The use of vasopressors to reduce post-intubation hypotension in critically ill adult patients undergoing emergent endotracheal intubation: a scoping review.

Introduction: Patients requiring emergent endotracheal intubation are at higher risk of post-intubation hypotension due to altered physiology in critical illness. Post-intubation hypotension increases mortality and hospital length of stay, however, the impact of vasopressors on its incidence and outcomes is not known. This scoping review identified studies reporting hemodynamic data in patients undergoing emergent intubation to provide a literature overview on post-intubation hypotension in cohorts that did and did not receive vasopressors.

A promoterless AAV6.2FF-based lung gene editing platform for the correction of surfactant protein B deficiency.

Surfactant protein B (SP-B) deficiency is a rare genetic disease that causes fatal respiratory failure within the first year of life. Currently, the only corrective treatment is lung transplantation. Here, we co-transduced the murine lung with adeno-associated virus 6.

Treatment-Resistant Wide-Complex Tachycardia in a Three-Year-Old Girl.

Wide-complex, monomorphic tachycardias represent a range of tachyarrhythmias. Such patients can present asymptomatically and hemodynamically stable, while others are in shock. The etiology of the rhythm can be difficult to determine in the emergency department, and although electrocardiogram findings may be helpful, a workup after stabilization may be necessary to determine the cause.

A palpable chest wall mass in a 4-year-old boy.

Empyema necessitans (EN) is a rare but dangerous complication of a lower respiratory tract infection. The diagnosis can be difficult to make and therefore delayed. We describe a case of a child with an atypical presentation of EN.

Gene therapy for Fabry disease: Progress, challenges, and outlooks on gene-editing.

Gene therapy is the delivery of a therapeutic gene for endogenous cellular expression with the goal of rescuing a disease phenotype. It has been used to treat an increasing number of human diseases with many strategies proving safe and efficacious in clinical trials. Gene delivery may be viral or non-viral, performed in vivo or ex vivo, and relies on gene integration or transient expression; all of these techniques have been applied to the treatment of Fabry disease.

A lung tropic AAV vector improves survival in a mouse model of surfactant B deficiency.

Surfactant protein B (SP-B) deficiency is an autosomal recessive disorder that impairs surfactant homeostasis and manifests as lethal respiratory distress. A compelling argument exists for gene therapy to treat this disease, as de novo protein synthesis of SP-B in alveolar type 2 epithelial cells is required for proper surfactant production. Here we report a rationally designed adeno-associated virus (AAV) 6 capsid that demonstrates efficiency in lung epithelial cell transduction based on imaging and flow cytometry analysis.

Interference chromatography: a novel approach to optimizing chromatographic selectivity and separation performance for virus purification.

Background: Oncolytic viruses are playing an increasingly important role in cancer immunotherapy applications. Given the preclinical and clinical efficacy of these virus-based therapeutics, there is a need for fast, simple, and inexpensive downstream processing methodologies to purify biologically active viral agents that meet the increasingly higher safety standards stipulated by regulatory authorities like the Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. However, the production of virus materials for clinical dosing of oncolytic virotherapies is currently limited-in quantity, quality, and timeliness-by current purification technologies.

Optimized Pre-Clinical Grade Production of Two Novel Lentiviral Vector Pseudotypes for Lung Gene Delivery.

Lung gene therapy requires efficient transduction of slow-replicating epithelia and stable expression of delivered transgenes in the respiratory tract. Lentiviral (LV) vectors have the ideal coding, expression, and transducing capacity required for gene therapy. A modified envelope glycoprotein from the Jaagsiekte Sheep Retrovirus, termed Jenv, is well suited for LV-mediated lung gene therapy due to its inherent lung tropism.

The U3 and Env Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Both Contribute to Tissue Tropism.

Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV) are small-ruminant betaretroviruses that share high nucleotide and amino acid identity, utilize the same cellular receptor, hyaluronoglucosaminidase 2 (Hyal2) for entry, and transform tissues with their envelope (Env) glycoprotein; yet, they target discrete regions of the respiratory tract-the lung and nose, respectively. This distinct tissue selectivity makes them ideal tools with which to study the pathogenesis of betaretroviruses. To uncover the genetic determinants of tropism, we constructed JSRV-ENTV chimeric viruses and produced lentivectors pseudotyped with the Env proteins from JSRV (Jenv) and ENTV (Eenv).

AAV-Mediated Gene Delivery to the Lung.

Adeno-associated virus (AAV) vectors are an efficient method of gene delivery to various tissues including the lung. Mouse models are often used as a preliminary preclinical model in order to advance AAV lung gene therapy vectors. In this chapter we describe an AAV purification protocol using heparin affinity chromatography as well as an intranasal and intratracheal method of delivering AAV vectors to the lungs of mice.

A Novel Triple-Mutant AAV6 Capsid Induces Rapid and Potent Transgene Expression in the Muscle and Respiratory Tract of Mice.

Gene therapy for the treatment of genetic disorders has demonstrated considerable therapeutic success in clinical trials. Among the most effective and commonly used gene delivery vectors are those based on adeno-associated virus (AAV). Despite these advances in clinical gene therapy, further improvements in AAV vector properties such as rapid intracellular processing and transgene expression, targeted transduction of therapeutically relevant cell types, and longevity of transgene expression, will render extension of such successes to many other human diseases.

Allogeneic Hematopoietic Cell Transplantation Using Treosulfan-Based Conditioning for Treatment of Marrow Failure Disorders.

Hematopoietic cell transplantation (HCT) is effective in the treatment of inherited marrow failure disorders and other nonmalignant diseases. Conventional myeloablative conditioning regimens have been associated with high transplant-related mortality, particularly in patients with comorbid conditions. Here we report on 14 patients with marrow failure disorders (Shwachman-Diamond syndrome, n = 3; Diamond Blackfan anemia, n = 4; GATA2 deficiency, n = 2; paroxysmal nocturnal hemoglobinuria, n = 4; and an undefined marrow failure disorder, n = 1) who underwent HCT on a prospective, phase II, multicenter clinical trial.

Rapid progression and mortality of lysosomal acid lipase deficiency presenting in infants.

Purpose: The purpose of this study was to enhance understanding of lysosomal acid lipase deficiency (LALD) in infancy.

Methods: Investigators reviewed medical records of infants with LALD and summarized data for the overall population and for patients with and without early growth failure (GF). Kaplan-Meier survival analyses were conducted for the overall population and for treated and untreated patients.

Human rhinovirus C infections in pediatric hematology and oncology patients.

Children with cancer and HSCT recipients are at high risk for common viral infections. We sought to define the viral etiology of ARI and identify risk factors. Nasal wash samples were collected from pediatric hematology-oncology patients and HSCT recipients with ARI during the 2003-2005 winter seasons.

Treosulfan-based conditioning and hematopoietic cell transplantation for nonmalignant diseases: a prospective multicenter trial.

Hematopoietic cell transplantation is an effective treatment for patients with nonmalignant diseases and for many is the only known cure. Conventional myeloablative regimens have been associated with unacceptably high early transplant-related mortality (TRM), particularly in patients with comorbid conditions. This prospective multicenter trial was designed to determine the safety and engraftment efficacy of treosulfan-based conditioning in patients with nonmalignant diseases.

The outcome of allogeneic hematopoietic cell transplantation for children with FMS-like tyrosine kinase 3 internal tandem duplication-positive acute myelogenous leukemia.

FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is a somatic mutation associated with poor outcome when treated with chemotherapy alone. In children, hematopoietic stem cell transplantation (HSCT) is recommended, but very limited data on outcome are reported. We determined the outcome of 29 children with FLT3/ITD-positive acute myelogenous leukemia (AML) who underwent allogeneic HSCT in 4 pediatric centers.

Targeted Busulfan therapy with a steady-state concentration of 600-700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant.

Busulfan (BU) has a narrow therapeutic window and the average concentration of BU at steady state (Css) is critical for successful engraftment in children receiving BU as part of the preparative regimen for allogeneic transplants. Sixteen patients with sickle cell disease (SCD) underwent allogeneic bone marrow transplant (BMT) from HLA-identical siblings. The preparative regimen consisted of intravenous BU 0.

Allogeneic hematopoietic stem cell transplantation for infants with idiopathic myelofibrosis.

IMF is a rare disease in children that can present during infancy and has a protracted course. The only known curative approach for this disease in adult patients is allogeneic HSCT. There are very few reports describing the long-term outcome of young children following stem cell transplantation for IMF.

New allergies after cord blood transplantation.

Background Aims: Umbilical cord blood transplantation (CBT) is an effective treatment for benign and malignant diseases. Late effects of CBT are not well described in the literature. In the present study, we present our experience of new-onset allergies in long-term survivors after CBT.

Incidence and risk factors for hypogammaglobulinemia in pediatric patients following allo-SCT.

We evaluated the incidence and risk factors for hypogammaglobulinemia after allogeneic hematopoietic SCT (HSCT) in pediatric patients. Ig levels were measured pre-transplant, every 2 weeks until day 100 and then monthly post SCT in 185 patients undergoing myeloablative HSCT. Median age was 9 years; 142 (77%) had malignant disease and 114 (62%) received stem cells from an unrelated source.