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. mannitolilyticainfection 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.

Estimating baseline creatinine values to define acute kidney injury in critically ill pediatric patients

Acute kidney injury (AKI) is a common complication in critically ill children. However, the common lack of baseline serum creatinine values affects AKI diagnosis and staging. Several approaches for estimating baseline creatinine values in those patients were evaluated. Methods: This single-center retrospective study enrolled pediatric patients with documented serum creatinine measurements within 3 months before admission and more than two serum creatinine measurements within 7 days after admission to the pediatric intensive care unit of a tertiary care children’s hospital between January 2016 and April 2020. Four different approaches for estimating AKI using serum creatinine measurements were compared: 1) back-calculation using age-adjusted normal reference glomerular filtration rates, 2) age-adjusted normal reference serum creatinine values, 3) minimum values measured within 7 days after admission, and 4) initial values upon admission. Results: The approach using minimum values showed the best agreement with the measured baseline value, with the largest intraclass correlation coefficient (0.623), smallest bias (–0.04), and narrowest limit of agreement interval (1.032). For AKI diagnosis and staging, the minimum values were 80.8% and 76.1% accurate, respectively. The other estimated baseline values underestimated AKI and showed poor agreement with baseline values before admission, with a misclassification rate of up to 42% (p < 0.001). Conclusion: Minimum values of serum creatinine measured within 7 days after hospital admission showed the best agreement with creatinine measured within 3 months before admission, indicating the possibility of using it as a baseline when baseline data are unavailable. Further large-scale studies are required to accurately diagnose AKI in critically ill children.

Association of vitamin D deficiency with clinical outcomes in critically ill Korean children

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.

Extracorporeal Membrane Oxygenation Cannula Malposition in the Azygos Vein in a Neonate with Right-Sided Congenital Diaphragmatic Hernia / 대한구급학회지

Malposition of the extracorporeal membrane oxygenation (ECMO) venous cannula in the azygos vein is not frequently reported. We hereby present such a case, which occurred in a neonate with right-sided congenital diaphragmatic hernia. Despite ECMO application, neither adequate flow nor sufficient oxygenation was achieved. On the cross-table lateral chest radiograph, the cannula tip was identified posterior to the heart silhouette, which implied malposition of the cannula in the azygos vein. After repositioning the cannula, the target flow and oxygenation were successfully achieved. When sufficient venous flow is not achieved, as in our case, clinicians should be alerted so they can identify the cannula tip location on lateral chest radiograph and confirm whether malposition in the azygos vein is the cause of the ineffective ECMO.

Clinical Characteristics of Patients with Bronchopulmonary Dysplasia Admitted to Pediatric Intensive Care Unit

PURPOSE: As the incidence of bronchopulmonary dysplasia (BPD) has increased, it is important to understand the clinical outcomes of BPD patients discharged from neonatal intensive care units (NICU). The purpose of our study was to describe the characteristics of BPD patients who are re-hospitalized in a pediatric intensive care unit (PICU) and to evaluate the prognostic outcome factors. METHODS: We retrospectively reviewed the medical records of BPD patients who were admitted to our PICU between May 2006 and November 2014. In total, we identified 101 cases which were divided into two groups, group 1, those who required intensive care for an acute illness or disease aggravation (n=62), and group 2, those who were admitted for post-operative care unrelated to having BPD as a control group (n=39). We subsequently compared the characteristics. RESULTS: Most patients in group 1 were aged less than 1 year, with weight below the 3rd percentile for age at the time of their PICU admission. The main cause for their admission was respiratory failure, requiring mechanical ventilation. When comparing the two groups, group 1 showed higher gestational age at birth, and a longer duration of mechanical ventilation, oxygen support, and NICU hospitalization than group 2. However, we failed to identify any factor significantly associated with the duration of the PICU stay, hospital stay, and mortality. Further large-scale, long-term follow-up studies will be necessary. CONCLUSION: As the majority of patients are admitted to PICU because of respiratory symptoms during their infantile period, careful follow-up with supportive care and prevention of respiratory infection are required.

Extracorporeal Membrane Oxygenation Cannula Malposition in the Azygos Vein in a Neonate with Right-Sided Congenital Diaphragmatic Hernia / 대한중환자의학회지

Malposition of the extracorporeal membrane oxygenation (ECMO) venous cannula in the azygos vein is not frequently reported. We hereby present such a case, which occurred in a neonate with right-sided congenital diaphragmatic hernia. Despite ECMO application, neither adequate flow nor sufficient oxygenation was achieved. On the cross-table lateral chest radiograph, the cannula tip was identified posterior to the heart silhouette, which implied malposition of the cannula in the azygos vein. After repositioning the cannula, the target flow and oxygenation were successfully achieved. When sufficient venous flow is not achieved, as in our case, clinicians should be alerted so they can identify the cannula tip location on lateral chest radiograph and confirm whether malposition in the azygos vein is the cause of the ineffective ECMO.

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.

Low Blood Selenium Concentrations in Critically Ill Children with Systemic Inflammatory Response Syndrome and Respiratory Dysfunction / 대한구급학회지

BACKGROUND: Selenium is an essential trace-element with antioxidant and immunological function. We studied the relationship between blood selenium concentrations, systemic inflammatory response syndrome (SIRS) and organ dysfunctions in critically ill children. METHODS: This was a retrospective, observational study of the blood selenium concentrations of critically ill children at the time of a pediatric intensive care unit admission. RESULTS: A total of 62 patients with a median age of 18 (5-180) months were included in this study. The mean of blood selenium concentration (microg/dl) was 8.49 +/- 2.42. The platelet count (r = -0.378) and PaCO2 (r = -0.403) showed negative correlations with blood selenium concentration, while PaO2/FiO2 (r = 0.359) and PaO2 (r = 0.355) showed positive correlations (p 300 (7.90 +/- 2.43 vs. 9.54 +/- 2.17, p = 0.018). Blood selenium concentrations were significantly lower in patient with PaO2/FiO2 300 (7.64 +/- 2.76 vs. 9.54 +/- 2.17, p = 0.018). CONCLUSIONS: Patients with systemic inflammatory response syndrome or respiratory dysfunction showed significantly low blood selenium concentrations.

Severe hypermagnesemia presenting with abnormal electrocardiographic findings similar to those of hyperkalemia in a child undergoing peritoneal dialysis / 소아과

In this report, we present a pediatric case of severe symptomatic hypermagnesemia resulting from the use of magnesium oxide as a laxative in a child undergoing continuous cyclic peritoneal dialysis for end-stage renal disease. The patient showed abnormal electrocardiography (ECG) findings, such as tall T waves, a widened QRS complex, and irregular conduction, which were initially misdiagnosed as hyperkalemia; later, the correct diagnosis of hypermagnesemia was obtained. Emergent hemodialysis successfully returned the serum magnesium concentration to normal without complications. When abnormal ECG changes are detected in patients with renal failure, hypermagnesemia should be considered.

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.

Two Cases of X-Linked Myotubular Myopathy with Novel MTM1 Mutations

BACKGROUND: Myotubular myopathy (MTM) is a congenital myopathy characterized by centrally placed nuclei in muscle fibers. Mutations in the myotubularin 1 gene (MTM1) have been identified in the most of the patients with the X-linked recessive form. CASE REPORT: This report describes two male infants with X-linked MTM (XLMTM). Both patients presented with generalized hypotonia and respiratory difficulties since birth. We did not perform a muscle biopsy in either patient, but their conditions were diagnosed by genetic testing of MTM1. One splicing mutation, c.63+1G>C, and a frame-shift mutation, c.473delA (p. Lys158SerfxX28), were identified. Neither mutation has been reported previously. CONCLUSIONS: Genetic testing for MTM1 is helpful for the differential diagnosis of floppy male infants. We suggest that advanced molecular genetic testing may permit a correct diagnosis while avoiding invasive procedures.

Extracorporeal Membrane Oxygenation Support in a Patient with Status Asthmaticus

Status asthmaticus is a rare, fatal condition, especially in children. Sometimes respiratory support is insufficient with a mechanical ventilator or medical therapy for patients with status asthmaticus. In such situations, early extracorporeal membrane oxygenation application is a useful method for treating refractory respiratory failure. We report on a case of a six-year-old, male child who underwent venovenous extracorporeal membrane oxygenation support for refractory status asthmaticus.

The Relationship between Early Changes in Respiratory Parameters and the Prognosis in Children with Acute Lung Injury / 소아알레르기및호흡기학회지

PURPOSE: The PaO2/FiO2 (P/F) ratio, oxygenation index (OI) and the ventilation index (VI) have been used as parameters of acute respiratory failure. This study was conducted to evaluate the relationship between the prognosis and early changes in the respiratory parameters in pediatric patients with acute lung injury (ALI). METHODS: This is a retrospective study of 97 patients who had ventilator care for more than 3 days due to acute respiratory failure between January 2008 and May 2009 in PICU of Asan Medical Center. RESULTS: The mean age was 3.7+/-5.0 years. This study included 58 males and 39 females. The mortality rate was 27.8%. There was no significant difference between the survivors and non-survivors in the initial P/F ratio, OI and VI. However, these parameters improved in the survivor group, unlike the non-survivor group whose parameters remained unchanged or worsened. When comparing the receiver operating characteristic (ROC) curve of the initial respiratory parameters and the changes in parameters for 3 days, the area under the ROC curves representing the changes in respiratory parameters for 3 days was significantly greater than that of initial respiratory parameters, thus indicating the parameter changes are more reliable predictors of mortality than the initial parameters. CONCLUSION: Early changes in respiratory parameters such as the P/F ratio, OI and VI, rather than initial parameters themselves, are more directly related to the prognosis of pediatric patients with ALI and would be useful in determining optimal treatment and predicting the prognosis.

Early Changes in the Sequential Organ Failure Assessment (SOFA) Score as a Prognostic Factor in Acute Respiratory Failure in Children with Mechanical Ventilator Support / 소아알레르기및호흡기학회지

PURPOSE: In pediatric acute respiratory failure patients requiring mechanical ventilator support, mortality is seldom related to respiratory disease alone, but more generally to multiple organ dysfunction syndrome. The purpose of this study is to evaluate whether early changes in the SOFA score (Delta-SOFA) are more effective for predicting the outcome than a single assessment upon admission for pediatric acute respiratory failure patients requiring mechanical ventilator support. METHODS: The medical records of pediatric patients with acute respiratory failure requiring mechanical ventilator support for more than 72 hours in the PICU of the Asan Medical Center Children's Hospital, Seoul, Korea, between January 2008 and May 2009 were retrospectively reviewed. RESULTS: Early Delta-SOFA showed a significantly stronger correlation with patient mortality compared with the initial SOFA score, PRISM III score and PELOD score (P<0.05). When analyzing the trends in the SOFA score during the first 72 hours, the mortality rate was significantly higher in children with increased and unchanged SOFA scores 72 hours after admission than in children with a decreased SOFA score. (14.5% vs. 42.9%, P<0.05) CONCLUSION: Regardless of the initial SOFA score, early serial evaluation of the SOFA scores during the first 3 days of PICU admission is a better indicator of the prognosis than a single assessment obtained at admission in acute respiratory failure patients mechanically ventilated for more than 3 days.

Effect of hyperglycemia on mortality rates in critically ill children / 소아과

PURPOSE: To verify the effect of hyperglycemia on mortality rates in critically ill children and to identify the blood glucose level that influences prognosis. METHODS: From July 2006 to June 2008, a total of 206 patients who were admitted to the pediatric intensive care unit (PICU) at Asan Medical Center and who survived for more than 7 days were retrospectively reviewed. We analyzed the maximum glucose value within 7 days in PICU, PRISM-III score and SOFA score within 24 hours, and mortality. We did not perform an adjustment analysis of drugs affecting glucose level. RESULTS: The maximum glucose level within 7 days in PICU was higher in the nonsurvival group than in the survival group. Using 4 cutoff values (125, 150, 175, and 200 mg/dL), the mortality of patients with hyperglycemia was found to be 13.0%, 14.4%, 19.8%, and 21.1%, respectively, and the cutoff values of 175 and 200 mg/dL revealed significant differences in mortalities between the hyperglycemic and normoglycemic groups. The PRISM-III score was not significantly different between the hyperglycemic and normoglycemic groups under a glucose cutoff value of 175 mg/dL, but the SOFA score was higher in the hyperglycemic group. Under a glucose cutoff value of 200 mg/dL, the PRISM-III score was higher in the hyperglycemic group, and the SOFA score did not differ between the 2 groups. CONCLUSION: Hyperglycemia with a maximal glucose value > or = 175 mg/dL during the first 7 days after PICU admission was associated with increased mortality in critically ill children.

Infections after Living Donor Liver Transplantation in Children

The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.

Nationwide surveillance of acute interstitial pneumonia in Korea / 소아과

PURPOSE: Acute interstitial pneumonia (AIP) is a rare disease, but its prognosis is fatal because of lack of efficient treatment modality. Recently, it has been reported that there was epidemic AIP in Korea. This study aims to investigate the past and current status of AIP in Korea. METHODS: We performed a nationwide survey and a prospective study. From August 6 to 15, 2008, a questionnaire survey was conducted to identify the prevalence, local distribution, and response to current treatments. The questionnaire was answered by pediatrician working in 23 referral centers in Korea. In addition, 5 referral centers in Seoul performed a preliminary prospective observational study by obtaining clinical data and specimens from appropriate patients. The Korea Centers for Disease Control and Prevention analyzed the samples for possible pathogens. RESULTS: The survey showed 78 AIP cases had occurred and 36 patients had died. Lung biopsy was performed only on 20 patients. In 2008, 9 AIP cases developed. In a prospective study, 9 (M:F=5:4) patients developed AIP in spring and 7 (78%) died, with the mean rate of death occurring 46 days after diagnosis. Human corona virus 229 E, cytomegalovirus, influenza A virus, influenza B virus, and parainfluenza virus were isolated from the respiratory specimens. CONCLUSION: This study showed nationwide prevalence of AIP in Korea. In addition, because of the high mortality rate and rapid progress, pediatricians need to be aware of the disease. Further studies and a nationwide network are required for reducing the morbidity and mortality rates related to AIP.

The Effect of Rush Immunotherapy with House Dust Mite in the Production of IL-5 and IFN-gamma from the Peripheral Blood T Cells of Asthmatic Children

Although the mechanisms are unclear, rush immunotherapy (RIT) may be effective to treat allergic diseases. We investigated the long-term modifications of cellular immunity as a mechanism of RIT. The RIT group, included 15 house dust mite (HDM)-sensitized asthmatic children, received RIT only with Dermatophagoides farinae (Der f) and Dermatophagoides pteronyssinus (Der p), whereas the control group, consisted of 10 HDM-sensitized asthmatic children, did not receive RIT. The asthma symptom scores and the skin reactivities to Der f were measured. The cellular proliferative responses and intracellular interleukin (IL)-5 and interferon (IFN)-gamma productions from peripheral blood T cells were also measured before, 8 weeks and 1 yr after RIT. The symptom scores, skin reactivity to Der f and cellular proliferative responses to Der f were decreased significantly after 8 weeks and maintained until 1 yr of RIT. The IFN-gamma/IL-5 ratio of the CD3(+) and CD4(+) cells were increased significantly after 8 weeks and maintained until 1 yr of RIT, while there were no changes in the control group. These data indicate that the continuous functional modification from Th2 to Th1 phenotype of the CD4(+) T cells are developed after RIT in the asthmatic children sensitized with HDM.

Outcome and risk factors of pediatric hemato-oncology patients admitted in pediatric intensive care unit / 소아과

PURPOSE: To evaluate the risk factors for mortality and prognostic factors in pediatric hemato-oncology patients admitted to the pediatric intensive care unit (PICU). METHODS: We retrospectively reviewed the medical records of pediatric hemato-oncology patients admitted at the PICU of the Asan Medical Center between September 2005 and July 2008. Patients admitted at the PICU for perioperative or terminal care were excluded. RESULTS: Total 88 patients were analyzed. Overall ICU mortality rate was 34.1%. Mean age at PICU admission was 7.0+/-5.7 years and mean duration of PICU stay was 18.1+/-22.2 days. Hematologic diseases contributed to 77.3% of all the primary diagnoses, and the primary cause of admission was respiratory failure (39.8%). The factors related to increased mortality were C-reactive protein level (P<0.01), ventilation or dialysis requirement (P<0.01), and hematopoietic stem cell transplantation (P<0.05). In all, 3 scoring systems were investigated [Number of Organ System Failures (OSF number), the Pediatric Risk of Mortality III (PRISM III) score, and the Sequential Organ Failure Assessment (SOFA) score]; higher score correlated with worse outcome (P<0.01). The Oncological Pediatric Risk of Mortality (O-PRISM) scores of the 21 patients who had received hematopoietic stem cell transplantation were higher among the non-survivors, but not statistically significant (P=0.203). CONCLUSION: The PRISM III and SOFA scores obtained within 24 hours of PICU admission were found to be useful as early mortality predictors. The highest OSF number during the PICU stay was closely related to poor outcome.