Extracorporeal life support for status asthmaticus: the breath of life that's often forgotten

Status asthmaticus continues to be significant cause of intensive care admission, morbidity, and mortality in pediatric populations. Furthermore, despite improved outpatient management and broader use of controller medications, patients with severe status asthmaticus account for a notable proportion of these admissions. There is variability in management and outcomes between institutions; however, early and aggressive management to avoid respiratory failure is paramount. In those patients who progress to develop severe respiratory failure, extracorporeal life support (ECLS) can be a life-saving therapy. Here, we briefly overview the use of ECLS for status asthmaticus, as reported through the Extracorporeal Life Support Organization, including the specific institutional experience at Children's Healthcare of Atlanta at Egleston, and consider how earlier initiation of ECLS may benefit patients with severe status asthmaticus refractory to conventional medical therapy

Extracorporeal Membrane Oxygenation: Beyond Conventional Indications

Over the last several years, the use of extracorporeal membrane oxygenation (ECMO) has exponentially increased. As the technology advanced, the rate of devastating complications has decreased somewhat, and the utility of ECMO has expanded beyond its conventional uses in cardiogenic shock and acute respiratory distress syndrome (ARDS). Currently, ECMO can be deployed in the perioperative period with high-risk surgeries where cardiac or respiratory compromise is anticipated. Moreover, it can be utilized in difficult airway patients or patients undergoing airway surgeries, thoracic surgery patients, trauma victims and many other conditions previously excluded. The aim of this review is to highlight the ECMO-patient interaction, the indications for ECMO in the non-cardiac surgery population, ECMO management and potential complications

Effects of down-regulating ornithine decarboxylase upon putrescine-associated metabolism and growth in Nicotiana tabacum L.

Transgenic plants of Nicotiana tabacum L. homozygous for an RNAi construct designed to silence ornithine decarboxylase (ODC) had significantly lower concentrations of nicotine and nornicotine, but significantly higher concentrations of anatabine, compared with vector-only controls. Silencing of ODC also led to significantly reduced concentrations of polyamines (putrescine, spermidine and spermine), tyramine and phenolamides (caffeoylputrescine and dicaffeoylspermidine) with concomitant increases in concentrations of amino acids ornithine, arginine, aspartate, glutamate and glutamine. Root transcript levels of S-adenosyl methionine decarboxylase, S-adenosyl methionine synthase and spermidine synthase (polyamine synthesis enzymes) were reduced compared with vector controls, whilst transcript levels of arginine decarboxylase (putrescine synthesis), putrescine methyltransferase (nicotine production) and multi-drug and toxic compound extrusion (alkaloid transport) proteins were elevated. In contrast, expression of two other key proteins required for alkaloid synthesis, quinolinic acid phosphoribosyltransferase (nicotinic acid production) and a PIP-family oxidoreductase (nicotinic acid condensation reactions), were diminished in roots of odc-RNAi plants relative to vector-only controls. Transcriptional and biochemical differences associated with polyamine and alkaloid metabolism were exacerbated in odc-RNAi plants in response to different forms of shoot damage. In general, apex removal had a greater effect than leaf wounding alone, with a combination of these injury treatments producing synergistic responses in some cases. Reduced expression of ODC appeared to have negative effects upon plant growth and vigour with some leaves of odc-RNAi lines being brittle and bleached compared with vector-only controls. Together, results of this study demonstrate that ornithine decarboxylase has important roles in facilitating both primary and secondary metabolism in Nicotiana

Volume 14

Table of Contents: Introduction: Dr. Amorette Barber From the Editor: Dr. Larissa Kat Tracy From the Designers: Rachel English, Rachel Hanson Hungry Like the Wolf: The Wolf as Metaphor in Paramount Network’s Yellowstone: Ireland Seagle “Floating Cities”: Illustrating the Commercial and Conservation Conflict of Alaskan Cruise Ship Tourism: Dalton C. Whitby What Can You Do When Your Genes are the Enemy? Current Applications of Gene Manipulation and the Associated Ethical Considerations: Cassandra Poole La doble cara: un tema romántico en las obras de Larra y Hawthorne: Rachel Cannon Resolving a Conflict: How to Teach Evolution to Students with a Religious Background: Heidi Parker-Combes A History of Secret Societies at Longwood University and Their Relationship to Student Power and Agency: Devon G. Shifflett Policy Brief: Addressing Petroleum Pollution in the Chesapeake Bay around Naval Station Norfolk: Antonio Harve

Extracorporeal membrane oxygenation in postcardiotomy patients: Factors influencing outcome

ObjectiveOur objective was to assess the morbidity and mortality in children requiring extracorporeal membrane oxygenator support after cardiac surgery and to determine factors influencing outcome.MethodsBetween January 2003 and June 2008, 58 patients required extracorporeal membrane oxygenator support after cardiac surgery. A retrospective study was performed and factors influencing outcome were determined by logistic regression modeling with the probability of outcome based on a combination of multivariate predictors.ResultsMedian age and weight were 12 days and 3.3 kg, respectively. Thirty-one patients had single ventricle repair and 27 had biventricular repair. Median duration of support with the oxygenator was 6 days. Thirty-nine (67%) patients were successfully weaned off the support, but only 24 (41%) survived to hospital discharge. Chief complications were renal failure (31%), neurologic complications (29%), and sepsis (16%). Multivariable logistic regression analysis identified 10 days or more of extracorporeal membrane oxygenation (odds ratio = 6.1), urine output less than 2 mL · kg−1 · h−1 in first 24 hours (odds ratio = 15), renal failure (odds ratio = 9.4), and pH less than 7.35 after 24 hours of extracorporeal membrane oxygenation (odds ratio = 82) as significant independent factors associated with failure to wean off extracorporeal membrane oxygenation. Factors associated with failure of hospital discharge despite successful decannulation were as follows: extracorporeal membrane oxygenator support time of 10 days or more, red blood cell transfusion of greater than 1000 mL/kg during the entire period of oxygenator support, and sepsis. Patients with single ventricle repair were at higher risk of hospital mortality.ConclusionLonger duration of extracorporeal membrane oxygenator support, low pH and urine output in the first 24 hours, and renal failure are significant factors associated with mortality during extracorporeal membrane oxygenator support. Exposure to high amounts of blood transfusion during extracorporeal oxygenation, extended extracorporeal membrane oxygenator support, and sepsis increase risk of death after successful decannulation

Teleost Growth Factor Independence (Gfi) Genes Differentially Regulate Successive Waves of Hematopoiesis

Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification. In mammals, Gfi1a regulates hematopoietic stem cells (HSC), myeloid and lymphoid populations, while its paralog, Gfi1b, regulates HSC, megakaryocyte and erythroid development. In zebrafish, gfi1aa is essential for primitive hematopoiesis; however, little is known about the role of gfi1aa in definitive hematopoiesis or about additional gfi factors in zebrafish. Here, we report the isolation and characterization of an additional hematopoietic gfi factor, gfi1b. We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish. Our functional analyses demonstrate that gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors, respectively. Loss of gfi1aa silences markers of early primitive progenitors, scl and gata1. Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis. We determine the epistatic relationships between the gfi factors and key hematopoietic transcription factors, demonstrating that gfi1aa and gfi1b join lmo2, scl, runx-1 and c-myb as critical regulators of teleost HSPC. Our studies establish a comparative paradigm for the regulation of hematopoietic lineages by gfi transcription factors.Stem Cell and Regenerative Biolog

Hemorrhage and thrombosis in COVID-19-patients supported with extracorporeal membrane oxygenation: an international study based on the COVID-19 critical care consortium

Background: Extracorporeal membrane oxygenation (ECMO) is a rescue therapy in patients with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19. While bleeding and thrombosis complicate ECMO, these events may also occur secondary to COVID-19. Data regarding bleeding and thrombotic events in COVID-19 patients on ECMO are sparse. Methods: Using the COVID-19 Critical Care Consortium database, we conducted a retrospective analysis on adult patients with severe COVID-19 requiring ECMO, including centers globally from 01/2020 to 06/2022, to determine the risk of ICU mortality associated with the occurrence of bleeding and clotting disorders. Results: Among 1,248 COVID-19 patients receiving ECMO support in the registry, coagulation complications were reported in 469 cases (38%), among whom 252 (54%) experienced hemorrhagic complications, 165 (35%) thrombotic complications, and 52 (11%) both. The hazard ratio (HR) for Intensive Care Unit mortality was higher in those with hemorrhagic-only complications than those with neither complication (adjusted HR = 1.60, 95% CI 1.28–1.99, p < 0.001). Death was reported in 617 of the 1248 (49.4%) with multiorgan failure (n = 257 of 617 [42%]), followed by respiratory failure (n = 130 of 617 [21%]) and septic shock [n = 55 of 617 (8.9%)] the leading causes. Conclusions: Coagulation disorders are frequent in COVID-19 ARDS patients receiving ECMO. Bleeding events contribute substantially to mortality in this cohort. However, this risk may be lower than previously reported in single-nation studies or early case reports. Trial registration ACTRN12620000421932 (https://covid19.cochrane.org/studies/crs-13513201)

Use of selective serotonin reuptake inhibitors and risk of re-operation due to post-surgical bleeding in breast cancer patients: a Danish population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRI) decrease platelet-function, which suggests that SSRI use may increase the risk of post-surgical bleeding. Few studies have investigated this potential association.</p> <p>Methods</p> <p>We conducted a population-based study of the risk of re-operation due to post-surgical bleeding within two weeks of primary surgery among Danish women with primary breast cancer. Patients were categorised according to their use of SSRI: never users, current users (SSRI prescription within 30 days of initial breast cancer surgery), and former users (SSRI prescription more than 30 days before initial breast cancer surgery). We calculated the risk of re-operation due to post-surgical bleeding within 14 days of initial surgery, and the relative risk (RR) of re-operation comparing SSRI users with never users of SSRI adjusting for potential confounders.</p> <p>Results</p> <p>389 of 14,464 women (2.7%) were re-operated. 1592 (11%) had a history of SSRI use. Risk of re-operation was 2.6% among never users, 7.0% among current SSRI users, and 2.7% among former users. Current users thus had an increased risk of re-operation due to post-operative bleeding (adjusted relative risk = 2.3; 95% confidence interval (CI) = 1.4, 3.9) compared with never users. There was no increased risk of re-operation associated with former use of SSRI (RR = 0.93, 95% CI = 0.66, 1.3).</p> <p>Conclusions</p> <p>Current use of SSRI is associated with an increased risk of re-operation due to bleeding after surgery for breast cancer.</p

ClinGen Variant Curation Interface: a variant classification platform for the application of evidence criteria from ACMG/AMP guidelines.

BACKGROUND: Identification of clinically significant genetic alterations involved in human disease has been dramatically accelerated by developments in next-generation sequencing technologies. However, the infrastructure and accessible comprehensive curation tools necessary for analyzing an individual patient genome and interpreting genetic variants to inform healthcare management have been lacking. RESULTS: Here we present the ClinGen Variant Curation Interface (VCI), a global open-source variant classification platform for supporting the application of evidence criteria and classification of variants based on the ACMG/AMP variant classification guidelines. The VCI is among a suite of tools developed by the NIH-funded Clinical Genome Resource (ClinGen) Consortium and supports an FDA-recognized human variant curation process. Essential to this is the ability to enable collaboration and peer review across ClinGen Expert Panels supporting users in comprehensively identifying, annotating, and sharing relevant evidence while making variant pathogenicity assertions. To facilitate evidence-based improvements in human variant classification, the VCI is publicly available to the genomics community. Navigation workflows support users providing guidance to comprehensively apply the ACMG/AMP evidence criteria and document provenance for asserting variant classifications. CONCLUSIONS: The VCI offers a central platform for clinical variant classification that fills a gap in the learning healthcare system, facilitates widespread adoption of standards for clinical curation, and is available at https://curation.clinicalgenome.org