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As the opioid epidemic escalates in westernized countries around the world, chronic opioid use during pregnancy has become a growing public health issue. There are increasing concerns that chronic maternal opioid use might adversely affect the developing fetal brain. Furthermore, the sudden discontinuation of the trans-placental opioid supply at birth puts newborns at acute risk for neonatal opioid withdrawal syndrome (NOWS). NOWS is a multi-system disorder that has been identified in approximately 50-80% of neonates exposed to opioids due to chronic maternal use. Clinically, NOWS affects the central and autonomic nervous systems as well as the gastrointestinal and respiratory tracts. The clinical features of NOWS include hyperirritability, high-pitched crying, restlessness, tremors, poor sleep, agitation, seizures, sweating, fever, poor feeding, regurgitation, diarrhea, and tachypnea. NOWS is currently diagnosed using a clinical scoring tool followed by toxicological confirmation of the presence of opioids in meconium or tissue specimens. The first-line treatments for NOWS are non-pharmacologic comfort measures. If these measures fail, neonates may be treated with opioids and/or sedatives. Since the severity of NOWS can be highly variable, it is quite difficult to predict which opioid-exposed neonates will require pharmacotherapy and prolonged hospitalization. Factors associated with maternal polysubstance use, including the use of illicit substances and tobacco, have been associated with the increased severity and duration of NOWS. Since neonates with NOWS are at increased risk for long-term adverse neurodevelopmental outcomes, ongoing monitoring beyond the neonatal period is essential., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The objective is to study previously unexplored trends of birth hospitalization and readmission costs for late preterm infants (LPIs) in the United States between 2005 and 2016. Methods: We conducted a retrospective analysis of claims data to study healthcare costs of birth hospitalization and readmissions for LPIs compared to term infants (TIs) using a large private insurance database. We used a generalized linear regression model to study birth hospitalization and readmission costs. Results: A total of 2,123,143 infants were examined (93.2% TIs; 6.8% LPIs). The proportion of LPIs requiring readmission was 4.2% compared to 2.1% of TIs, ( p < 0.001). The readmission rate for TIs decreased during the study period. LPIs had a higher mean cost of birth hospitalization (25,700 vs. 3300 USD; p < 0.001) and readmissions (25,800 vs. 14,300 USD; p < 0.001). For LPIs, birth hospitalization costs increased from 2007 to 2013, and decreased since 2014. Conversely, birth hospitalization costs of TIs steadily increased since 2005. The West region showed higher birth hospitalization costs for LPIs. Conclusions: LPIs continue to have a higher cost of birth hospitalization and readmission compared to TIs, but these costs have decreased since 2014. Standardization of birth hospitalization care for LPIs may reduce costs and improve quality of care and outcomes.

Purpose: The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure. Objective: This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates. Methods: This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24-48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%. Results: SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls ( p  < .05). Opioid-exposed neonates demonstrated higher NFCS at baseline ( p  = .003). Conclusions: Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS.

Mucolipidosis II α/beta (MLII) is an autosomal recessive disease in which a gene mutation leads to improper targeting of lysosomal enzymes with an end result of accumulation of lysosomes in the mitochondria resulting in a dysfunctional mitochondria. 1 Leigh syndrome (LS) is a rare progressive neurodegenerative disorder associated with dysfunctional mitochondria and oxidative phosphorylation. 4 Both disease processes typically present in infancy. 3 7 Herein, we present a case of an infant diagnosed with both mucolipidosis II and Leigh syndrome. Genetic analysis in this case revealed two mutations (NDUFA12 c.178C > T p.Arg60* and GNPTAB c.732&#95;733delAA) on the long arm of chromosome 12 as the etiology of MLII and LS in this neonate, respectively. We are unaware of any previously published cases of the presence of these two diseases occurring in the same patient. The complex clinical presentation of this case led to a delay in the diagnosis, and we believe that the clinical phenotypes of these two conditions were likely worsened. The genetic alterations presented in this case occurred as a result of mutations on chromosome 12. We suggest further investigation into the potential overlap in the pathophysiology, specifically the inheritance pattern, linkage disequilibrium, mitochondrial-lysosomal interaction, or crosstalk contributing to both diseases., Competing Interests: Conflict of Interest None declared., (© Thieme Medical Publishers.)

Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD., (© 2015 International Society for Neurochemistry.)

Obstacles to the widespread use of continuous renal replacement therapy (CRRT) include the need for anticoagulation, customized solutions, and complex protocols that carry an attendant risk for error, raise cost, and increase pharmacy and nursing workload. However, high solute clearance using CRRT with an effluent rate of 35 ml/kg per h has also recently been associated with improved survival in critically ill patients with acute renal failure. No published CRRT protocols using dilute regional citrate anticoagulation have achieved adequate metabolic control, effective anticoagulation, and high solute clearance in a practical, user-friendly, and economical manner. The safety and the efficacy of continuous venovenous hemodiafiltration at effluent rates of 35 ml/kg per h in critically ill acute renal failure patients were evaluated prospectively using a standardized bicarbonate-based dialysate; a systemic calcium infusion; and two separate trisodium citrate replacement solutions, a 0.67% solution and a 0.5% solution. All patients achieved adequate metabolic control, the desired effluent rate of 35 ml/kg per h, and high solute clearance. Use of the 0.67% citrate replacement solution resulted in mild alkalosis, whereas the 0.5% solution maintained appropriate acid-base balance. There was no difference in dialyzer survival between the 0.67 and 0.5% citrate groups (80 versus 82%; P = 0.60, Kaplan-Meier analysis). Dilute regional citrate as part of a CRRT protocol with a standard 25-mmol/L bicarbonate dialysate provides adequate metabolic control, high diffusive and convective clearance, and excellent dialyzer patency in a practical and cost-effective manner.