The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.

https://www.pnas.org/content/pnas/112/10/2978.full.pdf

Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance

Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Here we investigated doxorubicin-induced cytotoxicity in human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We found that doxorubicin and related anthracycline agents (e.g., daunorubicin, idarubicin, and epirubicin) significantly upregulated the expression of death receptors (DRs) (TNFR1, Fas, DR4 and DR5) in iPS-derived cardiomyocytes at both protein and mRNA levels. The resulting iPS-CMs cells underwent spontaneous apoptosis which was further enhanced by physiologically relevant death ligands including TNF-related apoptosis inducing ligand (TRAIL). Furthermore, TRAIL potentiated doxorubicin-induced decrease in beating rate and amplitude of iPS-derived cardiomyocytes. These data demonstrate that the induction of death receptors in cardiomyocytes is likely a critical mechanism by which doxorubicin causes cardiotoxicity.

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Doxorubicin induces cardiotoxicity through upregulation of death receptors mediated apoptosis in cardiomyocytes.

Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management

Immunogenic cell death in anticancer chemotherapy and its impact on clinical studies.

Anthracyclines have been widely used in children and adults to treat hematologic malignancies, soft-tissue sarcomas, and solid tumors However, anthracyclines come with both short- and long-term cardiotoxic effects, ranging from occult changes in myocardial structure and function to severe cardiomyopathy and heart failure that may result in cardiac transplantation or death Here, we review the progress made over the past two decades in understanding the molecular and genetic basis of anthracycline-induced cardiotoxicity; detecting and monitoring myocardial dysfunction; using adjunct cardioprotectant therapies, such as dexrazoxane; and improving cardioprotection with agents such as liposomal and pegylated doxorubicin Despite this increased understanding, preventing drug-induced cardiotoxicity while maintaining oncologic efficacy to achieve the highest quality of life over a lifespan remain cornerstones of successful anthracycline chemotherapy during childhood

Anthracycline-Induced Cardiotoxicity: A Review of Pathophysiology, Diagnosis, and Treatment

The Fontan operation and its modifications are currently the standard palliation in patients with single ventricle physiology The advantages of extracardiac conduit Fontan operation (ECF) have previously been described We evaluated the outcome of patients who underwent ECF operation at our center since the year 2000 to assess morbidity, mortality and New York Heart Association (NYHA) functional class in the current era Medical records of 97 patients who underwent ECF operation from November 2000 till October 2013 were reviewed to determine the diagnosis, age at surgery, surgical technique, postoperative complications, NYHA class at last follow-up, echocardiographic parameters, and most recent Holter monitor results The median age at surgery was 34 years with 4 total deaths until last follow-up (hospital mortality was 1 %, and mortality after hospital discharge was 3 %) Seventy-eight of the 97 patients (80 %) underwent fenestrated Fontan surgery Median duration of follow-up was 39 years (IQR 02-122 years) At the latest follow-up, 62 patients (67 %) were determined to be in NYHA class I, 25 patients (27 %) in NYHA class II, and 6 (6 %) patients in NYHA class III, and the median oxygen saturation was 92 % (IQR 86-96) There were 15 patients with history of preoperative arrhythmias and 6 of them required pacemaker placement at the time of surgery One patient developed ectopic atrial tachycardia, and 1 patient had clinical thromboembolism on follow-up Systolic function of the single ventricle by transthoracic echocardiogram at the latest follow-up was described as normal in 77 patients (83 %), fair in 15 patients (16 %), and poor in 1 patient (1 %) The results of our study show that patients who undergo extracardiac conduit Fontan operation in the modern era may have significantly less morbidity and mortality when compared to earlier years

Intermediate-Term Results After Extracardiac Conduit Fontan Palliation in Children and Young Adults with Single Ventricle Physiology—A Single-center Experience

Early primary graft failure after pediatric orthotopic heart transplantation (OHT) has a high mortality rate and can occur due to several causes including but not limited to prolonged graft ischemia time, suboptimal preimplant myocardial preservation, hyperacute rejection, and maladaptation of the graft to the host's hemodynamic status. Mechanical circulatory support with either extracorporeal membrane oxygenation (ECMO) or ventricular assist device has been used for the rescue of primary graft failure in pediatric patients after heart transplant. Cardiac arrest before ECMO initiation in these patients is associated with adverse neurologic outcome although those surviving to hospital discharge generally have excellent long-term outcome. We report a case of early primary graft failure after OHT who required ECMO support and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

Early primary graft failure after a pediatric heart transplant and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

Factors that determine early outcomes in neonates with congenital heart disease (CHD) supported with prolonged venoarterial extracorporeal membrane oxygenation (ECMO) are not known and contemporary multicenter data are limited. This Extracorporeal Life Support Organization registry-based retrospective cohort study included all neonates (age ≤28 days) with CHD supported with venoarterial ECMO >7 days at 111 centers in the United States from January 2011 to December 2020. The primary outcome was survival-to-hospital discharge, and the secondary outcome was ECMO survival (successful decannulation before hospital discharge or death). Of the 2,155 total ECMO runs, 948 neonates received prolonged ECMO (gestational age [mean ± SD] 37.9 ± 1.8 weeks; birth weight 3.1 ± 0.6 kg; ECMO duration 13.6 ± 11.2 days). The ECMO survival rate was 51.6% (489 of 948), and the survival-to-hospital discharge rate was 23.9% (226 of 948). Body weight at ECMO (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.44 to 0.78/kg), gestational age (OR 0.89, 95% CI 0.79 to 1.00 per week), risk-adjusted congenital heart surgery-1 score (OR 1.22, 95% CI 1.04 to 1.45), and pump flow at 24 hours (OR 1.11, 95% CI 1.04 to 1.18 per 10 ml/kg/min) were significantly associated with survival-to-hospital discharge. Pre-ECMO mechanical ventilation duration, time to extubation after ECMO decannulation, and length of stay were inversely associated with hospital survival. Patient-specific (higher body weight and gestational age) and CHD-related (lower risk-adjusted congenital heart surgery-1 score) attributes are associated with better outcomes in neonates who receive prolonged venoarterial ECMO. Further elucidation of the factors associated with reduced survival to discharge in ECMO survivors is needed. 

Survival-to-Hospital Discharge in Neonates With Congenital Heart Disease Supported With Prolonged Extracorporeal Membrane Oxygenation.

A 17-year-old 55 kg, 156 cm cachexic male was admitted with cough, abdominal distention, and anasarca. He reported shortness of breath making it difficult to participate in gym class. Examination demonstrated severe hepatomegaly, ascites, tachypnea, and pitting lower extremity edema. Laboratory evaluation showed elevated brain natriuretic peptide, reduced synthetic liver function, and preserved renal function. Echocardiogram and cardiac catherization data was as shown in Table 1. He was started on Milrinone, diuretics and oxygen therapy. 

Shashi Raj

Papers

Anthracycline-Induced Cardiotoxicity: A Review of Pathophysiology, Diagnosis, and Treatment

Intermediate-Term Results After Extracardiac Conduit Fontan Palliation in Children and Young Adults with Single Ventricle Physiology—A Single-center Experience

Early primary graft failure after a pediatric heart transplant and successful rescue with plasmapheresis, immunoglobulins, and alemtuzumab.

Survival-to-Hospital Discharge in Neonates With Congenital Heart Disease Supported With Prolonged Extracorporeal Membrane Oxygenation.

An alternative approach of heartmate 3 implantation in restrictive cardiomyopathy.