A phase Ib, open-label, single arm study to assess the safety, pharmacokinetics, and impact on humoral sensitization of SANGUINATE infusion in patients with end-stage renal disease.

The endeavor to study desensitization in kidney transplantation has not been matched by an effort to investigate strategies to prevent sensitization. In this study (NCT02437422), we investigated the safety, impact on sensitization, and pharmacokinetics of SANGUINATE (SG), a hemoglobin-based oxygen carrier, as a potential alternative to packed red blood cells (PRBC) in transplant candidates with end-stage renal disease (ESRD). Ten ESRD subjects meeting inclusion/exclusion (I/E) criteria were planned to receive three weekly infusions of SG (320 mg/kg). The study was stopped after five subjects were enrolled, and their data were analyzed after completing a follow-up period of 90 days. Two subjects had elevated troponin I levels in setting of SG infusion, one of which was interpreted as a non-ST elevation myocardial infarction. All other adverse events were transient. SG pharmacokinetic analysis showed mean (SD) Cmax , Tmax , AUC, and half-life of 4.39 (0.69) mg/mL, 2.42 (0.91) hours, 171.86 (52.35) mg h/mL, and 40.60 (11.96) hours, respectively. None of the subjects developed new anti-HLA antibodies following SG infusion and throughout the study period. In conclusion, SG is a potential alternative to PRBCs in ESRD patients considered for kidney transplantation as it was not associated with humoral sensitization. Larger studies in highly sensitized patients are required to further evaluate for potential safety signals.

The management of acute myocardial infarction in developing countries.

Developing countries contribute a major share to the global burden of cardiovascular disease. Acute myocardial infarction (AMI) in particular remains one of the leading causes of death in the developing world as well as in the developed world. While the risk factors, management and outcome of AMI have been extensively studied in the developed world, limited data is available on this subject from developing countries. The current review looks at the prevalence of the classical coronary artery disease risk factors in developing countries and their association with myocardial infarction, as well as the management and outcome of AMI patients in these countries.

Thiazolidinediones associated with recurrent pleural effusions post coronary artery bypass surgery.

We report the case of a patient in which thiazolidinediones (TZDs) were associated with recurrent pleural effusions post coronary artery bypass surgery, in spite of a normal left ventricular function. The potential mechanisms are discussed, particularly in relation to the "vascular leak syndrome". This finding has important implications for the management of diabetic patients who are referred for coronary artery bypass surgery and who are on TZDs for glycemic control.