Experience with enteral sulfonylurea monotherapy for extremely low birth weight infants with hyperglycemia.

Limited data are available on the effects of enteral sulfonylurea (SU) monotherapy in extremely low birth weight infants (ELBWIs) with hyperglycemia. Therefore, we report our experience with enteral SU monotherapy for hyperglycemic ELBWIs. We retrospectively evaluated 11 hyperglycemic ELBWIs (seven male infants, median gestational age = 24.9 wk) who received SU between January 2016 and December 2019. Blood glucose (BG) levels were monitored before and after SU initiation and evaluated for the occurrence of adverse effects. We administered SU at a median of 15 d (interquartile range [IQR]: 12-20 d) after birth, with the median maximum dose of 0.2 mg/kg/d (IQR: 0.125-0.3 mg/kg/d). Hyperglycemia improved in all patients, and the target BG levels were achieved without severe side effects at a median of 6 d (IQR: 4-8.5 d) after initiation of treatment. The incidence of hypoglycemia during SU treatment was observed in 18 events per 1000 patient hours; however, the patients were asymptomatic. Based on these results, enteral SU monotherapy may be considered as an option for hyperglycemic ELBWIs.

Risk factors for hyperglycemia in extremely low birth weight infants during the first 14 days.

BACKGROUND: There are limited data regarding the risk factors for hyperglycemia in extremely low birth weight infants (ELBWIs). The aim of this observational study was to investigate the incidence of hyperglycemia among ELBWIs during the first 14 days of life and identify independent risk factors for hyperglycemia development. METHODS: We retrospectively evaluated 55 ELBWIs (32 male infants) between January 2015 and March 2020. Hyperglycemia was diagnosed when the glucose level was ≥180 mg/dL. Demographic and clinical data were extracted from the patients' medical records. The risk factors associated with the onset of hyperglycemia were identified by Cox proportional hazards regression analysis with variables that had previously been identified as risk factors for hyperglycemia. RESULTS: Hyperglycemia developed in 23 patients (41.8%) within the first 14 days of life. Gestational age, chorioamnionitis, postnatal intravenous glucocorticoids, and probiotic type were included in the analysis. The results indicated that hyperglycemia was significantly associated with gestational age (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48-0.87; P = 0.004). Further, Bifidobacterium breve (B. breve M-16V) use was related to hyperglycemia in ELBWIs (HR, 2.95; 95% CI, 1.10-7.87; P = 0.031). CONCLUSION: Hyperglycemia was strongly associated with lower gestational age and B. breve M-16V use in our study population. Although probiotic supplementation may be beneficial for preterm infants to reduce the incidence of necrotizing enterocolitis, the dextrin used as an excipient in B. breve M-16V may lead to an undesirable carbohydrate load in ELBWIs.

Fatty acid composition of the methylotrophic yeast Komagataella phaffii grown under low- and high-methanol conditions.

In this study, we analysed the intracellular fatty acid profiles of Komagataella phaffii during methylotrophic growth. K. phaffii grown on methanol had significantly lower total fatty acid contents in the cells compared with glucose-grown cells. C18 and C16 fatty acids were the predominant fatty acids in K. phaffii, although the contents of odd-chain fatty acids such as C17 fatty acids were also relatively high. Moreover, the intracellular fatty acid composition of K. phaffii changed in response to not only carbon sources but also methanol concentrations: C17 fatty acids and C18:2 content increased significantly as methanol concentration increased, whereas C18:1 and C18:3 contents were significantly lower in methanol-grown cells. The intracellular content of unidentified compounds (Cn H2n O4 ), on the other hand, was significantly greater in cells grown on methanol. As the intracellular contents of these Cn H2n O4 compounds were significantly higher in a gene-disrupted strain for glutathione peroxidase (gpx1Δ) than in the wild-type strain, we presume that the Cn H2n O4 compounds are fatty acid peroxides. These results indicate that K. phaffii can coordinate intracellular fatty acid composition during methylotrophic growth in order to adapt to high-methanol conditions and that certain fatty acid species such as C17:0, C17:1, C17:2 and C18:2 may be related to the physiological functions by which K. phaffii adapts to high-methanol conditions.

The regulatory mechanism involved in the prostaglandin E2 disposition in carbon tetrachloride-induced liver injury.

Prostaglandin E2 (PGE2) exhibits hepatoprotective effects against various types of liver injury. However, there is little information on the disposition of endogenous PGE2 during liver injury. In the present study, we attempted to elucidate the mechanism involved in regulating PGE2 distribution during liver injury. Carbon tetrachloride (CCl4) was used to establish a liver injury mouse model. PGE2 was measured by LC-MS/MS. The plasma and hepatic PGE2 levels were significantly increased at 6 to 48 h after CCl4 treatment. The ratio of plasma levels of 13,14-dihydro-15-ketoPGE2 (PGEM), a major PGE2 metabolite, to PGE2 decreased significantly after CCl4 treatment. PGE2 synthesis and expression of enzymes related to PGE2 production were not induced, while the activity and mRNA expression of 15-prostaglandin dehydrogenase (15-PGDH/Hpgd), a major enzyme for PGE2 inactivation, decreased significantly in the liver of CCl4-treated mice compared to that of vehicle-treated control. The plasma and hepatic PGE2 levels were negatively correlated with the hepatic mRNA expression levels of Hpgd. Although the mRNA expression of organic anion transporting polypeptide 2A1 (OATP2A1/Slco2a1), a major PGE2 transporter, was upregulated, other hepatic OATPs decreased significantly at 24 h after CCl4 treatment. Immunohistochemical analysis indicated that 15-PGDH was mainly expressed in endothelial cells and that OATP2A1 was expressed at least in endothelial cells and Kupffer cells in the liver. These results suggest that the decreased 15-PGDH expression in hepatic endothelial cells is the principal mechanism for the increase in hepatic and plasma PGE2 levels due to the CCl4-induced liver injury.

Oral alendronate in pediatric chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) primarily affects children and adolescents, and is characterized by episodic sterile osteomyelitis over several years. No definitive treatment is available. Non-steroidal anti-inflammatory drugs (NSAID) are common first-line agents, but provide limited improvement in bone pain and do not affect disease duration. Several agents are utilized in the case of non-response to NSAID, including corticosteroids, methotrexate, and tumor necrosis factor-blocking agents. Bisphosphonates are increasingly being used. Most case series involve cyclic i.v. pamidronate, but this restricts the social lives of children and their families. Although oral medication has advantages over cyclic i.v. infusion because it does not require repeated hospital admissions, there have been no reports on treatment with oral bisphosphonates, such as alendronate, in pediatric CRMO patients. This case report describes the use of oral bisphosphonate as an alternative treatment in CRMO patients in whom standard therapy has failed.

Early initiation of steroid pulse therapy for neuromyelitis optica in an emergency room setting.

Case: A 40-year-old man presented to the emergency room with visual impairment, dysesthesia of lower legs, and urinary retention. Two days before admission, he was consulted to the neurology department due to bilateral optic neuritis and scheduled the magnetic resonance imaging of spine. However, the urinary retention deteriorated acutely and he came to the emergency room. On arrival, the plain magnetic resonance image of his spine showed diffuse hyperintensity signals of the spinal cord in T2-weighted images. He was diagnosed with neuromyelitis optica and steroid pulse therapy was initiated. Outcome: We began treatment immediately in the emergency room, cooperating with the neurology team. After admission, plasmapheresis was added for his fluctuating symptoms. On hospital day 7, he was discharged without complication. Conclusion: It is important to understand the various clinical manifestations of neuromyelitis optica. In emergency settings, immediate steroid therapy is necessary for better outcomes.