Diabetic retinopathy (DR) and age‐related macular degeneration (AMD) are two important leading causes of acquired blindness in developed countries. As accumulation of advanced glycation end products (AGEs) in retinal pigment epithelial (RPE) cells plays an important role in both DR and AMD, and the methylglyoxal (MGO) within the AGEs exerts irreversible effects on protein structure and function, it is crucial to understand the underlying mechanism of MGO‐induced RPE cell death. Using ARPE‐19 as the cell model, this study revealed that MGO induces RPE cell death through a caspase‐independent manner, which relying on reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, intracellular calcium elevation and endoplasmic reticulum (ER) stress response. Suppression of ROS generation can reverse the MGO‐induced ROS production, MMP loss, intracellular calcium increase and cell death. Moreover, store‐operated calcium channel inhibitors MRS1845 and YM‐58483, but not the inositol 1,4,5‐trisphosphate (IP3) receptor inhibitor xestospongin C, can block MGO‐induced ROS production, MMP loss and sustained intracellular calcium increase in ARPE‐19 cells. Lastly, inhibition of ER stress by salubrinal and 4‐PBA can reduce the MGO‐induced intracellular events and cell death. Therefore, our data indicate that MGO can decrease RPE cell viability, resulting from the ER stress‐dependent intracellular ROS production, MMP loss and increased intracellular calcium increase. As MGO is one of the components of drusen in AMD and is the AGEs adduct in DR, this study could provide a valuable insight into the molecular pathogenesis and therapeutic intervention of AMD and DR.

The role of intrauterine infection in the development of neonatal pulmonary disease is unclear and the impact of histological chorioamnionitis (HCAM) on respiratory outcomes in preterm infants remains controversial. The aim of this study was to explore the association between HCAM and neonatal respiratory outcomes in very-low-birth-weight (VLBW) preterm infants and evaluate the stepwise difference in the stage and severity of HCAM among neonatal respiratory outcomes. We retrospectively enrolled 129 VLBW preterm infants with placenta histopathology examinations in this study. HCAM was subdivided into 3 stages (early, intermediate, and advanced) according to the progression of the maternal inflammatory response. The perinatal characteristics, placental histopathology, and neonatal morbidities, including respiratory outcomes (respiratory distress syndrome (RDS), Wilson-Mikity syndrome (WMS) and bronchopulmonary dysplasia (BPD)), were collected for comparison. A total of 52.7% (68/129) of the infants had HCAM, including 23 early (stage 1), 30 intermediate (stage 2), and 15 advanced (stage 3) stage. There was no significant difference in the gestational age, birth body weight or mortality rate between the HCAM and non-HCAM groups. Mothers with HCAM had a significantly lower incidence of pre-eclampsia but a higher rate of premature rupture of membrane. They also had higher WBC counts and C-reactive protein levels before delivery. Neonates with HCAM had a lower incidence of RDS but were at a higher risk for developing WMS and BPD. After multivariate analysis adjustment, HCAM was still negatively associated with RDS (aOR = .069, p < .001) but without correlation with BPD. However, neonates with intermediate to advanced-stage HCAM had a higher risk of developing WMS and increased home oxygen usage rate compared to those with early-stage HCAM. HCAM has a protective effect from RDS in preterm neonates. Additionally, VLBW neonates with intermediate to advanced-stage HCAM are at risk for WMS.

Objective The incidence of patent ductus arteriosus (PDA), a major complication of prematurity, may be reduced by restricting fluid administration. Prophylactic fresh frozen plasma (FFP) transfusion may reduce the incidence of intraventricular hemorrhage in these infants, but risks transfusion-related volume overload. We conducted a retrospective study to investigate whether FFP transfusion is a risk factor for hemodynamically significant PDA (hsPDA) in very low birth weight (BW) premature infants. Study Design From January 2009 to December 2014, 102 premature infants with gestational age (GA) less than or equal to 30 weeks were admitted to a level III neonatal intensive care unit, and 88 patients were enrolled. Patients were further divided into non-hsPDA (n = 29) and hsPDA groups (n = 59). We retrospectively reviewed demographic characteristics and various perinatal and postnatal variables. Univariate and multivariable analyses were performed to identify risk factors for hsPDA. Results Compared with non-hsPDA patients, hsPDA patients had lower mean BW and GA, a higher incidence of severe respiratory distress symptoms, perinatal infection, use of surfactant, and need for FFP transfusion. However, multivariable logistic regression analysis showed that only FFP transfusion remained an independent risk factor for hsPDA (adjusted odds ratio = 3.880, 95% confidence interval: 1.214–12.402, p = 0.022) after adjusting for confounding factors. Conclusion FFP transfusion is a significant risk factor for the subsequent development of hsPDA in our study population. FFP transfusion may complicate the fluid management of premature infants and increase the risk of hsPDA. Key Points

Background/Objective: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac natriuretic hormone that cardiomyocytes release in response to ventricular stretch. It helps with the diagnosis of heart failure in adults, but this application in preterm infants has rarely been reported. This study aimed to evaluate whether NT-proBNP could be used for the early detection of reduced cardiac ejection fraction in preterm infants and the optimal timing for NT-proBNP assessment. Design/Methods: This prospective, single-center, observational study enrolled all preterm infants with NT-proBNP measurements from October 2014 to February 2022. They underwent echocardiographic examinations within 48 h of the NT-proBNP measurements. Reduced left ventricular ejection fraction was defined as below 60%. Receiver operator characteristic (ROC) curves were generated to assess the optimal NT-proBNP cutoff point for the early prediction of reduced cardiac ejection fraction. Results: A total of 68 preterm infants were enrolled, with a total of 134 NT-proBNP measurements being available for analysis. Reduced left ventricular ejection fraction was present in seven infants (10.3%) due to various underlying diseases. The NT-proBNP cutoff level for detecting reduced left ventricular ejection fraction was 9248 pg/mL, with 71.4% sensitivity and 60.8% specificity; the area under the curve was 0.623 (95% CI: 0.487~0.760). The threshold for the optimal postnatal age for applying NT-proBNP to detect reduced left ventricular ejection fraction was >2 days of life (AUC: 0.682; 95% CI: 0.518~0.845), with 70% sensitivity and 67.1% specificity. Conclusions: Although the NT-proBNP levels declined dramatically after birth, a NT-proBNP serum level of 9248 pg/mL might be helpful for the early detection of reduced ejection fraction in preterm infants, and the optimal age for detection was after 2 days of life.

Neonatal adrenal hemorrhage (NAH) is relatively uncommon in neonates and it is often noted accidently by abdominal ultrasonogram. Few studies discussed risk factors for and impacts of NAH. This study aimed to assess incidence, perinatal characteristics and follow-up outcomes in neonates with adrenal hemorrhage. This was a retrospective cohort study in a single institute from April 2008 to August 2018. All neonates who received abdominal ultrasonogram within seven days-of-life were recruited and divided in to 2 groups according to the presence of NAH. The perinatal characteristics and anthropometric measurements, the follow-up course and the clinical impact of NAH were reviewed in detail. 7217 neonates had received abdominal ultrasonogram within seven days-of-life and 29 of them (0.4%) were diagnosed with NAH. Mean gestation age was 38 ± 1.2 weeks and mean birth weight was 3406 ± 403 g. Most infants (96.6%) had unilateral hemorrhage over the right adrenal gland. Compared with the control group, infants with NAH were significantly heavier (3406 vs. 3094 gm, p < 0.001), longer in body length (50.1 vs. 48.8 cm, p < 0.001) and wider in chest girth (33.2 vs. 32.4 cm, p = 0.006). They also tended to be delivered via vaginal delivery with vacuum-extraction rather than cesarean section. The prevalence of nuchal cord, neonatal jaundice and subgaleal hemorrhage was higher in the NAH group. The hemorrhage area of adrenal gland had a positive correlation with the peak bilirubin level (r = 0.422, p < 0.001) and the days to resolution (r = 0.198, p = 0.033). All infants had resolution of AH before 7 months of age. NAH occurred more frequently in heavier neonates that were delivered via vaginal delivery with vacuum extraction. The hemorrhage involved mostly over the right adrenal gland. Neonatal jaundice was the major comorbidity. All infants had spontaneous resolution of AH before 7 months of age.

Vancomycin is commonly used for neonatal sepsis. However, consensus on an empirical neonatal vancomycin regimen remains uncertain. We aimed to reappraise the therapeutic optimum concerning vancomycin trough concentrations with empirical dosing and to evaluate the relationship between trough concentrations and predicted 24-h area under the curve (AUC₂₄). This was a 3-year retrospective study. Neonates who were admitted to the neonatal intensive care unit with available vancomycin trough concentrations were enrolled. Trough levels were obtained before the fourth dose. Achievement of goal trough after implementing the vancomycin dosing regimen was based on the Practical Neonatology Medical Manual, published by the National Taiwan University College of Medicine. A total of 46 neonates were included for analysis. Coagulase-negative staphylococci were the most commonly identified pathogens of sepsis. Among these patients, 22 achieved goal trough levels of 10-20 mcg/mL. Trough levels of 5-10 or >20 mcg/mL occurred in 13 and 11 patients, respectively. A moderately positive correlation between trough and predicted AUC₂₄ was found in all patients (Spearman's rho = 0.676, p < 0.001). In patients with body weight 1200-2000 g and postnatal age >7 days, the serum creatinine of those with trough levels >20 mcg/mL was significantly higher than those with goal trough levels (0.61 vs. 0.45 mg/dL, p = 0.01). Among those with trough levels >20 mcg/mL, 5 patients received ibuprofen for patent ductus arteriosus closing prior to vancomycin treatment (45%, 5/11), compared to only 3 patients with trough levels <20 mcg/mL (9%, 3/35) (p = 0.013). Only half of the neonates receiving empirical vancomycin regimen achieved goal trough levels of 10-20 mcg/mL. Higher serum creatinine or ibuprofen treatment may increase the risk of overly high trough levels. The vancomycin regimen needs further validation and modification to provide adequate dosing for optimal use in neonates.