An environmental risk assessment of IPD079Ea: a protein derived from Ophioglossum pendulum with activity against Diabrotica spp.In maize.

Farmers in North America face significant pressure from insects in their maize fields, particularly from corn rootworm (Diabrotica spp.). Research into proteins capable of insecticidal activity has found several produced by ferns. One protein, IPD079Ea, was derived from Ophioglossum pendulum and has shown activity against corn rootworm. An environmental risk assessment was conducted for maize event DP-915635-4, which provides control of corn rootworms via expression of the IPD079Ea protein. This assessment focused on IPD079Ea and characterized potential exposure and hazard to non-target organisms (NTOs). For exposure, estimated environmental concentrations (EECs) were calculated. For hazard, laboratory dietary toxicity studies were conducted with IPD079Ea and surrogate non-target organisms. Environmental risk was characterized by comparing hazard and exposure to calculate the margin of exposure (MOE). Based on the MOE values for DP-915635-4 maize, the IPD079Ea protein is not expected to result in unreasonable adverse effects on beneficial NTO populations at environmentally relevant concentrations.

Hospital survival following pediatric HSCT: changes in complications, ICU therapies and outcomes over 10 years.

Introduction: Hematopoietic stem cell transplantation (HSCT) is an increasingly utilized therapy for malignant and non-malignant pediatric diseases. HSCT complications, including infection, organ dysfunction, and graft-versus-host-disease (GVHD) often require intensive care unit (ICU) therapies and are associated with mortality. Our aims were to identify the HSCT characteristics, complications and ICU therapies associated with (1) survival, and (2) survival changes over a ten-year period in a national dataset. Methods: A national sample from the Health Facts (Cerner Corporation, Kansas City, MO) database from 2009 to 2018 was utilized. Inclusion criteria were age 30 days to <22 years and HSCT procedure code. For patients with >1 HSCT, the first was analyzed. Data included demographics, hospital length of stay (LOS), hospital outcome, transplant type and indication. HSCT complications included GVHD and infections. ICU therapies were positive pressure ventilation (PPV), vasoactive infusion, and dialysis. Primary outcome was survival to discharge. Statistical methods included bivariate analyses and multivariate logistic regression. Results: 473 patients underwent HSCT with 93% survival. 62% were allogeneic (89% survival) and 38% were autologous (98% survival). GVHD occurred in 33% of allogeneic HSCT. Infections occurred in 26% of all HSCT. ICU therapies included PPV (11% of patients), vasoactive (25%), and dialysis (3%). Decreased survival was associated with allogeneic HSCT (p < 0.01), GVHD (p = 0.02), infection (p < 0.01), and ICU therapies (p < 0.01). Survival improved from 89% (2009-2013) to 96% (2014-2018) (p < 0.01). Allogeneic survival improved (82%-94%, p < 0.01) while autologous survival was unchanged. Survival improvement over time was associated with decreasing infections (33%-21%, p < 0.01) and increasing vasoactive infusions (20%-28%, p = 0.05). On multivariate analysis, later time period was associated with improved survival (p < 0.01, adjusted OR 4.28). Discussion: Hospital survival for HSCT improved from 89% to 96% from 2009 to 2018. Factors associated with mortality included allogeneic HSCT, GVHD, infections and ICU therapies. Improving survival coincided with decreasing infections and increasing vasoactive use.

Extracorporeal Life Support for Cardiogenic Shock in Adult Congenital Heart Disease-An ELSO Registry Analysis.

There are minimal data on the use of venoarterial extracorporeal membrane life support (VA-ECLS) in adult congenital heart disease (ACHD) patients presenting with cardiogenic shock (CS). This study sought to describe the population of ACHD patients with CS who received VA-ECLS in the Extracorporeal Life Support Organization (ELSO) Registry. This was a retrospective analysis of adult patients with diagnoses of ACHD and CS in ELSO from 2009-2021. Anatomic complexity was categorized using the American College of Cardiology/American Heart Association 2018 guidelines. We described patient characteristics, complications, and outcomes, as well as trends in mortality and VA-ECLS utilization. Of 528 patients who met inclusion criteria, there were 32 patients with high-complexity anatomy, 196 with moderate-complexity anatomy, and 300 with low-complexity anatomy. The median age was 59.6 years (interquartile range, 45.8-68.2). The number of VA-ECLS implants increased from five implants in 2010 to 81 implants in 2021. Overall mortality was 58.3% and decreased year-by-year (ß= -2.03 [95% confidence interval, -3.36 to -0.70], p = 0.007). Six patients (1.1%) were bridged to heart transplantation and 21 (4.0%) to durable ventricular assist device. Complications included cardiac arrhythmia/tamponade (21.6%), surgical site bleeding (17.6%), cannula site bleeding (11.4%), limb ischemia (7.4%), and stroke (8.7%). Utilization of VA-ECLS for CS in ACHD patients has increased over time with a trend toward improvement in survival to discharge.

Extracorporeal cardiopulmonary resuscitation in adults and children: A review of literature, published guidelines and pediatric single-center program building experience.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an adjunct supportive therapy to conventional cardiopulmonary resuscitation (CCPR) employing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the setting of refractory cardiac arrest. Its use has seen a significant increase in the past decade, providing hope for good functional recovery to patients with cardiac arrest refractory to conventional resuscitation maneuvers. This review paper aims to summarize key findings from the ECPR literature available to date as well as the recommendations for ECPR set forth by leading national and international resuscitation societies. Additionally, we describe the successful pediatric ECPR program at Texas Children's Hospital, highlighting the logistical, technical and educational features of the program.

Characterization of the Spectrum of Activity of IPD079Ea: A Protein Derived From Ophioglossum pendulum (Ophioglossales: Ophioglossaceae) With Activity Against Western Corn Rootworm [Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae)].

Western corn rootworm (Diabrotica virgifera virgifera LeConte) is a major pest of corn in both North America and Europe and as such presents significant challenges for farmers. IPD079Ea protein is encoded by the ipd079Ea gene from Ophioglossum pendulum (a species of fern) and was found to have activity against western corn rootworm in multiple corn events transformed to express the IPD079Ea protein. In chronic laboratory hazard studies, IPD079Ea protein was fed to eleven species in the order Coleoptera and four species in the order Lepidoptera to assess the spectrum of activity. Activity was observed on certain species of the Chrysomelidae and Coccinellidae families, with western corn rootworm as the most sensitive insect tested. No adverse effects on mortality or other sublethal endpoints were observed on any species within Lepidoptera. Overall, IPD079Ea protein appears not to have broad insecticidal properties and has potential value as an effective trait to control western corn rootworm in agricultural systems.

Extracorporeal Membrane Oxygenation Support for Antineutrophil Cytoplasmic Antibody-associated Vasculitides: An ELSO Registry Analysis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides with pulmonary involvement include granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, and can present with life-threatening pulmonary hemorrhage in up to 40% of patients. Mortality in those patients who require intubation and mechanical ventilation can reach 77%. Extracorporeal membrane oxygenation (ECMO) can be used to support these patients through definitive diagnosis and treatment, although minimizing the risk of ventilator-induced lung injury. We aimed to determine factors associated with favorable outcomes in patients with (ANCA)-associated vasculitides supported on ECMO. We performed a retrospective observational study using the Extracorporeal Life Support Organization registry of pediatric and adult patients with ANCA-associated vasculitis supported on ECMO from 2010 to 2020. One hundred thirty-five patients were included for analysis. Many patients had renal involvement (39%) in addition to pulmonary involvement (93%). Survival was 73% in AAV patients supported on ECMO. The presence of pulmonary hemorrhage was not associated with worse outcomes in our cohort. Older age, the use of venoarterial ECMO, ECMO-cardiopulmonary resuscitation, or sustaining a cardiac arrest before ECMO was associated with decreased survival. In conclusion, venovenous ECMO should be considered as a supportive bridge to definitive diagnosis and treatment in (ANCA)-associated vasculitides, regardless if pulmonary hemorrhage is present.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Environmental risk assessment of the DvSSJ1 dsRNA and the IPD072Aa protein to non-target organisms.

Event DP-Ø23211-2 (hereafter referred to as DP23211) maize expresses the DvSSJ1 double-stranded RNA (DvSSJ1 dsRNA) and the IPD072Aa protein, encoded by the ipd072Aa gene. DvSSJ1 dsRNA and the IPD072Aa protein each provide control of corn rootworms (Diabrotica spp.) when expressed in plants. As part of the environmental risk assessment (ERA), the potential hazard to non-target organisms (NTOs) exposed to the DvSSJ1 dsRNA and the IPD072Aa protein expressed in DP23211 maize was assessed. Worst-case estimated environmental concentrations (EECs) for different NTO functional groups (pollinators and pollen feeders, soil dwelling detritivores, predators and parasitoids, aquatic detritivores, insectivorous birds, and wild mammals) were calculated using worst-case assumptions. Several factors that reduce exposure to NTOs under more realistic environmental conditions were applied, when needed to provide more environmentally relevant EECs. Laboratory bioassays were conducted to assess the activity of DvSSJ1 dsRNA or the IPD072Aa protein against selected surrogate species, and margins of exposure (MOEs) were calculated by comparing the Tier I hazard study results to worst-case or refined EECs. Based on specificity and MOE values, DvSSJ1 dsRNA and the IPD072Aa protein expressed in DP23211 maize are not expected to be harmful to NTO populations at environmentally relevant concentrations.

Improving Outcomes for Children Requiring Extracorporeal Membrane Oxygenation Therapy Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The objective of this study was to provide an updated review of survival for pediatric hematopoietic stem cell transplantation patients requiring extracorporeal membrane oxygenation therapy as well as characterize the demographics, clinical variables, and complications associated with mortality. DESIGN: Retrospective database review of the Extracorporeal Life Support Organization Registry from 1990 to 2019. SETTING: Extracorporeal membrane oxygenation centers reporting to Extracorporeal Life Support Organization. PATIENTS: Patients treated with extracorporeal membrane oxygenation greater than 28 days to 18 years old with International Classification of Diseases Ninth Revision, International Classification of Diseases Tenth Revision, and current procedural terminology codes consistent with hematopoietic stem cell transplantation were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, year of extracorporeal membrane oxygenation run, clinical variables, comorbid diagnoses, and extracorporeal membrane oxygenation complications were assessed in relation to the primary study outcome of survival to hospital discharge. Ninety patients were included in the final analysis. The overall survival rate for the study period was 19%. However, the survival rate in the last decade (2010-2019) improved to 26% (p = 0.01; odds ratio 9.4 [1.2-74.8]). Factors associated with decreased survival included comorbid malignancy, elevated peak inspiratory pressure in conventionally ventilated patients, and pulmonary and metabolic complications on extracorporeal membrane oxygenation. CONCLUSIONS: Pediatric patients posthematopoietic stem cell transplantation supported with extracorporeal membrane oxygenation have improving survival rates over time. With 26% of patients (16/62) surviving to hospital discharge in the last decade (2010-2019), history of hematopoietic stem cell transplantation may no longer be considered an absolute contraindication to extracorporeal membrane oxygenation. As advancements are made in hematopoietic stem cell transplantation therapies and extracorporeal membrane oxygenation management, the indications for life-saving extracorporeal membrane oxygenation support among patients posthematopoietic stem cell transplantation may expand accordingly.