Pediatric Home Mechanical Ventilation in Korea: the Present Situation and Future Strategy

BACKGROUND: The number of children using home mechanical ventilation (HMV) has increased markedly in Europe and North America, but little is known about the situation in Korea. We described the clinical characteristics of children using HMV and investigated the current situation of HMV utilization in children. METHODS: Data on HMV prescriptions in year 2016 for children under the age of 19 was retrieved from the National Health Insurance Service for nationwide information. For more detailed information, data from year 2016 to 2018 was also retrieved from a tertiary center, Severance Children's Hospital. RESULTS: Nationwide, 416 children were prescribed with HMV in 2016, with an estimated prevalence of 4.4 per 100,000 children, of which 64.2% were male and mean age was 6-year-old. The estimated number of patients using invasive ventilators via tracheostomy was 202 (49%). Neuromuscular diseases were the most frequent cause (217; 52%), followed by central nervous system diseases (142; 34%), and cardiopulmonary diseases (57; 14%). In the tertiary center, a total of 62 children were prescribed with HMV (19 [31%] with non-invasive ventilation; 43 [69%] with invasive ventilation]. The number of children with HMV increased from 11 in 2016 to 29 in 2018. The mean age for initiation of HMV was 3.1 years and male patients comprised 65%. The most frequent diagnostic reason for HMV was central nervous system diseases (68%), followed by cardiopulmonary diseases (19%) and neuromuscular diseases (13%). Five patients died during the study period and five patients weaned from HMV. CONCLUSION: This study provides insights on the present situation of HMV utilization in Korean children.

Serum Albumin as a Biomarker of Poor Prognosis in the Pediatric Patients in Intensive Care Unit / 대한중환자의학회지

BACKGROUND: Serum albumin as an indicator of the disease severity and mortality is suggested in adult patients, but its role in pediatric patients has not been established. The objectives of this study are to investigate the albumin level as a biomarker of poor prognosis and to compare it with other mortality predictive indices in children in intensive care unit (ICU). METHODS: Medical records of 431 children admitted to the ICU at Severance Hospital from January 1, 2012 to December 31, 2015 were retrospectively analyzed. Children who expired within 24 hours after ICU admission, children with hepatic or renal failure, and those who received albumin replacement before ICU admission were excluded. RESULTS: The children with hypoalbuminemia had higher 28-day mortality rate (24.60% vs. 9.28%, P < 0.001), Pediatric Index of Mortality (PIM) 3 score (9.23 vs. 8.36, P < 0.001), Pediatric Risk of Mortality (PRISM) III score (7.0 vs. 5.0, P < 0.001), incidence of septic shock (12% vs. 3%, P < 0.001), C-reactive protein (33.0 mg/L vs. 5.8 mg/L, P < 0.001), delta neutrophil index (2.0% vs. 0.6%, P < 0.001), lactate level (1.6 mmol/L vs. 1.2 mmol/L, P < 0.001) and lower platelet level (206,000/µl vs. 341,000/µl, P < 0.001) compared to the children with normal albumin level. PIM 3 (r = 0.219, P < 0.001) and PRISM III (r = 0.375, P < 0.001) were negatively correlated with serum albumin level, respectively. CONCLUSIONS: Our results highlight that hypoalbuminemia can be a biomarker of poor prognosis including mortality in the children in ICU.

Serum Albumin as a Biomarker of Poor Prognosis in the Pediatric Patients in Intensive Care Unit / 대한구급학회지

BACKGROUND: Serum albumin as an indicator of the disease severity and mortality is suggested in adult patients, but its role in pediatric patients has not been established. The objectives of this study are to investigate the albumin level as a biomarker of poor prognosis and to compare it with other mortality predictive indices in children in intensive care unit (ICU). METHODS: Medical records of 431 children admitted to the ICU at Severance Hospital from January 1, 2012 to December 31, 2015 were retrospectively analyzed. Children who expired within 24 hours after ICU admission, children with hepatic or renal failure, and those who received albumin replacement before ICU admission were excluded. RESULTS: The children with hypoalbuminemia had higher 28-day mortality rate (24.60% vs. 9.28%, P < 0.001), Pediatric Index of Mortality (PIM) 3 score (9.23 vs. 8.36, P < 0.001), Pediatric Risk of Mortality (PRISM) III score (7.0 vs. 5.0, P < 0.001), incidence of septic shock (12% vs. 3%, P < 0.001), C-reactive protein (33.0 mg/L vs. 5.8 mg/L, P < 0.001), delta neutrophil index (2.0% vs. 0.6%, P < 0.001), lactate level (1.6 mmol/L vs. 1.2 mmol/L, P < 0.001) and lower platelet level (206,000/µl vs. 341,000/µl, P < 0.001) compared to the children with normal albumin level. PIM 3 (r = 0.219, P < 0.001) and PRISM III (r = 0.375, P < 0.001) were negatively correlated with serum albumin level, respectively. CONCLUSIONS: Our results highlight that hypoalbuminemia can be a biomarker of poor prognosis including mortality in the children in ICU.

Inhibition of Neurite Outgrowth by Stably Expressed Go alpha in F11 Cells / 대한해부학회지

Heterotrimeric G proteins mediate signals generated by neurotransmitters and hormones. Among G proteins, Go is found in a large quantity in brain and growth cone membranes of neurons. In spite of its abundance in neurons, the role of Go is not fully understood. In the previous study, we showed that transient expression of the alpha subunit of Go (alpha o) modulated neurite outgrowth in F11 cells. It is possible that transient transfection may cause transient accumulation of the protein, which itself may alter differentiation process in non-specific manner. In this study, we determined that modulation of neurite outgrowth by alpha o was specific by evaluating the effect of alpha o in stably transformed F11 cells. F11 cells stably expressing the wild type alpha o (alphao(wt)) and a constitutively active form of alpha o (alpha oQ205L) were established. In normal F11 cells and alpha o-stable cell lines, the neurite length was measured in the presence of dibutyryl cAMP. In normal F11 cells, the average length of neurites was 57.9+/-7.0 microgram. In alpha o(wt)- and alpha o(Q205L)-expressing cells, the average length were 34.4+/-5.1 microgram 30.5+/-3.6 microgram, respectively. Thus, stable expression of alpha o(wt) and alpha o(Q205L) caused a decrease in neurite outgrowth by 40.6%, 47.3% respectively. This result indicates that modulation of neurite by alpha o was specific to the function of alpha o but not due to accumulation of exogenous proteins.

Overexpression of neurogenin1 induces neurite outgrowth in F11 neuroblastoma cells

Neurogenin1 (Ngn1) is a basic helix-loop-helix (bHLH) transcription factor expressed in neuronal precursors in the developing nervous system. The function of Ngn1 in neurogenesis has been shown in various aspects. In this study, we investigated the neurogenic potential of Ngn1 using neuroblastoma cell line, F11, which could be induced to differentiate into neurons in the presence of cAMP. To investigate the expression of Ngn1, expression vectors for the full-length and the C- terminal deletion mutant of Ngn1 were constructed and their transactivation potential was verified using reporter gene containing the E-box sequence. Overexpression of the full-length Ngn1 induced neurite outgrowth in F11 cells in the absence of cAMP. A C-terminal deletion mutant, Ngn1(1-197), inhibited neurite outgrowth induced by cAMP in F11 cells. These results indicate that the Ngn1 plays an important role in differentiation of neuroblastoma cells and the C terminus of Ngn1 is essential for the efficient differentiation.

Neuronal Differentiatin of P19 Cells / 대한해부학회지

P19, murine embryonal carcinoma (EC) cells can be induced to differentiate into neurons in the presence of retinoic acid (RA). To investigate neuronal differentiation of P19 cells in details, P19 aggregates were obtained in the presence or absence of RA, ascorbic acid (AA) and 2-mercaptoethanol (2-ME) in bacteriological Petri dishes. When the aggregates were transferred into the serum depleted medium, P19 cells exhibited dramatic morphological changes. Cells contained long and thin processes as detected in differentiated neurons. Western blot analysis showed that treatment of RA and AA induced expression of neuron-specific markers such as NCAM, NSE and Tuj1. Expression of GFAP was not detected, suggesting that P19 cells differentiate into neurons under our experimental condition. Immunocytochemical studies also revealed that treatment of RA and AA increased expression of NCAM and Tuj1. On the contrary, 2-ME was ineffective in the neuronal differentiation of P19 cells, which is consistent the results from the western blot analysis. These results suggest that differentiated P19 cells have similar characteristics to those of typically differentiated neurons. This study also suggests that P19 cells may provide useful tools to study neuronal differentiation in vitro.

A Computer Program for Understanding Brain Morphology and Magnetic Resonance Image / 한국의학교육

Understanding of brain morphology and magnetic resonance image(MRI) is essential for accurate diagnosis and treatment of the brain diseases. As education tools, the cadaver dissection, plastic models, and neuroanatomy books have been used for understanding brain morphology; and the MRI films and radiology books have been used for understanding brain MRI. Recently, due to the popularization of powerful personal computers, computer programs compensating the conventional education tools have been used. But these computer programs have a disadvantage that it is not possible to visualize the details of brain morphology or to compare the corresponding sectioned specimens and MRI. Therefore, we attempted to make a computer program which could visualize not only the details of brain morphology but also the corresponding sectioned specimens and MRI by using the brains removed from Korean cadavers. Three brains were removed from Korean cadavers. With a brain, 122 MRI and 122 serially-sectioned specimens with an 1.4mm interval were acquired and inputted into the computer. Ten brain structures were segmented, and 83 fine structures were designated on the images. With two brains, 27 dissected specimens were acquired and inputted into the computer. One-hundred two fine structures were designated on the images. Based on these images, a computer program for understanding brain morphology and MRI was made. The computer program, which was made in this study, visualized the corresponding sectioned specimens, MRI, and segmented images after sectioning a brain horizontally or at any angles. In addition, the computer program visualized the images of dissected brain. This computer program is helpful to understand brain morphology and MRI. This computer program is expected to be used through CD-title or Internet as an educational tool for medical students and doctors.