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A preterm infant, whose course was complicated by sepsis, necrotizing enterocolitis with jejunal perforation, intraventricular hemorrhage and cerebellar hemorrhage, suffered permanent and total paralysis below the neck from extravasation of parenteral nutrition fluids through a femoral venous catheter. MRI imaging revealed extravasation of fluid into the paraspinus musculature with extension into the spinal canal. This fluid was identified as hyperalimentation and intralipid. Postmortem examination found evidence of necrosis of the spinal cord as well as perforation of the right iliac vein.

The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation.

Technological advances in the intensive care of low birth weight (LBW) infants have resulted in major increases in their survival. New challenges in meeting their nutritional needs have emerged. Very low birth (VLBW) weight infants have very little body fat or glycogen reserves at birth, making them susceptible to starvation. If fed enterally, they require at least 120 calories/kg per day for growth. Numerous immaturities in the gastrointestinal tract and liver limit protein digestion, absorption, and metabolism. Several amino acids not considered essential to the older child or adult are essential to the VLBW infant. Supplying a high protein load with an inappropriate amino acid composition may lead to metabolic imbalances. The digestion and absorption of fats differs from the older child or adult. Lingual and gastric lipases are important, and the lack of bile acids limits fat absorption. Lipoprotein lipase deficiency causes problems when too much fat or fat of incorrect composition is provided. There are controversies regarding the most appropriate carbohydrate source, but research shows that lactose remains an important carbohydrate source for most of these infants. Calcium, magnesium, and phosphorus requirements pose questions in both enterally and parenterally nourished infants. Studies of iron usage suggest that VLBW infants fed either human milk or formula should receive iron supplements. Vitamin E may be helpful in preventing oxygen toxicity. Vitamin D deficiency contributes to bone demineralization and rickets. Controversy exists regarding the correlation between vitamin A nutrition and development of chronic lung disease. Guidelines have been developed for recommended intakes, but much needs to be learned to provide a sound scientific basis upon which to provide optimal nourishment for the high risk, LBW infant.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches.   Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: • Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: • A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). • Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100-500 µm) but shows little fluorescence at low ATP concentrations (10-100 nm) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future., (© 2023 Wiley-VCH GmbH.)

Hyperglycemia is commonly encountered in extremely preterm newborns and physiologically can be attributed to immaturity in several biochemical pathways related to glucose metabolism. Although hyperglycemia is associated with a variety of adverse outcomes frequently described in this population, evidence for causality is lacking. Variations in definitions and treatment approaches have further complicated the understanding and implications of hyperglycemia on the immediate and long-term effects in preterm newborns. In this review, we describe the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research. IMPACT: Hyperglycemia is common and less well described than hypoglycemia in extremely preterm newborns. Hyperglycemia can be attributed to immaturity in several cellular pathways involved in glucose metabolism in this age group. Hyperglycemia has been shown to be associated with a variety of adverse outcomes frequently described in this population; however, evidence for causality is lacking. Variations in definitions and treatment approaches have complicated the understanding and the implications of hyperglycemia on the immediate and long-term effects outcomes. This review describes the relationship between hyperglycemia and organ development, outcomes, treatment options, and potential gaps in knowledge that need further research., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Aim: To study the outcomes of very preterm infants with hyperglycaemia treated with Insulin., Methods: This is a systematic review of randomised controlled trials (RCTs) and observational studies. PubMed, Medline, EMBASE, Cochrane Library, EMCARE and MedNar databases were searched in May 2022. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model., Main Outcome Measures: Mortality and morbidities (e.g. Necrotising enterocolitis [NEC], retinopathy of prematurity [ROP]) in very preterm (<32 weeks) or very low birth weight infants (<1500 g) after treatment of hyperglycaemia with insulin., Results: Sixteen studies with data from 5482 infants were included. Meta-analysis of unadjusted ORs from cohort studies showed that insulin treatment was significantly associated with increased mortality [OR 2.98 CI (1.03 to 8.58)], severe ROP [OR 2.23 CI (1.34 to 3.72)] and NEC [OR 2.19 CI (1.11 to 4)]. However, pooling of adjusted ORs did not show significant associations for any outcomes. The only included RCT found better weight gain in the insulin group, but no effect on mortality or morbidities. Certainty of evidence was 'Low' or 'Very low'., Conclusion: Very low certainty evidence suggests that Insulin therapy may not improve outcomes of very preterm infants with hyperglycaemia., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: There is limited comprehensive literature focussing on the range of patient safety incidents related to parenteral nutrition (PN)., Objective: The aim of this review was to examine patient safety incidents related to the use of PN in all patient age groups., Methods: Literature published in the English language between January 2000 and April 2020 were searched across the MEDLINE, CINHAL and Embase databases. Articles were included if they contained PN-related patient safety incidents related to an avoidable event. No restrictions were applied to patient populations. The screening process was undertaken independently by two authors., Results: In total, 108 records were included in the review: 52 case studies, 54 observation studies (e.g. prevalence studies, surveys) and two experimental studies. All age groups were represented, with 62% of studies in paediatrics (of which two-thirds were neonates) and 23% in adults. They included all medication processes: prescribing, dispensing, compounding, administration and monitoring. Incidents were related to microbial contamination, venous access and specific components (e.g. lipid emulsion, amino acids, glucose, micronutrients and electrolytes) or the whole product. Incident outcomes ranging from near miss to death were reported. Intervention studies looked at the impact on patient safety incidents of computerised tools, healthcare processes, e.g. pharmacist screening, and standardisation. One study demonstrated more severe outcomes with paediatric than with adult PN., Conclusions: This review demonstrates the vast range of PN-related patient safety incidents in all patient age groups and all medication process stages. The need for a national study looking at patient safety incidents related to PN in England is highlighted., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Through a meta-analysis, we aimed to investigate whether neonatal hyperglycemia was associated with an increased risk of retinopathy of prematurity (ROP) by summarizing all available observational evidence. We searched online databases for studies published prior to December 2020; 26745 neonates with 3227 cases of ROP in 11 case-control studies and 997 neonates with 496 cases of hyperglycemia in 5 cohort studies were included. The results showed that the association between hyperglycemia and the occurrence of ROP was statistically significant in case-control studies (OR 3.93, 95% CI 2.36-6.53) and cohort studies (OR 1.70, 95% CI 1.11-2.60). Besides, the borderline significant association between the duration of hyperglycemia and ROP was observed in case-control studies (MD = 1.96, 95% CI 0.90-3.03; adjusted OR = 1.08, 95% CI 1.01-1.15). Furthermore, we found that the mean blood glucose level is higher in the ROP group than the non-ROP group in case-control studies (MD = 14.86, 95% CI 5.06-24.66) and the mean blood glucose level is higher in the hyperglycemia group than in the non-hyperglycemia group (MD = 86.54, 95% CI 11.03-162.05). However, after adjusting other confounders, the association between the mean blood glucose level and ROP varied in cohort studies (OR 1.96, 95% CI 1.23-3.13) and case-control studies (OR 1.02, 95% CI 1.00-1.05).Conclusion: This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. Further studies will be required to achieve a firm conclusion for hyperglycemia and ROP and promote a better understanding of the prevention of ROP.Trial registration: CRD42021228733 What is Known: • Hyperglycemia including the duration and daily mean blood glucose concentration has been associated with the risk of developing ROP in some clinical studies. Current evidence cannot reach a consensus on whether neonatal hyperglycemia is a risk factor for ROP. What is New: • This meta-analysis demonstrates that preterm infants with hyperglycemia have a tendency to increase the risk of ROP. • While the association between the mean blood glucose level and ROP remains inconclusive., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Stress-induced hyperglycemia is a frequent complication of neonatal sepsis. Hyperglycemia induces oxidative stress and immunosuppression. We investigated the glucose kinetics and effect of insulin administration during stress-induced hyperglycemia in a neonatal sepsis mouse model., Methods: A stock cecal slurry (CS) solution was prepared from adult cecums and 3.0 mg of CS/g (LD 40 ) was administered intraperitoneally to 4-day-old FVB mouse pups. Blood glucose levels were measured at 1.5, 3, 6, and 9 h post-sepsis induction and compared with basal levels. Two different doses of ultrafast-acting insulin were administered subcutaneously, and blood glucose levels and survival rates were monitored., Results: Blood glucose levels were significantly higher than those of baseline levels with a peak at 3 h, which progressively decreased from 6 to 9 h post-sepsis induction. Insulin treatment reduced post-sepsis-induced hyperglycemia at 1.5 and 3 h. The mortality rate of CS-only pups (39%) was similar to that of CS + 1 U/kg insulin pups (60%). However, the mortality rate of CS + 5 U/kg insulin pups (82%) was significantly higher than that of CS-only pups., Conclusions: Marked hyperglycemia was induced immediately after post-sepsis induction, and the high-dose insulin treatment increased mortality post-induction. Stress-induced hyperglycemia could therefore be a physiological and protective response for preterm sepsis, and aggressive treatment of this hyperglycemia might be contraindicated., (© 2019 Japan Pediatric Society.)

Modulation and control of stimuli responsive features of molecular assemblies in organized assemblies/cavitand macrocycles have received immense attention in many areas. In this study, we have established the formation of a discrete molecular assembly of thiazole orange (TO) dyes at the portals of the sulfobutylether β-cyclodextrin (SBE 7 βCD) macrocycle leading to the evolution of a strong and distinct emission band from aggregated TO. The supramolecular assembly promoted portal aggregation of TO in its 1 : 4 (SBE 7 βCD : TO) composition, characterized by absorption, fluorescence, circular dichroism, ITC and 1 H NMR measurements, was probed to be selectively responsive to tyramine among other biogenic amines/neurotransmitters. For the first time, the different extent of emission quenching of SBE 7 βCD : TO assembly in the presence of biogenic amines/neurotransmitters is translated to achieve a selective on-off fluorescence sensor for the detection of tyramine against other neurotransmitters with a limit-of-detection (LOD) as low as ∼575 nM (79 ppb). The emission features of the assembly with changes in temperature is found to be highly reproducible even after several temperature cycles and is promising to design an optical supramolecular thermometer in the ambient temperature range., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)