLDL triglycerides was approximately 45%. Glyceroneogenesis, in contrast to glycolysis, is the predominant source of triglyceride-glycerol carbon for VLDL triglycerides in subjects with type 2 diabetes mellitus. The contribution of glyceroneogenesis to triglyceride-glycerol is not affected by short (4 hours) infusion of insulin in type 2 diabetes mellitus.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.