Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Oxygen delivery-guided perfusion for the prevention of acute kidney injury: A randomized controlled trial

ObjectivesThe reduction of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery using an oxygen delivery-guided perfusion strategy (oxygen delivery strategy) for cardiopulmonary bypass management compared with a fixed flow perfusion (conventional strategy) remains controversial. The purpose of this study was to determine whether a oxygen delivery strategy would reduce the incidence of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery.MethodsWe randomly enrolled 300 patients undergoing cardiopulmonary bypass surgery. Patients were randomly assigned to a oxygen delivery strategy (maintaining a oxygen delivery index value >300 mL/min/m² through pump flow adjustments during cardiopulmonary bypass) or a conventional strategy (a target pump flow was determined on the basis of the body surface area). The primary end point was the development of acute kidney injury. Secondary end points were the red blood cell transfusion rate and number of red blood cell units, intubation time, postoperative length of stay in the intensive care unit and the hospital, predischarge estimated glomerular filtration rate, and hospital mortality.ResultsAcute kidney injury occurred in 20 patients (14.6%) receiving the oxygen delivery strategy and in 42 patients (30.4%) receiving the conventional strategy (relative risk, 0.48; 95% confidence interval, 0.30-0.77; P = .002). The secondary end points were not significantly different between strategies. In a prespecified subgroup analysis of patients who had nadir hematocrit less than 23% or body surface area less than 1.40 m², the oxygen delivery strategy seemed to be superior to the conventional strategy and the existence of quantitative interactions was suggested.ConclusionsAn oxygen delivery strategy for cardiopulmonary bypass management was superior to a conventional strategy with respect to preventing the development of acute kidney injury.     

Time course of arsenic species in red blood cells of acute promyelocytic leukemia (APL) patients treated with single agent arsenic trioxide

Background:Arsenic trioxide (ATO) is widely applied to treat acute promyelocytic leukemia (APL). To elucidate metabolism and toxicity of arsenic, we analyzed time course of arsenic species in red blood cells (RBCs) of APL patients.

Methods:Nine APL patients received ATO (0.16 mg/kg/day) through 18-h infusion. Blood was collected before daily administration (days 2 to 9), and at different time points on day 8. Inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were detected by HPLC-ICP-MS.

Results:Arsenic species reached C_max at 18 h on day 8. Arsenicals gradually accumulated during days 2 to 9, whereas their percentages remained almost constant. The general trend in red blood cells (RBCs) was iAs > MMA > DMA. MMA was consistently the predominant methylated arsenic metabolite in RBCs. iAs, MMA, and tAs (tAs = iAs + DMA + MMA) concentrations (P < 0.0001), MMA/DMA ratios (P = 0.0016) and iAs% (P = 0.0013) were higher in RBCs than in plasma.

Conclusions:Time course of arsenic species reveal kinetic characteristic of ATO metabolites in RBCs. Arsenic species accumulated with administration frequency. Arsenic species in RBCs were remarkably different from those in plasma. Time course of arsenic species in RBCs is important in ATO clinical application.     

Dermoscopy of subungual red comets associated with tuberous sclerosis complex

We report here our experience on the use of dermoscopy for the detection of subungual red comets, which are sometimes present in the nails of patients affected by tuberous sclerosis complex. Dermoscopy allowed us to visualize, with better resolution than the naked eye, very tortuous capillaries surrounded by a whitish halo and close parallel binary tortuous capillaries. In some cases, subungual red comets are associated with the presence of periungual or subungual fibromas, but their exact pathogenesis remains unknown.     

The secrets of human stem cell-derived transfusable RBC for targeted large-scale production and clinical applications: A fresh look into what we need most and lessons to be learned

Blood transfusion, using the safest conventional blood bioproducts, is an irreplaceable part of substitution therapy. It is considered the most essential supportive clinical intervention aimed to restore the health of patients in need. Nevertheless, numerous unresolved problems are still associated with current blood substitution therapy. To alleviate our dependency on blood donors, many investigators have been focusing on the quest for stem cell-derived blood cells in line with major developments in the field of regenerative medicine. The main objective is to provide a safe and highly standardized universal cultured red cell concentrate [CRBC] for all clinical applications, regardless of blood groups. Currently, we are close to overcoming some of the main obstacles in culturing cells. This concise report is a prelude to the immortalized cell lines that are ready for in vivo clinical trials. It is only through the sharing of experimental ideas and knowledge-based strategies that we will be able to achieve such an enormous task and better understand ‘’the one for all concept’’ of CRBCs and their universal usage in all clinical settings.