Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Subclinical hypothyroidism (SCH), characterized by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine levels, usually presents without symptoms, and is often discovered incidentally during routine blood test. The Task Force of the Korean Thyroid Association Committee of Clinical Practice Guidelines has established a guideline to evaluate and manage SCH; the guideline emphasizes the implementation of diagnostic criteria based on the TSH reference range for Koreans and focuses on the proven health benefits of levothyroxine (LT4) treatment. Based on the Korea National Health and Nutrition Examination Survey (2013-2015), serum TSH level of 6.8 mIU/L is considered the reference value for SCH. SCH can be categorized as mild (TSH 6.8-10.0 mIU/L) or severe (TSH ＞10.0 mIU/L), and patients are classified as adults (age ＜70 years) or elderly patients (age ≥70years) depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, along with the thyroid peroxidase antibody test, preferably 2-3 months after the initial evaluation. Usually, LT4 treatment is not recommended for mild SCH in adults; however, treatment is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and can be considered for coexisting dyslipidemia. LT4 treatment is not recommended for mild or even severe SCH in elderly patients, in general. Patients with SCH who receive LT4 treatment, the LT4 dosage should be personalized, and serum TSH levels should be monitored to ensure optimal LT4 dosage (dosage that is neither excessive nor insufficient). Patients with SCH who do not receive LT4 treatment require periodic follow-up at appropriate testing intervals determined by disease severity. The guideline also provides several educational points applicable in clinical settings.

Background: Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice. Methods: In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled. Results: Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42. Conclusion Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.