Novel Macrocyclic NLRP3 Inhibitors.

Aberrant activation of NLRP3 due to persistent tissue damage, misfolded proteins or crystal deposits has been linked to multiple chronic inflammatory disorders such as cryopyrin-associated periodic syndrome (CAPS), neurodegenerative diseases, gouty arthritis, and numerous others. Hence, there has been an increasing interest in NLRP3 inhibitors as therapeutics. A first generation of NLRP3 inhibitors bearing a sulfonylurea core such as MCC950 (developed by Pfizer) were discovered by phenotypic screening, however their mode of action was only elucidated later.

Cardiorespiratory Stability in Critically Ill Preterm Infants following Dexmedetomidine Initiation.

Objective:  This study aimed to evaluate cardiorespiratory status in preterm infants receiving dexmedetomidine using high-resolution physiologic data.

Study Design:  We analyzed preterm infants with continuous heart rate (HR) and oxygen saturation (SpO) data for 24 hours preceding and 48 hours following dexmedetomidine initiation. Invasive arterial blood pressure (ABP), when available, was analyzed.

Screening tools to evaluate the neurotoxic potential of botanicals: building a strategy to assess safety.

Areas Covered: This paper outlines the selection of NAMs, including in vitro assays using primary rat cortical neurons, zebrafish embryos, and . These assays aim to assess neurotoxic endpoints such as neuronal activity and behavioral responses. Microelectrode array recordings of rat cortical neurons provide insights into the impact of botanical extracts on neuronal function, while the zebrafish embryos and assays evaluate neurobehavioral responses.

Dexmedetomidine During Therapeutic Hypothermia: A Multicenter Quality Initiative.

Objectives: Sedation is typically used during neonatal therapeutic hypothermia (TH). This report describes a quality improvement (QI) initiative with the aim of decreasing opioid exposure during TH by implementing dexmedetomidine as the primary sedative agent.

Methods: This dual-center QI initiative used a multidisciplinary team to create a sedation algorithm for safe implementation of dexmedetomidine as first-line therapy during TH.

Bad Liver and a Broken Heart: Hepatitis B in the Newborn.

Hepatitis B viral infection is a significant source of morbidity and mortality worldwide. The United States has experienced a precipitous drop in acute hepatitis B infection after the introduction and widespread adoption of recombinant vaccines. Neonates experience significant risk from both vertical and horizontal hepatitis B exposure during a period of immaturity of the innate and adaptive immune systems.

Gabapentin as Adjunctive Therapy in Neonatal Opioid Withdrawal Syndrome: A Case Series.

Objective: We describe a single center experience with gabapentin as adjunctive therapy in infants with neonatal opioid withdrawal syndrome (NOWS).

Methods: We performed a retrospective chart review of infants receiving gabapentin for NOWS. Data points collected included patient's sex, gestational age, maternal opioid exposure, NOWS medication dosing and length of therapy, number of failed wean attempts, time to successful morphine wean and duration of morphine wean, length of stay in the neonatal intensive care unit (NICU), and NOWS medications at discharge.

Up in Smoke: The Impacts of Marijuana During Pregnancy.

Numerous drugs ingested during pregnancy can impact the developing fetus. Although some effects are apparent at birth as overt teratogenicity or profound neonatal withdrawal, others become apparent only after a careful long-term follow-up into childhood. Shifting legal and cultural attitudes toward marijuana have led to increased use during pregnancy.

A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma.

Asthma affects 339 million people worldwide, with an estimated 5-10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS.

Eyesight to the Blind-Pharmacotherapy for Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) places preterm infants at significant risk for blindness. Angiogenesis of retinal blood vessels relies on vascular endothelial growth factor (VEGF) released in response to physiologic in utero hypoxia. Relative hyperoxia and disruption in the supply of growth factors after preterm birth lead to cessation of normal vascular growth.

High Content Imaging and Quantification of Microglia Phagocytosis In Vitro.

Microglia function as the tissue-specific resident macrophages of the nervous system, performing immune and non-immune functions. These functions are critical to development and to maintain homeostasis in the nervous system throughout the lifespan, and during brain injury or disease. One method by which microglia maintain homeostasis is phagocytosis of aberrant proteins, extracellular debris, synapses, or apoptotic cells.

No Code-The Role of Sodium Bicarbonate and Naloxone in Neonatal Resuscitation.

Resuscitations in neonates and infants present caregivers with challenging decisions in a highly stressful environment. Consideration of the pathophysiology of cardiac arrest and respiratory failure prior to an emergency allows for thoughtful utilization of pharmacotherapy. It is vital to remember that establishment of an airway and delivery of breaths and chest compressions should be prioritized.

Assessment of compatibility of rhIGF-1/rhIGFBP-3 with neonatal intravenous medications.

Background: Recombinant human (rh)IGF-1/IGFBP-3 protein complex, administered as a continuous intravenous infusion in preterm infants, is being studied for the prevention of complications of prematurity.

Methods: We conducted in vitro studies to evaluate the physical and chemical compatibility of rhIGF-1/IGFBP-3 with medications routinely administered to preterm neonates. In vitro mixing of rhIGF-1/IGFBP-3 drug product with small-molecule test medications plus corresponding controls was performed.

Fentanyl Exposure in Preterm Infants: Five-Year Neurodevelopmental and Socioemotional Assessment.

Objective: To evaluate the association between cumulative fentanyl dose during neonatal intensive care and 5-year neurodevelopmental and socioemotional outcomes in very preterm infants.

Materials And Methods: Patient demographics and clinical factors during the perinatal and neonatal course were collected in 84 patients born between 23- and 30-weeks gestational age (GA). Cumulative fentanyl dose during neonatal intensive care was calculated.

Know the Code: Medications for Resuscitation in Neonates.

Resuscitations in the delivery room or the nursery cause significant stress for caregivers. Diligent preparation will improve the efficacy and safety of life-saving interventions and increase staff comfort. When establishment of an airway and delivery of positive pressure ventilation and chest compressions fail to result in return of spontaneous circulation, pharmacotherapeutic interventions should be considered.

The Impact of Dexmedetomidine Initiation on Cardiovascular Status and Oxygenation in Critically ill Neonates.

Dexmedetomidine is being increasingly used as a primary or adjunctive sedative agent in neonates. There are a paucity of high-quality, high-resolution physiologic data during administration, despite significant potential cardiorespiratory effects. Term and preterm infants admitted between January 2018 and July 2020 were screened for dexmedetomidine exposure.

Pharmacologic Analgesia and Sedation in Neonates.

Chronic pain and agitation in neonatal life impact the developing brain. Oral sweet-tasting solutions should be used judiciously to mitigate behavioral responses to mild painful procedures, keeping in mind that the long-term impact is unknown. Rapidly acting opioids should be used as part of premedication cocktails for nonemergent endotracheal intubations.

Five-year outcomes of premature infants randomized to high or standard loading dose caffeine.

Objective: To examine 5-year outcomes in children enrolled in a pilot randomized controlled trial of a high loading dose of caffeine after preterm birth.

Study Design: Seventy-four very low birth weight neonates were randomized within the first 24 h of life to receive a high (80 mg/kg) or standard (20 mg/kg) loading dose of caffeine citrate. At 5 years of age, we conducted standardized neurodevelopmental tests and collected parent reports of child socioemotional problems.

Neuroprotective Agents for Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) remains a significant source of long-term neurodevelopmental impairment despite overall improvements in survival without disability in neonates who undergo therapeutic hypothermia. Each phase in the evolution of hypoxic-ischemic injury presents potential pharmacologic targets for neuroprotective agents. Melatonin is a promising emerging therapy for early phases of ischemic injury, but utility is currently limited by the lack of pharmaceutical-grade products.

Antibiotic spectrum index: A new tool comparing antibiotic use in three NICUs.

Background: Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures.

Development of Protein-Specific Analytical Methodologies to Evaluate Compatibility of Recombinant Human (rh)IGF-1/rhIGFBP-3 with Intravenous Medications Co-Administered to Neonates.

The protein complex of recombinant human insulin-like growth factor-1 and insulin‑like growth factor binding protein‑3 (rhIGF-1/rhIGFBP-3; mecasermin rinfabate), is an investigational product for the prevention of complications of prematurity. Delivery of rhIGF-1/rhIGFBP-3 is by continuous central line intravenous infusion in preterm infants until endogenous IGF-1 production begins. Protein-specific analytical methodologies were developed to evaluate the compatibility of rhIGF-1/rhIGFBP-3 at low protein concentrations (∼2.

Successful Use of Intravenous Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Pediatric Patients.

 Methylnaltrexone is U.S. Food and Drug Administration (FDA) approved as a subcutaneous injection for adults with opioid-induced constipation (OIC).