Pediatric Extracorporeal Membrane Oxygenation in Korea: A Multicenter Retrospective Study on Utilization and Outcomes Spanning Over a Decade.

BACKGROUND: Over the last decade, extracorporeal membrane oxygenation (ECMO) use in critically ill children has increased and is associated with favorable outcomes. Our study aims to evaluate the current status of pediatric ECMO in Korea, with a specific focus on its volume and changes in survival rates based on diagnostic indications. METHODS: This multicenter study retrospectively analyzed the indications and outcomes of pediatric ECMO over 10 years in patients at 14 hospitals in Korea from January 2012 to December 2021. Four diagnostic categories (neonatal respiratory, pediatric respiratory, post-cardiotomy, and cardiac-medical) and trends were compared between periods 1 (2012-2016) and 2 (2017-2021). RESULTS: Overall, 1065 ECMO runs were performed on 1032 patients, with the annual number of cases remaining unchanged over the 10 years. ECMO was most frequently used for post-cardiotomy (42.4%), cardiac-medical (31.8%), pediatric respiratory (17.5%), and neonatal respiratory (8.2%) cases. A 3.7% increase and 6.1% decrease in pediatric respiratory and post-cardiotomy cases, respectively, were noted between periods 1 and 2. Among the four groups, the cardiac-medical group had the highest survival rate (51.2%), followed by the pediatric respiratory (46.4%), post-cardiotomy (36.5%), and neonatal respiratory (29.4%) groups. A consistent improvement was noted in patient survival over the 10 years, with a significant increase between the two periods from 38.2% to 47.1% (P = 0.004). Improvement in survival was evident in post-cardiotomy cases (30-45%, P = 0.002). Significant associations with mortality were observed in neonates, patients requiring dialysis, and those treated with extracorporeal cardiopulmonary resuscitation (P < 0.001). In pediatric respiratory ECMO, immunocompromised patients also showed a significant correlation with mortality (P < 0.001). CONCLUSION: Pediatric ECMO demonstrated a steady increase in overall survival in Korea; however, further efforts are needed since the outcomes remain suboptimal compared with global outcomes.

Clinical Manifestation of Ralstonia mannitolilytica Infection in Pediatric Patients and Epidemiological Investigation of Outbreaks.

BACKGROUND: Ralstonia mannitolilytica is a causative organism of nosocomial infections, particularly associated with contaminated water, and resistant to various antibiotics, including carbapenems. Several clusters of R. mannitolilytica infections appeared in children at our institute from August 2018 to November 2019. METHODS: From March 2009 to March 2023, all patients admitted to Asan Medical Center Children's Hospital in Seoul, Korea, with culture-confirmed R. mannitolilytica and corresponding clinical signs of infection were identified. Epidemiological and environmental investigations were conducted. Polymerase chain reaction (PCR) was performed for the genes of OXA-443 and OXA-444 on R. mannitolilytica isolates. RESULTS: A total of 18 patients with R. mannitolilytica infection were included in this study, with 94.4% (17/18) and 5.6% (1/18) being diagnosed with pneumonia and central line-associated bloodstream infection, respectively. All-cause 30-day mortality rate was 61.1% (11/18), and seven of the fatal cases were caused by R. mannitolilytica infection itself. The resistance rates to meropenem and imipenem werew 94.4% (17/18) and 5.6% (1/18), respectively. Although four out of nine meropenem-resistant R. mannitolilytica isolates had positive PCR results for OXA-443 and OXA-444 genes, there were no significant differences in antimicrobial susceptibility patterns. Environmental sampling identified R. mannitolylica at two sites: a cold-water tap of a water purifier and an exhalation circuit of a patient mechanical ventilator. After implementing and improving adherence to infection control policies, no additional R. mannitolilytica infection cases have been reported since December 2019. CONCLUSION: R. mannitolilytica can cause life-threatening infections with high mortality in fragile pediatric populations. To prevent outbreaks, healthcare workers should be aware of R. mannitolilytica infections and strive to comply with infection control policies.

Recent Improvement in Survival Outcomes and Reappraisal of Prognostic Factors in Pediatric Living Donor Liver Transplantation.

Living donor liver transplantation (LDLT) is a significant advancement for the treatment of children with end-stage liver disease given the shortage of deceased donors. The ultimate goal of pediatric LDLT is to achieve complete donor safety and zero recipient mortality. We conducted a retrospective, single-center assessment of the outcomes as well as the clinical factors that may influence graft and patient survival after primary LDLTs performed between 1994 and 2020. A Cox proportional hazards model was used for multivariate analyses. The trends for independent prognostic factors were analyzed according to the following treatment eras: 1, 1994 to 2002; 2, 2003 to 2011; and 3, 2012 to 2020. Primary LDLTs were performed on 287 children during the study period. Biliary atresia (BA; 52%), acute liver failure (ALF; 26%), and monogenic liver disease (11%) were the leading indications. There were 45 graft losses (16%) and 27 patient deaths (7%) in this population during the study period. During era 1 (n = 81), the cumulative survival rates at 1 and 5 years after LDLT were 90.1% and 81.5% for patients and 86.4% and 77.8% for grafts, respectively. During era 2 (n = 113), the corresponding rates were 92.9% and 92% for patients and 89.4% and 86.7% for grafts, respectively. During era 3 (n = 93), the corresponding rates were 100% and 98.6% for patients and 98.9% and 95.4% for grafts, respectively. In the multivariate analyses, primary diagnosis ALF, bloodstream infection, posttransplant lymphoproliferative disease, and chronic rejection were found to be negative prognostic indicators for patient survival. Based on generalized care guidelines and center-oriented experiences, comprehensive advances in appropriate donor selection, refinement of surgical techniques, and meticulous medical management may eventually realize a zero-mortality rate in pediatric LDLT.

Mitochondrial gene mutations in pediatric septic shock.

BACKGROUND: There has been a growing interest in the association between mitochondrial dysfunction and sepsis. However, most studies have focused on mitochondrial structural damage, functional aspects, or the clinical phenotypes in sepsis. The purpose of this study was to evaluate mitochondrial DNA (mtDNA) gene mutations in critically ill pediatric patients with septic shock. METHOD: Thirteen patients with severe sepsis or septic shock admitted to the pediatric intensive care unit (PICU) of a tertiary children's hospital were enrolled in this prospective observational study. Clinical data from electronic medical records were obtained. Whole-blood samples were collected within 24 h of PICU admission to perform PBMC isolation, mtDNA extraction, and mtDNA sequencing using next-generation sequencing. RESULTS: mtDNA sequencing revealed mutations in 9 of the 13 patients, presenting 27 point mutations overall, with 15 (55.6%) located in the locus related to adenosine triphosphate production and superoxide metabolism, including electron transport. CONCLUSION: In this pilot study, significant numbers of mtDNA point mutations were detected in critically ill pediatric patients with septic shock. These mutations could provide promising evidence for mitochondrial dysfunction in sepsis and a basis for further large-scale studies. IMPACT: This study is the first to examine mitochondrial DNA mutations in pediatric patients with septic shock using next-generation sequencing. A high frequency of mitochondrial DNA mutations was detected in these patients indicating an association with septic shock. This pilot study may provide a potential explanation for the association between mitochondrial dysfunction and septic shock on a genetic basis.

Modification of Pediatric Sequential Organ Failure Assessment Score Using Acute Kidney Injury Diagnostic Criteria.

OBJECTIVES: To develop a modified pediatric Sequential Organ Failure Assessment score using the acute kidney injury diagnostic criteria and evaluate its performance in predicting mortality. DESIGN: A single-center retrospective study. SETTING: Fourteen-bed PICU in a tertiary care academic children's hospital. PATIENTS: Critically ill children admitted to the PICU between January 2017 and September 2019 with at least more than two serum creatinine measurements-one for baseline and the other within the first 48 hours of PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 755 patients were included. Overall, 265 patients were diagnosed with acute kidney injury using the current acute kidney injury diagnostic criteria. The overall PICU mortality was 5.8%. Patients with acute kidney injury required more vasoactive-inotropic drugs and showed higher illness severity scores, including the Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, pediatric Sequential Organ Failure Assessment, and modified pediatric Sequential Organ Failure Assessment scores, as well as higher PICU mortality than patients without acute kidney injury (p < 0.001). As acute kidney injury stages increase, PICU mortality also increased (p < 0.001). Based on multivariable logistic regression analysis adjusted for age and sex, the modified pediatric Sequential Organ Failure Assessment score was an independent prognostic factor of PICU mortality. The modified pediatric Sequential Organ Failure Assessment score showed better performance in predicting PICU mortality (area under the receiver operating characteristic curve, 0.821; 95% CI, 0.759-0.882) than other severity scores (area under the receiver operating characteristic curve [95% CI] of Pediatric Risk of Mortality III, Pediatric Logistic Organ Dysfunction 2, and pediatric Sequential Organ Failure Assessment scores: 0.788 [0.723-0.853], 0.735 [0.663-0.807], and 0.785 [0.718-0.853], respectively). CONCLUSIONS: Acute kidney injury is prevalent and associated with poor clinical outcomes in critically ill children. The modified pediatric Sequential Organ Failure Assessment score, based on the acute kidney injury diagnostic criteria, showed improved performance in predicting PICU mortality. The modified pediatric Sequential Organ Failure Assessment score could be a promising prognostic factor for critically ill children.

Energy Expenditure in Mechanically Ventilated Korean Children: Single-Center Evaluation of a New Estimation Equation.

OBJECTIVES: Accurate assessments of energy expenditure are vital for determining optimal nutritional support, especially in critically ill children. We evaluated current methods for energy expenditure prediction, in comparison with indirect calorimetry, and developed a new estimation equation for mechanically ventilated, critically ill Korean children. DESIGN: Single-center retrospective study. SETTING: Fourteen-bed pediatric medical ICU in a tertiary care children's hospital. PATIENTS: Pediatric patients admitted to the PICU between October 2017 and September 2019 with a measured energy expenditure by indirect calorimetry. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total 95 pediatric patients (70 in derivation cohort for development of a new predictive equation and 25 in validation cohort) were included. Mean measured energy expenditure of group A was 66.20 ± 15.35 kcal/kg/d. All previously established predictive equations underestimated the predicted energy expenditure, compared with the measured energy expenditure, except the Food and Agriculture/World Health Organization/United Nations University equation. The Schofield-Height and Weight equation showed the best performance among the tested predictive equations for the entire cohort (least bias, -68.58 kcal/d; best percentage, 108.46% ± 33.60%) compared with the measured energy expenditure. It was also the best performing predictive equation in subgroup analysis by age, sex, nutritional status, and organ failure. Because some discrepancies remained between the measured energy expenditure and predicted energy expenditures, we developed a new estimation equation using multiple regression analysis and those variables significantly associated with our current measured energy expenditures: Energy expenditure = -321.264 + 72.152 × (body weight, kg)-1.396 × (body weight) + 5.668 × height (cm) + organ dysfunction* (*hematologic, 76.699; neurologic, -87.984). This new estimation equation showed the least bias and best percentage compared with previous predictive equations (least bias, 15.51 kcal/d; best percentage, 102.30% ± 28.10%). CONCLUSIONS: There are significant disparities between measured and calculated energy expenditures. We developed a new estimation equation based on measured energy expenditure data that shows better performance in mechanically ventilated Korean children than other equations. This new estimation equation requires further prospective validation in pediatric series with a range in body habitus.

Elevated central venous pressure is associated with increased mortality in pediatric septic shock patients.

BACKGROUND: Central venous pressure (CVP) is an important factor affecting capillary blood flow, and it is associated with poor outcomes in adult septic shock patients. However, whether a similar association exists in pediatric patients remains unclear. METHODS: We retrospectively analyzed data from patients admitted to our pediatric intensive care unit (PICU) between February 2009 and July 2015. Patients were divided into two groups-survivors and nonsurvivors-according to 28-day mortality. The associations between (a) mortality and CVP at 6, 24, 48, and 72 h after initiating treatment for established septic shock was analyzed and (b) initial serum lactic acid levels and 6-h CVP. RESULTS: Two hundred twenty-six patients were included in this study, and the mortality rate was 29.6% (67 deaths, nonsurvivor group). Initial serum lactic acid levels, Pediatric Risk of Mortality (PRISM) III score, and Vasoactive-Inotropic Score (VIS) within 24 h after PICU admission were significantly higher in the nonsurvivors than in survivors (1.3 [0.9, 2.4] vs. 3.9 [1.6, 8.0] mmol/l, 11.0 [7.0, 15.0] vs. 17.0 [10.0, 21.5], 12.0 [7.0, 25.0] vs. 22.5 [8.0, 55.0], respectively with p-values < 0.001, < 0.001, and 0.009, respectively). In addition, compared to survivors, a greater percentage of nonsurvivors required mechanical ventilation (92.5% vs. 51.6%, p <  0.001) and showed a greater extent of fluid overload at 48 h after admission (3.9% vs. 1.9%, p = 0.006), along with higher 6-h CVP (10.0 [7.0, 16.0] vs. 8.0 [5.0, 11.0] mmHg, p <  0.001). Patient survival according to levels of CVP (CVP < 8 mmHg, CVP 8-12 mmHg, or CVP > 12 mmHg) showed that the CVP > 12-mmHg group had significantly greater mortality rates (50.0%, p = 0.002) than the other groups (21.3% and 27.5%). Furthermore, multivariate analysis identified significant associations of CVP > 12 mmHg, serum lactic acid levels, and the need for mechanical ventilation with mortality (OR: 2.74, 1.30, and 12.51, respectively; 95% CI: 1.11-6.72, 1.12-1.50, and 4.12-37.96, respectively). CONCLUSIONS: Elevated CVP is an independent risk factor for mortality in pediatric septic shock patients.

Current Status of Pediatric Critical Care in Korea: Results of 2015 National Survey.

BACKGROUND: The aim of this study was to describe the structure, organization, management, and staffing of pediatric critical care (PCC) in Korea. METHODS: We directed a questionnaire survey for all Upper Grade General Hospitals (n = 43) in Korea in 2015. The first questionnaire was mainly about structure, organization, and staffing and responses were obtained from 32 hospitals. The second questionnaire was mainly about patients and management. Responses to second questionnaire were obtained from 18 hospitals. RESULTS: Twelve from 32 Upper Grade General Hospitals had pediatric intensive care units (PICUs) and 11 of them had the PICU which was exclusive for children. Total number of PICU beds in Korea was 113. The ratio of the number of PICU beds to the number of children was 1:77,460 in Korea and this ratio is lower than that of other developed countries. The mean number of beds in the PICUs was 9.4 ± 9.3 (range, 2-30). There were 16 medical doctors who were assigned for PCC and only 5 of them were full time pediatric intensivists. In the 18 Upper Grade General Hospitals that responded to the second questionnaire survey, there were 97 patients in the PICUs with an average number of 5.7 ± 7.2 (range, 0-22) on the survey day. The mean age of the patients was 3.4 ± 5.6 years. The mean length of hospital stay was 82 ± 271 days. The mean Pediatric Risk of Mortality score III was 9.4 ± 7.8 at the time of admission to the PICUs. CONCLUSION: There is a considerable shortage of PICU beds compared to those in developed countries. In addition, the proportion of PICUs with PCC specialists is much lower than those in the US and European countries.

Factors Associated With Mortality in Continuous Renal Replacement Therapy for Pediatric Patients With Acute Kidney Injury.

OBJECTIVES: To analyze the epidemiology of pediatric acute kidney injury requiring continuous renal replacement therapy and identify prognostic factors affecting mortality rates. DESIGN: Retrospective analysis. SETTING: PICU of a tertiary medical center. PATIENTS: One hundred-twenty three children diagnosed with acute kidney injury requiring continuous renal replacement therapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Vasoactive-Inotropic Score, arterial blood gas analysis, blood chemistry at continuous renal replacement therapy initiation, the extent of fluid overload 24 hours prior to continuous renal replacement therapy initiation, Pediatric Risk of Mortality III score at admission, and need for mechanical ventilation during continuous renal replacement therapy were compared in survivors and nonsurvivors. Out of 1,832 patient admissions, 185 patients (10.1%) developed acute kidney injury during the study period. Of these, 158 patients were treated with continuous renal replacement therapy, and finally, 123 patients were enrolled. Of the enrolled patients, 50 patients died, corresponding to a mortality rate of 40.6%. The survivor group and the nonsurvivor group were compared, and the following factors were associated with an increased risk of mortality: higher Pediatric Risk of Mortality III score at admission and Vasoactive-Inotropic Score when initiating continuous renal replacement therapy, increased fluid overload 24 hours before continuous renal replacement therapy initiation, and need for mechanical ventilation during continuous renal replacement therapy. The percentage of fluid overload difference between the survivors and the nonsurvivors was 1.2% ± 2.2% versus 4.1% ± 4.6%, respectively. Acidosis, elevated lactic acid and blood urea nitrogen, and lower serum creatinine level were laboratory parameters associated with increased mortality. On multivariate analysis, Vasoactive-Inotropic Score, need for mechanical ventilation, blood urea nitrogen, and creatinine level were statistically significant. (Odds ratio: 1.040, 6.096, 1.032, and 0.643, respectively.) CONCLUSIONS:: A higher Vasoactive-Inotropic Score, need for mechanical ventilation, elevated blood urea nitrogen, and lower creatinine level were associated with increased mortality in pediatric acute kidney injury patients who underwent continuous renal replacement therapy. Lower creatinine levels may be associated with increased mortality in the context of fluid overload, which is correlated with a reduced chance of survival.

Evaluation of Disseminated Intravascular Coagulation Scores in Critically Ill Pediatric Patients.

OBJECTIVES: Disseminated intravascular coagulation is a complex systemic thrombohemorrahgic disorder, which may contribute to organ failure. We aimed to compare the detection rate of the disseminated intravascular coagulation, early in the course of ICU admission, of the two disseminated intravascular coagulation scoring systems defined by International Society on Thrombosis and Hemostasis and Japanese Association for Acute Medicine criteria and the prognostic value of disseminated intravascular coagulation scores in critically ill pediatric patients. DESIGN: Single-center retrospective observational study. SETTING: PICU in a tertiary care children's hospital. PATIENTS: Pediatric patients admitted in the PICU between January 2013 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 191 patients were included. Among them, 15.7% and 29.8% of the patients were diagnosed with disseminated intravascular coagulation by International Society on Thrombosis and Hemostasis and Japanese Association for Acute Medicine criteria, respectively. The diagnostic concordance rate between the International Society on Thrombosis and Hemostasis and Japanese Association for Acute Medicine scoring systems was 52.6%. As the Pediatric Risk of Mortality III, the modified Sequential Organ Failure Assessment, and the Pediatric Multiple Organ Dysfunction Syndrome scores increased, the percentage of patients with disseminated intravascular coagulation increased stepwise. The disseminated intravascular coagulation scores correlated well with these severity scores. Overall, the 28-day mortality was 9.9%. There were significant differences in most variables consisting of the International Society on Thrombosis and Hemostasis and Japanese Association for Acute Medicine scoring systems between survivor and nonsurvivors. Patients detected to have disseminated intravascular coagulation by the International Society on Thrombosis and Hemostasis and Japanese Association for Acute Medicine scoring systems showed higher mortality than patients without disseminated intravascular coagulation. The areas under the receiver operating characteristic curve of the Japanese Association for Acute Medicine score and International Society on Thrombosis and Hemostasis score were 0.788 (95% CI, 0.675-0.900) and 0.716 (95% CI, 0.598-0.834), respectively. CONCLUSIONS: Both the International Society on Thrombosis and Hemostasis and the Japanese Association for Acute Medicine scoring systems are useful for detection of the disseminated intravascular coagulation in critically ill pediatric patients. These scores correlate well with other severity scores, including Pediatric Risk of Mortality III, modified Sequential Organ Failure Assessment, and Pediatric Multiple Organ Dysfunction Syndrome. Disseminated intravascular coagulation scores are also significantly associated with 28-day mortality, suggesting that these could be promising prognostic factors.

The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease.

From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea.

Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies.

RASopathies are a group of syndromes caused by germline mutations of the RAS/MAPK pathway. They include Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, and Noonan syndrome with multiple lentigines, which share many characteristic features including cardiac abnormalities. Here, we retrospectively reviewed the clinical manifestations and evaluated the genotype-phenotype associations with special focus on cardiac lesions of the patients with RASopathies. Cardiac symptoms were the most common initial presentation (27 %), except for admission to neonatal intensive care. Although there was a significant gap between the first visit to the hospital and the diagnosis of the genetic syndrome (19.9 ± 39.1 months), the age at the clinical diagnosis of the genetic syndrome was significantly lower in patients with CHD than in patients without CHD (47.26 ± 67.42 vs. 86.17 ± 85.66 months, p = 0.005). A wide spectrum of cardiac lesions was detected in 76.1 % (118/155) of included patients. The most common lesion was pulmonary stenosis, followed by atrial septal defect and hypertrophic cardiomyopathy (HCMP). About half of the pulmonary stenosis and HCMP patients progressed during the median follow-up period of 109.9 (range 9.7-315.4) months. Early rapid aggravation of cardiac lesions was linked to poor prognosis. MEK1, KRAS, and SOS1 mutations tend to be highly associated with pulmonary stenosis. Cardiologists may play important roles in early detection and diagnosis of RASopathies as well as associated CHDs. Due to the variety of clinical presentations and their progression of severity, proper management with regular long-term follow-up of these patients is essential.

Clinical and molecular characterisation of Holt-Oram syndrome focusing on cardiac manifestations.

BACKGROUND: Holt-Oram syndrome is characterised by CHD and limb anomalies. Mutations in TBX5 gene, encoding the T-box transcription factor, are responsible for the development of Holt-Oram syndrome, but such mutations are variably detected in 30-75% of patients. METHODS: Clinically diagnosed eight Holt-Oram syndrome patients from six families were evaluated the clinical characteristics, focusing on the cardiac manifestations, in particular, and molecular aetiologies. In addition to the investigation of the mutation of TBX5, SALL4, NKX2.5, and GATA4 genes, which are known to regulate cardiac development by physically and functionally interacting with TBX5, were also analyzed. Multiple ligation-dependent probe amplification analysis was performed to detect exonic deletion and duplication mutations in these genes. RESULTS: All included patients showed cardiac septal defects and upper-limb anomalies. Of the eight patients, seven underwent cardiac surgery, and four suffered from conduction abnormalities such as severe sinus bradycardia and complete atrioventricular block. Although our patients showed typical clinical findings of Holt-Oram syndrome, only three distinct TBX5 mutations were detected in three families: one nonsense, one splicing, and one missense mutation. No new mutations were identified by testing SALL4, NKX2.5, and GATA4 genes. CONCLUSIONS: All Holt-Oram syndrome patients in this study showed cardiac septal anomalies. Half of them showed TBX5 gene mutations. To understand the genetic causes for inherited CHD such as Holt-Oram syndrome is helpful to take care of the patients and their families. Further efforts with large-scale genomic research are required to identify genes responsible for cardiac manifestations or genotype-phenotype relation in Holt-Oram syndrome.

Extrarenal sequential organ failure assessment score as an outcome predictor of critically ill children on continuous renal replacement therapy.

BACKGROUND: The sequential organ failure assessment (SOFA) score is easy to calculate and has been well validated as an outcome predictor in critically ill adult patients. However, its use in children has been limited, mainly because of differences in basal reference levels of serum creatinine. METHODS: Data include 87 patients requiring continuous renal replacement therapy (CRRT) between January 2005 and July 2011. We modified the SOFA score by excluding the renal component to an extrarenal SOFA score, based on the assumption that CRRT may mitigate the renal effect on outcome and investigated the utility in predicting outcome with comparison with pediatric risk of mortality (PRISM) III, pediatric logistic organ dysfunction (PELOD), and SOFA scores. RESULTS: Results showed that 95.4 % (n = 83) had multiple organ dysfunction syndrome with an overall mortality of 50.6 %. The extrarenal SOFA score at CRRT initiation and ≥20 % fluid overload were significantly associated with mortality. In comparison with the predictive power of various scoring systems, the extrarenal SOFA score showed the largest area under the receiver operating characteristic curve (extrarenal SOFA 0.774, SOFA 0.770, PRISM III 0.660, and PELOD 0.650). CONCLUSIONS: The extrarenal SOFA score may be a useful prognostic marker in critically ill children treated with CRRT.

High prevalence of neonatal presentation in Korean patients with citrullinemia type 1, and their shared mutations.

Type 1 citrullinemia (CTLN1) often presents as a hyperammonemic encephalopathy in the neonatal period, but it can also develop in the late-infantile period and in adults. In addition, some patients can be identified in the presymptomatic period by neonatal or family member screening. In this study, twenty Korean patients with CTLN1 (19 families) were examined; fourteen patients with neonatal-onset, three with late-onset, and three that were identified presymptomatically. The 13 patients with hyperammonemic encephalopathy received continuous venovenous hemofiltration (CVVH) or peritoneal dialysis (PD). Although the hyperammonemia was relieved more effectively in the six patients on CVVH than the seven on PD, most of these patients suffered from severe neurologic deficits. Recurrent hyperammonemic episodes (7 pts, 35%), recurrent and reversible acute hepatic dysfunction (5 pts, 25%), and focal cerebral infarction (2 pts, 10%) were noted. The neonates with hyperammonemic encephalopathy had extensive brain injuries at the onset of hyperammonemia, followed by encephalomalacia and brain atrophy at quite an early age. Genetic testing for the ASS1 gene revealed a different mutation spectrum from those of other ethnicities; Three common mutations, c.421-2A>G (37.8%), c.1128-6_1188dup67 (18.9%), and p.Gly324Ser (16.2%), accounted for 73% of the mutations. The poor outcome was expected in patients with the peak ammonia level at onset over 600µmol/L, whose proportion was higher in the neonatal presentation group than in the presymptomatic/late presentation group. Our findings add to the current understanding of the ethnic diversity of CTLN1 from both clinical and genetic perspectives.

Toxic inhalational injury-associated interstitial lung disease in children.

Interstitial lung disease in children (chILD) is a group of disorders characterized by lung inflammation and interstitial fibrosis. In the past recent years, we noted an outbreak of child in Korea, which is possibly associated with inhalation toxicity. Here, we report a series of cases involving toxic inhalational injury-associated chILD with bronchiolitis obliterans pattern in Korean children. This study included 16 pediatric patients confirmed by lung biopsy and chest computed tomography, between February 2006 and May 2011 at Asan Medical Center Children's Hospital. The most common presenting symptoms were cough and dyspnea. The median age at presentation was 26 months (range: 12-47 months), with high mortality (44%). Histopathological analysis showed bronchiolar destruction and centrilobular distribution of alveolar destruction by inflammatory and fibroproliferative process with subpleural sparing. Chest computed tomography showed ground-glass opacities and consolidation in the early phase and diffuse centrilobular nodular opacity in the late phase. Air leak with severe respiratory difficulty was associated with poor prognosis. Although respiratory chemicals such as humidifier disinfectants were strongly considered as a cause of this disease, further studies are needed to understand the etiology and pathophysiology of the disease to improve the prognosis and allow early diagnosis and treatment.

Comparison of the clinical characteristics and clinical outcomes of culture-positive septic shock and culture-negative septic shock among pediatric patients.

OBJECTIVES: Among pediatric patients with septic shock, culture-negative septic shock (CNSS) is common but there have been limited data on its clinical characteristics and prognosis. We compared the clinical characteristics and clinical outcomes between culture-positive septic shock (CPSS) and CNSS in pediatric patients. DESIGN: Retrospective single-center study. SETTING: Pediatric intensive care unit (PICU) of a tertiary referral hospital. PATIENTS: All pediatric patients who were admitted to the PICU due to septic shock between January 2010 and November 2021, except for those with fungal or viral infections and those who expired on the day of admittance to the PICU. The primary outcome was 30-day mortality and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients (CPSS group, n = 185 [62.9%]; CNSS group, n = 109 [37.1%]) were included. The rates of 30-day mortality and in-hospital mortality (30-day mortality 22.7% vs 22%, in-hospital mortality 29.7% vs 25.7%) were not significantly different between the CPSS group and the CNSS group. The two groups showed comparable results in clinical outcomes such as the requirement for mechanical ventilator and renal replacement therapy, PICU stay duration, and the duration of MV and vasopressor/inotrope support. Among the CPSS group, 98 (53%) patients who were infected with multi-drug resistance (MDR) bacteria had significantly higher rates of 30-day mortality and in-hospital mortality than those infected with non-MDR bacteria. CONCLUSIONS: Among pediatric patients, the CPSS group and CNSS group did not show significant differences in clinical features and mortality. Among the CPSS group, those with MDR bacteria had poorer prognosis.

Disseminated Intravascular Coagulation as a Risk Factor for Clinical Outcome After Liver Transplantation in Pediatric Patients With Kasai Portoenterostomy Failure.

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication in critically ill pediatric patients. This study aimed to evaluate the association between pretransplant DIC and perioperative clinical outcomes of liver transplantation (LT) in pediatric patients with Kasai portoenterostomy (KPE) failure. METHODS: We enrolled pediatric patients who received LT after KPE failure between January 2005 and April 2021. We retrospectively reviewed the electronic medical records of included patients and evaluated the presence of DIC using the International Society on Thrombosis and Hemostasis (ISTH) criteria and association with perioperative clinical outcome. RESULTS: The study included 106 patients. Their median age and body weight at the time of pediatric intensive care unit (PICU) admission were 28.7 months and 9.25 kg, respectively. Of these patients, 23 had undergone pretransplant DIC (22%). Patients with pretransplant DIC required significantly more blood transfusions during operation. They had significantly higher serum lactate levels, pediatric end-stage liver disease scores, pediatric risk for mortality III (PRISM III) scores, longer durations of mechanical ventilator support, and longer PICU stays (all P < .05). CONCLUSIONS: The presence of pretransplant DIC in pediatric patients requiring LT after KPE failure was associated with poor clinical outcomes, which required more intensive and meticulous supportive management in the perioperative period of LT. DIC would be a promising prognostic factor in these patients.

Successful liver transplantation following veno-arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: a case report.

Massive pulmonary hemorrhage and other serious cardiopulmonary diseases in patients with fulminant hepatitis result not only in graft failure but also mortality after LT. ECMO is used to treat children with cardiorespiratory failure refractory to conventional intensive care. We describe a five-yr-old girl with genetically confirmed fulminant Wilson disease and severe pulmonary hemorrhage who underwent successful primary LT following veno-arterial ECMO. To our knowledge, this is the first report of successful primary LT in a patient using veno-arterial ECMO. The present case demonstrates that ECMO, as a bridging modality to LT, may be necessary to manage both massive pulmonary hemorrhage and possible graft loss because of hypoxemia.

Mitral valve replacement using mechanical prostheses in children: early and long-term outcomes.

Compared with mitral repair, mitral valve replacement is an uncommon procedure in children due to associated high mortality and morbidity rates. The present study investigated early and late outcomes after MVR with mechanical prostheses in children at our institution. Between January 1994 and December 2009, 19 children underwent MVR. Mean patient age was 7.6 ± 5.5 years (range 3 months-16 years), and mean body weight was 23.7 ± 15.1 kg (range 5.0-58.1 kg). Mean prosthesis size was 25.8 ± 4.2 mm (range 19-31 mm). There were no operative or late mortalities. Three patients showed decreased left-ventricular function before surgery, and one of them underwent successful heart transplantation due to progressive LV dysfunction at 10 months after MVR. The proportion of patients with freedom from reoperation at 10 years was 94.7 ± 5%. There were no major thromboembolic or bleeding episodes. Although the small number of patients in our study was a limitation, MVR in children was found to result in excellent early and long-term outcomes. It appears that MVR could be considered in children before LV dysfunction develops.