Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

The Impact of Implementing Critical Care Team on Open General Intensive Care Unit / 결핵및호흡기질환

BACKGROUND: There are a plethora of literatures showing that high-intensity intensive care unit (ICU) physician staffing is associated with reduced ICU mortality. However, it is not widely used in ICUs because of limited budgets and resources. We created a critical care team (CCT) to improve outcomes in an open general ICU and evaluated its effectiveness based on patients' outcomes. METHODS: We conducted this prospective, observational study in an open, general ICU setting, during a period ranging from March of 2009 to February of 2010. The CCT consisted of five teaching staffs. It provided rapid medical services within three hours after calls or consultation. RESULTS: We analyzed the data of 830 patients (157 patients of the CCT group and 673 patients of the non-CCT one). Patients of the CCT group presented more serious conditions than those of the non-CCT group (acute physiologic and chronic health evaluation II [APACHE II] 20.2 vs. 15.8, p<0.001; sequential organ failure assessment [SOFA] 5.5 vs. 4.6, p=0.003). The CCT group also had significantly more patients on mechanical ventilation than those in the non-CCT group (45.9% vs. 23.9%, p<0.001). Success rate of weaning was significantly higher in the CCT group than that of the non-CCT group (61.1% vs. 44.7%, p=0.021). On a multivariate logistic regression analysis, the increased ICU mortality was associated with the older age, non-CCT, higher APACHE II score, higher SOFA score and mechanical ventilation (p<0.05). CONCLUSION: Although the CCT did not provide full-time services in an open general ICU setting, it might be associated with a reduced ICU mortality. This is particularly the case with patients on mechanical ventilation.

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.

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.

Four Cases of Extracorporeal Membrane Oxygenation for Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) with severe pulmonary hypoplasia is associated with significant mortality. Recently, several new therapeutic methods have been suggested, such as high- frequency oscillatory ventilation and inhaled nitric oxide. For hypoxemic respiratory failure unresponsive to these advanced medical treatment options, extracorporeal membrane oxygenation (ECMO) serves as the last potentially effective treatment. An understanding of the pathophysiology of pulmonary hypertension associated with CDH led to a strategy involving preoperative stabilization and delayed surgical intervention with ECMO. We describe four cases of ECMO, including the first report of ECMO for neonatal CDH in Korea.

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.

Intraosseous line insertion education effectiveness for pediatric and emergency medicine residents / 소아과

PURPOSE: This study aimed to assess current knowledge of and training experiences with the intraosseous (IO) line among emergency medicine (EM) and pediatric residents who care for critically ill children and to evaluate the educational effectiveness of the IO line workshop. METHODS: During May and June 2008 , a workshops on IO line insertion was held for EM and pediatric residents. The workshop comprised a 45-min lecture and a 15-min hands-on session. Asemi-drill type EZ-IO machine was used for education. Self-assessment questionnaires gauged residents knowledge of and experiences with IO line insertion or bone marrow (BM) examination and their confidence with IO line insertion before and after the workshop. Performance tests were completed for skill evaluation. RESULTS: Forty-five pediatric residents and 22 EM residents participated in the workshop. The pre-educational questionnaire revealed that EM residents had more educational experience in IO line insertion than pediatric residents (p<0.001), while pediatric residents reported more experience in BM examination (p<0.001). The post-educational questionnaire showed a statistically significant higher percentage of correct answers (p<0.001). Although the pediatric residents inserted an IO line more quickly (P=0.001), most residents (88.7%) succeeded in IO line insertion on their first attempt; there was no difference in the groups success rates. Both groups showed higher confidence in performing IO line insertion after training (p<0.001). CONCLUSION: Observed educational effectiveness in both knowledge and confidence of IO line insertion skill suggest educational opportunities for pediatric and EM residents should be increased.

A case of hereditary hemorrhagic telangiectasia / 소아과

Hereditary hemorrhagic telagiectasia (HHT), which is characterized by the classic triad of mucocutaneous telangiectases, arteriovenous malformations (AVMs) and inheritance, is an autosomal dominant disorder. The characteristic manifestations of HHT are all due to abnormalities of the vascular structure. This report deals with the case of a 14-year-old girl with typical features of HHT that include recurrent epistaxis, mucocutanous telangiectases, pulmonary and cerebral AVMs and a familial occurrence.

Antithrombin-III as an early prognostic factor in children with acute lung injury / 소아과

PURPOSE: To evaluate the potential prognostic value of the antithrombin-III (AT-III) level in the children with acute lung injury (ALI), we analyzed several early predictive factors of death including AT-III level at the onset of ALI and compared the relative risk of them for mortality. METHODS: Over a 18-month period, a total of 198 children were admitted to our pediatric intensive care unit and 21 mechanically ventilated patients met ALI criteria, as defined by American-European consensus conference, i.e., bilateral pulmonary infiltrates and PaO2/FiO2 lower than 300 without left atrial hypertension. Demographic variables, hemodynamic and respiratory parameters, underlying diseases, as well as Pediatric Risk of Mortality-III (PRISM-III) scores and Lung Injury Score (LIS) at admission were collected. AT-III levels were measured within 3 hours after admission. These variables were compared between survivors and non-survivors and entered into a multiple logistic regression analysis to evaluate their independent prognostic roles. RESULTS: The overall mortality rate was 38.1% (8/21). Non-survivors showed lower age, lower lung compliance, higher PEEP, higher oxygenation index (OI), lower arterial pH, lower PaO2/FiO2, higher PRISM-III score and LIS, and lower AT-III level. PRISM-III score, LIS, OI and decreased AT-III level (less than 70%) were independently associated with a risk of death and the odds ratio of decreased AT-III level for mortality is 2.75 (95% confidence interval; 1.28-4.12) CONCLUSION: These results suggest that the decreased level of AT-III is an important prognostic factor in children with ALI and the replacement of AT-III may be considered as an early therapeutic trial.

Intellectual Outcome in Children with Congenital Hypothyroidism Treated from Early Life / 대한소아내분비학회지

PURPOSE: We did the IQ test to find out the effectiveness of the early treatment in children with congenital hypothyroidism. METHOD: The KEDI-WISC (Korean Educational Development Institute-Wechsler Intelligence Scale for Children) was carried out in the 45 patients, who were diagnosed as congenital hypothyroidism from March, 1991 to September, 2001 at the Soonchunhyang University Hospital and were treated soon after the diagnosis for at least 5 years after treatment. RESULTS: The proportion of male to female was 1:1.25 and the mean age at the diagnosis was 40.6+/-23.4 days and the 32 patients (71.1%) were diagnosed before the age of six weeks. There was 18 cases (40.0 %) of thyroid dyshormonogenesis, 16 cases (35.6%) of thyroid hypoplasia, 8 cases (17.8%) of ectopic thyroid and 3 cases (6.7%) of thyroid aplasia. The IQ scores of all children, except two, were in the normal range in terms of total, language and motor accomplishment. And there were no significant differences in both sex, age at diagnosis and causes. CONCLUSION: The IQ test revealed that the scores of most patients treated from early life under the impression of congenital hypothyroidism were in the normal range regardless of sex, age at diagnosis and causes.