Long-term impact of late pulmonary hypertension requiring medication in extremely preterm infants with severe bronchopulmonary dysplasia.

This study investigated whether late pulmonary hypertension (LPH) independently increases the risk of long-term mortality or neurodevelopmental delay (NDD) in extremely preterm infants (EPIs) with severe bronchopulmonary dysplasia (BPD). Using prospectively collected data from the Korean Neonatal Network, we included EPIs with severe BPD born at 22-27 weeks' gestation between 2013 and 2021. EPIs having severe BPD with LPH (LPH, n = 124) were matched 1:3 with those without pulmonary hypertension (PH) as controls (CON, n = 372), via propensity score matching. LPH was defined as PH with the initiation of medication after 36 weeks' corrected age (CA). Long-term mortality after 36 weeks' CA or NDD at 18-24 months' CA was analyzed. NDD was assessed using composite scores based on various neurodevelopmental assessment modalities. LPH had significantly higher long-term mortality or NDD (45.2% vs. 23.1%, P < 0.001), mortality (24.2% vs. 4.84%, P < 0.001), and NDD (68.4% vs. 37.8%, P = 0.001), respectively than CON, even after adjusting for different demographic factors. Multivariable regression demonstrated that LPH independently increased the risk of mortality or NDD (adjusted odds ratio, 1.95; 95% confidence intervals, 1.17-3.25). When LPH occurs in EPIs with severe BPD, special monitoring and meticulous care for long-term survival and neurodevelopment are continuously needed.

Current Status and Associated Factors of Post-Hemorrhagic Hydrocephalus in Infants of 22 to 28 Weeks Gestation With Severe Intraventricular Hemorrhage in Korea: A Nationwide Cohort Study.

BACKGROUND: Post-hemorrhagic hydrocephalus (PHH), a common complication of severe intraventricular hemorrhage (IVH) in very low birth weight (BW) infants, is associated with significant morbidity and poor neurological outcomes. The objective of this study was to assess the current status of PHH and analyze the risk factors associated with the necessity of treatment for PHH in infants born between 22 and 28 weeks of gestation, specifically those with severe IVH (grade 3 or 4). METHODS: The analysis was conducted on 1,097 infants who were born between 22-28 gestational weeks and diagnosed with severe IVH, using data from the Korean Neonatal Network. We observed that the prevalence of PHH requiring treatment was 46.3% in infants with severe IVH. RESULTS: Higher rates of mortality, transfer during admission, cerebral palsy, and ventriculoperitoneal shunt after discharge were higher in infants with PHH than in those without PHH. PHH in severe IVH was associated with a higher rate of pulmonary hemorrhage, seizures, and IVH grade 4 in the entire cohort. In addition, it was associated with a lower rate of small for gestational age and chorioamnionitis. In the subgroup analysis, high BW, outborn status, pulmonary hemorrhage, seizure, sepsis, and IVH grade 4 were associated with a higher incidence of PHH between 22 and 25 gestational weeks (GW). In infants born between 26 and 28 GW, a higher incidence of PHH was associated with seizures and IVH grade 4. CONCLUSION: It is necessary to maintain meticulous monitoring and neurological intervention for infants with PHH not only during admission but also after discharge. In addition, identifying the clinical factors that increase the likelihood of developing PHH from severe IVH is crucial.

Mesenchymal Stem Cells Reduce the Extracellular Mitochondrial DNA-Mediated TLR9 Activation in Neonatal Hyperoxia-Induced Lung Injury.

Mitochondrial DNA (mtDNA) released from dead or injured cells can activate inflammation, and mesenchymal stem cell (MSC) transplantation can reduce inflammation and injury. However, it has not been tested whether the release of mtDNA can be reduced by MSC transplantation. We hypothesized that the level of extracellular mtDNA would be increased after hyperoxia-induced lung injury but reduced after lung injury attenuation by MSC therapy in our newborn rat model. In an in vitro study using a rat lung epithelial L2 cell line, we found that the level of extracellular mtDNA was significantly increased with H2O2-induced cell death but reduced after MSC co-incubation. In an in vivo study, we confirmed that the levels of cell death, extracellular mtDNA, and inflammatory cytokines were significantly increased in hyperoxic newborn rat lungs but reduced after MSC transplantation. The levels of extracellular mtDNA were significantly and positively correlated with the levels of the inflammatory cytokines. The TLR9/MyD88/NF-κB pathway, which is activated by binding to mtDNA, was also significantly upregulated but downregulated after MSC transplantation. We found a significant positive correlation between inflammatory cytokines and extracellular mtDNA in intubated neonates. The levels of inflammatory cytokines and extracellular mtDNA changed over time in a similar pattern in transtracheal aspirate samples from intubated neonates. In conclusion, increased levels of extracellular mtDNA are associated with increased inflammation in hyperoxia-induced lung injury, and attenuation of lung inflammation by MSC therapy is associated with reduced levels of extracellular mtDNA.

Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants.

BACKGROUND: Though antenatal magnesium sulfate (MgSO4) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised. METHODS: We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24-31 weeks. RESULTS: Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18-24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group. CONCLUSION: Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.

Mesenchymal Stromal Cells Primed by Toll-like Receptors 3 and 4 Enhanced Anti-Inflammatory Effects against LPS-Induced Macrophages via Extracellular Vesicles.

Although it has been suggested that toll-like receptor (TLR) 3 and TLR4 activation alters mesenchymal stromal cells (MSCs)' immunoregulatory function as anti- or pro-inflammatory phenotypes, we have previously confirmed that TLR4-primed hUCB-MSCs alleviate lung inflammation and tissue injury in an E. coli-induced acute lung injury (ALI) mouse model. Therefore, we hypothesized that strong stimulation of TLR3 or TLR4 prompts hUCB-MSCs to exhibit an anti-inflammatory phenotype mediated by extracellular vesicles (EVs). In this study, we compared the anti-inflammatory effect of TLR3-primed and TLR4-primed hUCB-MSCs against an LPS-induced ALI in vitro model by treating MSCs, MSC-derived conditioned medium (CM), and MSC-derived extracellular vesicles (EVs). LPS-induced rat primary alveolar macrophage and RAW 264.7 cells were treated with naïve, TLR3-, and TLR4-primed MSCs and their derived CM and EVs. Flow cytometry and ELISA were used to evaluate M1-M2 polarization of macrophages and pro-inflammatory cytokine levels, respectively. LPS-stimulated macrophages showed significantly increased pro-inflammatory cytokines compared to those of the normal control, and the percentage of M2 macrophage phenotype was predominantly low. In reducing the inflammatory cytokines and enhancing M2 polarization, TLR3- and TLR4-primed MSCs were significantly more effective than the naïve MSCs, and this finding was also observed with the treatment of MSC-derived CMs and EVs. No significant difference between the efficacy of TLR3- and TLR-primed MSCs was observed. Strong stimulation of TLR3- and TLR4-stimulated hUCB-MSCs significantly reduced pro-inflammatory cytokine secretion from LPS-induced macrophages and significantly enhanced the M2 polarization of macrophages. We further confirmed that TLR-primed MSC-derived EVs can exert anti-inflammatory and immunosuppressive effects alone comparable to MSC treatment. We hereby suggest that in the LPS-induced macrophage in vitro model, EVs derived from both TLR3 and TLR4-primed MSCs can be a therapeutic candidate by promoting the M2 phenotype.

Optimal Protocols and Management of Clinical and Genomic Data Collection to Assist in the Early Diagnosis and Treatment of Multiple Congenital Anomalies.

Standardized protocols have been designed and developed specifically for clinical information collection and obtaining trio genomic information from infants affected with congenital anomalies (CA) and their parents, as well as securing human biological resources. The protocols include clinical and genomic information collection on multiple CA that were difficult to diagnose using pre-existing screening methods. We obtained human-derived resources and genomic information from 138 cases, including 45 families of infants with CA and their parent trios. For the clinical information collection protocol, criteria for target patient selection and a consent system for collecting and utilizing research resources are crucial. Whole genome sequencing data were generated for all participants, and standardized protocols were developed for resource collection and manufacturing. We recorded the phenotype information according to the Human Phenotype Ontology term, and epidemiological information was collected through an environmental factor questionnaire. Updating and recording of clinical symptoms and genetic information that have been newly added or changed over time are significant. The protocols enabled long-term tracking by including the growth and development status that reflect the important characteristics of newborns. Using these clinical and genetic information collection protocols for CA, an essential platform for early genetic diagnosis and diagnostic research can be established, and new genetic diagnostic guidelines can be presented in the near future.

Changes to Blood-Sampling Protocol to Reduce the Sampling Amount in Neonatal Intensive Care Units: A Quality Improvement Project.

(1) Background: This study aimed to evaluate whether the implementation of a modified blood-sampling protocol, which focused on need-based laboratory testing and minimized venous sampling by replacing it with point-of-care testing (POCT) via capillary puncture, successfully reduced iatrogenic blood loss, incidence of anemia, and the frequency of blood transfusion among extremely low-birth-weight infants (ELBWIs) without negatively affecting neonatal outcomes. (2) Methods: A retrospective analysis was conducted on 313 ELBWIs with a gestational age (GA) of between 23 and 28 weeks and born between 2013 and 2019. The infants were divided into two groups corresponding to the periods before (period I) and after (period II) the implementation of the modified blood-sampling protocol in January 2016. Propensity score matching was conducted to minimize selection bias. Clinical data, including the frequency and amount of blood sampling, the frequency and volume of blood transfusion, and clinical characteristics, such as gestational age, birth weight, and neonatal outcome data, were collected and compared between the two groups. (3) Results: No significant differences in GA or birth weight between the two periods were observed. The total sampling volume a month after birth (16.7 ± 4.1 mL vs. 15.6 ± 4.4 mL, p = 0.03) and the total sampling volume during hospitalization days (51.4 ± 29.7 mL vs. 44.3 ± 27.5 mL, p = 0.04) in period II were significantly lower than those in period I. There were no differences in terms of anemia (hemoglobin 10.8 ± 2.2 vs. 11.0 ± 1.9, p = 0.43) and mortality or morbidity, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and sepsis, between the two periods. Although the transfusion frequency and amount did not present significant differences between the periods, we observed a positive correlation between the transfusion frequency and sampling volume (coefficient: 0.09, 95% CI: 0.08-0.11). (4) Conclusions: The modified blood-sampling protocol effectively reduced the level of iatrogenic blood loss without negatively affecting the neonatal outcomes.

SOCS3 Protein Mediates the Therapeutic Efficacy of Mesenchymal Stem Cells against Acute Lung Injury.

Mesenchymal stem cells (MSCs) have been studied as novel therapeutic agents because of their immunomodulatory properties in inflammatory diseases. The suppressor of cytokine signaling (SOCS) proteins are key regulators of the immune response and macrophage modulation. In the present study, we hypothesized that SOCS in MCSs might mediate macrophage modulation and tested this in a bacteria-induced acute lung injury (ALI) mouse model. The macrophage phenotype was observed in RAW264.7 alveolar macrophages exposed to lipopolysaccharide (LPS) in an in vitro model, and in the ALI mouse model induced by tracheal administration of Escherichia coli (1 × 107 CFU in 0.05mL PBS). In LPS-exposed RAW264.7 cells, the levels of markers of M1 macrophages, such as CD86 and pro-inflammatory cytokines (IL-1α, IL-1ß, IL-6 and TNF-α), significantly increased, but they significantly reduced after MSC treatment. Meanwhile, the levels of markers of M2 macrophages, such as CD204 and anti-inflammatory cytokines (IL-4 and IL-10), increased after LPS exposure, and further significantly increased after MSC treatment. This regulatory effect of MSCs on M1/M2 macrophage polarization was significantly abolished by SOCS3 inhibition. In the E. coli-induced ALI model, tissue injury and inflammation in the mouse lung were significantly attenuated by the transplantation of MSCs, but not by SOCS3-inhibited MSCs. The regulatory effect of MSCs on M1/M2 macrophage polarization was observed in the lung injury model but was significantly abolished by SOCS3 inhibition. Taken together, our findings suggest that SOCS3 is an important mediator for macrophage modulation in anti-inflammatory properties of MSCs.

Neonatal Intensive Care Quality Level-Dependent Variations in the Survival Rate of Infants with a Birth Weight of 500 g or Less in Korea: A Nationwide Cohort Study.

OBJECTIVE: Recent evidence suggests that the survival of peri-viable infants with birth weight (BW) ≤500 g could be improved with better care practices in the neonatal intensive care unit (NICU). This study aimed to investigate the care quality level of NICU-dependent variations in the survival rate of infants with BW ≤500 g. METHODS: To determine the quality of NICU care-dependent variations in the survival rate, 226 eligible infants of BW ≤500 g and ≥22 weeks gestation registered in the Korean Neonatal Network between 2013 and 2017 were grouped according to the survival rates of infants at 23-24 weeks gestation, reflecting the care quality level of each NICU as group I (≥50%, n = 107) and group II (<50%, n = 119). RESULTS: The survival rate of group I infants (40.2%, 43/107) was significantly higher than that of group II infants (14.3%, 17/119). Significantly reduced deaths from birth to the age of 7 days due to cardiorespiratory causes were the primary contributors to improved survival. In multivariable Cox hazard model analyses, besides the gestational age and BW, antenatal steroid use, cesarean section, pH, and base excess at admission were associated with improved infant survival. CONCLUSIONS: The survival rate of pre-viable infants with BW ≤500 g could be improved by providing better NICU quality care practices, including better cardiorespiratory management starting from delivery room resuscitation.

Mesenchymal-Stem-Cell-Derived Extracellular Vesicles Attenuate Brain Injury in Escherichia coli Meningitis in Newborn Rats.

We recently reported that transplantation of mesenchymal stem cells (MSCs) significantly reduced bacterial growth and brain injury in neonatal meningitis induced by Escherichia coli (E. coli) infection in newborn rats. As a next step, to verify whether the MSCs protect against brain injury in a paracrine manner, this study was designed to estimate the efficacy of MSC-derived extracellular vesicles (MSC-EVs) in E. coli meningitis in newborn rats. E. coli meningitis was induced without concomitant bacteremia by the intra-cerebroventricular injection of 5 × 102 colony-forming units of K1 (-) E. coli in rats, at postnatal day 11. MSC-EVs were intra-cerebroventricularly transplanted 6 h after the induction of meningitis, and antibiotics were administered for three consecutive days starting at 24 h after the induction of meningitis. The increase in bacterial growth in the cerebrospinal fluid measured at 24 h after the meningitis induction was not significantly reduced following MSC-EV transplantation. However, an increase in brain cell death, reactive gliosis, and inflammation following meningitis were significantly attenuated after MSC-EV transplantation. Taken together, our results indicate that MSCs show anti-apoptotic, anti-gliosis, and anti-inflammatory, but not antibacterial effects, in an EV-mediated paracrine manner in E. coli-induced neonatal meningitis.

Effect of levothyroxine supplementation in extremely low birth weight infants with transient hypothyroxinemia of prematurity.

This study aimed to determine the short- and/or long-term outcomes of levothyroxine replacement therapy in extremely low birth weight (ELBW) infants with transient hypothyroxinemia of prematurity (THOP). The medical records of 335 ELBW infants with THOP were reviewed retrospectively to identify whether levothyroxine treatment affects short- and/or long-term outcomes at a corrected age of 2 years. The infants were arbitrarily grouped based on thyroxine (T4) (free T4 [fT4]) levels into group 1 (n = 142), which included infants with T4 (fT4) levels < 2.5 (0.5) ng/dl, and group 2 (n = 193), which included those with T4 (fT4) levels ranging from ≥ 2.5 (0.5) ng/dl to < 4.5 (0.9) ng/dl. Levothyroxine replacement therapy was not associated with beneficial short- or long-term outcomes in ELBW infants with THOP. Short-term outcomes, such as mortality and composite morbidities, and long-term outcomes, such as failure to achieve catch-up height at a corrected age of 2 years, were significantly higher in group 1 than in group 2, regardless of levothyroxine treatment status. Levothyroxine replacement therapy is not associated with short-or long-term advantages in ELBW infants with THOP. This study suggests that the severity of THOP may be the major determinant of adverse outcomes in ELBW infants with THOP, rather than levothyroxine treatment.

Increased Risk of Meconium-Related Ileus in Extremely Premature Infants Exposed to Antenatal Magnesium Sulfate.

INTRODUCTION: We experienced an increased incidence of meconium-related ileus (MRI) in extremely premature infants (EPIs) while adopting the antenatal magnesium sulfate (MgSO4) protocol for fetal neuroprotection in our neonatal intensive care unit. This study aimed to test whether antenatal MgSO4 use was associated with increased risk of MRI in EPIs. METHODS: The incidences of complicated MRI requiring aggressive enema or surgical intervention and other intestinal complications were compared among period 1 (January 2012-December 2013, n = 79), before adoption of the antenatal MgSO4 protocol for fetal neuroprotection; period 2 (January 2014-March 2016, n = 72), when the protocol was adopted; and period 3 (April 2016-September 2018, n = 75), when the protocol was temporarily withdrawn due to concern regarding intestinal complications in EPIs. RESULTS: Despite similar baseline clinical characteristics among infants across the study periods, the MRI and MRI with surgical treatment incidences were higher in period 2 than those in periods 1 and 3 (13% vs. 8% and 6%, p = 0.391, and 11% vs. 0% and 1%, p = 0.001, respectively). In multivariable analysis, exposure to antenatal MgSO4 independently increased the risk of MRI (adjusted odds ratio, 3.8; 95% confidence interval, 1.4, 10.6). CONCLUSION: Antenatal MgSO4 may increase the risk of MRI, frequently requiring surgical intervention, in EPIs with a gestational age of 25 weeks or less.

A Preterm Infant with Feeding Aspiration Diagnosed with BOR Syndrome, Confirmed Case by Whole-Genome Sequencing and Structural Variant Calling.

Branchiootorenal (BOR) syndrome is a rare autosomal dominant inherited disease with a prevalence of approximately 1 in 40,000 newborns. This disease is characterized by hearing loss, preauricular pits, branchial fistulas or cysts, and renal dysplasia. We discovered a case of BOR syndrome in a premature 2-week-old female infant with a gestational age of 32 weeks and two days. She and her family had major symptoms and a family history of BOR. BOR syndrome was confirmed by whole-genome sequencing and structural variant calling, which revealed an EYA1 exon 5-6 deletion. The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea.

Conservative Management of Patent Ductus Arteriosus Is Feasible in the Peri-Viable Infants at 22-25 Gestational Weeks.

The purpose of this study was to determine the natural course of hemodynamically significant (HS) patent ductus arteriosus (PDA) with conservative management and whether the presence or prolonged duration of HS PDA affected mortality/morbidities in infants at 22-25 weeks estimated gestational age (EGA). We retrospectively reviewed the medical records of 77 infants born at 22-25 weeks EGA, stratified into 22-23 weeks (n = 21) and 24-25 weeks EGA (n = 56). HS PDA was present in 77%, 76%, and 77%, and open ductus at discharge was 12%, 13%, and 12% in the total and at 22-23 and 24-25 weeks EGA infants, respectively. For backup rescue treatment, 7% and 5% of the infants received oral ibuprofen and device closure, respectively. A mortality rate of 9% was found in the HS PDA (+) infants, significantly lower than the 28% in HS PDA (-) infants. There are no significant differences in morbidities. In multivariate analyses, the presence and/or prolonged duration of HS PDA was not associated with increased mortality or morbidity. Spontaneous closure of HS PDA was achieved through conservative management in the peri-viable infants at 22-25 weeks EGA.

Mortality and Morbidities according to Time of Birth in Extremely Low Birth Weight Infants.

BACKGROUND: Although the overall quality of high-risk neonatal care has improved recently, there is still concern about a difference in the quality of care when comparing off-hour births and regular-hour births. Moreover, there are no data in Korea regarding the impact of time of birth on mortality and morbidities in preterm infants. METHODS: A total of 3,220 infants weighing < 1,000 g and born at 23-34 weeks in 2013-2017 were analyzed based on the Korean Neonatal Network data. Mortality and major morbidities were analyzed using logistic regression according to time of birth during off-hours (nighttime, weekend, and holiday) and regular hours. The institutes were sub-grouped into hospital group I and hospital group II based on the neonatal intensive care unit (NICU) care level defined by the mortality rates of < 50% and ≥ 50%, respectively, in infants born at 23-24 weeks' gestation. RESULTS: The number of births during regular hours and off-hours was similar. In the total population and hospital group I, off-hour births were not associated with increased neonatal mortality and morbidities. However, in hospital group II, increased early mortality was found in the off-hour births when compared to regular-hour births. CONCLUSION: Efforts to improve the overall quality of NICU are required to lower the early mortality rate in off-hour births. Also, other sensitive indexes for the evaluation of quality of NICU care should be further studied.

Conservative Non-intervention Approach for Hemodynamically Significant Patent Ductus Arteriosus in Extremely Preterm Infants.

While persistent patent ductus arteriosus (PDA) in preterm infants has been known to be associated with increased mortality and morbidities including bronchopulmonary dysplasia, and necrotizing enterocolitis, there is minimal evidence supporting their causal relationships, and most traditional medical and/or surgical treatments have failed to show improvements in these outcomes. As such, the pendulum has swung toward the conservative non-intervention approach for the management of persistent PDA during the last decade; however, the benefits and risks of this approach are unclear. In this mini review, we focused on whom, when, and how to apply the conservative non-intervention approach for persistent PDA, especially in extremely preterm infants.

The Impact of Surgical Intervention on Neurodevelopmental Outcomes in Very Low Birth Weight Infants: a Nationwide Cohort Study in Korea.

BACKGROUND: To investigate the incidence of surgical intervention in very low birth weight (VLBW) infants and the impact of surgery on neurodevelopmental outcomes at corrected ages (CAs) of 18-24 months, using data from the Korean Neonatal Network (KNN). METHODS: Data from 7,885 VLBW infants who were born and registered with the KNN between 2013 to 2016 were analyzed in this study. The incidences of various surgical interventions and related morbidities were analyzed. Long-term neurodevelopmental outcomes at CAs of 18-24 months were compared between infants (born during 2013 to 2015, n = 3,777) with and without surgery. RESULTS: A total of 1,509 out of 7,885 (19.1%) infants received surgical interventions during neonatal intensive care unit (NICU) hospitalization. Surgical ligation of patent ductus arteriosus (n = 840) was most frequently performed, followed by laser therapy for retinopathy of prematurity and laparotomy due to intestinal perforation. Infants who underwent surgery had higher mortality rates and greater neurodevelopmental impairment than infants who did not undergo surgery (P value < 0.01, both). On multivariate analysis, single or multiple surgeries increased the risk of neurodevelopmental impairment compared to no surgery with adjusted odds ratios (ORs) of 1.6 with 95% confidence interval (CI) of 1.1-2.6 and 2.3 with 95% CI of 1.1-4.9. CONCLUSION: Approximately one fifth of VLBW infants underwent one or more surgical interventions during NICU hospitalization. The impact of surgical intervention on long-term neurodevelopmental outcomes was sustained over a follow-up of CA 18-24 months. Infants with multiple surgeries had an increased risk of neurodevelopmental impairment compared to infants with single surgeries or no surgeries after adjustment for possible confounders.

Continuous Renal Replacement Therapy in Preterm Infants.

PURPOSE: Despite the increasing use of continuous renal replacement therapy (CRRT) in the neonatal intensive care unit (NICU), few studies have investigated its use in preterm infants. This study evaluated the prognosis of preterm infants after CRRT and identified risk factors of mortality after CRRT. MATERIALS AND METHODS: A retrospective review was performed in 33 preterm infants who underwent CRRT at the NICU of Samsung Medical Center between 2008 and 2017. Data of the demographic characteristics, predisposing morbidity, cardiopulmonary function, and CRRT were collected and compared between surviving and non-surviving preterm infants treated with CRRT. Univariable and multivariable analyses were performed to identify factors affecting mortality. RESULTS: Compared with the survivors, the non-survivors showed younger gestational age (29.3 vs. 33.6 weeks), lower birth weight (1359 vs. 2174 g), and lower Apgar scores at 1 minute (4.4 vs. 6.6) and 5 minutes (6.5 vs. 8.6). At the initiation of CRRT, the non-survivors showed a higher incidence of inotropic use (93% vs. 40%, p=0.017) and fluid overload (16.8% vs. 4.0%, p=0.031). Multivariable analysis revealed that fluid overload >10% at CRRT initiation was the primary determinant of mortality after CRRT in premature infants, with an adjusted odds ratio of 14.6 and a 95% confidence interval of 1.10-211.29. CONCLUSION: Our data suggest that the degree of immaturity, cardiopulmonary instability, and fluid overload affect the prognosis of preterm infants after CRRT. Preventing fluid overload and earlier initiation of CRRT may improve treatment outcomes.

Fabrication of diffraction gratings by top-down and bottom-up approaches based on scanning probe lithography.

Generation of diffraction gratings by top-down and bottom-up approaches based on scanning probe lithography is demonstrated. With regard to top-down fabrication, silicon nanostructured diffraction gratings are fabricated through one-dimensional (1D) dip-pen-nanolithography (DPN). Nanodot arrays (two-dimensional simple cubic lattice) of alkanethiol self-assembled monolayers (SAMs) are printed by 1D DPN on an Au-film-coated silicon substrate with lattice distances of 700, 1000, and 1200 nm. Silicon nanocircular pillars of length hundreds of nanometers are generated by sequential Au etching and reactive ion etching (RIE) of the 1D DPN printed sample. The performance of the silicon diffraction gratings as a microspectrometer is demonstrated through red, green, and blue color diffraction with white light incident at 45°. Moreover, arrays of zirconia nanoparticles (NPs) with an average diameter of visible wavelength (φ ≈ 470 nm) on an Au substrate are generated via bottom-up fabrication of the diffraction gratings. Microarrays of hydrophilic alkanethiol SAMs are obtained by polymer pen lithography (PPL). Self-assembly of zirconia NPs occurs after the passivation of hydrophobic alkanethiol SAMs of the PPL-printed sample. Fraunhofer diffraction with a square aperture is observed for the zirconia NP diffraction grating fabricated by the bottom-up approach.

A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets.

X-linked hypophosphatemic rickets is caused by loss-of-function mutations in PHEX, which encodes a phosphate-regulating endopeptidase homolog. We report a 26-year-old man with X-linked hypophosphatemic rickets who showed decreased serum phosphate accompanied by bilateral genu valgum and short stature. He had received medical treatment with vitamin D (alfacalcidol) and phosphate from the age of 3 to 20 years. He underwent surgery due to valgus deformity at the age of 14 and 15. Targeted gene panel sequencing for Mendelian genes identified a nonsense mutation in PHEX (c.589C>T; p.Gln197Ter) and a mosaic pattern where only 38% of sequence reads showed the variant allele. This mutation was not found in his mother, who had a normal phenotype. This is a case of a sporadic nonsense mutation in PHEX and up to date, this is the first case of a mosaic mutation in PHEX in Korea.