Building a NICU quality & safety infrastructure.

The American Academy of Pediatrics (AAP) Standards for Levels of Neonatal Care, published in 2023, highlights key components of a Neonatal Patient Safety and Quality Improvement Program (NPSQIP). A comprehensive Neonatal Intensive Care Unit (NICU) quality and safety infrastructure (QSI) is based on four foundational domains: quality improvement, quality assurance, safety culture, and clinical guidelines. This paper serves as an operational guide for NICU clinical leaders and quality champions to navigate these domains and develop their local QSI to include the AAP NPSQIP standards.

Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging.

In defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of consuming a diet with a 67% reduction of all amino acids (Low AA), or of isoleucine alone (Low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diet regimens effectively reduce adiposity and improve glucose tolerance, which were benefits that were not mediated by reduced calorie intake. Both diets improve specific aspects of frailty, slow multiple molecular indicators of aging rate, and rejuvenate the aging heart and liver at the molecular level. These results demonstrate that Low AA and Low Ile diets can drive youthful physiological and molecular signatures, and support the possibility that these dietary interventions could help to promote healthy aging in older adults.

Modulation of hepatic transcription factor EB activity during cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids by Pla2g15.

Cold exposure is an environmental stress that elicits a rapid metabolic shift in endotherms and is required for survival. The liver provides metabolic flexibility through its ability to rewire lipid metabolism to respond to an increased demand in energy for thermogenesis. We leveraged cold exposure to identify novel lipids contributing to energy homeostasis and found that lysosomal bis(monoacylglycero)phosphate (BMP) lipids were significantly increased in the liver during acute cold exposure. BMP lipid changes occurred independently of lysosomal abundance but were dependent on the lysosomal transcriptional regulator transcription factor EB (TFEB). Knockdown of TFEB in hepatocytes decreased BMP lipid levels. Through molecular biology and biochemical assays, we found that TFEB regulates lipid catabolism during cold exposure and that TFEB knockdown mice were cold intolerant. To identify how TFEB regulates BMP lipid levels, we used a combinatorial approach to identify TFEB target Pla2g15 , a lysosomal phospholipase, as capable of degrading BMP lipids in in vitro liposome assays. Knockdown of Pla2g15 in hepatocytes led to a decrease in BMP lipid species. Together, our studies uncover a required role of TFEB in mediating lipid liver remodeling during cold exposure and identified Pla2g15 as an enzyme that regulates BMP lipid catabolism.

A quality improvement initiative for neonatal hypoglycemia screening and management in a level III neonatal intensive care unit.

OBJECTIVE: To bring screening and management of neonatal hypoglycemia in alignment with the 2011 AAP hypoglycemia clinical report METHODS: A multidisciplinary team developed a quality improvement initiative for neonatal hypoglycemia in neonates ≥35 weeks gestational age in a Level III neonatal intensive care unit between July 2020 and December 2021. A key driver diagram identified interventions for plan-do-study-act testing with corresponding measures to implement a hypoglycemia management protocol and improve adherence to AAP guidelines. RESULTS: Time to first blood glucose measurement increased from 49.8 to 122.7 min of life and time to first enteral feed decreased from 14.2 to 3.6 h of life. Neonates receiving intravenous dextrose decreased from 97.1 to 24.7% and discharge rates as a mother-neonate dyad increased from 35 to 62.4%. CONCLUSIONS: Adherence to the AAP guidelines improved during testing and implementation of a hypoglycemia protocol and was associated with an increased mother-neonate dyad discharge rate.

First report of transfusing low-titer cold-stored type O whole blood to an extremely-low-birth-weight neonate after acute blood loss.

BACKGROUND: Multiple reports suggest that cold-stored low-titer type O whole blood (LTOWB) is becoming a preferred transfusion product for resuscitating massive hemorrhage across trauma, obstetrical, and pediatric services. However, we know of no reports of using this product for emergency transfusion of newborn infants after acute severe hemorrhage. CASE REPORT: We report our experience with emergency transfusion of re-warmed LTOWB using a fluid warmer for the resuscitation of a hypotensive 25-week gestation neonate following acute and severe placental abruption. The transfusion was tolerated well, without evidence of hemolysis or other complications. CONCLUSIONS: This is the first report of which we are aware of transfusing warmed LTOWB to a preterm neonate. Our positive experience leads us to speculate that this product could have a role for neonates following acute severe blood loss.

Loss of SNORA73 reprograms cellular metabolism and protects against steatohepatitis.

Dyslipidemia and resulting lipotoxicity are pathologic signatures of metabolic syndrome and type 2 diabetes. Excess lipid causes cell dysfunction and induces cell death through pleiotropic mechanisms that link to oxidative stress. However, pathways that regulate the response to metabolic stress are not well understood. Herein, we show that disruption of the box H/ACA SNORA73 small nucleolar RNAs encoded within the small nucleolar RNA hosting gene 3 (Snhg3) causes resistance to lipid-induced cell death and general oxidative stress in cultured cells. This protection from metabolic stress is associated with broad reprogramming of oxidative metabolism that is dependent on the mammalian target of rapamycin signaling axis. Furthermore, we show that knockdown of SNORA73 in vivo protects against hepatic steatosis and lipid-induced oxidative stress and inflammation. Our findings demonstrate a role for SNORA73 in the regulation of metabolism and lipotoxicity.

2-Hydroxypropyl-ß-cyclodextrin is the active component in a triple combination formulation for treatment of Niemann-Pick C1 disease.

Niemann-Pick type C1 (NPC1) disease is a fatal neurovisceral disease for which there are no FDA approved treatments, though cyclodextrin (HPßCD) slows disease progression in preclinical models and in an early phase clinical trial. Our goal was to evaluate the mechanism of action of a previously described combination-therapy, Triple Combination Formulation (TCF) - comprised of the histone deacetylase inhibitor (HDACi) vorinostat/HPßCD/PEG - shown to prolong survival in Npc1 mice. In these studies, TCF's benefit was attributed to enhanced vorinostat pharmacokinetics (PK). Here, we show that TCF reduced lipid storage, extended lifespan, and preserved neurological function in Npc1 mice. Unexpectedly, substitution of an inactive analog for vorinostat in TCF revealed similar efficacy. We demonstrate that the efficacy of TCF was attributable to enhanced HPßCD PK and independent of NPC1 protein expression. We conclude that although HDACi effectively reduce cholesterol storage in NPC1-deficient cells, HDACi are ineffective in vivo in Npc1 mice.

Optimal Timing to Utilize Olfactory Stimulation with Maternal Breast Milk to Improve Oral Feeding Skills in the Premature Newborn.

Background: Olfactory maturation is essential for successful oral feeding. Previous studies have suggested that olfactory stimulation with maternal breast milk may expedite oral feeding skills in the premature infant; however, the optimal developmental window to utilize this intervention and sex-specific responses to stimuli are largely unknown. Objectives: To determine individual responses to olfactory stimulation with mother's own milk (MOM) on feeding outcomes in premature newborns. Materials and Methods: Infants born between 28 0/7 and 33 6/7 weeks' gestation (n = 36) were randomized to receive either MOM or water (sham) stimulus during the learning process of oral feeding. Clinical and feeding outcomes were recorded. Statistical analyses examined the effect of stimulation with MOM on feeding outcomes stratified for age and sex. Results: Overall, there was no significant difference between sham infants compared with MOM infants in mean postmenstrual age of full oral feeds (sham: 35 5/7 versus MOM 36 0/7; p = 0.37). However, when stratified by gestational age (GA), infants born <31 weeks' gestation who received MOM stimulation learned to feed sooner than controls (p = 0.06), whereas infants born ≥31 weeks' gestation learned to feed later than controls (p = 0.20) with a significant interaction (p = 0.02) between the stimulus (MOM versus sham) and dichotomized GA (<31 versus ≥31 weeks). There were no sex differences in response to olfactory stimulus. Conclusions: Infants born <31 weeks' GA who received MOM stimulation learned to feed sooner than control infants and the impact of MOM is significantly different between infants born before or after 31 weeks GA. These data suggest there may be an optimal time in development to utilize maternal breast milk to expedite oral feeding maturation in the premature newborn.

Three-year clinical evaluation of two flowable composites.

OBJECTIVE: To evaluate the clinical efficacy of two flowable composite resins used to restore occlusal caries lesions. Tetric Flow (Vivadent) and Esthet-X Flow (Dentsply/Caulk) are composite resins with decreased filler loading (Tetric Flow: 67% filler by weight, 43% by volume; Esthet-X Flow: 61% filler by weight, 53% by volume) and lower viscosity compared to conventional composite resins. METHOD AND MATERIALS: Sixty-three teeth with occlusal caries were randomly assigned to calibrated practitioners who placed occlusal restorations (32 for Esthet-X Flow; 31 for Tetric Flow). After tooth preparation and caries removal, each material was inserted. A polyvinyl impression was made of each preparation and measured to record the preparation size. Prime and Bond NT (Dentsply/Caulk) was used to bond both flowable composites, which were incrementally placed and light cured for 20 seconds. Each restoration was evaluated at baseline (1 week after restoration placement) and 3, 6, 12, and 36 months for marginal discoloration, secondary caries, anatomical form, retention, polishability, marginal adaptation, and color match. Groups were compared at 3 years and the data analyzed statistically with a .05 level of significance using generalized estimating equations, with size of restoration compared to the modified Ryge criteria. RESULTS: Of the effects that were estimable, only color match exhibited a difference between treatment groups (P = .0467, favoring Esthet-X Flow). No other differences were observed between materials. Although no difference was observed between groups, marginal discoloration (P = .0164) and marginal adaptation (P = .0001) significantly worsened at 36 months. For polishability, a significant difference was observed at 36 months (P = .0066). No other outcomes changed significantly over time. Size of the restoration was found to be positively associated with worse outcome for color match (P = .0062 for area; P = .0439 for volume). CONCLUSION: Although flowable composite resins are advocated for occlusal restorations, this study suggests that they should be limited to small restorations such as preventive resin restorations having isthmus widths of one-quarter or less of intercuspal distance.

Evaluation of 30% carbamide peroxide at-home bleaching gels with and without potassium nitrate--a pilot study.

OBJECTIVES: This double-blind study examined the bleaching effectiveness of two 30% carbamide peroxide bleaching gels: one with 5% potassium nitrate (treatment A) and one without (treatment B). The treatment time was reduced for this pilot study to one hour per day for 10 days to determine whether the higher concentration would whiten teeth and to ascertain the tooth sensitivity and gingival effects of the 30% solution. METHOD AND MATERIALS: Forty subjects were selected with an initial tooth shade corresponding to Bioform shade guide B65 or darker. After obtaining consent, subjects were randomly divided into two groups (n = 20). Custom-fabricated bleaching trays were made for each subject. Trays did not extend onto the gingiva. Each subject was instructed in the placement and wear of the tray and bleach and supplied with one of the two bleaching gels. Subjects had 10 hours of treatment time with the bleaching gel. Photographs and shades (using a standardized Bioform shade guide) were taken at baseline and at final recall to determine bleaching effectiveness. Tooth sensitivity was measured at baseline and final recall by applying a pellet saturated with skin refrigerant to the tooth for 2 seconds. The sensitivity was recorded on a scale ranging from 1 to 10. Gingival index was also measured at baseline and at final recall. Data was analyzed with Wilcoxon rank-sum and Wilcoxon signed rank tests. RESULTS: No significant differences were found for changes in color, tooth sensitivity, and gingival condition between the two bleaching gels (P = .899, P = .375, and P = .056, respectively). Within each group, bleaching gel A and B significantly whitened teeth (P < .0001 for both groups). There were no significant changes in tooth sensitivity and gingival condition for gel A (P = .057 and .063, respectively) or gel B (P = .911 and .510, respectively). CONCLUSION: Thirty percent carbamide bleaching gels effectively whiten teeth without causing a significant increase in tooth sensitivity or changes in gingival condition. Potassium nitrate has little effect in sensitivity when treatment time is short.

Clinical evaluation of 2 flowable composites.

OBJECTIVE: This study evaluated the clinical efficacy of 2 flowable resin composites used to restore occlusal carious lesions. Tetric Flow (Vivadent) and Esthet-X Flow (Dentsply/Caulk) are resin composites with decreased filler loading and lower viscosity compared to conventional resin composites. METHOD AND MATERIALS: Sixty occlusal restorations (30 of each material) were placed. After tooth preparation and caries removal, each material was inserted with rubber dam isolation. Prime & Bond NT (Dentsply/Caulk) was used to bond both flowable composites, which were incrementally placed and light-cured for 20 seconds. Each restoration was evaluated at baseline (1 week after restoration placement), 3 months, 6 months, and 1 year for marginal discoloration, secondary caries, anatomic form, retention, polishability, marginal adaptation, and color match. Groups were compared at 1 year and the data analyzed statistically with a .05 level of significance. RESULTS: A marginally significant difference in color match was observed at 1 year (favoring Esthet-X Flow). No other differences were observed between materials. Marginal discoloration significantly worsened for all restorations at 6 months and 1 year, and marginal adaptation significantly worsened at 1 year for all restorations. A positive association between preparation size and sensitivity was detected at 3 months; no association was found at 6 months and 1 year. At 1 year, restoration size was positively associated with marginal adaptation. Despite some changes from baseline, all restorations were clinically acceptable at 1 year. CONCLUSION: Although flowable resin composites are advocated for occlusal restorations, it is recommended that they be limited to small and moderate-sized restorations.

Two-year clinical evaluation of a posterior resin composite using a fourth- and fifth-generation bonding agent.

This study evaluated the clinical performance of a posterior resin composite used with a fourth- and fifth-generation bonding agent. Sixty-two Class I and II restorations were placed with half the restorations restored with Gluma Solid Bond (a fourth-generation bonding system, or total etch two-step system) and the other half restored with Gluma Comfort Bond and Desensitizer (a fifth-generation bonding system, or total etch one-step system). Solitaire 2 was used as the restorative material for all restorations. The bonding systems and resin composite were used according to the manufacturer's instructions and all procedures were performed with rubber dam isolation. All restorations were evaluated at baseline, six months and one and two years. A modified USPHS scale was used to evaluate the restorations for marginal discoloration, recurrent caries, anatomic form, marginal adaptation and proximal contact. Statistical analysis revealed that at two years no significant differences were found between the two bonding agents. Overall, Solitaire 2 performed well clinically whether Gluma Solid Bond or Gluma Comfort Bond and Desensitizer was used. It was thus concluded that Solitaire 2 functions successfully when used as a posterior restorative material for at least two years.

Three-year clinical evaluation of a compomer and a resin composite as Class V filling materials.

The purpose of this study was to evaluate the placement of two restorative materials, including a compomer (F2000, 3M ESPE) and a resin composite (Silux Plus, 3M ESPE), in non-carious cervical lesions using a self-etching bonding agent (F2000 self-etching primer/adhesive) and a fifth generation bonding agent (Single Bond, 3M ESPE) and to evaluate and compare these restorations for marginal discoloration, secondary caries, anatomical form, retention, surface texture and marginal adaptation at baseline and annually for three years. F2000 and Silux Plus were used to restore the teeth with moderate-sized non-carious cervical lesions. F2000 was placed using two different bonding agents: F2000 self-etching primer/adhesive (F2000SE group) and Single Bond (F2000SB group); Silux Plus was placed as a control using Single Bond (SiluxSB group). Thirty restorations of each material/dentin adhesive combination were placed. All restorations were evaluated at baseline and annually for three years using a modified USPHS scale. At the end of the three-year recall, Silux Plus had significantly better surface texture than F2000 (p < 0.0001). In addition, marginal adaptation significantly worsened over time starting at one year, as compared with baseline, for all groups (p < 0.0001). When anatomic form was compared between F2000 and Silux Plus, the p-value was 0.085, demonstrating that F2000 was slightly better than Silux Plus. Likewise, when comparing marginal adaptation between the F2000SE and SiluxSB groups, the p-value was 0.064, demonstrating that F2000 with the self-etching primer had better margins than Silux Plus with Single Bond. No other differences were found among the groups.