The Implementation of an Emergency Medicine Telehealth System During a Pandemic.

BACKGROUND: In March of 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19)-a disease caused by a novel coronavirus-a pandemic, and it continued to spread rapidly in the community. Our institution implemented an emergency medicine telehealth system that sought to expedite care of stable patients, decrease provider exposure to COVID-19, decrease overall usage rate of personal protective equipment, and provide a platform so that infected or quarantined physicians could continue to work. This effort was among the first to use telehealth to practice emergency medicine in the setting of a pandemic in the United States. DISCUSSION: Outside the main emergency departments at each of 2 sites of our academic institution, disaster tents were erected with patient care equipment and medications, as well as technology to allow for telehealth visits. The triage system was modified to appropriately select low-risk patients with symptoms suggestive of COVID-19 who could be seen in these disaster tents. Despite some issues that needed to be addressed, such as provider discomfort, limited medication availability, and connectivity problems, the model was successful overall. CONCLUSIONS: Other emergency departments might find this proof of concept article useful. Telehealth will likely be used more broadly in the future, including emergency care. It is imperative that the health care system continues to adapt to respond appropriately to challenges such as pandemics.

Correction: Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis.

[This corrects the article DOI: 10.1371/journal.pone.0175936.].

Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis.

BACKGROUND: A host defense function for Alkaline phosphatases (ALPs) is suggested by the contribution of intestinal ALP to detoxifying bacterial lipopolysaccharide (endotoxin) in animal models in vivo and the elevation of ALP activity following treatment of human cells with inflammatory stimuli in vitro. However the activity of ALP in human plasma (primarily tissue-nonspecific ALP; TNAP) on lipopolysaccharide and other microbial products has not been assessed, nor has its expression been studied in preterm newborns, a vulnerable population at high risk of sepsis. In this context, the aim of our study was to characterize the activity of TNAP on Toll-like receptor (TLR) agonists and assess the concentrations of plasma ALP during late-onset sepsis in preterm newborns. METHODS: Recombinant human TNAP was incubated with microbial products and phosphate release was measured by malachite green assay. Plasma ALP activity was measured serially in a cohort of preterm (N = 129) infants at high risk of late-onset sepsis (LOS). RESULTS: TNAP dephosphorylates poly-inosine:cytosine (Toll-like receptor (TLR) 3 agonist) and LPS from Klebsiella pneumoniae and Salmonella minnesota (TLR4 agonists). Plasma ALP significantly increased postnatally over the first 4 weeks of life in preterm and term newborns. Bacteremic LOS in preterm infants (gestational age ≤ 30 weeks) was associated with significantly elevated plasma ALP at 4 weeks postnatal age. CONCLUSIONS: TNAP, the main circulating isozyme of ALP, de-phosphorylates TLR agonists, demonstrates a post-natal age dependent increase in preterm and term plasma across the first 4 weeks of life, and is elevated in association with preterm LOS.

Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine.

Extracellular adenosine, a key regulator of physiology and immune cell function that is found at elevated levels in neonatal blood, is generated by phosphohydrolysis of adenine nucleotides released from cells and catabolized by deamination to inosine. Generation of adenosine monophosphate (AMP) in blood is driven by cell-associated enzymes, whereas conversion of AMP to adenosine is largely mediated by soluble enzymes. The identities of the enzymes responsible for these activities in whole blood of neonates have been defined in this study and contrasted to adult blood. We demonstrate that soluble 5'-nucleotidase (5'-NT) and alkaline phosphatase (AP) mediate conversion of AMP to adenosine, whereas soluble adenosine deaminase (ADA) catabolizes adenosine to inosine. Newborn blood plasma demonstrates substantially higher adenosine-generating 5'-NT and AP activity and lower adenosine-metabolizing ADA activity than adult plasma. In addition to a role in soluble purine metabolism, abundant AP expressed on the surface of circulating neonatal neutrophils is the dominant AMPase on these cells. Plasma samples from infant observational cohorts reveal a relative plasma ADA deficiency at birth, followed by a gradual maturation of plasma ADA through infancy. The robust adenosine-generating capacity of neonates appears functionally relevant because supplementation with AMP inhibited whereas selective pharmacologic inhibition of 5'-NT enhanced Toll-like receptor-mediated TNF-α production in neonatal whole blood. Overall, we have characterized previously unrecognized age-dependent expression patterns of plasma purine-metabolizing enzymes that result in elevated plasma concentrations of anti-inflammatory adenosine in newborns. Targeted manipulation of purine-metabolizing enzymes may benefit this vulnerable population.