Loss of miR-144/451 alleviates β-thalassemia by stimulating ULK1-mediated autophagy of free α-globin.

Most cells can eliminate unstable or misfolded proteins through quality control mechanisms. In the inherited red blood cell disorder β-thalassemia, mutations in the β-globin gene (HBB) lead to a reduction in the corresponding protein and the accumulation of cytotoxic free α-globin, which causes maturation arrest and apoptosis of erythroid precursors and reductions in the lifespan of circulating red blood cells. We showed previously that excess α-globin is eliminated by Unc-51-like autophagy activating kinase 1 (ULK1)-dependent autophagy and that stimulating this pathway by systemic mammalian target of rapamycin complex 1 (mTORC1) inhibition alleviates β-thalassemia pathologies.

Clinical characteristics and outcomes of children with newly diagnosed acute myeloid leukemia and hyperleukocytosis managed with different cytoreductive methods.

Background: Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical utility is unknown, and low-dose cytarabine (LD-cytarabine) is used as an alternative method.

Methods: Children with newly diagnosed AML treated between 1997 and 2017 in institutional protocols were studied.

Gene Therapy and Gene Editing for β-Thalassemia.

After many years of intensive research, emerging data from clinical trials indicate that gene therapy for transfusion-dependent β-thalassemia is now possible. Strategies for therapeutic manipulation of patient hematopoietic stem cells include lentiviral transduction of a functional erythroid-expressed β-globin gene and genome editing to activate fetal hemoglobin production in patient red blood cells. Gene therapy for β-thalassemia and other blood disorders will invariably improve as experience accumulates over time.

Activation of γ-globin expression by hypoxia-inducible factor 1α.

Around birth, globin expression in human red blood cells (RBCs) shifts from γ-globin to β-globin, which results in fetal haemoglobin (HbF, αγ) being gradually replaced by adult haemoglobin (HbA, αβ). This process has motivated the development of innovative approaches to treat sickle cell disease and β-thalassaemia by increasing HbF levels in postnatal RBCs. Here we provide therapeutically relevant insights into globin gene switching obtained through a CRISPR-Cas9 screen for ubiquitin-proteasome components that regulate HbF expression.

Selumetinib for Refractory Pulmonary and Gastrointestinal Bleeding in Noonan Syndrome.

A 15-year-old-boy with Noonan syndrome and status post orthoptic heart transplant developed mixed mitral valve disease and underwent mechanical mitral valve replacement 6 months before presentation with acute respiratory distress. He developed massive pulmonary hemorrhage that required veno-venous extracorporeal membrane oxygenation (ECMO) support. He had a prolonged anticoagulation free ECMO course of 4 weeks, with ongoing recurrent pulmonary hemorrhage and underwent several rounds of coil embolization of aortopulmonary collaterals.

Effective therapies for sickle cell disease: are we there yet?

Sickle cell disease (SCD) is a common genetic blood disorder associated with acute and chronic pain, progressive multiorgan damage, and early mortality. Recent advances in technologies to manipulate the human genome, a century of research and the development of techniques enabling the isolation, efficient genetic modification, and reimplantation of autologous patient hematopoietic stem cells (HSCs), mean that curing most patients with SCD could soon be a reality in wealthy countries. In parallel, ongoing research is pursuing more facile treatments, such as in-vivo-delivered genetic therapies and new drugs that can eventually be administered in low- and middle-income countries where most SCD patients reside.

Phase I Dose-Finding, Safety, and Tolerability Trial of Romiplostim to Improve Platelet Recovery After UCB Transplantation.

Platelet recovery is delayed after umbilical cord blood transplant (UCBT). Romiplostim is a thrombopoietin receptor agonist that has the potential to improve platelet engraftment after UCBT. The purpose of this study was to determine the safety profile and maximum tolerated dose (MTD) of romiplostim and to investigate whether romiplostim accelerates platelet recovery post-UCBT.

Hereditary elliptocytosis-associated alpha-spectrin mutation p.L155dup as a modifier of sickle cell disease severity.

The broad phenotypic variability among individuals with sickle cell disease (SCD) suggests the presence of modifying factors. We identified two unrelated SCD patients with unusually severe clinical and laboratory phenotype that were found to carry the hereditary elliptocytosis-associated alpha-spectrin mutation c.460_462dupTTG (p.

RGL2 Deficiency Impairs Human Erythropoiesis By Altering Terminal Erythroid Differentiation and Apoptosis.

No relevant conflicts of interest to declare.

Predictors of Excess Patient Radiation Exposure During Chronic Total Occlusion Coronary Intervention: Insights From a Contemporary Multicentre Registry.

Background: High patient radiation dose during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) might lead to procedural failure and radiation skin injury.

Methods: We examined the association between several clinical and angiographic variables on patient air kerma (AK) radiation dose among 748 consecutive CTO PCIs performed at 9 experienced US centres between May 2012 and May 2015.

Results: The mean age was 65 ± 10 years, 87% of patients were men, and 35% had previous coronary artery bypass graft surgery (CABG).

Impact of Chronic Total Occlusion Revascularization Attempts on Subsequent Clinical Outcomes.

Objectives: We examined a contemporary, unselected cohort of patients with coronary chronic total occlusions (CTOs) to determine the impact of CTO revascularization on long-term outcomes.

Methods: We retrospectively assessed the impact of CTO revascularization on clinical outcomes of consecutive patients found to have a CTO during coronary angiography performed at our institution during 2011 and 2012. The primary endpoint was the incidence of a major adverse cardiac event (MACE, defined as a composite of death, myocardial infarction, stroke, and target-vessel revascularization [TVR]).

Near-Infrared Spectroscopy Analysis of Coronary Chronic Total Occlusions.

Objective: To examine the presence and localization of lipid-core plaque (LCP) in coronary vessels with chronic total occlusions (CTOs) using near-infrared spectroscopy (NIRS).

Methods: NIRS imaging was performed after guidewire crossing of the occlusion in 15 patients with CTOs. LCP was defined as ≥2 adjacent 2 mm yellow blocks on the block chemogram.

Contrast Utilization During Chronic Total Occlusion Percutaneous Coronary Intervention: Insights From a Contemporary Multicenter Registry.

Background: Administration of a large amount of contrast volume during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) may lead to contrast-induced nephropathy.

Methods: We examined the association of clinical, angiographic and procedural variables with contrast volume administered during 1330 CTO-PCI procedures performed at 12 experienced United States centers.

Results: Technical and procedural success was 90% and 88%, respectively, and mean contrast volume was 289 ± 138 mL.

Accuracy of remote chest X-ray interpretation using Google Glass technology.

Objectives: We sought to explore the accuracy of remote chest X-ray reading using hands-free, wearable technology (Google Glass, Google, Mountain View, California).

Methods: We compared interpretation of twelve chest X-rays with 23 major cardiopulmonary findings by faculty and fellows from cardiology, radiology, and pulmonary-critical care via: (1) viewing the chest X-ray image on the Google Glass screen; (2) viewing a photograph of the chest X-ray taken using Google Glass and interpreted on a mobile device; (3) viewing the original chest X-ray on a desktop computer screen. One point was given for identification of each correct finding and a subjective rating of user experience was recorded.

Prospective Evaluation of the Impact of Side-Holes and Guide-Catheter Disengagement From the Coronary Ostium on Fractional Flow Reserve Measurements.

Background: We prospectively examined the impact of side-holes and guide-catheter disengagement on fractional flow reserve (FFR) measurements.

Methods: Twenty-five patients undergoing clinically indicated FFR measurement for intermediate coronary artery stenosis were enrolled. Four FFR measurements were made in random order during intravenous adenosine infusion with: (a) an engaged side-hole guide catheter; (b) a disengaged side-hole guide catheter; (c) an engaged non-side-hole guide catheter; and (d) disengaged non-side-hole guide catheter.

Impact of crossing technique on the incidence of periprocedural myocardial infarction during chronic total occlusion percutaneous coronary intervention.

Objectives: We sought to evaluate the impact of crossing strategy on the incidence of periprocedural myocardial infarction (PMI) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Background: The optimal technique for crossing coronary CTOs remains controversial.

Methods: We retrospectively examined the incidence of PMI among 184 consecutive patients who underwent CTO PCI at our institution between 2012 and 2015.

Impact of Crossing Strategy on Intermediate-term Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention.

Background: There is ongoing controversy about the optimal crossing strategy selection for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), especially regarding the relative merits of antegrade dissection/re-entry and the retrograde approach.

Methods: We retrospectively examined the clinical outcomes of 173 consecutive patients who underwent successful CTO PCI at our institution between January 2012 and March 2015.

Results: The mean age was 65 ± 8 years, and 98% of the patients were men with a high prevalence of diabetes (60%), previous coronary artery bypass grafting (CABG) (31%), and previous PCI (54%).

Predictors and Outcomes of Side-Branch Occlusion in Coronary Chronic Total Occlusion Interventions.

Objectives: We investigated whether side-branch loss during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) could adversely impact clinical outcomes.

Background: Side-branch occlusion during PCI has been associated with periprocedural myocardial infarction and higher incidence of major adverse cardiac event (MACE), but has received limited study in CTO-PCI.

Methods: We retrospectively reviewed the medical records and coronary angiograms for 109 consecutive CTOPCI cases performed at our institution during 2012 and 2013.

Development and Validation of a Novel Scoring System for Predicting Technical Success of Chronic Total Occlusion Percutaneous Coronary Interventions: The PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) Score.

Objectives: This study sought to develop a novel parsimonious score for predicting technical success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) performed using the hybrid approach.

Background: Predicting technical success of CTO PCI can facilitate clinical decision making and procedural planning.

Methods: We analyzed clinical and angiographic parameters from 781 CTO PCIs included in PROGRESS CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) using a derivation and validation cohort (2:1 sampling ratio).

Determinants of operator and patient radiation exposure during cardiac catheterization: Insights from the RadiCure (RADIation reduction during cardiac catheterization using real-timE monitoring) trial.

Background: In the RadiCure study 505 catheterization procedures were 1:1 randomized to use or no use of real-time radiation monitoring. Use of the Bleeper Sv monitor resulted in a significant reduction in operator radiation exposure.

Methods: We examined the association between several baseline and procedural parameters with operator and patient radiation exposure using univariable and multivariable analysis in the 505 patients that were enrolled in RadiCure.

Optimizing Radiation Safety in the Cardiac Catheterization Laboratory: A Practical Approach.

Reducing radiation exposure during cardiovascular catheterization is of paramount importance for both patient and staff safety. Over the years, advances in equipment and application of radiation safety protocols have significantly reduced patient dose and operator exposure. This review examines the current status of radiation protection in the cardiac and vascular catheterization laboratory and summarizes best practices for minimizing radiation exposure.

Interpretation of Coronary Angiograms Recorded Using Google Glass: A Comparative Analysis.

Introduction: Google Glass (Google, Inc) is a voice-activated, hands-free, optical head-mounted display device capable of taking pictures, recording videos, and transmitting data via wi-fi. In the present study, we examined the accuracy of coronary angiogram interpretation, recorded using Google Glass.

Methods: Google Glass was used to record 15 angiograms with 17 major findings and the participants were asked to interpret those recordings on: (1) an iPad (Apple, Inc); or (2) a desktop computer.